Eljas Laufer

Aortic distensibility in patients with isolated hypercholesterolaemia, coronary artery disease, or cardiac transplant

The stiffness of the thoracic aorta can be assessed non-invasively. If aortic stiffness can be shown to be related to coronary heart disease, perhaps it can be used to identify which patients with hypercholesterolaemia are most likely to have atheromatous changes and thus to be selected for intensive cholesterol-lowering treatment. Hence the distensibility of the transverse aortic arch was measured by echocardiography of the aortic arch in four groups of patients--symptom-free patients with normal serum cholesterol; symptom-free patients with raised serum cholesterol; patients with coronary heart disease (all with raised serum cholesterol), and post-heart-transplant patients. In all groups distensibility fell with age. The regression slope was steeper (p less than 0.05) for patients with known coronary disease than for either of the disease-free groups, and among cardiac transplant recipients there was also a segregation of distensibility values between those with and without atheroma in their native hearts. The results indicate that aortic distensibility might be an indicator of coronary heart disease and that it might be useful in identifying which symptom-free subjects with modest hypercholesterolaemia should be treated aggressively.

Prevalence of cardiac structural and functional abnormalities in untreated primary hypertension.

We examined the prevalence of left ventricular structural and functional abnormalities in previously untreated subjects by performing echocardiography in 89 normal volunteers, 57 patients with established hypertension, and 38 patients with mild or borderline hypertension. We measured left ventricular mass, wall thickness, internal diameter, and wall thickness/radius ratio. Because of intergroup differences hi body size, we used covariance analysis to index these variables to a common value of 1.8 m2. No adjustment was needed for the wall thickness/radius ratio. Functional variables determined were fractional shortening and transmitral early/late flow velocity ratio (the latter was standardized by analysis of covariance to age 40 years). The prevalence of left ventricular mass index values more than 2 SD above the mean of the normal group was 30% in the patients with established hypertension and 12–15% hi the patients with mild hypertension. Corresponding figures for wall thickness index were 65% and 32% and for the wall thickness/radius ratio 60% and 40%. The prevalence of abnormality in the transmitral flow velocity was 28% in the patients with established hypertension and 12% in the patients with mild hypertension. A multivariate discriminant function that used combined anatomic and functional variables provided the most reliable classification; it was correct in 82% of normal subjects, 65% of patients with established hypertension, and 61% of patients with mild hypertension. The majority of patients with hypertension have cardiac structural or functional abnormalities, or both.

Effects of exercise and other nonpharmacological measures on blood pressure and cardiac hypertrophy

Reversal of left ventricular hypertrophy (LVH) is an important target of antihypertensive therapy. Nonpharmacological approaches such as weight reduction and exercise training have favorable effects on other risk factors. However, there are few data on their effects on LVH. Athletes have eccentric rather than concentric LVH. A 12-month exercise program in 13 unmedicated hypertensive subjects altered LV geometry, reducing LV wall thickness and increasing LV internal diameters (LVID). LV mass was unchanged, and the thickness/radius fell by 9%. Shorter-term studies have shown that the cardiac structural changes with a moderate exercise program occur rapidly and their onset lags only about 2 weeks behind blood pressure (BP) effects. Assessment of weight loss effects on LVH is complicated by the strong relationship between body weight and ventricular wall thickness. LVID, and LV mass. To some extent, this can be overcome by arbitrarily indexing to body surface area or height. The wall thickness/radius ratio is not related to body size. Weight reduction reduces BP and thickness/radius by 10% in controlled trials. Small studies have also reported reduction in LV mass after sodium restriction in hypertensive subjects. Studies with other nonpharmacological measures could make a substantial contribution to knowledge of their efficacy.

ECHOCARDIOGRAPHIC MEASUREMENT OF LEFT VENTRICULAR HYPERTROPHY IN UNTREATED ESSENTIAL HYPERTENSION

1. The prevalence of left ventricular hypertrophy (LVH) in human essential hypertension is uncertain. Echocardiography was used to calculate left ventriuclar wall thickness (WT), relative wall thickness (t/r) and left ventricular mass (LVM) in 52 normal subjects, 30 patients with borderline hypertension and 33 untreated patients with essential hypertension.

Effects of Nebivolol on Haemodynamics, Cardiac Dimensions and Function, Cardiovascular Reflexes and Biochemical Measures of Sympathetic Activity in Normal Human Subjects

SummaryNebivolol is a β-adrenergic antagonist with novel pharmacodynamic properties. We examined its effects in 8 normal subjects in a randomised double-blind, placebo-controlled crossover study. Nebivolol lowered resting and ambulatory blood pressure (BP). The latter fall averaged 11/10mm Hg after 1 week of therapy (both p < 0.01). The fall in BP was due to a reduction in total peripheral resistance. Stroke volume increased. Nebivolol reduced resting heart rate and heart rate responses to head-up tilting, Valsalva’s manoeuvre and mental challenge. However, BP responses to these stimuli were unaltered. The drug had no effect on plasma noradrenaline (norepinephrine) or on norepinephrine spillover or clearance, either at rest, during mental challenge or tilting. Despite markedly reducing resting heart rate, nebivolol had only a slight effect on left ventricular (LV) dimensions determined echocardiographically. LV systolic function was unchanged but there was evidence of effects on diastolic filling as nebivolol decreased deceleration time (p < 0.003) and pressure half-time.Nebivolol lowers BP and heart rate in normal subjects. Other aspects of sympathetic function are preserved, and mechanisms other than classical β1-adrenergic antagonism appear to be involved.

ABSENCE OF DETECTABLE REGRESSION OF HUMAN HYPERTENSIVE LEFT VENTRICULAR HYPERTROPHY FOLLOWING DRUG TREATMENT FOR 1 YEAR

1. The present study was designed to compare and contrast the effects of 1 year’s treatment with angiotensin‐converting enzyme inhibition (captopril 25–100 mg daily) and beta‐blockade (atenolol 50–100 mg daily) on hypertensive cardiac structure and function as well as the other established cardiovascular risk factors of high blood pressure (BP), lipid profile and blood glucose.

EVIDENCE FOR A ROLE FOR THE CARDIOVASCULAR AMPLIFIERS IN HUMAN PRIMARY HYPERTENSION

1. Hypertrophy of vascular and cardiac smooth muscle is present in human primary hypertension. The amplifier properties associated with hypertrophy play a major role in maintaining hypertension.