Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease: A Novel Analysis of the VITAL Trial Using Win Ratio and Hierarchical Composite Outcomes.

This study aimed to investigate whether n-3 fatty acid supplementation reduced cardiovascular disease (CVD) events in a novel analysis using hierarchical composite CVD outcomes based on win ratio in the VITamin D and OmegA-3 TriaL (VITAL). This was a secondary analysis of our VITAL randomized trial, which assessed the effects of marine n-3 fatty acids (1 g/day) and vitamin D3 on incident CVD and cancer among healthy older adults (n = 25,871). The primary analysis estimated win ratios of a composite of major CVD outcomes prioritized as fatal coronary heart disease, other fatal CVD including stroke, non-fatal myocardial infarction (MI), and non-fatal stroke, comparing n-3 fatty acids to placebo. The primary result was a nonsignificant benefit of this supplementation for the prioritized primary CVD outcome (reciprocal win ratio [95% confidence interval]: 0.90 [0.78-1.04]), similar to the 0.92 (0.80-1.06) hazard ratio in our original time-to-first event analysis without outcome prioritization. Its benefits came from reducing MI (0.71 [0.57-0.88]) but not stroke (1.01 [0.80 to 1.28]) components. For the primary CVD outcome, participants with low fish consumption at baseline benefited (0.79 [0.65-0.96]) more than those with high consumption (1.05 [0.85-1.30]). These results are consistent with, but slightly stronger than, those without outcome prioritization.

Omega-3 Fatty Acid Biomarkers and Incident Atrial Fibrillation.

BACKGROUND: The relationship between omega-3 fatty acids and atrial fibrillation (AF) remains controversial. OBJECTIVES: This study aimed to determine the prospective associations of blood or adipose tissue levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with incident AF. METHODS: We used participant-level data from a global consortium of 17 prospective cohort studies, each with baseline data on blood or adipose tissue omega-3 fatty acid levels and AF outcomes. Each participating study conducted a de novo analyses using a prespecified analytical plan with harmonized definitions for exposures, outcome, covariates, and subgroups. Associations were pooled using inverse-variance weighted meta-analysis. RESULTS: Among 54,799 participants from 17 cohorts, 7,720 incident cases of AF were ascertained after a median 13.3 years of follow-up. In multivariable analysis, EPA levels were not associated with incident AF, HR per interquintile range (ie, the difference between the 90th and 10th percentiles) was 1.00 (95% CI: 0.95-1.05). HRs for higher levels of DPA, DHA, and EPA+DHA, were 0.89 (95% CI: 0.83-0.95), 0.90 (95% CI: 0.85-0.96), and 0.93 (95% CI: 0.87-0.99), respectively. CONCLUSIONS: In vivo levels of omega-3 fatty acids including EPA, DPA, DHA, and EPA+DHA were not associated with increased risk of incident AF. Our data suggest the safety of habitual dietary intakes of omega-3 fatty acids with respect to AF risk. Coupled with the known benefits of these fatty acids in the prevention of adverse coronary events, our study suggests that current dietary guidelines recommending fish/omega-3 fatty acid consumption can be maintained.

A randomized clinical trial of omega-3 fatty acid and vitamin D supplementation on electrocardiographic risk profiles.

