The relation of coronary artery disease to plasma lipoproteins was examined in 104 men aged 35-65 years undergoing coronary angiography for suspected myocardial ischaemia. A score reflecting the number, degree, and length of stenoses in seven major coronary arteries was assigned to each angiogram. Lipid concentrations in lipoprotein subfractions were measured after preparative ultracentrifugation; plasma apolipoprotein concentrations were measured by electroimmunoassay.Men with high coronary scores tended to have lower plasma high-density lipoprotein (HDL) cholesterol concentrations and higher low-density lipoprotein (density 1 019-1-063 g/ml) cholesterol concentrations than subjects of similar age with low coronary scores (p0 1). The strongest relation, however, was with the cholesterol concentration in the HDL2 subfraction (density 1-063-1-125 g/ml) of HDL, which averaged 44% lower in the severely affected patients (p <0 005). No associations were found between the coronary score and HDL3 cholesterol, the cholesterol content of lipoproteins of density <1-019 g/ml, plasma triglyceride, or the concentrations of apolipoproteins AI, AU, and E.The high coronary scores associated with low HDL2

Immunization against components of the renin-angiotensin system offers a potential alternative to daily medication in some patients with hypertension or heart failure. Our primary objective was to determine whether a sustained antibody titre to Ang I (angiotensin I) can be achieved in hypertensive patients. The secondary objective was to determine whether the antibodies block the renin system. Patients (n=27) with essential hypertension responsive to an ACEi (angiotensin-converting enzyme inhibitor) or ARB (angiotensin blocker) were randomly assigned to receive three or four injections of the Ang I vaccine PMD3117 or aluminium hydroxide (Alhydrogel trade mark ) over a 6 week period. Antibody titre was measured prior to each injection and every 30 days until disappearance. Indices of renin blockade were changes in renin and aldosterone (blood and urine) and a within-patient comparison of the pre- and post-vaccination rise in 24 h ambulatory blood pressure after 2 weeks of withdrawal of ACEi or ARB. The anti-(Ang I) antibody titre rose from the second injection in both regimes and peaked on day 64. Median half-life was 85 (95% CI, 44 and 153) days (where CI is confidence interval). Vaccination did not influence blood pressure, but significantly blunted the fall in plasma renin following withdrawal of ACEi or ARB. At 42 days after the first injection, aldosterone excretion was decreased by PMD3117 to 6 (95% CI, 1 and 31)% of values in patients receiving Alhydrogel trade mark (P=0.012). In patients with essential hypertension, PMD3117 generated a prolonged antibody response to Ang I. Biochemical measurements show evidence of blockade of the renin system, but higher titres will be required to achieve a decrease in blood pressure.

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Precise quantitation of the effects of the non-selective beta adrenergic blocking drug propranolol (O.I5 mg/kg body weight) on left ventricularfunction, segmental wall motion, and diastolic pressure-volume relation in man has been performed. High fidelity left ventricular pressure measurements and simultaneous single-plane angiocardiograms were recorded on a video disc and volumes calculated by a light-pen computer system. Systolic segmental wall motion was computer analysed using the long axis-quadrasection method. Patients were transvenously atrially paced to maintain a constant heart rate.The haemodynamic effects ofpropranolol may vary depending upon the extent of pre-existing myocardial disease. In some patients ventricular function, as measured by ejection fraction, may be reduced. This reduction in ejection fraction appears to result from overall reduction in segmental wall motion, but also from accentuation of segmental wall abnormalities. These results are consistent with the thesis that beta adrenergic blocking drugs may inhibit compensatory sympathetic mechanisms.The diastolic effects of propranolol may include quite substantial increases in ventricular volumes in those patients with impaired cardiac function. With respect to the intact human ventricle, propranolol may increase diastolic volume for a given level of ventricular pressure. Thus, in a static sense, the ventricle in these patients could be viewed as being more compliant after propranolol administration. However, the fact that the lengthtension relation, as measured by the slope of the logarithmic pressure versus volume plot is unaltered by propranolol, suggests that the muscle comprising the ventricle itself exhibits no alteration in its passive elastic properties.The non-selective beta-adrenergic blocking drug propranolol is widely used in clinical practice for the treatment of patients with ischaemic heart disease, hypertension, arrhythmias, and obstructive cardiomyopathy.Many haemodynamic studies have been reported in the past documenting the effects of propranolol on ventricular function. Because propranolol has a strong negative chronotropic effect, it has not always been possible in these studies to isolate the direct

Patients with silent ischaemia and pain pathways presumed to be intact have an enhanced peripheral vasodilator response, and if this applied to the coronary vasculature it could provide a mechanism for limiting ischaemia to below the pain threshold. Patients with pure silent ischaemia have evidence of sympathetic autonomic dysfunction.