AJCC_April_2012 by IJCP

Asian

Journal of

IJCP Group of Publications

CLINICAL CARDIOLOGY

Dr Sanjiv Chopra Prof. of Medicine & Faculty Dean Harvard Medical School Group Consultant Editor

Volume 14, Number 12, April 2012

Dr Deepak Chopra Chief Editorial Advisor Dr KK Aggarwal CMD, Publisher, Group Editor-in-Chief Dr Veena Aggarwal MD, Group Executive Editor Dr Praveen Chandra Guest Editor, AJCC praveen.chandra@medanta.org

from the desk of group editor-in-chief 413 Five Things Physicians and Patients

should Question

KK Aggarwal

Assistant Editor: Dr Nagendra Chouhan, Dr Dharmendar Jain

AJCC Speciality Panel Advisory Board

International Dr Fayoz Shanl Dr Alain Cribier Dr Kohtian Hai Dr Tanhuay Cheem Dr Ayman Megde Dr Alan Young Dr Gaddy Grimes Dr Jung bo Geg Dr Rosli Mohd. Ali Dr S Saito National Dr Mansoor Hassan Dr RK Saran

Dr SS Singhal Dr Mohd. Ahmed Dr PK Jain Dr PK Gupta Dr Naresh Trehan Faculty Dr GK Aneja Dr Ramesh Thakur Dr Balram Bhargava Dr HK Bali Dr HM Mardikar Dr Sanjay Mehrotra Dr Vivek Menon Dr Keyur Parikh

Dr Ajit Mullasari Dr Kirti Punamiya Dr MS Hiramath Dr VS Narain Dr SK Dwivedi Dr Raja Baru Panwar Dr Vijay Trehan Dr Rakesh Verma Dr Suman Bhandari Dr Ravi Kasliwal Dr Atul Abhyankar Dr Tejas Patel Dr Samir Dani

review article 415 Newer Hypolipidemics on the Block

Archana Kaveri B, Bhavishya Kirthi Anna Walder, Manohar Prabu, Manjeshwar Shrinath Baliga

423 CAD: A True Pandemic and a

Comprehensive Surveillance System is the Need of the Hour

IJCP Editorial Board

Obstetrics and Gynaecology Dr Alka Kriplani, Dr Thankam Verma, Dr Kamala Selvaraj Cardiology Dr Praveen Chandra, Dr M Paul Anand, Dr SK Parashar Paediatrics Dr Swati Y Bhave, Dr Balraj Singh Yadav, Dr Vishesh Kumar Diabetology Dr Vijay Viswanathan, Dr CR Anand Moses, Dr Sidhartha Das, Dr A Ramachandran, Dr Samith A Shetty Dentistry Dr KMK Masthan, Dr Rajesh Chandna Gastroenterology Dr Ajay Kumar Dermatology Dr Hasmukh J Shroff Nephrology Dr Georgi Abraham Neurology Dr V Nagarajan

Journal of Applied Medicine & Surgery Dr SM Rajendran Anand Gopal Bhatnagar Editorial Anchor Advisory Bodies Heart Care Foundation of India Non-Resident Indians Chamber of Commerce & Industry World Fellowship of Religions

Princy Louis Palatty, Manasa M, Apoorva Naik,

G Kannan, NN Rajendran, JSN Murthy, GB Tharani

clinical study 429 Prevalence and Prognosis of Right

Ventricular Infarction in Acute Inferior Wall Infarction

R Vinoth kumar, SM Rajendran, SMK Swaminatha Gurukul, NN Anand, Padma

432 Efficacy and Tolerability of Trandolapril in

Mild-to-moderate Hypertension: A Double-blind Comparison with Enalapril

Jyothi R, Pundarikaksha HP, Srinivasa Prabhu NC, Girish K, Vasundhara K

photo quiz Published, Printed and Edited by Dr KK Aggarwal, on behalf of IJCP Publications Ltd. and Published at E - 219, Greater Kailash, Part - 1 New Delhi - 110 048 E-mail: editorial@ijcp.com

436 Cyanosis in an Older Woman

Printed at IG Printers Pvt. Ltd., New Delhi E-mail: igprinter@rediffmail.com printer_ig@yahoo.com

practice guidelines

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Editorial Policies The purpose of IJCP Academy of CME is to serve the medical profession and provide print continuing medical education as a part of their social commitment. The information and opinions presented in IJCP group publications reflect the views of the authors, not those of the journal, unless so stated. Advertising is accepted only if judged to be in harmony with the purpose of the journal; however, IJCP group reserves the right to reject any advertising at its sole discretion. Neither acceptance nor rejection constitutes an endorsement by IJCP group of a particular policy, product or procedure. We believe that readers need to be aware of any affiliation or financial relationship (employment, consultancies, stock ownership, honoraria, etc.) between an author and any organization or entity that has a direct financial interest in the subject matter or materials the author is writing about. We inform the reader of any pertinent relationships disclosed. A disclosure statement, where appropriate, is published at the end of the relevant article.

438 ACCF/AHA Release Guideline for Early

Cardiovascular Risk Assessment

around the globe 440 News and Views

lighter reading 442 Lighter Side of Medicine

Note: Asian Journal of Clinical Cardiology does not guarantee, directly or indirectly, the quality or efficacy of any product or service described in the advertisements or other material which is commercial in nature in this issue.

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from the desk of group editor-in-chief Dr KK Aggarwal

Padma Shri and Dr BC Roy National Awardee Sr. Physician and Cardiologist, Moolchand Medcity, New Delhi President, Heart Care Foundation of India Group Editor-in-Chief, IJCP Group and eMedinewS Chairman Ethical Committee, Delhi Medical Council Director, IMA AKN Sinha Institute (08-09) Hony. Finance Secretary, IMA (07-08) Chairman, IMA AMS (06-07) President, Delhi Medical Association (05-06) emedinews@gmail.com http://twitter.com/DrKKAggarwal Krishan Kumar Aggarwal (Facebook)

Five Things Physicians and Patients should Question American College of Cardiology 



Don’t perform stress cardiac imaging or advanced noninvasive imaging in the initial evaluation of patients without cardiac symptoms unless high-risk markers are present. Asymptomatic, lowrisk patients account for upto 45% of unnecessary ‘screening.’ Testing should be performed only when the following findings are present: Diabetes in patients >40-year-old; peripheral arterial disease or >2% yearly risk for coronary heart disease events. Don’t perform annual stress cardiac imaging or advanced noninvasive imaging as part of routine follow-up in asymptomatic patients. Performing stress cardiac imaging or advanced noninvasive imaging in patients without symptoms on a serial or scheduled pattern (e.g., every 1-2 years or at a heart procedure anniversary) rarely results in any meaningful change in patient management. This practice may, in fact, lead to unnecessary invasive procedures and excess radiation exposure without any proven impact on patients’ outcomes. An exception to this rule would be for patients more than five years after a bypass operation. Don’t perform stress cardiac imaging or advanced noninvasive imaging as a preoperative assessment in patients scheduled to undergo low-risk noncardiac surgery. Noninvasive testing is not useful for patients undergoing low-risk non-cardiac surgery (e.g. cataract removal). These types of tests do not change the patient’s clinical management or outcomes and will result in increased costs. Don’t perform echocardiography as routine follow-up for mild, asymptomatic native valve disease in adult patients with no change in signs or symptoms. Patients with native valve disease usually have years without symptoms before the onset of deterioration. An echocardiogram is not recommended yearly unless there is a change in clinical status. Don’t perform stenting of nonculprit lesions during percutaneous coronary intervention (PCI) for uncomplicated hemodynamically stable ST-segment elevation myocardial infarction (STEMI). Stent placement in a noninfarct artery during primary PCI for STEMI in a hemodynamically stable patient may lead to increased mortality and complications. While potentially beneficial in patients with hemodynamic compromise, intervention beyond the culprit lesion during primary PCI has not demonstrated benefit in clinical trials to date.

American Society of Nuclear Cardiology 

Don’t perform stress cardiac imaging or coronary angiography in patients without cardiac symptoms unless high-risk markers are present. Asymptomatic, low-risk patients account for upto 45% of inappropriate stress

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from the desk of group editor-in-chief testing. Testing should be performed only when the following findings are present: Diabetes in patients older than 40-year-old, peripheral arterial disease and >2% yearly coronary heart disease event rate. 



414

Don’t perform cardiac imaging for patients who are at low-risk: Chest pain patients at low-risk of cardiac death and myocardial infarction (based on history, physical exam, electrocardiograms and cardiac biomarkers) do not merit stress radionuclide myocardial perfusion imaging or stress echocardiography as an initial testing strategy if they have a normal electrocardiogram (without baseline ST-abnormalities, left ventricular hypertrophy, pre-excitation, bundle branch block, intraventricular conduction delay, paced rhythm or on digoxin therapy) and are able to exercise. Don’t perform radionuclide imaging as part of routine follow-up in asymptomatic patients: Performing stress radionuclide imaging in patients without symptoms on a serial or scheduled pattern (e.g., every 1-2 years or at a heart procedure anniversary) rarely results in any meaningful change in patient management. This practice may lead to unnecessary invasive procedures and excess radiation exposure without any proven impact on patients’ outcomes. An exception to this rule would be for patients more than five years after a bypass operation. Don’t perform cardiac imaging as a preoperative assessment in patients scheduled to undergo low- or intermediate-risk noncardiac surgery: Noninvasive testing is not useful for patients undergoing lowrisk noncardiac surgery or with no cardiac symptoms or clinical risk factors undergoing intermediate-risk noncardiac surgery. These types of testing do not change the patient’s clinical management or outcomes and will result in increased costs. Therefore, it is not appropriate to perform cardiac imaging procedures for noncardiac surgery risk assessment in patients with no cardiac symptoms, clinical risk factors or who have moderate-togood functional capacity. Use methods to reduce radiation exposure in cardiac imaging, whenever possible, including not performing such tests when limited benefits are likely. The key step to reduce or eliminate radiation exposure is appropriate selection of any test or procedure for a specific person, in keeping with medical society recommendations, such as appropriate use criteria. Healthcare providers should incorporate new methodologies in cardiac imaging to reduce patient exposure to radiation while maintaining high-quality test results.

Asian Journal of Clinical Cardiology, Vol. 14, No. 12, April 2012

review article

Newer Hypolipidemics on the Block Princy Louis Palatty*, Manasa M**, Apoorva Naik†, Archana Kaveri B†, Bhavishya Kirthi Anna Walder‡, Manohar Prabu‡, Manjeshwar Shrinath Baliga§

Abstract Hypolipidemics are much widely used in the present day scenario as a sure prophylactic to tackle cardiovascular disease and stroke, which are leading cause of death across the world. Moreover, hyperlipidemia is not just a metabolic disorder, but it also runs in family, making hypolipidemics more important and necessary. Hence, newer and more efficient drugs are being released. The statins and fibrates, especially rosuvastatin and fenofibrate, have a lot less complications then their early counterparts. Ezetimibe or orlistat reduce absorption of cholesterol; beclobrinic acid has a unique action. Chinese red-yeast rice has a pathetic hypolipidemic action. In this article, we have reviewed the status of new drugs like micronized fenofibrate, 1-methyl-4-piperidyl bis(p-chlorophenoxy) acetate, lentysine and gugulipid.

Keywords: Hypolipidemia, hypercholesterolemia, triacylglycerols, phospholipids, apoproteins, ezetimibe

ardiovascular diseases (CVDs) are the commonest cause of death the worldover. Hyperlipidemia is the harbinger of myocardial infarction and stroke. The incidence of hyperlipidemia is 42.9% in USA and similar in other countries also. Reducing the incidence of hyperlipidemia would reduce the deaths due to CVD. This review addresses the probable available agents that reduce cholesterol and triglyceride levels. Plasma lipids are transported in complexes called lipoproteins. Metabolic disorders that involve elevations in any lipoprotein species are termed hyperlipoproteinemias or hyperlipidemias. Hyperlipidemia denotes increased levels of triglycerides. Hyperlipidemia has become one of the most common problems in day-to-day life. The sedentary lifestyle today in particular has enhanced its risk, especially in upper middle class and upper class societies. Intake of fat and the carbohydrate rich diet style of India has also added to its increasing intensity. Some of them

*Professor Dept. of Pharmacology **2nd Year MBBS †4th Year MBBS ‡3rd Year MBBS §Dept. of Research and Development Fr. Muller Medical College, Mangalore, Karnataka Address for correspondence Dr Princy Louis Palatty Professor, Dept. of Pharmacology 302, Binary Homes, Kottara Ashoknagar, Mangalore - 575 006, Karnataka E-mail: drprincylouispalatty@gmail.com, drprincylouispalatty@yahoo.com

include refined low polyunsaturated fatty acids (PUFA) oils, increased use of egg and meet, ‘refined’ low fiber containing carbohydrates. Hyperlipoproteinemias or hyperlipidemias are included under metabolic disorders. Hence, more importance has to be given to these disorders to prevent further complications. Lipid and Lipoproteins Four major lipid classes are present in lipoproteins: Triacylglycerols (16%), phospholipids (30%), cholesterol (14%) and cholesteryl esters (36%) and a much smaller fraction of unesterified long-chain fatty acids (4%). This latter fraction, the free- fatty acids (FFA), is metabolically the most active of the plasma lipids. Because fat is less dense than water, the density of a lipoprotein decreases as the proportion of lipid to protein increases (Table 1). Four major groups of lipoproteins have been identified that are important physiologically and in clinical diagnosis. These are: i) Chylomicrons, derived from intestinal absorption of triacylglycerol and other lipids; ii) very lowdensity lipoproteins (VLDL or pre-β-lipoproteins), derived from the liver for the export of triacylglycerol; iii) low-density lipoproteins (LDL or β-lipoproteins), representing a final stage in the catabolism of VLDL and iv) high-density lipoproteins (HDL or β-lipoproteins), involved in cholesterol transport and also in VLDL and chylomicron metabolism. Triacylglycerol is the predominant lipid in chylomicrons and VLDL, whereas cholesterol and phospholipid are the predominant lipids in LDL and HDL, respectively (Table 1). Lipoproteins may be

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review article Table 1. Composition of Lipoproteins in Human Plasma Lipoprotein

Source

Density (g/ml)

Protein (%)

Lipid (%)

Main lipid component

Apoproteins

Chylomicrons

Intestine

<0.95

1-2

98-99

Triacylglycerol

A-I, A-II, A-IV, B-48, C-I, C-II, C-III, E

Liver (intestine)

0.95-1.006

7-10

90-93

Triacylglycerol

B-100, C-I,C-II, C-III

IDL

VLDL

1.006-1.019

Triacylglycerol, cholesterol

B-100, E

LDL

VLDL

1.019-1.063

Cholesterol

B-100

HDL

Liver, intestine, VLDL, chylomicrons

Phospholipids, cholesterol

A-I, A-II, A-IV, C-I, C-II, C-III, D, E

VLDL

HDL1

1.019-1.063

HDL2

1.063-1.210

HDL3

1.125-1.210

Pre-β-HDL Alb/FFA

>1.210 Adipose tissue

>1.281

separated according to their electrophoretic properties into α-, β- and pre-β-lipoproteins. The nonpolar lipid core consists of mainly triacylglycerol and cholesteryl ester and is surrounded by a single surface layer of amphipathic phospholipid and cholesterol molecules. These are oriented so that their polar groups face outward to the aqueous medium, as in the cell membrane. The protein moiety of a lipoprotein is known as an apolipoprotein or apoprotein, constituting nearly 70% of some HDL and as little as 1% of chylomicrons. Some apolipoproteins are integral and cannot be removed, whereas others are free to transfer to other lipoproteins.

