Effect of supplemental vitamin E for the prevention and treatment of cardiovascular disease

OBJECTIVE: To evaluate and synthesize the evidence on the effect of supplements of vitamin E on the prevention and treatment of cardiovascular disease. DESIGN: Systematic review of placebo-controlled randomized controlled trials; meta-analysis where justified. MEASUREMENTS AND MAIN RESULTS: Eighty-four eligible trials were identified. For the outcomes of all-cause mortality, cardiovascular mortality, fatal or nonfatal myocardial infarction, and blood lipids, neither supplements of vitamin E alone nor vitamin E given with other agents yielded a statistically significant beneficial or adverse pooled relative risk (for example, pooled relative risk of vitamin E alone = 0.96 [95% confidence interval (CI), 0.84 to 1.10]; 0.97 [95% CI, 0.80 to 1.90]; and 0.72 [95% CI, 0.51 to 1.02] for all-cause mortality, cardiovascular mortality, and nonfatal myocardial infarction, respectively. CONCLUSIONS: There is good evidence that vitamin E supplementation does not beneficially or adversely affect cardiovascular outcomes.     

Effect of calcium or vitamin D supplementation on vascular outcomes: A meta-analysis of randomized controlled trials

Background

Whether calcium or vitamin D supplementation reduces serious vascular outcomes in older people remains unclear. We conducted a meta-analysis based on randomized controlled trials to evaluate the effect of calcium or vitamin D supplementation on the risk of major cardiovascular outcomes.

Methods

We performed electronic searches in PubMed, Embase, and the Cochrane Library to identify relevant randomized controlled trials. Odds ratios (ORs) were used to measure the effect of calcium or vitamin D supplementation on the risk of major vascular outcomes with a random-effect model.

Results

Of the 1643 identified studies, we included 11 trials reporting data on 50,252 individuals. These studies reported 2685 major cardiovascular events, 1097 events of myocardial infarction, and 1350 events of stroke. Calcium or vitamin D supplementation did not have an effect on major cardiovascular events (OR, 1.03; 95% confidence interval [CI]: 0.94–1.12; P = 0.54), myocardial infarction (OR, 1.08; 95% CI: 0.96–1.22; P = 0.21), or stroke (OR, 1.01; 95% CI: 0.91–1.13; P = 0.80) when compared to the effect with a placebo. Subgroup analysis indicated that calcium supplementation alone might play an important role in increasing the risk of major cardiovascular events, myocardial infarction, and stroke, but this difference could not be identified as statistically significant. Furthermore, males seem to experience more harmful effects with supplements of calcium or vitamin D than the effects experienced by females.

Conclusions

Calcium supplementation might increase the risk of major cardiovascular events, myocardial infarction, and stroke compared to the risk with a placebo.     

A randomized factorial trial of vitamins C and E and beta carotene in the secondary prevention of cardiovascular events in women: results from the Women's Antioxidant Cardiovascular Study

BACKGROUND: Randomized trials have largely failed to support an effect of antioxidant vitamins on the risk of cardiovascular disease (CVD). Few trials have examined interactions among antioxidants, and, to our knowledge, no previous trial has examined the individual effect of ascorbic acid (vitamin C) on CVD. METHODS: The Women's Antioxidant Cardiovascular Study tested the effects of ascorbic acid (500 mg/d), vitamin E (600 IU every other day), and beta carotene (50 mg every other day) on the combined outcome of myocardial infarction, stroke, coronary revascularization, or CVD death among 8171 female health professionals at increased risk in a 2 x 2 x 2 factorial design. Participants were 40 years or older with a history of CVD or 3 or more CVD risk factors and were followed up for a mean duration of 9.4 years, from 1995-1996 to 2005. RESULTS: A total of 1450 women experienced 1 or more CVD outcomes. There was no overall effect of ascorbic acid (relative risk [RR], 1.02; 95% CI, 0.92-1.13 [P = .71]), vitamin E (RR, 0.94; 95% CI, 0.85-1.04 [P = .23]), or beta carotene (RR, 1.02; 95% CI, 0.92-1.13 [P = .71]) on the primary combined end point or on the individual secondary outcomes of myocardial infarction, stroke, coronary revascularization, or CVD death. A marginally significant reduction in the primary outcome with active vitamin E was observed among the prespecified subgroup of women with prior CVD (RR, 0.89; 95% CI, 0.79-1.00 [P = .04]; P value for interaction, .07). There were no significant interactions between agents for the primary end point, but those randomized to both active ascorbic acid and vitamin E experienced fewer strokes (P value for interaction, .03). CONCLUSION: There were no overall effects of ascorbic acid, vitamin E, or beta carotene on cardiovascular events among women at high risk for CVD.     

