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Table of Contents 14
ew Recommendations Managing N Depression During Pregnancy — Kimberly A. Yonkers, MD
18
The Burden of Uncontrolled Asthma — Reynold A. Panettieri, Jr., MD
112
anaging Symptomatic OA M of the Knee
— John C. Richmond, MD
114
Markers of Arterial Inflammation
— Bradley F. Bale, MD
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January 11, 2010 • Issue No. 2 Click here to view this article online.
Ne
Depres
Kimberly A. Yonkers, MD Professor of Psychiatry Professor of Obstetrics, Gynecology, and Reproductive Sciences Director, PMS & Perinatal Research Program Yale University School of Medicine
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ew Recommendations Managing
ssion During Pregnancy New recommendations have been unveiled to help physicians and patients weigh the risks and benefits of various treatment interventions for depression during pregnancy.
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t has been estimated that between 14% and 23% of pregnant women will experience depressive symptoms during their pregnancy. An investigation published in 2003 reported that about 13% of women take an antidepressant at some time during their pregnancy. “Depression in pregnant women frequently goes unrecognized and untreated for a host of reasons, including concerns about the safety of some treatments for pregnant patients and their offspring,” says Kimberly A. Yonkers, MD. “There may be risks associated with both untreated depression and the use of antidepressants that can complicate treatment decisions.”
A New Review An evidence-based report from the American Psychiatric Association (APA) and the American College of Obstetricians and Gynecologists (ACOG) has been published to assist clinicians and patients as they weigh the risks and benefits of various treatment options for
depression during pregnancy. The APA and ACOG convened a work group consisting of clinical research experts within the fields of obstetrics and gynecology, psychiatry, and pediatrics, which critically evaluated and summarized information about risks associated with depression and the use of antidepressants during pregnancy. The resulting recommendations were published jointly in the September 2009 issue of Obstetrics & Gynecology and the September/October 2009 issue of General Hospital Psychiatry. “Typically, OB-GYNs, nurse practitioners, and nurse midwives are the clinicians who most often see women who are pregnant,” says Dr. Yonkers. “They can be the first clinician to make a diagnosis of depression in some cases. Other times, they may be the first to observe depressive symptoms that are worsening. In the past, reproductive health practitioners have reported feeling ill-prepared to treat these patients because of the lack of
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Table
An Overview of Recommendations
Women Considering Pregnancy: • For women on medication with mild or no symptoms for 6 months or longer, it may be appropriate to taper and discontinue medication before becoming pregnant. • Medication discontinuation may not be appropriate in women with: - A history of severe, recurrent depression. - Psychosis.
- B ipolar disorder.
- Other psychiatric illness requiring medication. - A history of suicide attempts. • Women with suicidal or acute psychotic symptoms should be referred to a psychiatrist for aggressive treatment. Pregnant Women Currently on Depression Medication: • Psychiatrically stable women who prefer to stay on medication may be able to do so after consultation between their psychiatrist and OB-GYN to discuss risks and benefits. • Women who would like to discontinue medication may attempt medication tapering and discontinuation if they are not experiencing symptoms, depending on their psychiatric history. - Women with a history of recurrent depression are at a high risk of relapse if medication is discontinued. • Women with recurrent depression or who have symptoms despite their medication may benefit from psychotherapy to replace or augment medication. • Women with severe depression (with suicide attempts, functional incapacitation, or weight loss) should remain on medication. - If a patient refuses medication, alternative treatment and monitoring should be in place, preferably before discontinuation. Pregnant Women Not Currently on Depression Medication: • Psychotherapy may be beneficial in women who prefer to avoid antidepressant medication. • For women who prefer taking medication, risks and benefits of treatment choices should be evaluated and discussed, including factors such as: - Stage of gestation.
- Symptoms.
- History of depression. - Other conditions and circumstances (eg, a smoker, difficulty gaining weight). All Pregnant Women: • Regardless of circumstances, a woman with suicidal or psychotic symptoms should immediately see a psychiatrist for treatment. Source: Adapted from: Yonkers KA, et al. Obstet Gynecol. 2009;114:703-713.
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evidence-based guidance. With the publication of these recommendations, our hope is that we’ll better inform providers about current research on various depression treatment methods and improve clinicians’ understanding and ability to help with decision making.”