A-I 99

RNA editing enzyme. Apo C-I, C-II and C-III are smaller polypeptides (molecular mass 7,000-9,000 Da) freely transferable between several different lipoproteins. Apo E is found in VLDL, HDL, chylomicrons and chylomicron remnants; it accounts for 5-10% of total VLDL apolipoproteins in normal subjects. Apolipoproteins carry out several roles: 



Types of Apolipoproteins Lipids are transported in the plasma as lipoproteins. Apolipoproteins constitute one of the building blocks of lipoproteins, in turn fat. Some of them are A I-IV, B-48, B-100, C-I, II, III… D and E-10. One or more apolipoproteins (proteins or polypeptides) are present in each lipoprotein. The major apolipoproteins of HDL (β-lipoprotein) are designated A (Table 1). The main apolipoprotein of LDL (β-lipoprotein) is apolipoprotein B (apo B) (B-100), which is found also in VLDL. Chylomicrons contain a truncated form of apo B (B-48) that is synthesized in the intestine, while B-100 is synthesized in the liver. Apo B-100 is one of the longest single polypeptide chains known, having 4,536 amino acids and a molecular mass of 5,50,000 Da. Apo B-48 (48% of B-100) is formed from the same mRNA as apo B-100 after the introduction of a stop signal by an

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FFA



They form part of the structure of the lipoprotein, e.g., apo B. They are enzyme cofactors, e.g., C-II for lipoprotein lipase, A-I for lecithin: Cholesterol acyltransferase, or enzyme inhibitors, e.g., apo A-II and apo C-III for lipoprotein lipase, apo C-I for cholesteryl ester transfer protein. They act as ligands for interaction with lipoprotein receptors in tissues, e.g., apo B-100 and apo E for the LDL receptor, apo E for the LDL-receptorrelated protein (LRP), which has been identified as the remnant receptor, and apo A-I for the HDL receptor.

The functions of apo A-IV and apo D, however, are not yet clearly defined, although apo D is believed to be an important factor in human neurodegenerative disorders.

Familial Hyperproteinemia Lipoproteins are metabolized in liver. Like all other nutrients, defect of lipid metabolism also results in disorders. These are mainly classified as: (i) Hypoor hyperlipoproteinemia; (ii) primary or secondary disorder and (iii) inherited or acquired. Primary

review article disorders are usually inherited, while acquired involve abnormal lipoprotein patterns secondary to diseases like diabetes mellitus, hypothyroidism, kidney diseases and atherosclerosis. Secondary patterns are very similar to primary inherited conditions. Virtually all primary conditions are defects at some stage in lipoprotein formation, transport or destruction. All abnormalities are not harmful.

Familial Lipoprotein Lipase Deficiency (Type I) It is a condition of hypertriacylglycerolemia due to lipoprotein lipase (LPL) deficiency, abnormal LPL or apo C-II deficiency causing inactive LPL (Table 2). There is slow clearance of chylomicrons and VLDL, low levels of LDL and HDL; no increased risk of coronary disease.

Familial Hypercholesterolemia (Type IIa) This involves defective LDL receptors or mutation in ligand region of apo B-100, causing elevated LDL levels and hypercholesterolemia, resulting in atherosclerosis and coronary disease (Table 2).

Familial Type III Hyperlipoproteinemia It is broad-beta disease, or remnant removal disease also called ‘Familial dysbetalipoproteinemia’. It is due to deficiency in remnant clearance by the liver due to abnormality in apo E. Patients lack isoforms E3 and E4 and have only E2, which does not react with the E receptor (Table 2).

Familial Hypertriacylglycerolemia (Type IV) This is a condition of overproduction of VLDL often associated with glucose intolerance and hyperinsulinemia, resulting in rise of cholesterol level with VLDL (Table 2). LDL and HDL tend to be subnormal. This type of pattern is commonly associated with coronary heart disease (CHD), type 2 diabetes mellitus, obesity, alcoholism and administration of progestational hormones. Other Hyperlipoproteinemias Other hyperlipoproteinemias involve ‘hepatic lipase‘ deficiency leading to accumulation of large triacylglycerol-rich HDL and VLDL remnants. Patients have xanthomas and CHD. Cholesterol acyltransferase (LCAT) deficiency’ i.e. absence of LCAT leads to block in reverse cholesterol transport. HDL remains as nascent disk incapable of taking up and esterifying cholesterol hence, plasma concentrations of cholesteryl esters and lysolecithin

are low. An abnormal LDL fraction, lipoprotein X, is present, also found in patients with cholestasis. VLDL is abnormal (β-VLDL). ‘Familial lipoprotein excess’, which may result in premature CHD due to atherosclerosis, plus thrombosis due to inhibition of fibrinolysis. ’Familial hyperalphalipoproteinemia’ is a defect of increased concentration of HDL. It is a rare condition apparently beneficial to health and longevity. Complications of Hyperlipoproteinemia Hyperlipoproteinemia results in further complications, of which atherosclerosis is a serious one. It is recognized that triacylglycerols are independent risk factors. Atherosclerosis is characterized by deposition of cholesterol and cholesterol ester into artery wall. Diseases with prolonged elevation of LDL, VLDL, chylomicron remnants or LDL in blob are often accompanied by premature or more severe atherosclerosis. There is also an inverse relationship between HDL concentrations and CHD, marking the LDL: HDL cholesterol is a good predictive parameter. Genetic basis of Familial Dyslipidemia and Hypertension The genetic and environmental determinants of hypertension, lipid abnormalities and coronary artery disease (CAD) were studied for 15 years in Utah in population-based multigenerational pedigrees (2,500 subjects among 98 pedigrees), twin pairs (74 monozygous and 78 dizygous), hypertensive siblings (131 sibships) siblings with CAD before age 55 (45 sibships), and anecdotally ascertained pedigrees with type 2 diabetes (271 subjects among 16 pedigrees), LPL deficiency (106 subjects in a single pedigree), and familial hypercholesterolemia (502 heterozygotes among 50 pedigrees). Estimates of heritability ranged from 20 to 75% for blood pressures and blood lipids. A strong positive family history predicts a future occurrence of hypertension (relative risk [RR] = 3.8) and CAD (RR = 12.7). Segregating single-gene effects were found for several ‘intermediate phenotypes’ associated with hypertension (erythrocyte sodium-lithium countertransport, intraerythrocytic sodium, a relative fat pattern, total urinary kallikrein excretion and fasting insulin levels). Strong singlegene effects in segregation analysis were also found for LDL cholesterol, lipoprotein (a) (Lp[a]), low HDL cholesterol and high apo B. Deoxyribonucleic acid (DNA) markers of lipid abnormalities or

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review article Table 2. Frederickson’s Classification Hyperlipoproteinemias Type

Lipoprotein fraction elevated

Cholesterol level

TG level

Metabolic effect

Features

Management

Chylomicrons

Normal

Lipoprotein lipase deficiency

Eruptive xanthomas; hepatomegaly; pain abdomen

Restriction of fat

II A

LDL

Normal

LDL receptor defect; apo B+

Atherosclerosis, CAD, tuberous xanthoma

Low cholesterol and saturated fat. Give PUFA and drugs (statins)

II B

LDL and VLDL

Apo B + Apo C II+

Corneal arcus

III

Broad beta; VLDL and chylomicrons

Abnormal apo E; apo C-II +

Palmar xanthoma. High incidences of vascular disease

Reduction of weight, restriction of fat and cholesterol. Give PUFA and drugs

VLDL

Over production of VLDL; apo C-II +

Associated with diabetes mellitus, ischemic heart disease, obesity

Reduction of body weight. Restrict carbohydrate and cholesterol

VLDL chylomicrons

Normal

Secondary to other causes

Ischemic heart diseases

High PUFA intake, hypolipidemic drugs

hypertension have included LDL-receptor defects, LPL deficiency, high Lp(a), familial defective apo B, decreased quantitative levels of apo B, apo E phenotype, angiotensinogen and ‘glucocorticoid remediable aldosteronism (GRA) hypertension. Hyperlipidemia, Pregnancy and Pancreatitis Hypertriglyceridemia is a recognized complication of pregnancy. In patients with familial hypertriglyceridemia, the biochemical changes are greatly enhanced during pregnancy and may be associated with acute pancreatitis, a potentially fatal triad. Three patients were studied, in one of whom previously undiagnosed hyperlipidemia resulted in a fatal attack of fulminant acute pancreatitis. In the other two patients, this complication was avoided by close monitoring and restriction of dietary facts. A history of episodic abdominal cramps, often beginning in early childhood or the presence of lipemic fasting plasma should alert the clinician to the presence of severe familial hypertriglyceridemia. Early diagnosis allows for the institution of relatively simple management strategies, which diminish the risk of pancreatitis.

Pharmacotherapy Hence, treatment for hyperlipoproteinemias or hypolipidemias is very important. Hyperlipidemia needs to be

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controlled by means of diet mainly. Drugs serving this purpose are very useful and are the succour in familial disorders, which can’t be controlled by diet. Moreover, bringing down cholesterol levels is necessary to reduce risk of mortality and morbidity. Drugs are restored after at least a trial of or 3-month period of low fat diet with exercise. Along with all the use of drugs, dietary restriction is to be followed throughout (refer Table 3). Many drugs have been introduced over the years for the treatment of hyperlipidemia. These drug are mainly involved in reducing body cholesterols by either decreasing the synthesis (statins), increasing metabolism (fibrates), or by obstructing the absorption and increasing excretion (resins). The summary of these hyperlipidemic agents are in Table 4. Ezetimibe CHD is the leading cause of death in United States. The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III recommends new lower cholesterol levels, particularly for patients at moderate and high-risk for coronary disease. LDL cholesterol is primarily the target of hypolipidemic drugs. The NCEP ATP III recommends an LDL cholesterol goal of <100 mg/dl in high-risk patients and an LDL cholesterol goal of <70 mg/dl as a therapeutic option, especially in patients with very high-risk of CHD. Statins are

review article Table 3. Classification HMG-CoA reductase inhibitor Levostatin  Simvastatin  Pravastatin  Atorvastatin  Rosuvastatin  Fluvastatin Fibric acid derivatives 

     

Gemfibrozil Clofibrate Colesevelam Fenofibrate Bezafibrate Ciprofibrate

Bile acid binding resins Cholestyramine Colestipol  Colesevelam Others  



Ezetimibe: Sterol absorption inhibitor Beclobrinic acid: PG synthesis inhibitors Lentysine, gugulipid: Plant products Chinese red-yeast rice: Genetically modified

potent LDL cholesterol-lowering drugs, but they are not as effective as fibrates and niacin in improving levels of triglycerides or HDL cholesterol. Ezetimibe represents a new class of hypolipidemic drugs that inhibit cholesterol absorption in the small intestine. The combination of ezetimibe with statins has been more effective than monotherapy alone in many randomized trials. LDL cholesterol reduction with statin occurs mainly with the initial dose, with relatively smaller reductions seen at higher doses. Ezetimibe was also shown to be useful in various population subgroups such as African-Americans, men and women, elderly and aged, and also those with kidney disease. Fibric Acid Derivatives

Micronized Fenofibrate Fenofibrate reduces serum triglycerides, total cholesterol and LDL cholesterol and raises HDL cholesterol to clinically relevant degrees. Its spectrum of activity appears to exceed that recommended for types IV and V hyperlipidemia to encompass types IIa, IIb and III hyperlipidemias as well. To this extent, it may be considered a broader-spectrum fibrate than is indicated by its FDA approval. Adverse effects of fenofibrate appear to be similar to those of other fibrates and require routine monitoring (clinical, liver function). Long-term safety data are readily available from drug registries in many countries where the product has been available for nearly two decades. Costeffectiveness studies comparing fenofibrate with other hypolipidemics demonstrate benefits of fenofibrate over simvastatin in types IIa and IIb hyperlipidemia. The need for dosage titration of the micronized preparation from 67 mg/day upward to a final dose

of 200 mg/day is also not supported by peer-reviewed literature (except in the case of renal impairment). Although preliminary data on plaque regression are encouraging, published clinical studies evaluating the impact of fenofibrate on cardiovascular morbidity and mortality are awaited. Micronized fenofibrate is worthy of formulary inclusion.

