title: Adipocytokines, C-reactive protein, and cardiovascular disease: a population-based prospective study.
abstract: BACKGROUND
  Being overweight or obese is associated with a greater risk of coronary heart disease and stroke compared with normal weight. The role of the specific adipose tissue-derived substances, called adipocytokines, in overweight- and obesity-related cardiovascular disease (CVD) is still unclear.
  
  
  OBJECTIVE
  To investigate the associations of three adipose tissue-derived substances: adiponectin, leptin, and interleukin-6 with incident CVD in a longitudinal population-based study, including extensive adjustments for traditional and metabolic risk factors closely associated with overweight and obesity. C-reactive protein (CRP) was used as a proxy for interleukin-6.
  
  
  METHODS
  Prospective population-based study of 6.502 participants, 51.9% women, aged 30-60 years, free of CVD at baseline, with a mean follow-up time of 11.4 years, equivalent to 74,123 person-years of follow-up. As outcome, we defined a composite outcome comprising of the first event of fatal and nonfatal coronary heart disease and fatal and nonfatal stroke.
  
  
  RESULTS
  During the follow-up period, 453 composite CV outcomes occurred among participants with complete datasets. In models, including gender, age, smoking status, systolic blood pressure, treatment for hypertension, diabetes, body mass index (BMI), total cholesterol, high-density-lipoprotein cholesterol, homeostasis model assessment of insulin resistance, estimated glomerular filtration rate, adiponectin, leptin, and CRP, neither adiponectin (hazard ratio [HR] with 95% confidence interval [CI]: 0.97 [0.87-1.08] per SD increase, P = 0.60) nor leptin (0.97 [0.85-1.12] per SD increase, P = 0.70) predicted the composite outcome, whereas CRP was significantly associated with the composite outcome (1.19 [1.07-1.35] per SD increase, P = 0.002). Furthermore, in mediation analysis, adjusted for age and sex, CRP decreased the BMI-associated CV risk by 43% (95%CI 29-72).
  
  
  CONCLUSIONS
  In this study, neither adiponectin nor leptin were independently associated with CVD, raising questions over their role in CVD. The finding that CRP was significantly associated with an increased risk of CVD and decreased the BMI-associated CVD risk substantially, could imply that interleukin-6-related pathways may play a role in mediating overweight- and obesity-related CVD.
authors.affiliation: Department of Internal Medicine, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; Research Centre for Prevention and Health, the Capital Region of Denmark, Glostrup, Denmark.
authors.forename: Ekim
authors.initials: E
authors.lastname: Seven
authors.affiliation: Research Centre for Prevention and Health, the Capital Region of Denmark, Glostrup, Denmark.
authors.forename: Lise L N
authors.initials: LL
authors.lastname: Husemoen
authors.affiliation: Department of Cardiology P, Gentofte Hospital, University of Copenhagen, Gentofte, Denmark.
authors.forename: Thomas S G
authors.initials: TS
authors.lastname: Sehested
authors.affiliation: Department of Internal Medicine, Holbæk Hospital, University of Copenhagen, Holbæk, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Ibsen
authors.affiliation: Department of Internal Medicine, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Kristian
authors.initials: K
authors.lastname: Wachtell
authors.affiliation: Research Centre for Prevention and Health, the Capital Region of Denmark, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Experimental Research, Glostrup Hospital, Glostrup, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Linneberg
authors.affiliation: Department of Internal Medicine, Glostrup Hospital, University of Copenhagen, Glostrup, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jørgen L
authors.initials: JL
authors.lastname: Jeppesen
mesh_terms: D054392:Adipokines / Q000378:metabolism*; D000328:Adult; D000368:Aged; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000378:metabolism*; D002318:Cardiovascular Diseases / Q000453:epidemiology* / Q000209:etiology / Q000378:metabolism; D003718:Denmark / Q000453:epidemiology; D061345:Early Medical Intervention; D005260:Female; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D020738:Leptin / Q000378:metabolism*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications*; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D054392:Adipokines; D020738:Leptin; D002097:C-Reactive Protein