Inflammation as a mediator of the link between mild to moderate renal insufficiency and endothelial dysfunction in essential hypertension.
The relationship among inflammation (plasma high-sensitivity C-reactive protein [CRP]), endothelial function (hemodynamic response to acetylcholine [ACh] in the forearm), and renal function (serum creatinine and GFR [Modification of Diet in Renal Disease formula]) was investigated in 264 never-treated individuals with uncomplicated essential hypertension and serum creatinine within the normal range. Multiple regression models of renal function (creatinine) were constructed in sequence including Framingham risk factors as well the hemodynamic response to ACh and plasma CRP. The inclusion of endothelial function into a model based on Framingham risk factors added highly significant (P < 0.001) power to this model (+5%). Of note, in an alternative model that included CRP (instead of endothelial function), the creatinine variance explained by this factor was two times higher (+10%) than that associated with endothelial function in the first model. In the full model that included both endothelial function and CRP, CRP maintained a much stronger independent link with the outcome measure than endothelial function. In individuals with untreated, uncomplicated essential hypertension, multivariate modeling indicated that inflammation is a crucial mechanism mediating the endothelial-renal function link. The proatherogenic potential of inflammation associated with subtle impairment in renal function may contribute to the cardiovascular risk of essential hypertension.
Zoccali
Carmine
C
Consiglio Nazionale delle Ricerche-Instituto di Bio-Medicina, Clinical Epidemiology & Pathophysiology of Renal Diseases and Hypertension, Ospedali Riuniti, 89124 Reggio Calabria, Italy. carmine.zoccali@tin.it
Maio
Raffaele
R
Tripepi
Giovanni
G
Mallamaci
Francesca
F
Perticone
Francesco
F
D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006973:Hypertension / Q000150:complications* / Q000175:diagnosis*; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D008962:Models, Theoretical; D015999:Multivariate Analysis; D012044:Regression Analysis; D051437:Renal Insufficiency / Q000150:complications* / Q000175:diagnosis*; D012307:Risk Factors
D002097:C-Reactive Protein; D003404:Creatinine; D000109:Acetylcholine