Background: It has already been established that the consumption of alcoholic beverages increases high-density lipoprotein cholesterol (HDL-C) levels in dose–response. Methods and Results:A cross-sectional analysis was carried out with 6132 participants of both sexes aged between 35 and 74 years, who were active and retired workers from six Brazilian states. Heavy drinkers were categorized by sex: men > 210 g/week and women > 140 g/week; moderate drinkers: men ≤ 209 g/week and women ≤ 139 g/week. The HDL-C level was dichotomized into normal (40 mg/dL–82.9 mg/dL) and extremely high (≥83 mg/dL). We used binary logistic regression to assess associations between baseline alcohol intake and HDL-C, which were adjusted for sex, age, income, physical activity, kilocalories and body mass index (BMI), and we found an positive association between extremely high HDL-C and the excessive consumption of alcoholic beverages. These participants were mostly women with a high income, lower waist circumference, kilocalorie consumption and also a higher consumption in all categories of alcoholic beverages. Conclusion: Excessive alcohol consumption was associated with a higher probability of extremely high HDL-C. Full article

Oxylipins are the oxidation products of polyunsaturated fatty acids and have been implicated in neurodegenerative disorders, including dementia. Soluble epoxide hydrolase (sEH) converts epoxy-fatty acids to their corresponding diols, is found in the brain, and its inhibition is a treatment target for dementia. In this study, male and female C57Bl/6J mice were treated with an sEH inhibitor (sEHI), trans-4-[4-(3-adamantan-1-yl-ureido)-cyclohexyloxy]-benzoic acid (t-AUCB), for 12 weeks to comprehensively study the effect of sEH inhibition on the brain oxylipin profile, and modulation by sex. Ultra-high-performance liquid chromatography–tandem mass spectrometry was used to measure the profile of 53 free oxylipins in the brain. More oxylipins were modified by the inhibitor in males than in females (19 versus 3, respectively) and favored a more neuroprotective profile. Most were downstream of lipoxygenase and cytochrome p450 in males, and cyclooxygenase and lipoxygenase in females. The inhibitor-associated oxylipin changes were unrelated to serum insulin, glucose, cholesterol, or female estrous cycle. The inhibitor affected behavior and cognitive function as measured by open field and Y-maze tests in males, but not females. These findings are novel and important to our understanding of sexual dimorphism in the brain’s response to sEHI and may help inform sex-specific treatment targets. Full article

Biological sex and a high glycemic diet (HGD) contribute to dementia, yet little is known about the operative molecular mechanisms. Our goal was to understand the differences between males and females in the multi-genomic response of the hippocampal microvasculature to the HGD, and whether there was vasculoprotection via the inhibition of soluble epoxide hydrolase (sEHI). Adult wild type mice fed high or low glycemic diets for 12 weeks, with or without an sEHI inhibitor (t-AUCB), had hippocampal microvessels isolated by laser-capture microdissection. Differential gene expression was determined by microarray and integrated multi-omic bioinformatic analyses. The HGD induced opposite effects in males and females: the HGD-upregulated genes were involved in neurodegeneration or neuroinflammation in males, whereas in females they downregulated the same pathways, favoring neuroprotection. In males, the HGD was associated with a greater number of clinical diseases than in females, the sEHI downregulated genes involved in neurodegenerative diseases to a greater extent with the HGD and compared to females. In females, the sEHI downregulated genes involved in endothelial cell functions to a greater extent with the LGD and compared to males. Our work has potentially important implications for sex-specific therapeutic targets for vascular dementia and cardiovascular diseases in males and females. Full article

Background: Early assessment of carotid atherosclerotic plaque characteristics is essential for atherosclerotic cardiovascular disease (ASCVD) risk stratification and prediction. We aimed to identify different trajectories of lipid profiles and investigate the association of lipid trajectories with carotid atherosclerosis (CAS) progression in a large, longitudinal cohort of the Chinese population. Methods: 10,412 participants aged ≥18 years with ≥2 times general health checkups were included in this longitudinally prospective cohort study at Peking University Third Hospital. We used latent class trajectory models to identify trajectories of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C) over follow-up time (757 days, IQR: 388–844 days). Results: Participants with carotid plaque were more likely to be older, male, have higher body mass index, have a higher prevalence of hypertension and diabetes, and have a higher level of blood pressure, TG, TC, and LDL-C, compared with carotid intima-media thickness (cIMT) and normal group. Subjects were trichotomized according to different trajectory patterns into stable, moderate-stable, and elevated-increasing classes. TC ≥ 5.18 mmol/L and moderate-stable class (hazard ratio (HR): 1.416, 95% confidence interval (CI): 1.285–1.559, p: 0.000), TG ≥ 1.70 mmol/L and moderate-stable class (HR: 1.492, 95% CI: 1.163–1.913, p: 0.002), TG ≥ 1.70 mmol/L and elevated-increasing class (HR: 1.218, 95% CI: 1.094–1.357, p: 0.000), LDL-C ≥ 3.36 mmol/L and stable class (HR: 1.500, 95% CI: 1.361–1.653, p: 0.000) were statistically significant associated with CAS progression compared with the reference group. Conclusions: Borderline elevated baseline lipid (TC, TG, and LDL-C) with stable and elevated-increasing trajectories were associated with CAS progression. Long-term strategies for low-level lipid are beneficial for ASCVD management. Full article