Diagnostic Challenges & Consequences Identifying depression in pregnant women can be difficult because depressive symptoms often mimic usual experiences of pregnancy. “Some symptoms of depression, including changes in mood, energy level, appetite, and cognition, are normative in pregnancy,” explains Dr. Yonkers. “When these symptoms present, clinicians should view them as a cue to ask additional questions. We must also consider the likelihood that patients may be reluctant to admit feelings of depression. There is a belief that women are supposed to be happy when they’re pregnant, so they may be embarrassed to admit that they aren’t. Other women may view their depressed feelings as a character flaw rather than an illness, or they may believe that depression will reflect negatively on their capability of being a good mother.” Research has shown that depressive symptoms and use of antidepressant medications during pregnancy have been associated with negative consequences for newborns. Infants born to women with depression are at greater risk for irritability, less activity and attentiveness, and fewer facial expressions when compared with those born to mothers without depression. Depression during pregnancy is also associated with fetal growth changes and shorter gestation periods. Dr. Yonkers adds that some studies have linked fetal malformations, cardiac defects, pulmonary hypertension, and reduced birth weight to antidepressant use during pregnancy. “Furthermore, depressed women are more likely to have poor prenatal care and pregnancy complications (eg, nausea, vomiting, and preeclampsia) and to use drugs, alcohol, and nicotine,” she says.
Highlighting Key Recommendations According to the APA/ACOG report, some patients with mild-to-moderate depression can be treated with psychotherapy alone or in combination with medication. “There is no one-size-fits-all approach for managing depression during pregnancy,” Dr. Yonkers says. “Management approaches should depend on specific scenarios, patient characteristics, and severity of depression. The APA/ACOG report provides algorithms to help clinicians during their care of these women. It should be noted that there are more ways to inter-
As providers, we can’t only look at one part of the picture in isolation and simply take all patients off antidepressants. We need to recognize that our treatment strategies and decisions may have profound effects during pregnancy. —Kimberly A. Yonkers, MD vene than to simply medicate or do nothing. Pregnant women with severe recurrent depression should be considered for some sort of treatment, be it psychological, medical, or both.”
depressants. We need to recognize that our treatment strategies and decisions may have profound effects during pregnancy.”
One of the key recommendations of the APA/ACOG report is that there needs to be ongoing consultation between OB-GYNs, psychiatrists, and other healthcare providers during pregnancy (Table). “A collaborative approach is paramount,” says Dr. Yonkers. “The more communication there is within this triad of providers, the better. We should seek to form a united front when dealing with a severe depressive disorder in this patient group.”
Dr. Yonkers says that there is some existing research relating to antidepressant use in pregnancy, but more data are needed. “We have yet to adequately control for other factors that may influence birth outcomes, including maternal illness or health behaviors that can adversely affect pregnancy,” she says. “Few studies of antidepressants and birth outcomes assessed the mothers’ psychiatric condition. Confounding factors that influence birth outcomes—poor prenatal care and drug, alcohol, and nicotine use—are often not controlled in studies. Our recommendations may be utilized as a guide to foster more in-depth research. In the meantime, our hope is that they are used as a resource when caring for pregnant women who have or are at risk of developing major depressive disorder.”
Physicians and providers should remember that women taking antidepressants prior to pregnancy received these medications for good reason, says Dr. Yonkers. “As providers, we can’t only look at one part of the picture in isolation and simply take all patients off anti-
More Data Needed
Kimberly A. Yonkers, MD, has indicated to Physician’s Weekly that in the past year she has received an investigator initiated trial funded by Eli Lilly and has received study medication from Pfizer for an NIMH funded trial.
References Yonkers KA, Wisner KL, Stewart DE, et al. The management of depression during pregnancy: a report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists. Obstet Gynecol. 2009;114:703-713. Available at: http://journals.lww.com/greenjournal/Citation/2009/09000/The_Management_ of_Depression_During_Pregnancy__A.44.aspx Smith MV, Shao L, Howell H, Wang H, Poschman K, Yonkers KA. Success of mental health referral among pregnant and postpartum women with psychiatric distress. Gen Hosp Psychiatry. 2009;31:155-162. Yonkers KA. Parsing risk for the use of selective serotonin reuptake inhibitors in pregnancy. Am J Psychiatry. 2009;166:268-270. Yonkers KA, Smith MV, Lin H, Howell HB, Shao L, Rosenheck RA. Depression screening of perinatal women: an evaluation of the healthy start depression initiative. Psychiatr Serv. 2009;60:322-328. Spoozak L, Gotman N, Smith MV, Belanger K, Yonkers KA. Evaluation of a social support measure that may indicate risk of depression during pregnancy. J Affect Disord. 2009;114:216-223. Yonkers KA. The treatment of women suffering from depression who are either pregnant or breastfeeding. Am J Psychiatry. 2007;164:1457-1459.
