Plasma creatine concentration is associated with incident hypertension in a cohort enriched for the presence of high urinary albumin concentration: the Prevention of Renal and Vascular Endstage Disease study

Adrian Post*, Daan Kremer, J Casper Swarte, Sara Sokooti, Fabian A Vogelpohl, Dion Groothof, Ido P Kema, Erwin Garcia, Margery A Connelly, Theo Wallimann, Robin P F Dullaart, Casper F M Franssen, Stephan J L Bakker

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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OBJECTIVE: : Hypertension is a major risk factor for cardiovascular disease, kidney disease, and premature death. Increased levels of creatine kinase are associated with development of hypertension. However, it is unknown if creatine, a substrate of CK, is associated with the development of hypertension. We therefore, aimed to investigate the association between plasma creatine concentration and incident hypertension.

METHODS: We measured fasting plasma creatine concentrations by nuclear magnetic resonance spectroscopy in participants of the population-based PREVEND study. The study outcome was incident hypertension, defined as either a SBP of at least 140 mmHg, a DBP of at least 90 mmHg, or the new usage of antihypertensive drugs. Participants with hypertension at baseline were excluded.

RESULTS: We included 3135 participants (46% men) aged 49 ± 10 years. Mean plasma creatine concentrations were 36.2 ± 17.5 μmol/l, with higher concentrations in women than in men (42.2 ± 17.6 versus 29.2 ± 17.6 μmol/l; P < 0.001). During a median of 7.1 [interquartile range: 3.6-7.6] years of follow-up, 927 participants developed incident hypertension. Higher plasma creatine concentrations were associated with an increased risk of incident hypertension [HR per doubling of plasma creatine: 1.21 (95% confidence interval: 1.10-1.34); P < 0.001], which remained significant after adjustment for potential confounders. Sex-stratified analyses demonstrated higher plasma creatine that was independently associated with an increased risk of incident hypertension in men [hazard ratio: 1.26 (95% CI 1.11-1.44); P < 0.001], but not in women (hazard ratio: 1.13 (95% CI 0.96-1.33); P = 0.14]. Causal pathway analyses demonstrate that the association was not explained by sodium or protein intake.

CONCLUSION: Higher plasma creatine is associated with an increased risk of hypertension in men. Future studies are warranted to determine the underlying mechanisms.

Original languageEnglish
Pages (from-to)229-239
Number of pages11
JournalJournal of Hypertension
Issue number2
Early online date9-Aug-2021
Publication statusPublished - 1-Feb-2022


  • adults
  • creatine
  • hypertension
  • RISK
  • RAT

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