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


RESULTS
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<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).


CONCLUSIONS
In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance.
Sattar
Naveed
N
Division of Cardiovascular and Medical Sciences, Faculty of Medicine, University of Glasgow, Glasgow, Scotland, UK. nsattar@clinmed.gla.ac.uk
Murray
Heather M
HM
Welsh
Paul
P
Blauw
Gerard J
GJ
Buckley
Brendan M
BM
Cobbe
Stuart
S
de Craen
Anton J M
AJ
Lowe
Gordon D
GD
Jukema
J Wouter
JW
Macfarlane
Peter W
PW
Murphy
Michael B
MB
Stott
David J
DJ
Westendorp
Rudi G J
RG
Shepherd
James
J
Ford
Ian
I
Packard
Chris J
CJ
D000368:Aged; D000369:Aged, 80 and over; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000401:mortality; D015850:Interleukin-6 / Q000097:blood*; D053208:Kaplan-Meier Estimate; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000401:mortality*; D017035:Pravastatin / Q000627:therapeutic use; D012307:Risk Factors; D020521:Stroke / Q000209:etiology / Q000401:mortality*
D000924:Anticholesteremic Agents; D015415:Biomarkers; D015850:Interleukin-6; D005340:Fibrinogen; D002097:C-Reactive Protein; D017035:Pravastatin