Rational and design of the FAMILY study - High-risk coronary atherosclerosis among asymptomatic subjects with family history of myocardial infarction.

INTRODUCTION: A family history (FH) of premature coronary artery disease (CAD) is a major cardiovascular risk factor often underestimated by traditional scoring systems like SCORE2, which do not incorporate FH. The FAMILY trial (NCT07352111) is a prospective study investigating the role of cardiac CT (CCT) in identifying high-risk atherosclerosis in this specific population. RATIONAL AND OBJECTIVES: To enable personalized primary prevention, this study integrates genotypic and bio-humoral profiling with CCT plaque imaging in asymptomatic individuals with an FH of CAD. The primary objective of the study is to determine the prevalence of high-risk atherosclerosis in this specific cohort. METHODS: and Preliminary Data: We are prospectively enrolling asymptomatic first-degree relatives of patients with early-onset myocardial infarction (males <55, females <60 years). Participants undergo clinical evaluation, SCORE2 risk calculation, and advanced 256-slice CCT. High-risk atherosclerosis is defined by the presence of at least two high-risk plaque features and/or elevated volumes of low-attenuation/non-calcified plaque. A nested cohort (10-20%) of risk-reclassified patients will undergo comprehensive genetic profiling. Preliminary, data on the first 16 subjects enrolled (mean age 54 ± 6 years) were collected and analysed supporting the feasibility of the study. CONCLUSION: Traditional risk scores often underestimate CAD risk in individuals with a strong family history. By utilizing advanced CCT to detect high-risk atherosclerosis, the FAMILY trial aims to accurately reclassify patient risk and, potentially, guide early, targeted prevention. Feasibility data are presented but, given the limited size of this preliminary cohort, definitive conclusions await full enrolment.