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.

Exploring determinants of progression in Parkinson's disease. Is there a difference among Jewish ethnic groups?

INTRODUCTION: Parkinson's disease (PD) displays an individually variable rate of progression, of which the underlying mechanisms are largely unknown, but may involve genetic factors. In this study, we aimed to explore the effect of ethnic origin on PD progression rate in Israeli Jews, as expressed by time from onset until reaching Hoehn and Yahr stage 3 (HY3). METHODS: Consecutive patients with PD followed bi-annually at the Movement Disorders Institute at Sheba Medical Center, were included. Demographic data and clinical information, including age at PD onset (AO), H&Y staging, and family history of PD, were collected. Ethnicity was determined based on the parents' origin and was categorized as Ashkenazi Jews (AJ), Yemenite Jews (YJ), North African Jews (NAJ) and Oriental Jews (OJ) excluding YJ. Associations between the above variables and the time to HY3 were determined using Cox proportional hazards model. Survival curves were derived from the model. RESULTS: Of 707 patients [430 males, AJ: 458, YJ: 37, NAJ: 75 and OJ: 137] included in the analysis, 343 had reached HY3. In a multivariate analysis, a longer time to HY3 was significantly associated with a younger AO (HR = 1.07, p < 0.001). YJ showed a significantly shorter time to HY3 compared to AJ and OJ, but not compared to NAJ. Time to HY3 was significantly shorter for NAJ than for OJ. CONCLUSION: Jewish PD patients of Yemenite and North African origin may have a more rapid progression of PD, compared to those of Ashkenazi and Oriental origin, suggesting distinctive genetic influences.

Association between metabolic syndrome, diabetes mellitus and prostate cancer risk.

BACKGROUND: The worldwide incidence of diabetes mellitus is rapidly increasing. There is recent interest in the influence of glucose metabolism on oncogenesis. We investigated the role of diabetes mellitus and the metabolic syndrome (MS) on prostate cancer development. METHODS: This study consisted of 11 541 men with coronary heart disease screened to participate in a secondary cardiac prevention trial. MS was defined according to modified NCEP/ATP III criteria. Multivariable regression analysis accounting for competing risks was performed using a modified Cox proportional hazard model in order to assess the association between diabetes, the MS and the subsequent development of prostate cancer. RESULTS: At baseline, subjects were classified into one of the four groups: (1) 6119 (53%) with neither diabetic mellitus nor MS, (2) 3376 (29%) with the MS but without diabetes, (3) 560 (5%) with diabetes mellitus but without MS and (4) 1486 (13%) with both conditions. Median follow-up was 12.7 years (range 0-15.7 years). During follow-up, 459 new cases of prostate cancer were recorded. The age-adjusted hazard ratio (HR) for prostate cancer was reduced in diabetic patients compared with those without diabetes, 0.54 and 95% confidence interval of 0.40-0.73. No significant association was noted between the presence of MS and prostate cancer development. On multivariate analysis, diabetes mellitus continued to protect against the development of prostate cancer, this was more pronounced in the absence of MS (HR=0.43, P=0.01 for diabetes in the absence of MS; HR=0.64, P=0.08 in the presence of MS). CONCLUSIONS: The results of this study indicate an inverse association between type 2 diabetes mellitus and prostate cancer risk.

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.

Systematically missing confounders in individual participant data meta-analysis of observational cohort studies.

One difficulty in performing meta-analyses of observational cohort studies is that the availability of confounders may vary between cohorts, so that some cohorts provide fully adjusted analyses while others only provide partially adjusted analyses. Commonly, analyses of the association between an exposure and disease either are restricted to cohorts with full confounder information, or use all cohorts but do not fully adjust for confounding. We propose using a bivariate random-effects meta-analysis model to use information from all available cohorts while still adjusting for all the potential confounders. Our method uses both the fully adjusted and the partially adjusted estimated effects in the cohorts with full confounder information, together with an estimate of their within-cohort correlation. The method is applied to estimate the association between fibrinogen level and coronary heart disease incidence using data from 154,012 participants in 31 cohorts

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.