Quantitative rankings of multiple dietary patterns for their effects on non-communicable disease (NCD) biomarkers is lacking and would inform primary prevention strategies. Accordingly, a network meta-analysis (NMA) was conducted to compare and rank the effects of different dietary patterns on NCD biomarkers, and associations of dietary patterns’ underlying macronutrient composition with NCD biomarkers were determined by a nutritional geometry approach. Randomised controlled trials (RCTs) were eligible for inclusion if they enrolled healthy participants, employed food-based dietary pattern interventions without energy restriction, and reported NCD biomarker outcomes. NCD biomarkers were included as an outcome if ≥10 trials were available. A systematic search of five electronic databases identified 4008 records. Sixty-eight articles from 59 RCTs reporting lipids, glycemic, and inflammatory biomarkers were included for quantitative syntheses. Risk-of-bias was predominantly categorized as low or having some concerns, and confidence-of-evidence low. Relative to western habitual diet, the Mediterranean, Dietary Approaches to Stop Hypertension (DASH), dietary guidelines-based, plant-based, and low-fat diets reduced low-density lipoprotein cholesterol (mean difference range: −0.29 to −0.17 mmol/L), total cholesterol (−0.36 to −0.24 mmol/L), and apolipoprotein B (−0.11 to −0.07 g/L) (all p < 0.05); the Paleo, plant-based and dietary guidelines-based diets reduced homeostasis model assessment of insulin resistance (−0.95 to −0.35, all p < 0.05). No dietary pattern ranked consistently highest. The Paleo diet received the highest all-outcomes-combined average Surface Under the Cumulative Ranking Curve value (67%), followed by DASH (62%) and Mediterranean diets (57%), whereas western habitual diet was lowest (36%). Our findings were independent of macronutrient composition, highlighting the significance of dietary pattern-level analysis. Full article

No consensus has yet been reached on the associations of lipid variability (LV) with cardiovascular diseases (CVDs) and all-cause mortality. We aimed to quantify the associations of different types and metrics of LV with CVDs and all-cause mortality. PubMed, Medline, and Embase databases were searched for eligible cohort studies published until 14 December 2021. Lipids included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). Metrics of variability included standard deviation (SD), coefficient of variation (CV), and variation independent of the mean (VIM). The primary outcomes were CVDs and all-cause mortality. Random-effects meta-analysis was used to generate a summary of the relative risks (SRRs). Sources of heterogeneity were explored by subgroup analysis and meta-regression. A total of 11 articles based on seven cohorts were included. Participants in the top quartile of TC variability had an increased risk of CVDs (vs. bottom quartile: TC-CV: SRR 1.29, 95% CI 1.15-1.45; TC-SD: 1.28, 1.15–1.43; TC-VIM: 1.26, 1.13–1.41, respectively) and all-cause mortality (vs. bottom quartile: TC-CV: 1.28, 1.15–1.42; TC-SD: 1.32, 1.22–1.44; TC-VIM: 1.32, 1.25–1.40, respectively). Participants in the top quartile of HDL-C variability had an increased risk of CVDs (vs. bottom quartile: HDL-C-CV: 1.11, 1.07–1.15; HDL-C-SD: 1.18, 1.02–1.38; HDL-C-VIM: 1.18, 1.09–1.27, respectively) and all-cause mortality (vs. bottom quartile: HDL-C-CV: 1.29, 1.27–1.31; HDL-C-SD: 1.24, 1.09–1.41; HDL-C-VIM: 1.25, 1.22–1.27, respectively). LDL-C variability was also associated with an increased risk of CVDs (for top vs. bottom quartile; LDL-C-SD: 1.09, 1.02–1.17; LDL-C-VIM: 1.16, 1.02–1.32, respectively) and all-cause mortality (for top vs. bottom quartile; LDL-C-CV: 1.19, 1.04–1.36; LDL-C-SD: 1.17, 1.09–1.26, respectively). The relationships of TG variability with the risk of CVDs and all-cause mortality were inconclusive across different metrics. The effects of SRR became stronger when analyses were restricted to studies that adjusted for lipid-lowering medication and unadjusted for mean lipid levels. These findings indicate that the measurement and surveillance of lipid variability might have important clinical implications for risk assessment of CVDs and all-cause mortality. Full article