Prostaglandin Synthesis Inhibitors Beclobrinic acid is a new hypolipidemic agent, which inhibits in vitro human platelet activation by blocking prostaglandin synthesis. Effects and the mechanism of the antiplatelet actions of beclobrinic acid (BBA) free acid form of a new hypolipidemic agent beclobrate 2-[4-(4Chlorobenzyl)phenoxy]-2-methylbutyric acid ethyl ester; Ethyl(±)-2-[[α(-(4-chlorophenyl)-4-tolyl]oxy]-2methylbutyrate, were examined using human platelets. Platelet-rich plasma (PRP) which has been prelabeled with (14C)-serotonin was incubated with BBA for one minute before the addition of various agonists. BBA (0.1-1.5 mM) inhibited platelet aggregation and serotonin secretion induced by ADP, epinephrine, arachidonic acid and collagen in a concentrationdependent manner. BBA also inhibited arachidonic acid-induced production of malondialdehyde (MDA), a by-product of prostaglandins, in a concentrationdependent manner. However, upto 1.0 mM BBA did not inhibit platelet aggregation induced by U46619, a stable analog of prostaglandin H2. In other experiments, BBA also blocked thrombin-induced release of (3H)-arachidonic acid from platelet phospholipids. These findings suggest that: (a) BBA inhibits platelet aggregation and serotonin secretion by inhibiting prostaglandin synthesis at two steps: First, by interfering with the release of arachidonic acid from platelet phospholipids and second by inhibiting its conversion into prostaglandins and (b) BBA does not inhibit the action of prostaglandins on human platelets.

1-methyl-4-piperidyl bis(p-chlorophenoxy) Acetate (SaH 42-348): A New Hypolipidemic Agent Animal studies have shown a promising noble (SaH2-438) which is chemically 1-methyl-4-piperidyl bis (p-chlorophenoxy) acetate. This agent is 8-9 times more active on a weight for weight basis than chlorphenoxy isobutyric acid ethyl ester (CPIB) and in common with CPIB lowers the level of all major classes of serum lipid. No increase in liver lipid content was seen in animals treated with SaH 42-348, although hepatomegaly was seen after treatment

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review article Table 4. Summary of Hypolipidemic Agents Subclass

Mechanism of action

Effects

Clinical applications

Pharmacokinetics, toxicities, interactions

Inhibit HMG-CoA reductase

Reduce cholesterol synthesis and upregulate LDL receptors on hepatocytes modest reduction in triglyceride

Atherosclerotic vascular disease (primary and secondary prevention) acute coronary syndromes

Oral duration 12-24 hours Toxicity: Myopathy, hepatic dysfunction Interactions: CYP-dependent metabolism (3A4, 2C9) interacts with CYP inhibitors

Statins Atorvastatin, simvastatin, rosuvastatin

Fluvastatin, pravastatin, lovastatin: Similar but somewhat less efficacious Fibrates Fenofibrate, gemfibrozil

Peroxisome PPAR-α agonists

Decrease secretion of Hypertriglyceridemia, VLDL increase lipoprotein low HDL lipase activity increase HDL

Oral duration 3-24 hours Toxicity: Myopathy, hepatic dysfunction

Binds bile acids in gut prevents reabsorption increases cholesterol catabolism upregulates LDL receptors

Decreases LDL

Elevated LDL, digitalis toxicity, pruritus

Oral taken with meals not absorbed Toxicity: Constipation, bloating interferes with absorption of some drugs and vitamins

Elevated LDL, phytosterolemia

Oral duration 24 hours Toxicity: Low incidence of hepatic dysfunction, myositis

Bile acid sequestrants Colestipol

Cholestyramine, colesevelam: Similar to colestipol Sterol absorption inhibitor Ezetimibe

Blocks sterol transporter NPC1L1 in intestine brush border

Inhibits reabsorption of cholesterol excreted in bile decreases LDL and phytosterols

Niacin

Decreases Increases HDL decreases Low HDL elevated VLDL, LDL, Lp(a) catabolism of apo AI Lp(a), LDL and triglycerides reduces VLDL secretion from liver

with SaH 42-348 or with CPIB. Evidence available suggests that the mechanism of action of SaH 42-348 in lowering serum cholesterol in the rat differs from that of CPIB. Thus, it was not possible to demonstrate that SaH 42-348 inhibited cholesterol biosynthesis in vivo, while the inhibitory effect of CPIB was readily demonstrated. In addition, n-propylthiouracil (PTU) inhibited the hypocholesterolemic activity of CPIB in both normolipemic and hyperlipemic rats, whereas the activity of SaH 42-348 was unaffected by PTU.

Plant Sterols and Stenols Consumption of diet which is low in saturated and trans-fats yet high in fibers, lower the ‘bad cholesterol’

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Oral large doses Toxicity: Gastric irritation, flushing, low incidence of hepatic toxicity may reduce glucose tolerance

(LDL) that keep the heart and blood vessels healthy. ‘Phytosterols’ in fruits, vegetables, vegetable oils, nuts and seeds amounts to ‘plant sterols’ and ‘plant stenols’ that reduce absorption of cholesterol. Sources: Wheat, peanut, vegetable oil (corn, sesame, conola, and olive oil), almonds, brussels sprouts, etc. Plant sterols and stenols resemble cholesterol in terms of chemical structure. They prevent intestinal cholesterol absorption, hence lowering LDL. Studies have shown that, sterols and stenols lower LDL cholesterol by average 6% and perhaps 14% in four weeks. Daily requirement: 2 g/day as by NCEP.

review article Mechanism of Action Sterols and Stenols (Similar chemically to cholesterol) Cholesterol absorbed in intestine LDL levels in blood

Adverse Effect Plant sterols and stenols have been studied for >50 years. They are both safe and effective in lowering cholesterol. However, large doses may cause nausea, indigestion, diarrhea and also interferes with absorption of fat soluble vitamin. Pregnant and breastfeeding women should be cautious in term consumption. Moreover, they cannot substitute for cholesterol lowering medication and are advocated in combination, not monotherapy. These can be either obtained naturally from plants and their products (e.g., Lentysine, gugulipid) or from genetically modified once (e.g., red yeast rice). Few of plant hypolipidemic agents are discussed below.

Lentysine It is a new hypolipidemic agent from a mushroom. Lentysine is one of the naturally obtained hypolipidemic agent. It was recently discovered that few of the edible mushrooms contained a chemical named lentysine, which was found to act as a hypolipidemic agent. Hence, in patients with high fat diet, consumption of these mushrooms was found to be noted useful. Its action on serum and liver lipids in rats has been investigated. Lentysine markedly reduced serum cholesterol, phospholipids and triglycerides, both in intact rats and in animals fed a high fat diet. However, this substance showed no effect on liver lipid levels, and enlargement of liver was not observed in rats treated with lentysine.

active agents in this resin. Recent studies have shown that these compounds are antagonist ligands for the bile acid receptor farnesoid X receptor (FXR), which is an important regulator of cholesterol homeostasis. It is likely that this effect accounts for the hypolipidemic activity of these phytosteroids.

Cholesterol-lowering Effects of a Proprietary Chinese Red-yeast-rice Dietary Supplement Red yeast rice is one of the genetically modified rice, which contains hypolipidemic agent from yeast. The cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement was examined in an American population consuming a diet similar to the American Heart Association Step I diet using a doubleblind, placebo-controlled, prospectively randomized 12-week controlled trial at a university research center. Eighty-three healthy subjects with hyperlipidemia, who were not being treated with lipid-lowering drugs participated. Subjects were treated with red-yeast-rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol and HDL, and LDL cholesterol measured at Weeks 8, 9, 11 and 12. Cholesterol concentrations decreased significantly between baseline and 8-week in the red-yeast-rice-treated group compared with the placebo-treated group. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. Hence, red-yeast-rice proved to provide a new, novel, foodbased approach to lower cholesterol in the general population. Suggested Reading 1.

US Census Bureau population estimates. Available at:www.census.gov/popest/national/asrh/files/NCEST2008-ALLDATA-R-File 14.csv.

Centers for Disease Control and Prevention. Behavioral Risk Factor Surveillance System: prevalence and trends data. Available at: www.apps.nccd.cdc.gov/brfess/index. asp.

Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al; American Heart Association; National Heart, Lung, and Blood Institute. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 2005;112(17):2735-52.

Kromhout D, Menotti A, Kesteloot H, Sans S. Prevention of coronary heart disease by diet and lifestyle: evidence

Gugulipid It is another naturally occurring cholesterol-lowering agent. Gugulipid has been studied and was proved very much useful. The resin of the Commiphora mukul tree has been used in Ayurvedic medicine for >2,000 years to treat a variety of ailments. Studies in both animal models and humans have shown that this resin, termed gum gugul, can decrease elevated lipid levels. The stereoisomers E- and Z-guggulsterone have been identified as the

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review article from prospective cross-cultural, cohort, and intervention studies. Circulation 2002;105(7):893-8. 5.

Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation. 2002;105(9):1135-43.

Goldberg IJ, Merkel M. Lipoprotein lipase: physiology, biochemistry, and molecular biology. Front Biosci 2001;6: D388-405.

Christie WW. Lipid Analysis. 3rd edition, The Oily Press: Bridgwater; 2003.

Gurr MI, Harwood JL, Frayn K. Lipid Biochemistry. Blackwell Publishing 2002.

Dowhan W, Bogdanov M. Functional roles of lipids in membranes. In: Biochemistry of Lipids, Lipoproteins, and Membranes. 4th edition, Vance DE, Vance JE (Eds.), Elsevier, Amsterdam 2002:p.1-36.

10. Shelness GS, Sellers JA. Very-low-density lipoprotein assembly and secretion. Curr Opin Lipidol 2001;12(2): 151-7.

14. De Chalain TM, Michell WL, Berger GM. Hyperlipidemia, pregnancy and pancreatitis. Surg Gynecol Obstet 1988;167(6):469-73. 15. Katragadda S, Rai F, Arora R. Dual inhibition, newer paradigms for cholesterol lowering. Am J Ther 2010;17(4): e88-99. 16. Guay DR. Micronized fenofibrate: a new fibric acid hypolipidemic agent. Ann Pharmacother 1999;33(10): 1083-103. 17. Anwer K, Gabis J, Romstedt K, Gojer C, Huzoor-Akbar. Beclobrinic acid - a new hypolipidemic agent - inhibits in vitro human platelet activation by blocking prostaglandin synthesis. Life Sci 1985;37(1):63-70. 18. Alan R, Lawrence A, Robert S, Joseph H. Laboratory studies of methyl-4-piperidyl bis(p-chlorophenoxy) acetate (SaH 42-348):Sandoz pharmaceuticals, Research Department, Hanover, N.J., USA 17th January 1969.

11. Arner P. Human fat cell lipolysis: biochemistry, regulation and clinical role. Best Pract Res Clin Endocrinol Metab 2005;19(4):471-82.

19. Rokujo T, Kikuch H, Tensho A, Tsukitani Y, Takenawa T, Yoshida K. Iyakushigen Institute for Medical Research, Tokyo, Fujisawa Pharmaceutical Co. Ltd. 29 December 1969.

12. Russell DW. Cholesterol biosynthesis and metabolism. Cardiovasc Drugs Ther 1992;6(2):103-10.

20. Urizar NL, Moore DD. Gugulipid: a natural cholesterollowering agent. Annu Rev Nutr 2003;23:303-13.

13. Williams RR, Hunt SC, Hopkins PN, Wu LL, Hasstedt SJ, Berry TD, et al. Genetic basis of familial dyslipidemia and hypertension: 15-year results from Utah. Am J Hypertens 1993;6(11 Pt 2):319S-327S.

21. Heber D, Yip I, Ashley JM, Elashoff DA, Elashoff RM, Go VL. Cholesterol-lowering effects of a proprietary Chinese red-yeast-rice dietary supplement. Am J Clin Nutr 1999;69(2):231-6.

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review article

CAD: A True Pandemic and a Comprehensive Surveillance System is the Need of the Hour G Kannan*, NN Rajendran**, JSN Murthy†, GB Tharani‡

Abstract Coronary artery disease (CAD) occurs when the arteries that supply blood to the heart muscle harden and narrow. According to the Global Burden of Disease Study, the developing countries contributed 3.5 million of the 6.2 million global deaths from CAD in 1990. The prevalence of CAD in India has more than doubled in the past two decades. India topped the world with 1,531,534 cardiovascular disease-related deaths in 2002, and based on WHO report, 2009, CAD currently occupies the first place in cause of death. A comprehensive surveillance system of risk factors and CAD will be an invaluable public health research tool for monitoring population health status, guiding resource allocation and policy, identifying and prioritizing interventions for subpopulations at particular risk that would help to bring down the true pandemic which is on the climb.