Clinical outcomes in statin treatment trials: a meta-analysis.

OBJECTIVE: To determine the risk of cardiovascular events and death in patients receiving statin treatment for cholesterol regulation. METHODS: Systematic review and meta-analysis of all randomized controlled trials that were published as of April 15, 1997. Primary or secondary prevention trials or regression trials were eligible. MAIN OUTCOME MEASURES: All-cause mortality, fatal myocardial infarction (MI) or stroke, nonfatal MI or stroke, angina, and withdrawal from the studies. Both random- and fixed-effects models were run for the outcomes of interests, and results are expressed as odds ratios (ORs). Sensitivity analyses tested the impact of the study type and duration, statin treatment type, and control arm event rates. Intent-to-treat denominators were used whenever they were available, and the number needed to treat was calculated when appropriate. RESULTS: Seventeen studies (21 303 patients) were included (2 secondary prevention studies, 5 mixed primary-secondary prevention population studies, and 10 regression trials). Treatment groups included lovastatin (t = 5), pravastatin (t = 10), and simvastatin (t = 3). For all-cause mortality, the OR was 0.76 (95% confidence interval [CI], 0.67-0.86) in favor of receiving statin treatment; for fatal MI, the OR was 0.61 (95% CI, 0.48-0.78); for nonfatal MI, the OR was 0.69 (0.54-0.88); for fatal stroke, the OR was 0.77 (95% CI, 0.57-1.04); for nonfatal stroke, the OR was 0.69 (95% CI, 0.54-0.88); and for angina, the OR was 0.70 (95% CI, 0.65-0.76). CONCLUSIONS: Patients who received statin treatment demonstrated a 20% to 30% reduction in death and major cardiovascular events compared with patients who received placebo. This advantage was generally present across study types and statin treatment types and for patients with less severe dyslipidemias. The benefit in clinical outcomes was noticeable as early as 1 year.     

Long-Acting Calcium Antagonists in Patients with Coronary Artery Disease: A Meta-Analysis

Background

The use of calcium channel blockers (CCBs) in patients with coronary artery disease remains controversial, with reports of increased risk of myocardial infarction and all-cause mortality. Short-acting CCBs have an unfavorable hemodynamic profile. The role of long-acting CCBs in patients with coronary artery disease is unknown.

Methods

MEDLINE/CENTRAL/EMBASE database were searched from 1966 to August 2008 for randomized controlled trials of long-acting CCBs in patients with coronary artery disease with follow-up for at least 1 year. We extracted from the studies the baseline characteristics and 6 outcomes: all-cause mortality, cardiovascular mortality, nonfatal myocardial infarction, stroke, angina pectoris, and heart failure.

Results

Of the 100 randomized controlled trials of CCBs in patients with coronary artery disease, 15 studies evaluating 47,694 patients fulfilled our inclusion criteria. When compared with the comparison group (including placebo), CCBs were not associated with an increased risk of all-cause mortality (relative risk [RR] 0.99; 95% confidence interval [CI], 0.94-1.05), cardiovascular mortality (RR 1.03; 95% CI, 0.95-1.11), nonfatal myocardial infarction (RR 0.96; 95% CI, 0.87-1.06), or heart failure (RR 0.86; 95% CI, 0.71-1.05), and with a 21% reduction in the risk of stroke (95% CI, 0.70-0.89) and 18% reduction in the risk of angina pectoris (95% CI, 0.72-0.94). When compared with placebo, CCBs resulted in a 28% reduction in the risk of heart failure (95% CI, 0.73-0.92). The results were similar for both dihydropyridines and nondihydropyridine CCBs.

