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An editorial focuses on evaluating the potential for improving cardiovascular risk assessment by incorporating additional biomarkers into standard risk prediction models. It reviews a study which demonstrates modest but significant improvements in predicting cardiovascular events and mortality when biomarkers such as high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein are added to traditional risk equations.

Key Points: Question: Are APOE amino acid–altering variants, other than the common APOE alleles ε2 and ε4, associated with Alzheimer disease (AD) risk in individuals of African ancestry? Findings: In this exploratory case-control analysis that included 31 929 participants of African ancestry, stratified analyses demonstrated that the APOE ε3[R145C] missense variant was associated with an increased risk of AD among individuals with the ε3/ε4 genotype in a discovery cohort (odds ratio, 3.01), a replication cohort (odds ratio, 2.20), and an external validation cohort (odds ratio, 1.90). Meaning: These findings, with additional external validation, may inform AD genetic risk assessment in individuals of African ancestry. Importance: Numerous studies have established the association of the common APOE ε2 and APOE ε4 alleles with Alzheimer disease (AD) risk across ancestries. Studies of the interaction of these alleles with other amino acid changes on APOE in non-European ancestries are lacking and may improve ancestry-specific risk prediction. Objective: To determine whether APOE amino acid changes specific to individuals of African ancestry modulate AD risk. Design, Setting, and Participants: Case-control study including 31 929 participants and using a sequenced discovery sample (Alzheimer Disease Sequencing Project; stage 1) followed by 2 microarray imputed data sets derived from the Alzheimer Disease Genetic Consortium (stage 2, internal replication) and the Million Veteran Program (stage 3, external validation). This study combined case-control, family-based, population-based, and longitudinal AD cohorts, which recruited participants (1991-2022) in primarily US-based studies with 1 US/Nigerian study. Across all stages, individuals included in this study were of African ancestry. Exposures: Two APOE missense variants (R145C and R150H) were assessed, stratified by APOE genotype. Main Outcomes and Measures: The primary outcome was AD case-control status, and secondary outcomes included age at AD onset. Results: Stage 1 included 2888 cases (median age, 77 [IQR, 71-83] years; 31.3% male) and 4957 controls (median age, 77 [IQR, 71-83] years; 28.0% male). In stage 2, across multiple cohorts, 1201 cases (median age, 75 [IQR, 69-81] years; 30.8% male) and 2744 controls (median age, 80 [IQR, 75-84] years; 31.4% male) were included. In stage 3, 733 cases (median age, 79.4 [IQR, 73.8-86.5] years; 97.0% male) and 19 406 controls (median age, 71.9 [IQR, 68.4-75.8] years; 94.5% male) were included. In ε3/ε4-stratified analyses of stage 1, R145C was present in 52 individuals with AD (4.8%) and 19 controls (1.5%); R145C was associated with an increased risk of AD (odds ratio [OR], 3.01; 95% CI, 1.87-4.85; P = 6.0 × 10−6) and was associated with a reported younger age at AD onset (β, −5.87 years; 95% CI, −8.35 to −3.4 years; P = 3.4 × 10−6). Association with increased AD risk was replicated in stage 2 (R145C was present in 23 individuals with AD [4.7%] and 21 controls [2.7%]; OR, 2.20; 95% CI, 1.04-4.65; P =.04) and was concordant in stage 3 (R145C was present in 11 individuals with AD [3.8%] and 149 controls [2.7%]; OR, 1.90; 95% CI, 0.99-3.64; P =.051). Association with earlier AD onset was replicated in stage 2 (β, −5.23 years; 95% CI, −9.58 to −0.87 years; P =.02) and stage 3 (β, −10.15 years; 95% CI, −15.66 to −4.64 years; P = 4.0 × 10−4). No significant associations were observed in other APOE strata for R145C or in any APOE strata for R150H. Conclusions and Relevance: In this exploratory analysis, the APOE ε3[R145C] missense variant was associated with an increased risk of AD among individuals of African ancestry with the ε3/ε4 genotype. With additional external validation, these findings may inform AD genetic risk assessment in individuals of African ancestry. This exploratory case-control study assesses the association of APOE missense variants with risk of Alzheimer disease among individuals of African ancestry with the APOE ε3/ε4 genotype. [ABSTRACT FROM AUTHOR]

