Clinical and radiological testing for subclinical atherosclerosis in first-degree relatives of patients with premature coronary artery disease: feasibility and diagnostic yield

Abstract Background Premature atherosclerotic cardiovascular disease (ASCVD) is highly heritable. The screening of first-degree relatives (FDR) of patients with premature ASCVD is recommended but not routinely performed, and the diagnostic yield of different approaches to such screening is unknown. Purpose To determine the feasibility and diagnostic yield of clinical and radiological screening of FDRs of patients with premature coronary artery disease (CAD) in clinical setting. Method We recruited FDRs of patients with angiographically-proven CAD with stenosis of ≥50% who presented at the age of ≤50 years for males and ≤55 years for females. After clinical and laboratory assessment, patients with no personal history of cardiovascular disease underwent either coronary computed tomography angiography (CCTA), coronary calcium scoring assessment (CAC), or carotid ultrasound (CUS). Subclinical atherosclerosis was defined as 1) CAC score >100 Agatston units or >75% percentile for age and sex; 2) Stenosis >50% in at least one coronary artery or segment involvement scores >50th percentile in males and >75th in females; or, 3) Carotid plaque on ultrasonography. Results We enrolled 220 FDRs between 2017 and 2020, 129 completed clinical assessment (Figure 1). Of them, 28 (21.7%) had a personal history of ASCVD and 101 were tested for subclinical atherosclerosis. The characteristics of these patients are shown in Table 1. The most prevalent cardiovascular risk factors were dyslipidemia (40.6%), hypertension (22.8%), and obesity (21.8%). When assessed with the Framingham risk score calculator without adjustment for family history, only 5.1% and 28.6%, of patients had high or moderate cardiovascular risk, respectively. After adjusting for family history and the presence of statin-indicated conditions, 39.6% and 14.9% of patients were placed in high and moderate risk groups, respectively. Subclinical atherosclerosis was found in 43.6% of all patients (Figure 1) and 57.7% of patients over 40 years of age. The diagnostic yield of procedures was 29.6% for CUS, 37.8% for CCTA and 61.1% for CAC scoring. After the radiological assessment, 13.9% of patients were reclassified to a higher risk group (Table 1). Conclusion Non-invasive cardiovascular imaging detected subclinical atherosclerosis in 43.6% of healthy patients with a family history of premature ASCVD, moving 1 in 7 patients to a higher risk group and suggesting that this screening approach may improve risk prediction in this population. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Canadian Institutes of Health Research.St. Paul's Hospital Foundation and the Vancouver General Hospital Foundation. Figure 1Table 1

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