Premature Coronary Heart Disease in South Asians: Burden and Determinants

Purpose of review: While the burden of cardiovascular disease (CVD) is on the decline globally, it is on the rise among South Asians. South Asians are also believed to present early with coronary artery disease (CAD) compared with other ethnicities. Recent findings: South Asians have demonstrated a higher burden of premature CAD (PCAD) compared with other ethnicities. These findings are not limited to non-immigrant South Asians but have also been found in immigrant South Asians settled around the world. In this article, we first discuss studies evaluating PCAD among South Asians residing in South Asia and among South Asian immigrants in other countries. We then discuss several traditional risk factors that could explain PCAD in South Asians (diabetes, hypertension, dietary factors, obesity) and lipoprotein-associated risk (low HDL-C levels, higher triglycerides, and elevated apolipoprotein B levels). We then discuss several emerging areas of research among South Asians including the role of dysfunctional HDL, elevated lipoprotein(a), genetics, and epigenetics. Although various risk markers and risk factors of CAD have been identified in South Asians, how they impact therapy is not well-known. PCAD is prevalent in the South Asian population. Large-scale studies are needed to identify how this information can be rationally utilized for early identification of risk among South Asians, and how currently available therapies can mitigate this increased ris

Toward an effective exome-based genetic testing strategy in pediatric dilated cardiomyopathy

Purpose: We evaluated the diagnostic yield in pediatric dilated cardiomyopathy (DCM) of combining exome sequencing (ES)based targeted analysis and genome-wide copy-number variation (CNV) analysis. Based on our findings, we retrospectively designed an effective approach for genetic testing in pediatric DCM. Methods: We identified 95 patients (in 85 families) with pediatric onset of DCM. We initially excluded 13 of these families because they already had a genetic diagnosis, leaving a total of 31 probands for singlenucleotide polymorphism (SNP) array and trio-ES. We used Human Phenotype Ontology (HPO)-based filtering for our data analysis. Results: We reached a genetic diagnosis in 15/31 (48.4%) families. ES yielded a diagnosis in 13 probands (13/15; 86.7%), with most variants being found in genes encoding structural cardiomyocyte components. Two large deletions were identified using SNP array. If we had included the 13 excluded families, our estimated yield would have been 54%. Conclusion: We propose a standardized, stepwise analysis of (i) wellknown cardiomyopathy genes, (ii) CNVs, (iii) all genes assigned to HPO cardiomyopathy, and (iv) if appropriate, genes assigned to other HPO terms. This diagnostic approach yields the highest increase at each subsequent step and reduces analytic effort, cost, the number of variants of unknown clinical significance, and the chance of incidental findings