Inflammation, the metabolic syndrome, and risk of coronary heart disease in women and men

Abstract

Objective

This study examined whether inflammation adds to the prediction of coronary heart disease (CHD) beyond metabolic syndrome (MetS), and whether these associations differ between sexes.

Methods and results

Among 30,111 women from the Nurses’ Health Study and 16,695 men from the Health Professionals Follow-up Study without prior cardiovascular disease, 249 women and 266 men developed non-fatal myocardial infarction or fatal CHD during 8 and 6 years of follow-up, respectively. Controls were selected 2:1 within each cohort matched on age, smoking, and date of blood draw. Subjects with MetS had a significantly increased relative risk (RR) of CHD compared to individuals without MetS, and this RR was significantly higher in women (3.01; 95%-CI 1.98–4.57) than in men (1.62; 95%-CI 1.13–2.33; p interaction = 0.03). Adjustment for most inflammatory markers did not substantially attenuate the risk estimates, although the association was no longer significant in men after adjustment for CRP. Vice versa, associations of inflammatory markers with CHD risk among women were no longer significant after further adjustment for MetS. Among men, CRP and sICAM remained significant predictors of CHD independent of MetS.

Conclusions

MetS is a stronger predictor of CHD in women than in men. Most inflammatory markers did not add appreciable information beyond MetS to predict CHD; only CRP and sICAM remained independently predictive of CHD among men. The basis for these sex-based differences warrants further study.

Introduction

The metabolic syndrome (MetS) is a concept that encompasses metabolic abnormalities that tend to coexist to a greater degree than would be expected by chance alone, and which predispose individuals to an elevated risk of developing cardiovascular disease (CVD) and type 2 diabetes [1]. The National Cholesterol Education Program (NCEP) and the American Heart Association (AHA) as well as the International Diabetes Federation (IDF) have proposed algorithms to define MetS [2], [3]. These definitions agree on the essential components of MetS, namely, glucose intolerance, obesity, hypertension, and dyslipidemia [2], [3]. Inflammation – particularly elevated CRP – is also related to MetS and a risk factor for CVD [4], [5], [6], [7], [8]. However, in none of the current definitions is inflammation considered as a criterion to define MetS [2], [3], [9]. Further, a recent study suggested that the associations of CRP with factors that currently define MetS are not causal [10]. Nevertheless, results from the West of Scotland Coronary Prevention Study (WOSCOPS), the Women's Health Study (WHS), and the Framingham Offspring Study suggest that CRP is a significant predictor of coronary heart disease (CHD) even after controlling for MetS [11], [12], [13]; however, controversy remains about the magnitude of information that CRP may add for CHD prediction beyond MetS. Further, only the Framingham report included men and women, thus allowing comparisons between both sexes [13]. The aim of our study was to examine whether inflammatory markers add to the prediction of CHD beyond MetS in nested case control studies from the Nurses’ Health Study (NHS) and the Health Professionals Follow-up Study (HPFS); two well-described cohort studies of women and men. Further, we examined whether these associations differ between women and men.