Cardiovascular death and the metabolic syndrome: role of adiposity-signaling hormones and inflammatory markers.
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.


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 (P(trend) < 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.
Langenberg
Claudia
C
Department of Family and Preventive Medicine, School of Medicine, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0607, USA.
Bergstrom
Jaclyn
J
Scheidt-Nave
Christa
C
Pfeilschifter
Johannes
J
Barrett-Connor
Elizabeth
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002318:Cardiovascular Diseases / Q000401:mortality*; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D020521:Stroke / Q000401:mortality
D015415:Biomarkers; D006728:Hormones; D002097:C-Reactive Protein