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Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and

Background Heart fats (epicardial and paracardial adipose tissue [PAT]) are greater after menopause. Endogenous estrogen may regulate these fat depots. We evaluated the differential effects of hormone therapy formulations on heart fat accumulations and their associations with coronary artery calcification (CAC) progression in recently menopausal women from KEEPS (Kronos Early Estrogen Prevention Study). Methods and Results KEEPS was a multicenter, randomized, placebo-controlled trial of the effects of 0.45 mg/d oral conjugated equine estrogens and 50 µg/d transdermal 17β-estradiol, compared with placebo, on 48-month progression of subclinical atherosclerosis among 727 early menopausal women. CAC progression was defined if baseline CAC score was 0 and 48-month CAC score was >0 or if baseline CAC score was >0 and

Context and objectiveWe examined whether a prevalent caveolin-1 gene (CAV1) variant, previously related to insulin resistance, is associated with metabolic syndrome (MetS).Patients and methodsWe included subjects genotyped for the CAV1 variant rs926198 from two cohorts: 735 Caucasians from the HyperPATH multicenter study, and 810 Hispanic participants from the HTN-IR cohort.ResultsMinor allele carriers from HyperPATH cohort (57% of subjects) had higher Framingham risk scores, higher odds of diabetes (10.7% vs 5.7%, p=0.016), insulin resistance (44.3% vs 35.1%, p=0.022), low HDL (49.3% vs 39.6%, p=0.018) and MetS (33% vs 20.5%, p

Introduction Coronary artery disease (CAD) is the most common type of cardiovascular disease (CVD) worldwide and the leading cause of death in the Western Hemisphere (1). The condition gives rise [...], BACKGROUND. Ceramides are sphingolipids that play causative roles in diabetes and heart disease, with their serum levels measured clinically as biomarkers of cardiovascular disease (CVD). METHODS. We performed targeted lipidomics on serum samples from individuals with familial coronary artery disease (CAD) (n = 462) and population-based controls (n = 212) to explore the relationship between serum sphingolipids and CAD, using unbiased machine learning to identify sphingolipid species positively associated with CAD. RESULTS. Nearly every sphingolipid measured (n = 30 of 32) was significantly elevated in subjects with CAD compared with measurements in population controls. We generated a novel sphingolipid- inclusive CAD risk score, termed SIC, that demarcates patients with CAD independently and more effectively than conventional clinical CVD biomarkers including serum LDL cholesterol and triglycerides. This new metric comprises several minor lipids that likely serve as measures of flux through the ceramide biosynthesis pathway rather than the abundant deleterious ceramide species that are included in other ceramide-based scores. CONCLUSION. This study validates serum ceramides as candidate biomarkers of CVD and suggests that comprehensive sphingolipid panels should be considered as measures of CVD. FUNDING. The NIH (DK112826, DK108833, DK115824, DK116888, and DK116450); the Juvenile Diabetes Research Foundation (JDRF 3-SRA-2019-768-A-B); the American Diabetes Association; the American Heart Association; the Margolis Foundation; the National Cancer Institute, NIH (5R00CA218694-03); and the Huntsman Cancer Institute Cancer Center Support Grant (P30CA040214).

A recent large-scale meta-analysis of genome-wide studies has identified 95 loci, 59 of them novel, as statistically significant predictors of blood lipid traits; we tested whether the same loci explain the observed heterogeneity in response to lipid-lowering therapy with fenofibrate. Using data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN, n = 861) we fit linear mixed models with the genetic markers as predictors and high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol, and triglyceride concentrations as outcomes. For all four traits, we analyzed both baseline levels and changes in response to treatment with fenofibrate. For the markers that were significantly associated with fenofibrate response, we fit additional models evaluating potential epistatic interactions. All models were adjusted for age, sex, and study center as fixed effects, and pedigree as a random effect. Statistically significant associations were observed between the rs964184 polymorphism near APOA1 (P-value≤0.0001) and fenofibrate response for HDL and triglycerides. The association was replicated in the Pharmacogenetics of Hypertriglyceridemia in Hispanics study (HyperTG, n = 267). Suggestive associations with fenofibrate response were observed for markers in or near PDE3A, MOSC1, FLJ36070, CETP, the APOE-APOC1-APOC4-APOC2, and CILP2. Finally, we present strong evidence for epistasis (P-value for interaction =  0.0006 in GOLDN, 0.05 in HyperTG) between rs10401969 near CILP2 and rs4420638 in the APOE-APOC1-APOC4-APOC2 cluster with total cholesterol response to fenofibrate. In conclusion, we present evidence linking several novel and biologically relevant genetic polymorphisms to lipid lowering drug response, as well as suggesting novel gene-gene interactions in fenofibrate pharmacogenetics.

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56±16 yr, 25±4 kg/m²) and obese (17M/4F, 50±7 yr, 35±4 kg/m²) middle-aged individuals with HTN forwent antihypertensive medication use for ≤2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1±1.7%) and Obese (5.2±1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ~15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ~20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24±5 kg, non-obese: 21±5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored. NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies. [ABSTRACT FROM AUTHOR]