Unsupervised Learning Analysis of Triglycerides, Inflammation, Cholesterol, and the Risks of Incident Cardiovascular Disease and Type 2 Diabetes in the Women's Health Study.

Background: Traditional cardiovascular risk assessment entails investigator-defined exposure levels and individual risk markers in multivariable analysis. We sought to determine whether an alternative unbiased learning analysis might provide further insights into vascular risk.

Methods: We conducted an unsupervised learning (k-means cluster) analysis in the Women's Health Study (N=26 443) using baseline levels of triglycerides, high-sensitivity C-reactive protein, and low-density lipoprotein cholesterol to form novel exposures.

Identification of individuals who benefit from omega-3 fatty acid supplementation to prevent coronary heart disease: a machine-learning analysis of the VITAL.

Randomized controlled trials (RCTs) have demonstrated benefits of marine omega-3 polyunsaturated fatty acids (omega-3 FA) supplementation for the prevention of coronary heart disease (CHD). However, it has not been clear which individuals benefit the most from supplementation. We sought to develop an omega-3 effect score to stratify individuals according to their expected benefit from supplementation.

The potential of nighttime urine samples for epidemiologic research on sodium intake: Evidence from a population-based cohort study in Switzerland.

Background: The gold standard for measuring sodium intake is based on multiple 24-h urine sodium (UNa) collections, which are logistically complex and pose a high burden on study participants. Its major alternative, spot urine sampling, has been shown to lead to systematic bias in sodium intake estimation. Nighttime urine collections are a potential alternative, as they place a substantially lower burden on participants and are thus less likely to lead to underestimation of UNa compared with 24-h urinary collections.

Vitamin D and marine ω-3 fatty acids supplementation and leukocyte telomere length: 4-year findings from the VITamin D and OmegA-3 TriaL (VITAL) randomized controlled trial.

Background: Limited studies suggest that vitamin D or omega 3 fatty acids (n-3 FAs) supplementation may be beneficial for telomere maintenance, however, evidence from large randomized clinical trial is lacking.

Objective: We aimed to determine whether vitamin D or n-3 FAs supplementation reduce leukocyte telomere length (LTL) attrition over time by leveraging the VITamin D and OmegA-3 TriaL (VITAL) trial.

Methods: VITAL is a large, randomized, double-blind, placebo-controlled tr ial with a 2 x 2 factorial design of vitamin D3 (2,000 IU/day) and marine n-3 FAs (1 g/day) supplements for 5 years among a representative sample of 25,871 US females ≥55 and males ≥50 years of age.

Vitamin D supplementation vs. placebo and incident type 2 diabetes in an ancillary study of the randomized Vitamin D and Omega-3 Trial.

Observational and experimental evidence suggests that vitamin D plays a role in type 2 diabetes (T2D). However, prior randomized supplementation trials are limited to high-risk patients with prediabetes. Here we aim to evaluate whether vitamin D supplementation reduces risk of T2D in a general population of older US adults.

A Bayesian analysis of the VITAL trial: effects of ω-3 fatty acid supplementation on cardiovascular events.

Background: Effects of ω-3 fatty acids (FAs) supplementation on cardiovascular outcomes have been investigated in several randomized controlled trials (RCTs). The VITamin D and OmegA-3 TriaL (VITAL) is the largest trial that tested the effect of ω-3 FA supplementation (840 mg/d of eicosapentaenoic acid and docosahexaenoic acid in 1.2:1) in a primary prevention population in the United States, with nonsignificant results (P > 0.

Effects of cocoa extract supplementation and multivitamin/multimineral supplements on self-reported fractures in the Cocoa Supplement and Multivitamins Outcomes Study randomized clinical trial.

Osteoporosis is a major public health problem among older adults. Forty percent of older US adults take multivitamin/multimineral (MVM) supplementation. The effects of MVM supplementation on fractures are unclear.

Machine-learning approaches to predict individualized treatment effect using a randomized controlled trial.

Recent advancements in machine learning (ML) for analyzing heterogeneous treatment effects (HTE) are gaining prominence within the medical and epidemiological communities, offering potential breakthroughs in the realm of precision medicine by enabling the prediction of individual responses to treatments. This paper introduces the methodological frameworks used to study HTEs, particularly based on a single randomized controlled trial (RCT). We focus on methods to estimate conditional average treatment effect (CATE) for multiple covariates, aiming to predict individualized treatment effects.

Vitamin D Supplementation, Chronic Obstructive Lung Disease and Asthma Exacerbations, and Lung Function Decline.

Background: It remains unclear whether supplementation with vitamin D reduces risk of acute exacerbations of chronic obstructive lung disease (COPD) or asthma, major contributors to the world-wide burden of disease.

Objectives: To compare effects of vitamin D with placebo supplementation for the prespecified primary endpoints 1) acute exacerbations of COPD and 2) decline in pulmonary function measures of airflow obstruction. Prespecified secondary endpoints included asthma exacerbations and control.

Modifiable lifestyle factors in the primordial prevention of hypertension in three US cohorts.

Background: Evidence is lacking on the relative contributions of specific lifestyle factors and their overall contribution to prevention of hypertension, in particular early-onset hypertension.

Methods: This prospective cohort study included participants of the Nurses' Health Study (NHS, N = 52,780 women, aged 40-67 in 1986), the NHS II (N = 83,871 women, aged 27-46 in 1991), and the Health Professionals Follow-up Study (HPFS, N = 31,269 men, aged 40-75 in 1986), who were free from hypertension, cardiovascular disease and cancer at baseline. Four modifiable lifestyles were evaluated based on hypertension guidelines: BMI, moderate-to-vigorous physical activity, Dietary Approaches to Stop Hypertension (DASH) score, and alcohol intake.

