Cardiovascular Risk and Treatment Outcomes in Severe Hypercholesterolemia: A Nationwide Cohort Study

Background This study aimed to evaluate the cardiovascular risk and outcomes after lipid reduction in patients with severe hypercholesterolemia using a nationwide cohort. Methods and Results This study used the database from the National Health Insurance Service of Korea. Among individuals who underwent regular health examination and follow-up, 2 377 918 were enrolled and categorized into 3 groups with severe hypercholesterolemia according to low-density lipoprotein cholesterol (LDL-C) levels, namely, ≥260, 225 to 259, and 190 to 224 mg/dL groups, and a control group (<160 mg/dL). Risks of composite cardiovascular events (myocardial infarction, coronary revascularization, and ischemic stroke) and total mortality were compared. In statin new users, the outcomes after statin use were further analyzed according to posttreatment LDL-C levels. The prevalence of individuals with LDL-C≥190 mg/dL was 1 of 106. Adjusted hazard ratios of composite events and total mortality (median follow-up, 6.1 years) in the groups ranged up to 2.4 (log-rank P<0.0001) and 2.3 (log-rank P=0.0002), respectively, and were dependent on LDL-C levels. The risks of each event were up to 4.1-, 3.8-, and 1.9-fold higher, respectively, in these groups. The risk of composite events (median follow-up, 6.2 years) was lower after lipid lowering; particularly, the risk was lowest in the group showing LDL-C<100 mg/dL after treatment (hazard ratio, 0.56, log-rank P=0.043). Conclusions Using large Korean cohort data, our study proved incrementally elevated cardiovascular risk and clinical benefit associated with LDL-C<100 mg/dL in individuals with severe hypercholesterolemia. These results support aggressive lipid lowering and provide evidence for the LDL-C target in this population.