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September 14, 2009 Issue No. 35 Click here to view this article online.
The Burden of
Uncontrolled Asthma New survey data show that many patients are misinterpreting their level of asthma control, underscoring the need for better physician-patient communication.
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A
ccording to the Asthma and Allergy Foundation of America (AAFA), asthma affects more than 22 million Americans. Data from 2004 have shown that it accounts for 1.8 million emergency room visits, 500,000 hospitalizations, and 4,000 deaths each year. For children, asthma is associated with nearly 13 million missed days of school, ranking as the leading cause of school absenteeism. In adults, the disease leads to more than 10 million missed days of work annually. The AAFA recently conducted a nationwide telephone survey of asthma sufferers
and physicians to determine the existing gaps between awareness and perceptions of the disease. The survey was the second phase of the Asthma G.A.P. in America: General Awareness and Perceptions survey (www. AsthmaGap.com), which was initially launched in 2007 and revealed widespread misperceptions about asthma control.
Patient Misconceptions Persist The AAFA survey demonstrated that most asthma patients know the risks of “uncontrolled asthma,” but they misinterpret asthma control. “Patients are not realizing that asthma is a chronic disease that requires long-term therapy, even when asthma symptoms aren’t present,” says Reynold A. Panettieri, Jr., MD (Table 1). “Most patients—about 97%—understand that uncontrolled asthma poses serious health risks,
Reynold A. Panettieri, Jr., MD Robert L. Mayock and David A. Cooper Professor of Medicine Director, Airways Biology Initiative University of Pennsylvania Medical Center Adjunct Professor Wistar Institute
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There’s a striking divide between what patients know about their asthma and the actions they take to optimize control of their symptoms. — Reynold A. Panettieri, Jr., MD but 70% of those who had taken asthma controller medicines stopped their prescribed long-term treatment because they incorrectly believed their asthma was under control. Nearly a third didn’t believe that it’s harmful to stop taking controller medications if they’re not having symptoms.” When left untreated, the chronic inflammation that occurs in asthma can lead to progressive loss of lung function and other severe consequences. “For patients
Asthma Medication: Patient Beliefs & Usage
Table 1
•2 1% of asthma patients do not see risks associated with not taking controllers as instructed by their physician. •2 9% of asthma patients do not see risks associated with stopping their controller if they are not experiencing symptoms. •6 9% of asthma patients think that “quick-relief” medications can be used every day. •4 2% of asthma patients agree that it is appropriate to take controllers less regularly when symptoms decrease. •2 5% of asthma patients say it is appropriate to stop taking a controller when they are no longer experiencing asthma symptoms. • 92% of asthma patients report that controller medication works best when taken every day, but only 84% report taking their controller daily. •2 8% of asthma patients have stopped taking their controller medication. • N otable percentages of patients who have stopped taking their controller have had an asthma attack with considerable repercussions: - 21% required treatment with steroid pills. - 17% had an emergency doctor visit. - 12% missed work. - 12% went to the emergency room. Source: Adapted from: Asthma G.A.P. II Survey. September 2008. Available at: www.asthmagap.com/for-the-media/gap-survey-2-2008/general-data/.
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with persistent asthma, controller medications or maintenance therapies can help manage chronic lung inflammation,” Dr. Panettieri explains. “When taken over the long term, asthma controller medications have been shown to control disease-related symptoms and improve lung function. This survey shows that there’s a striking divide between what patients know about their asthma and the actions they take to optimize control of their symptoms.” Among all patients surveyed, many who had stopped taking their controller medications in the past 12 months reported experiencing a sudden asthma episode that led to some consequence. “The troubling part of this finding,” says Dr. Panettieri, “is that these problems are occurring even though 93% of patients indicated that controller medications work best when taken every day.”
