European Heart Journal最新文献

Despite significant advances in lipid-lowering therapeutics, residual lipid risk persists in patients with or at risk of atherosclerotic cardiovascular disease (ASCVD), even after optimizing low-density lipoprotein (LDL) cholesterol. Emerging evidence highlights the role of non-LDL cholesterol fractions, such as remnant cholesterol, lipoprotein(a) [Lp(a)], apolipoprotein B (apoB), and non-high-density lipoprotein (HDL) cholesterol, as key contributors to residual ASCVD risk. Remnant cholesterol, Lp(a), and LDL cholesterol represent three independent lipoprotein species causing ASCVD, while apolipoprotein B (apoB) and non-HDL cholesterol integrate the other three variables. Thus, clinically interpreting elevated apoB and non-HDL cholesterol is potentially complicated since remnants, Lp(a), and LDL cause ASCVD by different mechanisms and by varying proportions in different patients. Indeed, recent research into the pathophysiology of lipid-driven atherogenesis and development of ASCVD has revealed novel mechanisms that in turn suggest new therapeutic strategies targeting non-LDL lipid components. Elevated remnant cholesterol jointly with elevated LDL cholesterol contributes to arterial wall cholesterol deposition, plaque development, and ASCVD endpoints. Furthermore, the additional triglyceride content in remnant particles may theoretically promote intimal inflammation and possibly plaque rupture and erosion, independently contributing to atherogenesis and ASCVD. The lipid component and pro-inflammatory properties of Lp(a) could similarly contribute directly to atherosclerotic plaque development and ASCVD. In addition, the homology with plasminogen of the defining apolipoprotein(a) moiety of Lp(a) has long been speculated to confer anti-fibrinolytic and pro-thrombotic properties that could produce more severe ASCVD outcomes independent of atherogenesis. This review explores the evolving understanding of residual lipid risk in ASCVD, practical guidance for clinicians today, recent advances in therapeutic interventions, and their implications for clinical practice, aiming to optimize lipid management beyond LDL cholesterol reduction today and in the future.

Lipoprotein(a) [Lp(a)] is a significant, genetically determined contributor to the risk of atherosclerotic cardiovascular disease (ASCVD), which remains the leading cause of mortality worldwide despite successes in the management of LDL cholesterol. Lipoprotein(a) possesses increased atherogenicity, contributing to residual cardiovascular risk. Elevated Lp(a) levels affect a substantial proportion of the population, rendering this a potentially high-impact therapeutic target, but currently available lipid-lowering agents and lifestyle interventions have minimal impact on lowering Lp(a), and lipoprotein apheresis is the sole effective-but impractical-method to significantly reduce Lp(a). Recent advances in Lp(a)-targeted therapies, notably nucleic acid-based approaches (e.g. antisense oligonucleotides and small interfering RNAs) and a small molecule inhibitor of Lp(a) synthesis, demonstrated substantial and often durable Lp(a)-lowering effects in Phase II trials. Phase III trials of these agents are now underway to examine the impact of lowering Lp(a) levels on atherosclerotic cardiovascular disease outcomes, and their results may transform the landscape of cardiovascular risk reduction and management for patients with elevated Lp(a). This review summarizes existing lipid-lowering therapies' limited effects on Lp(a), provides an update on the array of emerging therapeutics and their safety and efficacy, and discusses ongoing Phase III trials as well as other potential benefits of Lp(a)-lowering, such as slowing progression of calcific aortic valve stenosis.

Background and aims: Ambient PM2.5 exposure is a known risk factor for acute myocardial infarction (AMI). Myocardial infarction with non-obstructive coronary arteries (MINOCA) represents a distinct subtype of AMI from myocardial infarction with obstructive coronary disease (MI-CAD). Public health measures during the COVID-19 pandemic may have altered exposure patterns, offering a natural experiment. This study investigated changes in the association between short-term exposure to PM2.5 and AMI subtypes following the COVID-19 pandemic.

Methods: Using data from the nationwide JROAD-DPC database, this study analysed 270 091 first-admission AMI patients, including 23 037 MINOCA, between April 2012 and March 2022. A time-stratified case-crossover design with conditional logistic regression estimated the odds ratio (OR) for each 10-μg/m³ increase in PM2.5 exposure at a 2-day lag. The study period was divided into pre-pandemic and post-pandemic phases using 7 April 2020, as the threshold. Sensitivity analyses used alternative pandemic onset dates.

Results: Each 10-μg/m³ increase in lag-2 PM2.5 was significantly associated with an increased risk of AMI. Although the ORs for overall AMI and MI-CAD remained largely unchanged between periods, a significant attenuation of the PM2.5-related risk for MINOCA was observed (pre-pandemic OR 1.303, 95% confidence interval [CI] 1.005-1.688; post-pandemic OR 1.230, 95% CI: .973-1.555; P for interaction = 0.017). Sensitivity analyses confirmed these findings.

Conclusions: Short-term exposure to PM2.5 is associated with increased risk of AMI. The observed reduction in MINOCA risk following the COVID-19 pandemic suggested that public health interventions aimed at reducing air pollution exposure may reduce cardiovascular risks, particularly in specific AMI subtypes.