Beneficial and adverse associations with arrhythmias have been reported for omega-3 fatty acids (omega-3 FA) and Vitamin D. The 12 lead electrocardiogram (ECG) contains quantitative measures reflecting diverse aspects of electrophysiology that might provide insights into mechanisms underlying these associations. In a pre-specified ancillary study of the VITaminD and omegA-3 (VITAL) trial, we examined the effect of 1 g of marine omega-3 FA per day, comprised of 460 mg eicosapentanoic acid and 380 mg of docosahexaenoic acid, and 2000 IU VitaminD3 per day on ECG characteristics associated with atrial and ventricular arrhythmias among individuals age 50 years or greater. A total of 911 study participants underwent ECGs at baseline and again at 2 years after the randomization. Individuals randomized to active omega-3 FA demonstrated significant net increase in PR-interval duration (p = 0.005) and P-wave duration (p = 0.03) as well significant net decrease in P-wave amplitude (p = 0.037) as compared to placebo. RMSSD increased to a greater extent in the omega-3 FA arm compared to placebo (p = 0.040). For Vitamin D3, the Cornell voltage increased to a lesser extent in the participants assigned to active treatment as compared to placebo (p = 0.044). There were no other significant differences in QRS, QTc, Cornell voltage or heart rate. Thus, randomized treatment with omega-3 FA supplements resulted in changes on the ECG that are potentially reflective of heightened vagal tone and/or slowing of intraatrial and AV conduction. Vitamin D3 supplementation resulted in modest reductions in progressive LV voltage suggestive of a potential antihypertrophic effect.Trial registration ClinicalTrials.gov Identifiers: NCT01169259, NCT02178410 (06/26/2010 and 06/30/2014).

Sex Differences in Atrial Fibrillation Risk: The VITAL Rhythm Study.

Importance: Women have a lower incidence of atrial fibrillation (AF) compared with men in several studies, but it is unclear whether this sex difference is independent of sex differences in prevalent cardiovascular disease (CVD), body size, and other risk factors. Objective: To examine sex differences in AF incidence and whether AF risk factors differ by sex in a contemporary cohort of men and women without prevalent CVD. Design, Setting, and Participants: This was a prospective cohort analysis within the Vitamin D and Omega-3 Trial (VITAL) Rhythm Study, a randomized trial that examined the effect of vitamin D and ω-3 fatty acid supplementation on incident AF among men 50 years or older and women 55 years or older without a prior history of prevalent AF, CVD, or cancer at baseline. Data were analyzed from September 29, 2020, to June 29, 2021. Exposures: Sex, height, weight, body mass index (BMI), body surface area (BSA), and other AF risk factors at study enrollment. Main Outcomes and Measures: Incident AF confirmed by medical record review. Results: A total of 25 119 individuals (mean [SD] age, 67.0 [7.1] years; 12 757 women [51%]) were included in this study. Over a median (IQR) follow-up of 5.3 (5.1-5.7) years, 900 confirmed incident AF events occurred among 12 362 men (495 events, 4.0%) and 12 757 women (405 events, 3.2%). After adjustment for age and treatment assignment, women were at lower risk for incident AF than men (hazard ratio [HR], 0.68; 95% CI, 0.59-0.77; P < .001). The inverse association between female sex and AF persisted after adjustment for race and ethnicity, smoking, alcohol intake, hypertension, diabetes (type 1, type 2, gestational), thyroid disease, exercise, and BMI (HR, 0.73; 95% CI, 0.63-0.85; P <.001). However, female sex was positively associated with AF when height (HR, 1.39; 95% CI, 1.14-1.72; P = .001), height and weight (HR 1.49, 95% CI, 1.21-1.82; P <.001), or BSA (HR, 1.25; 95% CI, 1.06-1.49; P = .009) were substituted for BMI in the multivariate model. In stratified models, risk factor associations with incident AF were similar for women and men. Conclusions and Relevance: In this cohort study, findings suggest that after controlling for height and/or body size, women without CVD at baseline were at higher risk for AF than men, suggesting that sex differences in body size account for much of the protective association between female sex and AF. These data underscore the importance of AF prevention in women.

Diabetes Mellitus, Race, and Effects of Omega-3 Fatty Acids on Incidence of Heart Failure Hospitalization.