Concern for Physicians The AAFA also assessed physician beliefs and attitudes on asthma (Table 2). About 80% of physicians revealed that they were concerned that if their patients stopped their asthma controller medications, they may face serious consequences, including frequent, unexpected hospitalizations and trips to the emergency room. About 55% of physicians believed that only between 40% and 60% of patients were taking their controllers as instructed. Of the 300 physicians surveyed, only two believed that 90% or 100% of their patients took their controllers as instructed. “Most physicians believe that it can be difficult to explain the role of inflammation to patients because airway inflammation is not transparent until acute symptoms are present,” Dr. Panettieri says. “This underscores the need for more physician-to-patient education about asthma control and appropriate therapies.”
Each time an exacerbation occurs, Dr. Panettieri says that physicians can often enable patients to get better with therapy. “However, we need to recognize that some patients will never have their lung function return to their pre-exacerbation levels. This loss-offunction effect is important to recognize. As such, physicians need to take steps toward focusing on the prevention of exacerbations.”
Action Plans Required Clinicians and patients also need to work collaboratively to enhance outcomes. “The first step to asthma control is for patients and physicians to create an asthma action plan, which may include a controller therapy,” Dr. Panettieri says. “Physicians should refer to current asthma management guidelines, such as those from the National Heart, Lung, and Blood Institute. Asthma is properly controlled when patients are able to carry out all their normal daily activities. When oral corticosteroid therapy is required, patients should experience a decrease in weekly symptoms—no more than two times per week—and in yearly asthma attacks—no more than one attack per year. Action plans should be developed for patients who may experience minor exacerbations as well as for situations in which major attacks occur. Proper care
Table 2
Physicians’ Attitudes Toward Asthma
• 98% of physicians believe there are serious risks associated with uncontrolled asthma. •8 6% of physicians think that their patients believe there are serious risks associated with uncontrolled asthma. •8 3% of physicians predicted their patients would agree that asthma controllers work best when taken every day. •7 8% of physicians believe that the main reason behind the difficulty of explaining the role of inflammation to patients is that airway inflammation is not apparent to patients until they are feeling symptoms. • 55% of physicians believe that between 40% and 60% of patients take their controllers as instructed. • 36% of physicians believe that it is appropriate for patients with moderate to severe asthma to take controller medications less regularly or stop taking them completely if symptoms subside. Source: Adapted from: Asthma G.A.P. II Survey. September 2008. Available at: www.asthmagap.com/for-the-media/gap-survey-2-2008/general-data/.
and treatment is paramount to helping patients gain better control of their asthma symptoms. Physicians should help their patients take action to better manage symptoms through appropriate treatment, tools, and resources, many of which are available at www.AsthmaGap.com.”
Reynold A. Panettieri, Jr., MD, has indicated to Physician’s Weekly that he has worked as a consultant and paid speaker for Merck and AstraZeneca, and has received grants/research aid from AstraZeneca and Immune Control.
References Asthma G.A.P. II Survey. Ipsos Public Affairs on behalf of AstraZeneca. September 2008. Available at: http://www.asthmagap.com/for-the-media/gap-survey-2-2008/general-data National Asthma Education and Prevention Program (NAEPP). Guidelines for the Diagnosis and Management of Asthma: General Mechanisms and Role in Therapy, October 16, 2007. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf National Heart, Lung and Blood Institute. Expert Panel Report 3 (EPR3): Guidelines for the Diagnosis and Management of Asthma. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm National Heart, Lung and Blood Institute. Asthma. Available at: http://www.nhlbi.nih.gov/health/dci/Diseases/Asthma/Asthma_Treatments.html Centers for Disease Control. Asthma Prevalence, Health Care Use and Mortality, 2003-2005. Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/ashtma03-05/asthma03-05.htm Asthma and Allergy Foundation of America. Asthma Facts and Figures. Available at: http://www.aafa.org/display.cfm?id=8&sub=42
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May 11, 2009 • Issue No. 18 Click here to view this article online.
Managing
Symptomatic OA
of the Knee
A
ccording to recent estimates, about 9.3 million adults have symptomatic osteoarthritis (OA) of the knee. The condition is estimated to affect 5% of all adults aged 26 and older, 17% of adults aged 45 and older, and 12.1% for adults aged 60 and older. The incidence of symptomatic OA of the knee increases with age, especially for women. Current trends suggest that the emotional and physical impact of OA will continue to increase in the future.
