1. The Heart in Hypertension Jamil Mayet

2. Left Ventricular Hypertrophy - a historical perspective Association between renal disease and LVH –Richard Bright 1836 Hypertrophy of large and small vessels related to LVH in kidney disease –George Johnson 1852 Vascular changes and LVH without renal disease –Gull and Sutton 1872 BP measured in life correlated with post-mortem heart weight –Evans 1921

3. Definition of LVH l Healthy cohort of subjects l No high BP, diabetes, CV disease, obesity l LVH defined as LVMI > mean + 2SD l Framingham Study LVMI > 131g/m 2 males; > 100g/m 2 females l Cornell, New York LVMI > 134g/m 2 males; > 110g/m 2 females Levy et al. Am J Cardiol 1987;59:956-60. Devereux et al. JACC 1984;4:1222-30.

4. Risk factors for LVH l Blood pressure l Age l Gender l Race l Genetic factors l Obesity l Physical activity

5. Pathophysiology of LVH l High BP   LV wall stress l Wall stress  1/ wall thickness l LV wall thickening   wall stress l Myocyte hypertrophy and  collagen matrix l Mediators: l Mechanical: preload & afterload l Neurohormonal: angiotensin II, sympathetic NS

6. Clinic versus mean 24 hour systolic BP and LVMI Mayet al et. J Cardiovasc Risk 1995;2:255-61.

7. Methods of detecting LVH l Clinical examination l Chest radiography l Electrocardiography l Echocardiography l (CT, MRI)

8. Sensitivity and specificity of ECG criteria for LVH Devereux et al 1983, Murphy et al 1985, Levy et al 1990, Lee et al 1992, Devereux et al 1993, Schillaci et al 1994, Crow et al 1995, Norman et al 1995, Chapman et al (in press)

9. Cardiothoracic ratio and CHD mortality: Whitehall study *Adjusted for age, BP, HR, cholesterol, smoking, angina and ECG ischaemia Hemingway et al. BMJ 1998; 316: 1353-4.

10. Cardiovascular risk in subjects with ECG-LVH: Framingham Age-adjusted risk-ratio *P<0.0001 Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

11. Risks of X-ray and ECG LVH: Framingham Data include men and women, aged 35-94 Age-adjusted biennial rate per 1000 Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

12. Penn convention for M-mode measurements l Peak of QRS l Endocardium excluded from SWT and PWT l Endocardium included in LVID LV mass = 1.04[(SWT+LVID+PWT) 3 - (LVID) 3 - 14g Divide by body surface area to get LV mass index LV cavity (LVID) Septum (SWT) Posterior wall (PWT) Devereux & Reichek Circulation 1977;55:613-8

13. ASE guidelines for M-mode measurements l Start of QRS l Endocardium included in SWT and PWT l Endocardium excluded from LVID LVM = 0.8{1.04[ (SWT+LVID+PWT) 3 - (LVID) 3 ]} + 0.6 g Divide by body surface area to get LV mass index LV cavity (LVID) Septum (SWT) Posterior wall (PWT) Devereux et al. Am J Cardiol 1986;57:450-8

14. Area-length method for calculation of LV mass LVmass=1.05[5/6(A1xL1)-5/6(A2xL2)] Divide by body surface area to get LV mass index Reichek et al. Circulation 1983;67:348-52

15. 4-year age-adjusted incidence of cardiovascular disease according to LVMI LVMI (g/m 2 ) Age-adjusted incidence/ 100 subjects Redrawn from Levy et al; NEJM 1990; 322: 1561-6.

16. Incidence of cardiovascular mortality according to presence or absence of LVH 4-year age-adjusted cardiovascular mortality P<0.001 P=ns Redrawn from Levy et al, NEJM 1990; 322: 1561-6.

