Current Atherosclerosis Reports最新文献

Purpose of review: Homozygous familial hypercholesterolaemia (HoFH) is characterized by marked elevation of low-density lipoprotein cholesterol (LDLC) and premature atherosclerotic cardiovascular disease. This is a review of novel pharmacological therapies to lower LDLC in patients with HoFH.

Recent findings: Novel therapies can be broadly divided by whether their efficacy is dependent or independent of residual low-density lipoprotein receptor (LDLR) function. Novel LDLR dependent therapies that reduce proprotein subtilisin kexin type 9 levels include monoclonal antibodies (alirocumab and evolocumab) and a small inhibitory RNA (inclisiran). LDLC reductions are highly variable and depend on residual LDLR function. Microsomal triglyceride inhibitors (lomitapide) and therapies that reduce angiopoietin like factor 3 (evinacumab and zodasiran) both reduce LDLC by approximately 50%, irrespective of residual LDLR function. Most patients with HoFH require multiple therapies to achieve LDLC targets. Better LDLC control with LDLR independent therapies is likely to improve the outlook for patients with HoFH while at the same time reducing the need for other therapies such as apheresis or hepatic transplantation.

Purpose of review: Atherosclerotic cardiovascular disease (ASCVD) is one of the most common causes of death globally and the leading one in the US. Elevated low-density lipoprotein (LDL) cholesterol is one of the main modifiable disease risk factors and statin therapies have been extensively studied in that regard. The present work presents the clinical trials derived evidence supporting the use of statins in primary and secondary cardiovascular disease prevention.

Recent findings: Statins are a major moderator of hepatic LDL cholesterol output, effectively reducing serum LDL cholesterol concentrations, in a dose-dependent manner. Their use as a single agent or in combination with other treatment modalities (ezetimibe, PCSK9 inhibitors etc.) has been proven to prevent ASCVD events and reduce cardiovascular disease incidence and mortality substantially. Their use is warranted as a first line agent in all secondary prevention patients, as well as those in primary prevention at high or very high risk for ASCVD events and based on the presence of specific modifiers, even in selected cases at moderate ASCVD risk. Their potency and dose should be tailored to the individual's cardiovascular risk and the tolerance to their potential adverse effects in order to achieve the guidelines-directed LDL goals. Statin therapies are the mainstay of therapy for ASCVD risk reduction and should be initiated in all patients at high enough of a risk, to reduce event rates, morbidity and mortality.

Purpose: Inflammation has been demonstrated to negatively impact patients in the peri-ACS period. This narrative review outlines the inflammatory response in ACS, highlighting the role of the NLRP3 inflammasome pathway following acute plaque rupture and coronary intervention and its potential as a pharmacologic target. RECENT: nvestigators have leveraged medications targeting the NLRP3 inflammasome currently used for other inflammatory pathologies, including colchicine, tocilizumab and anakinra. Investigation into these drugs in the peri-ACS period has yielded varying results, with the most encouraging findings in ACS patients treated with tocilizumab. More conflicting data exists for the role of colchicine and anakinra, with many studies limited in their power to detect clinical outcomes and heterogeneity in their patient populations and endpoints. Despite conflicting data, the NLRP3 remains an attractive therapeutic target in the peri-ACS period. Further investigation is required to prove benefit and safety with large clinical trials adequately powered for clinical outcomes.

Purpose of review: Atherosclerotic cardiovascular disease (ASCVD) and diabetes are leading causes of morbidity and mortality in the United States and globally. Statin medications, a cornerstone of ASCVD prevention and treatment strategies, have been demonstrated to cause hyperglycemia and new onset diabetes mellitus (NODM). The purpose of this review is to summarize existing and emerging knowledge around the intersection of statins and these two important clinical problems.

Recent findings: Since initial reporting of statin-induced hyperglycemia and NODM, the totality of available data corroborates an association between incident diabetes and statin use. A consensus that high-intensity statin and individuals with obesity or glycemic parameters approximating diabetes thresholds constitute the majority of risk exists. Alterations in insulin signaling, glucose transport and gastrointestinal microbiota are leading hypotheses underlying the mechanisms of statin-induced hyperglycemia. The probability of NODM based on an individual's risk factors and statin specific properties can be anticipated. This risk needs to be contextualized with the risk of ASCVD. In order to effectively adjudicate the risk of NODM, improvement in formulating and ultimately conveying a comprehensive ASCVD risk assessment to patients is necessary.

Purpose of review: Inflammation has been commonly known for the past decade as a part of the pathophysiology of atherosclerosis, along with lipid accumulation. However, some patients with optimized lipid-lowering therapy still have elevated inflammatory biomarkers. Anti-inflammation therapies were developed to eradicate this residual risk. We summarized the primary inflammatory pathway and recent clinical trials in anti-inflammation therapies.