OBJECTIVES: The primary aim was to evaluate whether prevalent type 2 diabetes (T2D) modifies the effects of omega-3 supplementation on heart failure (HF) hospitalization. The secondary aim was to examine if race modifies the effects of omega-3 supplements on HF risk. BACKGROUND: It is unclear whether race and T2D modify the effects of omega-3 supplementation on the incidence of HF. METHODS: In this ancillary study of the parent VITAL (Vitamin D and Omega-3 Trial)-a completed randomized trial testing the efficacy of vitamin D and omega-3 fatty acids on cardiovascular diseases and cancer, we assessed the role of T2D and race on the effects of omega-3 supplements on the incidence of HF hospitalization (adjudicated by a review of medical records and supplemented with a query of Centers for Medicare and Medicaid Services data). RESULTS: When omega-3 supplements were compared with placebo, the HR for first HF hospitalization was 0.69 (95% CI: 0.50-0.95) in participants with prevalent T2D and 1.09 (95% CI: 0.88-1.34) in those without T2D (P for interaction = 0.019). Furthermore, prevalent T2D modified the effects of omega-3 fatty acids on the incidence of recurrent HF hospitalization (HR: 0.53; 95% CI: 0.41-0.69 in participants with prevalent T2D vs HR: 1.07; 95% CI: 0.89-1.28 in those without T2D; P interaction <0.0001). In our secondary analysis, omega-3 supplementation reduced recurrent HF hospitalization only in Black participants (P interaction race × omega-3 = 0.0497). CONCLUSIONS: Our data show beneficial effects of omega-3 fatty acid supplements on incidence of HF hospitalization in participants with T2D but not in those without T2D, and such benefit appeared to be stronger in Black participants with T2D. (Intervention With Vitamin D and Omega-3 Supplements and Incident Heart Failure; NCT02271230; Vitamin D and Omega-3 Trial [VITAL]; NCT01169259 [parent study]).

Effect of Long-Term Marine É·-3 Fatty Acids Supplementation on the Risk of Atrial Fibrillation in Randomized Controlled Trials of Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Some, but not all, large-scale randomized controlled trials (RCTs) investigating the effects of marine É·-3 fatty acids supplementation on cardiovascular outcomes have reported increased risks of atrial fibrillation (AF). The potential reasons for disparate findings may be dose-related. METHODS: The MEDLINE and Embase databases were searched for articles and abstracts published between January 1, 2012, and December 31, 2020, in addition to a meta-analysis of large cardiovascular RCTs published in 2019. RCTs of cardiovascular outcomes of marine É·-3 fatty acids that reported results for AF, either as a prespecified outcome, an adverse event, or a cause for hospitalization, with a minimum sample size of 500 patients and a median follow-up of at least 1 year were included. RCTs specifically examining shorter-term effects of É·-3 fatty acids on recurrent AF in patients with established AF or postoperative AF were not included. The hazard ratio (HR) for the reported AF outcomes within each trial was meta-analyzed using random effects model with Knapp-Hartung adjustment and evaluated a dose-response relationship with a meta-regression model. RESULTS: Of 4049 screened records, 7 studies were included in the meta-analysis. Of those, 5 were already detected in a previous meta-analysis of cardiovascular RCTs. Among the 81 210 patients from 7 trials, 58 939 (72.6%) were enrolled in trials testing ≤1 g/d and 22 271 (27.4%) in trials testing >1 g/d of É·-3 fatty acids. The mean age was 65 years, and 31 842 (39%) were female. The weighted average follow-up was 4.9 years. In meta-analysis, the use of marine É·-3 fatty acid supplements was associated with an increased risk of AF (n=2905; HR, 1.25 [95% CI, 1.07-1.46]; P=0.013). In analyses stratified by dose, the HR was greater in the trials testing >1 g/d (HR, 1.49 [95% CI, 1.04-2.15]; P=0.042) compared with those testing ≤1 g/d (HR, 1.12 [95% CI, 1.03-1.22]; P=0.024; P for interaction <0.001). In meta-regression, the HR for AF increased per 1 g higher dosage of É·-3 fatty acids dosage (HR, 1.11 [95% CI, 1.06-1.15]; P=0.001). CONCLUSIONS: In RCTs examining cardiovascular outcomes, marine É·-3 supplementation was associated with an increased risk of AF. The risk appeared to be greater in trials testing >1 g/d.

Effect of Marine Omega-3 Fatty Acid and Vitamin D Supplementation on Incident Atrial Fibrillation: A Randomized Clinical Trial.