Conclusions

In patients with coronary artery disease, long-acting CCBs (either dihydropyridines or nondihydropyridines), were associated with a reduction in the risk of stroke, angina pectoris, and heart failure, with similar outcomes for other cardiovascular events as the comparison group.     

Effect of aspirin on mortality in the primary prevention of cardiovascular disease

Objective

The lack of a mortality benefit of aspirin in prior meta-analyses of primary prevention trials of cardiovascular disease has contributed to uncertainty about the balance of benefits and risks of aspirin in primary prevention. We performed an updated meta-analysis of randomized controlled trials of aspirin to obtain best estimates of the effect of aspirin on mortality in primary prevention.

Methods

Eligible articles were identified by searches of electronic databases and reference lists. Outcomes of interest were all-cause mortality, cardiovascular mortality, myocardial infarction, stroke, and bleeding. Data were pooled from individual trials using the DerSimonian-Laird random-effects model, and results are presented as relative risk (RR) and 95% confidence intervals (CIs).

Results

Nine randomized controlled trials enrolling 100,076 participants were included. Aspirin reduced all-cause mortality (RR 0.94; 95% CI, 0.88-1.00), myocardial infarction (RR 0.83; 95% CI, 0.69-1.00), ischemic stroke (RR 0.86; 95% CI, 0.75-0.98), and the composite of myocardial infarction, stroke, or cardiovascular death (RR 0.88; 95% CI, 0.83-0.94), but did not reduce cardiovascular mortality (RR 0.96; 95% CI, 0.84-1.09). Aspirin increased the risk of hemorrhagic stroke (RR 1.36; 95% CI, 1.01-1.82), major bleeding (RR 1.66; 95% CI, 1.41-1.95), and gastrointestinal bleeding (RR 1.37; 95% CI, 1.15-1.62). A lack of availability of patient-level data precluded exploration of benefits and risks of aspirin in key subgroups.

Conclusion

Aspirin prevents deaths, myocardial infarction, and ischemic stroke, and increases hemorrhagic stroke and major bleeding when used in the primary prevention of cardiovascular disease.     

Statin use and survival outcomes in elderly patients with heart failure

BACKGROUND: Coronary artery disease is a leading cause of heart failure. Statins are efficacious drugs for the primary and secondary prevention of coronary heart disease, but their value in persons with heart failure remains unknown. METHODS: We performed a population-based retrospective cohort study involving the entire province of Ontario, Canada, restricting participants to those aged 66 to 85 years who were free of cancer and who survived at least 90 days following hospitalization for newly diagnosed heart failure. The primary study outcome was the risk of death from all causes, nonfatal acute myocardial infarction, or nonfatal stroke among persons newly dispensed statins (n = 1,146) relative to those who were not (n = 27,682). RESULTS: The mean age of all participants was 76.5 years, and half were women. During the 7-year study period, death, acute myocardial infarction, or stroke occurred in 217 statin recipients (13.6 per 100 person-years) vs 12,299 nonrecipients (21.8 per 100 person-years; adjusted hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.63-0.83). Most of the benefit from statins was related to a reduction in all-cause mortality (adjusted HR, 0.67; 95% CI, 0.57-0.78). No significant reduction was seen for subsequent myocardial infarction (adjusted HR, 0.81; 95% CI, 0.63-1.03) or stroke (adjusted HR, 0.81; 95% CI, 0.53-1.25). CONCLUSIONS: Statin use is associated with a lower risk of death among seniors newly diagnosed as having congestive heart failure. While statin use has been previously shown to be efficacious in patients with coronary heart disease and stroke, we could not control for all prognostic risk factors in the present study, including left ventricular ejection fraction and serum lipid levels. Better evidence can direct clinicians about which patients with heart failure might benefit from these drugs.     

Relation of consumption of vitamin E, vitamin C, and carotenoids to risk for stroke among men in the United States.

