Estrogen replacement and coronary artery disease. Effect on survival in postmenopausal women.

The relationship among postmenopausal estrogen use, coronary stenosis, and survival was examined retrospectively in 2268 women undergoing coronary angiography. The patients were selected for study if their age was 55 years or older at the time of angiography or if they had previously undergone bilateral oophorectomy. Postmenopausal estrogen use in 1178 patients with coronary artery disease (greater than 70% stenosis) and 644 patients with mild to moderate coronary artery disease (5% to 69% stenosis) was compared with 446 control subjects (0% stenosis) using life-table analysis. Over 10 years of follow-up, there was no significant difference in survival among patients initially free of coronary lesions on arteriography who had either never used (377) or ever used (69) estrogens. Among patients with mild to moderate coronary stenosis, 10-year survival of those who had never used estrogens was 85.0% and it was 95.6% among 99 "ever users." Survival was 60.0% among those with more than 70% coronary stenosis who had never used estrogen and it was 97.0% among 70 ever users. The "never users" group were older (65 vs 59 years), had a lower proportion of cigarette smokers (40% vs 57.1%), a higher proportion of subjects with diabetes (21.7% vs 12.9%) and hyperlipidemia (58% vs 44%), and approximately equal numbers of hypertensives (56.0% vs 54.3%). Cox's proportional hazards model was used to estimate survival as a function of multiple covariables. Estrogen use was found to have a significant, independent effect on survival in women. We conclude that estrogen replacement after menopause prolongs survival when coronary artery disease is present, but it has less effect in the absence of coronary artery disease.

Clinical and pathophysiologic correlates of ST-T-wave abnormalities in coronary artery disease.

Clinical, hemodynamic and coronary angiographic data from 9,801 patients were evaluated to determine the correlates of ST-segment depression, with or without T-wave inversion, on the resting routine electrocardiogram. The relative risk (RR) of having a measured clinical or angiographic variable was computed whether or not ST-T-wave abnormalities were observed. ST-segment depression was seen significantly more often in subjects greater than 55 years of age (RR = 1.4) who were women (RR = 1.3) or nonwhite (RR = 1.5), were hypertensive (RR = 1.8), had diabetes mellitus (RR = 1.6) or who smoked cigarettes (RR = 1.5). Angiographic findings related to presence of ST-T-wave abnormalities included severe coronary obstruction (less than 70%), higher number of diseased vessels, and the presence of obstruction in the left anterior descending coronary artery. In a multivariate model, the most significant correlates of ST-T-wave abnormalities were presence of left ventricular contraction abnormality, followed by age, gender, presence of left anterior descending coronary artery disease, elevated end-systolic volume index, and a diagnosis of hypertension. Thus, electrocardiographic ST-T abnormalities has specific and significant clinical and pathophysiologic correlates.

Interactive effects of age and other risk factors on long-term survival after coronary artery surgery.

The effect of age at the time of coronary artery bypass graft surgery on postoperative survival was studied in 2,507 patients with significant coronary artery disease. Patients were subdivided into five groups based on age at the time of surgery: 20 to 39, 40 to 49, 50 to 59, 60 to 69 and greater than or equal to 70 years. The observed death rate was compared with that expected for subjects from the general U.S. population matched for age, gender, race and calendar year. For patients less than or equal to 59 years of age, the ratio of observed to expected death rates was significantly greater than unity (observed/expected = 4.9 for ages 20 to 39, 1.9 for ages 40 to 49 and 1.3 for ages 50 to 59 years, p less than 0.01). The prevalence of risk factors, including diabetes mellitus, hypertension, hypercholesterolemia and cigarette smoking, was evaluated in the different age subgroups. When patients were subdivided on the basis of history of cigarette smoking, the decreased relative survival rate of younger (less than 60 years old) patients existed only in those who smoked (observed/expected = 6.0 for ages 20 to 39, 2.2 for ages 40 to 49 and 1.4 for ages 50 to 59 years). In nonsmokers, observed/expected ratios for every age group were not significantly different from unity. Thus, the reduced relative survival rate of younger patients after coronary artery bypass graft surgery may be attributed to the interactive harmful effects of cigarette smoking.

Postmenopausal estrogen use and coronary atherosclerosis.

STUDY OBJECTIVE: To determine whether estrogen replacement therapy affects the prevalence of severely obstructive coronary arterial lesions defined by selective coronary arteriography. DESIGN: Case-control study. SETTING: Large, urban, university-affiliated referral hospital. PATIENTS: From a consecutive sample of 6452 women having coronary arteriography between 1972 and 1984, 2188 patients were eligible for study; others were excluded because they were nonmenopausal, had congenital heart defects, valvular heart disorders, primary myocardial disease, or no more than mild to moderate coronary artery disease. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hospital nurses routinely obtained medication histories. Staff invasive cardiologists interpreted coronary arteriograms. Clinical, laboratory, and angiographic data were abstracted from the cardiac catheterization reports and entered into a computerized registry. Postmenopausal estrogen use for 1444 cases of coronary artery disease (70% stenosis) was compared to that 744 controls (0% stenosis). The odds ratio estimate of the risk of coronary artery disease for estrogen users relative to the risk of coronary artery disease for nonusers was 0.44 (95% confidence interval, 0.29 to 0.67) after adjustment for age, cigarette smoking, diabetes, cholesterol, and hypertension. Postmenopausal estrogen replacement was a significant independent protective factor for coronary artery disease in a multivariate logistic regression model (P = 0.037). CONCLUSION: The data suggest that postmenopausal estrogen treatment reduces the risk for angiographically significant coronary artery disease.

