Magnesium and Vascular Dysfunction in Malignant Hypertension

Abstract

HomeHypertensionVol. 58, No. 2Magnesium and Vascular Dysfunction in Malignant Hypertension Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBMagnesium and Vascular Dysfunction in Malignant Hypertension Steven Van Laecke and Raymond Vanholder Steven Van LaeckeSteven Van Laecke Renal Division Ghent University Hospital Ghent, Belgium (Van Laecke, Vanholder) Search for more papers by this author and Raymond VanholderRaymond Vanholder Renal Division Ghent University Hospital Ghent, Belgium (Van Laecke, Vanholder) Search for more papers by this author Originally published13 Jun 2011https://doi.org/10.1161/HYPERTENSIONAHA.111.175828Hypertension. 2011;58:e7Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: January 1, 2011: Previous Version 1 To the Editor:We read with great interest the analysis by Shantsila et al,1 who established more distinct abnormalities in macrovascular and microvascular function when comparing patients with previous malignant hypertension and controlled blood pressure with high-risk hypertension patients with similar blood pressure without previous malignant hypertension. Malignant hypertension patients had an impaired endothelium-dependent response to acetylcholine, higher pulse wave velocity, and circulating endothelial cells.1 Both endothelium-dependent and -independent microvascular dysfunction were more pronounced in the malignant hypertension cohort despite similar blood pressure control at the time of analysis.1 Considering the persistence of endothelial dysfunction long after the initial diagnosis, the authors postulate that endothelial damage/dysfunction may be an integral part of the pathogenesis and tendency of malignant hypertension to recur. The authors further claim the absence of confounders known to influence endothelial function other than the assessed covariates in their analysis.We suggest that magnesium (Mg) deficiency might be a potential confounder. We recently demonstrated hypomagnesemia to be an independent predictor of vascular stiffness assessed by pulse wave velocity in renal transplant recipients.2 These findings are reminiscent of a role of Mg and its deficiency in altered vascular reactivity, tone, inflammation, remodeling, and endothelial dysfunction.3 Shechter et al4 observed a relationship between Mg levels and endothelial function in patients with coronary heart disease, which was assessed by endothelium-dependent, flow-mediated vasodilatation. Patients with malignant hypertension consistently demonstrate alterations in Mg metabolism.3 In rats with malignant hypertension, both extracellular and intracellular Mg levels are markedly reduced.3 Considering the emerging role for underlying mechanisms of altered Mg handling in hypertension, such as cellular Na+/Mg+ exchange and the impaired regulation of transient receptor of potential melastatin channels 6 and 7,3 the present findings urge us to exclude a predisposition toward malignant hypertension based on altered Mg handling, in association with endothelial dysfunction. This premise should be explored prospectively, because cross-sectional studies render hypotheses concerning causal pathways highly speculative.Another possible flaw in the present analysis is the significantly decreased kidney function in the malignant versus the high-risk hypertension cohort (P=0.001)1 despite excluding patients with a serum creatinine of >200 μmol/L. Endothelial dysfunction yet occurs very early in chronic kidney disease, partially through accumulation of uremic retention molecules, such as advanced glycation end products or asymmetrical dimethyl arginine, a potent mediator of endothelial dysfunction.5 Furthermore, chronic kidney disease predicts vascular stiffness. In addition, a biased distribution of endothelium-modifying drugs, such as statins and angiotensin-converting enzyme inhibitors, could hamper the interpretability, and data on inflammation and insulin resistance are lacking. Thus, we are afraid that the present findings, although interesting and potentially relevant, have not been corrected for a number of confounders to render their conclusions indisputable.In conclusion, the article by Shantsila et al1 offers food for thought, and its findings should be further explored in larger cohorts with a clear dissection of all of the potential confounders to potentially decipher the role of Mg and chronic kidney disease in endothelial dysfunction and the pathophysiology of malignant hypertension.Steven Van LaeckeRaymond Vanholder Renal Division Ghent University Hospital Ghent, BelgiumDisclosuresNone.FootnotesLetters to the Editor will be published, if suitable, as space permits. They should not exceed 1000 words (typed double-spaced) in length and may be subject to editing or abridgment.