BACKGROUND: Antioxidants increase the resistance of low-density lipoprotein to oxidation and may thereby reduce risk for atherosclerosis. OBJECTIVE: To determine whether intake of vitamin E, vitamin C, or carotenoids predict risk for total or ischemic stroke. DESIGN: Prospective observational study. SETTING: The Health Professionals Follow-up Study. PARTICIPANTS: 43,738 men 40 to 75 years of age who did not have cardiovascular disease or diabetes. MEASUREMENTS: Repeated and validated dietary assessments were done by using a self-administered 131-item food-frequency questionnaire, which included questions on dose and duration of vitamin supplement use. The follow-up period was 8 years. RESULTS: A total of 328 strokes occurred: 210 ischemic, 70 hemorrhagic, and 48 unclassified. After adjustment for age, smoking, hypertension, hypercholesterolemia, body mass index, physical activity, parental history of myocardial infarction, alcohol consumption, and total energy intake, the relative risk for ischemic stroke in the top quintile of vitamin E intake (median, 411 IU/d) compared with the bottom quintile (5.4 IU/d) was 1.18 (95% CI, 0.77 to 1.82). The relative risk for ischemic stroke in the top quintile of vitamin C intake (1167 mg/d) compared with the bottom quintile (95 mg/d) was 1.03 (CI, 0.66 to 1.59). Results for total stroke were similar. Associations of vitamin intake with hemorrhagic stroke were also nonsignificant, but the CIs were wide. Neither dose nor duration of vitamin E or vitamin C supplement use was related to risk for total or ischemic stroke. The relative risk for ischemic stroke was 1.16 (CI, 0.81 to 1.67) in men using 250 IU or more of vitamin E supplementation per day compared with men who used no vitamin E supplements and was 0.93 (CI, 0.60 to 1.45) in men using 700 mg or more of vitamin C supplementation per day compared with men who used no vitamin C supplements. A significant inverse relation between lutein intake and risk for ischemic stroke was seen but was not independent of other dietary factors. CONCLUSIONS: Vitamin E and vitamin C supplements and specific carotenoids did not seem to substantially reduce risk for stroke in this cohort. Modest effects, however, cannot be excluded.     

Vitamin supplement use in a low-risk population of US male physicians and subsequent cardiovascular mortality

BACKGROUND: Although basic research suggests that vitamins may have an important role in the prevention of cardiovascular diseases (CVD), the data from cohort studies and clinical trials are inconclusive. METHODS: This prospective cohort study was conducted among 83 639 male physicians residing in the United States who had no history of CVD or cancer. At baseline, data on use of vitamin E, ascorbic acid (vitamin C), and multivitamin supplements were provided by a self-administered questionnaire. Mortality from CVD and coronary heart disease (CHD) was assessed by death certificate review. RESULTS: Use of supplements was reported by 29% of the participants. During a mean follow-up of 5.5 years, 1037 CVD deaths occurred, including 608 CHD deaths. After adjustment for several cardiovascular risk factors, supplement use was not significantly associated with total CVD or CHD mortality. For vitamin E use, the relative risks (RRs) were 0.92 (95% confidence interval [CI], 0.70-1.21) for total CVD mortality and 0.88 (95% CI, 0.61-1.27) for CHD mortality; for use of vitamin C, the RRs were 0.88 (95% CI, 0.70-1.12) for total CVD mortality and 0.86 (95% CI, 0.63-1.18) for CHD mortality; and for use of multivitamin supplements, the RRs were 1.07 (95% CI, 0.91-1.25) for total CVD mortality and 1.02 (95% CI, 0.83-1.25) for CHD mortality. CONCLUSIONS: In this large cohort of apparently healthy US male physicians, self-selected supplementation with vitamin E, vitamin C, or multivitamins was not associated with a significant decrease in total CVD or CHD mortality. Data from ongoing large randomized trials will be necessary to definitely establish small potential benefits of vitamin supplements on subsequent cardiovascular risk.     

Relation between hypertension and cardiovascular events--implications for coronary prevention.

