American Diabetes Association
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Body Fat Distribution, Cardiometabolic Traits, and Risk of Major Lower-Extremity Arterial Disease in Postmenopausal Women

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posted on 2021-11-03, 20:33 authored by Guo-Chong Chen, Rhonda Arthur, Victor Kamensky, Jin Choul Chai, Bing Yu, Aladdin H. Shadyab, Matthew Allison, Yangbo Sun, Nazmus Saquib, Robert A Wild, Wei Bao, Andrew J. Dannenberg, Thomas E. Rohan, Robert C. Kaplan, Sylvia Wassertheil-Smoller, Qibin Qi

To assess the relationship between body fat distribution and incident lower-extremity arterial disease (LEAD).


We included 155,925 postmenopausal women with anthropometric measures from the Women’s Health Initiative who had no known LEAD at recruitment. A subset of 10,894 participants had body composition data quantified by dual energy X-ray absorptiometry (DXA). Incident cases of symptomatic LEAD were ascertained and adjudicated via medical record review.


We identified 1152 incident LEAD cases during a median 18.8 years follow-up. After multivariable adjustment and mutual adjustment, waist and hip circumference was positively and inversely associated with risk of LEAD, respectively (both P-trend values <0.0001). In a subset (n = 22,561) where various cardiometabolic biomarkers were quantified, a similar positive association of waist circumference with risk of LEAD was eliminated after adjustment for diabetes and HOMA-IR (P-trend = 0.89), whereas hip circumference remained inversely associated with the risk after adjustment for major cardiometabolic traits (P-trend = 0.0031). In the DXA subset, higher trunk fat (P-trend = 0.0081) and higher leg fat (P-trend <0.0001) was associated with higher and lower risk of LEAD, respectively. Further adjustment for diabetes, dyslipidemia, and blood pressure diminished the association for trunk fat (P-trend = 0.49), yet the inverse association for leg fat persisted (P-trend = 0.0082).


Among US postmenopausal women, a positive association of upper-body fat with risk of LEAD appeared to be attributable to traditional risk factors especially insulin resistance. Lower-body fat was inversely associated with risk of LEAD beyond known risk factors.


The WHI program is funded by the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C. Dr. Qi is supported by the NHLBI (K01HL129892, R01HL060712, and R01HL140976) and the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119268 and R01DK120870), and Dr. Kaplan is supported by the NHLBI (R01-HL146132-01).