國家心臟、肺臟、與血液機構；國家癌症機構；Donald W. Reynolds基金會贊助這項研究。Conen博士接受瑞士國家科學基金會的經費贊助。資深作者Paul M. Ridker醫師名列於布萊根婦女醫院與心臟血管疾病相關發炎性生物標記專利所有人清單。
Metabolic Syndrome in Women Linked to Increased Risk for PAD
By Laurie Barclay, MD
Medscape Medical News
September 16, 2009 — Metabolic syndrome (MetS) in women is associated with an increased risk for future symptomatic peripheral artery disease (PAD), according to the results of a prospective cohort study reported online in the September 8 issue of Circulation.
"...MetS is associated with incident myocardial infarction and stroke and is linked with subclinical inflammation," write David Conen MD, MPH, from the Center for Cardiovascular Disease Prevention, Brigham and Women's Hospital and Harvard Medical School in Boston, Massachusetts, and colleagues. "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.
The National Heart, Lung, and Blood Institute; the National Cancer Institute; and the Donald W. Reynolds Foundation supported this study. Dr. Conen was supported by a grant from the Swiss National Science Foundation. Senior author Paul M. Ridker, MD, MPH, is listed as a coinventor on patents held by the Brigham and Women's Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease.
