Cardiovascular consequences of obesity.

Obesity is common in populations that are overnourished and can become a significant public health problem. Obesity predisposes to non-insulin dependent diabetes mellitus, hypertension, dyslipidemia, cholelithiasis, some malignancies and osteoarthritis. These consequences that most directly affect the cardiovascular system are dyslipidemia and hypertension. Nations in which obesity is rare should learn from the experience of the countries where it is prevalent, that prevention of obesity is a public health measure rather than weight reduction.

Coronary artery disease in women.

The past three decades have seen coronary artery disease investigated almost exclusively in men. Data about this disease in women come from the longitudinal Framingham study and mortality statistics. According to the Framingham study, angina is more often the first symptom of coronary disease in women, while for men it is more often myocardial infarction. Post menopausal women are two to three times more likely to have a heart attack than premenopausal. Forty per cent of female cardiac patients versus 13% of men suffered a second heart attack. Sudden death, a frequent manifestation of coronary disease in men, occurs rarely in women until old age. Women aged 35 to 64 years were more vulnerable to risk factors of systolic blood pressure, blood glucose and excess weight than men. Cigarette smoking, highly correlated in men, was not a significant risk factor in women. The greater the number of risk factors, the greater the risk of developing coronary artery disease. Central or truncal obesity is associated with higher blood pressure and hyperinsulinemia which is thought to result in increases in atherogenic lipoproteins and decreases in high density lipoprotein cholesterol.

Systemic hypertension and the kidney in black patients.

Hypertension occurs more frequently in U.S. blacks than whites and is more severe. Blacks represent a disproportionate percentage of patients receiving dialysis treatment. This disproportion raises the question of whether the renal circulation of blacks is more sensitive to the damaging effects of elevated intraarterial pressure or whether it is structurally different in ways that would render it more prone to damage. The first part of the question has not been conclusively answered although some data support the hypothesis. For the second part, it is clear that malignant nephrosclerosis of blacks is different from that of whites in an absence of fibrinoid necrosis of arterioles and glomeruli and the presence of musculomucoid intimal hyperplasia of small arteries. Whether this is a genetically determined reaction to damage has not been determined. It is a widely held belief that the kidney is the cause of much essential hypertension. In fact 6 cases of essential hypertension in blacks have been "cured" by renal transplantation, strongly supporting the belief. Also blacks differ from whites in 2 ways that could be relevant for their increased prevalence of hypertension: they excrete sodium loads more slowly and have a markedly lower urinary kallikrein. The former could be responsible for the predominance of salt-dependent hypertension in blacks and the latter could reflect a racial deficiency in a naturally occurring vasodilator system.

The sympathetic nervous system and hypertension in primary aldosteronism.

To assess the role of the sympathetic nervous system in mineralocorticoid hypertension in humans, results from 24 patients with aldosterone-producing adenoma were compared with those in 27 appropriately matched essential hypertensive subjects and 26 normotensive subjects. Resting plasma catecholamine levels averaged 292 +/- 140 (SD) pg/ml in patients with aldosterone-producing adenoma, 305 +/- 101 in patients with essential hypertension, and 260 +/- 120 in normotensive subjects; none of the differences among the three groups was significant. With head-up tilt (60 degrees for 10 min) plasma catecholamine levels increased similarly in the aldosterone-producing adenoma and essential hypertensive groups (up to 681 +/- 111 and 611 +/- 57 pg/ml respectively, NS). beta-Blockade (propranolol, 10 mg i.v.) in eight aldosterone-producing adenoma patients decreased heart rate (from 78 +/- 5 to 68 +/- 3 beats/min, p less than 0.005) and cardiac output (from 5.5 +/- 0.4 to 4.6 +/- 0.3 liter/min, p less than 0.001), but left mean blood pressure unchanged (127 +/- 4 to 127 +/- 2 mm Hg). Combined alpha- and beta-blockade with phentolamine and propranolol in five patients with aldosterone-producing adenoma produced no detectable changes in blood pressure. Thus, results from biochemical, functional, and pharmacological studies in humans showed no evidence of enhanced peripheral sympathetic activity in the hypertension of primary aldosteronism.

The changing clinical spectrum of primary aldosteronism.

In a prospective study of 80 patients with primary aldosteronism (70 with adenoma and 10 with hyperplasia), "refractory" hypertension, hyperkinetic circulation, and hypovolemia were frequent occurrences. We found that measurements of serum potassium concentration and plasma renin activity were inadequate screening tests because of high rates of false-positive and false-negative results. The demonstration of excessive aldosterone production after three days of salt loading provided the best sensitivity (96 percent) and specificity (93 percent) in identifying patients with primary aldosteronism. Severe, persistent hypokalemia, increased plasma 18-hydroxycorticosterone values, and an anomalous postural decrease in the plasma aldosterone concentration, when present, provided the best indicators of the presence of an adenoma. Of three localizing procedures (selective adrenal venography, adrenal computed tomographic scan, and adrenal venous sampling for plasma aldosterone concentration) the measurement of adrenal venous plasma aldosterone concentration yielded 100 percent accuracy. These results indicate a wider clinical spectrum in primary aldosteronism than previously described. They also show that nonsuppressible aldosterone production is its most important diagnostic hallmark and the single best diagnostic screening procedure, and that adrenal venous sampling for plasma aldosterone concentration remains the most precise technique for identification and localization of tumors.

Selective hypoaldosteronism despite prolonged pre- and postoperative hyperreninemia in primary aldosteronism.

In a prospective study of 7 patients with aldosterone-producing adenoma (APA), long-term (6-72 months) preoperative stimulation of plasma renin activity (PRA) by diuretic therapy (spironolactone plus hydrochlorothiazide) did not prevent selective aldosterone deficiency postoperatively. In all patients aldosterone excretion rate (AER) fell to subnormal values (from a mean of 97 to 2.6 mug/24 h) following removal of APA, although PRA remained elevated. Generalized adrenocortical insufficiency was excluded by the demonstration of normal baseline plasma cortisol and urinary 17-OHCS and the appropriate response to ACTH stimulation. In 6 of 7 patients studied 1-3 months postoperatively, short-term (4 days) sodium deprivation evoked normal increases in PRA, but AER response was blunted (except in 1). Restudy of 3 of 6 patients after 6-12 months revealed that aldosterone production had returned to normal. These results indicate that renin deficiency is not the principal cause of postoperative selective hypoaldosteronism in these patients. On the other hand, they appear to substantiate the possibility raised by in vitro and in vivo studies that spironolactone can directly inhibit aldosterone biosynthesis.

Hyperkinetic heart in severe hypertension: a separate clinical hemodynamic entity.

A long-term study of established hypertension helped identify a well defined group of 10 patients who differed both clinically and hemodynamically from 59 patients with the more frequent form of this disease. Their cardiac output was significantly increased (P less than 0.001) despite a severe elevation of arterial pressure (average 212/125 mm Hg plus or minus 13.5/7.3[standard error[). All had labile hypertension of long standing (16.2 years average) that was difficult to control and always symptomatic; in all, the diagnosis of pheochromocytoma had to be specifically excluded. Increased myocardial contractility was suggested by (1) significant elevation of the rate of rise of isovolumic pressure (P less than 0.001), and (2) high ratio of cardiac output to cardiopulmonary volume (P less than 0.005). Beta adrenergic blockade with propranolol helped to alleviate symptoms and to control tachycardia but failed by itself to reduce arterial pressure.