Henrietta Reicher-Reiss

Usefulness of beta-blocker therapy in patients with non-insulin-dependent diabetes mellitus and coronary artery disease

The benefit of beta-blocker therapy in patients after myocardial infarction is well established. The use of beta blockers in the high-risk subgroup of patients with combined diabetes mellitus (DM) and coronary artery disease (CAD) remains controversial. From a database of 14,417 patients with chronic CAD who had been screened for participation in the Bezafibrate Infarction Prevention (BIP) study, 2,723 (19%) had non-insulin-dependent DM. Baseline characteristics and 3-year mortality were analyzed in patients with DM receiving (n = 911; 33%) and not receiving (n = 1,812; 67%) beta blockers. Total mortality during a 3-year follow-up was 7.8% in those receiving beta blockers compared with 14.0% in those who were not (a 44% reduction). A reduction in cardiac mortality of 42% between the 2 groups was also noted. Three-year survival curves showed significant differences in mortality with increasing divergence (p = 0.0001). After multiple adjustment, multivariate analysis identified beta-blocker therapy as a significant independent contributor to improved survival (relative risk = 0.58; 90% confidence interval 0.46 to 0.74). Within the diabetic population, the main benefit associated with beta-blocker therapy was observed in older patients, in those with a history of myocardial infarction, those with limited functional capacity, and those at lower risk. Thus, therapy with beta blockers appears to be associated with improved long-term survival in the high-risk subpopulation of patients with DM and CAD.

Elevated Serum Triglyceride Levels and Long-Term Mortality in Patients With Coronary Heart Disease: The Bezafibrate Infarction Prevention (BIP) Registry

BACKGROUND The association between elevated blood triglyceride levels and subsequent mortality risk in patients with established coronary heart disease (CHD) has been investigated rarely. The aim of the present study was to investigate this association. METHODS AND RESULTS We evaluated mortality over a mean follow-up time of 5. 1 years among 9033 male and 2499 female CHD patients who were screened for participation in the Bezafibrate Infarction Prevention (BIP) Study. A stepwise increase in mortality with increasing serum triglyceride levels was observed in patients with desirable or elevated serum total cholesterol levels and in patients with either desirable or abnormally low HDL cholesterol levels. Multivariate adjustment for factors other than HDL cholesterol yielded a slightly increased adjusted mortality risk with a 1-natural-log-unit elevation of triglyceride levels in men (hazard ratio [HR] 1.14, 95% CI 1.00 to 1.30) and women (HR 1.37, 95% CI 1.04 to 1.88). Excess covariate-adjusted risk was noted among patients with elevated total and LDL cholesterol and in women with HDL cholesterol levels >45 mg/dL. After additional adjustment for HDL cholesterol, the risk of mortality with a 1-natural-log-unit elevation of triglycerides declined in men (HR 1.09, 95% CI 0.94 to 1.26) and in women (HR 1.10, 95% CI 0.80 to 1.50). A trend for increased mortality risk remained in patients with elevated total and LDL cholesterol and in women with HDL cholesterol >45 mg/dL. CONCLUSIONS Elevated triglyceride levels were associated with a small, independent increased mortality risk in CHD patients. This risk may be increased among subgroups of patients with elevated total cholesterol and LDL cholesterol levels.

Circadian variation and possible external triggers of onset of myocardial infarction

PURPOSE To determine whether a circadian pattern in onset of symptoms existed and possible external triggers were implicated in the precipitation of acute myocardial infarction (AMI). PATIENTS AND METHODS One thousand eight hundred eighteen consecutive patients with AMI hospitalized in 14 of the 21 existing coronary care units in Israel during the study period were assessed. RESULTS The frequency of onset of symptoms by 6-hour intervals showed a predominant morning peak (6 AM to noon) (32%, p < 0.01) in comparison with the other three 6-hour intervals of the day. The preponderance of the morning peak persisted for subgroup analysis by gender (males 32%, females 31%); age (less than or equal to 65 years--32%; greater than 65 years--33%); diabetes mellitus (present or absent, 32%). However, patients with peripheral vascular disease and those with stroke in the past had a predominant evening peak. Possible external triggers of onset of AMI were present in 10% of patients. Exceptional heavy physical work, violent quarrel at work or at home, and unusual mental stress were the three most frequent possible external triggers reported immediately before or within the 24 hours preceding pain onset. Patients with possible external triggers were more likely to be males (85%) and were somewhat but not significantly younger (63.1 years) in comparison with patients without external triggers (73% and 64.3 years respectively). CONCLUSIONS In a large group of consecutive patients with AMI, a predominant cyclic morning peak of pain onset was found in comparison with the other hours of the day. Possible external triggers precipitating AMI were involved in a minority of cases, suggesting that endogenous changes occurring in the morning hours are generally responsible for the increased rate of myocardial infarction occurring after awakening.

