Increased Risk for PAD for Women with Metabolic Syndrome

David Conen, MD, MPH, from the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, writes that, MetS is associated with incident myocardial infarction and stroke and is linked with subclinical inflammation. "However, prospective data pertaining to MetS and future...PAD are sparse with few studies examining the role of inflammation. We therefore evaluated the relationship between MetS, inflammation, and incident PAD."

The study cohort consisted of 27,111 women who had no cardiovascular disease at baseline and who were enrolled in the Women's Health Study. During follow-up (median duration, 13.3 years), 114 women went on to have incident symptomatic PAD. Risk for PAD among women with and without MetS was compared with use of Cox proportional hazards models.

To determine associations between MetS and subclinical inflammation, the investigators measured high-sensitivity C-reactive protein (hsCRP) and soluble intercellular adhesion molecule-1 (sICAM-1) and used multivariable models to adjust for these biomarkers.

Risk for future PAD was increased by 62% in women with MetS (hazard ratio [HR], 1.62; 95% confidence interval [CI], 1.10 - 2.38). MetS remained significantly associated with PAD after multivariable adjustment (adjusted HR, 1.48; 95% CI, 1.01 - 2.18). For each additional MetS-defining trait (abdominal obesity, high blood pressure, low high-density lipoprotein cholesterol levels, high triglyceride levels, and abnormal glucose metabolism), there was a 21% increase in risk (adjusted HR, 1.21; 95% CI, 1.06 - 1.39).

Median levels of hsCRP were 4.0 mg/L in women with MetS and 1.5 mg/L (P < .0001) in women without MetS (P < .0001). For sICAM-1, levels were 374 ng/mL and 333 ng/mL, respectively. The risk associated with MetS was markedly decreased and was no longer significant when hsCRP and sICAM-1 were added to multivariable models (HR, 1.14; 95% CI, 0.75 - 1.73).

"MetS is associated with an increased risk of future symptomatic PAD in women," the study authors write. "This risk appears largely mediated by the effects of inflammation and endothelial activation."

Limitations of this study include a study cohort of women who are of predominantly Caucasian origin, limiting generalizability, and exclusion of subclinical PAD. In addition, this analysis used a modified version of the official Adult Treatment Panel III MetS definition.

"Prospective data from other cohorts are greatly needed not only to corroborate our results but also to further elucidate mechanistic links between risk factor clustering and onset of this disease," the study authors conclude.