A. F. Lever

Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley survey: comparison with men

Most epidemiological and intervention studies in patients with coronary artery disease have focused on men, the assumption being that such data can be extrapolated to women. However, there is little evidence to support this belief. We have completed a fifteen-year follow-up of 15,399 adults, including 8262 women, who lived in Renfrew and Paisley and were aged 45-64 years when screened between 1972 and 1976. We identified 490 deaths from coronary heart disease (CHD) in women and 878 in men. Women were more likely to have high cholesterol, to be obese, and to come from lower social classes than men, but they smoked less and had similar blood pressures. The relative risk--top to bottom quintile (95% Cl)--of cholesterol for coronary death after adjustment for all other risk markers was slightly greater in women (1.77 [1.45,2.16]) than in men (1.56 [1.32, 1.85]), but absolute and attributable risk were lower. Thus, women in the top quintile for cholesterol had lower coronary mortality (6.1 deaths per thousand patient years) than men in the bottom quintile (6.8 deaths per thousand patient years). Moreover, it was estimated that there would have been only 103 (21%) fewer CHD deaths in women, yet 211 (24%) fewer in men, if mortality had been the same for women and men in the lowest quintiles of cholesterol. Trends showing similar relative risks in these women, but lower absolute and attributable risks than in men, were present for smoking, diastolic blood pressure, and social class. There was no relation between obesity and coronary death after adjustment for other risks. Our results suggest that some other factors protect women against CHD. The potential for women to reduce their risk of CHD by changes in lifestyle may be less than for men.

Effects of UK 69 578: a novel atriopeptidase inhibitor.

UK 69 578 is a competitive inhibitor of endopeptidase 24.11 (the enzyme that degrades atrial natriuretic factor) in vitro. In vivo, UK 69 578 has renal and cardiovascular effects similar to low-dose atrial natriuretic factor infusion, and may be a useful agent in hypertension and heart failure.

MECHANISM OF RENAL HYPERTENSION

Renal hypertension of the two-kidney type is divided into three stages. In the first, hypertension results from the vasoconstrictor effect of angiotensin II. This persists to some extent in the second phase but there is in addition a slow-developing pressor effect, also resulting from angiotensin II and probably attributable to sodium. In the first two phases removal of the abnormal kidney corrects the hypertension. This fails in the third phase because changes in the opposite kidney maintain hypertension. Renin and angiotensin are probably not involved at this stage.

Combined treatment of severe intractable hypertension with captopril and diuretic.

The converting-enzyme inhibitor, captopril, in a dose of 450 mg daily, was given together with a diuretic to eleven patients with severe hypertension unresponsive to previous therapy. Sustained control of blood pressure was achieved. Plasma angiotensin II and aldosterone fell significantly, whereas plasma active and total renin, and blood-angiotensin-I concentrations increased. Adverse effects included temporary taste disturbance, tachycardia, nephrotic syndrome, and possible drug-induced Guillain-Barré neuropathy. The combination of captopril and diuretic is thus very effective in controlling refractory hypertension. However, because of the frequency and severity of side-effects it should probably be used only in patients whose blood pressure has previously been uncontrolled by other means.

CHANGES OF VASOPRESSIN IN HYPERTENSION: CAUSE OR EFFECT?

Plasma concentrations of arginine-vasopressin (antidiuretic hormone) have been measured in 40 patients with benign essential hypertension and 12 patients with malignant-phase hypertension. Values tended to be low in the benign phase and high in the malignant phase. 5 normal subjects were infused with synthetic arginine-vasopressin, producing plasma concentrations up to five times the highest value recorded in malignant-phase hypertension, without any effect on blood-pressure. There is no evidence that vasopressin has a direct role in the pathogenesis of benign essential hypertension or its transition to the malignant phase. On the contrary, abnormal vasopressin concentrations may be caused by hypertension.

Hypertension with aldosterone excess and low plasma-renin: preoperative distinction between patients with and without adrenocortical tumour.

