Fortuin, Floyd David

Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways. Beyond direct immunomodulators, GLP-1 receptor agonists and SGLT2 inhibitors provide both cardioprotective and anti-inflammatory benefits, reinforcing their expanding role post-ACS. Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic developments.

Background Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real‐world mortality data on valvular heart disease (VHD) in the United States remain limited. Methods and Results We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age‐adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22‐year study, there were 446 096 VHD deaths, accounting for 0.80% of all‐cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD‐related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2–8.5) to 6.6 (95% CI, 6.5–6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. Conclusions The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.

Background: Transcatheter aortic valve replacement (TAVR) is now an approved alternative to surgical aortic valve replacement for the treatment of severe aortic stenosis. As the clinical adoption of TAVR expands, it remains important to identify predictors of mortality after TAVR. We aimed to evaluate the impact of sex differences in aortic valve calcium score (AVCS) on long-term mortality following TAVR in a large patient sample. Methods: We included consecutive patients who successfully underwent TAVR for treatment of severe native aortic valve stenosis from June 2010 to May 2021 across all US Mayo Clinic sites with follow-up through July 2021. AVCS values were obtained from preoperative computed tomography of the chest. Additional clinical data were abstracted from medical records. Kaplan-Meier curves and Cox-proportional hazard regression models were employed to evaluate the effect of AVCS on long-term mortality. Results: A total of 2543 patients were evaluated in the final analysis. Forty-one percent were women, median age was 82 years (Q1: 76, Q3: 86), 18.4% received a permanent pacemaker following TAVR, and 88.5% received a balloon expandable valve. We demonstrate an increase in mortality risk with higher AVCS after multivariable adjustment ( P <0.001). When stratified by sex, every 500-unit increase in AVCS was associated with a 7% increase in mortality risk among women (adjusted hazard ratio, 1.07 [95% CI, 1.02–1.12]) but not in men. Conclusions: We demonstrate a notable sex difference in the association between AVCS and long-term mortality in a large TAVR patient sample. This study highlights the potential value of AVCS in preprocedural risk stratification, specifically among women undergoing TAVR. Additional studies are needed to validate this finding.