Υπέρταση και καρδιά
Factors influencing prognosis Risk factors Systolic and diastolic BP levels Levels of pulse pressure (in the elderly) Age (M>55 years; W>65 years) Smoking Dyslipidemia TC >5.0 mmol/l (115mg/dl) or: LDL-C >3.0 mmol/l (115mg/dl) or: HDL-C: M<1.0 mmol/l (40mg/dl) W <1.2 mmol/l (46 mg/dl) or: TG>1.7 mmol/l (150 Fasting plasma glucose 5.6-6.9 mmol/l (102-125mg/dl) Abdominal obesity (waist circumference >102cm (M), >88cm (W)) Family history of premature CV disease (M at age <55 years; W at age <65years)
Diabetes mellitus Fasting plasma glucose ≥7.0 mmol/l (126mg/dl) on repeated measurement or: Postload plasma glucose >11.0 mmol/l (198 mg/dl) Note: the cluster of three out of 5 risk factors among abdominal, obesity, altered fasting plasma glucose, BP ≥130/85 mmHg, low HDL cholesterol and high TG (as defined above) indicates the presence of metabolic syndrome.
Journal of Hypertension 2007;25:1751-1762
Subclinical organ damage Electorcardiographic LVH (Sokolow-Lyon >38mm; Cornell >2440 mm/ms) or: Echocardiographic LVH♦ (LVMI M≥125g/m2, W≥110 g/m2) Carotid wall thickening (IMT >0.9mm) or plaque Carotid – femoral pulse wave velocity >12 m/sec Ankle/Brachial BP index <0.9 Slight increase in plasma creatinine: M:115-133μmol/l (1.3-1.5mg/dl) W: 107-124μmol/l (1.2-1.4mg/dl) Low estimated glomerular filtration rate ♦ ♦ (<60ml/min/1.73m2) or creatinine clearance ♦ ♦♦ (<60ml/min) Microalbuminuria 30-300 mg/24h or albumin-creatinine ratio ≥ 22 (M); or ≥31 (W) mg/g creatinine Established CV or renal disease Cerebrovascular disease; ischaemic stroke; cerebral haemorrhage; transient ischaemic attack Heart disease; myocardial infarction; angina;coronary revascularization; heart failure Renal disease; diabetic nephropathy; renal impairement (serum creatinine M>133; W>124μmol/l; proteinuria (>300mg/24h) Peripheral artery disease Advanced retinopathy; haemorrhages or exudates, papiloedema
Consequences of Hypertension: Organ Damage Hypertension Transient ischemic attack, stroke
Retinopathy
LVH, CHD, CHF
Peripheral arterial disease
Chronic kidney disease
CHF=congestive heart failure; CHD=coronary heart disease; LVH=left ventricular hypertrophy. Chobanian AV et al. JAMA. 2003;289:25602003;289:2560-2572.
CV Complications of Untreated Hypertension (N=500) 50
50 45 40 35 Event rate (%)
30 25 20
18
15
16 12 8
10 5 0
2 Renal Failure
Stroke
Enceph
MI, myocardial infarction; CHF, chronic heart failure. Perera GA J. Chron Dis. 1955;1:33-42.
MI
Angina
CHF
Cardiovascular Mortality Risk Doubles with Each 20/10 mmHg BP Increment* 8
CV Mortality Risk
7 6 5 4 3 2 1 0
115/75
135/85
155/95
Systolic/Diastolic Blood Pressure (mmHg) * Individuals aged 40-69 years, starting at BP 115/75 mm Hg Lewington S, et al. Lancet. 2002;360:19032002;360:1903-1913
175/105
Effects of Hypertension on The Heart
z
Left Ventricular Hypertrophy Left Atrial Disease â&#x20AC;&#x201C; Atrial Fibrilation
z
Vascular Disease:
z
-Atherosclerosis
-Arteriosclerosis z
Heart Failure -Systolic -Diastolic
HYPERTENSION
↑BP
↑ Αng II ↓ΝΟ Subclinical inflammatory reaction
TARGET ORGAN DAMAGE
Pathogenesis of LVH Hemodynamic load
Neurohormonic System
• • • Non-modifiable Risk factors
• • •
Age Sex Race
SNS RAS Insulin
Modifiable factors
Subclinical Inflammation
• Salt intake • Obesity
Hypertensive cardiac disease Structural and functional adaptations Aortic dilatation
Diastolic dysfunction
LVH
LA enlargement
Impaired CFR CAD
Systolic dysfunction
Risk factor left ventricular hypertrophy Risk (x times) 8 6 4 2 0 Heart failure
CAD mortality
AMI
Stroke
30 years follow â&#x20AC;&#x201C; up Framingham population Kannel et al. 1983
Indications for Echocardiography in Hypertensive Patients
• Coexistent Heart Disease • Resistant Hypertension • Decision to Start Treatment Uncertain
Searching for subclinical cardiac damage (2007 ESH/ESC Guidelines) Electrocardiography should be part of all routine assessment of subjects with high BP in order to detect LVH, patterns of strain, ischaemia and arrhythmias. Echocardiography is recommended when a more sensitive detection of LVH is considered useful.
