Showing papers by "Charles H. Hennekens published in 2004"

Antipsychotic-induced weight gain and metabolic abnormalities: implications for increased mortality in patients with schizophrenia.

Abstract: Patients with schizophrenia have increased rates of morbidity and mortality due primarily to cardiovascular disease, compared with the general population. Case reports, case series, observational analytic epidemiologic studies, and randomized trials raise the possibility that some antipsychotic drugs add to this increased risk, likely due to drug-induced weight gain and associated metabolic abnormalities including hyperglycemia, diabetes mellitus, and dyslipidemia. This constella

Randomized Trials of Vitamin E in the Treatment and Prevention of Cardiovascular Disease

Abstract: Background: Observational epidemiological studies consistently show that individuals who choose to take high amounts of vitamin E through diet or supplements experience cardiovascular benefits, for which basic research provides plausible mechanisms. However, because the size of the postulated benefit is small to moderate, the confounding inherent in observational studies is as great as the effect size. Before the availability of randomized evidence, about 1 in 4 adults was taking vitamin E supplements in the United States. Methods: We conducted a computerized search of the English-language literature from 1990 to the present and found 7 large-scale randomized trials of the effectiveness vitamin E in the treatment and prevention of cardiovascular disease. Data were available on myocardial infarction, stroke, or cardiovascular death. Results: Six of the 7 trials showed no significant effect of vitamin E on cardiovascular disease. In an overview, vitamin E had neither a statistically significant nor a clinically important effect on any important cardiovascular event (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.94-1.03) or its components: nonfatal myocardial infarction (OR, 1.00; 95% CI, 0.92-1.09), nonfatal stroke (OR, 1.03; 95% CI, 0.93-1.14), or cardiovascular death (OR, 1.00; 95% CI, 0.94-1.05). Conclusions: The ORs and CIs provide strong support for a lack of statistically significant or clinically important effects of vitamin E on cardiovascular disease. The use of agents of proven lack of benefit, especially those easily available over the counter, may contribute to underuse of agents of proven benefit and failure to adopt healthy lifestyles. Arch Intern Med. 2004;164:1552-1556

Prolonged QTc interval and risks of total and cardiovascular mortality and sudden death in the general population: a review and qualitative overview of the prospective cohort studies.

Abstract: Background In certain subgroups of patients, prolongation of the QTc interval may increase total and cardiovascular mortality due to life-threatening ventricular arrhythmias and sudden death. Nonetheless, whether modest prolongation of the QTc interval in the general population has clinical importance remains unclear. Methods We conducted a literature search from 1990 forward to identify all published prospective cohort studies evaluating the association between prolonged QTc interval and risks of total and cardiovascular mortality as well as sudden death. We reviewed each of the studies individually and then conducted a qualitative overview. Results The 7 prospective cohort studies identified included 36 031 individuals. There were 2677 (8.7%) individuals with prolonged QTc interval, defined as 440 milliseconds or greater. Whereas 1 study reported no association between prolonged QTc interval and mortality (relative risk, 1.02; 95% confidence interval, 0.70-1.49), the other 6 reported inconsistent associations overall as well as across subgroups defined by various characteristics including age, sex, and comorbidities. The reported associations for both cardiovascular mortality and sudden death were also inconsistent. In the overview, the only consistent findings were for the subgroup of patients with prior cardiovascular disease, in which relative risks ranged from 1.1 to 3.8 for total mortality, from 1.2 to 8.0 for cardiovascular mortality, and from 1.0 to 2.1 for sudden death. Further, in individuals without prior cardiovascular disease, associations were either absent or greatly attenuated; specifically, relative risks ranged from 0.9 to 1.6 for total mortality, from 1.2 to 1.7 for cardiovascular mortality, and from 1.3 to 2.4 for sudden death. Conclusions There was no consistent evidence for increased risks of total or cardiovascular mortality or of sudden death, except perhaps for patients with prior cardiovascular disease. In the general population, if QTc interval prolongation is associated with any increase in mortality, that risk is likely to be small and difficult to detect reliably.

