The cardiovascular benefits of indiscriminate supplementation of omega-3 fatty acids; meta-analysis and decision-making approach.

AIM: The meta-analysis was conducted to estimate of the cardiovascular benefits of indiscriminate supplementation of omega-3 capsules. The results, expressed in terms of quality adjusted life years (QALY) intuitively understood by the general public, can be the basis for the (personal) decision on whether to take omega-3 supplements. METHODS: The results of meta-analysis of eight double-blind, placebo-controlled clinical trials are expressed in terms of QALY, using the Markov model and Monte Carlo simulations. RESULTS: Omega-3 supplementation results in a 8% decrease of the risk of cardiac death, unless the patients are treated by statins. Results indicate that omega-3 supplementation may prolong QALY by about a month. Old people gain less, whereas DM-2 patients and people with history of CV events gain more. DISCUSSION: Our analysis yielded an algorithm for estimating benefit from omega-3 supplementation, based on the age and the individual risk of CV events of the patient.

Adolescents' physical activity habits--results from a national health survey.

BACKGROUND: The MABAT Youth National Health and Nutrition Survey was conducted in Israel by the Ministry of Health and the Center for Disease Control. This article presents results of physical activity (PA) habits in Israel, in relation to recommendations by world health organizations. METHODS: Participants were 6274 adolescents, grades 7-12, enrolled in a cross-sectional, representative, school-based survey. Sufficient level of PA was defined as any moderate and vigorous level of PA that adds up daily to 60 min/day. Light PA was considered to be an insufficient level of PA. RESULTS: Only 10.5% of the participants reported performing sufficient PA. Large gender differences were found, with 17.7% of boys versus only 4.6% of girls meeting the guidelines. CONCLUSIONS: Results highlight the need to develop programmes for school children in Israel to promote PA. Such programmes have been initiated in many countries that have a large percentage of adolescents with a sedentary lifestyle.

Adult-onset diabetes among Arabs and Jews in Israel: a population-based study.

AIMS: To study the age at presentation and factors associated with adult-onset diabetes (≥ 20 years) among Arabs and Jews in Israel. METHODS: Participants (n = 1100) were randomly selected from the urban population of the Hadera District in Israel. The study sample was stratified into equal groups according to sex, ethnicity (Arabs and Jews) and age. Information on age at diabetes presentation, family history of diabetes, history of gestational diabetes, socio-demographic and lifestyle characteristics was obtained through personal interviews. Self reports of diabetes were compared with medical records and were found reliable (κ = 0.87). The risk for diabetes was calculated using Kaplan-Meier survival analysis. Factors associated with diabetes in both ethnic groups were studied using Cox proportional hazard model. RESULTS: The prevalence of adult-onset diabetes was 21% among Arabs and 12% among Jews. Arab participants were younger than Jews at diabetes presentation. By the age of 57 years, 25% of Arabs had diagnosed diabetes; the corresponding age among Jews was 68 years, a difference of 11 years (P < 0.001). The greater risk for diabetes among Arabs was independent of lifestyle factors, family history of diabetes and, among women, history of gestational diabetes; adjusted hazard ratio 1.70; 95% confidence interval 1.19-2.43. CONCLUSIONS: Arabs in Israel are at greater risk for adult-onset diabetes than Jews and are younger at diabetes presentation. Culturally sensitive interventions aimed at maintaining normal body weight and active lifestyle should be targeted at this population. Possible genetic factors and gene-environmental interactions underlying the high risk for diabetes among Arabs should be investigated.

Ethnic variations in acute ischemic stroke: findings from the National Acute Stroke Israeli Survey (NASIS).

