Metabolic Syndrome, Inflammation, and Risk of Symptomatic Peripheral Artery Disease in Women

Abstract

Background-The metabolic syndrome (MetS) is associated with incident myocardial infarction and stroke and is linked with subclinical inflammation; however, prospective data pertaining to MetS and future peripheral artery disease (PAD) are sparse, with few studies examining the role of inflammation. We therefore evaluated the relationship between MetS, inflammation, and incident PAD. Methods and Results-We conducted a prospective cohort study among 27 111 women free of baseline cardiovascular disease who were participating in the Women's Health Study. Subjects were followed for incident symptomatic PAD (nϭ114; median cohort follow-up 13.3 years). We used Cox proportional hazards models to compare PAD risk among women with and without MetS. We also evaluated relationships between MetS and subclinical inflammation as measured by high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 and adjusted for these biomarkers in multivariable models. Women with MetS had a 62% increased risk of future PAD (hazard ratio 1.62, 95% confidence interval 1.10 to 2.38). After multivariable adjustment, MetS remained significantly associated with PAD (adjusted hazard ratio 1.48, 95% confidence interval 1.01 to 2.18), with a 21% risk increase per additional MetS-defining trait (adjusted hazard ratio 1.21, 95% confidence interval 1.06 to 1.39). In women with and without MetS, respectively, median levels of high-sensitivity C-reactive protein were 4.0 versus 1.5 mg/L (PϽ0.0001), and median levels of soluble intercellular adhesion molecule-1 were 374 versus 333 ng/mL (PϽ0.0001). When high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1 were added to multivariable models, risk associated with MetS was substantially attenuated and no longer significant (hazard ratio 1.14, 95% confidence interval 0.75 to 1.73). Conclusions-MetS is associated with an increased risk of future symptomatic PAD in women. This risk appears to be mediated largely by the effects of inflammation and endothelial activation.

Features of Coronary Plaque in Patients With Metabolic Syndrome and Diabetes Mellitus Assessed by 3-Vessel Optical Coherence Tomography

“…Previous studies demonstrated that stratification by inflammatory status indicated by high-sensitive C reactive protein adds prognostic information to the diagnosis of MetS. 8,25 The lack of a significant association between MetS and FCT or TCFA in the present study likely results from the incompleteness of traditional MetS criteria. Additional information including inflammatory markers might be helpful for better differentiation of plaque vulnerability in addition to the diagnosis of MetS and DM.…”

“…We used a BMI cutoff of 29.4 kg/m 2 for men and 26.7 kg/m 2 for women as previously reported. 8,9 In addition, history of hypertension was used as an alternative for the presence of documented blood pressure ≥135/85 mm Hg because the majority of subjects had been treated with antihypertensive agents. Therefore, MetS was defined by the presence of 3 or more MetS factors of the following: (1) BMI ≥29.4 kg/m 2 for men and 26.7 kg/m 2 for women; (2) triglycerides ≥150 mg/dL; (3) high-density lipoprotein cholesterol ≤40 mg/dL; (4) history of hypertension; and (5) fasting blood glucose level ≥100 mg/dL, as shown in Figure 2.…”

The risk of peripheral artery disease in older adults - seven-year results of the getABI study

“…However, this association was shown by a larger cohort from the Women's Health Study (HR 1.48, 95 % CI 1.01 to 2.18) [22]. Recently, this association was confi rmed in the Cardiovascular Health Study for both symptomatic (HR 1.47, 95 % CI 1.11 to 1.94) and asymptomatic PAD (risk ratio 1.26, 95 % CI 1.00 to 1.58) [23].…”

Cranberry Supplement and Metabolic Risk Factors in Obese and Overweight Females

“…High oxidative stress (30) and elevated inflammatory markers such as IL-6 and tumor necrosis factor-α (TNF-α) (26,31) are implicated in people with MS. On the other hand, anti-inflammatory markers including adiponectin reduce in the course of the abnormalities of MS (32). MDA is a stable biomarker of lipid peroxidation and is highly correlated with MS (33,34).…”