Relationship between serum sex hormones and coronary artery disease in postmenopausal women.

Although sex hormones appear to be importantly involved in the development of coronary heart disease, apparently no study has yet reported an alteration in an endogenous sex hormone level in relation to coronary heart disease in women. In an attempt to determine whether any sex hormone abnormality might be a factor in the development of myocardial infarction in women, estradiol and testosterone, as well as sex hormone-binding globulin, insulin, dehydroepiandrosterone sulfate, and risk factors for myocardial infarction, were measured in relation to the degree of coronary artery disease (CAD) in 60 postmenopausal women undergoing coronary angiography. In a multiple-regression analysis with the degree of CAD as the dependent variable and free testosterone (FT), estradiol, age, body mass index, systolic blood pressure, cholesterol, smoking, and insulin as independent variables in the model, only FT (P < .008) and cholesterol (P = .01) were significantly related to the degree of CAD, both positively. To exclude a possible confounding effect due to prior myocardial infarction, the multiple-regression analysis was repeated for the subgroup of 49 patients remaining after excluding the 11 patients who had ever had a myocardial infarction; again only FT (P < .04) and cholesterol (P = .05) were significantly related to the degree of CAD. Neither total testosterone in place of FT nor HDL cholesterol in place of total cholesterol in the model was significantly related to CAD. Sex hormone-binding globulin and dehydroepiandrosterone sulfate, added individually to the model, showed no significant relationship to CAD. These results raise the possibility that in women an elevated FT level may be a risk factor for coronary atherosclerosis.

The association of hyperestrogenemia with coronary thrombosis in men.

Both hyperestrogenemia and hypotestosteronemia have been reported in association with myocardial infarction (MI) in men. It was previously observed that the serum testosterone concentration correlated negatively with the degree of coronary artery disease (CAD) in men who had never had a known MI. The present study investigated the relationship of sex hormone levels to the thrombotic component of MI by comparing these levels in 18 men who had had an MI (ie, thrombosis) and 50 men with no history of MI (ie, no thrombosis) whose degree of CAD was in the same range. The mean degree of CAD, age, and body mass index in these two groups was not significantly different. The mean serum estradiol level in the men who had had an MI (38.5 +/- 8.8 pg/mL) was higher (P = .002) than the level in the men who had not had an MI (31.9 +/- 7.1 pg/mL). The mean levels of testosterone, free testosterone, sex hormone-binding globulin, insulin, dehydroepiandrosterone sulfate, cholesterol, HDI, cholesterol, and systolic and diastolic blood pressure did not differ significantly. Estradiol was the only variable measured that showed a significant relationship to MI (P < .003 by multivariate logistic regression). These findings suggest that hyperestrogenemia may be related to the thrombosis of MI.

The association of hypotestosteronemia with coronary artery disease in men.

Hyperestrogenemia and hypotestosteronemia have been observed in association with myocardial infarction (MI) and its risk factors. To determine whether these abnormalities may be prospective for MI, estradiol and testosterone, as well as risk factors for MI, were measured in 55 men undergoing angiography who had not previously had an MI. Testosterone (r = -.36, P = .008) and free testosterone (r = -.49, P < .001) correlated negatively with the degree of coronary artery disease after controlling for age and body mass index. When the patient group was successively reduced to a final study group of 34 men by excluding the patients with other major disorders, the testosterone and free testosterone correlations persisted (r = -.43, P < .02 and r = -.62, P < .001, respectively). Neither estradiol nor the risk factors, except for high-density lipoprotein cholesterol, correlated with the degree of coronary artery disease in the final group. Testosterone correlated negatively with the risk factors fibrinogen, plasminogen activator inhibitor-1, and insulin and positively with high-density lipoprotein cholesterol. The correlations found in this study between testosterone and the degree of coronary artery disease and between testosterone and other risk factors for MI raise the possibility that in men hypotestosteronemia may be a risk factor for coronary atherosclerosis.

Effects of beta-adrenergic blockade with pindolol versus placebo in coronary patients with stable angina pectoris.

The effect of pindolol, a new beta-blocking agent, was evaluated in 12 patients with proven coronary disease (CAD) and angina pectoris. Evaluation was done using a double-blind crossover technique comparing pindolol at both 15 mg/day and 30 mg/day to placebo. Compared with placebo, pindolol slightly decreased the number of anginal episodes and nitroglycerin pills consumed while showing evidence of beta blockade during exercise. However, we could not demonstrate any effect on exercise endurance on the treadmill at either dose. Pindolol shows a modest beneficial effect on ischemic manifestations in CAD patients with angina pectoris.

Effects of nitroglycerin on the major determinants of myocardial oxygen consumption. An angiographic and hemodynamic assessment.

A direct and quantitative study of the effects of sublingually administered nitroglycerin on the major determinants of myocardial oxygen consumption was carried out in 10 patients, 7 with coronary artery disease. Left ventricular wall tension, estimates of the contractile state and heart rate were studied directly using simultaneous pressure measurements and angiographically obtained volume determinations. The peak systolic left ventricular wall tension decreased 15 percent after administration of nitroglycerin, suggesting a diminished myocardial oxygen requirement. Increased myocardial oxygen requirements were suggested by the occurrence of both positive chronotropic and inotropic effects. Heart rate increased 15 percent. The mean circumferential fiber shortening velocity increased 26 percent and the ejection fraction 30 percent; these findings, in association with a 23 percent reduction in left ventricular end-diastolic volume, were considered consistent with an increase in the contractile state. The mechanism of action of nitroglycerin seems to relate best to the decrease in systolic wall tension. The end-diastolic tension decreased 57 percent, suggesting the possibility that diastolic coronary blood flow may be augmented by diminished extravascular resistance to flow.

Inferior myocardial infarction and right coronary artery occlusive disease. A correlative study.

The present study represents an attempt to correlate the electrocardiogram and coronary arteriogram in patients with an inferior transmural infarct - or total occlusion of the right coronary artery. The influence of the collateral circulation on these findings was also evaluated. Fifty patients with a total occlusion of the right coronary artery had characteristic electrocardiographic changes of an inferior infarct in 44 per cent, very suspicious changes in 32 per cent, and no changes suggesting an inferior infarct in 24 per cent. However, in this latter group who had no evidence of an inferior infarct, we were able to recognize a small number who showed an anterior wall infarct. Collateral circulation was more frequently present and more extensive in those patients whose electrocardiograms did not show changes typical of inferior transmural infarction. This suggested that collateral circulation might minimize some of the electrocardiographic abnormalities which would normally result from occlusive disease of the right coronary artery. Another 50 patients, selected because of definite electrocardiographic evidence of typical inferior transmural infarction, were evaluated by coronary arteriography. Severe obstructive disease of the right coronary artery was present in 86 per cent of the group. In the remaining 7 patients (14 per cent) minimal or no disease was found. Infarction of the inferior wall may have resulted from occlusive disease of the anterior descending artery or have been the result of a right coronary artery occlusion with subsequent recanalization. We conclude from our study that a careful analysis of electrocardiographic abnormalities in theinferior leads will, with certain limitations, permit us to estimate the likelihood of a severe lesion in the right coronary artery, and, in the face of definite electrocardiographic evidence of an inferior infarct, to predict the diseased artery.