Angiopoietin-like protein 4 significantly predicts future cardiovascular events in coronary patients

Abstract

Background: Angiopoietin-like protein 4 (ANGPTL4) has been associated with cardiometabolic disorders including dyslipidemia and atherosclerosis in animal studies; in humans, however, its impact on metabolic traits and cardiovascular risk remains unclear.

Methods: We examined the association of plasma ANGPTL4 levels with the metabolic syndrome (harmonized consensus definition), with angiographically determined coronary artery disease (CAD), and with the risk of future cardiovascular events in a cohort of 490 patients undergoing coronary angiography for the evaluation of stable CAD. In addition, we investigated the influence of the tagging single nucleotide polymorphisms (SNPs) rs4076317, rs2278236, rs1044250, and rs11672433 as well as variant rs116843064 (E40K) of the ANGPTL4 gene on cardiovascular risk in a larger sample of 983 angiographied coronary patients including the above mentioned 490 subjects.

Results: Plasma ANGPTL4 was significantly higher in patients with the metabolic syndrome than in subjects without the metabolic syndrome (26.0 ± 19.4 ng/ml vs. 22.2 ± 19.7 ng/ml; p = 0.008). No significant association was found between ANGPTL4 and angiographically characterized coronary atherosclerosis. Prospectively, however, plasma ANGPTL4 significantly predicted future cardiovascular events both univariately (HR1.45 [1.16-1.82], p = 0.001) and after adjustment for standard cardiovascular risk factors (1.26 [1.01-1.58]; p = 0.045). Concordantly, rs4076317, rs2278236, and rs1044250 significantly affected the risk of future cardiovascular events (adjusted HRs 0.70 [0.54-0.90]; p = 0.005, 0.76 [0.61-0.94]; p = 0.012, and 1.30 [1.03-1.62]; p = 0.025, respectively).

Conclusions: We conclude that plasma ANGPTL4 levels as well as ANGPTL4 variants significantly predict cardiovascular events independently of conventional cardiovascular risk factors.

Keywords: Angiopoietin-like protein 4; Biomarkers; Cardiovascular events; Coronary artery disease; Metabolic syndrome; Single nucleotide polymorphisms.