Importance: Influenza is temporally associated with cardiopulmonary morbidity and mortality among those with cardiovascular disease who may mount a less vigorous immune response to vaccination. Higher influenza vaccine dose has been associated with reduced risk of influenza illness.Objective: To evaluate whether high-dose trivalent influenza vaccine compared with standard-dose quadrivalent influenza vaccine would reduce all-cause death or cardiopulmonary hospitalization in high-risk patients with cardiovascular disease.Design, Setting, and Participants: Pragmatic multicenter, double-blind, active comparator randomized clinical trial conducted in 5260 participants vaccinated for up to 3 influenza seasons in 157 sites in the US and Canada between September 21, 2016, and January 31, 2019. Patients with a recent acute myocardial infarction or heart failure hospitalization and at least 1 additional risk factor were eligible.Interventions: Participants were randomly assigned to receive high-dose trivalent (n = 2630) or standard-dose quadrivalent (n = 2630) inactivated influenza vaccine and could be revaccinated for up to 3 seasons.Main Outcomes and Measures: The primary outcome was the time to the composite of all-cause death or cardiopulmonary hospitalization during each enrolling season. The final date of follow-up was July 31, 2019. Vaccine-related adverse events were also assessed.Results: Among 5260 randomized participants (mean [SD] age, 65.5 [12.6] years; 3787 [72%] men; 3289 [63%] with heart failure) over 3 influenza seasons, there were 7154 total vaccinations administered and 5226 (99.4%) participants completed the trial. In the high-dose trivalent vaccine group, there were 975 primary outcome events (883 hospitalizations for cardiovascular or pulmonary causes and 92 deaths from any cause) among 884 participants during 3577 participant-seasons (event rate, 45 per 100 patient-years), whereas in the standard-dose quadrivalent vaccine group, there were 924 primary outcome events (846 hospitalizations for cardiovascular or pulmonary causes and 78 deaths from any cause) among 837 participants during 3577 participant-seasons (event rate, 42 per 100 patient-years) (hazard ratio, 1.06 [95% CI, 0.97-1.17]; P = .21). In the high-dose vs standard-dose groups, vaccine-related adverse reactions occurred in 1449 (40.5%) vs 1229 (34.4%) participants and severe adverse reactions occurred in 55 (2.1%) vs 44 (1.7%) participants.Conclusions and Relevance: In patients with high-risk cardiovascular disease, high-dose trivalent inactivated influenza vaccine, compared with standard-dose quadrivalent inactivated influenza vaccine, did not significantly reduce all-cause mortality or cardiopulmonary hospitalizations. Influenza vaccination remains strongly recommended in this population.Trial Registration: ClinicalTrials.gov Identifier: NCT02787044. [ABSTRACT FROM AUTHOR]