Why Is Echocardiography Useful In Hypertensive Patients? â&#x20AC;&#x153;No other biological variable (except advancing age) predicts cardiac risk better than left ventricular hypertrophyâ&#x20AC;?. (De Simone et al, J Hypertens 12;1129, 1994)
How Common is LVH in Hypertensive Patients? • ECG LVH in about 5% of ht patients • Echo LVH in 15-30% of unselected ht patients • Echo LVH in 20 to 60% of ht patients in referral centers
Prevalence of LVH (â&#x2030;Ľ 125/110 g/m2) in different hypertensive settings %
60
51 %
50 40
31 %
30 20
15 %
10 0
A
B
C
A Newly diagnosed hypertensives (Cuspidi et al J Hypertens 2006) B Treated hypertensives attending a specialist center (Cuspidi et al J Hum Hypertens 2008) C Refractory hypertensives (Cuspidi et al J Hypertens 2001)
Echocardiographic LVMI as a Predictor of CV Risk (Schillaci et al, Hypertens 2000; 35: 580) 5 4,34 4
CV Events per 100-pt 3 years
2,86 2,24
2 1
1,66 0,85
0 1st
2nd
3rd
4th
Quintiles of LVMI
5th
1652 hypertensives free of CV disease were enrolled within a period of 3 yrs (1998-2000) Followed up for 6 yrs At baseline: age>65yrs Sex Smoking DM LDL>160mg/dl LVH CKD End points: CAD, Stroke, all cause mortality and their composite
LVH vs CKD as predictors of CV events in hypertension: a Greek 6-year-follow-up study Tsioufis C, â&#x20AC;Ś, Stefanadis C. J Hypertension 2009
3.2 Fold
Regression of Hypertensive LVH: Results of 2000 Meta-Analysis P<0.05
P<0.09
vs Ă&#x;-blockers
LVM Regression (%)
0 -2 -4 -6 -8 -10 -12
Diuretics
BetaBlockers
ACEInhibitors
Ca++ Blockers
AII receptor Blockers
% De cre ase
Schmieder et al: J Am Coll Cardiol 2001;37:261-262A
LVH Regression: Cardiovascular Events in Hypertensives cardiovascular events in hypertensives subjects with regression of LVH versus those with persistent or new LVH LVH New/ LVH Regression Persistent Muiesan et al 1995 4/32 15/41
0.24 (0.07-0.84)
Verdecchia et al 1998 3/52
13/100
0.41 (0.11-1.51)
5/52
17/134
0.73 (0.25-2.10)
1/16
12/42
Cipriano et al 2001 Koren et al 2002 TOTAL
13/152
0.17 (0.02-1.40) 0.41 (0.21-0.78)
57/317 Favours LVH Regression
0.1
0.2
Favours New/Persistent LVH
0.5 1.0 odds ratio
2.0
5.0
Verdecchia et al 2003
Evaluation of LA size z
ECG
z
X-Ray
z
Echo
z
CT / MRI
z
Cath Lab
─
.
Evaluation of LA The role of ECG
P wave duration in lead II ≥ 0.12 s a negative P terminal force in V1 <0.03 mms the ratio of the duration of negative terminal P in V1 to the P-R segment equal to or greater than 1.0
-Overall predictive index of the electrocardiogram for LA enlargement was 63% -Absence of LA enlargement 78%. -Changes in P wave morphology may be used as a reasonably specific but less sensitive indicator of left atrial enlargement Waggoner AD, et al. Circulation 1976; 54: 553–7.
