Abstract
Risks of atherosclerotic events substantially vary even among patients with familial hypercholesterolemia (FH) with extremely high risk based on life-long exposure to high low-density lipoprotein cholesterol levels. This study aimed to examine the impact of the severe FH status defined by the International Atherosclerosis Society (IAS). Data of patients with FH (N = 1050, male = 490) who were admitted to Kanazawa University Hospital between 2000 and 2020 and who were followed up were retrospectively reviewed. The number of major adverse cardiac events (MACEs), including mortality associated with cardiovascular disease, acute coronary syndrome, and ischemic heart disease requiring coronary revascularization per 1000 person-years, was calculated. Hazard ratio was also calculated using Cox proportional model. Overall, 545 (51.9%) patients had severe FH. The median follow-up duration was 12.6 years. In total, 171 MACEs were recorded during the follow-up period. Severe FH was significantly associated with MACE (hazard ratio = 6.48, 95% confidence interval = 2.56-10.40, P = 1.2 × 10(-5)). The event rates per 1000 person-years in the primary prevention group of non-severe FH and severe FH, were 0.0 and 15.6, respectively. The event rates per 1000 person-years in the secondary prevention group of non-severe FH and severe FH, were 2.0 and 32.3, respectively. Patients with severe FH exhibited significantly higher risks in primary and secondary prevention settings. This simple criterion provides useful information for identifying patients with even higher risk who may need further management.