Importance: Data are limited regarding statin therapy for primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults 75 years and older.Objective: To evaluate the role of statin use for mortality and primary prevention of ASCVD in veterans 75 years and older.Design, Setting, and Participants: Retrospective cohort study that used Veterans Health Administration (VHA) data on adults 75 years and older, free of ASCVD, and with a clinical visit in 2002-2012. Follow-up continued through December 31, 2016. All data were linked to Medicare and Medicaid claims and pharmaceutical data. A new-user design was used, excluding those with any prior statin use. Cox proportional hazards models were fit to evaluate the association of statin use with outcomes. Analyses were conducted using propensity score overlap weighting to balance baseline characteristics.Exposures: Any new statin prescription.Main Outcomes and Measures: The primary outcomes were all-cause and cardiovascular mortality. Secondary outcomes included a composite of ASCVD events (myocardial infarction, ischemic stroke, and revascularization with coronary artery bypass graft surgery or percutaneous coronary intervention).Results: Of 326 981 eligible veterans (mean [SD] age, 81.1 [4.1] years; 97% men; 91% white), 57 178 (17.5%) newly initiated statins during the study period. During a mean follow-up of 6.8 (SD, 3.9) years, a total 206 902 deaths occurred including 53 296 cardiovascular deaths, with 78.7 and 98.2 total deaths/1000 person-years among statin users and nonusers, respectively (weighted incidence rate difference [IRD]/1000 person-years, -19.5 [95% CI, -20.4 to -18.5]). There were 22.6 and 25.7 cardiovascular deaths per 1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -3.1 [95 CI, -3.6 to -2.6]). For the composite ASCVD outcome there were 123 379 events, with 66.3 and 70.4 events/1000 person-years among statin users and nonusers, respectively (weighted IRD/1000 person-years, -4.1 [95% CI, -5.1 to -3.0]). After propensity score overlap weighting was applied, the hazard ratio was 0.75 (95% CI, 0.74-0.76) for all-cause mortality, 0.80 (95% CI, 0.78-0.81) for cardiovascular mortality, and 0.92 (95% CI, 0.91-0.94) for a composite of ASCVD events when comparing statin users with nonusers.Conclusions and Relevance: Among US veterans 75 years and older and free of ASCVD at baseline, new statin use was significantly associated with a lower risk of all-cause and cardiovascular mortality. Further research, including from randomized clinical trials, is needed to more definitively determine the role of statin therapy in older adults for primary prevention of ASCVD. [ABSTRACT FROM AUTHOR]

The author comments on a meta-analysis of data from three 2018 trials of the use of aspirin to prevent and manage atherothrombotic vascular events combined with data from 10 previous primary prevention trials. He describes challenges in conducting primary prevention trials involving aspirin. He also discusses the implications of the results which indicate that the estimated risks and benefits of aspirin for primary prevention were not materially altered with the addition of the 3 recent trials.

The article presents the findings of a medical research conducted on examining whether the regular intake of multivitamin supplementation reduces the risk of total and site-specific cancer events among men in long term. It mentions that randomized controlled trial was conducted on 14 641 U.S. male physicians aged 50 years or above. The research reveals that daily intake of multivitamin supplementation significantly lowered the risk of total cancer involving colorectal, skin, and prostate cancer among physicians. It discusses the complete methodology of the research.

The article focuses on research study in which researchers determine whether long-term multivitamin supplementation decreases the risk of major cardiovascular events among men. The study evaluated the balance of risks and benefits of a multivitamin, vitaminE, vitamin C and beta carotene in the prevention of cardiovascular diseases, cancer, eye disease, and cognitive decline among male physicians aged 50 years or older. The researchers found that the rates of major cardiovascular events were 11 per 1000 person-years in the multivitamin group and 10.8 per 1000 person-years in the placebo group.

The article discusses a study which determined the long-term effect of vitamin E and selenium on risk of prostate cancer in relatively healthy men. Statistical analysis showed the significant increase in the risk of prostate cancer among healthy men who received vitamin E dietary supplements. According to data, 620 men in the vitamin E group and 575 men in the selenium group developed prostate cancer, compared with 529 men in the placebo group. Data indicate the frequency of use of prostate-specific antigen (PSA) and digital rectal examination, as well as the rate of prostate cancer detection in all the treatment groups.

The article discusses a study which assessed the relationship between modifiable lifestyle factors and lifetime risk of heart failure in men. The study included 20,900 men participating in the Physicians' Health Study I from 1982 to 2008. It examined six modifiable lifestyle factors namely alcohol intake, breakfast cereal consumption, body weight, smoking, fruits and vegetable consumption and exercise. After a mean follow-up of 22.4 years, 1,200 of the study population developed heart failure. Study authors concluded that healthy lifestyle lowers the lifetime risk of heart failure.

The article presents a randomized controlled trial which examined whether long term supplementation with vitamins E and C reduced the risk of prostate or total cancer in men. The Physician's Health Study II, which began in 1997 and ended in 2007, included 14,641 male physicians in the U.S. initially aged 50 years or older. Participants took 400 IU of vitamin E every other day and 500 mg of vitamin C daily. The main outcome was prostate and total cancer. Researchers found that neither vitamin E nor C supplementation reduced the risk of prostate or total cancer.