Abstract A retrospective analysis of thirty-four patients with hypertension, hyperaldosteronism, and low plasma-renin is described. A single adrenocortical adenoma was found in twenty. No tumour was seen in eleven, and the adrenal glands of nine of these showed hyperplasia of the zona glomerulosa. A definite pathological diagnosis was not possible in three patients. Mean plasma concentrations of aldosterone, sodium, and total carbon dioxide were higher, while mean plasma concentrations of renin and potassium were lower in the tumour group, when compared with non-tumour patients. These differences were seen both in patients taking a controlled constant intake of sodium and potassium and in patients taking a normal unrestricted diet. Considerable overlap in each of the variables was found among individual patients, and straightforward analysis of the preoperative biochemical data did not permit a confident prediction of the adrenal lesion. However, a multidimensional computer-assisted analysis enabled complete separation of tumour and non-tumour groups and it is suggested that this technique may be of value in making the preoperative distinction in future cases.

Hyponatraemic hypertensive syndrome with renal-artery occlusion corrected by captopril.

Malignant hypertension with severe hyponatraemia, hypokalaemia, depletion of sodium and potassium, and elevated blood levels of renin, angiotensin I, angiotensin II, aldosterone, and arginine vasopressin developed in a woman with renal-artery occlusion. Plasma angiotensin II was disproportionately high in relation to exchangeable sodium. Captopril, by inhibiting conversion of angiotensin I to angiotensin II, further elevated the blood levels of renin and angiotensin I but corrected all other abnormalities. Unilateral nephrectomy was subsequently curative.

PLASMA ELECTROLYTES, RENIN, AND ALDOSTERONE IN THE DIAGNOSIS OF PRIMARY HYPERALDOSTERONISM: With a Note on Plasma-corticosterone Concentration

Abstract Plasma electrolytes, renin, and aldosterone concentrations were measured in 50 patients with primary hyperaldosteronism. Although plasma-potassium concentration varied over a considerable range in most cases, the levels were consistently lower than 3·7 meq. per litre in 27 patients, and intermittently so in all but 1 of the remainder. It is particularly important to avoid forearm exercise immediately before venepuncture if falsely high potassium values are to be avoided. Plasma-renin concentration was subnormal at least once in 42 patients, and consistently so in 24 of these. The remaining results were normal, most of them falling near the lower limit observed in normal subjects. In several cases sodium restriction caused distinct increases in plasma-renin concentration, and in 1 patient the final level was within the range found in sodium-deprived normal subjects. Plasma-aldosterone concentration was abnormally high on at least one occasion in 38 of the 39 patients in whom it was measured.

Quadric analysis in the preoperative distinction between patients with and without adrenocortical tumors in hypertension with aldosterone excess and low plasma renin

Abstract Retrospective assessment by means of computer-assisted quadric analysis of a series of 31 patients with aldosterone excess and low plasma renin permitted complete separation into two groups—those with, and those without adrenocortical adenoma. Application of these principles to 8 more patients was successful in all cases in correctly diagnosing the type of pathological lesion before operation. Study of four similar published series has shown that each of these could also be accurately differentiated into the two diagnostic categories by quadric analysis. However, probably because of interlaboratory variation, internal analysis using circumscribing quadrics established for each series individually was much more reliable than external analysis with reference to the quadrics of the original series. Quadric analysis, by enabling a confident prediction to be made before operation as to the presence or absence of an adrenocortical adenoma, has major value in the practical management of these patients. In particular, in the cases without adenoma, long-term or definitive spironolactone therapy may now be offered as a valid alternative to extensive bilateral adrenal resection. It is further suggested that the technique of quadric analysis is likely to have wide application in other diagnostic areas.

INTRAVENOUS LABETALOL IN SEVERE HYPERTENSION

1 Labetalol was administered by intravenous infusion or by the combination of intravenous bolus injection plus infusion to 15 patients with severe essential hypertension and to one with phaeochromocytoma. 2 With the infusion alone the reduction of arterial pressure was slow to develop and limited in degree, but with the combination of the bolus injection plus the infusion the reduction in pressure was more prompt, more pronounced and longer lasting. Apart from an uncomplicated syncopal attack in one patient, no serious side effects were encountered. 3 Subsequent treatment with oral labetalol usually required the addition of a diuretic to control the blood pressure probably due to sodium and fluid retention during treatment with labetalol alone.