Keywords: Coronary artery disease, pandemic, surveillance system, health status

oronary artery disease (CAD) occurs when the arteries that supply blood to the heart muscle harden and narrow (Bhati K, 2011; Heart Diseases, 2011). The result is the loss of oxygen and nutrients to myocardial tissue because of diminished coronary blood flow (Springhouse, 2005). This reduction in blood flow can lead to acute coronary syndrome (angina or myocardial infarction). CAD is on the climb and has become a true pandemic that respects no borders. Prevalence of CAD

Global Scenario The term ‘prevalence’ of CAD usually refers to the estimated population of people who are managing CAD at any given time (American Heart Association, 2004). The proportion of deaths due to CAD is projected to rise from 59% in 2002 to 69% in 2030 (Mathers and

*Assistant Professor Dept. of Pharmacy Practice, Faculty of Pharmacy Sri Ramachandra University, Porur, Chennai **Professor Swami Vivekananda College of Pharmacy, Erode, Chennai †Professor and Head Dept. of Cardiology, Sri Ramachandra University, Porur, Chennai ‡Professor and Head Saveetha Medical College, Thandalam, Chennai Address for correspondence Dr G Kannan Assistant Professor, Dept. of Pharmacy Practice, Faculty of Pharmacy Sri Ramachandra University, Porur, Chennai - 600 116 E-mail: kannagg2@yahoo.ca

Loncar, 2006). The WHO (2006) estimates that at least 20 million people survive CAD-related heart attacks and strokes every year around the world; many require continuing costly clinical care. By 2030, almost 23.6 million people will die from CADs, mainly from heart disease and stroke. These are projected to remain the single leading causes of death (WHO-Cardiovascular Disease: Prevention and Control, 2006). A recent evaluation of WHO in the cause of death in 2009, CAD and stroke were placed as first (7,185,353 deaths) and second (5,704,843 deaths) in rank among total deaths (6,830,586,985) of all kind of diseases. Moreover, the rate of death is rising more in the under-developed countries than the developed countries, because of their lifestyle and socioeconomic factors (WHO, 2009). According to the Global Burden of Disease Study, the developing countries contributed 3.5 million of the 6.2 million global deaths from CAD in 1990. The projections estimate that these countries will account for 7.8 million of the 11.1 million deaths due to CAD in 2020 (Murray et al, 1996). Disability-adjusted life years (DALYs) lost can be thought of as ‘healthy years of life lost’. They indicate the total burden of a disease, as opposed to simply the resulting deaths. Murray et al (1996) calculate that in India and China, a spectacular rise in the number of DALYs is expected in the coming years - from a figure of <25 million DALYs in each country in 1990, to 30 million and 35 million in India and China, respectively, in 2020. CAD is decreasing

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review article in many developed countries, but is increasing in developing and transitional countries, partly as a result of increasing longevity, urbanization and lifestyle changes. CAD is responsible for 10% of DALYs lost in low and middle-income countries and 18% in highincome countries (Global Burden of Coronary Heart Disease, 2002). CAD is the most common cause of death (and premature death) in the UK. One in 5 men and one in 7 women die from CAD. There are 94,000 deaths from CAD in the UK each year (Greenlund et al, 2006). With regard to incidence, data from the Atherosclerosis Risk In Communities (ARIC) and Cardiovascular Health Study indicate that annually, 7,85,000 Americans have a new coronary attack and 4,70,000 have a recurrent attack; in addition, approximately 1,95,000 silent myocardial infarctions occur each year. This assumes that 21% of the 9,35,000 first and recurrent myocardial infarctions are silent (Thom et al, 2001; Boland et al, 2002). Tables 1 and 2 depict the CAD prevalence in urban and rural population of developed countries and developing countries.

in urban than in rural population, with a greater prevalence in affluent groups (Chadha et al, 1990; Enas et al, 1992; Singh et al, 1997). Enas et al (1996) and Enas et al (1999). It is estimated that 9.2 million productive years of life were lost in India in 2000, with an expected increase to 17.9 million years in 2030. Table 3 depicts the CAD prevalence with respect to age group, sample size of the study population in different parts of India. Salient features of the CAD epidemic in India: 



Indian Scenario The prevalence of CAD in India has more than doubled in the past two decades. This has occurred both in the rural and urban populations, although it is higher



Incidence of CAD in young Indians is about 12-16%, which is higher than any other ethnic group (Mammi et al, 1991). Age-standardized estimates for DALYs lost due to CAD per 1,000 population in India are three times higher than in developed countries (Negus et al, 1994). About 5-10% of heart attacks occur in Indian men and women younger than 40 years (Mackay and Mensah, 2004). India topped the world with 1,531,534 cardiovascular disease-related deaths in 2002, and occupied first place in cause of death in current moment based on WHO report, 2009 (Yusuf et al, 2004; WHO, 2009). Median age of first heart attack in Indians is 53 years (WHO, 2009). 1,55,88,000 DALYs (WHO, 2009).

Table 1. CAD in Urban and Rural Population of Developed Countries Author

Year

Age group

Place

Sample size

CAD prevalence (%)

Calvet et al.

2010

45-75

France

300

50.0

Arzamendi et al.

2010

20-65

Developed countries

1,260

49.0

Iwasaki et al.

2011

30-70

Japan

135

9.20

Icaza et al.

2009

35-74

USA

General population

6.95

Kivimaki et al.

2011a

30-70

5,533

0.70

Jain et al.

2011

35-75

London (UK)

2,369

22.0

Kivimaki et al.

2011b

30-70

London (UK)

7,095

0.027

Ong et al.

2011

30-70

698

5.00

Stansby et al.

2011

473

30.0

Ebrahim et al.

2011

20-70

1,63,471

4.35

Secrest et al.

2011

24-32

USA

317

2.50

Oizumi et al.

2008

30-70

Japan

2,938

3.19

Idris et al.

2008

30-70

1,087

50.0

Konishi et al.

1990

40-59

Japan

8,835

88.0

Urban population

Rural population

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review article Table 2. CAD in Urban and Rural Population of Developing Countries (Excluding India) Author

Year

Age group

Place

Sample size

CAD prevalence (%)

Grau et al.

2010

30-70

France + Spain

420 + 562

0.98

Chin et al.

2009

30-70

Malaysia

2,030

10.35

Hatmi et al.

2007

20-45

Iran

3,000

25.75

Hariharan et al.

2010

30-70

Trinidad + Tobago

1,082

1.20

Sadeghi et al.

2006

35-70

Iran

6,498

29.90

Kalra et al.

2011

35-86

Nepal

142

38.00

Icaza et al.

2009

35-74

Chile

General population

1.80

Icaza et al.

2009

35-74

China

General population

0.85

Icaza et al.

2009

35-74

Spain

General population

3.70

Ozdemir et al.

2010

30-70

Turkey

33.33

Vaidya et al.

2009

35 - <

Eastern Nepal

5.70

Onat et al.

2010

45-74

Turkey

1,655

11.50

Pitsavos et al.

2008

30-70

Greek

2,172

1.36

PavloviÄ&#x2021; et al.

2004

37-56

Croatia

3,544

3.70

Urban population

Rural population

Table 3. Prevalence of CAD in Population of India Author

Year

Age group

Place

Sample size

CAD prevalence (%)

Geetha et al.

2011

30-70

Chennai (Tamil Nadu)

2,350

2.93

Mohan et al.

2010a

30-70

Chennai (Tamil Nadu)

5.40

Mohan et al.

2010b

30-70

Chennai (Tamil Nadu)

11.0

Kumaran et al.

2002

30-70

Mysore

435

21.75

Mohan et al.

2001

20-70

Chennai (Tamil Nadu)

1,262

11.0

Stein et al.

1996

Mysore

517

10.0

Begom et al.

1995

25-65

South India (Urban)

506

13.9

Singh et al.

2011

<15

Chandigarh

196

0.000045

Kumar et al.

2006

>35

North India (Urban + Rural)

7,169

3.96

Ahmad et al.

2005

25-70

Delhi (Urban)

14,000

0.2-0.9

Ahmad et al.

2005

25-70

Delhi (Rural)

14,000

0.1-0.4

Singh et al.

1997

25-64

Moradabad

3,575

1.5-3.0

Chadha et al.

1997

25-64

Delhi (Urban + Rural)

13,723

96.7 (Urban) + 27.1 (Rural)

Begom et al.

1995

25-65

North India (Urban)

506

61.6

Lanjewar et al.

2005

25-70

Mumbai

3,871

4.20

Rastogi et al.

2004

30-70

Western India

350

1.88

Pinto et al.

2004

35-64

Goa

371

13.2

Hazarika et al.

2002

30-70

Assam

1,015

61.0

Bhattacharyya

2003

30-70

Kolkata

28 + 62

39 + 60

South India

North India

West India

East India

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review article Need of the Hour Prospective studies on the relative role and importance of traditional and newer risk factors are urgently needed in Indians within the subcontinent as much of the knowledge of risk factors for CAD has been acquired from studies conducted in the Western population. It is widely believed that the association of these risk factors with CAD in different subpopulations needs to be ascertained, and there is speculation that differences might range from the frequency of presence of classical risk factors to their total absence or irrelevance in these populations. A cost-effective preventive strategy will need to focus on reducing risk factors both in the individual and in the population at large. Effective screening, evaluation and management strategies for CAD are well-established in high-income countries, but these strategies have not been fully implemented in India which was noted by Mohan et al (2001). A key factor that hampers the development of such preventive strategies in developing countries such as India is the meager amount (8%) of published literature on CAD research available from these countries (Mackay and Mensah, 2004). Of particular concern to India is not only the high burden of CAD, but also the effects of these diseases on the productive workforce aged 35-65 years. Heart diseases are rising in Asian Indians 5-10 years earlier than in other populations around the world. The mean age for first presentation of acute myocardial infarction in Indians is 53 years. CAD that manifests at a younger age can have devastating consequences for an individual, the family and society. Prevention of these deaths in young people is a nationâ&#x20AC;&#x2122;s moral responsibility (Sharma and Ganguly, 2005). A strategy involving prevention of CADs long before their onset will be more costeffective than providing interventions at a stage when the disease is well-established. Therefore, it is imperative to undertake large populationbased, prospective studies in developing countries such as India to identify CAD risk factors, both conventional and novel. Careful scrutiny of available scientific evidence for modifiable CAD risk factors (elevated serum total and LDL-C, low HDL-C, smoking, diabetes, hypertension, low level of physical activity and central obesity) in association with genetically predisposing factors like Lp(a) in Indian population may be helpful in formulating a more immediate CAD prevention strategy. Given the explosion of diabetes and CAD in India and in view of the differences in race, culture, way of life,

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diet, stress and strain and the myriad other factors, increased emphasis on lifestyle modification, including diet, exercise, weight reduction and whenever relevant, stress reduction, is urgently needed. A comprehensive surveillance system of risk factors and CAD will be an invaluable public health research tool for monitoring population health status, guiding resource allocation and policy, identifying and prioritizing interventions for subpopulations at particular risk, identifying disparities in outcomes and planning and evaluating health programs. Carefully planned prevention programs with intervention strategies by catching the vulnerable individuals at an early age could also be taken up in different parts of the country to prevent the twin epidemic of diabetes and CAD; as both have common causative factors, and prevention strategies could also be combined judiciously to prevent both disorders, as this would make it more cost-effective. Resources should be directed towards applying the existing knowledge base to tackle the CAD epidemic in policy, capacity building and research arenas. Control of the CAD epidemic in the Indian subcontinent is tenable in the foreseeable future, provided that policy makers, health professionals and the lay public in the Indian subcontinent acknowledge its potential impact and promptly act to address to make a major step towards CAD free society. Suggested Reading 1.

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Arzamendi D, Benito B, Tizon-Marcos H, Flores J, Tanguay JF, Ly H, et al. Increase in sudden death from coronary artery disease in young adults. Am Heart J 2011;161(3):574-80.

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22. Icaza G, Núñez L, Marrugat J, Mujica V, Escobar MC, Jiménez AL, et al. Estimation of coronary heart disease risk in Chilean subjects based on adapted Framingham equations. Rev Med Chill 2009;137(10):1273-82.

Chadha SL, Radhakrishnan S, Ramachandran K, Kaul U, Gopinath N. Epidemiological study of coronary heart disease in urban population of Delhi. Indian J Med Res 1990;92:424-30.

23. Idris I, Deepa R, Fernando DJ, Mohan V. Relation between age and coronary heart disease (CHD) risk in Asian Indian patients with diabetes: a cross-sectional and prospective cohort study. Diabetes Res Clin Pract 2008;81(2):243-9.

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24. Iwasaki M, Kuroda S, Nakayama N, Hokari M, Yasuda H, Saito H, et al. Clinical characteristics and outcomes in carotid endarterectomy for internal carotid artery stenosis in a Japanese population: 10-year microsurgical experience. J Stroke Cerebrovasc Dis 2011;20(1):55-61.

11. Ebrahim S, Taylor F, Ward K, Beswick A, Burke M, Davey Smith G. Multiple risk factor interventions for primary prevention of coronary heart disease. Cochrane Database Syst Rev 2011;(1):CD001561. 12. Enas EA, Garg A, Davidson MA, Nair VM, Huet BA, Yusuf S. Coronary heart disease and its risk factors in firstgeneration immigrant Asian Indians to the United States of America. Indian Heart J 1996;48(4):343-53.

25. Jain P, Kooner JS, Raval U, Lahiri A. Prevalence of coronary artery calcium scores and silent myocardial ischaemia was similar in Indian Asians and European whites in a cross-sectional study of asymptomatic subjects from a UK population (LOLIPOP-IPC). J Nucl Cardiol 2011;18(3):435-42.

13. Enas EA, Salim Yusuf. Third Meeting of the International Working Group on Coronary Artery Disease in South Asians. 29 March 1998, Atlanta, USA. Indian Heart J 1999;51(1):99-103.

26. Kivimäki M, Batty GD, Hamer M, Ferrie JE, Vahtera‑J, Virtanen M, et al. Using additional information on working hours to predict coronary heart disease: a cohort study. Ann Intern Med 2011b;154(7):457-63.

14. Enas EA, Yusuf S, Mehta JL. Prevalence of coronary artery disease in Asian Indians. Am J Cardiol 1992;70(9): 945-9.

27. Kivimäki M, Nyberg ST, Batty GD, Shipley MJ, Ferrie JE, Virtanen M, et al. Does adding information on job strain improve risk prediction for coronary heart disease beyond the standard Framingham risk score? The Whitehall II study. Int J Epidemiol 2011a May 9. (Epub ahead of print)

15. Geetha L, Deepa M, Anjana RM, Mohan V. Prevalence and clinical profile of metabolic obesity and phenotypic obesity in Asian Indians. J Diabetes Sci Technol 2011; 5(2):439-46. 16. Grau M, Bongard V, Fito M, Ruidavets JB, Sala J, Taraszkiewicz D, et al; REGICOR, GENES Investigators. Prevalence of cardiovascular risk factors in men with stable coronary heart disease in France and Spain Arch Cardiovasc Dis 2010;103(2):80-9. 17. Greenlund KJ, Giles WH, Keenan NL, et al. Heart disease and stroke mortality in the 20th century. In: Silent Victories: The History and Practice of Public Health in 20th Century America. Ward J, Warren C (Eds.), Oxford University Press: Oxford, England; 2006.