Biomarkers of glucose-insulin homeostasis and incident type 2 diabetes and cardiovascular disease: results from the Vitamin D and Omega-3 trial.

Background: Dysglycemia and insulin resistance increase type 2 diabetes (T2D) and cardiovascular disease (CVD) risk, yet associations with specific glucose-insulin homeostatic biomarkers have been inconsistent. Vitamin D and marine omega-3 fatty acids (n-3 FA) may improve insulin resistance. We sought to examine the association between baseline levels of insulin, C-peptide, HbA1c, and a novel insulin resistance score (IRS) with incident cardiometabolic diseases, and whether randomized vitamin D or n-3 FA modify these associations.

Use of Censored Data Methods to Estimate Blood Pressure Percentiles in US Adults.

Blood pressure (BP) levels are important modifiable risk factors for incident cardiovascular disease (CVD). However, many adults are on anti-hypertensive medication (MEDS) which lowers their BP but is a marker for increased CVD risk. To capture the association of BP and its treatment with risk, it is important to estimate BP levels in the absence of medication, i.

Inflammation, Cholesterol, Lipoprotein(a), and 30-Year Cardiovascular Outcomes in Women.

Background: High-sensitivity C-reactive protein (CRP), low-density lipoprotein (LDL) cholesterol, and lipoprotein(a) levels contribute to 5-year and 10-year predictions of cardiovascular risk and represent distinct pathways for pharmacologic intervention. More information about the usefulness of these biomarkers for predicting cardiovascular risk over longer periods of time in women is needed because early-life intervention represents an important risk-reduction method.

Methods: We measured high-sensitivity CRP, LDL cholesterol, and lipoprotein(a) levels at baseline in 27,939 initially healthy U.

Associations of Vitamin D-Related Biomarkers With Hypertension and the Renin-Angiotensin System in Men and Women.

Background: Vitamin D may prevent the development of hypertension through down-regulation of renin-angiotensin system. However, epidemiologic studies assessing the interrelation of vitamin D-related biomarkers with hypertension are sparse.

Methods: We examined the prospective associations between vitamin D-related biomarkers and the risk of hypertension in a nested case-control study.

Prediction of individual lifetime cardiovascular risk and potential treatment benefit: development and recalibration of the LIFE-CVD2 model to four European risk regions.

Aims: The 2021 European Society of Cardiology prevention guidelines recommend the use of (lifetime) risk prediction models to aid decisions regarding initiation of prevention. We aimed to update and systematically recalibrate the LIFEtime-perspective CardioVascular Disease (LIFE-CVD) model to four European risk regions for the estimation of lifetime CVD risk for apparently healthy individuals.

Methods And Results: The updated LIFE-CVD (i.

Joint effects of one year of marine omega-3 fatty acid supplementation and participant dietary fish intake upon circulating lipid mediators of inflammation resolution in a randomized controlled trial.

Objectives: We assessed the joint effects of omega (n)-3 fatty acid supplementation and dietary fish intake on systemic lipid mediators of inflammation among adults.

Methods: Within VITAL, a double-blind randomized controlled trial, adults were randomized to ω-3 fatty acids (460 mg EPA + 380 mg DHA/d) or placebo. We selected participants who reported low (<1 serving/mo) baseline dietary fish intake and matched them by age, sex, race, and trial arm to participants with self-reported highest fish intake (≥3.

Effects of Supplemental Vitamin D3, Omega-3 Fatty Acids on Physical Performance Measures in the VITamin D and OmegA-3 TriaL.

Context: Declining muscle strength and performance in older adults are associated with falls, fractures, and premature death.

Objective: This work aimed to determine whether supplementation with vitamin D3 or omega-3 fatty acids vs placebo for 2 years improves physical performance measures.

Methods: VITamin D and OmegA-3 TriaL (VITAL) was a double-blinded, placebo-controlled randomized trial of supplemental vitamin D3 and/or omega-3 fatty acids vs placebo in the prevention of cancer and cardiovascular disease in 25 871 US adults.

Vitamin D and Marine n-3 Fatty Acids for Autoimmune Disease Prevention: Outcomes Two Years After Completion of a Double-Blind, Placebo-Controlled Trial.

Objective: In the 5.3-year randomized, 2 × 2 factorial, double-blind, placebo-controlled Vitamin D and Omega-3 Trial (VITAL), vitamin D supplementation reduced autoimmune disease (AD) incidence (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.

Effect of multivitamin-mineral supplementation versus placebo on cognitive function: results from the clinic subcohort of the COcoa Supplement and Multivitamin Outcomes Study (COSMOS) randomized clinical trial and meta-analysis of 3 cognitive studies within COSMOS.

Background: Longer effects of multivitamin-mineral (MVM) supplementation on late-life cognitive function remain untested using in-person, detailed neuropsychological assessments. Furthermore, insufficient evidence exists for healthcare providers to recommend daily MVM supplements to prevent cognitive decline.

Objectives: This study aimed to test MVM effects on cognitive change using in-person, detailed neuropsychological assessments and conduct a meta-analysis within COSMOS (COcoa Supplement and Multivitamin Outcomes Study) cognitive substudies for a robust evaluation of MVM effects on cognition.

Risk Factors for the Development of New-Onset Persistent Atrial Fibrillation: Subanalysis of the VITAL Study.

Background: Sustained forms of atrial fibrillation (AF) are associated with lower treatment success rates and poorer prognosis compared with paroxysmal AF. Yet, little is known about risk factors that predispose to persistent AF on initial presentation. Our objective was to define risk factors associated with new-onset persistent AF.