👤 María Dolores Girón

A significant proportion of patients continue to experience cardiovascular (CV) events despite achieving recommended low-density lipoprotein cholesterol (LDL-C) targets, a phenomenon referred to as residual CV risk. Clinical evidence from large outcome trials highlights the impact of residual risk on cardiovascular disease (CVD) burden, underscoring the need for therapeutic strategies beyond LDL-C lowering. Residual CV risk arises from diverse mechanisms, including persistent atherogenic dyslipidaemia [elevated triglyceride-rich lipoproteins (TRL), high triglycerides (TG), low high-density lipoprotein cholesterol (HDL-C) levels and increased apolipoprotein B (ApoB), Lipoprotein(a) (Lp[a]) and non-HDL-C], chronic inflammation, metabolic disorders and a prothrombotic state. These abnormalities continue to drive atherosclerotic progression in optimally treated patients, underscoring that managing residual CV risk requires a multifaceted approach. Lifestyle and dietary interventions remain foundational, targeting weight reduction, smoking cessation or adoption of a Mediterranean diet. Pharmacological options include statins (as first-line therapy), or the use of ezetimibe, or bempedoic acid since they both have complementary effects to LDL-C lowering. Emerging therapies, including proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (ApoC3) and angiopoietin-like 3 (ANGPTL3) inhibitors, demonstrate potential efficacy in favourably modulating lipid profiles and targeting specific components of atherogenic dyslipidaemia (AD). Combination therapies tailored to individual lipid profiles show promise to reduce residual CV risk. The following review aims to provide a comprehensive overview of the latest evidence on the factors driving residual CV risk and the therapeutic interventions available to treat atherogenic dyslipidaemia beyond LDL-C reduction. Show less

Metabolically Dysfunctional-Associated Steatotic Liver Disease (MASLD) affects both metabolically healthy obese (MHO) individuals and metabolically unhealthy lean (MUL) individuals. Key genes linked to liver dysfunction, such as Show less

High-fat (HF) and rapid digestive (RD) carbohydrate diets during pregnancy promote excessive adipogenesis in offspring. This effect can be corrected by diets with similar glycemic loads, but low rates of carbohydrate digestion. However, the effects of these diets on metabolic programming in the livers of offspring, and the liver metabolism contributions to adipogenesis, remain to be addressed. In this study, pregnant insulin-resistant rats were fed high-fat diets with similar glycemic loads but different rates of carbohydrate digestion, High Fat-Rapid Digestive (HF-RD) diet or High Fat-Slow Digestive (HF-SD) diet. Offspring were fed a standard diet for 10 weeks, and the impact of these diets on the metabolic and signaling pathways involved in liver fat synthesis and storage of offspring were analyzed, including liver lipidomics, glycogen and carbohydrate and lipid metabolism key enzymes and signaling pathways. Livers from animals whose mothers were fed an HF-RD diet showed higher saturated triacylglycerol deposits with lower carbon numbers and double bond contents compared with the HF-SD group. Moreover, the HF-RD group exhibited enhanced glucose transporter 2, pyruvate kinase (PK), acetyl coenzyme A carboxylase (ACC) and fatty acid (FA) synthase expression, and a decrease in pyruvate carboxylase (PyC) expression leading to an altered liver lipid profile. These parameters were normalized in the HF-SD group. The changes in lipogenic enzyme expression were parallel to changes in AktPKB phosphorylation status and nuclear expression in carbohydrate-response element and sterol regulatory element binding proteins. In conclusion, an HF-RD diet during pregnancy translates to changes in liver signaling and metabolic pathways in offspring, enhancing liver lipid storage and synthesis, and therefore non-alcoholic fatty liver disease (NAFLD) risk. These changes can be corrected by feeding an HF-SD diet during pregnancy. Show less