The article presents a randomized controlled trial which examined whether selenium, vitamin E, or both could prevent prostate cancer and other diseases with little or no toxicity in healthy men. Participants were African American men 50 years or older and non-African American men 55 years or older with a serum prostate-specific antigen level of 4 ng/mL or less and a digital rectal examination showing no suspicion for prostate cancer. Prostate cancer was the main outcome. Secondary outcomes included lung, colorectal, and overall primary cancer. The median overall follow-up as of October 23, 2008 was 5.46 years. Researchers found that selenium or vitamin E, alone or in combination, did not prevent prostate cancer.

Context: Basic research and observational studies suggest vitamin E or vitamin C may reduce the risk of cardiovascular disease. However, few long-term trials have evaluated men at initially low risk of cardiovascular disease, and no previous trial in men has examined vitamin C alone in the prevention of cardiovascular disease.Objective: To evaluate whether long-term vitamin E or vitamin C supplementation decreases the risk of major cardiovascular events among men.Design, Setting, and Participants: The Physicians' Health Study II was a randomized, double-blind, placebo-controlled factorial trial of vitamin E and vitamin C that began in 1997 and continued until its scheduled completion on August 31, 2007. There were 14,641 US male physicians enrolled, who were initially aged 50 years or older, including 754 men (5.1%) with prevalent cardiovascular disease at randomization.Intervention: Individual supplements of 400 IU of vitamin E every other day and 500 mg of vitamin C daily.Main Outcome Measures: A composite end point of major cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, and cardiovascular disease death).Results: During a mean follow-up of 8 years, there were 1245 confirmed major cardiovascular events. Compared with placebo, vitamin E had no effect on the incidence of major cardiovascular events (both active and placebo vitamin E groups, 10.9 events per 1000 person-years; hazard ratio [HR], 1.01 [95% confidence interval {CI}, 0.90-1.13]; P = .86), as well as total myocardial infarction (HR, 0.90 [95% CI, 0.75-1.07]; P = .22), total stroke (HR, 1.07 [95% CI, 0.89-1.29]; P = .45), and cardiovascular mortality (HR, 1.07 [95% CI, 0.90-1.28]; P = .43). There also was no significant effect of vitamin C on major cardiovascular events (active and placebo vitamin E groups, 10.8 and 10.9 events per 1000 person-years, respectively; HR, 0.99 [95% CI, 0.89-1.11]; P = .91), as well as total myocardial infarction (HR, 1.04 [95% CI, 0.87-1.24]; P = .65), total stroke (HR, 0.89 [95% CI, 0.74-1.07]; P = .21), and cardiovascular mortality (HR, 1.02 [95% CI, 0.85-1.21]; P = .86). Neither vitamin E (HR, 1.07 [95% CI, 0.97-1.18]; P = .15) nor vitamin C (HR, 1.07 [95% CI, 0.97-1.18]; P = .16) had a significant effect on total mortality but vitamin E was associated with an increased risk of hemorrhagic stroke (HR, 1.74 [95% CI, 1.04-2.91]; P = .04).Conclusions: In this large, long-term trial of male physicians, neither vitamin E nor vitamin C supplementation reduced the risk of major cardiovascular events. These data provide no support for the use of these supplements for the prevention of cardiovascular disease in middle-aged and older men.Trial Registration: clinicaltrials.gov Identifier: NCT00270647. [ABSTRACT FROM AUTHOR]