28. Konishi M, Iso H, Iida M, Naito Y, Sato S, Komachi Y, et al. Trends for coronary heart disease and its risk factors in Japan: epidemiologic and pathologic studies. Jpn Circ J 1990;54(4):428-35. 29. Kumar R, Singh MC, Singh MC, Ahlawat SK, Thakur JS, Srivastava A, et al. Urbanization and coronary heart disease: a study of urban-rural differences in northern India. Indian Heart J 2006;58(2):126-30. 30. Kumaran K, Fall CH, Martyn CN, Vijayakumar M, Stein CE, Shier R. Left ventricular mass and arterial compliance: relation to coronary heart disease and its risk factors in South Indian adults. Int J Cardiol 2002;83(1):1-9.

18. Hariharan S, Chen D, Vialva M, Exeter H, Billingy I, Bobb KA, et al. Outcome evaluation of coronary artery bypass grafting surgery applying the EuroSCORE in a Caribbean developing country. Heart Surg Forum 2010;13(5):E287-91.

31. Lanjewar C, Jolly S, Mehta SR. Effects of aspiration thrombectomy on mortality in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis of the randomized trials. Indian Heart J 2009;61(4):335-40.

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32. Mackay J, Mensah G. The atlas of heart disease and stroke. World Health Organization, Centers for Disease Control and Prevention; 2004.

20. Hazarika NC, Biswas D, Narain K, Kalita HC, Mahanta J. Hypertension and its risk factors in tea garden workers of Assam. Natl Med J India 2002;15(2):63-8.

33. Mammi MV, Pavithran K, Abu Rahiman P, Pisharody R, Sugathan K. Acute myocardial infarction in north Kerala. A 20-year hospital based study. Indian Heart J 1991;43(2):93-6.

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review article 34. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11):e442. 35. Mohan V, Deepa R, Rani SS, Premalatha G; Chennai Urban Population Study (CUPS No. 5). Prevalence of coronary artery disease and its relationship to lipids in a selected population in South India: The Chennai Urban Population Study (CUPS No. 5). J Am Coll Cardiol 2001;38(3):682-7. 36. Mohan V, Vassy JL, Pradeepa R, Deepa M, Subashini S. The Indian type 2 diabetes risk score also helps identify those at risk of macrovascular disease and neuropathy (CURES-77). J Assoc Physicians India 2010a; 58:430-3. 37. Mohan V, Venkatraman JV, Pradeepa R. Epidemiology of cardiovascular disease in type 2 diabetes: the Indian scenario. J Diabetes Sci Technol 2010;4(1): 158-70. 38. Murray CJL, Lopez AD. The Global Burden of Disease: A Comprehensive Assessment of Mortality and Disability from Disease, Injuries and Risk Factors in 1990 and Projected to 2020. Harvard University Press: Boston, Ma; 1996. 39. Oizumi T, Daimon M, Jimbu Y, Wada K, Kameda W, Susa S, et al. Impaired glucose tolerance is a risk factor for stroke in a Japanese sample - the Funagata study. Metabolism 2008;57(3):333-8. 40. Onat A, Uğur M, Ciçek G, Ayhan E, Doğan Y, Kaya H, et al. The Turkish Adult Risk Factor survey 2009: similar cardiovascular mortality in rural and urban areas. Turk Kardiyol Dern Ars 2010;38(3):159-63. 41. Ong P, Athanasiadis A, Borgulya G, Voehringer M, Sechtem U. 3-year follow-up of patients with coronary artery spasm as cause of acute coronary syndrome: the CASPAR (coronary artery spasm in patients with acute coronary syndrome) study follow-up. J Am Coll Cardiol 2011;57(2):147-52. 42. Ozdemir H, Ciftçi E, Tapisiz A, Ince E, Tutar E, Atalay S, et al. Clinical and epidemiological characteristics of children with Kawasaki disease in Turkey. J Trop Pediatr 2010;56(4):260-2. 43. Pavlović M, Corović N, Gomzi M, Simić D, Jazbec A, Tiljak MK. Smoking habits, signs of chronic diseases and survival in inland and coastal regions of Croatia: a followup study. Coll Antropol 2004;28(2):689-700. 44. Pinto RJ, Bhagwat AR, Loya YS, Sharma S. Coronary artery disease in premenopausal Indian women: risk factors and angiographic profile. Indian Heart J 1992;44(2):99-101. 45. Pitsavos C, Kavouras SA, Panagiotakos DB, Arapi S, Anastasiou CA, Zombolos S, et al; GREECS Study Investigators. Physical activity status and acute coronary syndromes survival The GREECS (Greek Study of Acute Coronary Syndromes) study. J Am Coll Cardiol 2008; 27;51(21):2034-9. 46. Rastogi T, Vaz M, Spiegelman D, Reddy KS, Bharathi AV, Stampfer MJ, et al. Physical activity and risk of coronary heart disease in India. Int J Epidemiol 2004;33(4):759‑67.

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47. Secrest AM, Costacou T, Gutelius B, Miller RG, Songer TJ, Orchard TJ. Associations between socioeconomic status and major complications in type 1 diabetes: the pittsburgh epidemiology of diabetes complication (EDC) Study. Ann Epidemiol 2011;21(5):374-81. 48. Sharma M, Ganguly NK. Premature coronary artery disease in Indians and its associated risk factors. Vasc Health Risk Manag 2005;1(3):217-25. 49. Singh RB, Rastogi SS, Rao PV, Das S, Madhu SV, Das AK, et al. Diet and lifestyle guidelines and desirable levels of risk factors for the prevention of diabetes and its vascular complications in Indians: a scientific statement of The International College of Nutrition. Indian Consensus Group for the Prevention of Diabetes. J Cardiovasc Risk 1997;4(3):201-8. 50. Singh S, Aulakh R, Bhalla AK, Suri D, Manojkumar‑R, Narula N, et al. Is Kawasaki disease incidence rising in Chandigarh, North India? Arch Dis Child 2011;96(2): 137-40. 51. Springhouse (2005). Professional Guide to Diseases 8th edition, Lippincott Williams and Wilkins; 2005. 52. Stansby G, Mister R, Fowkes G, Roughton M, Nugara F, Brittenden J, et al; Prospective Registry and Evaluation of Peripheral Arterial Risks, Events and Distribution Investigators. High risk of peripheral arterial disease in the United Kingdom: 2-year results of a prospective registry. Angiology 2011;62(2):111-8. 53. Stein CE, Fall CH, Kumaran K, Osmond C, Cox V, Barker DJ. Fetal growth and coronary heart disease in South India. Lancet 1996;348:1269-73. 54. Thom TJ, Kannel WB, Silbershatz H, D’Agostino RB. Cardiovascular disease in the United States and preventive approaches. In: Hurst’s The Heart, Arteries and Veins. 10th edition, Fuster V, Alexander RW, O’Rourke RA (Eds.), McGraw-Hill: New York, NY 2001:3-7. 55. Vaidya A, Pokharel PK, Nagesh S, Karki P, Kumar S, Majhi S. Prevalence of coronary heart disease in the urban adult males of eastern Nepal: a population-based analytical cross-sectional study. Indian Heart J 2009;61(4):341-7. 56. WHO. Cardiovascular Disease: Prevention and Control. 2006,‑http://www.who.int/mediacentre/factsheets/fs317/ en/index.html. 57. World Health Organisation. Disease and injury regional estimates for 2004. Geneva, Switzerland. Available at: http://www.who.int/healthinfo/global_burden_disease/ estimates_regional/en/index.html. Accessed 5 September 2009. 58. Yusuf S, Hawken S, Ôunpuu S, Dans T, Avezum A, Lanas F, et al; INTERHEART Study Investigators. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet 2004;364:937-52.

clinical study

Prevalence and Prognosis of Right Ventricular Infarction in Acute Inferior Wall Infarction R Vinoth kumar*, SM Rajendran**, SMK Swaminatha Gurukul†, NN Anand‡, Padma‡

Abstract In patients with acute inferior wall infarction, right ventricular (RV) involvement is one of the strongest predictors of in-hospital deaths. In this study, we sought to evaluate the prognostic impact of RV infarction in patients with acute inferior wall infarction. The in-hospital clinical outcome of 50 patients admitted to the coronary care unit with acute inferior wall infarction was analyzed and the presence of RV infarction was diagnosed by ECG and echocardiography. The total incidence of RV infarction in acute inferior wall infarction was 40%. The incidence of hypotension is more in patients with RV infarction (80%) as compared to patients with isolated inferior wall infarction (30%). Patients with associated RV infarction had significantly higher incidence of major complications (85% vs 13%) and in-hospital mortality (25% vs 10%) compared to patients with isolated inferior wall infarction. This increased risk is related to the presence of RV myocardial involvement itself rather than the extent of left ventricular (LV) myocardial damage.

Keywords: Prognostic, RV infarction, in-hospital mortality

cute myocardial infarction (MI) remains among the most common problems encountered in Internal Medicine or Adult Cardiology. It is established that nearly 20 million persons suffer from coronary artery disease (CAD) in India and about 2.5 million die every year. Once considered rare and clinically unimportant, infarction of right ventricle (RV) is now recognized as a common clinical event occurring in one-third of patients with inferior wall MI (IWMI). Some anterior wall infarctions are also associated with RV infarction in 5% autopsies. Isolated RV infarction was also reported. The introduction of right precordial electrocardiography by Erhardt et al made identification and diagnosis of RVMI practical and easy. Clinical studies have identified RV involvement as a major prognostic indicator in patient with inferior wall infarction and its proper recognition and treatment have assured increasing importance. Material and Methods This study was conducted in Sree Balaji Medical College, Chrompet, Chennai, during the period of November 2007 to May 2009. A total number of 50 *Assistant Professor **Professor †Professor and Head ‡Associate Professor Dept. of General Medicine Sree Balaji Medical College, Chennai

patients admitted to intensive care unit (ICU) were studied. There were 40 male and 10 female patients ranging in age from 34 to 80 years. Patients with acute IWMI, which is evidenced by ST elevation >1 mm in II, III, aVF and substantial increase in cardiac enzymes (creatine phosphokinase-MB [CPK-MB]), were included and patients with previous history of MI and an anterior wall infarction were excluded from the study. History taking, physical examination, laboratory investigations were performed in all subjects. CPKMB level in serum was estimated 12-24 hours after the onset of symptoms, or at admission if the patient presented later than this period. CPK-MB was estimated photometrically. The normal values for our laboratory were upto 24 IU/l. All patients admitted in the ICU were put on continuous cardiac monitoring for at least 48 hours and later if required. Patients were seen at frequent intervals and meticulous progress notes were maintained. Results Fifty acute inferior wall infarction patients were studied. Twenty patients had evidence of RV infarction (40%). Average overall age in patients with RVMI was 53 and without RVMI was 55. The youngest in RVMI group was 38 years and that in the isolated IWMI group was 34 years. The commonest presentation among the patients in our study was original type of chest pain (90%). In this study, 30 patients were

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Clinical Study smokers. Out of 30 patients, 15 patients had RVMI and 15 patients had isolated IWMI. In this study, 19 patients had diabetes and 16 patients had hypertension. Of these 19 diabetics, seven patients had RVMI and 12 patients had inferior wall infarction without RVMI. Of the 16 hypertensives, six patients had RV infarction and 10 patients had inferior wall infarction without RV involvement. Hypotension was present in 25 patients (50%); 16 patients with RVMI had hypotension (80%). Six patients had bradycardia and jugular venous pressure (JVP) was raised in 25 patients. Five patients with RVMI had bradycardia (25%) and 16 patients with RVMI had increase JVP. In patients with RV infarction, RVS3 was noted in two patients and RVS4 in two patients. Complete heart block was present in six patients. Of those, five patients had RV infarction and one patient had IWMI without RV involvement. Incidence of complete heart block in patients with RV infarction in our study was 25%.

Cardiac Enzymes CPK-MB levels were raised in all patients with inferior wall infarction. In patients with RV infarction, it ranged from 68 to 116 IU/l with an average of 93.2 IU/l. In patients without RV infarction, it ranged from 62 to 128 IU/l with an average of 87.2.

Echocardiogram Of the 20 patients who had RV infarction, everyone showed hypokinesis of diaphragmatic wall of RV. Five patients showed RV dilatation and one showed tricuspid regurgitation. Among the 50 patients, 18 were thrombolyzed; of these, 12 did not have RV infarction and six had RV infarction. Fluid therapy was done in 13 patients with RV infarction. Amount of fluid varied from 1 to 2 liters of normal saline. There were eight deaths among the 50 study subjects. Of these eight deaths, five had RVMI and three had isolated IWMI. Discussion

60%

RV infarction

40%

Isolated IWMI

Figure 1.

Incidence of RVMI in acute IWMI varied from 5 to 43% in an autopsy series with a mean around 19%. Based on radionucleotide ventriculography of technetium pyrophosphate scintiography, Wacken et al found out the incidence of RV infarction in inferior wall infarction to be 37.5% and Braat et al found it to be 43%. In our study, the incidence of RV infarction in inferior wall was 40%, comparable with other results. There was no significant difference in the mean age in both groups of patients.

Isolated IWMI

RV infarction

0 1st degree heart block

Type 1 2nd degree Type 2 2nd degree heart block heart block

Figure 2.