BACKGROUND: We intended to determine ethnic differences in the characteristics, management and outcome of acute ischemic stroke between the Israeli Arab and Jewish populations. METHODS: A national survey was conducted in 2004 at all 28 hospitals in Israel. Information on demographics, transportation, risk factors, clinical presentation, stroke severity, type and subtype, management and clinical outcome was obtained. Mortality during the 36 months after hospitalization was assessed by matching with national mortality data. RESULTS: Of the 1,540 patients, 169 (11%) were Arabs and 1,371 (89%) were Jews. The mean age of Arab patients was 9 years younger than in Jewish patients (63 ± 11 vs. 72 ± 12 years). Also, Arabs were more likely to be obese (OR = 1.72; 95% CI: 1.19-2.50) and have diabetes (OR = 1.41; 95% CI: 1.01-1.96), while Jews were more likely to have dyslipidemia (OR = 1.56; 95% CI: 1.11-2.17). A greater percentage of the Arab patients arrived at the hospital independently (OR = 3.85; 95% CI: 2.56-5.56) and were less likely to arrive within 3 h of symptom onset (OR = 2.33; 95% CI: 1.39-3.85). Arabs suffered increased rates of lacunar stroke (OR = 1.67; 95% CI: 1.14-2.43) and were discharged home more often (OR = 2.40; 95% CI: 1.35-4.25). No differences in severity of stroke, management, complications, disability or mortality were found between the 2 groups. CONCLUSIONS: The unique characteristics of the Arab and Jewish populations should be considered when planning stroke-care services and culturally oriented public education programs.

Nutritional recommendations for preventing coronary heart disease in women: evidence concerning whole foods and supplements.

AIMS: Some food groups and supplements have been recommended for preventing coronary heart disease (CHD) in women. In this article, evidence on recommendations for some of these food groups (whole grains, fruits, vegetables, fish, nuts, and soy) and supplements (phytosterols, antioxidants, folic acid, and B-complex vitamins) is reviewed. Additionally, gender differences in nutritional requirements and recommendations are described. DATA SYNTHESIS: Studies of nutrition in women and those emphasizing gender differences in nutritional requirements were selected for this review. CONCLUSION: Observational data support the benefit of vegetables, fruits, and whole grains in CHD prevention. Trial data provide support for consuming fish at least twice a week, although women of childbearing age should limit their intake of fish that may contain high levels of mercury. Nuts are nutritious snacks but their caloric impact must be considered. Soy products do not affect low-density lipoprotein cholesterol (LDL-C) or CHD but may be beneficial in replacing high-fat meat. Foods supplemented with plant stanol/sterol-esters are recommended for reducing LDL-C. Antioxidant supplementation is not recommended for prevention of heart disease. A direct causal relationship between vitamin D deficiency and CHD has not been established. Homocysteine lowering through folic acid and B-complex vitamin supplementation has not been proven to improve CHD risk. More gender-specific analyses are needed to determine whether nutritional requirements differ between men and women.

C-reactive protein distribution and correlates among men and women with chronic coronary heart disease.

BACKGROUND: C-reactive protein (CRP) elevated in inflammation is associated with atherosclerotic disease. We describe the distribution of CRP and its association with coronary heart disease (CHD) risk factors in a large CHD patient group. METHODS: This analysis comprises 2,723 male and 256 female CHD patients, included in the Bezafibrate Infarction Prevention (BIP) study. High sensitive CRP levels were determined in frozen plasma samples. RESULTS: CRP distribution, was normalized upon log transformation. Levels among women were higher than in men in the entire group (4.4 vs. 3.5 mg/l) and in each age group. Co-morbidities, smoking, lower education level, and use of cardiovascular drugs, were associated with elevated CRP levels in both sexes. The correlation between CRP and body mass index (BMI), insulin and glucose was stronger among women. The explained variability in CRP level was larger in women (20%) compared to men (13%). Among women, BMI explained 10% of CRP variability, whereas the contribution of each variable among men was significantly smaller. CONCLUSIONS: Among men and women with CHD, CRP level was correlated with traditional risk factors and to a lesser degree to manifestation of CHD. BMI is the main contributor to CRP variability, explained by these factors among women.

Elevated systolic blood pressure as a predictor of long-term cancer mortality: analysis by site and histologic subtype in 10,000 middle-aged and elderly men.

The association of a casual reading of blood pressure (BP) in 1963 to subsequent 15-year cancer mortality was examined in a cohort of 10,059 middle-aged and elderly men. Systolic BP (SBP), but not diastolic BP, predicted significantly long-term cancer mortality occurring in 369 subjects. The covariate-adjusted relative risk (RR) estimated by Cox's proportional hazard model was 1.10 [95% confidence interval (CI), 1.00-1.21]. In patients aged less than 60 at the beginning of the study, increased cancer mortality was mainly observed in association with SBP of more than 150 mm Hg. In subjects aged 60 or above, the estimated RR was 1.21 (95% CI, 1.03-1.42). Exclusion of 40 men in whom diagnosis made prior to 1963 or death occurred through 1965 did not alter the results. An excess mortality in men who reported pharmacologic treatment for hypertension while under follow-up was fully accountable by their age, BP, and smoking habits. Analysis by site suggested that the association was mainly due to increased mortality from cancer of the digestive and genitourinary organs (estimated RR's, respectively, 1.20 and 1.26; 95% CI's, respectively, 1.03-1.39 and 0.99-1.59). Analysis by histologic subtype suggests an association with adenocarcinoma (RR = 1.19, 95% CI, 1.04-1.37) but not squamous cell or transitional cell carcinomas, myeloma, lymphomas, and leukemias.