Evaluation of LA The role of echo
Μέγεθος αρ κόλπου
Κίνηση τοιχωμάτων αριστερού κόλπου
Ανατομική ακεραιότητα και κίνηση μεσοκολπικού διαφράγματος
Μέγεθος/λειτουργικότητα ωτίου Παρουσία ή μη ήχων αντίθεσης, θρόμβου ή άλλης μάζας εντός της κοιλότητας αυτού
Δυναμική ροής αίματος σε είσοδο ωτίου, ταχύτητας ροής πνευμονικών φλεβών και διαμιτροειδική ροή
LA size The role of Echocardiography z
z
z
Transverse dimension (1.9-4.0 cm ή 1,0-2,0 cm/m²)
A ratio of transverse atrial to transverse aortic root dimension greater than 1.17 LA Volume (20±6 ml/m², 32ml/m² the upper limit) (Wang Y, et al. Chest 1984; 86:595-601)
Which is the most reliable index of LA size? The LA volume is the best index of LA size estimation because z LA enlarges asymmetrically, becomes less spherical as it enlarges Lester et al. Am J Cardiol 1999; 84:829-832 z LAVI was more strongly associated with the presence of CVD than LAD/BSA Pritchett AM, et al. J Am Coll Cardiol 2003; 41: 1036-1043 z In subjects with sinus rhythm LAV is a more robust marker of CV events
than LA area or diameter z In subjects with AF the predictive value of LA size for CV events was poor, irrespective of the method of LA size quantitation Tsang et al, JACC 2006;47:1018-23
Determinants of LA Size In the absence of mitral valve disease z z
24h SBP/DBP
(Staessen JA, et al. JAMA 1999; 282:539-546)
BMI
(Sasson Z et al. Can J Cardiol 1996; 12:257-263)
z LVM
(Mansoor GA, et al. Blood Pressure Monitoring 2003; 8:3-7)
z
Diastolic dysfunction
z Age
(Tsang TS et al. Am J Cardiol 2002; 90:1284-1289) (Tsang TS et al. Am J Cardiol 2002; 90:1284-1289)
Positive relation between left atrial volume index and LVMI /BNP in the early stages of hypertension
C.Tsioufis et al, Journal of Hypertension 2006
Aortic stiffness and diastolic dysfunction 1,1
1
r = - 0.437 p<0.001
Average Em/Am
0,9
0,8
0,7
0,6
0,5
0,4 5
7
9
11
13
15
17
PWV (cm/sec)
C.Tsioufis, et al. Journal Hypertens 2005;23:1745-1750
Cardiac Pathology and Ischemic Stroke Cardiac pathology
LVH or atrial enlargement AF Left atrial blood stasis and emboli formation Thrombotic or embolic event
Ischemic stroke
Adapted from Vaziri SM et al Circulation 1994:89:724–730; Hart RG et al Ann Intern Med 2003;138:831–838; Fyrenius A et al Heart 2001;86(4):448–455; Shinokawa N Chest 2001;120(3):840–846.
How often AF in hypertension ?
ATTIKA, EPIC, ATHENS, DIDIMA, NEMEA Hypertensives : 25-40% of the Greek population Atrial arrhythmias 25-50% AF:1-9% (3H : 3%)
Progression from Hypertension to Heart Failure Obesity Diabetes
LVH
Diastolic Dysfunction
HF
Hypertension Smoking Dyslipidaemia Diabetes
Normal LV Structure & Function
MI LV Remodelling
Time: decades
Death
Systolic Dysfunction
Subclinical LV Dysfunction
Overt Heart Failure
Time: months
Heart Failure Development: PopulationAttributable Risk Prevalence Hypertension MI Angina Pectoris Diabetes LVH Valvular Disease
male female
1
1.5
3.0 4.5 Hazard Ratio
(%)
Attributable Risk (%)
60 62 10 3 11 9 8 5 4 3 5 8
39 59 34 13 5 6 6 12 4 5 7 8
7.5 Levy et al 1996
Influence of LVH on Incident Heart Failure Cardiovascular Health Study: a prospective, longitudinal, population-based study in 2506 subjects with 6-7 years follow-up Incident heart failure free survival by LV mass gender-specific quartiles.
