Plasma creatine concentration is associated with incident hypertension in a cohort enriched for the presence of high urinary albumin concentration

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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.

The cardinal finding of the current study was that higher plasma creatine concentrations were independently associated with an increased risk of incident hypertension. Furthermore, we demonstrated that this association between plasma creatine concentration and the risk of incident hypertension is significantly modified by sex. Higher plasma creatine was independently associated with an increased risk of incident hypertension in men but not in women. Causal pathway analyses demonstrated that this association was not explained by sodium or potassium intake, nor by total and animal-based protein intake documented by urinary urea and sulphate excretion, respectively. 

These findings implicate a potential role of creatine in the pathophysiology of hypertension. Future studies are warranted to define in more detail the underlying mechanisms for these sex-based differences of the association between plasma creatine and incident hypertension. 

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