Context: Folate, vitamin B(6), and vitamin B(12) are thought to play an important role in cancer prevention.Objective: To evaluate the effect of combined folic acid, vitamin B(6), and vitamin B(12) treatment on cancer risk in women at high risk for cardiovascular disease.Design, Setting, and Participants: In the Women's Antioxidant and Folic Acid Cardiovascular Study, 5442 US female health professionals aged 42 years or older, with preexisting cardiovascular disease or 3 or more coronary risk factors, were randomly assigned to receive either a daily combination of folic acid, vitamin B(6), and vitamin B(12) or a matching placebo. They were treated for 7.3 years from April 1998 through July 31, 2005.Intervention: Daily supplementation of a combination of 2.5 mg of folic acid, 50 mg of vitamin B(6), and 1 mg of vitamin B(12) (n = 2721) or placebo (n = 2721).Main Outcome Measures: Confirmed newly diagnosed total invasive cancer or breast cancer.Results: A total of 379 women developed invasive cancer (187 in the active treatment group and 192 in the placebo group). Compared with placebo, women receiving the active treatment had similar risk of developing total invasive cancer (101.1/10,000 person-years for the active treatment group vs 104.3/10,000 person-years for placebo group; hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.79-1.18; P = .75), breast cancer (37.8/10,000 person-years vs 45.6/10,000 person-years, respectively; HR, 0.83; 95% CI, 0.60-1.14; P = .24), or any cancer death (24.6/10,000 person-years vs 30.1/10,000 person-years, respectively; HR, 0.82; 95% CI, 0.56-1.21; P = .32).Conclusion: Combined folic acid, vitamin B(6), and vitamin B(12) treatment had no significant effect on overall risk of total invasive cancer or breast cancer among women during the folic acid fortification era.Trial Registration: clinicaltrials.gov Identifier: NCT00000541. [ABSTRACT FROM AUTHOR]

The article reports on the results of research which was conducted in an effort to evaluate the effect of combined folic acid, vitamin B6 and vitamin B12 treatment on cancer in women at high risk for cardiovascular disease. Researchers studied 5,442 U. S. female health professionals with preexisting cardiovascular disease for 7.3 years. They found that combined folic acid, vitamin B6 and vitamin B12 treatment had no significant effect on overall risk of total invasive cancer or breast cancer during the folic acid fortification era.

Context: Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.Objective: To test whether a combination of folic acid, vitamin B6, and vitamin B12 lowers risk of CVD among high-risk women with and without CVD.Design, Setting, and Participants: Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B6, and vitamin B12 or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.Intervention: Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B6, and 1 mg of vitamin B12.Main Outcome Measures: A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.Results: Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10,000 person-years vs 219.2/10,000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10,000 person-years vs 39.5/10,000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10,000 person-years vs 36.8/10,000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10,000 person-years vs 49.6/10,000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 micromol/L (95% CI, 1.54-2.96 micromol/L).Conclusion: After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.Trial Registration: clinicaltrials.gov Identifier: NCT00000541. [ABSTRACT FROM AUTHOR]

Context: High plasma homocysteine levels are a risk factor for mortality and vascular disease in observational studies of patients with chronic kidney disease. Folic acid and B vitamins decrease homocysteine levels in this population but whether they lower mortality is unknown.Objective: To determine whether high doses of folic acid and B vitamins administered daily reduce mortality in patients with chronic kidney disease.Design, Setting, and Participants: Double-blind randomized controlled trial (2001-2006) in 36 US Department of Veterans Affairs medical centers. Median follow-up was 3.2 years for 2056 participants aged 21 years or older with advanced chronic kidney disease (estimated creatinine clearance < or =30 mL/min) (n = 1305) or end-stage renal disease (n = 751) and high homocysteine levels (> or = 15 micromol/L).Intervention: Participants received a daily capsule containing 40 mg of folic acid, 100 mg of pyridoxine hydrochloride (vitamin B6), and 2 mg of cyanocobalamin (vitamin B12) or a placebo.Main Outcome Measures: The primary outcome was all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, amputation of all or part of a lower extremity, a composite of these 3 plus all-cause mortality, time to initiation of dialysis, and time to thrombosis of arteriovenous access in hemodialysis patients.Results: Mean baseline homocysteine level was 24.0 micromol/L in the vitamin group and 24.2 micromol/L in the placebo group. It was lowered 6.3 micromol/L (25.8%; P < .001) in the vitamin group and 0.4 micromol/L (1.7%; P = .14) in the placebo group at 3 months, but there was no significant effect on mortality (448 vitamin group deaths vs 436 placebo group deaths) (hazard ratio [HR], 1.04; 95% CI, 0.91-1.18). No significant effects were demonstrated for secondary outcomes or adverse events: there were 129 MIs in the vitamin group vs 150 for placebo (HR, 0.86; 95% CI, 0.67-1.08), 37 strokes in the vitamin group vs 41 for placebo (HR, 0.90; 95% CI, 0.58-1.40), and 60 amputations in the vitamin group vs 53 for placebo (HR, 1.14; 95% CI, 0.79-1.64). In addition, the composite of MI, stroke, and amputations plus mortality (P = .85), time to dialysis (P = .38), and time to thrombosis in hemodialysis patients (P = .97) did not differ between the vitamin and placebo groups.Conclusion: Treatment with high doses of folic acid and B vitamins did not improve survival or reduce the incidence of vascular disease in patients with advanced chronic kidney disease or end-stage renal disease.Trial Registration: clinicaltrials.gov Identifier: NCT00032435. [ABSTRACT FROM AUTHOR]

