Epicardial Fat Volume, Cardiac Function, and Incident Heart Failure: The Rotterdam Study.

Background Larger epicardial fat volume (EFV) has been associated with increased risks of cardiovascular disease and atrial fibrillation. Yet, evidence on the association of EFV with cardiac function and incident heart failure (HF) remains scarce. Methods and Results We included 2103 participants (mean age, 68 years; 54.4% women) from the prospective population-based RS (Rotterdam Study) with computed tomography-based EFV and repeated echocardiography-based assessment of left ventricular (LV) systolic and diastolic function. Linear mixed effects and Cox-proportional hazard regression models, adjusted for cardiovascular risk factors, were used to assess the associations of EFV with repeated measurements of echocardiographic parameters and with incident HF. During a median follow-up of 9.7 years, 124 HF events occurred (incidence rate, 6.37 per 1000 person-years). For LV systolic function, 1-SD larger EFV was associated with 0.76 (95% CI, 0.54-0.98) mm larger LV end-diastolic dimension, 0.66 (95% CI, 0.47-0.85) mm larger LV end-systolic dimension, and 0.56% (95% CI, -0.86% to -0.27%) lower LV ejection fraction. Interactions between EFV and time were small. For LV diastolic function, 1-SD larger EFV was associated with 1.02 (95% CI, 0.78-1.27) mm larger left atrial diameter. Larger EFV was also associated with incident HF (hazard ratio per 1-SD increase in EFV, 1.34 [95% CI, 1.07-1.68] per 1-SD larger EFV). Conclusions We report an independent association between EFV with new-onset HF in the general population. EFV seems to exert its influence on HF through different pathways contributing to deteriorations in systolic function and larger left atrial size in part, likely through mechanical restraint and hypertrophy.

Dietary protein intake and all-cause and cause-specific mortality: results from the Rotterdam Study and a meta-analysis of prospective cohort studies.

Evidence for associations between long-term protein intake with mortality is not consistent. We aimed to examine associations of dietary protein from different sources with all-cause and cause-specific mortality. We followed 7786 participants from three sub-cohorts of the Rotterdam Study, a population-based cohort in the Netherlands. Dietary data were collected using food-frequency questionnaires at baseline (1989-1993, 2000-2001, 2006-2008). Deaths were followed until 2018. Associations were examined using Cox regression. Additionally, we performed a highest versus lowest meta-analysis and a dose-response meta-analysis to summarize results from the Rotterdam Study and previous prospective cohorts. During a median follow-up of 13.0 years, 3589 deaths were documented in the Rotterdam Study. In this cohort, after multivariable adjustment, higher total protein intake was associated with higher all-cause mortality [e.g. highest versus lowest quartile of total protein intake as percentage of energy (Q4 versus Q1), HR = 1.12 (1.01, 1.25)]; mainly explained by higher animal protein intake and CVD mortality [Q4 versus Q1, CVD mortality: 1.28 (1.03, 1.60)]. The association of animal protein intake and CVD was mainly contributed to by protein from meat and dairy. Total plant protein intake was not associated with all-cause or cause-specific mortality, mainly explained by null associations for protein from grains and potatoes; but higher intake of protein from legumes, nuts, vegetables, and fruits was associated with lower risk of all-cause and cause-specific mortality. Findings for total and animal protein intake were corroborated in a meta-analysis of eleven prospective cohort studies including the Rotterdam Study (total 64,306 deaths among 350,452 participants): higher total protein intake was associated with higher all-cause mortality [pooled RR for highest versus lowest quantile 1.05 (1.01, 1.10)]; and for dose-response per 5 energy percent (E%) increment, 1.02 (1.004, 1.04); again mainly driven by an association between animal protein and CVD mortality [highest versus lowest, 1.09 (1.01, 1.18); per 5 E% increment, 1.05 (1.02, 1.09)]. Furthermore, in the meta-analysis a higher plant protein intake was associated with lower all-cause and CVD mortality [e.g. for all-cause mortality, highest versus lowest, 0.93 (0.87, 0.99); per 5 E% increment, 0.87 (0.78, 0.98), for CVD mortality, highest versus lowest 0.86 (0.73, 1.00)]. Evidence from prospective cohort studies to date suggests that total protein intake is positively associated with all-cause mortality, mainly driven by a harmful association of animal protein with CVD mortality. Plant protein intake is inversely associated with all-cause and CVD mortality. Our findings support current dietary recommendations to increase intake of plant protein in place of animal protein.Clinical trial registry number and website NTR6831, https://www.trialregister.nl/trial/6645.