Abstract
Background/ObjectivesInflammatory biomarkers have been associated with stroke and mortality, but inflammation may also have detrimental effects beyond acute events. We hypothesized that serum concentrations of interleukin-6 (IL6) and lipoprotein-associated phospholipase A2 (LpPLA2) were inversely associated with long-term functional decline independently of vascular risk factors, stroke and myocardial infarction (MI) occurring during follow-up.DesignProspective population based cohort studySettingThe Northern Manhattan StudyParticipants (including the sample size)Race/ethnically diverse stroke-free individuals in northern Manhattan aged ≥40 years (n = 3298).InterventionNoneMeasurementsAnnual functional assessments 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 IL6 (n = 1679), LpPLA2 mass (n = 1912) and activity (n = 1937). Separate mixed models estimated standardized associations between each biomarker and baseline functional status and change over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and MI occurring during follow-up.ResultsMean age was 69 (SD 10) years, 35% were male, 53% Hispanic, 74% hypertensive, and 16–24% diabetic. LogIL6 was associated with decline in BI over time (-0.13 points per year, 95% CI -0.24, -0.02) and marginally with baseline BI (-0.20, 95% CI -0.40, 0.01). LpPLA2 activity levels were associated with baseline BI (-0.36, 95% CI -0.68, -0.04) but not change over time, and LpPLA2 mass levels were not associated with either.ConclusionIn 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.
Highlights
Inflammatory pathways have been implicated in various disease processes, including vascular and cerebrovascular disease, neurodegenerative conditions, and arthritis
Separate mixed models estimated standardized associations between each biomarker and baseline functional status and change over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and myocardial infarction (MI) occurring during follow-up
Lipoprotein-associated phospholipase-A2 (LpPLA2) activity levels were associated with baseline Barthel index (BI) (-0.36, 95% CI -0.68, -0.04) but not change over time, and LpPLA2 mass levels were not associated with either
Summary
Race/ethnically diverse stroke-free individuals in northern Manhattan aged 40 years (n = 3298). Annual functional assessments with the Barthel index (BI), for a median of 13 years. BI was analyzed as a continuous variable (range 0–100). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Laboratory studies were collected, including IL6 (n = 1679), LpPLA2 mass (n = 1912) and activity (n = 1937). Separate mixed models estimated standardized associations between each biomarker and baseline functional status and change over time, adjusting for demographics, vascular risk factors, social variables, cognition, and depression measured at baseline, and stroke and MI occurring during follow-up
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