Key Points Question Are trajectories of overall cardiovascular health over time, as assessed by the cardiovascular health score repeatedly in 2006, 2008, and 2010, associated with subsequent risk of cardiovascular disease? Findings In this population-based study of 74 701 Chinese adults, 5 cardiovascular health score trajectories were identified. Relative to the lowest measured trajectory, the highest measured trajectory was associated with a 79% lower subsequent risk of cardiovascular disease after adjusting for age, sex, educational level, income, occupation, alcohol intake, and serum high-sensitivity C-reactive protein concentrations at baseline. Meaning Long-term cardiovascular health trajectories may be associated with subsequent cardiovascular disease morbidity.

In cross-sectional studies and short-term clinical trials, it has been suggested that there is a positive dose-response relation between alcohol consumption and HDL concentrations. However, prospective data have been limited. We sought to determine the association between total alcohol intake, the type of alcohol-containing beverage, and the 6-y (2006-2012) longitudinal change in HDL-cholesterol concentrations in a community-based cohort. A total of 71,379 Chinese adults (mean age: 50 y) who were free of cardiovascular diseases and cancer and did not use cholesterol-lowering agents during follow-up were included in the study. Alcohol intake was assessed via a questionnaire in 2006 (baseline), and participants were classified into the following categories of alcohol consumption: never, past, light (women: 0-0.4 servings/d; men: 0-0.9 servings/d), moderate (women: 0.5-1.0 servings/d; men: 1-2 servings/d), and heavy (women: >1.0 servings/d; men: >2 servings/d). HDL-cholesterol concentrations were measured in 2006, 2008, 2010, and 2012. We used generalized estimating equation models to examine the associations between baseline alcohol intake and the change in HDL-cholesterol concentrations with adjustment for age, sex, smoking, physical activity, obesity, hypertension, diabetes, liver function, and C-reactive protein concentrations. An umbrella-shaped association was observed between total alcohol consumption and changes in HDL-cholesterol concentrations. Compared with never drinkers, past, light, moderate, and heavy drinkers experienced slower decreases in HDL cholesterol of 0.012 mmol · L · y (95% CI: 0.008, 0.016 mmol · L · y), 0.013 mmol · L · y (95% CI: 0.010, 0.016 mmol · L · y), 0.017 mmol · L · y (95% CI: 0.009, 0.025 mmol · L · y), and 0.008 mmol · L · y (95% CI: 0.005, 0.011 mmol · L · y), respectively ( < 0.0001 for all), after adjustment for potential confounders. Moderate alcohol consumption was associated with the slowest increase in total-cholesterol:HDL-cholesterol and triglyceride:HDL-cholesterol ratios. We observed a similar association between hard-liquor consumption and the HDL-cholesterol change. In contrast, greater beer consumption was associated with slower HDL-cholesterol decreases in a dose-response manner. Moderate alcohol consumption was associated with slower HDL-cholesterol decreases; however, the type of alcoholic beverage had differential effects on the change in the HDL-cholesterol concentration.

Heart failure (HF) affects 5.7 million in the U.S., and despite well-established pharmacologic therapy, the 5-year mortality rate remains near 50%. Furthermore, the mortality rate for HF has not declined in years, highlighting the need for new therapeutic options. Omega-3 polyunsaturated fatty acids (ω3-PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are important regulators of cardiovascular health. However, questions of efficacy and mechanism of action have made the use of ω3-PUFAs in all cardiovascular disease (CVD) controversial. Here, we review recent studies in animal models of HF indicating ω3-PUFAs, particularly EPA, are cardioprotective, with the results indicating a threshold for efficacy. We also examine clinical studies suggesting that ω3-PUFAs improve outcomes in patients with HF. Due to the relatively small number of clinical studies of ω3-PUFAs in HF, we discuss EPA concentration-dependency on outcomes in clinical trials of CVD to gain insight into the perceived questionable efficacy of ω3-PUFAs clinically, with the results again indicating a threshold for efficacy. Ultimately, we suggest that the main failing of ω3-PUFAs in clinical trials might be a failure to reach a therapeutically effective concentration. We also examine mechanistic studies suggesting ω3-PUFAs signal through free fatty acid receptor 4 (Ffar4), a G-protein coupled receptor (GPR) for long-chain fatty acids (FA), thereby identifying an entirely novel mechanism of action for ω3-PUFA mediated cardioprotection. Finally, based on mechanistic animal studies suggesting EPA prevents interstitial fibrosis and diastolic dysfunction, we speculate about a potential benefit for EPA-Ffar4 signaling in heart failure preserved with ejection fraction.

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Aims Free fatty acid receptor 4 (Ffar4) is a G-protein coupled receptor for endogenous medium/long-chain fatty acids that attenuates metabolic disease and inflammation. However, the function of Ffar4 in the heart is unclear. Given its putative beneficial role, we hypothesized that Ffar4 would protect the heart from pathologic stress. Methods and Results In mice lacking Ffar4 (Ffar4KO), we found that Ffar4 is required for an adaptive response to pressure overload induced by transverse aortic constriction (TAC), identifying a novel cardioprotective function for Ffar4. Following TAC, remodeling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-days post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signaling and oxylipin synthesis as well as reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, activation of Ffar4 attenuated cardiac myocyte death from oxidative stress, while 18-HEPE rescued Ffar4KO myocytes. Systemically, Ffar4 maintained pro-resolving oxylipins and attenuated autoxidation basally, and increased pro-inflammatory and pro-resolving oxylipins, including 18-HEPE, in high density lipoproteins post-TAC. In humans, Ffar4 expression decreased in heart failure, while the signaling-deficient Ffar4 R270H polymorphism correlated with eccentric remodeling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. Conclusions Our data indicate that Ffar4 in cardiac myocytes responds to endogenous fatty acids, reducing oxidative injury, and protecting the heart from pathologic stress, with significant translational implications for targeting Ffar4 in cardiovascular disease.