OBJECTIVE: To study the relation between hypertension and cardiovascular events--stroke, myocardial infarction (MI), heart failure (HF), and chronic renal failure (CRF)--and to define implications for cardiovascular disease prevention. DESIGN: Cross-sectional study, in two stages, but with retrospective information about major cardiovascular events. SETTING: Primary care health centers (Lisbon Regional Health Administration). MATERIAL AND METHODS: Participants: 3228 patients, 1100 male (439 aged up to 60 years and 661 aged 60 years) and 2128 females (860 aged up to 60 years and 1268 aged 60 years). The study covered stroke, myocardial infarction, heart failure, chronic renal failure with co-variables of age, gender, body mass index (BMI), blood pressure, heart rate, antihypertensives, diabetes, total cholesterol, dyslipidemic therapy, and smoking. The group without hypertension (normotensives) and hypertensives--treated with antihypertensives and/or with systolic/diastolic blood pressure > or = 140/90 mmHg (n = 2169)--were compared, using logistic regression, to identify nonfatal cardiovascular complications associated with hypertension. Forward conditional logistic regression was used to test the multivariate models. The level of significance was taken to be 5%. The statistical packages Stata and SPSS were used. RESULTS: The analysis included 2839 cases (389 missing). The absolute frequencies of categorical variables were: smoking (n = 343); stroke (n = 150); myocardial infarction (n = 90); heart failure (n = 174); renal failure (n = 34); hypercholesterolemia (n = 864); diabetes (n = 375); male gender (n = 976) and female gender (n = 1863). The regression equation included the following factors: age (p < 0.001; OR = 1.068 and 95% CI 1061-1.075); body weight (p = 0.001; OR = 1.020 and 95% CI 1.008-1.032); stroke (p = 0.007; OR = 2.523 and 95% CI 1.286-4.951); HF (p = 0.013; OR = 2.449 and 95% CI 1.205-4.979); diabetes (p < 0.001; OR = 1.894 and 95% CI 1.328-2.701); hypercholesterolemia (p < 0.001; OR = 1.693 and 95% CI 1.350-2.123); and BMI (p < 0.001; OR = 1.006 and 95% CI 1.003-1.010). CONCLUSIONS: Nonfatal stroke was associated with hypertension, as was heart failure, but neither nonfatal myocardial infarction nor chronic renal failure were. Control of hypertension is therefore expected to be more efficacious in reducing cerebrovascular events than those caused by coronary heart disease.     

Use of medications and dietary supplements in later years among male former top-level athletes

BACKGROUND: The association between sports participation and later need of medications and dietary supplements is unknown. SUBJECTS AND METHODS: Male athletes (N = 2026) who had represented Finland in international events from 1920 through 1965 and 1401 control subjects who had been classified healthy at the age of 20 years participated in this population-based cohort study. MAIN OUTCOME MEASURES: The main outcome measures were reimbursable medications for hypertension, cardiac insufficiency, coronary heart disease, diabetes, and asthma identified from the national registry from 1970 through 1998 as well as the use of nonsteroidal anti-inflammatory drugs, antacids, and specific vitamin and mineral supplements for at least 60 days during the past year reported by questionnaire in 1985. RESULTS: Among former top-level athletes compared with controls, the probability of initiating medication was decreased for cardiac insufficiency (age-adjusted hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.50-0.74; P<.001), coronary heart disease (age-adjusted HR, 0.72; 95% CI, 0.58-0.89; P=.002), and asthma (age-adjusted HR, 0.47; 95% CI, 0.36-0.66; P<.001). Furthermore, the risk of initiation of treatment with regular medication for hypertension (age-adjusted HR, 0.73; 95% CI, 0.54-1.00; P=.046) and diabetes (age-adjusted HR, 0.38; 95% CI, 0.20-0.73; P=.004) was reduced for endurance athletes but not for power athletes. In 1985, compared with control subjects, athletes used fewer nonsteroidal anti-inflammatory drugs (age-adjusted odds ratio [OR], 0.48; 95% CI, 0.35-0.67; P<.001) and antacids (age-adjusted OR, 0.49; 95% CI, 0.31-0.77; P=.002) but more vitamin A (age-adjusted OR, 1.87; 95% CI, 1.24-2.82; P=.003), vitamin B (age-adjusted OR, 2.26; 95% CI, 1.64-3.12, P<.001), vitamin C (age-adjusted OR, 1.96; 95% CI, 1.45-2.63; P<.001), selenium (age-adjusted OR, 1.62; 95% CI, 1.15-2.28; P=.006), and iron (age-adjusted OR, 2.35; 95% CI, 1.33-4.15; P=.003) supplements. CONCLUSION: The need for long-term therapy for cardiac disease and asthma as well as for treatment with nonsteroidal anti-inflammatory drugs and antacids is reduced among former top-level athletes, but the use of dietary supplements is increased.     

Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) was a randomized, double-blind, active, controlled clinical trial conducted to determine whether newer antihypertensive agents, including doxazosin, an alpha-blocker, differ from chlorthalidone, a diuretic, with respect to coronary heart disease (CHD) and other cardiovascular disease (CVD) events in hypertensive patients at high risk of CHD. In February 2000, the doxazosin treatment arm was discontinued, and findings through December 1999 were reported. This report includes an additional 9232 participant-years and 939 CVD events. At 623 clinical centers, patients (aged >or=55 years) with hypertension and at least 1 other CHD risk factor were randomly assigned to either chlorthalidone or doxazosin. The primary outcome measure was the combined occurrence of fatal CHD or nonfatal myocardial infarction (MI), analyzed by intent to treat; prespecified secondary outcome measures included all-cause mortality, stroke, combined CHD (fatal CHD, nonfatal MI, hospitalized angina, and coronary revascularization), and combined CVD (combined CHD, stroke, angina treated outside the hospital, heart failure, and peripheral arterial disease). Mean follow-up was 3.2 years. There was no difference in primary outcome between the arms (relative risk [RR], 1.02; 95% confidence interval [CI], 0.92 to 1.15). All-cause mortality also did not differ (RR, 1.03; 95% CI, 0.94 to 1.13). However, the doxazosin arm compared with the chlorthalidone arm had a higher risk of stroke (RR, 1.26; 95% CI, 1.10 to 1.46) and combined CVD (RR 1.20; 95% CI, 1.13 to 1.27). These findings confirm the superiority of diuretic-based over alpha-blocker-based antihypertensive treatment for the prevention of CVD.     

beta1- and beta2-adrenergic receptor gene variation, beta-blocker use and risk of myocardial infarction and stroke

BACKGROUND: The benefits of beta-blocker therapy may depend on underlying genetic susceptibility. METHODS: We investigated the interaction of common variation in beta1 and beta2 adrenergic receptor (AR) genes with beta-blocker use on the risks of myocardial infarction (MI) and ischemic stroke in a case-control study. Participants were treated pharmacologically for hypertension, aged 30-79 years, with incident MI (n = 659) or ischemic stroke (n = 279) between 1995 and 2004, and 2,249 matched controls. RESULTS: We observed an interaction of beta-blocker use with beta1-AR gene variation on MI risk (P value, 6 degrees of freedom: 0.01) and ischemic stroke risk (P value, 6 degrees of freedom: 0.04). Compared with use of other antihypertensive medications, beta-blocker use was associated with higher MI risk in carriers of one or two copies of rs#17875422 (Odds ratio (OR): 2.66, 95% confidence interval (CI); 1.26-5.60) but not in homozygous carriers of the common allele (OR: 0.88, 95% CI: 0.73-1.07). Another variant, rs#2429511, interacted with beta-blocker use on both MI and ischemic stroke risks. beta-blocker use was associated with higher risk of combined MI and ischemic stroke in carriers of rs#2429511 (OR: 1.24, 95% CI: 1.03-1.50) but not in homozygous carriers of common allele (OR: 0.70, 95% CI: 0.51-0.94). beta-blocker use did not interact with beta2-AR gene variation on the risks of MI and ischemic stroke. CONCLUSIONS: These results, which require replication, suggest genetic variants in the beta1-AR gene may determine whether to use beta-blockers in hypertension for the primary prevention of cardiovascular disease.     

