Status of glucose metabolism in patients with heart failure secondary to coronary artery disease.
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Biomedical subjects
Publications and source records attributed to Solomon Behar.
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OBJECTIVES: The goal of this study was to assess soluble intercellular adhesion molecule-1 (sICAM-1) level as a predictor of future acute coronary events in patients with chronic coronary heart disease (CHD). BACKGROUND: Increased sICAM-1 concentration has been shown to be associated with the incidence of CHD in healthy persons. Its significance in patients with CHD has been scarcely investigated. METHODS: We designed a prospective, nested case-control study. Sera were collected from patients with CHD enrolled in a secondary prevention trial that evaluated the efficacy of bezafibrate in reducing coronary events. We measured baseline sICAM-1 concentration in the sera of patients who developed subsequent cardiovascular events (cases: n = 136) during follow-up (mean: 6.2 years) and in age- and gender-matched controls (without events: n = 136). RESULTS: Baseline serum concentrations of sICAM-1 were significantly higher in cases versus controls (375 vs. 350 ng/ml; p < 0.05). Each 100 ng/ml increase in sICAM-1 concentration was associated with 1.27 (95% confidence interval [CI]: 1.00 to 1.63) higher relative odds of coronary events. Soluble ICAM-1 concentration in the highest quartile (>394 ng/ml) was associated with significantly higher odds of coronary events (compared with the lowest quartile), even after multivariate adjustment (2.31, 95% CI: 1.02 to 5.50). After adding fibrinogen and total white blood cell count to the multivariate model, the relative odds were 2.12 (95% CI: 0.88 to 5.35) and 2.70 (95% CI: 1.10 to 7.05), respectively. CONCLUSIONS: Elevated sICAM-1 concentration in CHD patients is associated with increased risk of future coronary events independent of other traditional risk factors.
Unlike thrombolytic agents, there are conflicting data regarding the time-dependent effect of aspirin treatment on outcome in acute myocardial infarction (AMI). We sought to evaluate the impact of timing of aspirin administration (before vs after thrombolysis) on mortality of patients with AMI. Our study included 1,200 patients with ST elevation AMI treated with thrombolysis. Early (n = 364) versus late (n = 836) users were defined as those receiving emergency aspirin before versus after initiation of thrombolysis, respectively. Time (median) from symptom onset to initiation of aspirin treatment was significantly shorter in early versus late users (1.6 vs 3.5 hours; p <0.001). There were no significant differences between the 2 groups with respect to baseline clinical characteristics. Early aspirin users were more likely to develop reischemia, to be treated with beta blockers, to be referred to coronary angiography, percutaneous transluminal coronary angioplasty, or coronary artery bypass graft surgery. Early users experienced lower mortality at 7 days (2.5% vs 6.0%, p = 0.01), 30 days (3.3% vs 7.3%, p = 0.008), and 1 year (5.0% vs 10.6%, p = 0.002) than late users. This survival benefit persisted for patients with and without previous aspirin therapy or revascularization and after adjustment for baseline characteristics and therapies at 7 days (odds ratio 0.36, 95% confidence interval 0.15 to 0.79), at 30 days (odds ratio 0.39, 95% confidence interval 0.17 to 0.82), and at 1 year (odds ratio 0.41, 95% confidence interval 0.21 to 0.74). Our study proposes a time-dependent benefit from aspirin in patients with AMI treated with thrombolysis.
PURPOSE: Little is known about the advantages and disadvantages of participation in a clinical trial for patients with coronary heart disease. We hypothesized that participation itself in a long-term clinical trial with regular clinical evaluation and adjustment of treatments might lead to survival gain among patients with coronary artery disease who agreed or refused to participate in the Bezafibrate Infarction Prevention study. SUBJECTS AND METHODS: The study was performed in 18 university hospitals. There were 3502 patients who fulfilled the inclusion criteria. Among them, 3122 patients signed informed consent and were included in the study ("participants"), whereas 380 declined to participate ("nonparticipants"). For all participants, routine visits to the clinics were scheduled bimonthly for study medication distribution and compliance assessment, and every 4 months for clinical evaluation and management. Nonparticipants continued with community-based treatment and were followed only for mortality. RESULTS: The two groups were similar with regard to age, sex, and the prevalence of most cardiovascular diseases, risk factors, and medications, except that participants were more likely to have presented with an anginal syndrome (1788 [57%] vs. 190 [50%]) and to have symptomatic heart failure (754 [25%] vs. 66 [18%]). During follow-up (mean [+/- SD], 7.7 +/- 0.8 years), 475 patients died. All-cause mortality was similar in participants (n = 423 [13.6%]) and nonparticipants (n = 52 [13.7%]). In a multivariate analysis, participation in the clinical trial was not associated with all-cause mortality (hazard ratio [HR] = 0.96; 95% confidence interval [CI]: 0.70 to 1.30) or cardiac mortality (HR = 1.12; 95% CI: 0.72 to 1.74). CONCLUSION: Participation in a long-term clinical trial in a country with readily accessible community-based medicine may not lead to survival gain in patients with coronary artery disease.
