Global inflammation predicts cardiovascular risk in women: a report from the Women's Ischemia Syndrome Evaluation (WISE) study.
BACKGROUND
Measurement of C-reactive protein (CRP), a marker of inflammation, is recommended to improve cardiovascular disease (CVD) risk stratification. However, no studies have collectively evaluated how inflammatory markers cluster empirically and relate to angiographic coronary artery disease and CVD events.


METHODS
From the WISE study, 580 women with fasting plasma samples of inflammatory markers (interleukin [IL]-6, IL-18, tumor necrosis factor alpha, transforming growth factor beta, CRP, serum amyloid A [SAA], and intercellular adhesion molecules) were analyzed over a median of 4.7 years follow-up. All women were referred for coronary angiography (1996-2000) to evaluate suspected myocardial ischemia.


RESULTS
In factor analysis, a "proinflammation" factor (cluster) loaded on IL-6, CRP, and SAA (r = 0.63-0.87); a "proinflammation and anti-inflammation" cluster loaded on IL-18 and tumor necrosis factor alpha (r = 0.72, 0.77); and an "immunosuppressive" factor loaded singly on transforming growth factor beta (r = 0.96). No cluster was independently associated with angiographic coronary artery disease. However, quartile increases of the "proinflammation" cluster (IL-6, CRP, and SAA) yielded death rates of 2.6%, 7.2%, 13.1%, 26.6%, respectively (P < .0001). Women with > or = 2 of 3 proinflammation markers in the upper quartile had an adjusted relative risk of death of 4.21 (95% CI 1.91-9.25), a higher conferred risk than any single marker alone, all of which were roughly equally predictive.


CONCLUSIONS
Although IL-6, CRP, and SAA all predict CVD risk in women, development of global measures of inflammation and simply counting the number of markers with high levels improve CVD risk stratification. In addition, results indicate that the adverse impact of inflammation may be largely through other mechanisms than promotion of atherogenesis (ie, destabilization of vulnerable plaques).
Kip
Kevin E
KE
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA. kipk@edc.pitt.edu
Marroquin
Oscar C
OC
Shaw
Leslee J
LJ
Arant
Christopher B
CB
Wessel
Timothy R
TR
Olson
Marian B
MB
Johnson
B Delia
BD
Mulukutla
Suresh
S
Sopko
George
G
Merz
C Noel Bairey
CN
Reis
Steven E
SE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000097:blood / Q000150:complications / Q000276:immunology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000150:complications; D018836:Inflammation Mediators / Q000097:blood; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000150:complications / Q000276:immunology*; D012307:Risk Factors; D013577:Syndrome
D018836:Inflammation Mediators