Patients with OA of the knee often experience joint pain, stiffness, and functional deficits. Effective treatments and prevention strategies for OA of the knee have emerged. The primary goals of treatment are to achieve pain relief and to improve or maintain functional status. Most treatments have been associated with some known risks, especially invasive procedures, and contraindications vary widely. In December 2008, the American Academy of Orthopaedic Surgeons (AAOS) released a clinical practice guideline for knee OA, updating guidelines that were last published in the 1990s. Available online at www.aaos.org, the new guideline focuses largely on treatments that are less invasive than knee replacement surgery.
Inform Patients About Options John C. Richmond, MD Professor, Orthopedic Surgery Tufts University School of Medicine Staff Surgeon New England Baptist Hospital
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Treatment for symptomatic OA of the knee, according to the AAOS guidelines, should be based on the premise that physicians have informed patients about the available treatments and procedures that are applicable to them. Ensuring informed decision making is essential to achieving and sustaining good outcomes. Clinician input—based on experience with
Physicians need to collaborate with other care providers and patients to weigh the potential risks and benefits of interventions under consideration. — John C. Richmond, MD conservative management and surgical skills—can increase the probability of identifying patients who’ll benefit from specific treatment options. Physicians need to collaborate with other care providers and patients to weigh the potential risks and benefits of interventions under consideration.
Encourage Weight Loss The AAOS guidelines provide information on patient education, lifestyle modifications, and physical rehabilitation when managing symptomatic OA of the knee. Patients should be encouraged to participate in self-management educational programs and incorporate more physical activity into their lives. Overweight patients are encouraged to lose a minimum of 5% of their body weight and maintain their lower weight with diet and exercise to avoid invasive procedures and treatments. Physical rehabilitation is often beneficial as well. Patients should be directed to participate in low-impact aerobic fitness exercises. Range of motion and flexibility exercises and quadriceps strengthening should also be encouraged.
When to Use Therapies, Interventions, & Surgery For patients with symptomatic OA of the knee, the AAOS guidelines recommend patellar taping for short-term pain relief and improvement in function. Intra-articular corticosteroids are suggested for shortterm pain relief. Analgesics such as acetaminophen and NSAIDs can also be used for pain relief, but the guidelines note that people at high risk for gastrointestinal bleeding need to consider other analgesics, such as topical NSAIDs, non-selective oral NSAIDs plus a gastro-protective agent, or COX-2 inhibitors. With regard to surgery, an important recommendation in the guidelines surrounds use of arthroscopy to manage symptomatic OA. The guidelines recommend against performing arthroscopy with debridement or lavage in patients with a primary diagnosis. However, arthroscopic partial meniscectomy or loose body removal can be a treatment option in patients who also have primary signs and symptoms of a torn meniscus and/or a loose body. The key is to be selective when deciding which patients should receive arthroplasty to manage symptomatic OA of the knee.
John C. Richmond, MD, has indicated to Physician’s Weekly that he has or has had no financial interests to report.
References American Academy of Orthopaedic Surgeons. Guideline on the treatment of osteoarthritis (OA) of the knee. Available at: www.aaos.org Richmond JC. Surgery for osteoarthritis of the knee. Med Clin North Am. 2009;93:213-222. American Academy of Orthopaedic Surgeons. The Burden of Musculoskeletal Diseases in the United States. American Academy of Orthopaedic Surgeons; 2008. Samson DJ, Grant MD, Ratko TA, Bonnell CJ, Ziegler KM, Aronson N. Treatment of Primary and Secondary Osteoarthritis of the Knee. Rockville, MD: Agency for Healthcare Research and Quality; 2007. Report No. 157. Zhang W, Moskowitz RW, Nuki MB, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidleines and systematic review of current research evidence. Osteoarthritis Cartilage. 2007;15:981-1000. Zhang W, Moskowitz RW, Nuki MB, et al. OARSI recommendations for management of hip and knee osteoarthritis, part II:OARSI evidence-based, expert consensus guidelines. Osteoarthritis Cartilage. 2007;16:137-162.
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August 31, 2009 • Issue No. 33 Click here to view this article online.
Markers of
Arterial Inflammation T
raditional risk factor identification remains an important approach to preventing cardiovascular disease (CVD), but catching the known risk factors alone fails to identify many people with hidden CVD risk. Approximately 50% of all coronary events strike people with low-to-moderate cholesterol levels, and about 20% occur in people with none of the four major risk factors (high cholesterol, high blood pressure, smoking, or diabetes). As such, there is a critical need to improve the ability to identify all at-risk patients.