OBJECTIVE: Reducing time to reperfusion therapy is one of the goals in the management of acute myocardial infarction (AMI). We assessed the association between timing of aspirin administration and outcome of patients with AMI. PATIENTS: We studied 922 consecutive AMI patients with ST-segment elevation in Killip class I-III on admission. Patients were divided into two groups based upon the timing of emergency aspirin administration: before (early aspirin users) or after (late aspirin users) hospital admission. RESULTS: Early aspirin users (n = 338; 37%) were younger, less likely to be women, and more likely to smoke (p < 0.006) than late users (n = 584; 63%). Other baseline and clinical characteristics were similar. Early aspirin users were more likely to be treated with thrombolysis or primary percutaneous transluminal coronary angioplasty. Compared with late users, early aspirin users had significantly lower in-hospital complications and lower mortality rates at 7 (2.4 vs. 7.3%, p = 0.002) and 30 days (4.9 vs. 11.1%, p = 0.001). By multivariate adjustment, pre-hospital aspirin was an independent determinant of survival at 7 (odds ratio 0.43; 95% confidence interval 0.18-0.92) and at 30 days (odds ratio, 0.60; 95% confidence interval 0.32-1.08). Survival benefit associated with aspirin persisted for subgroups treated or not with reperfusion therapy. CONCLUSIONS: Outcome of AMI patients treated with aspirin is improved by pre-hospital administration. Our findings suggest that emergency pre-hospital aspirin might facilitate early reperfusion.
BACKGROUND AND PURPOSE: Inflammation is considered to be involved in the pathogenesis of ischemic stroke. Our purpose was to assess the role of soluble intercellular adhesion molecule-1 (sICAM-1) concentration, a marker of inflammation, in predicting future ischemic stroke among patients at risk because of chronic coronary heart disease. METHODS: We obtained baseline serum samples from patients with chronic coronary heart disease enrolled in the Bezafibrate Infarction Prevention trial (n=3090), which assessed the efficacy of bezafibrate in secondary prevention. Using a prospective nested case-control design, we measured baseline sICAM-1 concentration in sera of patients who developed ischemic stroke during a mean follow-up of 8.2 years (cases, n=134) and in age- and sex-matched controls without any subsequent cardiovascular events (n=134). RESULTS: Baseline serum concentrations of sICAM-1 were significantly higher in cases compared with controls (379 versus 350 ng/mL, P<0.05). sICAM-1 concentration at the highest quartile (>394 ng/mL) was associated with significantly higher relative odds of ischemic stroke compared with the lower concentrations after adjustment for potential confounding variables (relative odds, 2.1; 95% CI, 1.1 to 4.3). After fibrinogen and total white blood cell count were added to the multivariable model, the relative odds were 2.1 (95% CI, 1.1 to 4.2) and 2.2 (95% CI, 1.1 to 4.8), respectively. The risk associated with raised concentrations of sICAM-1 seemed to be highest for large disabling strokes of cardioembolic origin. CONCLUSIONS: Elevated concentrations of sICAM-1, a marker of inflammation, are associated with increased risk of ischemic stroke, independent of other traditional cerebrovascular risk factors and of plasma fibrinogen, among patients at increased risk because of manifest coronary heart disease.
