【論文摘要】FH Management in Korea

Soo Lim

《海峽循環醫學雜誌》 1卷2S期 (2019/09) Pp. 25-25

https://doi.org/10.6907/SCJ.201909/SP_1(2).0020

摘要

Heterozygous familial hypercholesterolemia (heFH) is a common genetic disease of autosomal dominant status and is a global health problem. In Western surveys it has been known as one frequency per 500 population, but in recent studies it is reported that there is one per 217-250 people. The most common causative gene is the LDLR gene, rarely caused by PCSK9 or apoB gene mutations. The risk of cardiovascular disease is significantly higher in patients with heFH because they are exposed to high-density lipoprotein-cholesterol (LDL-C). HeFH is reported to cause early cardiovascular disease in 50% of men and 25% of women without treatment, and cardiovascular relative risk is as high as 3.5-16 times. Therefore, it is very important to properly diagnose the patient early and prevent vascular complications. (1) Diagnosis A man ＜50 years or a woman ＜60 year who has early coronary artery disease or family history of FH can be suspected to have heFH. At this time, it is necessary to confirm that there is no cause of secondary hypercholesterolemia. Diagnosis of heFH can be based on clinical criteria or DNA mutation. In Korea, the criteria for clinical diagnosis, such as Simon Broome criteria, Dutch criteria, and the criteria for Make Early Diagnosis to Prevent Early Death (MEDPED) are used to diagnose heFH. In a study of Korean heterozygous familial hypercholesterolemia, we have suggested an LDL cholesterol level of more than 225 mg/dL, which is appropriate for predicting related gene mutation patients. Because heFH is a high-risk group for coronary artery disease, it is not appropriate to perform risk calculations with general cardiovascular risk calculations. (2) Treatment ① General principle Management in heFH includes lifestyle correction, lipid-lowering regimens, and tests for atherosclerotic cardiovascular disease (ASCVD). Diet management and smoking cessation are important for lifestyle correction. Medication is also actively needed. When deciding on medication, consideration should also be given to concomitant medication, concomitant diseases, side effects, and to inform the patient or caregiver that medication should be lifelong. ② Target of treatment The first goal of treatment in heFH is to lower LDL cholesterol by over 50% using statins. Thereafter, the goal is LDL-cholesterol (LDL-C) ＜100 mg/dL (without coronary artery disease or other major risk factors) or ＜70 mg/dL (with coronary artery disease or other major risk factors). As this approach is difficult to achieve with many heFH patients, lowering LDL-C to the lowest possible level (especially in high-risk patients) is a realistic therapeutic goal. ③ Therapeutic drugs Using statins as the primary drug, it is recommended to try to reach the LDL-C target. Next, ezetimibe can be added as a secondary drug if the target is not reached. Many patients with heFH may not achieve the goal with statin-ezetimibe combination therapy. In these patients, bile acid sequestrants (cholestyramine) or PCSK9 inhibitors can be used as a tertiary drug. In particular, the PCSK9 inhibitor is recommended to patients with ASCVD, patients with LDL-C ＞180 mg/dL even without ASCVD even after the highest dose of statin-ezetimibe combination, and patients with LDL-C ＞140 mg/dL with multiple ASCVD risk factors even after the highest dose of statin-ezetimibe combination. When there is side effect of statin, it is possible to use secondary drug or tertiary drug instead of statin.