Cardiogenic shock complicating acute myocardial infarction in patients without heart failure on admission: Incidence, risk factors, and outcome

PURPOSE Patients with large myocardial infarction (MI) presenting with clinical signs of heart failure are at increased risk for subsequent development of cardiogenic shock and death. Little is known, however, about the development of cardiogenic shock among patients with acute MI presenting without clinical signs of heart failure. The aim of the present study was to examine the incidence, predictors for occurrence, and outcome of in-hospital development of cardiogenic shock among patients with acute MI without heart failure on admission. PATIENTS AND METHODS Clinical data of 5,839 consecutive patients hospitalized with acute MI were analyzed. RESULTS Of 3,465 (59%) patients without heart failure on admission (Killip class I), 89 (2.6%) developed cardiogenic shock during their hospital stay. This represented 24% of all cases of in-hospital cardiogenic shock in the entire group. Cardiogenic shock developed more than 24 hours after admission in 66% of cases. All but three patients with cardiogenic shock died whereas a 5% in-hospital mortality was found among patients without cardiogenic shock. Independent predictors for in-hospital shock were age (for a 10-year increment, adjusted relative odds [RO] = 2.45, 90% confidence interval [CI] = 1.50 to 4.02); female gender (RO = 1.51, 90% CI = 0.91 to 2.50); history of angina (RO = 2.64, 90% CI = 1.36 to 3.76); history of stroke (RO = 2.12, 90% CI = 1.26 to 6.35); peripheral vascular disease (RO = 1.99, 90% CI = 0.95 to 4.18); peak lactate dehydrogenase (LDH) greater than four times the normal (RO = 3.16, 90% CI = 1.79 to 5.57); and hyperglycemia on admission (RO = 3.52, 90% CI = 2.13 to 5.84). Patients with six risk factors (excluding LDH values) had an estimated probability of 35% for developing in-hospital cardiogenic shock. CONCLUSIONS (1) A significant proportion of MI patients who developed cardiogenic shock during hospitalization were free of heart failure on admission. (2) Our study identified several risk factors facilitating early identification of subgroups at risk for cardiogenic shock within otherwise low-risk patients.

Ten-year survival after acute myocardial infarction: Comparison of patients with and without diabetes

Abstract In a prospective study among 5839 consecutive patients after acute myocardial infarction (AMI), the prognosis of men and women with diabetes was compared with that of patients without diabetes after AMI. The prevalence of insulin-treated diabetes or diabetes treated with oral hypoglycemic drugs was 2% and 8% among men and 6% and 12% among women respectively. After multiple regression analysis, the odds ratio for in-hospital mortality was 1.26 (95% confidence interval [CI] 0.82 to 1.92) for non-insulin-treated men with diabetes and 2.24 (95% CI 1.14 to 4.38) for those treated with insulin. Among women, these odds ratios were 1.46 (95% CI 0.90 to 2.36) and 1.80 (0.93 to 3.51), respectively. The 10-year relative risk for death was 1.32 (95% CI 1.10 to 1.58) for men with non-insulin-treated diabetes and 1.75 (95% CI 1.26 to 2.45) for men treated with insulin. For women, the respective relative risks for 10-year mortality were 1.41 (95% CI 1.10 to 1.82) for those treated with oral hypoglycemic drugs and 2.59 (95% CI 1.89 to 3.56) for diabetic women treated with insulin. We conclude that (1) diabetes requiring treatment emerged as an independent predictor of short- and long-term mortality after AMI; (2) diabetic women had a worse long-term prognosis than diabetic men after AMI; and (3) diabetic patients treated with insulin had the worst short- and long-term prognosis after AMI in both genders. (Am Heart J 1997;133:290-6.)

