Effects of Add-on Therapy Consisting of a Selective Mineralocorticoid Receptor Blocker on Arterial Stiffness in Patients with Uncontrolled Hypertension

Abstract

Objective Aldosterone plays an important role in the pathogenesis of atherosclerosis; however, the significance of mineralocorticoid receptor blockade for atherosclerosis has not been fully elucidated. In this study, the effect of add-on eplerenone on the degree of arterial stiffness was examined in patients with uncontrolled hypertension. Methods Forty-seven uncontrolled hypertensive patients who had previously been treated with antihypertensive drugs were examined retrospectively. Thirty-two patients received add-on therapy consisting of eplerenone (Group E) and 15 patients received add-on therapy with a Calcium channel blocker (CCB) or an increased dose of CCB (Group C) in addition to their baseline medications. Both the systolic blood pressure (SBP) and diastolic blood pressure (DBP) values were significantly decreased at two and 12 months in Group C. In contrast, neither the SBP nor DBP values were significantly changed at two months and eventually decreased at 12 months in Group E. The degree of arterial stiffness, as evaluated according to the cardioankle vascular index (CAVI), did not improve at either two or 12 months in Group C, whereas the CAVI values improved as early as at two months and the improvement was sustained at 12 months in Group E. The extent of change in the CAVI was not associated with the level of changes in the SBP or DBP values in Group E. Conclusion Treatment with eplerenone added to the patient's baseline medications improves the degree of arterial stiffness as early as at two months after the beginning of treatment, independent of the blood pressure-lowering actions of these drugs in patients with uncontrolled hypertension.

Mineralocorticoid Receptor in Calcium Handling of Vascular Smooth Muscle Cells

“…Pharmacological inhibition of MR has also demonstrated beneficial effects such as increased lumen and outer diameters of the middle cerebral artery of spontaneously hypertensive stroke-prone rats [62]. Moreover, in a clinical study, treatment with the MR antagonist eplerenone improves the degree of arterial stiffness in hypertensive patients [63]. In conclusion, these studies support that VSMC-MR plays a direct role in vascular remodeling.…”

Organ damage changes in patients with resistant hypertension randomized to renal denervation or spironolactone: The DENERVHTA (Denervación en Hipertensión Arterial) study

“…In patients with early chronic kidney disease treated with a renin‐angiotensin system blocker, the addition of spironolactone led to a reduction in both PWV and AIx75 even after adjusting for BP variation . In another study, the addition of eplerenone in patients with uncontrolled hypertension reduced arterial stiffness as evaluated according to the cardio‐ankle vascular index, and this reduction was not associated with changes in BP. Even less information is available on changes in carotid wall thickness with both treatments, and none is available in patients with RH.…”

Potential Role of Antihypertensive Medications in Preventing Excessive Arterial Stiffening

“…In this regard, inhibition of RAAS using angiotensin converting enzyme (ACE), AT-1R and MR antagonists appears to be superior compared to other antihypertensive medications [53-56]. Targeting the MR is emerging as a useful approach in combination therapy that reduces arterial stiffness [57-59]. This is also supported by studies showing reversal of the increased arterial stiffness in chronic kidney disease patients after undergoing renal transplantation [60] and in subjects with aldosterone producing adenomas after adrenectomy [61].…”