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The Cardiovascular Health Study

Joshua I. Barzilay, MD; Caroline Blaum, MD, MS; Tisha Moore, BA; Qian Li Xue, PhD; Calvin H. Hirsch, MD; Jeremy D. Walston, MD; Linda P. Fried, MD, MPH

Arch Intern Med. 2007;167(7):635-641.

Background  Our research group has previously shown that the geriatric syndrome of frailty is associated with features of the metabolic syndrome (MetS) on cross-sectional analysis.

Methods  To test whether MetS and its physiologic determinants—insulin resistance as measured by homeostasis model assessment score (IR-HOMA), increased inflammation and coagulation factor levels, and elevated blood pressure—are associated with incident frailty, we studied a subcohort of participants from the Cardiovascular Health Study observed from 1989/1990 through 1998/1999: 3141 community-dwelling adults, aged 69 to 74 years, without frailty and illnesses that increase inflammation markers or mimic frailty. The association of baseline MetS, IR-HOMA, levels of inflammation and coagulation factors, and systolic blood pressure (SBP) with time to onset of frailty was adjusted for demographic and psychosocial factors and incident events. Our main outcome measure was incident frailty.

Results  Metabolic syndrome was not significantly associated with incident frailty (hazard ratio, 1.16 (95% confidence interval [CI], 0.85-1.57). On the other hand, IR-HOMA and C-reactive protein levels were associated with incident frailty: for every standard deviation increment the hazard ratio for frailty was 1.15 (95% CI, 1.02-1.31) and 1.16 (95% CI, 1.02-1.32), respectively. The white blood cell count and factor VIIIc levels had a borderline association. Elevated systolic blood pressure had no association. Similar trends were found for incident prefrailty, a condition that precedes frailty.

Conclusions  Two physiologic components of MetS— IR-HOMA and inflammation—are associated with incident frailty. Based on these results, IR-HOMA can be considered part of a larger process that leads to generalized decline.

Author Affiliations: Kaiser Permanente of Georgia (Dr Barzilay) and the Division of Endocrinology, Emory University School of Medicine, Atlanta (Dr Barzilay); Division of Geriatric Medicine, University of Michigan (Dr Blaum and Ms Moore), and Veterans Affairs Ann Arbor Healthcare System (Dr Blaum), Ann Arbor; Department of Medicine and Center on Aging and Health (Dr Xue), Department of Geriatrics (Dr Walston), and Division of Geriatric Medicine and Gerontology (Dr Fried), The Johns Hopkins Medical Institutions, Baltimore, Md; and Division of General Medicine, University of California at Davis, Sacramento (Dr Hirsch).

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