Abstract
Background:
Inflammatory biomarkers have been previously associated with stroke and mortality, but inflammation may also have detrimental effects beyond acute events. The association of these biomarkers with functional status is not well defined. We hypothesized that serum levels of high-sensitivity C-reactive protein (CRP), lipoprotein-associated phospholipase A2 (LpPLA2), and tumor necrosis factor receptor-1 (TNFR1) predict long-term functional status independently of vascular risk factors and stroke and myocardial infarction (MI) occurring during follow-up.
Methods:
In the prospective, multiethnic Northern Manhattan Study, stroke-free individuals in northern Manhattan aged >=40 years had annual assessments of disability with the Barthel index (BI), for a median of 13 years. BI was analyzed as a continuous variable (range 0-100). Baseline demographics, risk factors, and laboratory studies were collected, including CRP (n=2240), LpPLA2 activity (n=1912), and TNFR1 (n=1863). Separate generalized estimating equation models estimated standardized associations between each biomarker and 1) baseline functional status and 2) change in function over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and MI occurring during follow-up.
Results:
Mean age was 69 (SD 10) years, 36% were male, 54% Hispanic, 74% had hypertension, 22% diabetes; 337 MIs and 369 first strokes occurred during follow-up. CRP (-0.41, 95% CI -0.82 to 0.002) and LpPLA2 (-0.40, 95% CI -0.75 to -0.04) were associated with baseline BI but not change over time. TNFR1 was associated with baseline BI (-0.93, 95% CI -1.59 to -0.26) and change over time (-0.36 BI points per year, 95% CI -0.69 to -0.03).
Conclusions:
In this large population-based study, higher serum inflammatory biomarker levels were associated with disability, even when adjusting for baseline covariates and stroke and MI occurring during follow-up. Elevated TNFR1 predicted greater disability over time, suggesting that systemic inflammation may contribute to long-term functional decline and disability.