Blood lipids and first-ever ischemic stroke/transient ischemic attack in the Bezafibrate Infarction Prevention (BIP) Registry: high triglycerides constitute an independent risk factor.

BACKGROUND: Despite unclear associations between blood lipids, including fractionated cholesterol and triglycerides, and stroke, recent evidence demonstrates that lipid-modifying agents decrease the risk of stroke in patients with coronary heart disease (CHD). METHODS AND RESULTS: Patients with documented CHD who were screened for but not included in the Bezafibrate Infarction Prevention study and had no history of stroke or transient ischemic attack (TIA) (n=11 177) were followed up. At baseline, medical histories were obtained and blood lipids assessed at a central study laboratory. During a 6- to 8-year follow-up period, 941 patients were identified as having nonhemorrhagic cerebrovascular disease, of whom 487 had verified ischemic stroke (per clinical findings and brain CT) or TIA. Patients experiencing an ischemic stroke/TIA had higher mean levels of triglycerides, lower levels of HDL cholesterol, and lower percentages of cholesterol contained in the HDL cholesterol moiety (%HDL; P<0.01 for all). In a logistic regression model, the adjusted ORs for developing an ischemic stroke/TIA were 1.27 (95% CI 1.01 to 1.60) associated with triglycerides >200 mg/dL and 0.87 (95% CI 0.78 to 0.97) associated with a 5% decrease in %HDL. The increased risk associated with high triglycerides was found across subgroups of age, sex, patient characteristics, and cholesterol fractions. CONCLUSIONS: High triglycerides constitute an independent risk factor for ischemic stroke/TIA across subgroups of age, sex, patient characteristics, and cholesterol fractions, whereas high %HDL was an independent protective factor among patients with CHD. These findings support the role of blood lipids, including triglycerides, as important modifiable stroke risk factors.

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.

Relation between the metabolic syndrome and ischemic stroke or transient ischemic attack: a prospective cohort study in patients with atherosclerotic cardiovascular disease.

BACKGROUND AND PURPOSE: The combination of risk factors known as the metabolic syndrome is receiving increased attention, but prospective data on the syndrome's association with ischemic cerebrovascular events are scarce. We explored the relation of metabolic syndrome versus frank diabetes with first-ever ischemic stroke or transient ischemic attack (TIA) in a large cohort of patients with atherosclerotic cardiovascular disease. METHODS: Patients with coronary heart disease, screened for a clinical trial, underwent an extensive medical evaluation and follow-up for cerebrovascular disease over 4.8 to 8.1 years. National Cholesterol Education Program Adult Treatment Panel III criteria were used to define the metabolic syndrome, with body mass index substituted for waist circumference. Patients with previously diagnosed diabetes or with a fasting plasma glucose level >125 mg/dL (> or =7.0 mmol/L) were considered diabetic. RESULTS: The study sample comprised 14,284 patients, of which 3703 (26%) fulfilled the criteria for the metabolic syndrome without diabetes and 3500 others (25%) the criteria for diabetes. Adjusting for stroke risk factors, patients with the metabolic syndrome without diabetes exhibited a 1.49-fold increased odds for ischemic stroke or TIA (95% confidence interval [CI], 1.20 to 1.84), whereas those with frank diabetes had a 2.29-fold increased odds (95% CI, 1.88 to 2.78). The relative odds for ischemic stroke or TIA, associated with presence of the metabolic syndrome per se, were 1.39 (95% CI, 1.10 to 1.77) in men but 2.10 (95% CI, 1.26 to 3.51) in women. Although all components of the metabolic syndrome were associated with increased risk for ischemic stroke or TIA, impaired fasting glucose and hypertension were the strongest predictors of risk. CONCLUSIONS: The presence of the metabolic syndrome, even without diabetes, in patients with pre-existing atherosclerotic vascular disease identifies patients at increased risk for ischemic stroke or TIA. The suggestion of more pronounced risk associated with the metabolic syndrome in women deserves further assessment in other cohorts.

