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.

Figure 1

Multivariable adjusted RR of CHD in women (Panel a) and men (Panel b) with MetS as compared to their counterparts without MetS (=reference group) with and without further adjustment for inflammatory markers. Dots indicate RRs; lines indicate 95%-confidence intervals. Each dot represents a separate model adjusted for age, smoking status, date of blood draw, parental history of CHD before age 60, alcohol consumption, and physical activity, with without further adjustment for the inflammatory marker(s) listed on the x-axis. In women additionally adjusted for fasting status, and HRT use. Note that RRs are plotted on a logarithmic scale.

Figure 1

Multivariable adjusted RR of CHD in women (Panel a) and men (Panel b) with MetS as compared to their counterparts without MetS (=reference group) with and without further adjustment for inflammatory markers. Dots indicate RRs; lines indicate 95%-confidence intervals. Each dot represents a separate model adjusted for age, smoking status, date of blood draw, parental history of CHD before age 60, alcohol consumption, and physical activity, with without further adjustment for the inflammatory marker(s) listed on the x-axis. In women additionally adjusted for fasting status, and HRT use. Note that RRs are plotted on a logarithmic scale.

Figure 2

Multivariable adjusted RR of CHD in women (Panel a) and men (Panel b) according to categories of CRP and presence or absence of MetS. Dots indicate RR; lines indicate 95%-confidence intervals. Subjects without MetS and CRP levels <1 mg/L were used as the reference category. Models adjusted for age, smoking status, date of blood draw, parental history of CHD before age 60, alcohol consumption, and physical activity. In women additionally adjusted for fasting status, and HRT use. Note that RRs are plotted on a logarithmic scale. *The upper boundary of the 95%-confidence interval for the RR of women with MetS and CRP levels <1 mg/L was 15.85.

Figure 2

Multivariable adjusted RR of CHD in women (Panel a) and men (Panel b) according to categories of CRP and presence or absence of MetS. Dots indicate RR; lines indicate 95%-confidence intervals. Subjects without MetS and CRP levels <1 mg/L were used as the reference category. Models adjusted for age, smoking status, date of blood draw, parental history of CHD before age 60, alcohol consumption, and physical activity. In women additionally adjusted for fasting status, and HRT use. Note that RRs are plotted on a logarithmic scale. *The upper boundary of the 95%-confidence interval for the RR of women with MetS and CRP levels <1 mg/L was 15.85.