October 18, 2018
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Lp(a) levels strongly correlated with CVD risk

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In a meta-analysis of patients treated with statins, pretreatment and on-treatment levels of lipoprotein(a) “showed an independent approximately linear relation with cardiovascular disease risk,” researchers wrote in The Lancet.

The researchers analyzed 29,069 patients (mean age, 62 years; 28% women) from seven randomized statin outcomes trials who had repeat Lp(a) measurements.

HRs for CV events, defined as fatal or nonfatal CHD, stroke or revascularization procedures, were calculated for patients stratified by Lp(a) levels: less than 15 mg/dL (reference group): 15 mg/dL to less than 30 mg/dL; 30 mg/dL to less than 50 mg/dL; and 50 mg/dL or more.

Among the cohort, statin therapy reduced LDL by a mean of 39% (95% CI, –43 to –35) but did not significantly affect Lp(a) levels, Peter Willeit, MD, from the department of neurology, Medical University of Innsbruck, Austria, and colleagues wrote.

Linear relationship

Increased CV event risk occurred starting at baseline Lp(a) levels of 30 mg/dL and on-treatment Lp(a) levels of 50 mg/dL, the researchers wrote.

After adjustment for age and sex, compared with the baseline Lp(a) less than 15 mg/dL group, HRs for CV events were 1.04 (95% CI, 0.91-1.18) for the 15 mg/dL to less than 30 mg/dL group, 1.11 (95% CI, 1-1.22) for the 30 mg/dL to less than 50 mg/dL group and 1.31 (95% CI, 1.08-1.58) for the 50 mg/dL or more group, according to the researchers.

When stratified by on-statin Lp(a), HRs for CV events compared with the on-treatment Lp(a) less than 15 mg/dL group were 0.94 (95% CI, 0.81-1.1) for the 15 mg/dL to less than 30 mg/dL group, 1.06 (95% CI, 0.94-1.21) for the 30 mg/dL to less than 50 mg/dL group and 1.43 (95% CI, 1.15-1.76) for the 50 mg/dL or more group, Willeit and colleagues wrote.

Further adjustment for previous CVD, diabetes, smoking, systolic BP, LDL and HDL did not change the results.

The association of on-statin Lp(a) with CV events was stronger than that of on-placebo Lp(a) (P for interaction = .01) and was more prominent in younger patients (P for interaction = .008), according to the researchers.

“This study provides a rationale for testing the lipoprotein(a)-lowering hypothesis in cardiovascular disease outcomes trials,” Willeit and colleagues wrote.

A final frontier

In a related editorial, Gerald F. Watts, MD, DSc, from the School of Medicine, Faculty of Health and Medical Sciences, University of Western Australia, Perth, and the Lipid Disorders Clinic, department of cardiology, Royal Perth Hospital, and Michael B. Boffa, PhD, from the department of biochemistry and Robarts Research Institute, Schulich School of Medicine & Dentistry, University of Western Ontario in Canada, wrote that “lipoprotein(a) is one of the final frontiers for resolving residual risk for atherosclerotic cardiovascular disease.”

“The definitive test of the lipoprotein(a) hypothesis relies on the future application of potent RNA-based therapies that can specifically lower lipoprotein(a),” they wrote. “The present study by Willeit and colleagues provides a rationale for clinical outcome trials, particularly in high-risk patients with lipoprotein(a) concentrations of 50 mg/dL or higher receiving optimum LDL cholesterol-lowering therapy, but the required level of reduction of lipoprotein(a) and the corresponding anticipated effect size on atherosclerotic cardiovascular events remain to be defined precisely.” – by Erik Swain

Disclosures: Boffa reports he has a research contract with Ionis. Watts reports he serves on advisory boards for Amgen, Gemphire, Regeneron and Sanofi and has research contracts with Amgen, Regeneron and Sanofi. Willeit reports he received consultant fees from Novartis and travel reimbursement from Bayer, Daiichi Sankyo and Sanofi Aventis. Please see the study for all other authors’ relevant financial disclosures.