Uri Goldbourt

Major types of dietary fat and risk of coronary heart disease: a pooled analysis of 11 cohort studies

BACKGROUND Saturated fatty acid (SFA) intake increases plasma LDL-cholesterol concentrations; therefore, intake should be reduced to prevent coronary heart disease (CHD). Lower habitual intakes of SFAs, however, require substitution of other macronutrients to maintain energy balance. OBJECTIVE We investigated associations between energy intake from monounsaturated fatty acids (MUFAs), polyunsaturated fatty acids (PUFAs), and carbohydrates and risk of CHD while assessing the potential effect-modifying role of sex and age. Using substitution models, our aim was to clarify whether energy from unsaturated fatty acids or carbohydrates should replace energy from SFAs to prevent CHD. DESIGN This was a follow-up study in which data from 11 American and European cohort studies were pooled. The outcome measure was incident CHD. RESULTS During 4-10 y of follow-up, 5249 coronary events and 2155 coronary deaths occurred among 344,696 persons. For a 5% lower energy intake from SFAs and a concomitant higher energy intake from PUFAs, there was a significant inverse association between PUFAs and risk of coronary events (hazard ratio: 0.87; 95% CI: 0.77, 0.97); the hazard ratio for coronary deaths was 0.74 (95% CI: 0.61, 0.89). For a 5% lower energy intake from SFAs and a concomitant higher energy intake from carbohydrates, there was a modest significant direct association between carbohydrates and coronary events (hazard ratio: 1.07; 95% CI: 1.01, 1.14); the hazard ratio for coronary deaths was 0.96 (95% CI: 0.82, 1.13). MUFA intake was not associated with CHD. No effect modification by sex or age was found. CONCLUSION The associations suggest that replacing SFAs with PUFAs rather than MUFAs or carbohydrates prevents CHD over a wide range of intakes.

In-hospital and 1-year mortality in 1,524 women after myocardial infarction. Comparison with 4,315 men.

We determined in-hospital and 1-year prognoses after acute myocardial infarction (MI) in 5,839 consecutive patients derived from 14 of 21 coronary care units in Israel during 1981-1983. Age-adjusted in-hospital mortality was 23.1% in 1,524 women and 15.7% in 4,315 men (p less than 0.0005). One-year age-adjusted mortality rates in patients surviving hospitalization were 11.8% in women and 9.3% in men (p = 0.03). Cumulative age-adjusted 1-year mortality rates were 31.8% in women and 23.1% in men (p less than 0.0005). Relative odds of mortality, covariate-adjusted for major prognostic factors that included age, prior MI, congestive heart failure, and infarct location by electrocardiogram, indicated that female gender was independently and significantly associated with increased mortality both during hospitalization (relative odds, 1.72; 95% confidence interval, 1.45-2.04) and at 1 year after discharge (relative odds, 1.32; 95% confidence interval, 1.05-1.66). In separate multivariate analyses for each gender, a major factor that emerged as a predictor of outcome in women, but not in men, was a reported history of diabetes mellitus, both for in-hospital mortality and for 1-year mortality. However, even in the nondiabetics in this population, female gender was a significant, independent predictor of in-hospital mortality. The findings of the present study substantiate that women fare worse than men after suffering an acute MI, that increased age does not fully account for the increased mortality in women, and that diabetic women are at particularly high risk once MI has occurred.

