Effects of angiotensin II type 1 receptor blocker on ambulatory blood pressure variability in hypertensive patients with overt diabetic nephropathy

Abstract

Previous studies have shown increases in ambulatory short-term blood pressure (BP) variability to be related to cardiovascular disease. In this study, we examined whether the angiotensin II type 1 receptor blocker (ARB) would improve ambulatory shortterm BP variability in hypertensive patients with diabetic nephropathy. A total of 30 patients with type II diabetes, along with hypertension and overt nephropathy, were enrolled in this randomized, two-period, crossover trial of 12 weeks of treatment with losartan (50 mg daily) and telmisartan (40 mg daily). At baseline and at the end of each treatment period, 24-h ambulatory BP monitoring with power spectral analysis of heart rate and measurements of proteinuria, estimated glomerular filtration rate and brachial-ankle pulse wave velocity (baPWV) were performed. After 12 weeks of treatment, 24-h, daytime and nighttime shortterm BP variability, assessed on the basis of the coefficient of variation of ambulatory BP, was significantly decreased by telmisartan. Both losartan and telmisartan reduced urinary protein excretion and baPWV. However, compared with losartan, telmisartan significantly decreased urinary protein excretion, baPWV and low-frequency (LF)-to-high-frequency (HF) ratio, an index of sympathovagal balance. Multiple regression analysis showed significant correlations between urinary protein excretion and baPWV, 24-h LF-to-HF ratio, nighttime systolic BP and 24-h short-term systolic BP variability. These results suggest that ARB, particularly telmisartan, is effective in reducing proteinuria in hypertensive patients with overt diabetic nephropathy, partly through inhibitory effects on ambulatory short-term BP variability and sympathetic nerve activity, in addition to its longer duration of action on nighttime BP reduction.

Sympathoinhibition caused by orally administered telmisartan through inhibition of the AT1 receptor in the rostral ventrolateral medulla of hypertensive rats

“…These results are compatible with a previous clinical study, which indicated that TLM (40 mg per day) causes sympathoinhibition to a greater extent than losartan (50 mg per day) in hypertensive patients with diabetic nephropathy. 29 We also previously demonstrated that orally administered atorvastatin, azelnidipine or amlodipine also causes sympathoinhibition through the reduction of oxidative stress in the RVLM of SHRSPs. [45][46][47] However, the results of the present study could not directly elucidate the clinical benefits of TLM in hypertensive patients because the dose of TLM in the present study is not a clinical dose, and there are no clinical trials demonstrating the same reduction in heart rate obtained in the present study.…”

“…In a previous clinical study, TLM, an ARB, is effective in reducing short-term ambulatory blood pressure variability and SNS activation in hypertensive patients with diabetic nephropathy. 29 However, in other clinical studies, ARBs do not have the same beneficial effects on the autonomic nervous system. 30,31 Moreover, it has not been determined whether the sympathoinhibition caused by orally administered ARBs is a class effect of ARBs.…”

The coefficient variation of home blood pressure is a novel factor associated with macroalbuminuria in type 2 diabetes mellitus

“…20 Furthermore, previous human studies have also shown increases in ambulatory BP variability to be related to atherosclerosis, urinary protein excretion and cardiovascular disease in Japanese patients with type 2 diabetes. [21][22][23] It was postulated that the presence of advanced atherosclerosis and impaired baroreflex sensitivity, which was associated with diabetic neuropathy, could lead to increased variability in BP in diabetic patients.…”

Questionable link between normo- to microalbuminuria and home-measured blood pressure variability in hypertension

“…5,6 Short-term BP variability has also been suggested to be clinically relevant because hypertensive patients with similar mean 24 h BP values exhibit more severe organ damage when their short-term BP variability is greater. [7][8][9][10][11][12][13][14] With respect to home-measured BP, several clinical studies (both long-term followup surveys and cross-sectional studies) have provided an epidemiological basis for supporting the greater accuracy of home BP monitoring than clinic BP measurement for the prognosis of fatal and nonfatal cardiovascular disease (CVD). There is a general consensus that home BP monitoring is more convenient, more readily available and less costly than ambulatory BP monitoring, but ambulatory BP monitoring has been recognized to be superior for certain clinical problems, for example, for the detection of non-dippers or sleep BP in patients with chronic renal disease, autonomic neuropathies or sleep apnea, and for the estimation of short-term BP variability.…”