ω3-Polyunsaturated fatty acids for heart failure: Effects of dose on efficacy and novel signaling through free fatty acid receptor 4.

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 that 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 that 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 that EPA prevents interstitial fibrosis and diastolic dysfunction, we speculate about a potential benefit for EPA-Ffar4 signaling in heart failure preserved with ejection fraction.

Smell and Taste Dysfunction Is Associated with Higher Serum Total Cholesterol Concentrations in Chinese Adults.

Background: 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.Objective: We examined the cross-sectional association between taste and smell dysfunction and blood cholesterol concentrations.Methods: 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.Results: 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 (P-trend = 0.005). No significant differences were observed in LDL cholesterol, HDL cholesterol, and TG concentrations across groups with different numbers of chemosensory dysfunctions (P-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 (P-interaction < 0.05 for all).Conclusions: 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.

[Role of vaccination in chronic disease prevention and control].

Chronic non-communicable disease is a major public health problem affecting the health of residents in china. Evidence shows that, in addition to four major risk factors, i.e. unreasonable dietary, lack of physical activity, smoking and drinking, epidemic and severe outcome of chronic disease is associated with many infectious diseases. Increasingly cancers have been shown to have an infectious etiology. There is also a significantly increased risk of infectious disease such as influenza, pneumonia and other infectious disease in people with pre-existing chronic non-communicable diseases like diabetes, heart disease, and lung diseases. And more than that, there is a high risk of susceptibility to death and severe outcomes among them. Epidemiological studies has confirmed, that through targeted vaccine inoculation, liver cancer, cervical cancer can be effectively prevented, while influenza or pneumonia vaccine are related to reduced risk of hospitalization or death and hospitalization expenses regarding with a variety of chronic diseases. World Health Organization and several other professional organizations have put forward recommendations on vaccine inoculation of chronic disease patients. Programs targeting infectious factors are also an important aspect of chronic diseases prevention and control, therefore, related researches need to be strengthened in the future.

[Comparison of HbA1c and oral glucose tolerance test for diagnosing diabetes].

OBJECTIVE: To compare the performance of glycated hemoglobin (HbA1c) and oral glucose tolerance test (OGTT) in diagnosing diabetes and pre-diabetes in the general population. METHODS: A total of 1416 subjects from Nanchang, Jiangxi Province and Wuhan, Hubei Province who have participated the 2010 Chinese Nutrition and Health Survey were studied and their HbA1c were measured. The glycemic levels and distribution of the subjects diagnosed with diabetes and pre-diabetes by OGTT and HbA1c were compared. Receiver operating characteristic curves were constructed to determine the sensitivity and specificity of HbA1c in detecting diabetes as defined by OGTT. RESULTS: According to the 1999 WHO criteria, 86 subjects were diagnosed with diabetes and 262 were with pre-diabetes. Comparing with OGTT, the sensitivity and specificity of HbA1c > or = 6.5% was 41.9% and 98.9%. Subjects with diabetes diagnosed by HbA1c and OGTT were not consistent, and they have different HbA1c level. The HbA1c level of 5.7% - 6.4% was associated with a sensitivity of 78.6% and a specificity of 55.1% in detecting impaired glucose regulation (IGR). Cases with pre-diabetes identified by HbA1c 5.7% - 6.4% were different from those with IGR. They had lower fasting glucose and 2-hour plasma glucose after glucose load than those with IGR. CONCLUSION: Among this studied population, HbA1c > or = 6.5% showed high specificity but low sensitivity for detecting glucose-defined diabetes. The performance of HbA1c of 5.7% -6.4% in screening pre-diabetes is poor.

Eicosapentaenoic acid and Arachidonic acid Protection Against Left Ventricle Pathology: the Multi-Ethnic Study of Atherosclerosis.

Background: We have shown that ω3 polyunsaturated fatty acids (PUFAs) reduce risk for heart failure, regardless of ejection fraction status. Ventricular remodeling and reduced ventricular performance precede overt hear failure, however there is little insight into how PUFAs contribute to maladaptive signaling over time. PUFAs are agonists for regulatory activity at g-protein coupled receptors such as Ffar4, and downstream as substrates for monooxygenases (e.g lipoxygenase, cytochrome p450, or cyclooxygenase (COX)) which mediate intracellular adaptive signaling. Methods: Plasma phospholipid PUFA abundance at Exam 1 as mass percent EPA, DHA, and arachidonic acid (AA) from the Multi-Ethnic Study of Atherosclerosis (MESA) were evaluated using pathway modeling to determine the association with time-dependent changes in left ventricular (LV) mass (LVM), end-diastolic LV volume (EDV), and end-systolic volume (ESV) measured by cardiac MRI at Exams 1 and 5. Ejection fraction (EF) and mass:volume (MV) were calculated posteriorly from the first three. Results: 2,877 subjects had available MRI data. Participants with low AA and EPA had accelerated age-dependent declines in LVM. Males with low AA and EPA also had accelerated declines in EDV, but among females there was no PUFA association with EDV declines and exam 5 EDV status was positively associated with AA. Both sexes had nearly the same positive association of AA with changes in ESV. Conclusion: Plasma phospholipid AA and EPA are prospectively associated with indices of heart remodeling, including ventricular remodeling and performance. Combined AA and EPA scarcity was associated with the most accelerated age-related changes and exam 5 status, while the greatest benefits were found among participants with both PUFAs. This suggests that both PUFAs are required for optimal slowing of age-related declines in ventricular function.

