The challenge of hypertension EDWARD D. FREIS, M.D. ypertension is one of the few im- portant cardiovascular diseases that can be effectively treated. The recently completed cooperative study by the Veterans Administration has provided conclusive evidence that the cardiovascular and renal compli- cations specifically associated with even moderate hypertension can be greatly reduced or prevented by con- tinuously lowering the blood pres- sure with antihypertensive agents. The effectiveness of such prophy- laxis will, of course, depend on the extent of organ damage already present. If treatment is begun be- fore vascular changes develop and is continuously maintained, there is every reason to believe that hyper- tensive complications can be gener- ally eliminated. The most useful drugs for treat- ing patients with mild or moderate chronic hypertension are the thia- zides, reserpine, hydralazine, and alpha-methyldopa. Regimens for se- vere hypertension (diastolic blood pressure averaging 115 mm Hg or higher) include first, combinations of thiazides, reserpine, and hydrala- zine. Fixed-dose combinations of these agents should be avoided, how- ever, in the initial stages of dose ad- justment, but may be substituted la- ter if available in the doses found most effective in a particular pa- tient. Second, a diuretic plus alpha- methyldopa is often effective in se- vere hypertension and is particularly useful in renal failure. The third and final regimen, a diuretic plus guan- ethidine, will often control the blood pressure when other antihyperten- sive agents fail. Guanethidine must be carefully titrated in each patient to avoid excessive orthostatic hyper- tension. It is important to take a long-term view in treating hypertension. The physician’s goal is to prevent cardio- vascular complications that may arise ten or 20 years in the future. Reaching that goal requires the pa- tient’s cooperation, of course. And unfortunately, recent surveys indi- cate that approximately half the pa- tients started on antihypertensive drug therapy had discontinued it by the time the surveys were made. Why do patients stop taking the drugs? In most instances the reason given suggested that the physician had not sufficiently impressed upon the patient the need for lifelong treatment. Hypertension is asymptomatic un- til serious complications occur. In fact, patients often feel better when their blood pressures are uncon- trolled than when they are reduced, especially if the antihypertensive drugs produce side effects. It is un- realistic to expect a patient to be well motivated unless he thoroughly un- derstands that continuous treatment is necessary to prevent future seri- ous complications, Also, side effects require the physician’s careful at- tention if long-term adherence to the drug regimen is to be expected. Drug-related side effects must be differentiated from other, unrelated complaints; and if the side effects are sufficiently troublesome to threaten continued adherence to the regimen, a different drug should be substituted. EFFECTS OF HIGH BLOOD PRESSURE ON THE CARDIOVASCULAR SYSTEM DIASTOLIC BLOOD PRESSURE mm Hg SUBDIVISION 130+ 129 - 105 104 - 90 ( intima and media, kidney, spleen, ARTERIOLES ANDY pancreas, brain SMALL ARTERIES RAPID DEVELOPMENT fibrinoid necrosis hyalinosis hyperplasia hyalinosis hyperplasia GRADUAL DEVELOPMENT minimal hyalinosis and hyperplasia in brain microaneurysms microaneurysms fewer microaneurysms > age 45 \ > age 45 aorta, coronary, distention distention distention carotid, cerebral, LARGE ARTERIES fragmentation of elastica fragmentation of elastica fragmentation of elastica renal, iliac callagen proliferation collagen proliferation collagen proliferation atheroma atheroma \ in aorta medial necrosis less medial necrosis no medial necrosis ( dilatation hypertrophy hypertrophy failure coronary atheroma coronary atheroma HEART dilatation dilatation failure failure 60 myocardial infarction sudden death myocardial infarction sudden death Patients vary so much in their re- sponses to individual drugs, with re- spect to both effectiveness and side effects, that it is frequently neces- ary at first to use trial-and-error methods, testing one drug and then another. If the patient understands this need from the beginning, he will be more willing to cooperate, because he will realize that the physician is attempting to tailor a regimen that will be both effective and well toler- ated over the long term. The attitude of the physician and his knowledge and skill in handling the drugs are all-important in obtaining this co- operation. Hypertension predisposes to early development of atherosclerosis. Al- though therapy has been effective in preventing complications such as hemorrhagic strokes, nephrosclero- sis, and congestive heart failure, it has been less successful in prevent- ing atherosclerotic complications, particularly myocardial infarction and