This article focuses on a large, prospective study of the association between migraine with and without aura and the subsequent risk of overall and specific cardiovascular disease in women. The methods of the study, main outcome measures, and results are detailed. Active migraine with aura was linked to a heightened risk of major cardiovascular disease, myocardial infarction, ischemic stroke, and mortality from ischemic cardiovascular disease, as well as coronary revascularization and angina. Active migraine without aura was not connected with an increased risk of any cardiovascular event.

Context: Basic research and observational evidence as well as results from trials of colon polyp recurrence suggest a role for aspirin in the chemoprevention of cancer.Objective: To examine the effect of aspirin on the risk of cancer among healthy women.Design, Setting, and Participants: In the Women's Health Study, a randomized 2 x 2 factorial trial of aspirin and vitamin E conducted between September 1992 and March 2004, 39 876 US women aged at least 45 years and initially without previous history of cancer, cardiovascular disease, or other major chronic illness were randomly assigned to receive either aspirin or aspirin placebo and followed up for an average of 10.1 years.Intervention: A dose of 100 mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other day.Main Outcome Measures: Confirmed newly diagnosed invasive cancer at any site, except for nonmelanoma skin cancer. Incidence of breast, colorectal, and lung cancer were secondary end points.Results: No effect of aspirin was observed on total cancer (n = 2865; relative risk [RR], 1.01; 95% confidence interval [CI], 0.94-1.08; P = .87), breast cancer (n = 1230; RR, 0.98; 95% CI, 0.87-1.09; P = .68), colorectal cancer (n = 269; RR, 0.97; 95% CI, 0.77-1.24; P = .83), or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (n = 205; RR, 0.78; 95% CI, 0.59-1.03; P = .08). There was also no reduction in cancer mortality either overall (n = 583; RR, 0.95; 95% CI, 0.81-1.11; P = .51) or by site, except for lung cancer mortality (n = 140; RR, 0.70; 95% CI, 0.50-0.99; P = .04). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found.Conclusions: Results from this large-scale, long-term trial suggest that alternate day use of low-dose aspirin (100 mg) for an average 10 years of treatment does not lower risk of total, breast, colorectal, or other site-specific cancers. A protective effect on lung cancer or a benefit of higher doses of aspirin cannot be ruled out. [ABSTRACT FROM AUTHOR]