An overview of the 4 randomized trials of aspirin therapy in the primary prevention of vascular disease

BACKGROUND: In the primary prevention of cardiovascular disease, in contrast to the recommendations of the American College of Chest Physicians and the American Heart Association, the US Food and Drug Administration recently stated that there was insufficient evidence to judge whether aspirin therapy decreases the risk of a first myocardial infarction. OBJECTIVE: To perform an overview of the 4 primary prevention trials of aspirin therapy to obtain the most reliable estimates of the effects of aspirin therapy on various vascular disease end points. METHODS AND RESULTS: These 4 trials included more than 51,000 subjects and 2284 important vascular events. Those assigned to aspirin therapy experienced significant reductions of 32% (95% confidence interval [CI], 21%-41%) for nonfatal myocardial infarction and 13% (95% CI, 5%-19%) for any important vascular event. There were possible small but nonsignificant increases in risks of vascular disease-related death (1%; 95% CI, -12% to 16%) and nonfatal stroke (8%; 95% CI, -12% to 33%). When strokes were subdivided by type, there was no significant effect of aspirin therapy on the risk of ischemic stroke, but, while based on small numbers, there was a 1.7-fold apparent increase (95% CI, 6%-269%) in the risk of hemorrhagic stroke, which did achieve statistical significance. CONCLUSIONS: For the primary prevention of vascular disease, aspirin therapy confers significant beneficial effects on first myocardial infarction and, as a result, on any important vascular event; these effects are clinically important. Whether there is any reduction in vascular disease-related death or stroke associated with treatment remains unclear because of inadequate numbers of events in the primary prevention trials completed to date. More data on hemorrhagic stroke are also needed. In addition, randomized trial data, especially in women but also in men, are needed to help to formulate a rational public health policy for individuals at usual risk. Meanwhile, these data provide evidence for a significant benefit of aspirin therapy in the primary prevention of myocardial infarction.     

Angiotensin-converting enzyme inhibitors in coronary artery disease and preserved left ventricular systolic function: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. BACKGROUND: The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. METHODS: An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I(2). RESULTS: There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). CONCLUSIONS: The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function.     

Antioxidants vitamin C and vitamin E for the prevention and treatment of cancer

OBJECTIVE: To evaluate the evidence of the supplements vitamin C and vitamin E for treatment and prevention of cancer. METHODS: Systematic review of trials and meta-analysis. DATA SOURCES AND MAIN RESULTS: Thirty-eight studies showed scant evidence that vitamin C or vitamin E beneficially affects survival. In the ATBC Cancer Prevention Study Group, no statistically significant effect of treatment was seen for any cancer individually, and our pooled relative risk (regardless of tumor type) for alpha-tocopherol alone was 0.91 (95% confidence interval [CI]: 0.74, 1.12). All cause mortality was not significant. In the Linxian General Population Trial, the relative risks for cancer death for vitamin C (combined with molybdenum) was 1.06 (95% CI: 0.92, 1.21) and for vitamin E (combined with beta-carotene and selenium) was 0.87 (95% CI: 0.76, 1.00). We identified only 3 studies that reported statistically significant beneficial results: vitamin C (in combination with BCG) was found to be beneficial in a single trial of bladder cancer and vitamin E (in combination with omega-3 fatty acid) increased survival in patients with advanced cancer. In the ATBC trial, in analyses of 6 individual cancers, the prevention of prostate cancer in subjects treated with alpha-tocopherol was statistically significant (RR=0.64, 95% CI: 0.44, 0.94). CONCLUSIONS: The systematic review of the literature does not support the hypothesis that the use of supplements of vitamin C or vitamin E in the doses tested helps prevent and/or treat cancer in the populations tested. There were isolated findings of benefit, which require confirmation.     

Periodontal disease and risk of subsequent cardiovascular disease in U.S. male physicians

