Systemic Hypertension

General Considerations

Systemic Hypertension
Hypertension is a major modifiable risk factor for cardiovascular disease that can, if untreated, result in serious morbidity and mortality from cardiac, cerebrovascular, vascular, and renal disease. In excess of 62 million persons in the United States are estimated to have hypertension, and only slightly more than half of these individuals are aware of their diagnosis. Of those, only a third are at their therapeutic goal. The potential for death and disability is therefore quite high and represents a serious public health issue. Once the diagnosis of hypertension is made and therapy instituted, elevated blood pressure can be lowered, reducing the risk of cardiovascular disease in the vast majority of patients. Major trials in large populations have conclusively demonstrated that treating mild-to-moderate hypertension significantly decreases fatal and nonfatal stroke, coronary events, and renal failure. The wide array of antihypertensive therapy is very effective in reducing blood pressure. Despite similar blood pressure and overall mortality reductions, the reductions in incidence of stroke, coronary ischemic events, heart failure, and renal failure are not the same for all classes of antihypertensive agents. The reasons for these differences have not been totally explained and are the topic of much speculation.
A growing body of direct and inferential evidence suggests that reduction of blood pressure should not be the only goal of antihypertensive therapy. Therapy should also be directed toward controlling all of the patients' cardiovascular risk factors, including dyslipidemia, smoking, and diabetes mellitus.

Pathophysiology & Etiology

Until recently, high blood pressure was synonymous with hypertension; now, however, data suggest that there is considerably more to hypertension than increased blood pressure. Several metabolic and functional abnormalities have even been observed in the children of hypertensive patients prior to blood pressure elevation that are similar to, but of a lesser magnitude than, those found in their parents. Hypertension is also associated with insulin resistance and glucose intolerance. Insulin levels are consistently higher in hypertensive patients than in normotensive controls. This condition of hyperinsulinemia is worsened by thiazide diuretics, especially in the presence of b-blocker therapy. Hyperinsulinemia produces a proliferation of vascular smooth muscle and fibrous tissue and adversely affects the serum lipid profile.

Renin and angiotensin levels are also important factors in determining both the response to therapy and the prognosis. Hypertensive patients with high renin levels have a greater incidence of myocardial infarction than do similar patients with lower levels. Normotensive young adults with a family history of hypertension have been found to have thicker left ventricular (LV) walls and alterations of LV diastolic filling in comparison with control subjects. Although not frankly abnormal, these latter two findings are similar to but less severe than those observed in hypertensive patients. Renal reserve also appears diminished in the children of hypertensive parents.

Hypertension, therefore, is a multisystem disorder with involvement of the cardiovascular, neuroendocrine, and renal systems with a strong genetic component.

Clinical Findings

Blood pressure is a continuous variable with a reasonably normal, or bell-shaped-curve, distribution across the general population. High blood pressure has been classically defined as a diastolic pressure of greater than 90 mm Hg, a systolic pressure greater than 140 mm Hg, or both. The higher the blood pressure, the greater the risk of a cardiovascular events; conversely, the lower the blood pressure, the lower the cardiovascular risk. It is important to stress that isolated systolic hypertension, a systolic pressure of greater than 140 mm Hg with a diastolic pressure of less than 90 mm Hg, is abnormal and requires attention.
The diagnosis of hypertension should not be based on measurements taken at a single office visit. Elevated readings should be confirmed at a second or third visit to establish the diagnosis, and any factors that might elevate blood pressure should be excluded. For example, the patient should refrain from smoking for at least 30 min prior to blood pressure measurement. The blood pressure should be measured, with a cuff of the appropriate size, after at least 5 min of rest in a seated or supine position. The cuff should cover approximately one third of the length of the upper arm and should completely or almost completely encircle the arm. Too small a cuff may overestimate the true blood pressure because it may only partially compress the artery, requiring a higher pressure for total occlusion. The measurements should be made twice in both arms, for a total of four measures. The average of the two measurements in the arm with the higher values is used as the baseline value of blood pressure. Systolic blood pressure is indicated by the phase 1 Korotkoff sound (onset) and diastolic pressure by phase 5, or disappearance, in adults. In children, phase 4, or muffling, has been suggested as the best indicator of diastolic pressure.

