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Functional Decline in Patients With and Without Peripheral Arterial Disease: Predictive Value of Annual Changes in Levels of C-Reactive Protein and D-Dimer

¹ Northwestern University's Feinberg School of Medicine, Chicago, Illinois.
² Laboratory of Epidemiology, Demography, and Biometry, and³ Clinical Research Branch, National Institute on Aging, National Institutes of Health, Bethesda, Maryland.
⁴ University of California at San Diego, California.
⁵ Harvard Medical School, Boston, Massachusetts.

Address correspondence to Mary McGrae McDermott, MD, 675 N. St Clair, Suite 18-200, Chicago, IL 60611. E-mail: mdm608{at}northwestern.edu

Background. Inflammation may be a potential mechanism of aging-related functional decline. We determined whether greater annual increases in levels of high sensitivity C-reactive protein (hsCRP) and D-dimer predicted greater decline in functioning among persons with and without lower extremity peripheral arterial disease (PAD).

Methods. We prospectively studied 296 men and women with PAD and 191 without PAD. Objective measures of functioning, hsCRP, and D-dimer were obtained at baseline and annually for 3 years (mean follow-up = 36.3 ± 6.4 months).

Results. Among PAD participants, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk performance (–2.63 ft/mg/L, p =.039) but not in other functional outcomes. Higher prior year absolute hsCRP levels were associated with greater declines in 6-minute walk (–2.93 ft/mg/L, p =.022), summary performance score (–0.038/mg/L, p =.017), and rapid paced 4-meter walk (–0.29 cm/s/mg/L, p =.026) during the subsequent year. Among participants without PAD, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk (–7.47 ft/mg/L, p =.002), usual-pace 4-meter walk (–0.33 cm/s/mg/L, p <.001), fast paced 4-meter walk (–0.56 cm/s/mg/L, p =.003), and the summary performance score (–0.029 mg/L, p <.001). There were no consistent associations between D-dimer levels and functional decline.

Conclusion. These findings suggest that inflammation may play a role in functional decline in persons with and without PAD.