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.

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.

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 (chi2 = 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.

Secular decrease in blood pressure and reduction in mortality from cardiovascular disease in Israeli workers.

The reasons for the dramatic reduction in age-adjusted mortality from cardiovascular disease (CVD) since the 1970s in developed countries remain uncertain. In the following study we compare the cardiovascular and all-cause mortality rates over an 11-year period in two well-defined employed male cohorts aged 40-69 years old recruited 24 years apart. Blood pressure and other risk markers for CVD were assessed at the time of inception (1963 for 10 048 male civil servants and 1985-1987 for 2237 male industrial workers). Compared to the 1987 cohort, the 1963 cohort show an increase of 8.7 mmHg in the mean systolic blood pressure (SBP) (95% confidence interval (CI): 7.7, 9.6) and a concomitant hazard ratio for CVD mortality of 1.47 (95% CI: 1.16, 1.87). After adding SBP to the analysis, the hazard ratio for CVD mortality in the 1963 cohort decreased to 1.18 (95% CI: 0.88, 1.43). Adding the other risk modifiers to the analysis did not modify the hazard ratio to the same extent. Similar results were obtained for all-cause mortality. We conclude that declining blood pressure values are a major factor in explaining the secular decrease in CVD mortality over a period of 24 years in Israel.

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.

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.

Meta-analyses of antihypertensive therapy: Are some of them misleading?

Meta-analysis has become a very popular tool to compare the efficacy of different antihypertensive regimens. Combining results from various outcome studies may provide evidence to guide the therapeutic approach even before results from large prospective studies are available. However, meta-analysis may be misleading if it is not done meticulously. Some meta-analyses that received broad news media coverage in the recent years were misleading. One analysis suggested that the use of short-acting nifedipine in moderate to high doses in patients with coronary disease increased mortality. This claim was refuted later by observational studies. Based on another meta-analysis, it was claimed that diuretics and beta-blockers are equally effective in reducing cardiovascular morbidity and mortality. Another more careful meta-analysis, omitting one study in which most patients were on combination therapy and not on beta-blocker monotherapy, showed the superiority of diuretic versus b-blocker treatment in the elderly. Calcium antagonists were recently blamed for increasing the rate of myocardial infarction and congestive heart failure in hypertensive patients, and therefore their use was not recommended as first-line therapy in hypertension. This recommendation was based on a meta-analysis subject to major drawbacks and was misleading. Another notion based on meta-analysis was that angiotensin converting enzyme inhibitors reduce left ventricular mass more than diuretics. This notion was refuted by three large randomized studies. A recent meta-analysis, which showed a similar blood pressure lowering effect for all angiotensin receptor blockers, was refuted by head-to-head studies. Thus, when performed correctly, meta-analysis can be an important tool, but when uncritically employed, it is prone to be misleading.

Antihypertensive therapy and the risk of malignancies.