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Complete heart block

VPC

Ventricular tachycardia

Clinical Study Increased incidence of RV infarction in patients having chronic respiratory disease has been studied by Virmani et al and Klade. In our study, out of 40 male patients, 30 gave history of smoking for >10 years. Out of those 30, 15 patients had RV infarction. This indicates that smoking significantly increases the risk of development of acute MI. A study conducted by Gottelieb et al showed a better prognosis for smokers, but no such findings were obtained in our study. Cohn et al described a high incidence of systemic venous congestion and hypotension in their patients with RV infarction. Candell Fierre et al found similar hemodynamic disturbances in patients with RV infarction. In our study, the incidence of hypotension and raised JVP in patients with RV infarction was 80%, whereas it was only 30% in patients without RV infarction. These results correlate with the study conducted by Cohn et al. In Zehender study, bradycardia was found in 9% of patients with RV infarction and 3% of patients without RV infarction. Incidence of heart block with varying degrees was 25% in our study. In our study, out of 50 patients, 18 patients received thrombolytic therapy and 30 patients did not receive thrombolytic therapy. In the nonthrombolytic group, five patients died, whereas in thrombolytic group three patients died. The most common cause for contraindication for thrombolytic therapy was late presentation. In Zehender’s study, the mortality rate associated with RV infarction was 31%, whereas in isolated IWMI it was 6%. In our study, the mortality rate associated with RV infarction was 25% and mortality associated with isolated IWMI was 10%. These results correlate with the study conducted by Zehender et al. Conclusion Fifty patients admitted with acute inferior wall infarction were studied for the evidence of RV infarction by electrocardiogram. The incidence of RV infarction is 40%. Presence of systemic hypotension and raised JVP were observed in significant number of RV infarct

patients. This study also points out the utility of V4R in diagnosing RV infarction in patients with inferior wall infarction. All patients with RV infarction showed ST elevation in V4R. Thrombolysis was given only in 38% of patients. There was no significant difference in overall mortality between the thrombolyzed group and nonthrombolyzed group. Mortality associated with RV infarction is 25%, whereas mortality in isolated IWMI is only 10%. This shows that presence of RV infarction has a bad prognosis in patients with IWMI. This study based on ECG findings alone, for diagnosis of RV infarction has its own limitations. Evaluation of the presence and extent of RV infarction by other noninvasive investigation remains of utmost importance. Yet, this was an attempt for early recognition of RV infarction in patient with inferior wall infarction and to study the unique hemodynamic and conduction disturbance to aid in the proper management. Suggested reading 1.

Erhardt LR, Sjõgen A, Wahlberg I. Single right-sided precordial lead in the diagnosis of right ventricular involvement in inferior wall infarction. Am Heart J 1976;91(5):571-6.

Pasterrak RC, Braunwald E, Sobel BE. Acute myocardial infarction. In: Braunwald’s Heart disease. A Textbook of Cardiovascular Medicine. Vol II, 7th edition, WB Saunders 2005:p.1103-67.

Braunwald E, Sobel BE. Acute myocardial infarction. In: Braunwald’s Heart diseases: A Textbook of Cardiovascular Medicine. Vol II, 7th edition, WB Saunders.

Braat SH, Brugada P, de Zwaan C, Coenegracht JM, Wellens HJ. Value of electrocardiogram in diagnosing right ventricular involvement in patients with an acute inferior wall myocardial infarction. Br Heart J 1983;49(4):368-72

Cohn JN, Guiha NH, Border MI, Limas CJ. Right ventricular infarction. Clinical and hemodynamic features. Am J Cardiol 1974;33(2):209-14.

Zehender KK, Kapser W, Kauder E, Schõnthaler M, Geibel A, Olschewski M, et al. Right ventricular infarction as an independent predictor of prognosis after acute inferior myocardial infarction. N Engl J Med 1993;328(14):981-8.

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clinical study

Efficacy and Tolerability of Trandolapril in Mildto-moderate Hypertension: A Double-blind Comparison with Enalapril Jyothi R*, Pundarikaksha HP**, Srinivasa Prabhu NC†, Girish K‡, Vasundhara K*

Abstract Objective: To compare the efficacy and tolerability between trandolapril and enalapril in mild-to-moderate hypertension. Material and Methods: This was a prospective, double-blind, parallel, comparative clinical trial involving 120 patients with mild-to-moderate hypertension. Patients were randomized to receive trandolapril 2-4 mg once-daily and enalapril 5-10 mg once-daily. The participants were followed for eight weeks. Results: Both the drugs achieved effective control of blood pressure (BP) at the end of eight weeks. The mean reduction in systolic BP (SBP) was 22.17 mmHg with trandolapril and 21.47 mmHg with enalapril group; the mean reduction of diastolic BP (DBP) was 9.57 mmHg with trandolapril and 11.13 mmHg with enalapril. Adverse events developed in 11 (18.3%) and 12 (20%) patients in trandolapril and enalapril group, respectively. Conclusion: The efficacy and tolerability of trandolapril was comparable to enalapril in mild-to-moderate hypertension with minor adverse events.

Keywords: Hypertension, ACEIs, trandolapril, enalapril

ypertension is one of the most prevalent vascular diseases in the world and posses a major public health problem. Angiotensinconverting enzyme inhibitors (ACEIs) are accepted as first-line therapy in the treatment of hypertension and heart failure.1 The principle antihypertensive effect is through renin-angiotensin-aldosterone (RAA) mechanism.2 They offer distinct advantages such as preventing or reversing cardiovascular remodeling,3 diabetic complications,4 improving endothelial function5 and also enhancing fibrinolysis.6 The American Heart Association and American College of Cardiology (AHA/ACC) recommend ACEIs as standard therapy in patients who are at high-risk for cardiovascular morbidity and mortality.7 In recent years, there has been a rapid growth in the number of

ACEIs entering the market. Most have claimed some sort of advantages based on differences in pharmacokinetics, metabolism or tissue ACE binding. Trandolapril is a new nonsulfhydryl lipophilic ACEI. The main pharmocodynamic effects of trandolapril are achieved by reduction in plasma angiotensin-II levels, which leads to a reduction in total peripheral vascular resistance, blood pressure (BP) and decreased sodium and water retention by the kidney.8 It has an effective long duration of action in the dose of 2-4 mg daily and is well-tolerated with minor adverse events.9 Few studies were done in Indian population to compare its efficacy and tolerability with other ACEIs. The present study was undertaken to compare the efficacy and tolerability of trandolapril with enalapril in mild-tomoderate essential hypertension. Material and Methods

*Assistant Professor **Professor and Head †Professor ‡Associate Professor Dept. of Pharmacology Kempegowda Institute of Medical Sciences, Bangalore Address for correspondence Dr Jyothi R Assistant Professor, Dept. of Pharmacology No-3, KIMS Staff Quarters, KIMS Campus BSK-II Stage, Bangalore - 70, Karnataka E-mail: sanjyoth03@yahoo.co.in

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The present study was a randomized, double-blind, parallel, comparative clinical trial carried out in Kempegowda Institute of Medical Sciences Hospital and Research Centre, Bangalore, over a period of one year. The study protocol was approved by the Institution Ethical Committee, and conducted in accordance with the Declaration of Helsinki. After obtaining written informed consent, 120 patients

Clinical Study of either sex in the age group of 20-60 years with mild-to-moderate hypertension (sitting diastolic BP [DBP] between 90-110 mmHg) were recruited for the study. Patients who were previously receiving antihypertensive medication were given two weeks’ washout prior to entry into the study. Patients with the following conditions were excluded from the study; pregnant and lactating women, patients with history of drug allergy or intolerance to ACEIs, patients unwilling to comply with the protocol requirement, patients with severe hypertension, patients already on antihypertensive drugs or other medications known to affect the outcome of the study, patients who had participated in other clinical trials in the past one month, patients with history or evidence of renal, hepatic or neurological disease, patients with uncontrolled diabetes and patients with suspected bilateral renal artery stenosis or single kidney. A detailed medical history, clinical examination, anthropometric measurements and baseline laboratory investigations were carried out. Patients fulfilling the study criteria were randomly assigned to two groups of 60 each to receive either trandolapril 2 mg or enalapril 5 mg. The BP was recorded at baseline, at 2, 4 and 8 weeks. BP was recorded 3 times at each visit after five minutes of rest in a sitting posture. Compliance was monitored by pill count method. Patients were monitored for adverse events throughout the study period. Laboratory investigations like Hb%, WBC count, blood urea, serum creatinine, lipid profile, serum electrolytes (sodium and potassium), FBS, urine analysis and ECG were done at baseline and at the end of eight weeks. Romhilt-Esters point score system10 was used to detect left ventricular hypertrophy (LVH) by using ECG. Data was expressed in percentages and mean ± SD. Student ‘t’ test was used to find the significance of systolic BP (SBP) and DBP between the two groups. ANOVA was used to find the significance of SBP and DBP during the study period within each group. Results Out of 120 patients, 64 were men and 56 women. The mean age in trandolapril and enalapril group was 51.21 ± 6.0 and 50.57 ± 6.16 years, respectively. Sixty-eight (56.66%) patients were from urban and 52 (43.33%) from rural area. The mean SBP at baseline in the trandolapril group was 151.57 ± 7.63 mmHg compared with 151.07 ± 7.14 mmHg in the enalapril group. The mean DBP at baseline

Table 1. Demographic and Basic Characteristics Characteristics

Trandolapril

Enalapril

Age (years)

51.20 ± 6.01

51.57 ± 6.16

Sex: Male/Female (N)

33/27

31/29

Location: Urban/Rural (N)

28/32

40/20

Basal SBP (Mean ± SD) mmHg 151.57 ± 7.63

151.07 ± 7.14

Basal DBP (Mean ± SD) mmHg

100.53 ± 5.66

98.40 ± 4.49

N = 60 in each group. Values are mean ± standard deviation (SD)

Table 2. Comorbid Conditions in Study Groups Comorbid conditions Type 2 diabetes mellitus

Trandolapril

Enalapril

11 (18.3)

9 (15)

Obesity

18 (30)

16 (26.7)

Diabesity

5 (8.3)

6 (10)

LVH

5 (8.3)

6 (10)

Numbers in parenthesis indicates percentage.

in the trandolapril group was 98.40 ± 4.49 mmHg compared with 100.53 ± 5.66 mmHg in the enalapril group (Table 1). There were no significant differences between the two groups with respect to demographic and baseline characteristics. The most frequent comorbid conditions present in both groups included type 2 diabetes mellitus in 16.66% (n = 20), obesity (body mass index [BMI] ≥25 kg/m2) in 28.33% (n = 34), diabesity in 9.16% (n = 11) and LVH based on ECG changes in 9.16% (n = 11) of patients (Table 2). At the end of two and four weeks, 38% and 75% of the study subjects in trandolapril group and 27% and 58% in the enalapril group achieved reduction in DBP to <90 mmHg and reduction in DBP at four weeks was shown to be significant (p < 0.05). The dose of trandolapril was increased from 2-4 mg in 25% (n = 15) and enalapril from 5-10 mg in 41.7% (n = 25) of patients at the end four weeks in patients who did not show DBP reduction to <90 mmHg with the initial dose. The mean SBP/DBP in the trandolapril group was 151.57 ± 7.63/98.40 ± 4.49 at baseline, 144.30 ± 7.12/ 94.27 ± 4.58 after two weeks, 137.13 ± 6.16/91.45 ± 3.02 after four weeks and 129.40 ± 1.12/88.83 ± 1.34 after eight weeks. Mean fall in SBP and DBP was shown to be 22.17 and 9.57 mmHg (Table 3). The mean SBP/ DBP in the enalapril group was 151.07 ± 7.14/100.53 ± 5.66 at baseline, 143.73 ± 7.34/95.80 ± 4.75 after two weeks, 136.23 ± 6.19/ 91.87 ± 2.85 after four weeks and 129.60 ± 0.81/89.23 ± 1.17 after eight weeks.

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Clinical Study Table 3. Changes in SBP and DBP in Trandolapril and Enalapril Groups during the Study Visits

Trandolapril

Enalapril

SBP

DBP

SBP

DBP

Basal

151.57 ± 7.63

98.40 ± 4.49

151.07 ± 7.14

100.53 ± 5.66

2 weeks

144.30 ± 7.12

94.27 ± 4.58

143.73 ± 7.34

95.80 ± 4.75

4 weeks

137.13 ± 6.16

91.45 ± 3.02

136.23 ± 6.19

91.87 ± 2.85

8 weeks

129.40 ± 1.12

88.83 ± 1.34

129.60 ± 0.81

89.23 ± 1.17

Values are mean ± standard deviation (SD). No statistical significance between two groups.

Table 4. Adverse Events in the Study Group Adverse events

Trandolapril

Enalapril

Cough

4 (6.66)

3 (5)

Giddiness

1 (1.66)

4 (6.66)

Headache

2 (3.33)

Fatigue

1 (1.66)

2 (3.33)

Myalgia

2 (3.33)

1 (1.66)

Abdominal discomfort

1 (1.66)

0 (0)

11 (18.33)

12 (20)

Total

Numbers in parenthesis indicates percentage.

Mean fall in SBP and DBP was shown to be 22.17 and 9.57 mmHg (Table 3). Mean fall in SBP and DBP was shown to be 21.47 and 11.23 mmHg. There was no significant difference in mean fall in SBP and DBP in both groups. ECG was recorded in all patients at baseline and at the end of eight weeks. Eleven patients from both groups had pre-existing changes suggestive of LVH. Out of 11, one patient in trandolapril group showed partial reversal of LVH. All laboratory parameters both at baseline and at the end of eight weeks were within normal limits. Adverse events were encountered in 18.33% (n = 11) and 20% (n = 12) of patients in trandolapril and enalapril group, respectively. Cough (6.6%), headache (3.3%) and myalgia (3.3%) were experienced in the trandolapril group. Giddiness (6.6%), cough (5%), headache (3.3%) and fatigue (3.3%) were seen in the enalapril group (Table 4). The most common adverse event from both groups was cough in 5.8% (n = 7). All the adverse events were mild, transient and did not require any treatment, discontinuation of medication or withdrawal from the study. Discussion In the present study, reduction in DBP to <90 mmHg was achieved in 75% of patients who received

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trandolapril 2 mg and in 58% of those who received enalapril 5 mg for four weeks. All patients achieved target DBP reduction by the end of eight weeks after doubling of dose in both groups. Similar findings were observed in studies carried out by Shankar et al,11 they had shown that 98.4% patients with trandolapril and 93% with enalapril achieved target DBP reduction at the end of eight weeks. In the present study, mean reduction in SBP and DBP was 22.17 and 9.57 mmHg in trandolapril group. In two noncomparative trials, where trandolapril was administered for a period of two weeks to 12 months in mild-to-moderate hypertension, mean reduction in SBP ranged from 7 to 31 mmHg and in DBP from 8 to 20 mmHg.12,13 Many controlled clinical trials have found that trandolapril produces clinically significant BP reduction and achieves target BP level in patients with hypertension.14,15 The observations reflect that trandolapril is equally efficacious and comparable to enalapril and that trandolapril offers a satisfactory approach for reduction of BP in mild-tomoderate hypertension. In this study, one patient from trandolapril group with LVH showed partial reversal. Schmieder16 observed in a meta-analysis that ACEIs brought about early and significant decrease in LVH mass and wall thickness in 13% of patients with a mean duration of 25 weeks. In this regard, there is a need to conduct further studies to confirm the observation. In the present study, cough was the common adverse event in both the groups, which accounted for 6.66% and 5% of patients, respectively. Many studies have proposed that bradykinin and substance P were responsible for the production of cough.17,18 In many studies, it was observed that the incidence of cough ranged from 2.3-39.1% and drug withdrawal was minimal.19,21 In the present study, we observed that cough was mild, transient and did not require discontinuation of medication or withdrawal from the study.

