SCREENING FOR INHERITED DYSLIPIDEMIAS AND SUBCLINICAL ATHEROSCLEROSIS IN FIRST DEGREE RELATIVES OF PATIENTS WITH PREMATURE CORONARY ARTERY DISEASE: DIAGNOSTIC YIELD AND IMPACT ON PATIENTS MANAGEMENT

Abstract

BACKGROUND The screening of first-degree relatives (FDR) of patients with premature atherosclerotic cardiovascular disease (ASCVD) is recommended due to its high heritability. However, in practice such screening is not routinely performed, and the diagnostic yield of different approaches to screening and its impact on patient management is unknown. METHODS AND RESULTS We recruited FDRs of patients who presented with angiographically-confirmed ASCVD with stenosis of ≥ 50% of an epicardial coronary artery at the age of ≤ 50 years for males and ≤ 55 years for females. FDRs with no personal history of ASCVD underwent clinical assessment of cardiovascular risk and presence of inherited dyslipidemias, including familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), and elevated lipoprotein(a); and radiological testing for subclinical atherosclerosis (Figure 1). We enrolled 220 FDRs between 2017 and 2020, of which 129 completed clinical assessment (Figure 1). Of these, 28 had a personal history of ASCVD and 101 completed the full assessment. Patient characteristics are shown in Table 1. Based on the evaluation with modified FRS calculator and presence of statin-indicated conditions, 39.6% and 14.9% of patients were placed in high and moderate risk groups, respectively. In total, 24.1% of FDRs had an inherited dyslipidemias: 8.9% met clinical criteria for FH, 5.9% for FCHL, and 8.9% had lipoprotein(a) ≥ 500 mg/L. Of these, 22.2%, 40.0%, and 66.7%, respectively, had relatives with premature ASCVD with the same type of dyslipidemia. Subclinical atherosclerosis was detected in 43.6% of FDRs, and in 57.7% of those over 40 years of age. The diagnostic yield of each imaging modality was 29.6% for carotid ultrasound, 37.8% for cardiac CT and 61.1% for calcium scoring. Imaging led to upwards risk reclassification of 13.9% (Table 1). Based on this screening, lipid-lowering therapy was initiated in 29.7% of FDRs, and treatment was intensified in an additional 13.8%, while 7.9% had no change to treatment and 43.6% received therapeutic lifestyle change counselling. CONCLUSION A combination of clinical screening and non-invasive imaging identified the presence of an inherited dyslipidemia in one-quarter of FDRs of patients with premature ASCVD, and detected subclinical atherosclerosis in more than 40%. These findings led to treatment changes in more than 40% of these FDRs. These findings suggest that this screening approach may improve risk management in this population. The screening of first-degree relatives (FDR) of patients with premature atherosclerotic cardiovascular disease (ASCVD) is recommended due to its high heritability. However, in practice such screening is not routinely performed, and the diagnostic yield of different approaches to screening and its impact on patient management is unknown. We recruited FDRs of patients who presented with angiographically-confirmed ASCVD with stenosis of ≥ 50% of an epicardial coronary artery at the age of ≤ 50 years for males and ≤ 55 years for females. FDRs with no personal history of ASCVD underwent clinical assessment of cardiovascular risk and presence of inherited dyslipidemias, including familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), and elevated lipoprotein(a); and radiological testing for subclinical atherosclerosis (Figure 1). We enrolled 220 FDRs between 2017 and 2020, of which 129 completed clinical assessment (Figure 1). Of these, 28 had a personal history of ASCVD and 101 completed the full assessment. Patient characteristics are shown in Table 1. Based on the evaluation with modified FRS calculator and presence of statin-indicated conditions, 39.6% and 14.9% of patients were placed in high and moderate risk groups, respectively. In total, 24.1% of FDRs had an inherited dyslipidemias: 8.9% met clinical criteria for FH, 5.9% for FCHL, and 8.9% had lipoprotein(a) ≥ 500 mg/L. Of these, 22.2%, 40.0%, and 66.7%, respectively, had relatives with premature ASCVD with the same type of dyslipidemia. Subclinical atherosclerosis was detected in 43.6% of FDRs, and in 57.7% of those over 40 years of age. The diagnostic yield of each imaging modality was 29.6% for carotid ultrasound, 37.8% for cardiac CT and 61.1% for calcium scoring. Imaging led to upwards risk reclassification of 13.9% (Table 1). Based on this screening, lipid-lowering therapy was initiated in 29.7% of FDRs, and treatment was intensified in an additional 13.8%, while 7.9% had no change to treatment and 43.6% received therapeutic lifestyle change counselling. A combination of clinical screening and non-invasive imaging identified the presence of an inherited dyslipidemia in one-quarter of FDRs of patients with premature ASCVD, and detected subclinical atherosclerosis in more than 40%. These findings led to treatment changes in more than 40% of these FDRs. These findings suggest that this screening approach may improve risk management in this population.