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Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study

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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.

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Acknowledgments

We are indebted to Ellen Kohlsdorf (data management), Wolfgang Fleischhauer (case ascertainment), and Wolfgang Bernigau (statistical assistance) in EPIC-Potsdam, and to Marie-Luise Groß (case ascertainment), and Jutta Schmitt (data management) in EPIC-Heidelberg. This work was supported by a grant from the German Heart Research Foundation. Measurements of PTH and 25(OH)D3 in the subcohort were paid by a grant from the Federal Ministry of Education and Research (BMBF FZK0315668).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standard

Study procedures have been approved by the Ethics Committee of the Medical Association of the State of Brandenburg and by the Ethics Committee of the Heidelberg University Medical School, respectively for Potsdam and Heidelberg, and have therefore been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. All participants gave their written informed consents priori to their inclusion in the study.

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Authors and Affiliations

  1. Research Group Cardiovascular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee, 114-116, 14558, Nuthetal, Germany

    Romina di Giuseppe & Cornelia Weikert

  2. Division of Cancer Epidemiology, German Cancer Research Center, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Tilmann Kühn & Rudolf Kaaks

  3. Institute of Agricultural and Nutritional Sciences, Human Nutrition Group, Martin Luther University Halle-Wittenberg, Von-Danckelmann-Platz 2, 06120, Halle (Saale), Germany

    Frank Hirche & Gabriele I. Stangl

  4. Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke, Arthur-Scheunert-Allee, 114-116, 14558, Nuthetal, Germany

    Brian Buijsse & Heiner Boeing

  5. Department of Clinical Medicine, University of Bergen, P.O. Box 7804, 5020, Bergen, Norway

    Jutta Dierkes

  6. Division of Endocrinology, Diabetology, Nephrology, Vascular Disease and Clinical Chemistry, Department of Internal Medicine, University of Tübingen, Otfried-Müller-Str. 10, 72076, Tübingen, Germany

    Andreas Fritsche

  7. Institute for Social Medicine, Epidemiology and Health Economics, Charité University Medical Center, Luisenstr. 57, 10117, Berlin, Germany

    Cornelia Weikert

  8. German Centre for Cardiovascular Research (DZHK), Partner Site Berlin, Germany

    Romina di Giuseppe & Cornelia Weikert

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  1. Romina di Giuseppe
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  2. Tilmann Kühn
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  9. Gabriele I. Stangl
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  10. Cornelia Weikert
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Correspondence to Romina di Giuseppe.

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di Giuseppe, R., Kühn, T., Hirche, F. et al. Plasma fibroblast growth factor 23 and risk of cardiovascular disease: results from the EPIC-Germany case-cohort study. Eur J Epidemiol 30, 131–141 (2015). https://doi.org/10.1007/s10654-014-9982-4

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