Clinical Study Conclusion The present study suggests that the efficacy and tolerability of trandolapril were comparable to enalapril in mild-to-moderate hypertension. Both drugs effectively controlled SBP and DBP at the end of eight weeks and were well-tolerated with few minor adverse events.

Acknowledgment Authors are thankful to M/s Hetero Drugs, Hyderabad for providing the clinical supplies.

References 1.

Hoffman BB. Therapy of Hypertension. In: Goodman and Gilman’s The Pharmacological Basis of Therapeutics. 11th edition, Brunton LL, Lazo JS, Parker KL (Eds.) McGrawHill Co: New York 2006:p. 845-50.

World Health Organization. Hypertension Control. World Health Organization. Geneva. 1996. WHO Technical Reports Series. 862.

Reddy R, Chahoud G, Mehta JL. Modulation of cardiovascular remodeling with statins: fact or fiction? Curr Vasc Pharmacol 2005;3(1):69-79.

Ramos-Nino ME, Blumen SR. Benefits of ACE inhibitors in diabetes. Clin Med Therapeut 2009;1:1041-51.

Parmley WW. Evolution of angiotensin-converting enzyme inhibition in hypertension, heart failure, and vascular protection. Am J Med 1998;105(1A):27S-31S.

Dézsi L. Fibrinolytic actions of ACE inhibitors: a significant plus beyond antihypertensive therapeutic effects. Cardiovasc Res 2000;47(4):642-4.

Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, et al; American College of Cardiology/ American Heart Association. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to revise the 1995 Guidelines for the Evaluation and Management of Heart Failure). J Am Coll Cardiol 2001;38(7):2101-13.

Diaz A, Ducharme A. Update on the use of trandolapril in the management of cardiovascular disorders. Vasc Health Risk Manag 2008;4(6):1147-58.

Wiseman LR, McTavish D. Trandolapril. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in essential hypertension. Drugs 1994;48(1):71-90.

10. Hsieh BP, Pham MX, Froelicher VF. Prognostic value of electrocardiographic criteria for left ventricular hypertrophy. Am Heart J 2005;150(1):161-7.

11. Shankar PK, Vidyasagar S, Adiga S, Naidu MU, Usha Rani P, Rao D, et al. Efficacy and tolerability of trandolapril in mild to moderate hypertension - a double blind comparative clinical trial with enalapril in Indian population. Indian J Physiol Pharmacol 2006;50(4):421-6. 12. Backhouse CI, Orofiamma B, Pauly NC. Long-term therapy with trandolapril, a new nonsulfhydryl ACE inhibitor, in hypertension: a multicenter international trial. Investigator Study Group. J Cardiovasc Pharmacol 1994;23 Suppl 4:S86-90. 13. Poirier L, Bourgeois J, Lacourcière Y. Once-daily trandolapril compared with the twice-daily formulation in the treatment of mild to moderate essential hypertension: assessment by conventional and ambulatory blood pressures. J Clin Pharmacol 1993;33(9):832-6. 14. Pepine CJ, Handberg EM, Cooper-DeHoff RM, Marks RG, Kowey P, Messerli FH, et al; INVEST Investigators. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003;290(21):2805-16. 15. Tytus RH, Burgess ED, Assouline L, Vanjaka A. A 26week, prospective, open-label, uncontrolled, multicenter study to evaluate the effect of an escalating-dose regimen of trandolapril on change in blood pressure in treatmentnaive and concurrently treated adult hypertensive subjects (TRAIL). Clin Ther 2007;29(2):305-15. 16. Schmieder RE, Martus P, Klingbeil A. Reversal of left ventricular hypertrophy in essential hypertension. A meta-analysis of randomized double-blind studies. JAMA 1996;275(19):1507-13. 17. Dendorfer A, Wolfrum S, Dominiak P. Pharmacology and cardiovascular implications of the kinin-kallikrein system. Jpn J Pharmacol 1999;79(4):403-26. 18. Ho CY, Gu Q, Hong JL, Lee LY. Prostaglandin E(2) enhances chemical and mechanical sensitivities of pulmonary C fibers in the rat. Am J Respir Crit Care Med 2000;162(2 Pt 1):528-33. 19. Adalet K, Buyukozturk K. Trandolapril in overweight patients with mild-to-moderate essential hypertension: the Turkish multicentre trandolapril study. Curr Ther Res 1996;57(12):980-9. 20. Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J, et al; PEACE Trial Investigators. Angiotensin-converting-enzyme inhibition in stable coronary artery disease. N Engl J Med 2004;351(20): 2058-68. 21. Gosse P, Vaur L, Dutrey-Dupagne C, Genes N, Destrée D, Elkik F. Evaluation of trandolapril alone or in combination with a calcium channel blocker in hypertensive patients over 60 years of age. Ann Cardiol Angeiol (Paris) 1995;44(9):517-24.

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photo quiz

Cyanosis in an Older Woman

n 82-year-old woman presented to the emergency department with right-sided leg pain and paresthesias that had lasted for five days. The patient had been bedridden for several years because of dementia. Examination revealed diffusely scattered cyanosis on the foot (see accompanying figure), ankle, and calf, but sparing the knee. Peripheral pulses, including popliteal, posterior tibial, and dorsal pedis, were absent on the affected side. Question Based on the patientâ&#x20AC;&#x2122;s history and physical examination, which one of the following is the most likely diagnosis?

C. Diabetic gangrene.

A. Blue toe syndrome.

D. Diffuse acute limb ischemia.

B. Buerger disease.

E. Postthrombotic syndrome. See the following page for discussion.

Source: Adapted from Am Fam Physician. 2010;81(12):1491-1492.

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photo quiz Discussion

Summary Table

The answer is D: diffuse acute limb ischemia.

Condition

Characteristics

Diffuse acute limb ischemia is caused by a sudden decrease in limb perfusion that threatens limb viability within two weeks of the acute event. The condition is called critical limb ischemia when symptoms last for more than two weeks.1

Blue toe syndrome

Acrocyanosis with strong pedal pulse and warm foot

Buerger disease

Skin examination typically shows a cool, pale extremity with delayed capillary refill. The level of occlusion is generally one joint above the line of demarcation between the normal and ischemic areas. The classic symptoms of large artery occlusion are described as the five Ps: pain, paleness, pallor, paresthesia, and paralysis. Irreversible damage occurs within six hours of ischemia. When arterial occlusion occurs in the setting of well-developed collateral circulation, the symptoms may be less remarkable (e.g., intolerance to ambulation, modest pain, paresthesia). Limb ischemia is more common in lower extremities than in upper extremities. Diagnosis can be made using arterial Doppler evaluation and angiography. Angiography is confirmatory and demonstrates the location and severity of the obstruction.2

Small and medium vessel vasculitis causing ischemic pain and ulceration; more common in smokers and persons of Asian descent

Diabetic gangrene

Nonhealing ulcer, typically in persons with long-standing history of diabetes mellitus and multiple foot infections

Diffuse acute limb ischemia

Progressive pain, paleness, pallor, paresthesia, and paralysis

Postthrombotic syndrome

Pain, swelling, and heaviness; stasis ulcer may develop

Acute limb ischemia is usually caused by embolic events, and therefore warrants investigation for an embolic source. Most embolic events are of cardiac or large artery origin. Cardiac disorders that can cause embolism include atrial fibrillation, myocardial infarction, and ventricular aneurysm. Atherosclerosis, or aneurysm of the aorta and other large arteries, is another embolic source of embolism. Although less common, a venous thrombus may enter systemic circulation through a patent foramen ovale or other septal defect.2 Arterial thrombosis may occur in atheromatous, aneurysmal, or traumatized vessels. Treatment of embolism includes prompt initiation of heparin to prevent propagation of the clot,1 followed by intra-arterial thrombolytic therapy with urokinase or surgical intervention (embolectomy or a bypass procedure). Nonviable tissue requires debridement, and amputation if necessary.3 Delayed amputation increases the risk of infection, myoglobinuria, acute renal failure, and hyperkalemia. After successful limb salvage, continuous anticoagulation with heparin followed by oral warfarin is recommended to prevent recurrence.2 Blue toe syndrome is an acute embolic event at the digital artery that leads to sudden, painful cyanosis in the toe despite strong pedal pulse and a warm foot.4 This condition is analogous to transient ischemic attack

in the central nervous system and leads to an impending ischemic event. Buerger disease is inflammation of distal arteries and veins causing ischemic pain and ulceration. Pathology shows inflammation of vessels; however, atherosclerosis is typically absent. Risk factors include Asian descent and cigarette smoking.2 Diabetic gangrene manifests as a nonhealing ulcer, typically on the toe. It is caused by the combination of arterial atherosclerosis and peripheral nerve damage. Diabetic gangrene typically develops after long-standing diabetes mellitus with multiple foot infections. Postthrombotic syndrome is a common complication of deep venous thrombosis. Typical features include pain, swelling, and heaviness; a stasis ulcer may develop.5 REFERENCES 1.

Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG; TASC II Working Group. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Vasc Surg. 2007;45(suppl S): S5-67.

Creager MA, Dzau VJ. Vascular disease of the extremities. In: Fauci AS, Braunwald E, Kasper DL, et al., eds. Harrison’s Principles of Internal Medicine. 17 ed. New York, NY: McGraw-Hill; 2008.

Clagett GP, Sobel M, Jackson MR, Lip GY, Tangelder M, Verhaeghe R. Antithrombotic therapy in peripheral artery occlusive disease: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 suppl):609S-626S.

Karmody AM, Powers SR, Monaco VJ, Leather RP. “Blue toe” syndrome. An indication for limb salvage surgery. Arch Surg. 1976;111(11):1263-1268.

Kahn SR. The post-thrombotic syndrome: progress and pitfalls. Br J Haematol. 2006;134(4):357-365.

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practice guidelines

ACCF/AHA Release Guideline for Early Cardiovascular Risk Assessment

therosclerotic cardiovascular disease is the leading cause of death among adults in the United States. Because coronary heart disease (CHD) has a long asymptomatic latent period, there is an opportunity for early preventive measures. The American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) have created a guideline to assist physicians with the early cardiovascular risk assessment of asymptomatic adults. The goal of this assessment is to guide targeted preventive efforts based on the patientâ&#x20AC;&#x2122;s individual risk. Initial evaluation includes broadly categorizing patients by risk. Further intervention is based on these risk assessments.

therapy in the following patients: men 50 years and older and women 60 years and older with a lowdensity lipoprotein cholesterol level less than 130 mg per dL (3.37 mmol per L) who are not on lipid-lowering medications, hormone therapy, or immunosuppressant therapy and do not have clinical CHD, diabetes mellitus, chronic kidney disease, severe inflammatory conditions, or contraindications to statins. Measurement of C-reactive protein levels may be reasonable in younger patients with intermediate cardiovascular risk, but is not recommended for high-risk patients.

Recommendations

Microalbuminuria. Urinalysis to detect microalbuminuria is reasonable in patients with hypertension or diabetes, and may be reasonable in intermediate-risk patients without these conditions.

Global Risk Scoring Global risk scores (e.g., Framingham Risk Score) that include multiple traditional cardiovascular risk factors effectively combine individual risk factor measurements into a single quantitative estimate of risk. These scores should be used in all cardiac risk assessment evaluations to guide the initiation of targeted preventive measures.

Family History and Genomic Testing Family history of atherothrombotic cardiovascular disease should be obtained, although genotype testing is not recommended.

Laboratory Testing Lipoprotein and Apolipoprotein. Lipid measurements, including lipoprotein levels, apolipoprotein levels, and particle size/density, beyond the standard lipid profile are not recommended. Natriuretic Peptide. Measurement of natriuretic peptide levels is not recommended. C-Reactive Protein. Measurement of C-reactive protein levels can be useful in selecting candidates for statin Source: Adapted from Am Fam Physician. 2011;84(2):234-235.

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A1C. Measurement of A1C levels may be reasonable in patients without diabetes to assess cardiovascular risk.

Lipoprotein-Associated Phospholipase A2. Measurement of lipoprotein-associated phospholipase A2 levels may be reasonable in intermediate-risk patients.

Imaging and Other Testing Resting Electrocardiography (ECG). Resting ECG is reasonable in patients with hypertension or diabetes, and may be considered in patients without these conditions. Transthoracic Echocardiography. Echocardiography to detect left ventricular hypertrophy may be considered in patients with hypertension, but is not recommended in those without hypertension. Carotid Intima-Media Thickness. Measurement of carotid intima-media thickness is reasonable in intermediaterisk patients; however, high-quality results are dependent on properly performing the test. Brachial/Peripheral Flowâ&#x20AC;&#x201C;Mediated Dilation. Peripheral arterial flowâ&#x20AC;&#x201C;mediated dilation is not recommended. Arterial Stiffness. Measurement of arterial stiffness is not recommended outside of research settings.

practice guidelines Ankle-Brachial Index. Measurement of ankle-brachial index is reasonable for intermediate-risk patients. Exercise and stress ECG. Exercise ECG may be considered in intermediate-risk patients (including sedentary adults who are considering a vigorous exercise program), particularly if non-ECG markers, such as exercise capacity, are noted. Stress Echocardiography. Stress echocardiography is not recommended in low- or intermediate-risk patients. It is used mainly in the advanced cardiac evaluation of symptomatic patients to estimate prognosis in those with known coronary artery disease and to assess those with known or suspected valvular heart disease. Myocardial Perfusion Imaging. Stress myocardial perfusion imaging may be considered in patients with diabetes or a strong family history of CHD, or if a previous risk assessment suggested high risk of CHD. It is not

indicated for patients with low or intermediate risk, and is used mainly in the advanced cardiac evaluation of symptomatic patients and to estimate prognosis in patients with known coronary artery disease. Calcium Scoring Methods. Measurement of cardiac calcium levels is reasonable in patients with intermediate risk (10 to 20 percent 10-year risk), may be reasonable in those with low to intermediate risk (6 to 10 percent 10year risk), and is not recommended in patients with low risk (less than 6 percent 10-year risk). Measurement of cardiac calcium levels is reasonable in patients 40 years and older with diabetes. Coronary Computed Tomography Angiography. Coronary computed tomography angiography is not recommended. Magnetic Resonance Imaging. Magnetic resonance imaging for detection of vascular plaque is not recommended.