BACKGROUND AND PURPOSE: Ischemic stroke and coronary heart disease (CHD) share risk factors and pathogenic process, ie, atherosclerosis and thrombosis. We examined the relationship between severity of angina pectoris and its accompanying characteristics and the risk of incident ischemic stroke. METHODS: We traced 3122 patients with stable CHD, included in a secondary prevention trial of lipid modification, the Bezafibrate Infarction Prevention trial. CHD was documented by a history of myocardial infarction > or =6 months and < 5 years before enrollment and/or stable angina pectoris with evidence of ischemia confirmed by ancillary diagnostic testing. Severity of angina pectoris was assessed according to the Canadian Cardiovascular Society angina classification, and heart failure functional class according to the New York Heart Association (NYHA) classification. Patients with severe heart failure or unstable angina on enrollment were excluded. RESULTS: During a mean follow-up period of 8.2 years, 186 patients developed an ischemic stroke. The cumulative rate of ischemic stroke increased in a dose-response manner from 4.7% in patients with no angina to 5.7%, 8.4%, and 12.9% in patients with angina classes 1, 2, and 3, respectively (P<0.001). Patients with NYHA functional class 1 had a 5.5% rate of ischemic stroke versus 7.3% and 9.6% in patients with classes 2 and 3, respectively (P=0.05). In a Cox proportional-hazard model adjusting for conventional risk factors and potential confounders, the hazard ratio associated with angina class 1 was 1.20 (95% CI, 0.83 to 1.74); class 2, 1.66 (95% CI, 1.12 to 2.45); and class 3, 2.35 (95% CI, 1.08 to 5.13), as compared with patients with no angina. Hazard ratios of ischemic stroke associated with conventional risk factors were 1.55 for a 10-year age increment, 2.16 for diabetes mellitus, 1.81 for current smoking, and 1.29 for a 20 mm Hg increase in systolic blood pressure. CONCLUSIONS: Severity of angina pectoris in patients with stable CHD predicts an increased risk of subsequent ischemic stroke. The association between angina class and incident ischemic stroke is independent of traditional vascular risk factors.
BACKGROUND: Clinical studies showing an association between immigration and increased prevalence of coronary risk factors or mortality rate in patients with coronary artery disease are scarce. OBJECTIVES: To compare the risk profile and mortality of coronary patients born in Israel with those who immigrated to Israel, and to determine whether recent immigration is associated with greater risk among immigrants from the Soviet Union. METHODS: Demographic, clinical, and laboratory data were collected on chronic coronary artery disease patients from 18 Israeli medical centers during the screening period of the Bezafibrate Infarction Prevention Study in the early 1990s. Data on mortality after a mean 7.7 year follow-up were obtained from the Israel Population Registry. RESULTS: While significant differences in mortality (14.7% vs. 18.5%, P < 0.001) were observed between Israeli-born patients and immigrants respectively, the mortality in these groups was similar when compared within specific age groups. Immigrants suffered more from hypertension and angina pectoris, and their New York Heart Association functional limitation class was higher, as compared to their Israeli-born counterparts. A multivariate analysis of mortality comparing patients from the Soviet Union who immigrated after 1970 with those who immigrated before 1970 showed an increased risk for newer immigrants, with a hazard ratio of 1.69 (95% confidence interval 1.19-2.40) for those immigrating between 1970 and 1984, and 1.68 (95% CI 1.01-2.28) for those immigrating between 1985 and 1991. CONCLUSION: The worse profile and prognosis observed among patients who recently emigrated from the Soviet Union cannot be explained by traditional risk factors for CAD such as smoking, diabetes, hypertension, and lipid disorders. Further investigation, including variables such as psychological stress to which immigrants are more exposed than others, is needed.
