Endothelial function, blood pressure control, and risk modification: impact of irbesartan alone or in combination

Integrated Blood Pressure Control Dovepress open access to scientific and medical research Review Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 54.37.163.172 on 12-Jul-2018 For personal use only. Open Access Full Text Article Endothelial function, blood pressure control, and risk modification: impact of irbesartan alone or in combination This article was published in the following Dove Press journal: integrated Blood Pressure Control 18 May 2010 Number of times this article has been viewed Giuseppe Derosa Sibilla AT Salvadeo Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy Introduction Hypertension and cardiovascular risk Correspondence: Giuseppe Derosa Department of Internal Medicine and Therapeutics, University of Pavia, Ple C Golgi, 2-27100 Pavia, Italy Tel +39 038 252 6217 Fax +39 038 252 6259 Email submit your manuscript | www.dovepress.com Dovepress 6081 Powered by TCPDF (www.tcpdf.org) Abstract: Irbesartan, an angiotensin II type 1 receptor antagonist, is approved as monotherapy, or in combination with other drugs, for the treatment of hypertension in many countries worldwide. Data in the literature suggest that irbesartan is effective for reducing blood pressure over a 24-hour period with once-daily administration, and slows the progression of renal disease in patients with hypertension and type 2 diabetes. Furthermore, irbesartan shows a good safety and tolerability profile, compared with angiotensin II inhibitors and other angiotensin II type 1 receptor antagonists. Thus, irbesartan appears to be a useful treatment option for patients with hypertension, including those with type 2 diabetes and nephropathy. Irbesartan has an inhibitory effect on the pressor response to angiotensin II and improves arterial stiffness, vascular endothelial dysfunction, and inflammation in hypertensive patients. There has been considerable interest recently in the renoprotective effect of irbesartan, which appears to be independent of reductions in blood pressure. In particular, mounting data suggests that irbesartan improves endothelial function, oxidative stress, and inflammation in the kidneys. Recent studies have highlighted a possible role for irbesartan in improving coronary artery inflammation and vascular dysfunction. In this review we summarize and comment on the most important data available with regard to antihypertensive effect, endothelial function improvement, and cardiovascular risk reduction with irbesartan. Keywords: blood pressure, hypertension, endothelial function, irbesartan, antihypertensive drugs, combination therapy Several studies have shown that elevated blood pressure (BP) is a major risk factor for cardiovascular morbidity and mortality. This relationship is strong and continuous in a range of patient populations and age groups.1–5 Most of the major guidelines for the treatment of hypertension recommend that individuals with a BP $ 140/90 mmHg should be regarded as hypertensive, and treated in order to keep BP below this threshold. Systolic BP and diastolic BP (SBP and DBP, respectively) targets generally must be lower in patients at high cardiovascular risk and in those with diabetes or renal disease.6,7 Nearly 40 years ago, data from the Framingham Heart Study showed that SBP was more closely associated with the risk of cardiovascular disease than DBP. Although DBP was shown to be a more useful predictor of cardiovascular risk in hypertensive patients younger than 45 years, for the majority of hypertensive patients, the ability of SBP to predict ischemic cardiovascular disease was not improved by addition of Integrated Blood Pressure Control 2010:3 21–30 21 © 2010 Derosa and Salvadeo, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited. Integrated Blood Pressure Control downloaded from https://www.dovepress.com/ by 54.37.163.172 on 12-Jul-2018 For personal use only. Derosa and Salvadeo DBP data. The superior predictive ability of SBP was more recently confirmed by the Prospective Studies Collaboration, a meta-analysis of 61 prospective observational studies that recorded BP and cause-specific mortality.5 In this study, Lewington et al found that SBP at baseline was more informative than DBP as a predictor of stroke and mortality from ischemic heart disease. Moreover the study concluded that, in middle-aged individuals, prolonged reductions in usual SBP of only 2 mmHg would lead to substantial reductions in the incidence of death secondary to stroke (a 7% reduction) and other vascular causes (10%).5,11 These data are supported by those of Stamler et al who found that SBP had a stronger association with cardiovascular risk than DBP in middle-aged and elderly individuals. At every level of DBP in this population, a higher SBP value was associated with greater cardiovascular risk and lower life expectancy.12 Recently, Benetos et al aimed to determine whether the high cardiovascular mortality rate in treated hypertensive patients was due to hypertension or to the presence of associated risk factors and/or diseases. Using cardiovascular mortality data from treated hypertensive patients (n = 8893) and from untreated age- and gender-matched normotensive and hypertensive controls (n = 25,880) enrolled in the Investigations Préventives et Cliniques cohort, Benetos et al observed that the two-fold increase in cardiovascular and coronary mortality found in treated hypertensive patients persisted after adjustment for cardiovascular risk factors. Adjustment for SBP was necessary to make the mortality rates similar in the two populations. Subsequent inclusion of DBP in the model did not modify the between-group risk ratio. These results suggest that the increased cardiovascular mortality in treated hypertensive patients is mainly due to uncontrolled SBP levels.13 Moreover, the incidence of most adverse cardiovascular events appears to follow a circadian pattern, reaching a peak in the morning shortly after waking and arising. The activity of many physiologic parameters fluctuates in a cyclical manner over 24 hours. It has been suggested that, during the post-awakening hours, the phases of hemodynamic, hematologic, and humoral cycles synchronize, thus creating an environment that predisposes to atherosclerotic plaque rupture and thrombosis in susceptible individuals. BP and heart rate follow a clear circadian rhythm. The increased SBP and DBP in the morning may act as a trigger for cardiovascular events, including myocardial infarction and stroke. The clinical implication of these observations is that antihypertensive therapy should provide BP control over the entire interval between doses.14 22 Powered by TCPDF (www.tcpdf.org) submit your manuscript | www.dovepress.com Dovepress Dovepress There is strong evidence that sustain the high variability of BP over 2 (...truncated)