Importance: Atrial fibrillation (AF) is the most common heart rhythm disturbance, continues to increase in incidence, and results in significant morbidity and mortality. The marine omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and vitamin D have been reported to have both benefits and risks with respect to incident AF, but large-scale, long-term randomized trial data are lacking. Objective: To test the effects of long-term administration of marine omega-3 fatty acids and vitamin D on incident AF. Design, Setting, and Participants: An ancillary study of a 2 × 2 factorial randomized clinical trial involving 25 119 women and men aged 50 years or older without prior cardiovascular disease, cancer, or AF. Participants were recruited directly by mail between November 2011 and March 2014 from all 50 US states and were followed up until December 31, 2017. Interventions: Participants were randomized to receive EPA-DHA (460 mg/d of EPA and 380 mg/d of DHA) and vitamin D3 (2000 IU/d) (n = 6272 analyzed); EPA-DHA and placebo (n = 6270 analyzed); vitamin D3 and placebo (n = 6281 analyzed); or 2 placebos (n = 6296 analyzed). Main Outcomes and Measures: The primary outcome was incident AF confirmed by medical record review. Results: Among the 25 119 participants who were randomized and included in the analysis (mean age, 66.7 years; 50.8% women), 24 127 (96.1%) completed the trial. Over a median 5.3 years of treatment and follow-up, the primary end point of incident AF occurred in 900 participants (3.6% of study population). For the EPA-DHA vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.24; P = .19). For the vitamin D3 vs placebo comparison, incident AF events occurred in 469 (3.7%) vs 431 (3.4%) participants, respectively (hazard ratio, 1.09; 95% CI, 0.96-1.25; P = .19). There was no evidence for interaction between the 2 study agents (P = .39). Conclusions and Relevance: Among adults aged 50 years or older, treatment with EPA-DHA or vitamin D3, compared with placebo, resulted in no significant difference in the risk of incident AF over a median follow-up of more than 5 years. The findings do not support the use of either agent for the primary prevention of incident AF. Trial Registration: ClinicalTrials.gov Identifiers: NCT02178410; NCT01169259.

Guidance for Rebooting Electrophysiology Through the COVID-19 Pandemic From the Heart Rhythm Society and the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology: Endorsed by the American College of Cardiology.

Coronavirus disease 2019 (COVID-19) has presented substantial challenges to patient care and impacted health care delivery, including cardiac electrophysiology practice throughout the globe. Based upon the undetermined course and regional variability of the pandemic, there is uncertainty as to how and when to resume and deliver electrophysiology services for arrhythmia patients. This joint document from representatives of the Heart Rhythm Society, American Heart Association, and American College of Cardiology seeks to provide guidance for clinicians and institutions reestablishing safe electrophysiological care. To achieve this aim, we address regional and local COVID-19 disease status, the role of viral screening and serologic testing, return-to-work considerations for exposed or infected health care workers, risk stratification and management strategies based on COVID-19 disease burden, institutional preparedness for resumption of elective procedures, patient preparation and communication, prioritization of procedures, and development of outpatient and periprocedural care pathways.

Vitamin D, Marine n-3 Fatty Acids, and Primary Prevention of Cardiovascular Disease Current Evidence.

