Oxidative damage, platelet activation, and inflammation to predict mobility disability and mortality in older persons: results from the health aging and body composition study.

Cesari M; Kritchevsky SB; Nicklas B; Kanaya AM; Patrignani P; Tacconelli S; Tranah GJ; Tognoni G; Harris TB; Incalzi RA; Newman AB; Pahor M; Health ABC study; Cesari, Matteo; Kritchevsky, Stephen B; Nicklas, Barbara; Kanaya, Alka M; Patrignani, Paola; Tacconelli, Stefania; Tranah, Gregory J

<bold>Background: </bold>Inflammation, oxidative damage, and platelet activation are hypothesized biological mechanisms driving the disablement process. The aim of the present study is to assess whether biomarkers representing these mechanisms predicted major adverse health-related events in older persons.<bold>Methods: </bold>Data are from 2,234 community-dwelling nondisabled older persons enrolled in the Health Aging and Body Composition study. Biomarkers of lipid peroxidation (ie, urinary levels of 8-iso-prostaglandin F(2α)), platelet activation (ie, urinary levels of 11-dehydro-thromboxane B(2)), and inflammation (serum concentrations of interleukin-6) were considered as independent variables of interest and tested in Cox proportional hazard models as predictors of (severe) mobility disability and overall mortality.<bold>Results: </bold>The sample's (women 48.0%, whites 64.3%) mean age was 74.6 (SD 2.9) years. During the follow-up (median 11.4 years), 792 (35.5%), 269 (12.0%), and 942 (42.2%) events of mobility disability, severe mobility disability, and mortality occurred, respectively. Only interleukin-6 showed significant independent associations with the onset of all the study outcomes. Higher levels of urinary 8-iso-prostaglandin F(2α) and 11-dehydro-thromboxane B(2) independently predicted increased risk of death (hazard ratio 1.10, 95% confidence interval 1.03-1.19 and hazard ratio 1.14, 95% confidence interval 1.06-1.23, respectively). No significant interactions of gender, race, cardiovascular disease, diabetes, and antiplatelet drugs were detected on the studied relationships.<bold>Conclusions: </bold>The inflammatory marker interleukin-6 is confirmed to be a robust predictor for the onset of negative health-related events. Participants with higher urinary levels of 8-iso-prostaglandin F(2α) and 11-dehydro-thromboxane B(2) presented a higher mortality risk.

Journals of Gerontology Series A: Biological Sciences & Medical Sciences, 2012, Vol 67A, Issue 6, p671

1079-5006

Academic Journal

10.1093/gerona/glr246