Study of the association of markers of central and peripheral arterial stiffness with renal function in patients with arterial hypertension, diabetes mellitus and chronic kidney disease.

RATIONALE AND OBJECTIVES: Increased aortic or central arterial stiffness (CAS) is a major factor in cardiovascular morbidity and mortality in patients with vascular risk factors. Decreased glomerular filtration rate (GFR) and increased urinary albumin excretion (uALB) are associated with lethal and non-lethal cardiovas-cular events. The pathophysiological mechanisms of this association are not fully defined. The aim of this study was: 1.- To analyse the CAS, comparing several markers, in subjects with arterial hypertension (HTN), diabetes mellitus (DM), chronic kidney disease (CKD) and their combination. 2.- To study the possible association of CAS with renal dysfunction (decrease in GFR and increase in uALB).

MATERIAL AND METHODS: A total of 286 subjects were included, divided into several groups: Control (n:38); HTN (n:51); DM without CKD (n:26); CKD without DM (n:77); CKD with DM (n:94). Several indices obtained by applanation tonometry were used to determine the CAS: carotid-femoral pulse velocity (VPc-f); central pulse pressure (cPP); augmentation index standardised to a cardiac frequency of 75 L/min (IA75); peripheral/aortic arterial stiffness gradient (ASGp-a). As a marker of peripheral arterial resistance, the carotid-radial pulse velocity (PVc-r) was determined. The ASGp-a was calculated from the PVc-r/PVc-f ratio. The subendocardial viability index (iBuckberg) was obtained from the aortic pulse wave. Multiple regression, binary logistic regression, and multinomial regression were used to study the association between arterial stiffness markers and renal function.

RESULTS: The adjusted values of the PVc-f [(median (interquartile range) (m/s)] were significantly higher in subjects with DM [(9 (1.2)], CKD [(9.4 (0.7)] and DM with CKD [(10.9 (0.7)] than in the control group [(8.2 (1.3)] and group with HTN [(8.3 (0.9)], (p: 0.001). Patients with DM with CKD had higher PVc-f values than all other groups (p: 0.001). The ASGp-a of the patients was significantly lower than that of the controls, and the group with DM with CKD had significantly lower values than the other groups. The cPP in the DM with CKD group was significantly higher than in the other groups. All patients had an AI75 higher than the control group. When all aortic stiffness markers were introduced together in the regression, PV c-f was the only one that, after multivariate adjustment, was independently and inversely associated with GFR (β; -4, p: 0.001) and predicted the presence of GFR decrease (<60 mL/min/1.73 m2), [(OR (95%CI): 1.50 (1.17-1.92; p: 0.001]. The PVc-f was the only index directly associated with albuminuria (β: 0.15, p: 0.02) and predicted the existence of abnormal albuminuria (>30 mg/g), [(OR; 1.66 (1.25-2.20), p: 0.001)]. The PVc-f was also associated with the iBuckberg (β: -2.73, p: 0.01). Multinomial regression confirmed that PVc-f is a significant determinant of GFR and uALB. On the other hand, the increase in PVc-f and the presence of DM contribute significantly to the magnitude of albuminuria.

CONCLUSIONS: Aortic stiffness increases in the presence of vascular risk factors such as hypertension, DM and CKD. This increase is greater when DM and CKD coexist. Increased aortic stiffness is inversely associated with GFR and directly with uALB, and is predictive of decreased GFR and abnormal uALB. The VPc-f is the parameter of aortic stiffness that is most consistently associated with renal dysfunction. Increased aortic stiffness could be one of the pathomechanisms linking renal dysfunction to cardiovascular events.