Whether marine omega-3 fatty acid (n-3 FA) or vitamin D supplementation can prevent cardiovascular disease (CVD) in general populations at usual risk for this outcome is unknown. A major goal of VITAL (Vitamin D and Omega-3 Trial) was to fill this knowledge gap. In this article, we review the results of VITAL, discuss relevant mechanistic studies regarding n-3 FAs, vitamin D, and vascular disease, and summarize recent meta-analyses of the randomized trial evidence on these agents. VITAL was a nationwide, randomized, placebo-controlled, 2×2 factorial trial of marine n-3 FAs (1 g/d) and vitamin D3 (2000 IU/d) in the primary prevention of CVD and cancer among 25 871 US men aged ≥50 and women aged ≥55 years, including 5106 blacks. Median treatment duration was 5.3 years. Supplemental n-3 FAs did not significantly reduce the primary cardiovascular end point of major CVD events (composite of myocardial infarction, stroke, and CVD mortality; hazard ratio [HR], 0.92 [95% CI, 0.80-1.06]) but were associated with significant reductions in total myocardial infarction (HR, 0.72 [95% CI, 0.59-0.90]), percutaneous coronary intervention (HR, 0.78 [95% CI, 0.63-0.95]), and fatal myocardial infarction (HR, 0.50 [95% CI, 0.26-0.97]) but not stroke or other cardiovascular end points. For major CVD events, a treatment benefit was seen in those with dietary fish intake below the cohort median of 1.5 servings/wk (HR, 0.81 [95% CI, 0.67-0.98]) but not in those above (P interaction=0.045). For myocardial infarction, the greatest risk reductions were in blacks (HR, 0.23 [95% CI, 0.11-0.47]; P interaction by race, 0.001). Vitamin D supplementation did not reduce major CVD events (HR, 0.97 [95% CI, 0.85-1.12]) or other cardiovascular end points. Updated meta-analyses that include VITAL and other recent trials document coronary risk reduction from supplemental marine n-3 FAs but no clear CVD risk reduction from supplemental vitamin D. Additional research is needed to determine which individuals may be most likely to derive net benefit from supplementation. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01169259.

Association of Dietary Magnesium Intake with Fatal Coronary Heart Disease and Sudden Cardiac Death.

Background: Postmenopausal women represent the highest population-based burden of cardiovascular disease, including sudden cardiac death (SCD). Our understanding of the etiology and risk factors contributing to fatal coronary heart disease (CHD) and SCD, particularly among women, is limited. This study examines the association between dietary magnesium intake and fatal CHD and SCD. Materials and Methods: We examined 153,569 postmenopausal women who participated in the Women's Health Initiative recruited between 1993 and 1998. Magnesium intake at baseline was assessed using a validated food frequency questionnaire, adjusting for energy via the residual method. Fatal CHD and SCD were identified over an average follow-up of 10.5 years. Results: For every standard deviation increase in magnesium intake, there was statistically significant risk reduction, after adjustment for confounders, of 7% for fatal CHD (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.89-0.97), and 18% risk reduction for SCD (HR 0.82, 95% CI 0.58-1.15) the latter of which did not reach statistical significance. In age-adjusted quartile analysis, women with the lowest magnesium intake (189 mg/day) had the greatest risk for fatal CHD (HR 1.54, 95% CI 1.40-1.69) and SCD (HR 1.70, 95% CI 0.94-3.07). This association was attenuated in the fully adjusted model, with HRs of 1.19 (95% CI 1.06-1.34) for CHD and 1.24 (95% CI 0.58-2.65) for SCD for the lowest quartile of magnesium intake. Conclusions: This study provides evidence of a potential inverse association between dietary magnesium and fatal CHD and a trend of magnesium with SCD in postmenopausal women. Future studies should confirm this association and consider clinical trials to test whether magnesium supplementation could reduce fatal CHD in high-risk individuals.

Marine n-3 Fatty Acids and Prevention of Cardiovascular Disease and Cancer.