Prospective study of sleep duration, snoring and risk of heart failure.

OBJECTIVE: To investigate whether nighttime sleep duration and snoring status were associated with incident heart failure (HF). METHODS: A prospective study was conducted based on Kailuan cohort including 93 613 adults free of pre-existing cardiovascular diseases. Sleep duration and snoring status were assessed by self-reported questionnaire. Incident HF cases were ascertained by medical records. Cox proportional hazards model was applied to calculate the HR and 95% CI of risk of developing HF. Mediation analysis was used to understand whether hypertension and diabetes mediated the association between sleep duration, snoring and HF. Data analysis was performed from 1 June 2021 to 1 June 2022. RESULTS: During a median follow-up of 8.8 years, we documented 1343 incident HF cases. Relative to sleep duration of 7.0-7.9 hour/night, short sleep duration was associated with higher risk of developing HF: adjusted HR was 1.24 (95% CI 1.01 to 1.55) for <6 hours/night and 1.29 (95% CI 1.06 to 1.57) for 6.0-6.9 hours/night, after adjustment for potential confounders such as age, sex, smoking, hypertension and diabetes. A similar 20%-30% higher risk of incident HF was found in individuals reporting occasional or frequent snoring relative to never/rare snorers: adjusted HR was 1.32 for occasional snoring (95% CI 1.14 to 1.52) and 1.24 (95% CI 1.06 to 1.46) for frequent snoring. Presence of diabetes significantly mediated the association between both short sleep duration and snoring and HF risk and hypertension significantly mediated the snoring-HF relationship. CONCLUSION: Short sleep duration and snoring were associated with high risk of HF.

Free fatty acid receptor 4 responds to endogenous fatty acids to protect the heart from pressure overload.

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, remodelling was worsened in Ffar4KO hearts, with greater hypertrophy and contractile dysfunction. Transcriptome analysis 3-day post-TAC identified transcriptional deficits in genes associated with cytoplasmic phospholipase A2α signalling and oxylipin synthesis and the reduction of oxidative stress in Ffar4KO myocytes. In cultured adult cardiac myocytes, Ffar4 induced the production of the eicosapentaenoic acid (EPA)-derived, pro-resolving oxylipin 18-hydroxyeicosapentaenoic acid (18-HEPE). Furthermore, the 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 signalling-deficient Ffar4 R270H polymorphism correlated with eccentric remodelling in a large clinical cohort paralleling changes observed in Ffar4KO mice post-TAC. CONCLUSION: 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.

[Current status and research advances of high-temperature hazards in rice]. / æ°´ç¨»é«˜æ¸©çƒ­å®³çš„ç ”ç©¶çŽ°çŠ¶ä¸Žè¿›å±•.

High temperature stress occurs frequently in rice due to global warming. High-temperature hazard during the booting-flowering and grain-filling stages is one of the major factors limiting rice yield and quality. Here, we summarized the occurrence characteristics (identification, classification, region, and time) of high-temperature hazards, and the effects of high temperature on rice growth and development, including physiology, grain yield, and grain quality. Furthermore, we reviewed molecular biology aspects including quantitative trait locus mapping, transcriptome analysis, proteome analysis, and the monitoring, early warning, risk assessment of high-temperature hazards in rice. The defensive measures against high temperature in rice including selecting heat-resistant varieties, improving field management practices and spraying exogenous substances were intensively described. Finally, future research work on high-temperature hazards in rice was prospected to provide the scientific support for rice high-temperature defense, agricultural disaster reduction, and agricultural efficiency improvement.

Sedentary time, metabolic abnormalities, and all-cause mortality after myocardial infarction: A mediation analysis.

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 = 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 time-mortality 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.

Predicting Risk for Incident Heart Failure With Omega-3 Fatty Acids: From MESA.

