Current Atherosclerosis Reports最新文献

Purpose of review: This review aims to explore the epidemiology of lipoprotein(a) [Lp(a)] by its structural and genetic make-up variation amongst ancestry groups.

Recent findings: Lipoprotein(a) [Lp(a)] is a genetically determined lipoprotein particle, causally implicated in atherosclerotic cardiovascular disease (ASCVD) and calcific aortic valve stenosis (CAVS). Given its genetic basis, studies have shown marked ancestry-related differences in different races and ethnicities. Lp(a) plasma concentrations vary by more than 100-fold among individuals, primarily due to LPA gene polymorphisms and the number of kringle-IV type 2 (KIV2) repeats, which define apolipoprotein(a) [apo(a)] isoform size. Individuals of African descent have the highest median concentrations, followed by South Asians, with Hispanics/Latinos and East Asians having lower levels. Admixed populations display heterogeneity reflecting genetic ancestry. Despite differences in absolute levels, the relative ASCVD risk per unit increase in Lp(a) is consistent across groups, highlighting the universal atherogenicity of elevated Lp(a). Small apo(a) isoforms are associated with higher Lp(a) concentrations and risk, though isoform size is mainly a surrogate for Lp(a) burden. Despite a strong genetic basis and disproportionate burden in some populations, ancestry-specific testing guidelines are limited and testing rates remain low. Therapies targeting LPA transcription are in development, with outcome trials underway. Integrating ancestry-informed perspectives with universal risk principles is essential for equitable prevention and treatment. Routine, one-time Lp(a) testing enables cost-effective early risk stratification as Lp(a)-directed therapies emerge.

Purpose of review: The PI3K/Akt/mTOR (phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin) signaling pathway is pivotal in regulating cellular functions such as growth, proliferation, survival, and metabolism. Dysregulation of this pathway contributes to the pathogenesis of multiple diseases, including cancer, metabolic disorders, and cardiovascular diseases, notably atherosclerosis. This review outlines the role of the PI3K/Akt/mTOR pathway in the progression of atherosclerosis, emphasizing its involvement in endothelial protection, vascular smooth muscle cell proliferation and migration, as well as inflammatory modulation.

Recent findings: The pathway affects atherosclerosis through several mechanisms: it both protects and can harm the blood vessel lining, controls how muscle cells in vessel walls grow, move and die, and influences inflammation. These processes critically affect how plaques form, become unstable, and progress. Current drug treatments and procedures targeting this pathway show promise, though existing therapies often lack specificity. Understanding the many roles the PI3K/Akt/mTOR pathway plays in atherosclerosis offers important insights for creating targeted treatments. While current approaches show potential, we urgently need new interventions that specifically target this pathway to address heart disease complexity and improve patient results. Future studies should focus on developing more precise treatments to effectively reduce atherosclerosis.

Purpose of review: Cardiovascular-kidney-metabolic (CKM) syndrome involves complex interactions among cardiovascular, renal, and metabolic disorders. This review provides an overview of the mechanistic aspects of the epithelial-mesenchymal transition (EMT) and analyzes the regulatory impact of various statins on EMT-associated signaling pathways.

Recent findings: EMT and endothelial-to-mesenchymal transition (EndoMT) are crucial in the development of cardiac fibrosis, vascular remodeling, and interstitial fibrosis. Several signaling pathways, including the TGF-β/Smad, Wnt/β-catenin, MAPK, and Notch signaling pathways, as well as oxidative stress and inflammatory mediators, regulate these processes. Statins exert significant biological effects by downregulating proinflammatory cytokines, suppressing ROS, and inhibiting EMT-related signaling pathways. Statins can also inhibit EndoMT and reduce the progression of vascular fibrosis and atherosclerosis in the context of cardiovascular diseases. Similarly, in renal disorders such as chronic kidney disease (CKD) and diabetic nephropathy, statins reduce EMT in renal tubular epithelial cells by targeting pathways such as Smad and MAPK. CKM syndrome involves complex interactions among cardiovascular, renal, and metabolic disorders. Among the factors implicated in the pathophysiology of CKM, the EMT process is recognized as a key biological process. Evidence from preclinical and clinical studies supports the emerging role of statins as promising agents in managing CKM through modulating EMT. Therefore, understanding the diverse mechanisms of statins may lead to the development of more effective therapeutic strategies against CKM's fibrotic and inflammatory complications.