Context: Basic research provides plausible mechanisms and observational studies suggest that apparently healthy persons, who self-select for high intakes of vitamin E through diet or supplements, have decreased risks of cardiovascular disease and cancer. Randomized trials do not generally support benefits of vitamin E, but there are few trials of long duration among initially healthy persons.Objective: To test whether vitamin E supplementation decreases risks of cardiovascular disease and cancer among healthy women.Design, Setting, and Participants: In the Women's Health Study conducted between 1992 and 2004, 39 876 apparently healthy US women aged at least 45 years were randomly assigned to receive vitamin E or placebo and aspirin or placebo, using a 2 x 2 factorial design, and were followed up for an average of 10.1 years.Intervention: Administration of 600 IU of natural-source vitamin E on alternate days.Main Outcome Measures: Primary outcomes were a composite end point of first major cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death) and total invasive cancer.Results: During follow-up, there were 482 major cardiovascular events in the vitamin E group and 517 in the placebo group, a nonsignificant 7% risk reduction (relative risk [RR], 0.93; 95% confidence interval [CI], 0.82-1.05; P = .26). There were no significant effects on the incidences of myocardial infarction (RR, 1.01; 95% CI, 0.82-1.23; P = .96) or stroke (RR, 0.98; 95% CI, 0.82-1.17; P = .82), as well as ischemic or hemorrhagic stroke. For cardiovascular death, there was a significant 24% reduction (RR, 0.76; 95% CI, 0.59-0.98; P = .03). There was no significant effect on the incidences of total cancer (1437 cases in the vitamin E group and 1428 in the placebo group; RR, 1.01; 95% CI, 0.94-1.08; P = .87) or breast (RR, 1.00; 95% CI, 0.90-1.12; P = .95), lung (RR, 1.09; 95% CI, 0.83-1.44; P = .52), or colon cancers (RR, 1.00; 95% CI, 0.77-1.31; P = .99). Cancer deaths also did not differ significantly between groups. There was no significant effect of vitamin E on total mortality (636 in the vitamin E group and 615 in the placebo group; RR, 1.04; 95% CI, 0.93-1.16; P = .53).Conclusions: The data from this large trial indicated that 600 IU of natural-source vitamin E taken every other day provided no overall benefit for major cardiovascular events or cancer, did not affect total mortality, and decreased cardiovascular mortality in healthy women. These data do not support recommending vitamin E supplementation for cardiovascular disease or cancer prevention among healthy women. [ABSTRACT FROM AUTHOR]

Context Physical inactivity and body mass index (BMI) are established independent risk factors in the development of type 2 diabetes; however, their comparative importance and joint relationship with diabetes are unclear. Objective To examine the relative contributions and joint association of physical activity and BMI with diabetes. Design, Setting, and Participants Prospective cohort study of 37 878 women free of cardiovascular disease, cancer, and diabetes with 6.9 years of mean follow-up. Weight, height, and recreational activities were reported at study entry. Normal weight was defined as a BMI of less than 25; overweight, 25 to less than 30; and obese, 30 or higher. Active was defined as expending more than 1000 kcal on recreational activities per week. Main Outcome Measure Incident type 2 diabetes, defined as a new self-reported diagnosis of diabetes. Results During the follow-up, 1361 cases of incident diabetes occurred. Individually, BMI and physical activity were significant predictors of incident diabetes. Compared with normal-weight individuals, the multivariate-adjusted hazard ratio (HR) was 3.22 (95% confidence interval [CI], 2.69-3.87) for overweight individuals and 9.09 (95% CI, 7.62-10.8) for obese individuals. For overall activity (kilocalories expended per week), compared with the least active first quartile, the multivariate-adjusted HRs were 0.91 (95% CI, 0.79-1.06) for the second quartile, 0.86 (95% CI, 0.74-1.01) for the third, and 0.82 (95% CI, 0.70-0.97) for the fourth (P for trend = .01). In the combined analyses, overweight and obese participants, whether active or inactive, had significantly elevated risks, compared with normal-weight active individuals. The multivariate-adjusted HRs were 1.15 (95% CI, 0.83-1.59) for normal-weight inactive, 3.68 (95% CI, 2.63-5.15) for overweight active, 4.16 (95% CI, 3.05-5.66) for overweight inactive, 11.5 (95% CI, 8.34-15.9) for obese active, and 11.8 (95% CI, 8.75-16.0) for obese inactive participa... [ABSTRACT FROM AUTHOR]

Context: Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce. Objective: To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension. Design, Setting, and Participants: A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected. Main Outcome Measure: Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg. Results: During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as... [ABSTRACT FROM AUTHOR]

Reports on a study done on the use of analgesics and renal function in men. Study focused on healthy men with moderate use of analgesics such as acetaminophen and aspirin; Outcome measures of elevated creatinine levels and reduced creatinine clearance; Results; Conclusion that moderate analgesic use in initially healthy men is not associated with increased risk of renal dysfunction.

Presents a study to examine whether cholesterol lowering with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors reduces the risks of stroke and total mortality. Data sources; Trial selection; Data extraction; Data synthesis; Conclusion.

An introduction is presented in which the editor discusses various reports within the issue on topics including importance of cardiac imaging tools for incidental findings like myocardial scar, assessment of patients with chest pain, and developments in cardiovascular medicine.

