Influence of antihypertensive therapy with cilazapril and hydrochlorothiazide on the stiffness of the aorta

Abstract

The purpose of this study was to examine the effects of the angiotensin-converting enzyme (ACE) inhibitor cilazapril on the elastic properties of the aorta. A standard diuretic antihypertensive drug, hydrochlorothiazide, served for comparisons. Increased aortic stiffness leads to a reduction of the buffering windkessel function and is a major component in the pathophysiology of systolic hypertension, inducing an increase in left ventricular afterload and arterial pulsatile stress as well as a decrease in the subendocardial blood supply. Stiffness of arteries increases with age and blood pressure, and depends on the functional elastic structures of the aortic wall. ACE inhibitors have been shown to directly influence elastic properties of peripheral arteries. Seventeen patients with mild to moderate essential hypertension (age 45-67 years) were treated for 3 months double-blind randomized with either cilazapril (C) 5 mg daily (n = 9) or hydrochlorothiazide (HCTZ) 25 mg daily (n = 8). Aortic elastic properties were noninvasively assessed by measurement of pulse wave velocity along the aorta at rest and during isometric handgrip stress. Accelerated pulse wave velocity indicates elevated arterial stiffness and vice versa. A pressure standardized index of aortic cross-sectional distensibility (2 m) was calculated from arterial mean pressure and pulse wave velocity. Compared with pretreatment values, both therapies significantly reduced blood pressure and pulse wave velocity at rest (C: 9.4 +/- 0.9 vs. 7.7 +/- 0.7 m/sec; HcTZ: 8.9 +/- 0.3 vs. 7.8 +/- 0.4 m/sec; means +/- SEM p < 0.05). During isometric stress only C showed a significant decrease in pulse wave velocity (C: 11.3 +/- 0.8 vs. 9.1 +/- 0.8 m/sec; HCTZ: 9.9 +/- 0.5 vs. 9.0 +/- 0.5 m/sec; means +/- SEM p < 0.05). The index 2m at rest and during handgrip increased significantly (p < 0.05) after C but not after HCTZ. With cilazapril we obtained steeper slopes for the treatment-induced reductions in blood pressure and pulse wave velocity for both rest and handgrip stress values. Correlation of the data at rest and during stress revealed a direct relationship between blood pressure and pulse wave velocity. HCTZ linearly extended the relation observed before treatment toward lower values of blood pressure and corresponding pulse wave velocity without changing the relation per se. Cilazapril, in contrast, moved the relation between these variables and decelerated the pulse wave velocities to a greater extent than would have been expected from the corresponding blood pressure reduction (delta approximately 1 m/sec). These results in patients with mild to moderate essential hypertension support the idea that ACE inhibitors, in addition to reducing blood pressure, may exert an additional hemodynamic effect in improving the elastic properties of the aorta.

Clinical predictors of the response to short-term thiazide treatment in nondiabetic essential hypertensives

“…24,25 In the present study, age, baseline SBP and pulse pressure were positively correlated to the effects of SBP reduction by thiazide treatment, suggesting the possible early presence of increased stiffness of large arteries even in a cohort of mainly middle-aged hypertensives. 26,27 Accordingly, thiazide diuretics either alone or in combination may have particular beneficial effects not only on elderly patients 28,29 but also on younger patients with increased arterial or aortic stiffness as that shown in the present study.…”

Ramipril Reduces Large-Artery Stiffness in Peripheral Arterial Disease and Promotes Elastogenic Remodeling in Cell Culture

“…21 Such effects are sustained with longer-term therapy. [22][23][24][25][26][27][28][29][30][31][32][33] In particular, the Complior Study, involving Ϸ2000 hypertensive patients and 6 months of treatment with perindopril, reported Ϸ1 m/s reduction in carotid to femoral PWV. 34 The current study demonstrates that similar PWV reductions are possible after 6 months ramipril therapy in PAD patients, a group with established atherosclerosis.…”

The effect of antihypertensive drugs on vascular compliance

“…Compared with hydrochlorothiazide, cilazapril improved aortic stiffness in hypertensive patients over a 3-month period, as measured by reduced pulse wave velocity during isometric handgrip [41]. Quinapril regressed left ventricular hypertrophy, reduced the iliac intimal-mediallumen ratio, and increased pulse wave velocity independently of blood pressure reduction in a 6-month study of 15 hypertensive patients [42].…”