Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events?

• Published in: PLoS medicine 2009-06, Vol.6 (6), p.e1000099-e1000099
• Main Authors: Sattar, Naveed, Murray, Heather M, Welsh, Paul, Blauw, Gerard J, Buckley, Brendan M, Cobbe, Stuart, de Craen, Anton J M, Lowe, Gordon D, Jukema, J Wouter, Macfarlane, Peter W, Murphy, Michael B, Stott, David J, Westendorp, Rudi G J, Shepherd, James, Ford, Ian, Packard, Chris J
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Anticholesteremic Agents - therapeutic use; Biomarkers - blood; C-Reactive Protein - metabolism; Cardiovascular Disorders/Myocardial Infarction; Cardiovascular Disorders/Vascular Biology; Female; Fibrinogen - metabolism; Humans; Inflammation - complications; Inflammation - mortality; Interleukin-6 - blood; Kaplan-Meier Estimate; Male; Myocardial Infarction - etiology; Myocardial Infarction - mortality; Pravastatin - therapeutic use; Public Health and Epidemiology/Epidemiology; Risk Factors; Stroke - etiology; Stroke - mortality
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1000099

Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke. In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p