Lp (a) >50 mg/dl predicts atherosclerotic cardiovascular events in patients with heterozygous familial hypercholesterolemia who achieved LDL-C <2.6 mmol/l

Abstract

Abstract Introduction Lipoprotein (a) [Lp (a)] is a plasma lipoprotein which exhibits atherogenic properties. Lp(a) ≥50 mg/dl has been recently shown to associate with a risk of atherosclerotic cardiovascular diseases (ASCVD) in patients with heterozygous familial hypercholesterolemia (HeFH). While current guideline recommends lowering LDL-C as a first-line therapeutic approach in HeFH subjects, it remains to be fully determined whether an elevated level of Lp(a) confers additional ASCVD risks in HeFH patients who achieved a lower LDL-C level. Purpose To investigate cardiovascular outcomes in HeFH subjects with a lower LDL-C but an elevated Lp(a) levels. Methods 182 HeFH patients with on-treatment LDL-C <2.6 mmol/l under lipid-lowering therapies were analyzed. Clinical characteristics and MACE (= a composite of all-cause death, ACS, stroke, PAD and coronary revascularization) were compared in HeFH subjects with Lp(a) ≥ vs. <50 mg/dl. Results The averaged LDL-C and Lp (a) levels were 1.9 mmol/l and 26.8 mg/dl, respectively. 19.2% of study subjects exhibited Lp(a)≥50 mg/dl. HeFH patients with Lp(a) ≥50 mg/dl were more likely to be older and have a history of hypertension, but these comparisons did not meet statistical significance. There was no significant difference in on-treatment LDL-C, HDL-C and Triglyceride level (Table). However, during the observational period (median=4.7 years), there was a 2.7-fold (95% CI, 1.41–5.02; p=0.004) greater likelihood of experiencing MACE in subjects with Lp(a) ≥50 mg/dl (picture). Even after adjusting clinical demographics, Lp(a) ≥50 mg/dl remained an independent predictor for the occurrence of MACE (hazard ratio=2.53, 95% CI: 1.29–4.82, p<0.001). Conclusions Despite achieving on-treatment LDL-C <2.6 mmol/l, an elevated risk of MACE was observed in HeFH patients with Lp(a) ≥50 mg/dl. Our findings suggest an increased level of Lp(a) as a risk stratification marker and a potential therapeutic target in patients with HeFH. Clinical outcome Funding Acknowledgement Type of funding source: None