The number of elderly patients experiencing myocardial infarction (MI) is growing rapidly, and their hospital mortality rate remains high, although mortality after acute MI declined in the 1990s. The in-hospital and first-year mortality rates in 5,839 patients with acute MI in 1981-1983 were compared with 1,014 consecutive patients admitted in 1992 to the coronary care units in Israel. The clinical characteristics of gender, prior MI, and acute MI location were similar in the age subgroups in both periods. Patients admitted in 1981-1983 did not receive thrombolytic therapy, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass grafting (CABG), whereas in those admitted in 1992, the frequency of thrombolytic therapy in the age subgroups at or below 55 years, 56-74 years, and at or above 75 years decreased with advanced age (56%, 48%, and 24%, respectively, P is less than.0001). The frequency of PTCA also declined (11%, 7%, and 3%, respectively, P is less than.002). The in-hospital mortality rate for the entire study population declined from 18% in 1981-1983 to 11% in 1992 (adjusted odds ratio [OR] 0.49; 95% confidence interval, 0.39-0.62). The decline in in-hospital mortality was more marked among patients aged 56-74 (18.0%-10.0%; OR 0.48) and those aged at or above 75 years (35.0%-21.5%; OR 0.44), than among patients aged at or below 55 years (6.9%-4.3%; OR 0.70). This decline was most marked in reperfused patients, particularly the very elderly (OR 0.31; 95% CI 0.14-0.69). The cumulative first-year mortality declined by 40% (from 25.5% in 1981-1983 to 17.9% in 1992, hazard ratio (HR) 0.61; 95% CI 0.52-0.72). The decline was more marked among patients aged 56-74 years (26.2%-16.5%; HR 0.56) and those aged at or above 75 years (49.6%-37.6%; HR 0.58) than among counterparts aged at or below 55 years (10.2%-7.9%; HR 0.86). The decline was most marked in reperfused patients, particularly the very elderly (HR 0.31; 95% CI 0.16-0.59). In conclusion, (1) during the last decade in Israel, cumulative first-year mortality after an acute MI declined by 40% and was most marked in patients aged greater than 55 years and in particular the very elderly (at or above 75 years); (2) the main improvement in survival was achieved early after the acute MI, and was maintained thereafter during the first postinfarction year; 3) the favorable outcome in 1992 is related to changes in patients management, mainly reperfusion therapy (thrombolysis, PTCA, CABG); and (4) reperfusion therapy in elderly patients with acute MI should be considered systematically unless specific contraindications are present.
BACKGROUND: The significance of admission blood glucose level in nondiabetic patients with heart failure (HF) is unknown. We examined the possible association between admission glucose levels and outcome in a large cohort of hospitalized patients with HF. METHODS: We analyzed the data of 4102 patients with HF, who were hospitalized during a prospective national survey. The present study focuses on a subgroup of 1122 nondiabetic patients with acute HF who were admitted because of acute HF or exacerbation of chronic HF. RESULTS: In-hospital mortality was twice as high in patients with admission blood glucose levels in the third tertile (7.2%) compared with the first (3%) and second (4%) tertiles (P = .02). Furthermore, mortality risk was correlated with admission glucose levels; each 18-mg/dL (1-mmol/L) increase in glucose level was associated with a 31% increased risk of in-hospital mortality (adjusted odds ratio, 1.31; 95% confidence interval, 1.10-1.57; P = .003) and a 12% increase in 60-day mortality (adjusted hazard ratio, 1.12; 95% confidence interval, 1.01-1.25; P = .04). Admission blood glucose levels remained an independent predictor of in-hospital and 60-day mortality even after the exclusion of 315 patients (28%) with acute myocardial infarction and HF. The 6- and 12-month mortality rates were similar in patients with and without abnormal admission blood glucose levels. CONCLUSIONS: Elevated admission blood glucose levels are associated with increased in-hospital and 60-day mortality, but not 6-month or 1-year mortality, in nondiabetic patients hospitalized because of HF.
In a nationwide survey conducted in all 26 hospitals in Israel during February and March 2000, data were collected on 2133 consecutive acute coronary syndrome patients. The patients were divided into three age subgroups: <65 years (n=974), 65-74 years (n=500), and > or =75 years (n=639). The frequency of no anginal pain/atypical symptoms on presentation increased with age for all acute coronary syndrome patients (14%, 21%, and 32%, in the three age subgroups, respectively; p for trend <0.0001). The frequency of ST-elevation on admission electrocardiogram decreased with advancing age (59%, 46%, and 42%, in the three age subgroups, respectively; p for trend <0.0001), whereas ST-depression gradually increased (14%, 24%, and 28%, respectively; p for trend <0.0001). In multivariate analysis, variables associated with no anginal pain/atypical symptoms on presentation (in decreasing order) were: history of heart failure, age, lack of past angina, diabetes, and nonsmoking. ST-elevation was inversely associated with no anginal pain/atypical symptoms on admission (odds ratio, 0.48; 95% confidence interval, 0.37-0.63). The use of acute reperfusion therapy significantly declined with advancing age. Seven-day, 30-day, and 1-year mortality increased with advancing age. No anginal pain/atypical symptoms on presentation were associated with an increased early and late mortality in all three age subgroups.