👤 Martha Gulati

Lipoprotein(a) (Lp(a)) is increasingly recognised as an independent and causal risk factor for atherosclerotic cardiovascular disease. Although the underlying mechanisms remain incompletely defined, evidence supports a multifactorial role for Lp(a) in atherogenesis. Lp(a) contributes to endothelial dysfunction, promotes vascular inflammation and enhances lipid retention and oxidation within the arterial wall. These changes drive foam cell formation and smooth muscle cell activation, hallmarks of early plaque development. In addition, Lp(a) exerts prothrombotic effects through structural homology with plasminogen, interfering with fibrinolysis and promoting thrombosis, which may increase the risk of plaque rupture and acute events. Collectively, these overlapping mechanisms underscore the unique contribution of Lp(a) to both the development and progression of atherosclerosis. As novel targeting therapies emerge, a deeper understanding of Lp(a) biology will be essential for translating these insights into clinical benefit. Show less

The 2025 American Society for Preventive Cardiology meeting highlighted evolving strategies in cardiovascular disease prevention, spanning risk models based on traditional risk factors, emerging biomarkers, novel therapeutics, and digital health innovations. Key discussions addressed lipoprotein(a) [Lp(a)] and inflammation as a causal risk factor, their clinical management, and readiness for targeted therapies; optimal systolic blood pressure targets informed by recent randomized controlled trials; and ongoing debate regarding apolipoprotein B versus low-density lipoprotein cholesterol (LDL-C) as the primary lipid target. Advances in digital health emphasized prevention through artificial intelligence, health equity in technology, and the growing role of wearables. Imaging emerged as a central theme, with sessions highlighting its role in risk assessment, monitoring treatment response, and refining prevention strategies, especially in young adults. Sessions on women's cardiovascular health underscored female-specific risk enhancers and limitations of current risk prediction models. Additional debates addressed the use of polygenic risk scores in young adults and strategies for universal screening with LDL-C, hsCRP, and Lp(a). Heart failure prevention was highlighted as a critical frontier, with emphasis on stage-based risk stratification, early identification of subclinical disease, and targeted interventions to avert progression to symptomatic heart failure. Updates on renal denervation reaffirmed its safety, efficacy, and durability as an adjunctive therapy in resistant hypertension. Collectively, these highlights emphasize the rapid evolution of preventive cardiology, integrating precision risk stratification, digital tools, and novel therapies into routine care. Show less

Alzheimer's disease contributes to 60-70% of all dementia cases in the general population. Belonging to the BIN1/amphiphysin/RVS167 (BAR) superfamily, the bridging integrator (BIN1) has been identified to impact two major pathological hallmarks in Alzheimer's disease (AD), i.e., amyloid beta (Aβ) and tau accumulation. Aβ accumulation is found to increase by BIN1 knockdown in cortical neurons in late-onset AD, due to BACE1 accumulation at enlarged early endosomes. Two BIN1 mutants, KR and PL, were identified to exhibit Aβ accumulation. Furthermore, BIN1 deficiency by BIN1-related polymorphisms impairs the interaction with tau, thus elevating tau phosphorylation, altering synapse structure and tau function. Even though the precise role of BIN1 in the neuronal tissue needs further investigation, the authors aim to throw light on the potential of BIN1 and unfold its implications on tau and Aβ pathology, to aid AD researchers across the globe to examine BIN1, as an appropriate target gene for disease management. Show less

Background Anacetrapib is the only cholesteryl ester transfer protein inhibitor proven to reduce coronary heart disease (CHD). However, its effects on reverse cholesterol transport have not been fully elucidated. Macrophage cholesterol efflux (CEC), the initial step of reverse cholesterol transport, is inversely associated with CHD and may be affected by sex as well as haptoglobin copy number variants among patients with diabetes mellitus. We investigated the effect of anacetrapib on CEC and whether this effect is modified by sex, diabetes mellitus, and haptoglobin polymorphism. Methods and Results A total of 574 participants with CHD were included from the DEFINE (Determining the Efficacy and Tolerability of CETP Inhibition With Anacetrapib) trial. CEC was measured at baseline and 24-week follow-up using J774 macrophages, boron dipyrromethene difluoride-labeled cholesterol, and apolipoprotein B-depleted plasma. Haptoglobin copy number variant was determined using an ELISA assay. Anacetrapib increased CEC, adjusted for baseline CEC, risk factors, and changes in lipids/apolipoproteins (standard β, 0.23; 95% CI, 0.05-0.41). This CEC-raising effect was seen only in men ( Show less