Serum Angiopoietin-Like Protein 2 Is a Novel Risk Factor for Cardiovascular Disease in the Community

Jun Hata, Naoko Mukai, Masaharu Nagata, Tomoyuki Ohara, Daigo Yoshida, Hiro Kishimoto, Mao Shibata, Yoichiro Hirakawa, Motoyoshi Endo, Tetsuro Ago, Takanari Kitazono, Yuichi Oike, Yutaka Kiyohara, Toshiharu Ninomiya

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)


Objective - Angiopoietin-like protein 2 (ANGPTL2), a proinflammatory mediator, has been reported to accelerate the development of insulin resistance, endothelial dysfunction, and atherosclerosis in mice. However, no cohort studies have examined the relationship between serum ANGPTL2 levels and the development of cardiovascular disease (CVD) in a general population. Approach and Results - A total of 3005 community-dwelling Japanese aged ≥40 years without a history of CVD were divided into 4 groups according to the quartiles of serum ANGPTL2 concentrations (Q1, lowest and Q4, highest) and followed up for 10 years. The hazards ratios and their 95% confidence intervals for the development of CVD (coronary heart disease or stroke) were estimated using a Cox proportional hazards model. During the follow-up, 219 first-ever CVD events were observed. The risk of CVD increased significantly with elevating ANGPTL2 levels after adjustment for age, sex, serum total cholesterol, use of lipid-lowering agents, ECG abnormalities, smoking habits, alcohol intake, and regular exercise (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.27 [0.80-2.04]; Q3, 1.48 [0.95-2.32]; and Q4, 1.85 [1.20-2.85]; P=0.003 for trend). After additional adjustment for metabolic syndrome components and serum high-sensitivity C-reactive protein levels as an inflammatory marker, the association was attenuated but remained significant (hazards ratios [95% confidence interval], Q1, 1.00 [reference]; Q2, 1.21 [0.76-1.94]; Q3, 1.38 [0.87-2.17]; and Q4, 1.66 [1.05-2.60]; P=0.02 for trend). Conclusions - Our findings suggest that elevated serum ANGPTL2 levels are a novel risk factor for the development of CVD in the general population. This association is partially mediated by metabolic disorders and inflammation.

Original languageEnglish
Pages (from-to)1686-1691
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number8
Publication statusPublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine


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