BACKGROUND: Higher intake of marine n-3 (also called omega-3) fatty acids has been associated with reduced risks of cardiovascular disease and cancer in several observational studies. Whether supplementation with n-3 fatty acids has such effects in general populations at usual risk for these end points is unclear. METHODS: We conducted a randomized, placebo-controlled trial, with a two-by-two factorial design, of vitamin D3 (at a dose of 2000 IU per day) and marine n-3 fatty acids (at a dose of 1 g per day) in the primary prevention of cardiovascular disease and cancer among men 50 years of age or older and women 55 years of age or older in the United States. Primary end points were major cardiovascular events (a composite of myocardial infarction, stroke, or death from cardiovascular causes) and invasive cancer of any type. Secondary end points included individual components of the composite cardiovascular end point, the composite end point plus coronary revascularization (expanded composite of cardiovascular events), site-specific cancers, and death from cancer. Safety was also assessed. This article reports the results of the comparison of n-3 fatty acids with placebo. RESULTS: A total of 25,871 participants, including 5106 black participants, underwent randomization. During a median follow-up of 5.3 years, a major cardiovascular event occurred in 386 participants in the n-3 group and in 419 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.80 to 1.06; P=0.24). Invasive cancer was diagnosed in 820 participants in the n-3 group and in 797 in the placebo group (hazard ratio, 1.03; 95% CI, 0.93 to 1.13; P=0.56). In the analyses of key secondary end points, the hazard ratios were as follows: for the expanded composite end point of cardiovascular events, 0.93 (95% CI, 0.82 to 1.04); for total myocardial infarction, 0.72 (95% CI, 0.59 to 0.90); for total stroke, 1.04 (95% CI, 0.83 to 1.31); for death from cardiovascular causes, 0.96 (95% CI, 0.76 to 1.21); and for death from cancer (341 deaths from cancer), 0.97 (95% CI, 0.79 to 1.20). In the analysis of death from any cause (978 deaths overall), the hazard ratio was 1.02 (95% CI, 0.90 to 1.15). No excess risks of bleeding or other serious adverse events were observed. CONCLUSIONS: Supplementation with n-3 fatty acids did not result in a lower incidence of major cardiovascular events or cancer than placebo. (Funded by the National Institutes of Health and others; VITAL ClinicalTrials.gov number, NCT01169259 .).

Folic Acid, Vitamin B6, and Vitamin B12 in Combination and Age-Related Cataract in a Randomized Trial of Women.

PURPOSE: To examine the incidence of cataract and cataract extraction in a trial of folic acid and vitamins B6 and B12. METHODS: In a randomized, double-masked, placebo-controlled trial, 5442 female health professionals aged 40 years or older with preexisting cardiovascular disease (CVD) or three or more CVD risk factors were randomly assigned to receive a combination of folic acid (2.5 mg/day), vitamin B6 (50 mg/day), and vitamin B12 (1 mg/day), or placebo. A total of 3925 of these women did not have a diagnosis of cataract at baseline and were included in this analysis. The primary endpoint was age-related cataract, defined as an incident age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review. Extraction of incident age-related cataract was a secondary endpoint of the trial. RESULTS: During an average of 7.3 years of treatment and follow-up, 408 cataracts and 275 cataract extractions were documented. There were 215 cataracts in the combination treatment group and 193 in the placebo group (hazard ratio, HR, 1.10, 95% confidence interval, CI, 0.90-1.33; p = 0.36). For the secondary endpoint of cataract extraction, there were 155 in the combination treatment group and 120 in the placebo group (HR 1.28, 95% CI 1.01-1.63; p = 0.04). CONCLUSIONS: In this large-scale randomized trial of women at high risk of CVD, daily supplementation with a combination of folic acid, vitamin B6, and vitamin B12 had no significant effect on cataract, but may have increased the risk of cataract extraction.

Dietary Fat Intake Is Differentially Associated with Risk of Paroxysmal Compared with Sustained Atrial Fibrillation in Women.

