Michelle A. Albert

The VITamin D and OmegA-3 TriaL (VITAL): Rationale and Design of a Large Randomized Controlled Trial of Vitamin D and Marine Omega-3 Fatty Acid Supplements for the Primary Prevention of Cancer and Cardiovascular Disease

Data from laboratory studies, observational research, and/or secondary prevention trials suggest that vitamin D and marine omega-3 fatty acids may reduce risk for cancer or cardiovascular disease (CVD), but primary prevention trials with adequate dosing in general populations (i.e., unselected for disease risk) are lacking. The ongoing VITamin D and OmegA-3 TriaL (VITAL) is a large randomized, double-blind, placebo-controlled, 2 x 2 factorial trial of vitamin D (in the form of vitamin D(3) [cholecalciferol], 2000 IU/day) and marine omega-3 fatty acid (Omacor fish oil, eicosapentaenoic acid [EPA]+docosahexaenoic acid [DHA], 1g/day) supplements in the primary prevention of cancer and CVD among a multi-ethnic population of 20,000 U.S. men aged ≥ 50 and women aged ≥ 55. The mean treatment period will be 5 years. Baseline blood samples will be collected in at least 16,000 participants, with follow-up blood collection in about 6000 participants. Yearly follow-up questionnaires will assess treatment compliance (plasma biomarker measures will also assess compliance in a random sample of participants), use of non-study drugs or supplements, occurrence of endpoints, and cancer and vascular risk factors. Self-reported endpoints will be confirmed by medical record review by physicians blinded to treatment assignment, and deaths will be ascertained through national registries and other sources. Ancillary studies will investigate whether these agents affect risk for diabetes and glucose intolerance; hypertension; cognitive decline; depression; osteoporosis and fracture; physical disability and falls; asthma and other respiratory diseases; infections; and rheumatoid arthritis, systemic lupus erythematosus, thyroid diseases, and other autoimmune disorders.

Alcohol Consumption and Plasma Concentration of C-Reactive Protein

Background—Moderate alcohol intake has been associated with lower cardiovascular mortality. However, data evaluating the relationship between C-reactive protein (CRP), a predictor of cardiovascular risk, and alcohol consumption are sparse. Methods and Results—The relationship between alcohol consumption and CRP was evaluated in a cross-sectional survey and over time among 1732 men and 1101 women participating in the Pravastatin Inflammation/CRP Evaluation Study. CRP levels were lower in those with moderate alcohol intake versus light or occasional intake: in 5 categories of alcohol intake (no alcohol or <1 drink monthly, 1 to 3 drinks monthly, 1 to 4 drinks weekly, 5 to 7 drinks weekly, and ≥2 drinks daily), median CRP levels were 2.60 mg/L (interquartile range (IQR), 1.20 to 5.30 mg/L), 2.20 mg/L (IQR, 1.00 to 4.40 mg/L), 1.70 mg/L (IQR, 0.80 to 3.80 mg/L), 1.60 mg/L (IQR, 0.80 to 3.30 mg/L), and 1.80 mg/L (IQR, 0.80 to 2.90 mg/L), respectively. This relationship was present among men, women not taking hormone replacement therapy, nonsmokers, and those individuals with and without a history of cardiovascular disease (all P <0.001). In multivariate analysis, the relationship between alcohol consumption and CRP remained significant after controlling for multiple traditional cardiovascular risk factors. Alcohol consumption did not significantly affect the change in CRP or lipid levels associated with statin use. Conclusion—Moderate alcohol consumption was associated with lower CRP concentrations than no or occasional alcohol intake, an effect that was independent of alcohol-related effects on lipids. Alcohol may attenuate cardiovascular mortality in part through an anti-inflammatory mechanism.

Plasma Concentration of C-Reactive Protein and the Calculated Framingham Coronary Heart Disease Risk Score

Background—Although C-reactive protein (CRP) predicts vascular risk, few data are available evaluating the relation between CRP and the Framingham Coronary Heart Disease Risk Score (FCRS). Methods and Results—CRP levels were compared with calculated 10-year FCRS in a cross-sectional survey of 1666 individuals free of cardiovascular disease. Among men and women not using hormone replacement therapy (HRT), CRP levels were significantly related to 10-year Framingham Coronary Heart Disease Risk categories [total cholesterol (TC) score for men and women:r =0.29 and r =0.22, respectively; LDL cholesterol score for men and women:r =0.29 and r =0.22, respectively, all probability values <0.01]. However, CRP levels correlated minimally with individual components of the FCRS, which included age (rmen=0.17, rwomen=−0.003), TC (rmen=−0.02, rwomen=−0.006), HDL-C (rmen=0.13), LDL-C (rmen=−0.0002, rwomen=0.012), blood pressure (rmen=0.18, rwomen=0.22), diabetes (rmen=0.10, rwomen=0.07), and smoking (rmen=0.16, rwomen=0.14) status. For women taking HRT, no significant relation was observed between CRP and the FCRS, although the power to detect effects in this subgroup is limited. Conclusions—Our data demonstrate that CRP levels significantly correlate with calculated 10-year Framingham Coronary Heart Disease Risk in men and women not taking HRT but correlate minimally with most individual components of the FCRS. These data provide additional support for continued evaluation of CRP as a potential adjunct in the global prediction of cardiovascular risk.

Impact of Traditional and Novel Risk Factors on the Relationship Between Socioeconomic Status and Incident Cardiovascular Events

Background— Persons of lower socioeconomic status have greater cardiovascular risk than those of higher socioeconomic status. However, the mechanism through which socioeconomic status affects cardiovascular disease (CVD) is uncertain. Virtually no data are available that examine the prospective association between novel inflammatory and hemostatic CVD risk indicators, socioeconomic status, and incident CVD events. Methods and Results— We assessed the relationship between 2 indicators of socioeconomic status (education and income), traditional and novel CVD risk factors (high sensitivity C-reactive protein, soluble intercellular adhesion molecule-1, fibrinogen, and homocysteine), and incident CVD events among 22 688 apparently healthy female health professionals participating in the Womens Health Study. These women were followed up for 10 years for the development of myocardial infarction, ischemic stroke, coronary revascularization, and cardiovascular death. More educated women were less likely to be smokers; had a lower prevalence of hypertension, diabetes, and obesity; and were more likely to participate in vigorous physical activity than less educated women. At baseline, median total cholesterol, low-density lipoprotein, triglyceride, C-reactive protein, intercellular adhesion molecule-1, fibrinogen, and homocysteine levels for women in 5 categories of education (<2 years of nursing education, 2 to <4 years of nursing education, a bachelors degree, a masters degree, and a doctoral degree) and 6 categories of income [≤

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Socioeconomic Status and Incident Type 2 Diabetes Mellitus: Data from the Women's Health Study

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