Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

Abstract

Objective— Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. Approach and Results— This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene ( LPA ) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter ( P <0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. Conclusions— Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

Prevention of cardiovascular complications in patients with Lp(a)-hyperlipoproteinemia and progressive cardiovascular disease by long-term lipoprotein apheresis according to German national guidelines

“…Careful consideration of the entire clinical course after diagnosis of CVD is mandatory. In Pro(a)LiFe patients it took a median period of 4.7 years before patients were recognized to have Lp(a)-HLP associated progressive CVD, and LA was initiated [1]. …”

“…All elements of the prospective analysis were conceived before the study was executed, including the design of the research plan, and selection of the appropriate LA patient population. Comparison of the incidence of cardiovascular events in patients with Lp(a)-HLP and progressive CVD with a pre-defined uniform observation period retrospectively 2 years before and prospectively 5 years after commencing chronic LA was posed as endpoint [1, 5]. …”

Genetics of Dyslipidemia and Ischemic Heart Disease

“…Agents that target apo(a) synthesis have been suggested (aspirin, estrogen, and antisense oligonucleotides) [61]. Apheresis of Lp(a) can acutely lower Lp(a) levels [62]. PCSK9 inhibitors also can lower Lp(a) levels [63].…”

Lipid Biomarkers for Risk Assessment in Acute Coronary Syndromes

“…However, two recent observational studies have hinted that Lp(a) lowering by apheresis may lower events [30,33]. The newest lipid-improving treatment phenom, PCSK9 inhibitors, also shows promise.…”