Carbohydrate & Lipid Metabolism Research Unit, Department of Medicine, University of the Witwatersrand, Johannesburg, South Africa.
Circulation. 2011 Nov 15;124(20):2202-7. doi: 10.1161/CIRCULATIONAHA.111.042523. Epub 2011 Oct 10.
Homozygous familial hypercholesterolemia is an inherited disorder caused by mutations in both low-density lipoprotein receptor alleles, which results in extremely elevated plasma low-density lipoprotein cholesterol concentrations and very early morbidity and mortality due to cardiovascular disease.
To evaluate the impact of advances in lipid-lowering (predominantly statin) therapy on cardiovascular disease morbidity and mortality in a large cohort of patients with homozygous familial hypercholesterolemia, the records of 149 patients (81 females, 68 males) from 2 specialized lipid clinics in South Africa were evaluated retrospectively. Homozygous familial hypercholesterolemia was diagnosed by confirmation of mutations in genes affecting low-density lipoprotein cholesterol or by clinical criteria. A Cox proportional hazard model with time-varying exposure was used to estimate the risk of death and major adverse cardiovascular events among statin-treated patients compared with statin-naive patients. The hazard ratio for benefit from lipid therapy, calculated with the Cox proportional hazards model for the end point of death, was 0.34 (95% confidence interval 0.14-0.86; P=0.02), and for the end point of major adverse cardiovascular events, it was 0.49 (95% confidence interval 0.22-1.07; P=0.07). This occurred despite a mean reduction in low-density lipoprotein cholesterol of only 26.4% (from 15.9±3.9 to 11.7±3.4 mmol/L; P<0.0001) with lipid-lowering therapy.
Lipid-lowering therapy is associated with delayed cardiovascular events and prolonged survival in patients with homozygous familial hypercholesterolemia.
家族性高胆固醇血症是一种由低密度脂蛋白受体等位基因的突变引起的遗传性疾病，导致血浆低密度脂蛋白胆固醇浓度极高，以及心血管疾病导致的极早发病和死亡。
为了评估降脂治疗（主要是他汀类药物）对南非 2 个专门的脂质诊所的 149 名患者（81 名女性，68 名男性）的大队列中家族性高胆固醇血症患者的心血管疾病发病率和死亡率的影响，回顾性评估了这些患者的记录。家族性高胆固醇血症通过确认影响低密度脂蛋白胆固醇的基因的突变或通过临床标准来诊断。使用具有时间变化暴露的 Cox 比例风险模型来估计他汀类药物治疗患者与他汀类药物未治疗患者之间的死亡和主要不良心血管事件的风险。使用 Cox 比例风险模型计算的血脂治疗获益的风险比，终点为死亡，为 0.34（95%置信区间为 0.14-0.86；P=0.02），终点为主要不良心血管事件，为 0.49（95%置信区间为 0.22-1.07；P=0.07）。尽管降脂治疗后低密度脂蛋白胆固醇平均降低仅 26.4%（从 15.9±3.9 降至 11.7±3.4 mmol/L；P<0.0001），但仍有这种获益。
降脂治疗与家族性高胆固醇血症患者的心血管事件延迟和生存延长相关。
