4944The contribution of familial hypercholesterolemia (FH) to premature coronary artery disease decreased by 2-fold between 1998 and 2018 in a founder population with high prevalence of FH

Background Familial hypercholesterolemia (FH) is an autosomal dominant trait associated with high risk of premature coronary artery disease (CAD). The worldwide prevalence of FH is estimated at 1:250 to 1:500. In certain populations, including French Canadians (FC), the prevalence is significantly higher however. From 1995 to 1998, FH contributed to 9.6% of angiographically proven CAD in a FC founder population, the burden being the highest in men aged <50 years (20.6%). In the past 2 decades, powerful statins, ezetimibe and other low-density lipoprotein-Cholesterol (LDL-C) modulators, such as PCSK9 inhibitors, have been progressively introduced and several FH diagnosis scoring systems or guidelines have been developed and disseminated in order to facilitate FH recognition and management. The impact of these measures on the FH burden is however not documented. Purpose To compare the burden of FH twenty years apart in FC patients hospitalized for CAD. Methods Lipid profiles, cardiovascular risk factors and FH status of 1,132 FC patients who were hospitalized for a CAD event and who consecutively attended the cardiovascular disease clinic in 2017 and 2018 were compared to those of 2,506 who consecutively presented angiographically proven CAD two decades ago. FH status was based on Simon Broome and FH Canada definitions. In 1998, all consenting CAD patients were also molecularly screened for the most prevalent FH causing mutations in FC. Comparisons between groups were performed using Chi-square and independent samples Student's t-test. Results Most patients in both cohorts were males (74.5% vs 73.9% in 1998 vs. 2018, respectively). At admission, mean LDL-C (± SD) was 3.99±1.67 in 1998 vs. 2.22±1.06 in 2018 (p<0.001). The proportion of patients who were treated with a statin or another lipid lowering agent was 32.9% in 1998 compared to 67.6% in 2018 (p<0.001) and the drug regimen was also significantly different. In 1998, 24.6% of patients had LDL-C >5.0 mmol/L at admission compared to 4.2% in 2018. Definite FH was diagnosed in 9.6% of patients in the 1998 cohort compared to 4.7% in the 2018 cohort (p<0.001). FH patients hospitalized for CAD were significantly older in 2018 than in 1998 (56.3±11.3 vs. 49.2±10.9 in men, p=0.001; 61.1±11.8 vs. 53.2±12.3 in women, p=0.02). In the same period, the relative burden of diabetes and other lipid disorders, including high-density lipoprotein dysmetabolism significantly increased (p<0.001). Conclusions Over a period of 20 years, in a founder population with a high prevalence of FH, the contribution of FH to hospitalizations for CAD decreased by 2-fold and affected patients now tend to be hospitalized at an older age than 2 decades ago. This suggests that early diagnosis and more effective management of FH in the last 2 decades have contributed to significantly decrease its burden. Acknowledgement/Funding ECOGENE-21, Amgen, Sanofi