In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.

• Keywords
• Atherogenic dyslipidemia, Diabetes, Inflammation, PROMINENT, Pemafibrate (K-877), Remnant cholesterol, Residual cardiovascular risk, SPPARMalpha, Selective peroxisome proliferator-activated receptor alpha modulator, Triglycerides, Visceral obesity,
• MeSH
• Benzoxazoles adverse effects   therapeutic use   MeSH
• Patient Safety MeSH
• Biomarkers blood   MeSH
• Butyrates adverse effects   therapeutic use   MeSH
• Molecular Targeted Therapy MeSH
• Dyslipidemias blood   diagnosis   drug therapy   MeSH
• Risk Assessment MeSH
• Hypolipidemic Agents adverse effects   therapeutic use   MeSH
• Cardiovascular Diseases blood   diagnosis   prevention & control   MeSH
• Consensus MeSH
• Humans MeSH
• Lipids blood   MeSH
• PPAR alpha agonists   metabolism   MeSH
• Risk Factors MeSH
• Signal Transduction MeSH
• Treatment Outcome MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH
• Names of Substances
• (R)-2-(3-((benzoxazol-2-yl-d4 (3-(4-methoxyphenoxy-d7)propyl)amino)methyl)phenoxy) butanoic acid MeSH Browser
• Benzoxazoles MeSH
• Biomarkers MeSH
• Butyrates MeSH
• Hypolipidemic Agents MeSH
• Lipids MeSH
• PPAR alpha MeSH
• PPARA protein, human MeSH Browser

BACKGROUND: Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD). METHODS AND RESULTS: We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test. In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification. CONCLUSIONS: In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.

• Keywords
• APOE genotype, Coronary heart disease, Gene–environment interaction, Smoking,
• MeSH
• Alleles MeSH
• Apolipoprotein E4 genetics   MeSH
• Adult MeSH
• Genotype * MeSH
• Heterozygote MeSH
• Gene-Environment Interaction MeSH
• Cohort Studies MeSH
• Coronary Disease genetics   MeSH
• Smoking adverse effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Risk Factors MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH
• Systematic Review MeSH
• Names of Substances
• Apolipoprotein E4 MeSH

BACKGROUND: Laparoscopic greater curvature plication (LGCP) is an emerging bariatric procedure that reduces the gastric volume without implantable devices or gastrectomy. The aim of this study was to explore changes in glucose homeostasis, postprandial triglyceridemia, and meal-stimulated secretion of selected gut hormones [glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), ghrelin, and obestatin] in patients with type 2 diabetes mellitus (T2DM) at 1 and 6 months after the procedure. METHODS: Thirteen morbidly obese T2DM women (mean age, 53.2 ± 8.76 years; body mass index, 40.1 ± 4.59 kg/m2) were prospectively investigated before the LGCP and at 1- and 6-month follow-up. At these time points, all study patients underwent a standardized liquid mixed-meal test, and blood was sampled for assessment of plasma levels of glucose, insulin, C-peptide, triglycerides, GIP, GLP-1, ghrelin, and obestatin. RESULTS: All patients had significant weight loss both at 1 and 6 months after the LGCP (p ≤ 0.002), with mean percent excess weight loss (%EWL) reaching 29.7 ± 2.9% at the 6-month follow-up. Fasting hyperglycemia and hyperinsulinemia improved significantly at 6 months after the LGCP (p < 0.05), with parallel improvement in insulin sensitivity and HbA1c levels (p < 0.0001). Meal-induced glucose plasma levels were significantly lower at 6 months after the LGCP (p < 0.0001), and postprandial triglyceridemia was also ameliorated at the 6-month follow-up (p < 0.001). Postprandial GIP plasma levels were significantly increased both at 1 and 6 months after the LGCP (p < 0.0001), whereas the overall meal-induced GLP-1 response was not significantly changed after the procedure (p > 0.05). Postprandial ghrelin plasma levels decreased at 1 and 6 months after the LGCP (p < 0.0001) with no significant changes in circulating obestatin levels. CONCLUSION: During the initial 6-month postoperative period, LGCP induces significant weight loss and improves the metabolic profile of morbidly obese T2DM patients, while it also decreases circulating postprandial ghrelin levels and increases the meal-induced GIP response.

• MeSH
• Time Factors MeSH
• Diabetes Mellitus, Type 2 complications   metabolism   MeSH
• Gastrointestinal Hormones metabolism   MeSH
• Gastroplasty methods   MeSH
• Ghrelin metabolism   MeSH
• Glucagon-Like Peptide 1 metabolism   MeSH
• Weight Loss * MeSH
• Homeostasis MeSH
• Body Mass Index MeSH
• Blood Glucose metabolism   MeSH
• Laparoscopy * MeSH
• Middle Aged MeSH
• Humans MeSH
• Obesity, Morbid metabolism   surgery   MeSH
• Follow-Up Studies MeSH
• Postprandial Period MeSH
• Triglycerides metabolism   MeSH
• Treatment Outcome MeSH
• Gastric Inhibitory Polypeptide metabolism   MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Evaluation Study MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Gastrointestinal Hormones MeSH
• Ghrelin MeSH
• Glucagon-Like Peptide 1 MeSH
• Blood Glucose MeSH
• Triglycerides MeSH
• Gastric Inhibitory Polypeptide MeSH

BACKGROUND: Majority of studies that focused on the influence of abdominal obesity on lipoprotein profile, were conducted in the fasting conditions. The effects of visceral fat accumulation on postprandial lipoprotein concentrations have not yet been studied in details. We therefore focused on the postprandial lipoprotein profile in otherwise healthy men and women with abdominal obesity and their comparison with the control group of volunteers with normal waist circumference. The concentration of lipoprotein classes and subclasses was measured before and 4 hours after a standard meal by linear polyacrylamide gel electrophoresis. RESULTS: A statistically significant postprandial rise in triacylglycerol concentration occurred in all subjects. VLDL increased 4 hours after meal in all subjects except the women with normal waist circumference. The concentration of large IDL particles increased in both non-obese men and women. In women with abdominal obesity, however, it decreased, while in obese men there was no statistically significant change. The concentration of small and medium-sized IDL particles decreased in all volunteers. Analyzing subclasses changes of large, medium-sized and small LDL particles we saw no significant shift in their concentrations except the subclass of large LDL particles, which decreased in men. Concentrations of medium and small HDL particles decreased postprandially in all volunteers with normal waist circumference. However, they remained unchanged in subjects with abdominal obesity. CONCLUSIONS: We observed significant postprandial changes of the lipoprotein profile, but the nature and extent of these changes depended on gender and presence of abdominal obesity.

• MeSH
• Obesity, Abdominal blood   MeSH
• Adult MeSH
• Cholesterol, HDL blood   MeSH
• Cholesterol, LDL blood   MeSH
• Humans MeSH
• Waist Circumference MeSH
• Postprandial Period MeSH
• Sex Factors MeSH
• Triglycerides blood   MeSH
• Particle Size MeSH
• Cholesterol, VLDL blood   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cholesterol, HDL MeSH
• Cholesterol, LDL MeSH
• Triglycerides MeSH
• Cholesterol, VLDL MeSH