AIMS: To assess the relationship between antihypertensive therapy and malignancy. METHODS AND RESULTS: A MEDLINE search for English-language articles published between January 1966 and August 1999 identified 29 prospective studies that reported cancer incidence or mortality and 28 case-control studies that reported specific drug use in cancer patients and controls. The association between rauwolfia derivatives and breast cancer was analysed in 5852 cases and 9776 controls, yielding an odds ratio (OR) of 1.25 (95% CI, 1.09-1.44). The association between diuretics and renal cell carcinoma was analysed in 4389 cases and 6566 controls, yielding a pooled OR of 1.54 (95% CI, 1.41-1.68). The association between atenolol and cancer death was analysed pooling three randomized controlled studies, including 1879 treated patients and 3078 non-treated patients, yielding a pooled OR of 1.36 (95% CI, 1.02-1.82); however, data from non-randomized studies did not confirm the latter. The association between calcium antagonists and malignancy was analysed pooling five randomized controlled studies, including 5451 treated patients and 5207 untreated ones, yielding a pooled OR of 0.78 (CI, 0.60-1.00). A meta-analysis of an additional five longitudinal studies, including 9087 treated patients and 15 559 non-treated patients, yielded a pooled OR of 1.04 (CI, 0.91-1.19). The association between ACE inhibitors and malignancy was analysed pooling two randomized controlled trials involving 1585 treated patients and 1567 non-treated patients, yielding a pooled OR of 1.57 (95% CI, 0.97-2.57); however, non-randomized studies showed no association or a decreased risk for malignancy with ACE inhibitors. CONCLUSIONS: With the exception of diuretics and renal cell carcinoma, the association between antihypertensive drugs and malignancy was either low grade (rauwolfia), uncertain (atenolol), absent (ACE inhibitors), or absent with a yet to be investigated inverse association (calcium antagonists). Ongoing long-term prospective studies with cardiovascular drugs should carefully monitor the risk of malignancy.

Antihypertensive therapy in diabetic hypertensive patients.

BACKGROUND: We analyzed the available data to assess the benefits of antihypertensive therapy in hypertensive patients with diabetes mellitus. PROCEDURE: A MEDLINE search of English-language articles published until June 1999 was undertaken using the terms diabetes mellitus, hypertension or blood pressure (BP), and therapy. 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. 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 to 2.77 for cardiovascular events, 2.25 to 3.66 for cardiovascular mortality, and 1.73 to 2.18 for total mortality). Intensive BP control to levels lower than 130/85 mm Hg was beneficial in diabetic hypertensive patients. All four 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 BP. CONCLUSIONS: Intensive control of BP 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. Combination of more than one drug is frequently required to control BP and may be more beneficial than monotherapy.

Prognosis of patients with a recurrent acute myocardial infarction before and in the reperfusion era--a national study.

BACKGROUND: Patients with recurrent acute myocardial infarction (AMI) are at increased risk for morbidity and mortality. We compared the outcome of patients with recurrent AMI hospitalized in coronary care units in the prereperfusion and reperfusion eras. METHODS: The study population comprised 2 large-scale cohorts with recurrent AMI: (1) 1415 (24%) of 5839 consecutive patients with AMI hospitalized in 1981 to 1983 (Secondary Prevention Reinfarction Israeli Nifedipine Trial [SPRINT] Registry) and (2) 1093 (25%) of 4317 patients with AMI from three national surveys performed in 1992 to 1996. RESULTS: Patients in the 1990s had significantly lower rates of heart failure and cardiogenic shock. The 7-day mortality declined from 18% in 1981-1983 to 10% in 1992-1996 (adjusted odds ratio [OR] 0.57 [0.44-0.75]), the 30-day mortality rate from 26% to 16% (OR 0.56 [0.44-0.71]), and the 1-year mortality rate from 39% to 26% (adjusted hazard ratio [HR] 0.64 [0.54-0.75]), respectively. In the 1992-1996 cohort, the adjusted risk of 7-day, 30-day, and 1-year mortality for patients with recurrent AMI treated with thrombolysis in comparison to patients without thrombolysis was OR 1.69 (1.07-2.65), 1.52 (1.03-2.23), and HR 1.18 (0.90-1.55), respectively. The mortality rate among patients treated with early percutaneous transluminal coronary angioplasty/coronary artery bypass grafting was 3% versus 12% at 7 days (OR 0.36 [0.16-0.73]), 7% versus 18% at 30 days (OR 0.45 [0.25-0.77]), and 16% versus 29% at 1 year (HR 0.64 [0.46-0.96]), in comparison to patients without revascularization. CONCLUSION: The prognosis of patients with recurrent AMI improved significantly during the reperfusion era. Although thrombolysis may have a limited therapeutic effect among patients with recurrent AMI, an interventional approach seems more appropriate when indicated. A randomized trial of thrombolysis versus early revascularization is needed in patients with recurrent AMI.