Hypertension

Hypertension is an important public health challenge in the United States because of its high prevalence and the concomitant increase in the risk of cardiovascular/renal disease. As many as 43 million Americans have hypertension, which is defined as a systolic blood pressure (SBP) 140 mm Hg and/or a diastolic BP (DBP) 90 mm Hg and/or taking antihypertensive medications. Hypertension is often portrayed as a “silent killer” because patients with mild or moderate hypertension are often asymptomatic. When symptoms appear as a result of organ damage, therapeutic options are limited. Although the symptoms produced by these organ complications (MI, HF, stroke, or chronic renal failure) are associated with decreased QoL, possible alterations in QoL in patients with mild to moderate hypertension who do not have such complications remain controversial. Declines in QoL seen in aging populations complicate the analysis of a potential relationship between “asymptomatic” hypertension and QoL in older patients.Hypertension is the most important modifiable risk factor for coronary heart disease (the leading cause of death in the US population), stroke (the third leading cause of death), congestive heart failure, end-stage renal disease, and peripheral vascular disease.The goal of antihypertensive therapy is to abolish the risks associated with blood pressure (BP) elevation without adversely affecting quality of life. It is well established that effective blood pressure (BP) control reduces the risk of cardiovascular disease and stroke in patients with hypertension.For every 20mmHg decrease in systolic BP (SBP), there are 30 and 40% reductions in ischaemic heart disease and stroke mortality, respectively.

Age-associated increases in hypertension prevalence derive from changes in arterial structure and function accompanying aging. Large vessels become less distensible, which increases pulse wave velocity, causing late systolic blood pressure (SBP) augmentation and increasing myocardial oxygen demand. Reduction of forward flow also occurs, limiting organ perfusion. These undesirable alterations are enhanced with coronary stenosis or excessive drug-induced diastolic blood pressure (DBP) reduction. Autonomic dysregulation contributes to orthostatic hypotension (a risk factor for falls, syncope, and cardiovascular [CV] events) and orthostatic hypertension (a risk factor for left ventricular hypertrophy [LVH], coronary artery disease [CAD], and cerebrovascular disease). Progressive renal dysfunction, because of glomerulosclerosis and interstitial fibrosis with a reduction in glomerular filtration rate (GFR) and other renal homeostatic mechanisms such as membrane sodium/ potassium–adenosine triphosphatase, fosters hypertension through increased intracellular sodium, reduced sodium– calcium exchange, and volume expansion. Microvascular damage contributes to chronic kidney disease (CKD) as reduced renal tubular mass provides fewer transport pathways for potassium excretion.

Compliance to prescribed antihypertensive regimen is essential to achieve the target BP. Among many factors, the complexity and tolerability of the antihypertensive regimen are two major determinants of patient compliance. In a recent meta-analysis by Law et al of 354 randomized, double-blind trials, the mean placebo-corrected reduction in BP with monotherapy was only 9.1/5.5 mm Hg. There was little difference in this regard between a diuretic, b-blocker, angiotensinconverting enzyme (ACE) inhibitor, angiotensin receptor blocker (ARB), or calcium channel blocker (CCB). Similar results were found in the Treatment of Mild Hypertension study, in which comparable BP reduction was observed after long-term treatment with a diuretic, b-blocker, CCB, a-blocker, and ACE inhibitor.Multiple antihypertensive agents needed to achieve the target BP control in majority of the patients add to the complexity of such therapy. The combination of two antihypertensive drugs is recommended by the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) in patients with blood pressure (BP) not adequately controlled with antihypertensive monotherapy or as first-line therapy in patients at high risk.Fixed-dose combinations of antihypertensive agents effectively lower BP and help simplify the therapeutic regimen and increase compliance.

In response to a rising demand for highly effective and tolerable fixed-dose combinations with amlodipine, a combination of olmesartan-amlodipine was developed that was able to reduce BP by −30.1/−19.0 mmHg in doses up to 40/10 mg in a recent study. Almost maximal BP reduction was achieved as early as four weeks after treatment initiation and was sustained throughout the eight-week study period. Tolerability was good, with a reduction of incidence of edema, known to be increased with amlodipine monotherapy at high doses. Fixed-dose combinations of antihypertensive drugs improve patient compliance which, in turn, is associated with a reduction in hospitalization and cardiovascular events. The results of the COACH (Combination of Olmesartan Medoxomil and Amlodipine Besylate in Controlling High Blood Pressure) study, a clinical trial that assessed the efficacy and safety of amlodipine besylate (dihydropyridine CCB) in combination with olmesartan medoxomil (ARB) in patients with mild-to-severe hypertension, have been published elsewhere. Here we report a prespecified subgroup analysis of the COACH study in patients with diabetes, Blacks, elderly (X65 years) patients and those who are overweight/obese with a BMIX30 kg/m 2.