Several lipid-related hormones and peptides, such as glucagon-like peptide-1 and leptin, are involved in the regulation of taste and smell function. However, to our knowledge, it remains unknown whether these chemosensory functions are associated with lipid profiles. We examined the cross-sectional association between taste and smell dysfunction and blood cholesterol concentrations. With the use of a questionnaire, we assessed chronic smell and taste dysfunction in 12,627 Chinese participants (10,418 men and 2209 women; mean age: 54.4 y) who did not take hypolipidemic agents. Participants were categorized into 3 groups based on the number of smell and taste dysfunctions, ranging from 0 (best) to 2 (worst). A general linear model was used to test differences in serum concentrations of total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides (TGs) across groups with different smell and taste status after adjusting for age, sex, education, occupation, smoking, drinking, obesity, and history of cardiovascular disease, cancer, and head injury. The prevalence of smell and taste dysfunction was 2.4% and 1.2%, respectively. Worse smell and taste dysfunction was associated with higher total cholesterol concentrations (-trend = 0.005). No significant differences were observed in LDL cholesterol, HDL cholesterol, and TG concentrations across groups with different numbers of chemosensory dysfunctions (-trend > 0.1 for all). The associations between chemosensory dysfunction and total cholesterol concentrations were more pronounced in participants aged ≤60 y and in those who were nonsmokers relative to their counterparts (-interaction < 0.05 for all). In this large cross-sectional study, chemosensory dysfunction was associated with higher serum total cholesterol concentrations among Chinese adults. Prospective studies are needed to investigate the temporal relation between these chemosensory dysfunctions and hypercholesterolemia.

Background: Sedentary time was associated with myocardial infarction (MI) and metabolic diseases in previous studies. Purpose: To investigate whether sedentary time measured before disease onset was associated with all-cause mortality among MI survivors and whether the sedentary time-mortality association was mediated by physical activity status and metabolic phenotypes. Methods: In this prospective community-based cohort including 101,510 Chinese adults, we used sedentary time, evaluated at 2006 (baseline), to predict further all-cause mortality among individuals who then developed new onset MI from 2006 to December 2013 (n ¼ 989). The post-MI mortality was ascertained after the first non-fatal MI until December 2014. We assessed the mediating effects of physical inactivity and metabolic factors on the sedentary timemortality association. Results: During 7 years follow up, 180 deaths occurred among these participants with incident MI. Prolonged sedentary time was associated with a higher risk of mortality among MI survivors. The adjusted hazard ratio (HR) of mortality for sedentary time 4-8 hours/day versus <4 hours/day, was 1.62 (95% confidence interval (CI) 1.14-2.31). A high amount of sedentary time (>4 hours/day) and inactive physical activity had an increased risk of all-cause mortality (HR: 2.74, 95% CI 1.34-5.60), relative to those with sedentary time 4 hours/day and moderate/vigorous physical activity. Physical inactivity and metabolic factors mediated a small proportion (9.2 % for all) of the total association between sedentary time and post-MI mortality. Conclusion: High sedentary time was significantly associated with all-cause mortality among MI survivors, independent of physical activity status and metabolic abnormalities.

BackgroundThe relation between tea consumption and age‐related changes in high‐density lipoprotein cholesterol (HDL‐C) concentrations remains unclear, and longitudinal human data are limited. The aim of current study was to examine the relation between tea intake and longitudinal change in HDL‐C concentrations.Methods and ResultsBaseline (2006) tea consumption was assessed via a questionnaire, and plasma HDL‐C concentrations were measured in 2006, 2008, 2010, and 2012 among 80 182 individuals (49±12 years of age) who did not have cardiovascular diseases or cancer, or did not use cholesterol‐lowering agents both at baseline (2006) and during the follow‐up period (2006–2012). The associations between baseline tea consumption and rate of change in HDL‐C concentrations were examined using generalized estimating equation models. Tea consumption was inversely associated with a decreased rate of HDL‐C concentrations (P‐trend <0.0001) in the fully adjusted model. The adjusted mean difference in the HDL‐C decreased rate was 0.010 (95% confidence interval, 0.008, 0.012) mmol/L per year for tea consumers versus nonconsumers (never or less than once/month group). Interactions between tea consumption and age, sex, lifestyle scores, and metabolic syndrome (all P‐interaction <0.0001) were identified. The associations between greater tea consumption and slower decrease in HDL‐C concentrations were more pronounced in men, individuals aged 60 or older, individuals with a lower lifestyle score, and individuals with metabolic syndrome (all P‐trend <0.0001).ConclusionsTea consumption was associated with slower age‐related decreases in HDL‐C concentrations during 6 years of follow‐up.Clinical Trial Registration URL: http://www.chictr.org. Unique identifier: ChiCTR‐TNRC‐11001489.