The blood pressure obtained in the physician's office, however, does not always accurately represent that experienced by the patient during routine daily living. About 20–30% of patients with mildly elevated office blood pressure may have a hyperadrenergic response to having their blood pressure measured. This hyperreactivity is called white-coat, pseudo-, or office hypertension and may be related to anxiety from merely being in the physician's office or clinic. If the blood pressure is measured in a nonthreatening situation by a friend or relative or with an automated device, the blood pressure in these individuals may be normal. Blood pressure hyperreactivity should be suspected in patients who have persistently elevated blood pressure in the office and normal pressure measurements out of the office or in patients who have hypotensive symptoms but remain hypertensive in the office despite therapy. It has not been clearly established whether the blood pressure in these individuals is truly normal or whether they have an early or different form of hypertension. Several studies have found alterations in cardiac structure and function that are somewhere between those found in normotensive subjects and those found in hypertensive patients. No large outcome studies are available.

The best way to evaluate a patient with suspected white-coat hypertension is to use an automated ambulatory blood pressure device that measures the blood pressure periodically throughout the day and night. The patient quickly becomes accustomed to the small, light-weight, portable device, and a representative series of recordings can be obtained. The accuracy of these devices allows separation of those patients with true elevations of blood pressure from those who are hyperreactors. The devices are also useful in evaluating patients with episodic hypertension and those with borderline blood pressure elevations who already have evidence of involvement of the heart, kidneys, or vasculature. Automated blood pressure monitoring can be used to evaluate the duration and effectiveness of antihypertensive medication; correlate blood pressure with damage to the heart, kidneys, or blood vessels; and determine the prognosis. Its value in routine evaluation of hypertensive patients has not been clearly established, however.

Treatment

The treatment of hypertension has evolved over the past four decades as we have accumulated knowledge of the natural history, pathophysiology, and risk factors for hypertension as well as the effects of therapy and the interactions of these factors. The goal of treating high blood pressure is to reduce blood pressure and thereby prevent or reverse end-organ damage without causing significant side effects or requiring unacceptable changes in lifestyle. We now have many classes of antihypertensive agents that effectively lower blood pressure, either alone or in conjunction with an agent from another class of drugs. Because of the potentially detrimental metabolic changes caused by some agents, their failure to reduce the incidence of myocardial infarction, and the multisystem involvement of hypertension, it is essential to choose a regimen that effectively lowers blood pressure without causing abnormalities. The following recommendations incorporate data from large long-term trials and experimental evidence from human and animal studies.
Nonpharmacologic therapy and coronary risk factor reduction should be initiated in all patients once the diagnosis of sustained hypertension is made. Individuals with mild (systolic BP, 140–159; diastolic, 90–99) or moderate (systolic, 160–179; diastolic, 100–109) hypertension can be treated with nonpharmacologic therapy for 3–6 months. If this fails to reduce blood pressure to below 140/90 mm Hg within that time, pharmacologic therapy should be initiated. If end-organ damage is already present at diagnosis, or if other major coronary risk factors such as diabetes or dyslipidemia are present, pharmacologic therapy should be initiated once the diagnosis has been made. Individuals with severe hypertension (systolic BP higher than 180; diastolic higher than 110) should have both nonpharmacologic and drug therapy initiated once the diagnosis is made.

Prognosis
Significant reductions in blood pressure definitely reduce the incidence of stroke, renal and cardiac failure, and acute coronary syndromes. We must attempt to prevent cardiac and vascular disease by taking into account all the relevant prognostic factors, not just blood pressure alone. Because coronary artery disease is the most common adverse outcome of hypertension, we must choose antihypertensive drugs not only for their blood pressure-lowering properties, but also for their effects on other critical cardiovascular, metabolic, and renal end-points. Aggressive control of all of the cardiac risk factors is essential for optimal outcomes in hypertensive patients.