Effect of thrombolytic therapy on the evolution of significant mitral regurgitation in patients with a first inferior myocardial infarction.

OBJECTIVES: This study was designed to test the hypothesis that reperfusion therapy with thrombolysis will prevent the development of significant mitral regurgitation in patients with inferior myocardial infarction. BACKGROUND: The value of thrombolytic therapy in patients with inferior or posterior wall myocardial infarction has been controversial. We hypothesized that successful reperfusion therapy with intravenous thrombolysis may reduce the incidence and severity of postinfarction mitral regurgitation in this patient group. METHODS: We prospectively studied 104 patients with a first inferior myocardial infarction. Thrombolytic therapy was administered to 55 patients (treatment group) 3.2 +/- 2.1 h after the onset of symptoms. The other 49 patients formed the control group. Doppler echocardiographic color flow imaging was performed in all patients within 24 h, at 7 to 10 days and at 28 to 30 days after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3). RESULTS: No significant differences in baseline clinical characteristics were observed between the treatment and control groups. The overall incidence rates of significant mitral regurgitation at 24 h, 7 to 10 days and at 28 to 30 days were 10 (10%) of 104 patients, 18 (17%) of 104 patients and 11 (11%) of 100 patients, respectively. Multivariate analysis reveals the following independent predictors of the occurrence of significant mitral regurgitation: female gender (at 7 to 10 days, odds ratio 5.3, 90% confidence interval [CI] 1.8 to 15.5; at 28 to 30 days, odds ratio 3.7, 90% CI 1.1 to 12.7), heart failure (at 7 to 10 days, odds ratio 7.7, 90% CI 2.2 to 26.9) and transient complete atrioventricular block (at 24 h of myocardial infarction, odds ratio 5.8, 90% CI 1.2 to 27). Compared with the control group, the treatment group exhibited marked reduction in the incidence of significant mitral regurgitation at 24 h (16% vs. 4%; odds ratio 0.1, 90% CI 0.0 to 0.7); at 7 to 10 days (24% vs. 11%; odds ratio 0.3, 90% CI 0.1 to 0.9) and at 28 to 30 days (15% vs. 7%; odds ratio 0.4, 90% CI 0.1 to 1.6). Severe (grade 3) mitral regurgitation developed in five patients in the control group but in no patient in the treatment group. CONCLUSIONS: Thrombolytic therapy in the patients with a first inferior myocardial infarction was associated with a reduced incidence of significant mitral regurgitation. These results support the use of such therapy in patients with inferior myocardial infarction.

Comparative case fatality analysis of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial: variation by country beyond predictive profile. The Investigators of the International Tissue Plasminogen Activator/Streptokinase Mortality Trial.

OBJECTIVES: This study was designed to examine the variation in mortality rates among countries participating in the International Tissue Plasminogen Activator/Streptokinase Mortality Trial. BACKGROUND: Despite uniform inclusion and exclusion criteria and protocol in this trial, 30-day mortality rates (irrespective of treatment allocation) ranged from 4.2% to 14.8% among the participating countries. METHODS: With use of the risk factors identified by a multi-variate logistic model, the total study group was classified into deciles on the basis of each patient's risk profile and individual probability of dying within 30 days. Expected mortality rates were then calculated and compared with actual mortality for each decile of the total study group, as well as for patients from each country. RESULTS: Independent risk factors for mortality were older age (odds ratio 1.97 for each 10-year increment), systolic hypotension (blood pressure < 95 mm Hg) at entry (odds ratio 3.7), Killip class > 1 at entry (odds ratio 3.5), history of antecedent angina (odds ratio 1.23 to 1.49), history of diabetes mellitus (odds ratio 1.64), previous infarction (odds ratio 1.23) and history of never smoking (odds ratio 1.37). The overall mortality rate among the 1,612 patients in risk deciles 9 and 10 was 26%; for the 1,606 patients in deciles 1 and 2 it was 1.2%, with a sensitivity of 58.6% and a specificity of 83.7%. The logistic model closely predicted and explained the different mortality rates for most countries (the differences between expected and actual mortality were nonsignificant). However, in the total study group, the difference between the expected and actual mortality was significant (p < 0.001). This difference was mainly ascribed to the two countries with the highest and lowest mortality rates. When the patients from these two countries were excluded from the analysis, the overall difference became nonsignificant. CONCLUSIONS: These findings suggest that the recognized risk factors associated with increased case fatality in acute myocardial infarction account only in part for mortality differences across or within populations.

