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

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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
Number of pages11
JournalJournal of Hypertension
Publication statusE-pub ahead of print - 9-Aug-2021

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