Brachial Pressure–Independent Reduction in Carotid Stiffness After Long-Term Angiotensin-Converting Enzyme Inhibition in Diabetic Hypertensives

Abstract

Abstract-Hypertension and diabetes are associated with an increased arterial stiffness. A direct blood pressureindependent effect of angiotensin-converting enzyme inhibitors on arterial stiffness has never been unequivocally demonstrated. In this mechanistic study, we used an experimental design in which patients responding to 1 month treatment with 4 mg perindopril were randomized double-blind to either 4 mg perindopril or 8 mg perindopril for 6 months. We determined carotid distensibility with echotracking and applanation tonometry at baseline and after the 7-month treatment period in 57 essential hypertensive patients with type 2 diabetes (age 63Ϯ7 years). We monitored ambulatory blood pressure at baseline and after treatment. After 7 months treatment, 24-hour ambulatory blood pressure significantly decreased, with no significant difference between 4 mg and 8 mg perindopril. Carotid distensibility increased more after 8 mg perindopril compared with 4 mg perindopril (8 mg ; ANOVA, dose-period interaction, PϽ0.05). Carotid internal diameter and elastic modulus were significantly lower after 8 mg perindopril compared with 4 mg perindopril, independent of blood pressure reduction. These results indicate a dose-dependent and blood pressure-independent reduction in carotid stiffness under chronic treatment with an angiotensin-converting enzyme inhibitor. They suggest that arterial distensibility was increased through an inward remodeling, leading to a reduction in wall stress, thus reducing elastic modulus. They also suggest that long-term administration of high doses (8 mg) of perindopril is required to improve carotid structure and function in hypertensive patients with type 2 diabetes.

Elevated circulating endothelial microparticles and brachial–ankle pulse wave velocity in well-controlled hypertensive patients

“…Hypertension is accompanied by the reduced arterial elasticity and impaired endothelial function, which synergistically contribute to the pathogenesis of vascular disease. 1,6,9,19 In our study, hypertensive patients displayed both elevated levels of circulating EMPs and faster baPWV, which was consistent with the earlier studies. 19,20 Therefore, it is believed that antihypertensive treatment for patients with hypertension should restore the vascular dysfunction.…”

“…1 Although antihypertensive pharmacotherapy with the specific and arbitrary goal to modify BP profiles significantly reduced vascular events, emerging evidence indicates that with equivalent effects on lowering blood pressure, some but not all antihypertensive agents, lead to more reduction of vascular events. 2,3 This apparently beneficial effects beyond BP lowering may be, at least in part, because of further improvement of agent-related vascular properties, [2][3][4][5][6] suggesting that the evaluation of vascular function may be useful complement to brachial BP levels, and may provide more sensitive and specific markers for the vascular risk stratification.…”

Acute effects of renin-angiotensin system blockade on arterial function in hypertensive patients

“…8,9,[11][12][13][14]39 Recent data support that quinapril and captopril are equally efficient in modifying important surrogate end points with prognostic significance, such as left ventricular mass. 11 On the other hand, some studies have underscored that an improvement of arterial function in hypertensives may benefit prognosis, 5,7 but there are no trials to directly compare different ACEIs with regard to outcomes.…”

“…8,50 We used telmisartan 80 mg, since this dose may result in a greater arterial effect compared with lower doses. 50 On the other hand, studies that compared the acute endothelial effects of different ACEIs showed that increasing the dose of the low-tissue affinity ACEI does not modify the effect on arterial function.…”

“…5 Likewise, there are data showing that the reversal of endothelial dysfunction, that is present in hypertensive patients, 6 may benefit prognosis. 7 Drugs that block the renin-angiotensin system (RAS), such as angiotensin converting enzyme (ACE) inhibitors (ACEIs), may improve cardiovascular structure and function, [8][9][10][11][12][13] and this effect is not fully explained by the respective BP change. [8][9][10]12,14 However, different ACEIs may not confer a same degree of organoprotection, and this is perhaps due to dissimilarities in their propensity to penetrate vascular tissue and inhibit the tissue ACE.…”