Recent findings: Colchicine Cardiovascular Outcomes Trial (COLCOT) and LoDoCo2 (Colchicine Reduces Risk of Major Cardiovascular Events in Chronic Coronary Disease) found that low-dose colchicine significantly reduced cardiovascular death, myocardial infarction (MI), ischemic stroke and coronary revascularization in patients with recent MI within 30 days and chronic coronary disease respectively. The US Food and Drug Administration approved low-dose colchicine in 2023 for patients with established atherosclerotic cardiovascular disease (ASCVD). However, its use was limited for chronic kidney disease (CKD) patients. Reduction in Inflammation in Patients with Advanced Chronic Renal Disease Utilizing Antibody Mediated Interleukin-6 Inhibition (RESCUE) was conducted using Ziltivekimab, an IL-6 ligand monoclonal antibody and found that it significantly reduced high-sensitivity C-reactive protein, an inflammatory surrogate marker. There is an ongoing phase-3 clinical trial, Ziltivekimab Versus Placebo Cardiovascular Outcomes in Participants with Atherosclerotic Cardiovascular Disease, Chronic Kidney Disease, and Systemic Inflammation trial (ZEUS), which will be essential for further anti-inflammation therapy for patients with CKD. Numerous clinical trials have investigated anti-inflammation therapies. Colchicine is by far the only one that has the potential to be widely used due to its cost-effectiveness. Further research is needed on other novel anti-inflammation therapies and their real-world implementation.

Purpose of review: Plaque erosion is the second leading cause of coronary thrombosis following plaque rupture and represents a key pathophysiological process underlying acute coronary syndromes that can culminate in sudden coronary death. While the precise mechanisms and risk factors driving plaque rupture are well-established, those for erosion have only recently been explored. This review summarizes current literature on the characteristics and risk factors favoring plaque erosion.

Recent findings: Plaque erosion is characterized by a defective endothelial layer in the intima, promoting thrombus formation in the presence of an intact fibrous cap. It is more common in younger women (< 50 years) and smokers. Pathologic intimal thickening or fibroatheroma are common underlying lesions. Risk factors include gender, age, smoking, and disturbances in shear flow. Advances in pathogenic and molecular mechanisms, such as endothelial shear stress, neutrophil activation, and toll-like receptor-2 pathways, are discussed. Understanding the major risk factors for plaque erosion can inform diagnostics and therapeutics to prevent the progression of arterial thrombosis.

Purpose of review: We review treatment criteria in the pediatric population, provide practical advice on how and when to prescribe statins, and share tips to improve compliance.

Recent findings: Although long-term outcome studies of cardiovascular-related events, such as myocardial infarction (MI) and stroke, are lacking in this population, statin therapy initiated during adolescence has been shown to be safe and effective for up to 20 years of continuous use. HMG-CoA reductase inhibitors (statins) are the most effective class of drugs for lowering low-density lipoprotein cholesterol (LDL-C) in children and adolescents.

Purpose of the review: Atherosclerotic plaques result from imbalanced lipid metabolism and maladaptive chronic immune responses. Class B scavenger receptors are lipid transporters and regulators of their metabolism. The purpose of this review is to explore recent structural findings of these membrane-associated receptors, with particular focus on their higher-order oligomeric organization and impact on lipid transport.

Recent findings: Class B scavenger receptors have evidence for oligomerization, with recent efforts placed on identifying residues and motifs responsible for mediating this process. The first studies correlating scavenger receptor oligomerization to function are described. This review highlights two emerging hypotheses regarding the function of scavenger receptor oligomerization. The first is a hydrophobic channel created by self-association of receptors to promote transport. The second hypothesis suggests that homo-oligomerization stabilizes receptors, prevents internalization and thereby promotes transport indirectly. Novel computational and in vitro experimental techniques with purified receptors are also described.

Purpose of review: To summarize selected late-breaking science on cardiovascular disease (CVD) prevention presented at the 2024 European Society of Cardiology (ESC) Congress.

Recent findings: Key studies from the 2024 ESC Congress highlight advances in (CVD) management. Apolipoprotein A-1 infusions reduced risk in acute myocardial infarction patients with high LDL cholesterol. Plozasiran cut triglycerides and apolipoprotein C-III levels, lowering pancreatitis risk. A 14-year study linked smoking among youth to cardiac abnormalities. Baseline hsCRP, LDL-C, and Lp(a) were strong predictors of 30-year outcomes in women. Alternative LDL-lowering strategies matched high-intensity statins in effectiveness of LDL-C lowering and reduced diabetes risk. Early combination lipid lowering therapy improved outcomes post-myocardial infarction. Nordic and Mediterranean diets were linked to lower atherosclerotic CVD risk. The findings from the 2024 ESC Congress highlight significant advancements in CVD prevention, including novel lipid-lowering therapies, biomarker-based risk prediction, and lifestyle interventions. These studies underscore the importance of early and personalized treatment strategies to mitigate long-term cardiovascular risk.

Purpose of the review: This review is intended to serve as guidance for care providers working with children who have dyslipidemia and exhibit picky eating behaviors.

Recent findings: Picky eating behaviors in children can be very stressful for caregivers and children alike, even if they may not reach clinical significance. In the setting of lipid disorder treatment, picky eating can present an even greater challenge, since many of the foods considered most heart-healthy are not often considered "kid-friendly". Care providers should validate caregivers' concerns, screen for picky eating and be prepared to provide guidance to parents and a referral to a specialist, if needed. This review contains an itemized list of points to focus on with families and additional resources.