Impact of genetic background as a risk factor for atherosclerotic cardiovascular disease: A protocol for a nationwide genetic case-control (CV-GENES) study in Brazil.

Atherosclerotic Cardiovascular Disease (ASCVD) represents the leading cause of death worldwide, and individual screening should be based on behavioral, metabolic, and genetic profile derived from data collected in large population-based studies. Due to the polygenic nature of ASCVD, we aimed to assess the association of genomics with ASCVD risk and its impact on the occurrence of acute myocardial infarction, stroke, or peripheral artery thrombotic-ischemic events at population level. CardioVascular Genes (CV-GENES) is a nationwide, multicenter, 1:1 case-control study of 3,734 patients in Brazil. Inclusion criterion for cases is the first occurrence of one of the ASCVD events. Individuals without known ASCVD will be eligible as controls. A core lab will perform the genetic analyses through low-pass whole genome sequencing and whole exome sequencing. In order to estimate the independent association between genetic polymorphisms and ASCVD, a polygenic risk score (PRS) will be built through a hybrid approach including effect size of each Single Nucleotide Polymorphism (SNP), number of effect alleles observed, sample ploidy, total number of SNPs included in the PRS, and number of non-missing SNPs in the sample. In addition, the presence of pathogenic or likely pathogenic variants will be screened in 8 genes (ABCG5, ABCG8, APOB, APOE, LDLR, LDLRAP1, LIPA, PCSK9) associated with atherosclerosis. Multiple logistic regression will be applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI), and population attributable risks will be calculated. Clinical trial registration: This study is registered in clinicaltrials.gov (NCT05515653).

Percutaneous coronary intervention or medical therapy in patients with severe aortic stenosis and coronary artery disease undergoing transcatheter aortic valve implantation: a real-world analysis using data from an international network.

Patients undergoing transcatheter aortic valve implantation (TAVI) due to severe aortic stenosis have a high prevalence of coronary artery disease (CAD). As many of them have high surgical risk, CAD treatment in this group has typically been carried out with optimal medical treatment or paired with percutaneous coronary intervention (PCI). However, the best approach in this scenario is not well established. We aimed to evaluate 5-year cardiovascular outcomes in patients with aortic stenosis and chronic CAD treated with medical treatment alone compared to PCI coupled with medical therapy before or during TAVI. We used data from a large multinational electronic health record network (TriNetX). Patients aged 18 years or older with severe aortic stenosis and CAD who underwent TAVI in the last 10 years before the analysis were considered eligible. Five-year Kaplan-Meier curves and hazard ratios were calculated. We identified 19 058 patients undergoing isolated TAVI and 2277 patients undergoing TAVI and PCI. Using propensity matching scores, 2277 patients in each group were compared. The 5-year cumulative incidence of MACE was 22.92% in the isolated TAVI group, vs. 25.91% in the PCI-TAVI group. The probability of the composite primary outcome was not significantly different between the isolated TAVI group vs. the PCI-TAVI group [53.1 vs. 47.6%, adjusted hazard ratio (HR) 0.92, 95% confidence interval (CI), 0.80-1.05]. In a real-world study of patients with CAD and severe aortic stenosis, the 5-year probability of death, acute coronary syndrome and ischemic stroke did not differ between patients undergoing isolated TAVI compared to patients undergoing PCI before or during TAVI.