Calcium antagonists and mortality in patients with coronary artery disease: A Cohort study of 11,575 patients☆

OBJECTIVES This study sought to establish the risk ratio for mortality associated with calcium antagonists in a large population of patients with chronic coronary artery disease. BACKGROUND Recent reports have suggested that the use of short-acting nifedipine may cause an increase in overall mortality in patients with coronary artery disease and that a similar effect may be produced by other calcium antagonists, in particular those of the dihydropyridine type. METHODS Mortality data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention study (5,843 with and 5,732 without calcium antagonists) after a mean follow-up period of 3.2 years. RESULTS There were 495 deaths (8.5%) in the calcium antagonist group compared with 410 in the control group (7.2%). The age-adjusted risk ratio for mortality was 1.08 (95% confidence interval [CI] 0.95 to 1.24). After adjustment for the differences between the groups in age and gender and the prevalence of previous myocardial infarction, angina pectoris, hypertension, New York Heart Association functional class, peripheral vascular disease, chronic obstructive pulmonary disease, diabetes and current smoking, the adjusted risk ratio declined to 0.97 (95% CI 0.84 to 1.11). After further adjustment for concomitant medication, the risk ratio was estimated at 0.94 (95% CI 0.82 to 1.08). CONCLUSIONS The current analysis does not support the claim that calcium antagonist therapy in patients with chronic coronary artery disease, whether myocardial infarction survivors or others harbors an increased risk of mortality.

Primary Ventricular Tachycardia in Acute Myocardial Infarction: Clinical Characteristics and Mortality

OBJECTIVE To examine the immediate and long-term clinical and prognostic significance of primary ventricular tachycardia, defined as tachycardia of ventricular origin occurring within 48 hours of acute myocardial infarction in patients without hemodynamic compromise (Killip class I). DESIGN Prospective cohort study. SETTING Intensive coronary care units in eight regional, referral, and university hospitals. PATIENTS A total of 162 patients with primary ventricular tachycardia, both sustained and nonsustained (study group), and 2578 counterparts without ventricular tachycardia (reference group). MEASUREMENTS In-hospital rates of atrial fibrillation, atrioventricular block, congestive heart failure, cardiogenic shock, and cardiac arrest. In-hospital and 1-year follow-up rates of sudden death, nonsudden cardiac death, and noncardiac death. RESULTS The study and reference groups had similar mortality (in-hospital, 6.8% and 9.6%, P greater than 0.2 and at 1 year after discharge, 3.7% and 5.4%, P greater than 0.2, respectively) and in-hospital complication rates (atrioventricular block, 13.0% and 9.7%, P greater than 0.2; cardiogenic shock, 3.7% and 3.0%, P greater than 0.2; cardiac arrest, 1.8% and 4.4%, P greater than 0.2, respectively). Patients with sustained ventricular tachycardia (28 patients) compared with those with nonsustained ventricular tachycardia (134 patients) had higher rates of polymorphic tachycardia (50% compared with 6%, P = 0.001), in-hospital total cardiac mortality (21% compared with 4%, P = 0.003) and sudden-death mortality (14% compared with 2%, P = 0.001); they also showed a trend toward a higher in-hospital mortality than the reference group (21.4% compared with 9.6%, P = 0.15) but had no increased mortality 1 year after discharge (4.6% compared with 5.4%, P greater than 0.2). CONCLUSIONS As a group, patients with primary ventricular tachycardia do not differ from counterparts without primary ventricular tachycardia in their in-hospital clinical course and 1-year prognosis. Primary sustained ventricular tachycardia is often polymorphic and carries worse in-hospital prognosis than nonsustained tachycardia. However, it does not predict recurrent ventricular tachycardia or increased sudden-death rates during the next year.

A prospective study of plasma fibrinogen levels and the risk of stroke among participants in the bezafibrate infarction prevention study.

PURPOSE Plasma fibrinogen has emerged as an important predictor of cardiovascular disease, but few data are available on its association with stroke. We sought to determine if plasma fibrinogen is a marker of increased risk or a direct causative risk factor for stroke. SUBJECTS AND METHODS Patients from the Bezafibrate Infarction Prevention Study, a placebo-controlled, randomized clinical trial of secondary prevention of coronary heart disease by lipid modification with bezafibrate retard (400 mg daily), were studied. Plasma fibrinogen levels were measured at baseline and yearly thereafter. Stroke, a prospectively monitored endpoint, was systematically assessed regarding stroke type, subtype, and functional outcome. RESULTS Mean baseline fibrinogen levels were significantly higher in patients subsequently having a cerebrovascular event (140 strokes, 36 transient ischemic attacks; mean follow-up, 6.2 years) than in patients who did not (375 vs. 349 mg/dL, P <0.0001). Fibrinogen levels did not differ significantly by the type, subtype, or severity of the cerebrovascular event. Risk of ischemic stroke increased from 3.3% in the lowest tertile (baseline fibrinogen <314 mg/dL) to 7.% in the middle tertile (fibrinogen 314 to 373 mg/dL) to 10% in the upper tertile (fibrinogen >373 mg/dL, P <0.001). Adjusting for age, blood pressure, and other covariates, fibrinogen levels in the upper tertile were associated with more than a twofold increase in risk of ischemic stroke compared with in the lowest tertile (hazard ratio = 2.6; 95% confidence interval: 1.5 to 4.3). We did not find fibrinogen change from baseline to be related to subsequent ischemic stroke events. CONCLUSION Plasma fibrinogen is a strong predictor of, rather than a direct causative factor for, subsequent stroke among patients at increased risk owing to manifest coronary heart disease.