% free of incident HF
100
LV mass (g) Quartiles
96
1,2 92
3 88
84 0
500
1000 1500 2000 time to incident HF (days)
2500
4 Gardin et al 2001
Hypertension as a Risk Factors for the Development of Heart Failure
Influential factors beyond blood pressure control:
• Left Ventricular Hypertrophy • Diabetes • Atrial Fibrillation
Reduction in Heart Failure Risk by SBP Reduction slope = 26% risk reduction per 10 mm decrease in SBP p<0.001
Relative risk
2.0
1.0
0.5
2003 BPLTTC trials regression line for BPLTTC trials recent trials
-16
-12 -8 -4 0 4 Difference in SBP reduction between trial arms (mm Hg)
Results of the Randomised Trials of Antihypertensive Drug Therapy Fatal/Nonfatal Stroke
Fatal/Nonfatal CHD
Vascular Deaths
Heart Failure
0
Risk reduction (%)
-10
-16%
-20
-21%
-30 -40
-38% -50
-52% Collins and Macmahon 1994 Moser & Herbert 1996
Effect of Antihypertensive Therapy on all CV Events: Comparison of Newer & Older Drugs Stroke Coronary Heart Disease Heart Failure Major CV Events CV Death ACEI CCB
Total Mortality New Drugs Better Older Drugs Better 0.75
1.0 Relative Risk (95% CIs)
1.3 BPLTTC 2003
Risk of Cardiovascular Events by SBP in Untreated Subjects: 36-Year Follow-Up in the Framingham Study
Systolic Pressure (mm Hg) MI <120 8.2
Age-Adjusted Biennial Rate/1000 Age35-64 Yr Age 65-94 Yr Stroke CHF MI Stroke CHF 2.2 3.7 11.6 16.7 19.3
120-139
10.9
2.6
2.7
23.3
18.8
9.2
140-159
22.7
6.5
6.0
42.5
17.4
25.1
>160
22.5
12.3
15.6
51.6
36.9
33.8
Results of randomised trials of antihypertensive drug therapy STROKE Randomised trials Epidemiological data
CHD Randomised trials Epidemiological data
0
10 20 30 40 % reduction / 6 mm Hg fall in diastolic blood pressure
50
Collins and Peto, 1994
Στους έχοντες ιστορικό καρδιαγγειακής νόσου: η σύσταση για ΣΑΠ<130mmHg συνοδεύθηκε με αντικρουόμενα αποτελέσματα (130-139/80-85 mmHg) (post hoc analysis: όφελος μέχρι τιμή ΑΠ 120/75mmHg)
ESH 2009
INVEST Study Επίπτωση ΕΜ και ΑΕΕ ανάλογα με την ΔΑΠ κατά την θεραπεία
JACC 2009;54(20):1827-34
INVEST Study Αλληλεπίδραση της επαναγγείωσης με την ΔΑΠ κατά την θεραπεία στην έκβαση των ασθενών
JACC 2009;54(20):1827-34
Χαμηλή ΔΑΠ και καρδιαγγειακά επεισόδια ΗΟΤ-INVEST-ACTION-Syst-Eur:
Υπάρχει μία σχέση τύπου J καμπύλης ανάμεσα στη ΔΑΠ κατά την θεραπεία (στα όρια 70-80mmHg) και την ΣΝ σε ασθενείς υψηλού κινδύνου (ηλικιωμένοι, με YAK, με ΣΝ) χωρίς ενδείξεις επιβάρυνσης για τον εγκέφαλο ή τους νεφρούς.
The Heart in Hypertension Ventricular Ectopy, Ventricular Fibrillation, Sudden Cardiac Death
Coronary Coronary Ischemia Ischemia Diastolic Diastolic Heart Heart Failure Failure
Heart Failure Atrial Atrial Fibrillation Fibrillation
Systolic Systolic Heart Heart Failure Failure
Post Myocardial Infarction
Diuretic Post-Myocardial Infarction
β-blocker
ACE Inhibitor
ARB
9
9
9
Calcium Antagonist
Aldosterone Antagonist
9
Ventricular Remodeling After Myocardial Infarction
Initial Infarct
Expansion of Infarct Hours to Days
Jessup M, Brozena S. N Engl J Med 2003;348:2007:20072003;348:2007:2007-18.
Global Remodeling Days to Months
Χαμηλή ΔΑΠ και καρδιαγγειακά επεισόδια ΕΠΙΣΗΜΑΝΣΕΙΣ 1. Αυτό δεν θα πρέπει να αποθαρρύνει τους γιατρούς από την επιθετική αντιμετώπιση της ΑΠ αφού το 1/3 των υπερτασικών δεν είναι στον στόχο <140/90 mmHg 2. Διαφορετική επίδραση των αντιυπερτασικών στη πίεση σφυγμού (β-αναστολείς vs αναστολείς ΣΡΑΑ) στη καρδιακή συχνότητα στη ΥΑΚ και την στεφανιαία εφεδρεία