Purpose of review: This review aims to evaluate the effectiveness of GLP-1 receptor agonists, and metabolic and bariatric surgery in managing childhood obesity and associated conditions. It discusses current trends, challenges, and the potential of these treatments to improve cardiometabolic health in children and adolescents.

Recent findings: Lifestyle modifications, though recommended as first-line therapy, show modest efficacy in weight management. GLP-1 receptor agonists like liraglutide and semaglutide have demonstrated significant weight loss and improvement in metabolic outcomes. Bariatric surgery, particularly Roux-en-Y gastric bypass, and vertical sleeve gastrectomy have shown substantial long-term benefits in weight reduction and remission of comorbidities in adolescents with severe obesity. While early intervention with lifestyle changes is recommended for prevention and management of obesity in children, pharmacotherapy, and surgical options may be needed. Utilizing these approaches can optimize weight loss and improve long-term health outcomes, highlighting the need for a multidisciplinary strategy to address this growing public health issue.

Purpose of review: Atherosclerosis is considered to be an inflammatory disease due to the presence of macrophages and T-cells within the artery plaques. Atherosclerotic plaques contain significant levels of oxidised low density lipoprotein (oxLDL) suggesting it is a source of the observed inflammation. In this systematic review, the PubMed, Medline and Scopus databases were searched for studies on the inflammatory effects of oxLDL and therapeutic treatments intended to prevent inflammation in humans or human-derived cell lines.

Recent findings: Out of the 65 articles that passed through a full-text examination of the inflammatory effects of oxLDL, eight were considered suitable for inclusion in the study. Fifty studies out of 75 studies which were subjected to full-text review of anti-inflammatory agents were selected. Three out of 4 studies that measured the effect of oxLDL stimulation on interleukin (IL)-1β reported significant increase in IL-1β level, while 4 out of 6 studies that measured IL-6 reported significant increase in IL-6 level. Four out of 6 studies that measured tumour necrosis factor (TNF)-α reported significant increase in TNF-α after oxLDL stimulation, while 2 studies reported significant increase in caspase-1 activation by oxLDL. Although some of the studies on the anti-inflammatory agents demonstrated significant inhibition of inflammation, none of the anti-inflammatory agents directly targeted oxLDL immune activation. It is evident that there is an interplay between cholesterol and vascular cells in the pathogenesis of atherosclerosis, but there is a gap between the suggested effects of oxLDL in literatures and actual intrinsic effects of oxLDL on the vascular cells.

Purpose of review: Vitamin D deficiency is associated with increased cardiovascular morbidity and mortality through pathways that foster atherosclerosis. This review aims to clarify the relationship between serum vitamin D and peripheral artery disease (PAD), while evaluating the prognostic implications and diagnostic utility of vitamin D deficiency in PAD patients.

Recent findings: Patients with PAD, displayed significantly lower serum vitamin D levels compared to non-PAD individuals, mean difference (MD), - 2.12ng/mL (95%CI:-4.13 to - 0.12). Individuals with vitamin D deficiency (< 20 ng/mL) exhibited a higher prevalence of PAD relative to those with insufficient or sufficient levels, odds ratio (OR), 1.52 (95%CI:1.07-2.18). Unadjusted prognostic factor analysis displayed an increased hazard for PAD occurrence among deficient patients, hazard ratio (HR), 1.04 (95%CI:1.02-1.06), an outcome that failed to retain its statistical significance upon parameter adjustment, adjusted HR, 1.01 (95%CI:0.99-1.03). Diagnostic accuracy analysis displayed the poor performance of the 20ng/mL threshold with pooled sensitivity and specificity of 0.76 (95%CI:0.55-0.90) and 0.34 (95%CI:0.17-0.57). Further analysis identified a negative predictive value (NPV) of 94% for the 19.65ng/mL threshold, indicating a 6% prevalence of PAD above this cutoff. While this review displayed both decreased vitamin D concentrations for PAD patients and an increased prevalence of PAD among patients with vitamin D deficiency, the prognostic effect of vitamin D on the development of PAD remains inconclusive. Despite the poor performance of vitamin D deficiency as a diagnostic marker, the NPV displayed by the analysis further supports the possible association between vitamin D deficiency and PAD.

