Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 12, Issue 3, 2014

Data collected over a 30-year period have demonstrated the increasing prevalence of hypertension with age. Aging is an inevitable part of life and brings along two inconvenient events: physiologic decline and disease state. High blood pressure (HBP) is an important risk factor for cardiovascular morbidity and mortality, particularly in the elderly. It is a significant and often asymptomatic chronic disease, which requires optimal control and persistent adherence to prescribed medication to reduce the risks of cardiovascular, cerebrovascular and renal disease. Hypertension in the elderly patients represents a management dilemma to geriatric and cardiovascular specialists and other practitioners. Furthermore, with the wide adoption of multiple drug strategies targeting subgroups of hypertensive patients with specific risk conditions to lower blood pressure (BP), difficult questions arise about how aggressive treatment of elderly patients should be. The purpose of the following chapter article is to review the pathophysiology of aging as well as the epidemiology and the clinical assessment of high blood pressure (HBP) in older people.

High blood pressure is a major cardiovascular risk factor. The prevalence of hypertension increases with aging. As a consequence of changes in arterial wall that leads to arterial stiffness, the majority of elderly patients suffer isolated systolic hypertension. The evidence strongly supports that hypertension in the elderly is associated with an increase in stroke risk and cardiovascular mortality and morbidity. Several trials have shown the benefits of treating hypertension in elderly patients. Even in the very old patients, the use of antihypertensive agents such as calcium channel blockers, thiazide and thiazide-like diuretics, and inhibitors of the renin-angiotensin system reduce the risk of complications in those patients. However, most patients will need two or more drugs to reach the recommended goals. Hypertension in the elderly has special conditions that must be assessed in the evaluation of the patient (as pseudohypertension and white coat hypertension), and issues that may affect the therapeutic choice and the response to treatment, as comorbidities and polypharmacy.

Beta-blockers are considered as suitable drugs to treat essential hypertension also in elderly patients and they are currently recommended for treatment of hypertension, even in older patients, by the ESH/ESC Guidelines. Different meta-analyses and results of some large clinical trials have shown that here is no clinically difference between β-blockers and other drug classes in decreasing high blood pressure in elderly hypertensive patients. The new vasodilating β-blockers, as nebivolol, carvedilol and celiprolol, offer additional important advantages, compared with traditional β-blockers. The cardio-protective effect of β-blockers (except atenolol) is not inferior to that obtained with other drug classes which is independent of age and gender of the patients.

The aging population is rapidly increasing, and is mainly due to medical advances and the control of chronic diseases, with a real worldwide increase in the elderly population. Special emphasis has been placed on the management of hypertension in the geriatric patient, since its long-term benefits have been shown to prevent both cerebral and cardiac infarctions. Calcium channel blockers have been shown to be effective in this condition in the elderly. Their success depends on their mechanism of action, as well as on the physiological changes observed, and on the aging process itself, which include cardiac hypertrophy, calcification of cardiac valves, and a decrease in the excitation-conduction system. There is thickening of the tunica intima of the arteries, and the production of nitric oxide at cellular level decreases with age, along with an increase in endothelin 1, which leads to vascular endothelium dysfunction. In the kidneys, there is a decrease in prostacyclin, endothelial hyperpolarization factor, as well as the Klotho anti-aging protein, which leads to an increase in blood pressure. Calcium channel blocker drugs have been shown to be effective in any age group for the management of hypertension, and are safe in the elderly patients. These drugs block L-type calcium channels, with the long-acting or latest generation dihydropyridines being the most effective of this group. Several studies, including SYST-EUR2, NORDIL, and STOP-2, have demonstrated the effectiveness of these drugs in the geriatric patient. The prescribing of long-acting calcium channel blocker drugs in a single dose is the most recommended. The safety in the use of this drug group has been demonstrated in the treatment of hypertension in the elderly patient, with a level of effectiveness similar to other widely used drugs.

Systolic arterial hypertension is the most common variable of the hypertensive disease and it is mainly concentrated in individuals who are 60 years old and older. At a global level, such population is rapidly growing in every society. In senior persons, losing weight and lowering sodium consumption helps decreasing Blood pressure (BP). Using antihypertensive medications reduces cardiovascular mortality. In this chapter the management of BP with diuretics is discussed.

Resistant hypertension (RH) is a prevalent medical problem across all ages but is more frequent in elderly patients. This entity has to be distinguished from clinical settings which may simulate it such as apparent hypertension (pseudohypertension) or apparently resistant hypertension (pseudoresistant hypertension) [1]. An appropriate therapy for RH can be achieved by the addition of second line antihypertensive drugs: antialdosteronic diuretics, central agents, alpha blockers, direct vasodilating agents, and exogenous nitric oxide donors. These antihypertensive drugs are considered as second line drugs since they are less effective as monotherapy to reduce blood pressure (they induce counte regulatory responses that limit their antihypertensive effect such as volume expansion or reflex tachycardia) and prevent cardiovascular events, or due to significant adverse effects (postural hypotension, sedation, hyperkalemia). Second line drugs are also used when there is allergy or intolerance to the first line ones [2, 3].

Hypertension is a major cardiovascular risk factor that increases morbidity and mortality in the elderly because, numerous factors contribute to development and progression of hypertension in elderly patients, including excessive salt intakes, obesity, physical inactivity and stress. Hypertension treatment usually results in a combination of both, pharmacologic and non-pharmacologic measures. These latter are an essential part of treatment and cannot be replaced by the medication. Non pharmacologic management known as lifestyle modifications has a pivotal role in non-hypertensive and hypertensive individuals. In case of non-hypertensive or pre-hypertensive patients it can prevent hypertension development and in hypertensive people it has the capacity to lower blood pressure levels as well as modify cardiovascular complications. Older people tend more often to treatment resistance so it is increasingly necessary to have other therapeutic resources for patients with difficult control of disease. Minimally invasive techniques are developing that might improve the course of the disease and prevent its complications by a more extended time.In this chapter, we will review components of nonpharmacological treatment of hypertension focusing on the geriatric patient.