Abstract 5790: High Levels of Homocysteine and D-dimer Are Associated With Faster Functional Decline Among Men and Women With Lower Extremity Peripheral Arterial Disease
BACKGROUND. We assessed associations of baseline biomarker levels with functional decline among participants with lower extremity peripheral arterial disease (PAD).
METHODS. Participants were 352 men and women with an ankle brachial index (ABI) < 0.90 who attended a baseline and up to three annual follow-up visits. Baseline levels of homocysteine, C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer were obtained. Participants performed a six-minute walk test and the short physical performance battery (SPPB) at baseline and annually. The SPPB is a composite measure of lower extremity functioning scored on a 0 –12 scale (12= best). Outcomes were average annual decline in six-minute walk distance, average annual decline in the SPPB, and mobility loss. Mobility loss was defined as becoming unable to walk 1/4 mile or walk up and down one flight of stairs without assistance, among those without baseline mobility limitations. Results adjust for age, sex, race, body mass index, ABI, smoking, comorbidities, and other potential confounders.
RESULTS. The 352 participants were average age 75±8 and 47% were women. The average ABI was 0.63 ± 0.16 and 33% had diabetes mellitus. Average baseline six-minute walk distance and SPPB scores were 1,101 feet ± 432 and 9 ± 3, respectively. Adjusting for confounders, higher CRP levels were associated with more rapid decline in six-minute walk performance (1st (lowest) Tertile -50 feet/year; 2nd Tertile -44 feet/year; 3rd (highest) Tertile -65 feet/year, p trend value = 0.04). Higher CRP levels were also associated with more rapid decline in the SPPB (1st (lowest) Tertile 0.3/year; 2nd Tertile -0.3/year; 3rd (highest) Tertile -0.5/year, p trend = 0.02). Similarly, higher levels of homocysteine were associated with more rapid decline in the SPPB (1st Tertile 0.3/year; 2nd Tertile -0.4/year; 3rd Tertile -0.5/year, p trend = 0.03). Higher levels of homocysteine were also associated with higher rates of mobility loss, p trend = 0.04). IL-6 and D-dimer were not significantly associated with declining functional performance.
CONCLUSIONS. This study demonstrates, for the first time, that higher baseline levels of CRP and homocysteine are associated with faster rates of decline in functional performance among men and women with PAD.