Calcium Channel Blocking Agents and Risk of Cancer in Patients With Coronary Heart Disease

OBJECTIVES This analysis sought to estimate the risk ratio for cancer incidence and cancer-related mortality associated with the use of calcium channel blocking agents (CCBs) in a large group of patients with chronic coronary heart disease (CHD). BACKGROUND Recent publications contend that the use of short-acting CCBs may double the risk of cancer incidence and possibly increase mortality in hypertensive patients. METHODS Cancer incidence data were obtained for 11,575 patients screened for the Bezafibrate Infarction Prevention (BIP) study, one-half of whom were treated at the time of screening with CCBs, over a mean follow-up period of 2.8 years. Cause-specific mortality was available through September 1996 (mean follow-up 5.2 years). The statistical power of detecting an odds ratio > or = 1.5 (given the cancer incidence rate of 2.1 in the nonusers of CCBs) was 0.91. The power declined to 0.77, 0.54 and 0.41, with declining odds ratios of 1.4, 1.3 and 1.25, respectively. RESULTS Of 246 incident cancer cases, 129 occurred among the users (2.3%) and 117 among nonusers of CCBs (2.1%). After adjustment for age, gender and smoking, the odds ratio estimates for all cancers combined was 1.07 (95% confidence interval [CI] 0.83 to 1.37) for CCB users relative to nonusers. The adjusted risk ratio for all-cause mortality for age, gender and smoking and pertinent prognostic clinical characteristics was estimated at 0.94 (95% CI 0.85 to 1.04). The adjusted risk ratio for cancer-related mortality was 1.03 (95% CI 0.75 to 1.41). CONCLUSIONS Patients with CHD treated with CCBs exhibited a similar risk of cancer incidence and total and cancer-related mortality compared with nonusers of CCBs. This analysis provides a certain assurance that CCB use in middle-aged and elderly patients with CHD is not associated with a meaningful difference in cancer incidence and related mortality.

The outcome of patients with a first non-Q wave acute myocardial infarction presenting with ST segment depression, ST segment elevation, or no ST deviations on the admission electrocardiogram

UNLABELLED We evaluated the prognosis of patients with a first non-Q wave myocardial infarction according to their admission electrocardiogram. Hospital and 1-year mortality rates in patients with ST elevation (15%, and 21% respectively) and ST depression (17%, and 27% respectively) were similar and significantly higher than in patients with no ST changes (3%, and 10% respectively). Likewise, the adjusted hospital and 1-year mortality risks of patients with ST elevation or depression were comparable but higher than the corresponding mortality risk of patients with no ST deviations. The cumulative 5-year mortality rate was highest among patients with ST segment depression (51%) compared to patients with ST elevation (34%) or no ST deviation (21%), (p<0.001 for both comparisons). The adjusted 5-year mortality risk of patients with ST depression was higher (HR: 1.83, 95% C.I., 1.17-2.83) compared to patients with baseline ST elevation (HR-1.33, 95% C.I., 0.83-2.12) or patients with no ST changes (reference group). Patients with baseline ST segment elevation and coexistent ST segment depression in other electrocardiogram leads, had a higher in-hospital mortality rate (19%) compared to counterparts without concomitant ST depression (10%) and a tendency for higher in-hospital mortality risk but not for subsequent 1- and 5-year mortality risks. CONCLUSIONS Patients with a first non-Q wave MI with ST elevation or depression on admission have similar hospital and 1-year mortality risk, but the long-term mortality risk is higher among patients with ST segment depression. Patients with ST elevation and concomitant ST segment depression are at increased risk for mortality during the index hospitalization.