Part of the disease process in CVD involves arterial inflammation, which may occur at any point—from its inception to the culmination in a vascular event (eg, a heart attack or stroke). Reliable tests for vascular inflammation are available and can benefit clinicians when predicting CVD risk. Inflammatory markers may further help identify a substantial number of patients with hidden cardiovascular risk. When these people are
identified early, medical management can be initiated and sustained to help patients avoid CVD events.
Assessing Key Markers Highly sensitive C-reactive protein (hs-CRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are two well-established markers of arterial inflammation. While hs-CRP is a good test to identify inflammation in the body, the measure frequently lacks the ability to identify inflammation that’s specific to just the arteries. Factors such as infection and arthritis will cause hs-CRP levels to be elevated, so this marker cannot be relied upon as a definite indicator of increased CVD risk. In fact, the Framingham Study measured hs-CRP and determined that it wasn’t an independent predictor of CVD risk. Other recent research suggests that hs-CRP may not be involved in the atherosclerotic process, but more research is needed before any definitive conclusions can be made. Lp-PLA2 is a cardiovascular-specific inflammatory enzyme that has been implicated in the formation of vulnerable, rupture-prone plaques. In more than 65 studies, Lp-PLA2 was associated with CVD risk. Testing for
Bradley F. Bale, MD Founder Center for Heart Attack and Stroke Prevention, Spokane, WA Clinical Assistant Professor, School of Medicine Adjunct Professor, School of Nursing Texas Tech University Medical Director, Heart Health Program Grace Clinic
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Experts recommended the Lp-PLA2 test be used in patients with moderate or higher risk for heart attack or stroke. —Bradley F. Bale, MD it was approved by the FDA for coronary heart disease risk assessment in 2003 and for ischemic stroke risk assessment in 2005. In the June 2008 American Journal of Cardiology, experts recommended the Lp-PLA2 test be used in patients with moderate or higher risk for heart attack or stroke. This includes: • People at any age with two or more traditional CVD risk factors. • Anyone 55 and older. • Smokers. • Patients with prediabetes or diabetes. • Anyone with known vascular disease. The Lp-PLA2 test is now the only blood test approved to assess stroke risk. Periodontal inflammation is the only non-arterial inflammation shown to affect LpPLA2 levels; arthritis and other forms of infection do not appear to increase levels.
Analyzing Lp-PLA2 Involvement
A study published in the September 9, 2008 issue of Circulation demonstrated that using darapladib—an experimental drug designed to block the activity of LpPLA2 in the walls of arteries in patients with known coronary artery disease—prevented the enlargement of the necrotic core of atherosclerotic lesions. Advancement of the necrotic core has been linked to an increased risk of a cardiovascular event. The study demonstrated that Lp-PLA2 appears to be a therapeutic target in the atherosclerotic disease process. Considering the growing body of data emerging on the role of arterial inflammation and its involvement in the atherosclerotic disease process, it appears LpPLA2 may be superior to hs-CRP testing. This is clinically relevant because improving the ability to identify patients earlier in the disease process can enable clinicians to take immediate and aggressive actions to enhance outcomes.
Bradley F. Bale, MD, has indicated to Physician’s Weekly that he has worked as a consultant for de Code Genetics and as a paid speaker for Abbott, Takeda, and Berkeley Heart Lab. He has also received grants/research aid from KOS and Abbott.
References Leon AS, Wilmore JH, Ewy GA, et al. Endurance exercise training reduces lipoprotein-associated phospholipase A2 (LP-PLA2) in young white adults: the HERITAGE family study. Med Sci Sports Exerc. 2007;39(suppl):S312. Identifying the Vulnerable Patient with Rupture-Prone Plaque Available at: http://www.ajconline.org/article/S0002-9149(08)00684-X/fulltext Khot UN, Khot MB, Bajzer CT, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290:898-904. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115-126 Wang TJ, Gona P, Larson MG, et al. Multiple biomarkers for the prediction of first major cardiovascular events and death. N Engl J Med. 2006;355:2631-2639. Ballantyne C, Hoogeveeen R, Bang H, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study. Arch Intern Med. 2005;165:1-7. Serruys PW, García-García HM, Buszman P, et al. Effects of the direct lipoprotein-associated phospholipase A(2) inhibitor darapladib on human coronary atherosclerotic plaque. Circulation. 2008;118:1172-1182.
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