Calcium channel blocking agents and risk of cancer in patients with coronary heart disease. Benzafibrate Infarction Prevention (BIP) Study Research Group.

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.

Aspirin and mortality in patients treated with angiotensin-converting enzyme inhibitors: a cohort study of 11,575 patients with coronary artery disease.

OBJECTIVES: The purpose of this study was to investigate the significance of the possible negative interaction between aspirin and angiotensin-converting enzyme (ACE) inhibitors. BACKGROUND: Several provocative reports have recently suggested that aspirin is unsafe in patients with heart failure and has negative interaction with ACE inhibitors that might attenuate their beneficial effects upon survival. METHODS: We analyzed mortality data of 11,575 patients with coronary artery disease screened for the Bezafibrate Infarction Prevention trial. A total of 1,247 patients (11%) were treated with ACE inhibitors. Of them, 618 patients (50%) used aspirin. RESULTS: Five-year mortality was lower among patients on ACE inhibitors and aspirin than patients on ACE inhibitors without aspirin (19% vs. 27%; p < 0.001). After adjusting for confounders, treatment with aspirin and ACE inhibitors remained associated with lower mortality risk than using ACE inhibitors only (relative risk [RR] = 0.71; 95% confidence interval [CI] = 0.56 to 0.91). Subgroup analysis of 464 patients with congestive heart failure treated with ACE inhibitors revealed 221 patients (48%) on aspirin and 243 patients not on aspirin. Although clinical characteristics and therapy were similar, patients taking aspirin experienced lower mortality than patients who did not (24% vs. 34%; p = 0.001). After adjustment, treatment with aspirin was still associated with lower mortality (RR = 0.70; 95% CI = 0.49 to 0.99). CONCLUSIONS: Among coronary artery disease patients with and without heart failure who are treated with ACE inhibitors, the use of aspirin was associated with lower mortality than treatment without aspirin. Our findings contradict the claim that aspirin attenuates the beneficial effect of ACE inhibitors and supports its use in patients with coronary artery disease treated with ACE inhibitors.

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.

High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal?

OBJECTIVE: To analyze the available data to assess the benefits of antihypertensive therapy in hypertensive patients with diabetes mellitus. METHODS: A MEDLINE search of English-language articles published until June 1999 was undertaken with the use of the terms diabetes mellitus, hypertension or blood pressure, and therapy. Pertinent articles cited in the identified reports were also reviewed. Included were only prospective randomized studies of more than 12 months' duration that evaluated the effect of drug treatment on morbidity and mortality in diabetic hypertensive patients. We estimated the risk associated with combination of diabetes mellitus and hypertension and the effect of treatment on morbidity and mortality. RESULTS: The coexistence of diabetes mellitus doubled the risk of cardiovascular events, cardiovascular mortality, and total mortality in hypertensive patients (approximate relative risk of 1.73-2.77 for cardiovascular events, 2.25-3.66 for cardiovascular mortality, and 1.73-2.18 for total mortality). Intensive blood pressure control to levels lower than 130/85 mm Hg was beneficial in diabetic hypertensive patients. All 4 drug classes-diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and calcium antagonists-were effective in reducing cardiovascular events in diabetic hypertensive patients. In elderly diabetic patients with isolated systolic hypertension, calcium antagonists reduced the rate of cardiac end points by 63%, stroke by 73%, and total mortality by 55%. In more than 60% of diabetic hypertensive patients, combination therapy was required to control blood pressure. CONCLUSIONS: Intensive control of blood pressure reduced cardiovascular morbidity and mortality in diabetic patients regardless of whether low-dose diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, or calcium antagonists were used as a first-line treatment. A combination of more than 1 drug is frequently required to control blood pressure and may be more beneficial than monotherapy.

Major factors in the development of diabetes mellitus in 10,000 men.

The average annual incidence of diabetes among 8,688 adult men followed up for five years was 8.0/1,000 with Asian, African and Israeli-born having higher rates than European-born. Multivariate analysis of the findings suggested the following: the most significant variables associated with the development of diabetes are overweight and peripheral vascular disease; the high incidence of diabetes in immigrants from Asia and Africa might be an example of Neel's "thrifty genotype" or failure of adaptation to relatively rapid environmental changes; serum cholesterol level, blood pressure, uric acid level, and education were important also; and the probability of developing diabetes within five years rises from 17/1,000 (when the major variables are low or absent) to 450/1,000 (when they are high and present). This has important clinical implications.

