Effects of a Long-Term Treatment With Aliskiren or Ramipril on Structural Alterations of Subcutaneous Small-Resistance Arteries of Diabetic Hypertensive Patients

Abstract

Abstract-Structural alterations of subcutaneous small-resistance arteries are associated with a worse clinical prognosis in hypertension and non-insulin-dependent diabetes mellitus. The effects of the direct renin inhibitor aliskiren on microvascular structure were never previously evaluated. Therefore, we investigated the effects of aliskiren in comparison with those of an extensively used angiotensin-converting enzyme inhibitor, ramipril, on peripheral subcutaneous small-resistance artery morphology, retinal arteriolar structure, and capillary density in a population of patients with non-insulin-dependent diabetes mellitus. Sixteen patients with mild essential hypertension and with a previous diagnosis of non-insulin-dependent diabetes mellitus were included in the study. Patients were then randomized to 1 of the 2 active treatments (aliskiren 150 mg once daily, n=9; or ramipril 5 mg once daily, n=7). Each patient underwent a biopsy of the subcutaneous fat from the gluteal region, an evaluation of retinal artery morphology (scanning laser Doppler flowmetry), and capillary density (capillaroscopy), at baseline and after 1 year of treatment. Subcutaneous small arteries were dissected and mounted on a pressurized micromyograph, and the media-to-lumen ratio was evaluated. A similar office blood pressure-lowering effect and a similar reduction of the wall-to-lumen ratio of retinal arterioles were observed with the 2 drugs. Aliskiren significantly reduced media-to-lumen ratio of subcutaneous small-resistance arteries, whereas ramipril-induced reduction of media to lumen ratio was not statistically significant. No relevant effect on capillary density was observed. In conclusion, treatment with aliskiren or ramipril was associated with a correction of microvascular structural alterations in patients with non-insulin-dependent diabetes mellitus. An increased media-to-lumen ratio of subcutaneous smallresistance arteries is a potent predictor of cardiovascular events in patients with increased blood pressure values, [10][11][12] part of them being also diabetics.10,11 Antihypertensive treatment is able to regress structural alterations in subcutaneous small-resistance arteries of essential hypertensive patients 13 ; however, despite similar blood pressure-lowering effects, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptors blockers, and calcium channel blockers proved to be more effective than diuretics and β-blockers in terms of reduction in the media-to-lumen ratio. 13 The extent of the reduction in the media-to-lumen ratio of subcutaneous small-resistance arteries was recently demonstrated to be an independent predictor of cardiovascular events in essential hypertension. 14 However, in patients with diabetes mellitus, it seems more difficult to obtain a complete regression of small-resistance artery structural alterations, despite prolonged treatment. 15-18A possible explanation is related to the presence, in patients with diabetes mellitus, of hypertrophic remodeling of small arteries, which repre...

Blood pressure normalization via pharmacotherapy improves cutaneous microvascular function through NO‐dependent and NO‐independent mechanisms

“…These findings, which indicate no structural alteration occurred with blood pressure normalization, are inconsistent with other published findings, likely due to the different vessels examined and methods used to determine vessel structure. Currently, technology is in its infancy for direct measurements of cutaneous microvessel structure outside of the nail fold.…”

Effects of age, blood pressure and antihypertensive treatments on retinal arterioles remodeling assessed by adaptive optics

“…Recently developed adaptive optics camera (AOC), which is a novel, accurate optoelectronic method, can provide noninvasively qualitative and quantitative microvascular morphometry of the different anatomical component of small vessels at a near-histological scale in the human retina [7]. Few studies of the effect of blood pressure decrease on retinal vascular morphometry reported long-term improvement in arteriolar narrowing in small hypertensive or diabetic populations and data on short-term modifications are scarce [6][7][8][9][10][11]. AOC noninvasive technology enables large-scale in-vivo measurements of retinal small arteries remodeling through the evaluation of wall-to-lumen ratio (WLR) and its components: wall thickness and lumen internal diameter.…”

Dual renin-angiotensin system blockade and vascular remodeling

“…Clinical data have shown that the antihypertensive effectiveness of aliskiren is similar to that of the other major antihypertensive agents. In experimental and clinical studies, the hemodynamic effects of aliskiren and ramipril were similar, and both treatments induced similar pressure control in hypertensive and diabetic patients [26,27]. Clinical and experimental studies and data from the real world suggest that aliskiren is a very potent antihypertensive agent, particularly when administered in combination with other RAS blockers as well as in low-sodium states [28].…”

“…Nonetheless, aliskiren given on top of valsartan in hypertensive patients reduced blood pressure more than placebo; therefore, it is uncertain whether the more pronounced effect on vascular remodeling and arterial stiffness was because of blood pressure reduction or an independent amplifying effect of dual RAS blockade. In previous studies, ARBs or aliskiren given on top of other antihypertensive medications including RAS blockers or calcium channel blockers improved the remodeling of peripheral resistance arteries independently of blood pressure control [25,27]. Further evaluation on this issue is warranted, to clarify whether aliskiren may exert blood pressure-independent effects on vascular remodeling in distinct vascular beds particularly when given in combination with ARBs.…”

“…Nevertheless, it is questionable whether dual RAS blockade is effective in terms of safety particularly in high cardiovascular risk patients, such as diabetic patients, taking optimal treatment (including full dose of ACE inhibitors or ARBs) with good blood pressure control before aliskiren treatment [29]. Furthermore, although aliskiren seems to have a similar effect in reducing vascular remodeling of resistance arteries as compared with ACE inhibitors, a more pronounced effect has been observed in peripheral resistance arteries with respect to retinal arterioles in high cardiovascular diabetic patients [27].The study by Jumar et al[17] is one of the few studies that investigated the effect of dual RAS blockade in hypertensive patients. The results show that aliskiren given on top of ARBs in patients with primary hypertension and no other cardiovascular risk factors presented no clear effect on vascular parameters.…”