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around the globe

News and Views Non-HDL-C levels linked to risk for cardiovascular events Levels of non-high-density lipoprotein cholesterol (non-HDL-C) among users of statins is linked to the risk for a major cardiovascular event, such as a heart attack or stroke, more strongly than are levels of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB). The finding, from a meta-analysis of data from eight trials comprising a total of 62,154 patients, is published in the March 28 issue of JAMA. (Source: Medscape) Frequent chocolate consumption linked to lower BMI A recent study showed that frequent chocolate consumption was associated with lower body mass index (BMI), even when adjusting for calorie intake, saturated fat intake and mood. Beatrice A. Golomb, MD, PhD, associate professor of medicine at the University of California, San Diego and colleagues described their findings in a research letter published in the March 26 issue of the Archives of Internal Medicine. (Source: Medscape)

Infection May Trigger Venous Clots A new study found that factors increasing the risk of hospitalization for venous thromboembolism included: Infection (especially respiratory tract infection), erythropoiesis-stimulating drugs and blood transfusion. These factors, particularly infection, are not included in traditional risk assessment for hospitalized patients. (Mary Rogers, PhD, of the University of Michigan in Ann Arbor, and colleagues in Circulation: Journal of the American Heart Association.) Statins Often Ignored After Surgery A new study has shown that failure to restart statins after head and neck surgery is associated with an elevated risk for death and other cardiovascular adverse outcomes. Among patients who died or had a myocardial infarction, unstable angina, stroke or congestive heart failure at 30 days, 75% had been chronic statin users and had not had the treatment restarted within four days after the surgery, reported Vineet Chopra, MD, of the University of Michigan in Ann Arbor. (Annual meeting of the Society of Hospital Medicine.) AAA Repair Weaker for Women

It is time to adopt a consistent definition of frailty and simple metrics to evaluate older adults with cardiovascular disease (CVD), according to a review. Evidence, although sparse, suggests that simple, well-established performance measures can be highly predictive of clinical outcomes in these patients, reported Rebecca Gary, PhD, RN, from the Nell Hodgson Woodruff School of Nursing at Emory University in Atlanta. (Source: Medpage Today)

Women have a lower chance of surviving elective open abdominal aortic repair, and this retrospective evaluated whether the same holds true for elective endovascular aneurysm (EVAR) repair. For women, elective EVAR resulted in significantly greater mortality rates than men and a greater incidence of intraoperative and postoperative complications. (Manish Mehta, MD, MPH, of the Institute for Vascular Health and Disease at Albany Medical College in Albany, N.Y., and colleagues reported in April issue of the Journal of Vascular Surgery.)

Coronary stents provide solid long-term results in younger adults

Be Cautious When Giving Painkillers To Patients With High Cholesterol

Young adults who received coronary artery stents through age 40 had excellent short- and long-term results, and the Italian researchers who reported this finding say the devices should be the treatment of choice in this age group. (Source: Medscape)

One should not give long-term nonsteroidal antiinflammatory drugs (NSAIDs) such as naproxen to patients with high cholesterol. In a swine model study published in the journal Surgery, Dr Frank Sellke, chief of cardiothoracic surgery and research at Rhode Island

Clearer meaning of frailty needed in CVD

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around the globe Hospital found that a high-cholesterol diet reduced blood flow to the heart muscle in animal models with chronic heart disease when given daily naproxen. They also found reduced levels of prostacyclin, a compound that dilates blood vessels and prevents blood clots. These findings suggest that there may be a stronger risk of negative effects on the heart in patients who have high cholesterol levels and are taking NSAIDs as a form of pain or inflammation relief. (Source: (http://csinews.emedinews in/2012/04/10/be cau-tious-when-giving-painkillers-to-patients-with-highcholesterol/) Most Fat People Don’t Think They Are Fat: Study NEW DELHI: How many fat people think they are fat? “Hardly,” said half a dozen doctors TOI spoke to. Most of them said, “Majority of our obese patients don’t think they are fat enough to be in trouble.” Experts now say misperception of weight is becoming a major barrier to weight loss - a serious problem in India which has seen a nearly 20% increase in overweight population rates between 1998 and 2005. Take for example a recent University of Illinois study by researchers who surveyed over 3,500 college applicants. More than a third couldn’t report their weight accurately and overweight and obese men were more likely to underestimate their weight than women. In physical exams, the height, weight and BMI of 3,622 18- to 20-year-old applicants to the Mexican University were recorded. Around 33.6% were overweight or obese, but only 16.9% described themselves as being in those categories. Women seemed to be a better judge of their weight than men with the gap between the former’s perception and reality on their weight being smaller-

27.8% of women were actually overweight or obese, but only 21.2% believed that they were. The study findings have serious implications for India where currently, one in 5 men and over one in 6 women are overweight. In some urban areas, the rates are as high as 40%. (Source: TOI, Apr. 9, 2012) Mitral Regurgitation: Early Hazard, Later Gains Following TAVI Moderate-to-severe mitral regurgitation (MR) is relatively common in patients undergoing transcatheter aortic valve implantation and is associated with a doubling in risk of 30-day death, a new series suggests. Beyond this initial period, however, survival among MR patients is just as good as among patients with no MR, and MR itself is likely to improve over time, authors of a new analysis say. (Source: Medscape) Cardiac Biomarkers In NonValvular AF Two common cardiac biomarkers - troponin I and N-terminal pro-B-type natriuretic peptide (NT-pro BNP) can improve risk prediction among patients with nonvalvular atrial fibrillation (AF), a RE-LY substudy showed. Elevations of both biomarkers were associated with greater risks of stroke or systemic embolism, vascular mortality and a composite of thromboembolic events, according to Ziad Hijazi, MD, of Uppsala University in Sweden, and colleagues. High troponin I levels also were associated with increased risks of myocardial infarction (MI) and major bleeding, the researchers reported online in Circulation: Journal of the American Heart Association. [Medpage]

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lighter reading

One day I decided to quit… I quit my job, my relationship, my spirituality. I wanted to quit my life. I went to the woods to have one last talk with God. “God”, I said. “Can you give me one good reason not to quit?”

“Yes.” He said, “Give me glory by rising as high as you can”. I left the forest and bring back this story. I hope these words can help you see that God will never give up on you. He will never give up on you. Never regret a day in your life. —Dr GM Singh

His answer surprised me. “Look around”, He said. “Do you see the fern and the bamboo?”

“When I planted the fern and the bamboo seeds, I took very good care of them. I gave them light. I gave them water. The fern quickly grew from the earth. Its brilliant green covered the floor. Yet nothing came from the bamboo seed. But I did not quit on the bamboo. In the second year the Fern grew more vibrant and plentiful. And again, nothing came from the bamboo seed. But I did not quit on the bamboo”. He said. “In the third year, there was still nothing from the bamboo seed. But I would not quit. In the fourth year, again, there was nothing from the bamboo seed. “I would not quit.” He said. “Then in the fifth year a tiny sprout emerged from the earth. Compared to the fern it was seemingly small and insignificant. But just 6 months later the bamboo rose to over 100 feet tall. It had spent the five years growing roots. Those roots made it strong and gave it what it needed to survive. I would not give any of my creations a challenge it could not handle.” He said to me. “Did you know, my child, that all this time you have been struggling, you have actually been growing roots.” “I would not quit on the bamboo. I will never quit on you”.

Laugh a While

“Yes”, I replied.

Feline Physics

Law of Cat Inertia A cat at rest will tend to remain at rest, unless acted upon by some outside force-such as the opening of cat food, or a nearby scurrying mouse. —Dr GM Singh

An optimist is the human personification of spring.

quotes

An Inspirational Story

Lighter Side of Medicine

—Susan J. Bissonette

The attempt to silence a man is the greatest honour you can bestow on him. It means that you recognize his superiority to yourself. —Joseph Sobran

Dr. Good and Dr. Bad Situation: A patient had an episode of TIA.

Start aspirin 150 mg/day

Start aspirin 300 mg/day

©IJCP Academy

Don’t compare yourself to others.” He said. “The bamboo had a different purpose than the fern. Yet, they both make the forest beautiful.” Your time will come, “God said to me.” You will rise high! “How high should I rise?” I asked. How high will the bamboo rise?” He asked in return. “As high as it can?” I questioned.

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Lesson: The recommended dose of aspirin for stroke prevention is 300 mg/day as against coronary artery disease prevention where the dose is 150 mg/day.

Dr KK Aggarwal

Asian

Journal of

CLINICAL CARDIOLOGY

Information for Authors

Manuscripts should be prepared in accordance with the ‘Uniform requirements for manuscripts submitted to biomedical journals’ compiled by the International Committee of Medical Journal Editors (Ann. Intern. Med. 1992;96: 766-767). Asian Journal of Clinical Cardiology strongly disapproves of the submission of the same articles simultaneously to different journals for consideration as well as duplicate publication and will decline to accept fresh manuscripts submitted by authors who have done so. The boxed checklist will help authors in preparing their manuscript according to our requirements. Improperly prepared manuscripts may be returned to the author without review. The checklist should accompany each manuscript. Authors may provide on the checklist, the names and addresses of experts from Asia and from other parts of the World who, in the authors’ opinion, are best qualified to review the paper. Covering letter -

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The covering letter should explain if there is any deviation from the standard IMRAD format (Introduction, Methods, Results and Discussion) and should outline the importance of the paper. Principal/Senior author must sign the covering letter indicating full responsibility for the paper submitted, preferably with signatures of all the authors. Articles must be accompanied by a declaration by all authors stating that the article has not been published in any other Journal/Book. Authors should mentioned complete designation and departments, etc. on the manuscript.

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All pages should be numbered consecutively beginning with the title page.

departments and institutions where the work was performed, name of the corresponding authors, acknowledgment of financial support and abbreviations used. - The title should be of no more than 80 characters and should represent the major theme of the manuscript. A subtitle can be added if necessary. - A short title of not more than 50 characters (including inter-word spaces) for use as a running head should be included. - The name, telephone and fax numbers, e-mail and postal addresses of the author to whom communications are to be sent should be typed in the lower right corner of the title page. - A list of abbreviations used in the paper should be included. In general, the use of abbreviations is discouraged unless they are essential for improving the readability of the text. Summary - The summary of not more than 200 words. It must convey the essential features of the paper. - It should not contain abbreviations, footnotes or references. Introduction - The introduction should state why the study was carried out and what were its specific aims/objectives. Methods - These should be described in sufficient detail to permit evaluation and duplication of the work by others. - Ethical guidelines followed by the investigations should be described. Statistics The following information should be given: - The statistical universe i.e., the population from which the sample for the study is selected. - Method of selecting the sample (cases, subjects, etc. from the statistical universe). - Method of allocating the subjects into different groups. - Statistical methods used for presentation and analysis of data i.e., in terms of mean and standard deviation values or percentages and statistical tests such as Student’s ‘t’ test, Chi-square test and analysis of variance or non-parametric tests and multivariate techniques.

Note: Please keep a copy of your manuscript as we are not responsible for its loss in the mail. Manuscripts will not be returned to authors.

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Discussion -

This should consist of a review of the literature and relate the major findings of the article to other publications on the subject. The particular relevance of the results to healthcare in India should be stressed, e.g. practicality and cost.

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Illustrations must be drawn neatly by an artist and photographs must be sent on glossy paper. No captions should be written directly on the photographs or illustration. Legends to all photographs and illustrations should be typed on a separate sheet of paper. All illustrations and figures must be referred to in the text and abbreviated as ‘Fig.’. Please complete the following checklist and attach to the manuscript: 1. Classification (e.g. original article, review, selected summary, etc.)_______________________________

Paintal AS. Impulses in vagal afferent fibres from specific pulmonary deflation receptors. The response of those receptors to phenylguanide, potato S-hydroxytryptamine and their role in respiratory and cardiovascular reflexes. Q. J. Expt. Physiol. 1955;40:89-111.

2. Total number of pages ________________________

Books

6. Suggestions for reviewers (name and postal address)

Stansfield AG. Lymph Node Biopsy Interpretation Churchill Livingstone, New York 1985.

Indian 1.____________Foreign 1._ _______________

2.____________

2._ _______________

Articles in Books

3.____________

3._ _______________

Strong MS. Recurrent respiratory papillomatosis. In: Scott Brown’s Otolaryngology. Paediatric Otolaryngology Evans JNG (Ed.), Butterworths, London 1987;6:466-470.

4.____________

4._ _______________

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The legend must include enough information to permit interpretation of the figure without reference to the text.

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3. Number of tables ____________________________ 4. Number of figures ___________________________ 5. Special requests _____________________________

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Online Submission Also e-issue @ www.ijcpgroup.com For Editorial Correspondence

Dr KK Aggarwal

Group Editor-in-Chief Asian Journal of Clinical Cardiology E - 219, Greater Kailash, Part - 1, New Delhi - 110 048. Phone: 011-40587513 E-mail: editorial@ijcp.com, emedinew@gmail.com Website: www.ijcpgroup.com