Cardiovascular Death and the Metabolic Syndrome

Role of adiposity-signaling hormones and inflammatory markers

  1. Claudia Langenberg, MD12,
  2. Jaclyn Bergstrom, MS1,
  3. Christa Scheidt-Nave, MD3,
  4. Johannes Pfeilschifter, MD4 and
  5. Elizabeth Barrett-Connor, MD1
  1. 1Department of Family and Preventive Medicine, School of Medicine, University of California, San Diego, California
  2. 2Department of Epidemiology and Public Health, University College London Medical School, London, U.K.
  3. 3Robert Koch Institute, Epidemiology and Health Monitoring, Berlin, Germany
  4. 4Lutherhaus Hospital, Essen, Germany
  1. 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

Abstract

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.

Footnotes

  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

    • Accepted February 27, 2006.
    • Received December 6, 1005.
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