High dose treatment with angiotensin II receptor blocker in patients with hypertension: Differential effect of tissue protection versus blood pressure lowering
Introduction
The renin–angiotensin–aldosterone system (RAAS) plays an integral role in cardiovascular homeostasis through its effects on vascular tone and volume. The final mediator of the RAAS cascade Angiotensin II modulates blood pressure, causes myocardial cell hypertrophy and fibrosis, and promotes the inflammatory cascade in the atherosclerotic lesions. Local Angiotensin II formation contributes to cell injury, endothelial dysfunction, and fibroblast proliferation, vascular toxicity and fibrosis [1], [2], [3]. Interruption of the RAAS with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs) reduces cardiovascular mortality [4], [5], [6] and renal disease progression [7], [8]. Aggressive inhibition of RAAS at the tissue level might afford the best cardiovascular protection. However, dosages of ACEIs and ARBs used in practice are currently aimed only at reducing blood pressure and there is no known dose-response for cardiovascular and renal protection.
Measurements of arterial elasticity, using arterial pulse-wave contour analysis, provides useful information regarding vascular health and can be regarded as a valid marker of generalized atherosclerosis [9], [10]. Moreover, aortic pulse wave velocity is a predictor of cardiovascular mortality [11], [12], [13]. Estimation of vascular compliance may serve not only for cardiovascular risk assessment but also for monitoring of treatment interventions. The present study was designed to determine the effect of different doses of the angiotensin II receptor blocker, Candesartan, on arterial compliance, inflammatory and metabolic parameters in hypertensive patients with multiple cardiovascular risk factors.
Section snippets
Subjects
In a monocentric study, 69 patients diagnosed as suffering of hypertension and at least one additional cardiovascular risk factor were recruited from the outpatient clinic and evaluated for the study. Following a washout period of 2–4 weeks, of medications affecting RAAS, all patients were randomized into three groups: group 1 included patients treated with high dose Candesartan (32 mg), group 2 included patients treated with conventional doses of Candesartan (16 mg), group 3 included patients
Results
Of the 69 patients recruited to the study 67 completed the 6-month treatment period (22 patients from group 1, 23 patients from group 2, 22 from group 3). Clinical characteristics of the three study groups are present in Table 1. As can be seen all three patient groups were similar with respect to age, gender distribution, presence of cardiovascular risk factors, and baseline blood pressure level. Concomitant medications, which might affect arterial compliance parameters, like statins and
Between group comparisons
As can be seen in Table 1, all three patient groups were similar at baseline in terms of hemodynamic, metabolic and inflammatory parameters. Moreover, during the whole period of 6 months changes in BP were similar in all three groups: no difference in delta-SBP (p = 0.58) as well in delta-DBP (p = 0.69) were detected between groups. However, significant across-group differences were detected at baseline for LAEI, driven by the difference between group 1 and 3 (p = 0.024). Baseline SAEI also differed
Discussion
The prominent finding of the present study is that angiotensin II receptor blockade induced by Candesartan significantly improves large and small artery elasticity in hypertensive patients with multiple cardiovascular risk factors. This effect on arterial wall is independent of the blood pressure lowering effect and extends beyond simple BP reduction. In addition, treatment with high doses of Candesartan improves arterial stiffness to a greater extent than conventional doses of Candesartan,
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