The findings of a recent large, long-term study demonstrate that metabolic syndrome greatly raises a woman’s chance of developing symptomatic peripheral arterial disease (PAD). PAD, in turn, raises the risks of heart disease and stroke (Circulation. 2009; 120:1041-1047).

A group of researchers undertook a prospective evaluation of 27,111 Women’s Health Study participants, age 45 years and older, who were free of cardiovascular disease to determine who would develop PAD.

One-quarter of the participants had at least three of the cardiovascular risk factors necessary for a diagnosis of metabolic syndrome, with the most prevalent trait being HDL <50 mg/dL.

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During a median follow-up of 13.3 years, the investigators confirmed the occurrence of 114 symptomatic PAD events, including 111 cases of intermittent claudication and three cases of peripheral arterial revascularization not preceded by claudication.

According to the data, the risk for developing symptomatic PAD was 62% higher for women with metabolic syndrome than for those without.

Women with one or two traits of metabolic syndrome had a 2.5-fold increased risk of PAD compared with those who had no traits.Women with established metabolic syndrome had a threefold increased risk of developing PAD compared with those without metabolic syndrome.

Finally, PAD risk jumped by 21% for every additional characteristic of metabolic syndrome present beyond the three used to establish the diagnosis.

The investigators also noted strong ties among metabolic syndrome, PAD, and two markers of inflammation: high-sensitivity C-reactive protein and soluble intercellular adhesion molecule-1. Women with metabolic syndrome exhibited substantially increased levels of these two markers, but precisely how inflammation combined with metabolic syndrome leads to PAD remains unclear.

Although not a trait of metabolic syndrome, smoking was by far the strongest risk factor for PAD in this study population. “Women who smoke had a 12.7-fold increased risk of developing PAD compared with nonsmokers,” investigators note.

In another PAD-related trial, research shows that the ankle-brachial index (ABI) can be used to screen for asymptomatic PAD. One study compared circulation in the ankle and the arm to identify asymptomatic PAD in about one-fourth of a group of 102 individuals at high risk for a vascular event. The report was published online ahead of print August 27, 2009, in Stroke.