sudden death. Because of the in- creased susceptibility of the hyper- tensive patient to coronary artery disease, special attention should be paid to other risk factors. Elimina- tion of cigarette smoking and die- tary measures to lower an elevated serum cholesterol level are, there- fore, important additional therapeu- “tic measures. The most difficult question for the physician to decide at present is whether lifelong antihypertensive treatment is justified in patients with mild or borderline hyperten- sion. Much experimental evidence in animals, as well as pathologic obser- vations in man, indicates that the cardiovascular damage associated with hypertension is secondary to elevated blood pressure per se. We also have definitive evidence that antihypertensive drug treatment prevents this vascular damage and reduces morbidity and mortality in male patients with diastolic blood pressures persistently in the range of 100 mm Hg or higher. It is rea- sonable to assume that the same holds true for women. Life insurance statistics and other €pidemiologic surveys indicate that average life expectancy is reduced CARDIOVASCULAR REVIEW/1972 with even slight elevations of sys- tolie or diastolic blood pressure. It is tempting, therefore, to treat all pa- tients who show any elevation above 139/89 mm Hg, particularly those less than 45 years of age. If every man or woman exhibiting a blood pressure of 140 mm Hg systolic or 90 mm Hg diastolic were started on lifetime therapy, approximately 30 million adults in the U.S. would be taking antihypertensive drugs. Does available evidence justify such a radical step-——_one that would tax ex- isting medical resources ? Evidence indicates that the risk of cardiovascular complications in hy- pertension is directly related to the level of blood pressure—the milder the hypertension the lower the risk. Further, the often-quoted life insur- ance statistics relating borderline hypertension to reduction in life ex- pectancy are apt to be misleading, because the results are based on a reading taken at one point in time. Insurance statistics indicate, for example, that of a group of 100 men, 35 years of age, with a diastolic blood pressure of 90 mm Hg, a con- siderably larger number will be dead in 20 years than in a similar group with an initial diastolic blood pres- sure of 80 mm Hg. Such statistics do not tell us, however, that when the 100 men with initial diastolics of 90 reach age 45, some will have de- veloped progressive hypertension with diastolics above 110 mm Hg. Nor do they tell us that in others diastolic pressures will have revert- ed to 80 mm Hg or less. The excess mortality rate may come almost en- tirely from the men whose blood pressures progress into the higher range. Would it be justifiable to treat the men whose hypertension either would not progress or would revert spontaneously to normotensive lev- els? Obviously not. Drug therapy is not entirely innocuous, and it repre- sents an additional expense and in- convenience to the patient. There is no reason, therefore, to rush into treatment when such patients are first seen. If there is no evidence of organic changes nothing is lost if the patients are followed for a year or two to determine which way the hypertension is moving. If it is stable or on a downward trend, treatment should be withheld and the patient re-examined period- ically. If, however, there is progres- sion, with the diastolic persisting in the neighborhood of 100 mm Hg or more, or if there is any funduscopic, ECG, or renal evidence of hyperten- sive disease, treatment should then be instituted without further delay. When there is a family history of hypertension with resulting cardio- vascular complications, the chances are great that the patient is destined to follow the family pattern. These patients should be treated earlier than those without such a history. A final consideration is the work- load the physician must assume in the long-term treatment of a disease as ubiquitous as essential hyperten- sion. Allied health personnel should be utilized to the fullest possible ex- tent in routine follow-up. They can be trained to interview the patient, record blood pressure, and renew prescriptions for medication. The physician can be consulted when there is a need to modify the thera- peutic regimen. Local health agencies such as the heart association can be relied on to provide information about the na- ture of hypertension and its rela- tionship to cardiovascular disease, emphasizing the importance of treatment in the prevention of fu- ture complications. Through such a division of labor, the physician will be able to concentrate his efforts on those aspects of medical manage- ment that require his special knowl- edge and skills. 7 Dr. Freis is senior medical investigator at the Veterans Administration Hospital and professor of medicine at Georgetown University School of Medicine, Washington, D.c. 61