The authors reflect on the right time to use aspirin to prevent cardiovascular diseases (CVD) like myocardial infarction and stroke. They claim that the adverse effects of aspirin like serious gastrointestinal bleeding and hemorrhagic stroke underlie the clinical decision of when to use the drug. Also cited are the British Doctors' Trial, the Physicians' Health Study, and the Japanese Primary Prevention Project (JPPP) involving aspirin.

An introduction to the journal is presented in which the editors discuss the issue's focus on cardiovascular disease (CVD).

The authors discuss the evolution of the methods and technologies to measure and modify the level of cholesterol. Military physician Nikolaj Anitschkow introduced the cholesterol-fed animal model which showed that modifying the diet could cause atherosclerosis. German chemist Adolf Windaus received a Nobel prize in 1928 for understanding the structure of cholesterol. A simple lipid panel is used to assess the lipoprotein cholesterol (LDL-C) levels.

The author discusses the concept of a single pill or polypill which contains several cardiovascular medications. He notes the discussions of combination pills for primary or secondary prevention of cardiovascular disease (CVD) which are consistent with the growing interest in the importance of noncommunicable diseases. He explains the logic for the polypill and describes some proposed formulations for a CVD polypill.

Two letter to the editor are presented in response to the article "Multivitamins in the prevention of cancer in men: the Physicians' Health Study II randomized controlled trial" by Gaziano JM, Sesso HD, Christen WG, et al in 2012 issue.

Am introduction is presented in which the author discusses several issue related to researches in cardiovascular system which includes resuscitation of the heart, cardiac risk factors and platelet inhibition used with patients with acute coronary syndromes.

The article informs the decrease in death rate due to heart diseases in the U.S. after the year 1960. It informs that this decline has taken place due to the deployment of diagnostic tools and treatments of higher-risk patients in the country. Information regarding the limited availability of physician's tools including a stethoscope, an electrocardiography machine and a blood pressure cuff for making the patient comfortable during the year 1960 is presented. The use of safe and reliable direct current cardioverter-defibrillator for preventing fatal arrhythmia in 1960 is mentioned. It highlights the transformation that took place with the development of life-saving hospital based interventions including cardiac imaging devices, open heart surgery and catheter-based technologies.

An introduction to the journal is presented in which the editors discuss various reports published within the issue including ones by J. H. Traverse et al. on intracoronary bone marrow stem cells, V. Prasad and R. O. Bonow on cardiac biomarkers and G. F. Tomaselli on cardiovascular disease (CVD).

The author describes the evolution of epidemiology from early descriptive studies to the massive cohorts with hundreds of thousands of participants. He cites several factors which contributed to the evolution of population science, such as the discovery of biomarkers and the advent of DNA analysis. He offers information on the opportunities posed by the randomized trial, the cohort study and the exploration of the human genome. He also mentions the main benefit of refining, advancing and applying epidemiologic science.

The authors comments on a study published within the issue which reported trends in cholesterol levels and treatment in the U.S. since 1999. An overview of the research findings is offered. The authors contend that the study has highlighted the decreasing rates of screening, awareness and treatment of patients receiving low density lipoprotein cholesterol medications. The author presents some factors that should be considered when deciding who should be treated.

Howard D. Sesso and J. Michael Gaziano respond to a letter to the editor about their article "Vitamins E and C in the Prevention of Cardiovascular Disease in Men: The Physicins' Health Study II Randomized Controlled trial" in a previous issue.

A response by T. Kurth, J.M. Gaziano, NR Cook, G. Legroscino, HC Diener and JE Buring to a letter to the editor about their article "Migraine and the risk of cardiovascular disease in women," in the 2006 vol. 296 issue.

The article presents a letter to the editor regarding the article "Migraine and risk of cardiovascular disease in women," by T. Kurth, J.M. Gaziano, N.R. Cook, G. Logroscino, H.C. Diener, and J.E. Buring, in the July 19, 2006 issue.

An introduction is presented in which the editor discusses the guidelines for manuscripts on cardiovascular disease to- be considered for publication.

The article invites manuscripts from readers for a theme issue on cardiovascular disease, to be published in November 2013 issue of the periodical.