title: Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study.
abstract: Increased fibroblast growth factor 23 (FGF23) concentrations have emerged as a novel risk factor for heart failure and stroke but not for myocardial infarction (MI). Yet, most studies on MI were conducted in coronary artery disease (CAD) patients and the elderly. Evidence is unclear in subjects without CAD and for stroke subtypes. We investigated the relationships between FGF23 and overall major cardiovascular endpoints, incident MI, ischemic (IS) and haemorrhagic stroke (HS) in middle-aged adults without pre-existing cardiovascular disease. We used a case-cohort study nested within the European Prospective Investigation into Cancer and Nutrition-Germany, including a randomly drawn subcohort (n = 1,978), incident MI (n = 463) and stroke cases (n = 359 IS; n = 88 HS) identified during a mean follow-up of 8.2 years. Compared with participants with FGF23 levels in the lowest quartile, those in the highest quartile had a 36% increased risk for cardiovascular events [hazard ratio: 1.36, 95% confidence interval (CI): 1.02-1.82] after adjustment for established cardiovascular risk factors, patahyroid hormone and 25-hydroxyvitamin D3 levels, dietary calcium and phosphorus intake, and kidney function. However, sub-analyses revealed significant relationships with risk of MI and HS, but not IS. Compared with the lowest quartile, individuals in the top two FGF23 quartiles had a 1.62 (95% CI 1.07-2.45) fold increased risk for MI and a 2.61 (95% CI 1.23-5.52) fold increase for HS. Increased FGF23 emerged as a risk factor for both MI and HS. Further studies are warranted to confirm these results and to identify underlying mechanisms.
authors.affiliation: Research Group Cardiovascular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee, 114-116, 14558, Nuthetal, Germany, romina.digiuseppe@dife.de.
authors.forename: Romina
authors.initials: R
authors.lastname: di Giuseppe
authors.forename: Tilmann
authors.initials: T
authors.lastname: Kühn
authors.forename: Frank
authors.initials: F
authors.lastname: Hirche
authors.forename: Brian
authors.initials: B
authors.lastname: Buijsse
authors.forename: Jutta
authors.initials: J
authors.lastname: Dierkes
authors.forename: Andreas
authors.initials: A
authors.lastname: Fritsche
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Gabriele I
authors.initials: GI
authors.lastname: Stangl
authors.forename: Cornelia
authors.initials: C
authors.lastname: Weikert
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology*; D005260:Female; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000097:blood*; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000453:epidemiology; D011159:Population Surveillance; D011446:Prospective Studies; D012307:Risk Factors; D017678:Sex Distribution; D020521:Stroke / Q000097:blood* / Q000453:epidemiology
chemical_list: D015415:Biomarkers; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23