👤 Guy De Backer

Based on data from the EUROASPIRE IV survey, we aimed at assessing the possible residual risk tracked by serum apolipoprotein B in coronary patients with elevated serum triglycerides. All samples from the total EUROASPIRE IV survey (n = 7998) with low serum total cholesterol (<4.5 mmol/L) and high serum triglycerides (≥1.7 mmol/L) were used to analyse apolipoprotein A-I (apoA-I) and apolipoprotein B (apoB) concentrations (n = 938). We selected a similar number of participants (n = 938) with low total cholesterol and with low triglycerides (<1.0 mmol/L). In addition, phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) as well as paraoxonase-1 (PON-1), angiopoietin-like (ANGPTL)-3 and ANGPTL-8 were analysed in randomly selected participants. Despite the lower low-density lipoprotein cholesterol (LDL-C) concentration in the patients with TG ≥ 1.7 mmol/L (1.89 ± 0.44 mmol/L) than those with TG < 1.0 mmol/L (1.99 ± 0.43 mmol/L), p < 0.0001), serum total cholesterol, apoB, and HbA1c were all significantly (p < 0.0001) higher in patients with TG ≥ 1.7 mmol/L. In addition, high-density lipoprotein cholesterol (HDL-C), apoA-I, and CETP activity were significantly lower (p < 0.001) in these patients. The prevalence of obesity and diabetes was higher in the participants with TG ≥ 1.7 mmol/L than in those with TG < 1.0 mmol/L (52.6 % vs 21.9 % and 41.3 % vs. 20.0 %). Statin treatment is mainly decreasing serum LDL-C concentration, but apoB measurements with excess serum triglycerides carried by apoB-containing lipoproteins could provide more specific information about the risk assessment of cardiovascular disease in atherogenic dyslipidemia. Show less

To quantify international variations in lipid-lowering therapies (LLT) use among patients with coronary heart disease (CHD) and attainment of European guideline-recommended lipid goals. INTERASPIRE is an observational study (2020-23) covering 14 countries from all WHO regions. Patients (18-79 years) hospitalized in the preceding 6-36 months with CHD were invited for standardized interviews and examination, with central laboratory analyses for low-density lipoprotein cholesterol (LDL-C), non-HDL-C, and apolipoprotein B (apoB). Valid lipid data meeting quality control standards were available from 13 countries. Lipid goals followed the 2019 guidelines of the European Atherosclerosis Society and the European Society of Cardiology: LDL-C < 1.4 mmol/L, non-HDL-C < 2.2 mmol/L, and apoB <65 mg/dL.Among 4061 patients (78.8% male, mean age 60.3 years), between index event and interview, 66.3% had no change in treatment intensity. LLT use at interview was largely statin monotherapy: 49.6% high-intensity (inter-country range 5.3%-77.3%) and 24.1% low/moderate-intensity (inter-country range 5.1%-70.1%). Otherwise, 12.2% (inter-country range 0.2%-41.1%) were on combination therapy, and 12.7% on no LLT (inter-country range 3.5%-36.7%). Goal attainment for LDL-C was 17.5%. Corresponding non-HDL-C and apoB goals were achieved by 29.9% and 29.2%, respectively. Higher-income countries (defined by the World Bank's 2024-25 classification of income levels) did better in goal attainment than lower-middle-income countries. In this international study, contemporary lipid goals were not achieved in most CHD patients, with lower-middle-income countries having the worst goal attainment. Contributory factors include absence of any LLT use, low use of combinations and a failure to up-titrate LLT to achieve guideline targets. Show less

Vps34 PI3K is thought to be the main producer of phosphatidylinositol-3-monophosphate, a lipid that controls intracellular vesicular trafficking. The organismal impact of systemic inhibition of Vps34 kinase activity is not completely understood. Here we show that heterozygous Vps34 kinase-dead mice are healthy and display a robustly enhanced insulin sensitivity and glucose tolerance, phenotypes mimicked by a selective Vps34 inhibitor in wild-type mice. The underlying mechanism of insulin sensitization is multifactorial and not through the canonical insulin/Akt pathway. Vps34 inhibition alters cellular energy metabolism, activating the AMPK pathway in liver and muscle. In liver, Vps34 inactivation mildly dampens autophagy, limiting substrate availability for mitochondrial respiration and reducing gluconeogenesis. In muscle, Vps34 inactivation triggers a metabolic switch from oxidative phosphorylation towards glycolysis and enhanced glucose uptake. Our study identifies Vps34 as a new drug target for insulin resistance in Type-2 diabetes, in which the unmet therapeutic need remains substantial. Show less