Are lean smokers at increased risk of lung cancer? The Israel Civil Servant Cancer Study.

BACKGROUND: Whether leanness is related to an increased risk of lung cancer is controversial. OBJECTIVE: To examine the association of leanness with lung cancer incidence in a sample of Israeli men. METHODS: The 23-year lung cancer incidence (1963 through 1986) was determined by linkage to the Israel Cancer Registry in 9975 male civil servants aged 40 through 69 years at initial examination in 1963. In 198,298 person-years of follow-up, 153 cases of lung cancer were identified. In 1963, body mass index (BMI) and cigarette smoking status were determined; in the 1968 reexamination, lung function tests were performed and BMI was reassessed. RESULTS: Adjusted for age, smoking, and city by Cox regression, BMI was exponentially inversely related to lung cancer incidence, with a relative risk of 2.3 (95% confidence interval [CI], 1.4 to 3.8) comparing the lowest fifth of BMI (< 22.93 kg/m2) with the highest. The association was evident in light, moderate, and heavy smokers. Among smokers, the adjusted relative risk was 3.7 (95% CI, 1.9 to 7.3) for the lowest fifth of BMI. The associations were stronger for men in the lowest 10th of the BMI distribution (< 21.38 kg/m2). Controlling for lung function did not materially change the results. The adjusted population-attributable fraction associated with the lowest fifth of BMI among smokers was 20.4% (95% CI, 10.1% to 29.9%). Survival analysis showed that the association of BMI with lung cancer persisted throughout follow-up. CONCLUSIONS: The association shown between thinness and lung cancer incidence, particularly in smokers, was not attributable to the confounding factors studied, preclinical weight loss, or competing risks. Thinness in smokers may lead to, or may reflect, enhanced host susceptibility.

Early administration of nifedipine in suspected acute myocardial infarction. The Secondary Prevention Reinfarction Israel Nifedipine Trial 2 Study.

BACKGROUND: The administration of nifedipine, 30 mg/d, between 7 and 22 days after hospitalization for an acute myocardial infarction (Secondary Prevention Reinfarction Israel Nifedipine Trial study) showed no effect on subsequent mortality and morbidity. Since a possible indication of benefit was observed in patients with a second- or higher-order infarction, a second trial was conducted with a higher dose (60 mg/d), early administration (usually within 3 hours of hospital admission), and in high-risk patients only. METHODS: A total of 1358 men and women with suspected acute myocardial infarction (MI), judged not to require calcium antagonist therapy, were randomized to receive nifedipine, 60 mg/d, or placebo between November 1985 and July 1986. Study medication was discontinued in 352 patients because they did not exhibit study criteria for MI or lacked high-risk criteria, or because they decided to discontinue the study. Thus, the treated high-risk group included 1006 patients, of whom 826 were successfully titrated to the target dose of 60 mg/d and were treated for up to 6 months. RESULTS: In the 1006 patients, mortality was 18.7% among those randomized to nifedipine and 15.6% in the patients randomized to placebo. This reflected an increased mortality of 7.8% as compared with 5.5% during the first 6 days in the nifedipine and placebo groups, respectively (adjusted mortality odds ratio by logistic regression, 1.60; 95% confidence interval, 0.86 to 3.00). Among the 826 patients who continued treatment, mortality was equal in the nifedipine (9.3%) and placebo (9.5%) groups. No differences in the rates of nonfatal MI (5.1% and 4.2% in the nifedipine and placebo groups, respectively), hospitalization due to unstable angina, and frequency of chest pain reported during follow-up were observed. An increased rate of sudden death (4.9%) in the placebo group in comparison with the nifedipine group (2.3%) was not statistically significant on post hoc testing, nor was an effect of nifedipine demonstrable in post hoc analyses by congestive heart failure status of randomized patients. CONCLUSION: Nifedipine as a prophylactic treatment in patients immediately after acute MI or in survivors recovering 1 week or longer after acute MI appears ineffective. Early routine administration of nifedipine in acute MI, other than to patients in whom it may be specifically indicated (eg, those with Prinzmetal's variant angina or severe hypertension) may be hazardous and seems to be contraindicated.

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.