Fish Consumption and Incidence of Stroke A Meta-Analysis of Cohort Studies

Background and Purpose— Results from observational studies on fish consumption and risk of stroke are inconsistent. We quantitatively assessed the relationship between fish intake and incidence of stroke using a meta-analysis of cohort studies. Methods— We searched the Medline and Embase databases (1966 through October 2003) and identified 9 independent cohorts (from 8 studies) that provided a relative risk (RR) and corresponding 95% CI for total or any type of stroke in relation to fish consumption. Pooled RR and 95% CI of stroke were estimated by variance-based meta-analysis. Results— Compared with those who never consumed fish or ate fish less than once per month, the pooled RRs for total stroke were 0.91 (95% CI, 0.79 to 1.06) for individuals with fish intake 1 to 3 times per month, 0.87 (95% CI, 0.77 to 0.98) for once per week, 0.82 (95% CI, 0.72 to 0.94) for 2 to 4 times per week, and 0.69 (95% CI, 0.54 to 0.88) for ≥5 times per week (P for trend= 0.06). In stratified analyses of 3 large cohort studies with data on stroke subtypes, the pooled RRs across 5 categories of fish intake were 1.0, 0.69 (95% CI, 0.48 to 0.99), 0.68 (95% CI, 0.52 to 0.88), 0.66 (95% CI, 0.51 to 0.87), and 0.65 (95% CI, 0.46 to 0.93) for ischemic stroke (P for trend= 0.24); and 1.0, 1.47 (95% CI, 0.81 to 2.69), 1.21 (95% CI, 0.78 to 1.85), 0.89 (95% CI, 0.56 to 1.40), and 0.80 (95% CI, 0.44 to 1.47) for hemorrhagic stroke (P for trend= 0.31). Conclusions— These results suggest that intake of fish is inversely related to risk of stroke, particularly ischemic stroke. Fish consumption as seldom as 1 to 3 times per month may protect against the incidence of ischemic stroke.

Angina pectoris among 10,000 men: II. Psychosocial and other risk factors as evidenced by a multivariate analysis of a five year incidence study

The major independent role played by anxiety and severe psychosocial problems (especially family ones) is demonstrated by this multivariate analysis of a five year prospective study of the development of new angina pectoris among almost 10,000 adult men (average annual incidence = 5.7/1,000). The independent effect of these two variables is considerably augmented by the other significant risk factors of age, total serum cholesterol, systolic or diastolic blood pressure, certain electrocardiographic abnormalities and diabetes mellitus. The presence of all seven risk factors (at a high level) increases the probability of angina pectoris developing within five years to 289/1,000 from 14/1,000, when these factors are low or absent. The wifes love and support is an important balancing factor, which apparently reduces the risk of angina pectoris even in the presence of high risk factors. The implications of these findings to the pathophysiology and prevention of angina are stressed.

Factors Predictive of Long-Term Coronary Heart Disease Mortality among 10,059 Male Israeli Civil Servants and Municipal Employees

Over 10,000 male civil servants and municipal employees in Israel, aged 40 years and above, underwent an extensive clinical, biochemical, anthropometric, sociodemographic and psychosocial evaluation in 1963, 1965 and 1968. Follow-up for mortality was continued through 1986. Over 23 years, a number of previously established risk factors for coronary heart disease (CHD) incidence were found to predict mortality. The long-term follow-up assisted in illustrating temporal patterns. A single causal assessment of blood pressure retained high prediction for long-term mortality. Blood lipids, while significantly associated with both coronary and all-cause mortality, exhibited a small contribution to the latter, when compared to hypertension, cigarette smoking habits and diabetes. Weak associations of long-term coronary mortality with the dietary intake patterns of fatty acids, as reported at baseline, were probably fully mediated by the effect of the diet on serum cholesterol. Religious orthodoxy appeared to provide a degree of immunity, part of which was independent of life-style correlates. A number of now well-established associations in cardiovascular epidemiology were first demonstrated, or amplified, in the study. Patterns of ethnic diversity in the risk factor and prevalence rates of CHD persisted, as viewed from the angle of mortality rates, over nearly a quarter of a decade, highlighting the enigma of a migrant country as a cardiovascular melting pot.

Diabetes mellitus in midlife and the risk of dementia three decades later

Objective: To examine the association between diabetes in midlife (1963–1968) and dementia more than three decades later (1999–2001). Methods: The authors characterized dementia using standard methods for 1,892 participants among 2,606 survivors of 10,059 participants in the Israeli Ischemic Heart Disease study, a longitudinal investigation of the incidence of and risk factors for cardiovascular disease among Jewish male civil servants in Israel. Face to face interviews were conducted with the 652 subjects identified as possibly demented by the Modified Telephone Interview for Cognitive Status. Logistic regression analysis was performed to assess the association of diabetes with dementia controlling for sociodemographic and cardiovascular variables compared to those with no cognitive impairment. Results: Of 1,892 assessed subjects (mean age 82 at assessment), 309 (16.3%) had dementia. Diabetic subjects had significantly more dementia than non-diabetic subjects (χ2 = 7.54, df = 1, p = 0.006, OR 2.83 [95% CI = 1.40 to 5.71]). Those who survived to the time of this study were younger and healthier than those who died. Conclusions: Evidence for diabetes as a risk factor for dementia was found, similar to other epidemiologic studies. In contrast to the earlier studies, however, the authors linked diabetes in midlife to dementia more than three decades later in the very old survivors of a large male cohort.