17. Risks associated with LVM and geometry LVMI (g/m 2 ) RWT Total mortality* Cardiovascular events † % patients Koren et al. Ann Int Med 1991; 114: 345-352. *P<0.001, † P=0.03

18. Regression of LVH by drug treatment: meta-analysis of RCTs Schmieder et al. JAMA 1996; 275: 1507-1513 Mean %  in LVMI Between treatment P<0.01

19. Prognostic significance of Echo LVM regression Events/ 100 patient years Verdecchia et al. Circulation 1998; 97: 48-54 * † *P=0.04, †P=0.0004 after adjustment for age.

20. Prognostic significance of ECG voltage changes: Framingham OR for CV events (2 years) * * *P<0.05 Levy et al. Circulation 1994; 90: 1786-1793

21. Age-adjusted risk of congestive heart failure by hypertensive status <140/90 >160/90 Kannel WB. Framingham

22. The progression from hypertension to congestive heart failure 5143 subjects in Framingham study 392 new cases of clinical CCF after mean follow up of 20 years In 91% hypertension antedated CCF MI present in 52% of hypertensive men and 34% of hypertensive women with CCF Median survival after CCF diagnosis in ht 1.37 years in men and 2.48 in women Levy et al. JAMA 1996;275:1557-62

23. Age-adjusted BP parameters and CHF risk <120 120- 139 140-159 >159<70 70-7980-89 >89<54 54- 67 >67 Hazard Ratio Chae et al. JAMA199;281:634-9

24. Arterial stiffening in hypertension Increased PW velocity with early wave reflection Increased central systolic pressure and lower diastolic pressure Discrepancy between central and peripheral pressures lessened Therefore peripheral BP underestimates central effects

25. Reducing arterial stiffness as a therapeutic goal Later wave reflection reduces peak central pressure which is caused by summation of systolic wave and reflected wave In periphery peak pressure is not a summation wave and so there is less of a decrease Reducing stiffness causes preferential decrease in central compared with peripheral pressures

27. Non-pharmacological approaches to reducing arterial stiffness Increased arterial stiffness in obese subjects with improvement following weight reduction Moderate aerobic exercise increases arterial compliance Subjects with high salt intake have better arterial distensibility than those with low intake. Improvement following salt restriction

28. Stiffness impact LV regression Outcome data  -blockers ?++ No ACE-inhibitors +++ No  -blockers ++Yes  -blockers ‘extra’ ++?? No Ca ++ antagonists +++++Yes thiazides ++/++Yes + Relation between vascular and LV impacts of antihypertensives

29. Diastolic heart failure Symptoms/signs of heart failure with normal or mildly impaired LV systolic function Prevalence depends on clinical definition of heart failure May be up to 30% of cases with heart failure Diastolic dysfunction in hypertensives is very common, particularly in those with LVH

30. Pathophysiology of diastolic dysfunction Impaired relaxation –Energy dependent and sensitive to ischaemia Coronary artery disease Microvascular ischaemia (arteriolar rarefaction, arteriole wall thickening, perivascular fibrosis, endothelial dysfunction, relative myocyte hypertrophy) Decreased compliance –Increase in myocardial collagen

31. Echocardiographic assessment 2D echo to assess systolic function Doppler echo –Transmitral flow E/A wave ratio E wave deceleration time –IVRT

32. Doppler patterns of diastolic dysfunction Impaired relaxation –Reduced E/A ratio –Increased EDT –Increased IVRT Restriction –LA pressure increases due to myocardial stiffness –High peak E wave velocity –Short EDT –Very short IVRT

35. Treatment of diastolic heart failure Treat underlying cause eg ischaemia Impaired relaxation –Theoretically rate-limiting agents effective Beta-blockers, verapamil Reduce HR and prolong diastole Reduce myocardial oxygen demand Lower BP and reduce LVH

36. Treatment of diastolic heart failure Restriction –Drugs which reduce fibrosis and lower LA pressure theoretically should be effective ACEI AII blockers Diuretics –If LA pressure lowered too much cardiac output significantly worsened Can cause significant morbidity