The association between circulating endostatin levels and incident myocardial infarction

Toralph Ruge,Axel C Carlsson,Jan-Håkan Jansson,Stefan Söderberg,Anders Larsson,Johan Ärnlöv

doi:10.1080/14017431.2018.1547839

Abstract

Objective. Increased levels of circulating endostatin have been observed in patients with prevalent ischemic heart disease. However, the association between circulating endostatin, and incident myocardial infarction (MI) is less studied. Our main aim was to study the association between circulating endostatin and incident MI in the community adjusted for established cardiovascular risk factors in men and women. Design. Circulating endostatin was measured in a nested case control study based on three large community-based Swedish cohorts, including 533 MI cases, and 1003 age-, sex- and cohort-matched controls. Odds ratios (OR) with 95% confidence intervals (CI) were calculated with adjustments for established cardiovascular risk factors. Results. Higher endostatin was associated with a higher incidence of MI independently of established cardiovascular risk factors (OR 1.19, 95% CI 1.03–1.37, p = .02), but this association was abolished after additional adjustment for C-reactive protein. Sex-stratified analyses suggest that the association was substantially stronger in women as compared to men. Conclusions. In our community based sample, higher endostatin predicted incident myocardial infarction predominantly in women but not independently of CRP. Thus, our findings do not support a broad utility of endostatin measurements for the prediction of incident myocardial infarction in clinical practice.

Highlights

Collagen XVIII is a major component of the basal membranes and cleavage of collagen XVIII during extra cellular matrix remodelling increases the levels of endostatin, a biologically active fragment with anti-angiogenic and antifibrotic activity [1]
Experimental studies suggest a causal role for endostatin in the development of atherosclerosis [3,4] and previous clinical studies have shown that patients with prevalent atherosclerotic disease portray elevated circulating endostatin levels [5–7]
The Odds ratios (OR) estimates for the crude association between endostatin and outcome were similar when the three cohorts were investigated separately (VIP 1.44, 95% confidence intervals (CI) 1.25–1.66, MONICA 1.54, 95% CI 0.90–2.65, and Mammary Screening Program (MSP) 1.91 95% CI 1.31–2.80)

Summary

Introduction

Collagen XVIII is a major component of the basal membranes and cleavage of collagen XVIII during extra cellular matrix remodelling increases the levels of endostatin, a biologically active fragment with anti-angiogenic and antifibrotic activity [1]. Endostatin has been thoroughly studied in the field of malignant diseases, and the circulating levels have been suggested to reflect extra cellular matrix turnover in patients with malignant diseases [2]. Experimental studies suggest a causal role for endostatin in the development of atherosclerosis [3,4] and previous clinical studies have shown that patients with prevalent atherosclerotic disease portray elevated circulating endostatin levels [5–7]. We hypothesized that elevated levels of endostatin are causally involved in the development of MI. We investigated the association between endostatin and incident MI in a nested case control analyses in three large community-based cohorts, with prespecified stratified analyses in men and women

Methods

Results

Conclusion