OBJECTIVES: We sought to prospectively assess whether self-reported periodontal disease is associated with subsequent risk of cardiovascular disease in a large population of male physicians. BACKGROUND: Periodontal disease, the result of a complex interplay of bacterial infection and chronic inflammation, has been suggested to be a predictor of cardiovascular disease. METHODS: Physicians' Health Study I was a randomized, double-blind, placebo-controlled trial of aspirin and beta-carotene in 22,071 U.S. male physicians. A total of 22,037 physicians provided self-reports of presence or absence of periodontal disease at study entry and were included in this analysis. RESULTS: A total of 2,653 physicians reported a personal history of periodontal disease at baseline. During an average of 12.3 years of follow-up, there were 797 nonfatal myocardial infarctions, 631 nonfatal strokes and 614 cardiovascular deaths. Thus, for each end point, the study had >90% power to detect a clinically important increased risk of 50%. In Cox proportional hazards regression analysis adjusted for age and treatment assignment, physicians who reported periodontal disease at baseline had slightly elevated, but statistically nonsignificant, relative risks (RR) of nonfatal myocardial infarction, (RR, 1.12; 95% confidence interval [CI], 0.92 to 1.36), nonfatal stroke (RR, 1.10; CI, 0.88 to 1.37) and cardiovascular death (RR, 1.20; CI, 0.97 to 1.49). Relative risk for a combined end point of all important cardiovascular events (first occurrence of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death) was 1.13 (CI, 0.99 to 1.28). After adjustment for other cardiovascular risk factors, RRs were all attenuated and nonsignificant. CONCLUSIONS: These prospective data suggest that self-reported periodontal disease is not an independent predictor of subsequent cardiovascular disease in middle-aged to elderly men.     

Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis

Objective

Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease.

Methods

Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n = 1), stable angina (n = 1), or stroke/transient ischemic attack (n = 4). A random effects model was used to combine results from individual trials.

Results

Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke.

Conclusion

In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.     

Comparison of glucagons like peptide-1 receptor agonists and dipeptidyl peptide-4 inhibitors regarding cardiovascular safety and mortality in type 2 diabetes mellitus: A network meta-analysis

AimThe effects of dipeptidyl peptide-4 inhibitors (DPP-4is) and sodium-glucose cotransporter-2 inhibitors (SGLT-2is) on type 2 diabetes mellitus (T2DM) on cardiovascular events and all-cause mortality were compared.MethodsThe literature on DPP-4is and SGLT-2is treatment of T2DM was searched through Pubmed, Embase, and the web of science databases with the search deadline May 15, 2020. Network meta-analysis (NMA) was used to compare the effects of two types of inhibitors on cardiovascular events (major adverse cardiovascular events (MACE), nonfatal myocardial infarction (MI), nonfatal stroke, and cardiovascular (CV) death) and all-cause mortality in T2DM patients.ResultsA total of 15 articles were screened, including 125,796 patients. Compared with DPP-4is, SGLT-2is can significantly reduce MACE [OR: 0.86 95% CI (0.78, 0.92)], CV death [OR: 0.85 95% CI (0.71, 1.01)], nonfatal MI [OR: 0.84 95%CI (0.74, 0.95)] and all-cause mortality [OR: 0.78 95% CI (0.69, 0.89)]. For nonfatal stroke, DPP-4is and SGLT-2is have no statistically significant difference [OR: 0.99 95% CI (0.91, 1.07)].ConclusionThese data indicate that SGLT-2is is more beneficial to MACE and all-cause mortality in T2DM patients than DPP-4is.     

Association of Depression and Cardiovascular Disease

BackgroundCardiovascular disease remains the leading worldwide cause of mortality. There has been increased awareness of the impact of psychological health on cardiovascular disease. In particular, major depression has been linked to increased all-cause mortality, development of cardiovascular disease, and worse outcomes in those with existing cardiovascular disease.MethodsWe conducted a meta-analysis assessing the incidence of cardiovascular disease and cardiovascular disease outcomes among those with major depressive disorder.ResultsAmong 26 studies of 1,957,621 individuals, depression was associated with increased risk of incident stroke (hazard ratio [HR] 1.13; 95% confidence interval [CI], 1.00-1.28), myocardial infarction (HR 1.28; 95% CI, 1.14-1.45), congestive heart failure (HR 1.04; 95% CI, 1.00-1.09), or any cardiovascular disease (HR 1.16; 95% CI, 1.04-1.30). Depression was associated with increased risk of all-cause mortality (HR 1.43; 95% CI, 1.27-1.60), cardiovascular disease mortality (HR 1.44; 95% CI, 1.27-1.63), and congestive heart failure mortality (HR 3.20; 95% CI, 1.29-7.94).ConclusionDepression has a significant negative impact on development of cardiovascular disease and on cardiovascular disease outcomes. Further efforts to understand and mitigate these impacts are prudent.