Clinical and genetic characteristics of coronary artery disease in Chinese young adults: Rationale and design of the prospective Genetic characteristics of coRonary Artery disease in ChiNese young aDults (GRAND) study

Background: Emerging evidence indicates that the worldwide incidence of early-onset coronary artery disease (EOCAD) is increasing. The genetic background has been assumed to harbor pathogenic risk, although the existing findings are mainly restricted to Caucasians. Little is known regarding the clinical profiles of patients with EOCAD and the extent to which genetic factors are related to disease susceptibility and outcomes in Asian people, especially ethnic Chinese. Methods and Results: The Genetic characteristics of coRonary Artery disease (CAD) in ChiNese young aDults (GRAND) study is a multicenter, hospital-based observational clinical study, combined of case-control design and longitudinal prospective cohort. Six thousand nationally representative patients who underwent coronary angiography at 38 centers have been enrolled since May 2017. Clinical data of patients with EOCAD (aged ≤45 years) are collected at the baseline to delineate conventional risk factors, clinical profiles, and therapeutic options of EOCAD and compared with data for patients with late-onset CAD (aged ≥65 years) and age-matched controls without CAD. The patients are followed for 3 years to trace major adverse cardiovascular (CV) events: cardiac death, nonfatal myocardial infarction, and ischemia-driven revascularization. Functional variants contributing to EOCAD risk are identified by high-depth whole-exome sequencing. The genetic profiles are further linked to disease severity and prognosis. A multi-dimensional risk score is established to predict prevalent EOCAD and incident CV events among young Chinese adults. Conclusions: The GRAND study will generate a thorough understanding of the clinical characteristics and genetic basis of EOCAD and may pave the way for genetic screening, early prevention, and future drug discovery for CAD in young Chinese generations.