OBJECTIVES: The aim of this study was to determine if plasma eicosapentaenoic acid (EPA) abundance (%EPA) is associated with reduced hazard for primary heart failure (HF) events in the MESA (Multi-Ethnic Study of Atherosclerosis) trial. BACKGROUND: Clinical trials suggest that omega-3 polyunsaturated fatty acids (ω3 PUFAs) prevent sudden death in coronary heart disease and HF, but this is controversial. In mice, the authors demonstrated that the ω3 PUFA EPA prevents contractile dysfunction and fibrosis in an HF model, but whether this extends to humans is unclear. METHODS: In the MESA cohort, the authors tested if plasma phospholipid EPA predicts primary HF incidence, including HF with reduced ejection fraction (EF) (EF <45%) and HF with preserved EF (EF ≥45%) using Cox proportional hazards modeling. RESULTS: A total of 6,562 participants 45 to 84 years of age had EPA measured at baseline (1,794 black, 794 Chinese, 1,442 Hispanic, and 2,532 white; 52% women). Over a median follow-up period of 13.0 years, 292 HF events occurred: 128 HF with reduced EF, 110 HF with preserved EF, and 54 with unknown EF status. %EPA in HF-free participants was 0.76% (0.75% to 0.77%) but was lower in participants with HF at 0.69% (0.64% to 0.74%) (p = 0.005). Log %EPA was associated with lower HF incidence (hazard ratio: 0.73 [95% confidence interval: 0.60 to 0.91] per log-unit difference in %EPA; p = 0.001). Adjusting for age, sex, race, body mass index, smoking, diabetes mellitus, blood pressure, lipids and lipid-lowering drugs, albuminuria, and the lead fatty acid for each cluster did not change this relationship. Sensitivity analyses showed no dependence on HF type. CONCLUSIONS: Higher plasma EPA was significantly associated with reduced risk for HF, with both reduced and preserved EF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Association of Trajectory of Cardiovascular Health Score and Incident Cardiovascular Disease.

Importance: The American Heart Association 2020 Strategic Impact Goals target an improvement in overall cardiovascular health, as assessed by 7 health metrics (smoking, body weight, physical activity, diet, plasma glucose level, plasma cholesterol level, and blood pressure). Objective: To examine whether trajectories of overall cardiovascular health over time, as assessed by the cardiovascular health score (CHS) in 2006, 2008, and 2010, are associated with subsequent risk of CVD. Design, Setting, and Participants: The Kailuan study is a prospective, population-based study that began in 2006. The cohort included 74 701 Chinese adults free of myocardial infarction, stroke, and cancer in or before 2010. In the present study, CHS trajectories were developed from 2006 to 2010 to predict CVD risk from 2010 to 2015. Data analysis was performed from January 1, 2006, to December 31, 2015. Exposures: The CHS trajectories during 2006-2010 were identified using latent mixture models. Main Outcomes and Measures: Incident CVD events (myocardial infarction and stroke) during 2010-2015 were confirmed by review of medical records. The CHS trajectories were determined using 7 cardiovascular health metrics scored as poor (0 points), intermediate (1 point), and ideal (2 points); total score ranges from 0 (worst) to 14 (best). Based on the baseline CHS and patterns over time, 5 trajectories were categorized (low-stable, moderate-increasing, moderate-decreasing, high-stable I, and high-stable II). Results: Of the 74 701 adults included in the study (mean [SD] age at baseline, 49.6 [11.8] years), 58 216 (77.9%) were men and 16 485 (22.1%) were women. Five CHS trajectories were identified from 2006 to 2010: low-stable (n = 4393; range, 4.6-5.2), moderate-increasing (n = 4643; mean increase from 5.4 to 7.8), moderate-decreasing (n = 14 853; mean decrease from 7.4 to 6.3), high-stable I (n = 36 352; range, 8.8-9.0), and high-stable II (n = 14 461; range, 10.9-11.0). During 5 years of follow-up, 1852 incident CVD cases were identified. Relative to the low-stable trajectory, the high-stable II trajectory was associated with a lower subsequent risk of CVD (adjusted hazard ratio, 0.21; 95% CI, 0.16-0.26, after adjusting for age, sex, educational level, income, occupation, alcohol intake, and serum high-sensitivity C-reactive protein concentration at baseline). Conclusions and Relevance: Cardiovascular health trajectories may be associated with subsequent CVD risk.

Tea Consumption and Longitudinal Change in High-Density Lipoprotein Cholesterol Concentration in Chinese Adults.

BACKGROUND: The 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 RESULTS: Baseline (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). CONCLUSIONS: Tea consumption was associated with slower age-related decreases in HDL-C concentrations during 6 years of follow-up. CLINICAL TRIAL REGISTRATION: URL: www.chictr.org. Unique identifier: ChiCTR-TNRC-11001489.

Longitudinal study of alcohol consumption and HDL concentrations: a community-based study.

Background: 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.Objective: 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.Design: 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.Results: 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-1 · y-1 (95% CI: 0.008, 0.016 mmol · L-1 · y-1), 0.013 mmol · L-1 · y-1 (95% CI: 0.010, 0.016 mmol · L-1 · y-1), 0.017 mmol · L-1 · y-1 (95% CI: 0.009, 0.025 mmol · L-1 · y-1), and 0.008 mmol · L-1 · y-1 (95% CI: 0.005, 0.011 mmol · L-1 · y-1), respectively (P < 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.Conclusion: 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.