The Heart in HypertensionThe Heart in Hypertension

Jamil Mayet

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

Definition of LVH Healthy cohort of subjects No high BP, diabetes, CV disease, obesity LVH defined as LVMI > mean + 2SD

Framingham Study

LVMI > 131g/m2 males; > 100g/m2 females Cornell, New York

LVMI > 134g/m2 males; > 110g/m2 females

Levy et al. Am J Cardiol 1987;59:956-60. Devereux et al. JACC 1984;4:1222-30.

Risk factors for LVH Blood pressure

Age Gender Race Genetic factors Obesity Physical activity

Pathophysiology of LVH

High BP LV wall stress Wall stress 1/ wall thickness LV wall thickening wall stress Myocyte hypertrophy and collagen matrix Mediators:

Mechanical: preload & afterload Neurohormonal: angiotensin II, sympathetic NS

Clinic versus mean 24 hour systolic BP and LVMI

24 hour mean SBP v. LVMI (r=0.48, p<0.01)

0

50

100

150

200

250

0 100 200 300

LVMI (gm2)2

4 h

our

SB

P (

mm

Hg)

Relationship between mean 24 hour SBP and LVMI

Linear (Relationship between mean 24 hour SBP and LVMI)Linear (Relationship between mean 24 hour SBP and LVMI)Clinic SBP v. LVMI: (r=0.28,

p<0.05)

0

50

100

150

200

250

0 100 200 300LVMI (g/m2)

Clin

ic S

BP

(m

mH

g)

Mayet al et. J Cardiovasc Risk 1995;2:255-61.

Methods of detecting LVH

Clinical examination Chest radiography Electrocardiography Echocardiography (CT, MRI)

Sensitivity and specificity of ECG criteria for LVH

Sensitivity Specificity

Sokolow-Lyon 15-30 73-100

Cornell voltage 7-45 93-100

Romhilt-Estes point score 6-50 85-99

Minnesota code 3-1 3-15 88-99

Framingham criteria 3-17 98-100

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)

Cardiothoracic ratio and CHD mortality:Whitehall study

Cardiothoracic ratio Hazard ratio for CHD*

<0.4 1.0

0.4-0.439 1.02 (0.61-1.73)

0.44-0.449 1.02 (0.60-1.74)

0.45-0.469 1.33 (0.81-2.20)

0.47- 1.65 (1.01-2.70)

*Adjusted for age, BP, HR, cholesterol, smoking, angina and ECG ischaemia

Hemingway et al. BMJ 1998; 316: 1353-4.

Cardiovascular risk in subjects with ECG-LVH: Framingham

Cardiovascular outcome

Men Women

Coronary heart disease 3.0* 4.6* Stroke 5.8* 6.2* Peripheral arterial disaese 2.7 5.3* Cardiac failure 15.0* 12.8*

Age-adjusted risk-ratio

*P<0.0001 Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

Risks of X-ray and ECG LVH:Framingham

No X-ray enlargement X-ray enlargement

No ECG-LVH 171 253

ECG-LVH 669 1072

Data include men and women, aged 35-94

Age-adjusted biennial rate per 1000

Kannel. Eur Heart J 1992; 13 (suppl D): 82-88

Penn convention for M-mode measurements

Peak of QRS Endocardium excluded from SWT

and PWT 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

ASE guidelines for M-mode measurements

Start of QRS Endocardium included in SWT and

PWT 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

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

4-year age-adjusted incidence of cardiovascular disease according to LVMI

0

2

4

6

8

10

12

14

16

18

<75 75-94 95-116 117-

Males

Females

LVMI (g/m2)

Ag

e-a

dju

ste

d i n

c id

enc

e/ 1

00 s

ub

ject

s

Redrawn from Levy et al; NEJM 1990; 322: 1561-6.

Incidence of cardiovascular mortality according to presence or absence of LVH

00.5

11.5

22.5

33.5

44.5

5

Men Women

No LVH

LVH

4-y

ea

r ag

e-a

dju

ste

dca

rdio

vasc

ula

r m

ort

ality

P<0.001 P=ns

Redrawn from Levy et al, NEJM 1990; 322: 1561-6.

Risks associated with LVM and geometry

0

10

20

30

40

>125 <125 >125 <125

<0.45

>0.45

LVMI (g/m2) LVMI (g/m2)

RWT

Total mortality* Cardiovascular events†

% p

atie

nts

Koren et al. Ann Int Med 1991; 114: 345-352.*P<0.001, †P=0.03

Regression of LVH by drug treatment:meta-analysis of RCTs

-14

-12

-10

-8

-6

-4

-2

0

Diuretics B-blockers CCB's ACE-I

Schmieder et al. JAMA 1996; 275: 1507-1513

Mea

n %

in

LV

MI

Between treatment P<0.01

Prognostic significance of Echo LVM regression

0

1

2

3

4

5

6

7

All LVH

Regressors Non-regressors

Eve

nts/

100

pat

ient

yea

rs

Verdecchia et al. Circulation 1998; 97: 48-54

*

†

*P=0.04, †P=0.0004 after adjustment for age.

Prognostic significance of ECG voltage

changes: Framingham

0

0.5

1

1.5

2

Decreased voltage Increased voltage

Males FemalesOR

for

CV

eve

nts

(2 y

ears

)

*

*

*P<0.05Levy et al. Circulation 1994; 90: 1786-1793

Age-adjusted risk of congestive heart failure by hypertensive status

0

20

40

60

80

100

Ann

ual i

ncid

ence

/ 10

,000

Women Men

NormotensiveBorderlineHypertensive <140/90

>160/90

Kannel WB.Framingham

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

Age-adjusted BP parameters and CHF risk

0

0.5

1

1.5

2

2.5

SBP (mmHg) DBP (mmHg) PP (mmHg)<120 120-

139140-159>159 <70 70-7980-89>89 <54 54-

67>67

Hazard

Ratio

Chae et al. JAMA199;281:634-9

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

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

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

Stiffnessimpact

LVregression

Outcomedata

-blockers ?+ + No

ACE-inhibitors +++ +++ No

-blockers + + Yes

-blockers ‘extra’ ++ ?? No

Ca++ antagonists +++ ++ Yes

thiazides + +/++ Yes +

Relation between vascular and LV impacts of antihypertensives

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

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

Echocardiographic assessment

• 2D echo to assess systolic function

• Doppler echo– Transmitral flow

• E/A wave ratio• E wave deceleration time

– IVRT

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

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

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