Prognostic value of the pressure-volume ratio in patients with coronary artery disease.

To determine if the peak-systolic pressure/end-systolic volume ratio [PSP/ESV], a load-insensitive index of left ventricular function, predicted perioperative mortality and long-term survival after coronary artery bypass surgery or medical treatment, 4,829 patients with coronary artery disease were studied retrospectively. Cardiac volumes, ejection fraction, and PSP/ESV ratio were computed using standard methods, and follow-up was performed using annual questionnaires. PSP/ESV ratio values were not significantly different (p = .09) between those who died during hospitalization (n = 101) after coronary surgery and those who were discharged. Long-term follow-up in surgically treated patients demonstrated a 97% 3-year and 93% 5-year survival for those with PSP/ESV over 2.292. These were significantly greater (p = .0026) in value in patients with PSP/ESV less than 1.237 (3-year and 5-year survival of 92 and 79.2%, respectively). In the medical group, survival rate for those with PSP/ESV over 2.292 at 5 years was 89.3%, while for those with PSP/ESV less than 1.237 it was 52.5% (p less than .001). Multivariate analysis, however, showed ejection fraction to be a more significant predictor of survival in both the groups compared with PSP/ESV ratio. Thus, PSP/ESV ratio does predict long-term survival in coronary disease patients treated either surgically or medically. Ejection fraction was nevertheless a more powerful predictor of outcome.

Natural history of left anterior descending coronary artery obstruction: significance of location of stenoses in medically treated patients.

We examined the prognostic significance of an obstructive lesion in the proximal left anterior descending (LAD) coronary artery. Five-year or longer follow-up data were examined from 311 patients with greater than 70% obstruction of the LAD treated without surgery. Mortality was compared in subsets with lesions proximal to and distal to the first septal perforating artery. Survival curves were worse in patients with proximal than with distal LAD disease (p less than 0.05); lesion location remained a significant determinant of survival when ejection fraction, age, and sex were controlled using a Cox regression model. However, when patient subsets were examined, survival with proximal LAD disease was worse than with distal obstruction only in the presence of an associated right coronary artery lesion and an ejection fraction of less than 40% (p less than 0.01). Patients with proximal LAD plus right coronary lesions had a 5-year mortality rate (34.08 +/- 8.9%) that was not significantly (p greater than 0.05) different from that of a group of 66 patients with greater than 50% narrowing of the left main coronary artery (24.02 +/- 4.3%). Thus, proximal LAD disease is more significant than is a distal lesion only in the presence of right coronary obstruction. This two-vessel combination results in a mortality rate as high as that associated with left main coronary artery obstruction.

Natural history of chronic mitral insufficiency: relation of peak systolic pressure/end-systolic volume ratio to morbidity and mortality.

The ratio of peak systolic pressure to end-systolic volume (PSP/ESV) is a measure of contractility that is relatively independent of loading conditions. To define the relation of this index to the natural history of chronic mitral insufficiency, follow-up studies were performed in 76 patients. All had isolated mitral insufficiency and were followed up for an average of 48 months. None underwent surgery. Cardiac volumes, ejection fraction and PSP/ESV ratio were calculated and Cox multiple regression analyses were performed to determine the relation of functional status, ejection fraction and PSP/ESV ratio to morbidity and mortality. Twenty-three patients died during follow-up; in 70% of those who died, the PSP/ESV ratio was reduced below the 20th percentile. However, as an independent predictor of mortality, this ratio was less sensitive (p greater than 0.05) than ejection fraction (p less than 0.01). Similarly, functional status change was predicted more accurately by ejection fraction (p less than 0.01) than by the PSP/ESV ratio (p greater than 0.05). Thus, although a decreased PSP/ESV ratio was associated with a higher mortality rate, other clinical and laboratory variables were superior to this index for determining morbidity and mortality in patients with isolated mitral insufficiency.

The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time.

The effect of steady-state increases in systemic arterial pressure on the duration of left ventricular ejection time was studied in 11 normal male subjects. Methoxamine, a pressor amine of predominantly vasoconstrictor activity but lacking significant inotropic effect, was administered intravenously resulting in an average increase in mean arterial pressure of 27 mm Hg. Heart rate was held constant by high right atrial pacing, and there was no significant change in cardiac output. During methoxamine infusion, when stroke volume, heart rate, and inotropic state were held constant, left ventricular ejection time increased as mean arterial pressure increased. There was a highly significant correlation between the increase in mean systolic blood pressure and the prolongation of left ventricular ejection time (r = 0.870). In one subject, an increase in mean systolic pressure of 75 mm Hg prolonged left ventricular ejection time 55 msec, producing paradoxical splitting of the second heart sound. The prolongation of left ventricular ejection time during infusion was not blocked by the prior intravenous administration of atropine sulfate or propranolol hydrochloride, thus ruling out both vagal inhibition of the left ventricle and reflex withdrawal of sympathetic tone as its cause. In three subjects, left ventricular end diastolic pressure was measured and found to be significantly increased. This finding suggests that the normal left ventricle maintains a constant stroke volume in the presence of an increased pressure load by the Frank Starling mechanism. This study concludes that arterial pressure must be included as a prime determinant of left ventricular ejection time along with stroke volume, heart rate, and inotropic state in intact man.