Absence of interaction between atorvastatin or other statins and clopidogrel: results from the interaction study

Abstract: Background Some, but not all, post hoc analyses have suggested that the antiplatelet effects of clopidogrel are inhibited by atorvastatin. We sought to address this issue prospectively by performing serial measurements of 19 platelet characteristics using conventional aggregometry, rapid analyzers, and flow cytometry. Methods The Interaction of Atorvastatin and Clopidogrel Study (Interaction Study) was designed for patients undergoing coronary stenting. All patients (n = 75) received 325 mg of aspirin daily for at least 1 week and 300 mg of clopidogrel immediately prior to stent implantation. They had been taking atorvastatin (n = 25), any other statin (n = 25), or no statin (n = 25) for at least 30 days prior to stenting. The main outcome measure was comparison of platelet biomarkers 4 and 24 hours after clopidogrel administration between study groups. Results At baseline, patients from both statin groups exhibited diminished platelet aggregation and reduced platelet expression of G–protein-coupled protease-activated thrombin receptor (PAR)-1. There were no significant differences in measured platelet characteristics among the study groups 4 and 24 hours after clopidogrel intake, with the exception of a lower collagen-induced aggregation at 24 hours and a constantly diminished expression of PAR-1 in patients treated with any statin. Conclusions Statins in general, and atorvastatin in particular, do not affect the ability of clopidogrel to inhibit platelet function in patients undergoing coronary stenting. These prospective data also suggest that statins may inhibit platelets directly via yet unknown mechanism(s) possibly related to the regulation of the PAR-1 thrombin receptors.

The National Cholesterol Education Program Diet vs a Diet Lower in Carbohydrates and Higher in Protein and Monounsaturated Fat

Abstract: Background: In the United States, obesity is a major clinical and public health problem causing diabetes, dyslipidemia, and hypertension, as well as increasing cardiovascular and total mortality. Dietary restrictions of calories and saturated fat are beneficial. However, it remains unclear whether replacement of saturated fat with carbohydrates (as in the US National Cholesterol Education Program [NCEP] diet) or protein and monounsaturated fat (as in our isocaloric modified lowcarbohydrate [MLC] diet, which is lower in total carbohydrates but higher in protein, monounsaturated fat, and complex carbohydrates) is optimal.

Hypertension: trends, risks, drug therapies and clinical challenges in African Americans.

Abstract: In the United States, cardiovascular disease (CVD) is the leading killer accounting for about 1 million fatalities annually, with hypertension being a major risk factor for stroke, coronary heart disease (CHD), cardiovascular (CV) death, heart failure, and end-stage renal disease--all of which have higher prevalence in African Americans, who also experience greater severity at clinical presentation. In numerous randomized trials and meta-analyses, drug therapy for hypertension has been shown to reduce blood pressure by 4-6 millimeters of mercury (mm Hg) with resultant decreases in stroke of 35%-40%, CHD of 20%-25%, and CV death of about 25%. Cardiovascular drug therapies of proven benefit, including diuretics, angiotensin converting enzyme (ACE inhibitors), and beta-blockers, are safe and effective, alone and in combination. Since African Americans with hypertension tend to have a more severe presentation, they will be even more likely to require multiple drug therapies, which also will include diuretics and calcium channel blockers. Effective strategies to encourage widespread use of these therapies of proven benefit would provide progress toward decreasing the adverse mortality experiences, especially CVD, among African Americans.

An update on clinical trials in pacing: is dual chamber pacing better?

Abstract: Purpose of reviewAs pacemaker technology has increased in complexity and now offers a variety of additional capabilities, there is uncertainty as to which pacing mode offers more benefit—dual-chamber or single-chamber.Recent findingsTwo large-scale randomized trials, the Canadian Trial of Physiologi