Risk Factors and Segment-Specific Carotid Arterial Enlargement in the Atherosclerosis Risk in Communities (ARIC) Cohort

BACKGROUND AND PURPOSE B-mode ultrasound imaging affords the opportunity to quantify both intimal-medial thickness (IMT) and lumen diameter of extracranial carotid arteries in ambulatory populations. Since the relation of IMT to lumen diameter may be complex, we asked whether cardiovascular disease risk factors (previously shown to be associated with greater arterial IMT) are related to smaller lumen diameters. METHODS We used B-mode ultrasound to quantify lumen diameter, interadventitial diameter, and IMT of the extracranial carotid arteries and assessed the relationship of these measures to body mass index, smoking, low-density lipoprotein (LDL) and high-density lipoprotein cholesterol, hypertension, and diabetes in 6088 male and 7493 female participants in the Atherosclerosis Risk in Communities (ARIC) cohort. RESULTS Smoking, hypertension, and LDL cholesterol were consistently related to greater IMT in the common and internal carotid arteries of men and women, as has been previously reported. In the internal carotid artery, smoking, hypertension, and LDL cholesterol were consistently related to smaller lumens. In the common carotid artery, body mass index, smoking, and hypertension were related to significantly larger, and LDL cholesterol to smaller, lumens. Thus, only LDL cholesterol was consistently associated with smaller lumens in both the common and internal carotid arteries. CONCLUSIONS Risk factors relate positively to IMT in both the common and internal carotid arteries and inversely with lumen diameter in the internal carotid artery, in parallel with their relation to clinical events. However, their association with lumen diameters of the common carotid artery in population-based samples is more complex, and in some cases adverse levels of risk factors may be associated with larger lumens.

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.

Rationale and design of a secondary prevention trial of increasing serum high-density lipoprotein cholesterol and reducing triglycerides in patients with clinically manifest atherosclerotic heart disease (the bezafibrate infarction prevention trial)

Controlled clinical trials have demonstrated the efficacy of reducing the blood levels of low-density lipoprotein cholesterol in reducing the incidence of coronary artery disease in hypercholesterolemic middle-aged men. However, a similar reversibility of the risk of coronary artery disease has not been demonstrated for high-density lipoprotein cholesterol elevation and triglyceride reduction. Therefore, the effect of administering 400 mg of bezafibrate retard daily versus placebo (double blind) to patients with myocardial infarction preceding randomization by 6 months to 5 years, or a clinically manifest anginal syndrome documented by objective evidence of dynamic myocardial ischemia, or both, is being investigated. Three thousand subjects (aged 45 to 74 years) are being enrolled from 19 cardiac departments in Israel, with total serum cholesterol between 180 and 250 mg/dl, high-density lipoprotein cholesterol < or = 45 mg/dl and triglycerides < or = 300 mg/dl. In addition, low-density lipoprotein cholesterol concentrations are required to be < or = 180 mg/dl (< or = 160 mg/dl for patients aged < 50 years). Patients needing lipid-modifying therapy, exhibiting > or = 1 prespecified exclusion criterion or not giving informed consent, or a combination, are not randomized. The primary end points for evaluating efficacy are the incidence of fatal and nonfatal myocardial infarction, and sudden death. The hypothesized effect of bezafibrate administration under the aforementioned protocol is to reduce an estimated cumulative end point event incidence of > or = 15% by 20 to 25% over an average follow-up period of 6.25 years, through early 1998, when the last patient recruited will have completed 5 years.(ABSTRACT TRUNCATED AT 250 WORDS)

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 syndromes 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 (≥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.