Purpose of review: This literature review summarizes recent interventions to enhance cardiac rehabilitation (CR) participation, enrollment, and completion among women and their impact on CR outcomes.

Recent finding: Despite well-documented benefits of CR, CR remains underutilized nationally and globally, more so among women than men. Barriers to CR participation reported by women have not changed significantly over time. Recent approaches to improving women's enrollment, adherence, and completion have included home-based CR and telerehabilitation, incorporation of more diverse exercise modalities, and women-focused or women-only CR programming. Despite some encouraging results, most approaches have shown only modest benefits, and study interpretation is often limited by small study sizes, a lack of randomization, and highly selected samples. CR remains underutilized among women, contributing to poor health outcomes. Novel approaches to CR show promise, but further research is necessary to evaluate their impact on cardiovascular events, physiologic outcomes, and quality of life.

Purpose of review: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and atherosclerotic cardiovascular disease (ASCVD) are familiar co-attendants, while two-way pathophysiological relationships between them are incompletely determined. Mechanisms-insulin resistance, dyslipidemia, inflammation, and endothelial dysfunction-that underlie MASLD-induced atherogenesis are discussed in the narrative. Ascertainment of tools for the risk stratification of ASCVD in the population is also made.

Recent findings: In the last five years, the findings of the cohort studies show MASLD severity is related to subclinical atherosclerosis and future cardiovascular events. New biomarkers (e.g., apolipoprotein B, adipokines) and imaging techniques (e.g., coronary CT angiography) enhance the prediction of risk over the traditional factors. New treatments-GLP-1 receptor agonists and SGLT2 inhibitors-appear to decrease the hepatic steatosis and endpoints of ASCVD, but the use of statins is suboptimal due to the perceived safety issue of the liver. MASLD is a marker and mediator of the risk of ASCVD and thus warrants joint screening and management strategies. Incorporating MASLD-related biomarkers within cardiovascular risk models may be helpful for early detection. High priority for the future is large-scale, randomly controlled clinical studies of combined metabolic therapies to gain dual optimal benefits for the liver and the heart.

Purpose of review: This review summarizes key findings from cardiovascular disease prevention studies presented at the 2025 European Society of Cardiology (ESC) Conference. It highlights trials on novel therapies, vaccination, blood pressure management, and the use of technology and risk scores to guide treatment.

Recent findings: The CONFIDENCE trial showed that a combination of finerenone and empagliflozin significantly reduced the urine albumin-creatinine ratio in patients with type 2 diabetes mellitus and chronic kidney disease. The DANFLU-2 trial found that the high-dose influenza vaccine was associated with fewer cardio-respiratory hospitalizations in older adults compared to the standard dose. The RETREAT FRAIL trial demonstrated that tapering antihypertensive medications in frail, elderly patients safely reduced pill burden without increasing all-cause mortality and adverse cardiovascular (CV) and non-CV outcomes. In diagnostics, the AI-Gatekeeper trial showed an AI tool reduced unnecessary advanced imaging for coronary artery disease (CAD) by 76%, lowering costs without compromising safety. The CAC CV-PREVITAL trial found that adding a coronary artery calcium score to standard risk assessment improved blood pressure control. The REBOOT-CNIC trial challenged a paradigm, showing that beta-blockers provided no significant benefit in post-myocardial infarction patients without reduced ejection fraction. A Post hoc analysis of SURMOUNT-5 found that tirzepatide offers a more pronounced long-term reduction in cardiovascular disease risk compared with semaglutide for adults with obesity and without diabetes. The NATURE-Legacy trial provided compelling evidence for the "legacy benefit" of early, modest reductions in LDL-C and blood pressure. The AIMHY-INFORM Dual Therapy Arm highlighted ethnic differences in blood pressure responses to dual therapy, while the OUTREACH trial demonstrated that providing feedback to patients on antihypertensive adherence using urine testing improved medication adherence. The 2025 ESC Conference featured several impactful studies on cardiovascular disease prevention, highlighting the importance of a multifaceted approach that incorporates the strategic integration of AI and a deeper understanding of patient-specific factors. As cardiovascular disease remains the leading global cause of death, these findings underscore the necessity of moving toward more personalized, evidence-based, and technologically-driven preventive care to improve patient outcomes and reduce the overall disease burden.