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Diabetes Care 29:1363-1369, 2006
DOI: 10.2337/dc05-2385
© 2006 by the American Diabetes Association
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Cardiovascular and Metabolic Risk
Original Article

Cardiovascular Death and the Metabolic Syndrome

Role of adiposity-signaling hormones and inflammatory markers

Claudia Langenberg, MD1,2, Jaclyn Bergstrom, MS1, Christa Scheidt-Nave, MD3, Johannes Pfeilschifter, MD4 and Elizabeth Barrett-Connor, MD1

1 Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, California
2 Department of Epidemiology and Public Health, University College London Medical School, London, U.K.
3 Robert Koch Institute, Epidemiology and Health Monitoring, Berlin, Germany
4 Lutherhaus Hospital, Essen, Germany

Address correspondence and reprint requests to Professor Elizabeth Barrett-Connor, Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0607. E-mail: ebarrettconnor{at}ucsd.edu

OBJECTIVE— Levels of adiposity-signaling hormones and inflammatory markers are less favorable in individuals with the metabolic syndrome; their role in the association between the metabolic syndrome and cardiovascular mortality remains unclear.

RESEARCH DESIGN AND METHODS— We conducted a prospective study of 977 men and 1,141 women aged 40–94 years in 1984–1987, followed for mortality for a maximum of 20 years. Adiponectin, leptin, ghrelin, interleukin-6 (IL-6), C-reactive protein (CRP), and Adult Treatment Panel III–defined metabolic syndrome components were measured in fasting blood samples obtained in 1984–1987. Cox-proportional hazards models were used in survival analyses.

RESULTS— The age- and sex-adjusted hazard ratio (HR) (95% CI) for coronary heart disease (CHD) mortality associated with the metabolic syndrome was 1.65 (1.25–2.18) (P < 0.001); this association did not differ significantly by sex, age, or diabetic status (P > 0.2 for each interaction). The association between the metabolic syndrome and CHD mortality was not materially changed after adjustment for adiponectin, leptin, and ghrelin; it was attenuated by 25% after adjustment for IL-6 and 35% after adjustment for CRP. CHD mortality increased linearly with greater levels of IL-6 and CRP (Ptrend < 0.001 for each); the age- and sex-adjusted HRs comparing highest versus lowest quarter were 3.0 (1.87–4.89) for IL-6 and 2.1 (1.41–3.21) for CRP. IL-6, but not CRP, remained a significant predictor of CHD mortality in models including both inflammatory markers and the metabolic syndrome.

CONCLUSIONS— Adiposity-signaling hormones and inflammatory markers explain little to some of the association between the metabolic syndrome and CHD mortality. IL-6 levels predict CHD mortality independently of CRP.

Abbreviations: CHD, coronary heart disease • CRP, C-reactive protein • CVD, cardiovascular disease • HRT, hormone replacement therapy • IL-6, interleukin-6


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