BACKGROUND: Dietary fats have effects on biological pathways that may influence the development and maintenance of atrial fibrillation (AF). However, associations between n-3 (ω-3) polyunsaturated fatty acids and AF are inconsistent, and data on other dietary fats and AF risk are sparse. OBJECTIVES: We examined the association between dietary fatty acid (FA) subclasses and risk of incident AF and explored whether these associations differed for sustained and paroxysmal AF. METHODS: We conducted a prospective cohort study in 33,665 women ≥45 y old without cardiovascular disease (CVD) and AF at baseline in 1993. Fat intake was estimated from food frequency questionnaires at baseline and in 2004. Incident AF was confirmed by medical records through October 2013. AF patterns were classified according to the most sustained form of AF within 2 y of diagnosis. Cox proportional hazards models with the use of a competing risk model approach estimated the RR. RESULTS: Over 19.2 y, 1441 cases of incident AF (929 paroxysmal and 467 persistent/chronic) were confirmed. Intakes of total fat and FA subclasses were not associated with risk of AF. Saturated fatty acids (SFAs) and monounsaturated fatty acids (MUFAs) were differentially associated with AF patterns. The RR for a 5% increment of energy from SFAs was 1.47 (95% CI: 1.04, 2.09) for persistent/chronic and 0.85 (95% CI: 0.66, 1.08) for paroxysmal AF (P-difference = 0.01). For MUFAs, the RR for a 5% increment was 0.67 (95% CI: 0.46, 0.98) for persistent/chronic and 1.03 (95% CI: 0.78, 1.34) for paroxysmal AF, although the difference between patterns was not significant (P-difference = 0.07). CONCLUSIONS: Dietary fat was not associated with risk of incident AF in women without established CVD or AF. High SFA and low MUFA intakes were associated with greater risk of persistent or chronic, but not paroxysmal, AF. Improving dietary fat quality may play a role in the prevention of sustained forms of AF. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.

Effect of long-term supplementation with folic acid and B vitamins on risk of depression in older women.

BACKGROUND: Homocysteine-lowering nutrients may have preventive/ameliorative roles in depression. AIMS: To test whether long-term B-vitamin/folate supplementation reduces depression risk. METHOD: Participants were 4331 women (mean age 63.6 years), without prior depression, from the Women's Antioxidant and Folic Acid Cardiovascular Study - a randomised controlled trial of cardiovascular disease prevention among 5442 women. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), vitamin B6 (50 mg/d) and vitamin B12 (1 mg/d) or a matching placebo. Average treatment duration was 7 years. The outcome was incident depression, defined as self-reported physician/clinician-diagnosed depression or clinically significant depressive symptoms. RESULTS: There were 524 incident cases. There was no difference between active v. placebo groups in depression risk (adjusted relative risk 1.02, 95% CI 0.86-1.21, P = 0.81), despite significant homocysteine level reduction. CONCLUSIONS: Long-term, high-dose, daily supplementation with folic acid and vitamins B6 and B12 did not reduce overall depression risk in mid-life and older women.

Ventricular tachycardia in cardiac sarcoidosis: characterization of ventricular substrate and outcomes of catheter ablation.

BACKGROUND: Cardiac sarcoid-related ventricular tachycardia (VT) is a rare disorder; the underlying substrate and response to ablation are poorly understood. We sought to examine the ventricular substrate and outcomes of catheter ablation in this population. METHODS AND RESULTS: Of 435 patients with nonischemic cardiomyopathy referred for VT ablation, 21 patients (5%) had cardiac sarcoidosis. Multiple inducible VTs were observed with mechanism consistent with scar-mediated re-entry in all VTs. Voltage maps showed widespread and confluent right ventricular scarring. Left ventricular scarring was patchy with a predilection for the basal septum, anterior wall, and perivalvular regions. Epicardial right ventricular scar overlay and exceeded the region of corresponding endocardial scar. After ≥1 procedures, ablation abolished ≥1 inducible VT in 90% and eliminated VT storm in 78% of patients; however, multiple residual VTs remained inducible. Failure to abolish all inducible VTs was because of septal intramural circuits or extensive right ventricular scarring. Multiple procedure VT-free survival was 37% at 1 year, but VT control was achievable in the majority of patients with fewer antiarrhythmic drugs compared with preablation (2.1±0.8 versus 1.1±0.8; P<0.001). CONCLUSIONS: Patients with cardiac sarcoidosis and VT exhibit ventricular substrate characterized by confluent right ventricular scarring and patchy left ventricular scarring capable of sustaining a large number of re-entrant circuits. Catheter ablation is effective in terminating VT storm and eliminating ≥1 inducible VT in the majority of patients, but recurrences are common. Ablation in conjunction with antiarrhythmic drugs can help palliate VT in this high-risk population.