Interleukin-1 genotypes modulate the long-term effect of lipoprotein(a) on cardiovascular events: The Ioannina Study.

Abstract

BACKGROUND:

Lipoprotein(a) [Lp(a)] is a genetic risk factor for cardiovascular disease (CVD), and proinflammatory interleukin-1 (IL-1) genotypes may influence Lp(a)-mediated CVD events. The genotype IL-1(+) is associated with higher rates of inflammation than IL-1(-) genotype. Targeting IL-1β was recently shown to decrease CVD events independent of low-density lipoprotein-cholesterol levels.

OBJECTIVE:

The objective of the study is to assess the modulatory effect of IL-1 genotypes on risk mediated by Lp(a) METHODS: We assessed whether IL-1 genotypes modulate the effect of Lp(a) on major adverse cardiovascular events (cardiovascular death, myocardial infarction, and stroke/transient ischemic attack) and angiographically determined coronary artery disease (CAD). IL-1 genotypes and Lp(a) were measured in 603 patients without diabetes mellitus undergoing angiography. Major adverse cardiovascular events and CAD were assessed over a median of 45 months.

RESULTS:

In multivariable-adjusted analysis, Lp(a) was associated with major adverse cardiovascular events (hazard ratio [HR] [95% confidence interval {CI}]: 2.95 [1.16-7.54], P = .023) and CAD (odds ratio [OR] [95% CI]: 1.84 [1.12-3.03], P = .016) comparing quartile 4 vs quartile 1. In Cox regression analysis, IL-1(+) patients with Lp(a) above the median (>9.2 mg/dL) had a worse event-free cumulative survival (HR [95% CI]: 3.59 [1.07-12.03], P = .039) compared to IL-1(-) patients with Lp(a) below the median. In IL-1(+) patients aged ≤60 years, Lp(a) was also associated with angiographically determined CAD (OR [95% CI]: 2.90 [1.07-7.86], P = .036) comparing quartile 4 vs quartile 1 but not IL-1(-) patients.

CONCLUSION:

Proinflammatory IL-1(+) genotypes modulate the risk of Lp(a) long-term CVD events and CAD. These data suggest that the dual genetic contributions of elevated Lp(a) levels and IL-1(+) genotypes may identify younger subjects at particularly high risk for CVD events.

• Authors: Katerina K Naka, Aris Bechlioullis, Aikaterini Marini, Dimitrios Sionis, Konstantinos Vakalis, Georgios Triantis, Leon Wilkins, John Rogus, Kenneth S Kornman, Joseph L Witztum, Lynn Doucette-Stamm, Lampros K Michalis, Sotirios Tsimikas
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2018 Mar - Apr Vol. 12 Issue 2 Pg. 338-347 ISSN: 1933-2874 [Print] United States
• PMID: 29310992 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Interleukin-1
• Lipoprotein(a)

Topics

• Aged
• Biomarkers (metabolism)
• Cardiovascular Diseases (diagnosis, genetics)
• Coronary Artery Disease (diagnosis, genetics)
• Female
• Genotype
• Humans
• Interleukin-1 (genetics)
• Lipoprotein(a) (genetics)
• Logistic Models
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Prospective Studies
• Risk Factors
• Time Factors