The challenge of hypertension EDWARD D. FREIS, M.D. H ypertension is one of the few im- of thiazides, reserpine, and hydrala- portant cardiovascular diseases zine. Fixed-dose combinations of that can be effectively treated. The these agents should be avoided, how- recently completed cooperative study ever, in the initial stages of dose ad- by the Veterans Administration has justment, but may be substituted la- provided conclusive evidence that ter if available in the doses found the cardiovascular and renal compli- most effective in a particular pa- cations specifically associated with tient. Second, a diuretic plus alpha- even moderate hypertension can be methyldopa is often effective in se- greatly reduced or prevented by con- vere hypertension and is particularly tinuously lowering the blood pres- useful in renal failure. The third and sure with antihypertensive agents. final regimen, a diuretic plus guan- The effectiveness of such prophy- ethidine, will often control the blood laxis will, of course, depend on the pressure when other antihyperten- extent of organ damage already sive agents fail. Guanethidine must present. If treatment is begun be- be carefully titrated in each patient fore vascular changes develop and is to avoid excessive orthostatic hyper- continuously maintained, there is tension. every reason to believe that hyper- It is important to take a long-term tensive complications can be gener- view in treating hypertension. The ally eliminated. physician's goal is to prevent cardio- The most useful drugs for treat- vascular complications that may ing patients with mild or moderate arise ten or 20 years in the future. chronic hypertension are the thia- Reaching that goal requires the pa- zides, reserpine, hydralazine, and tient's cooperation, of course. And alpha-methyldopa. Regimens for se- unfortunately, recent surveys indi- vere hypertension (diastolic blood cate that approximately half the pa- pressure averaging 115 mm Hg or tients started on antihypertensive higher) include first, combinations 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 SUBDIVISION intima and media aorta. coronary, carotid, cerebral, LARGE ARTERIES rena'. i'iac in aorta HEART i 130+ DIASTOLIC BLOOD PRESSURE mm Hg 129.105 104 -90 GRADUAL DEVELOPMENT RAPID DEVELOPMENT fibrinoid necrosis hyalinosis hyperplasia microaneurysms distention fragmentation of elastica collagen proliferation medial necrosis dilatation failure hyalinosis minimal hyalinosis hyperplasia and hyperplasia microaneurysms fewer microaneurysms > age 45 > age 45 distention distention fragmentation of elastica fragmentation of elastica collagen proliferation collagen proliferation atheroma atheroma less medial necrosis no medial necrosis hypertrophy hypertrophy coronary atheroma coronary atheroma dilatation dilatation failure failure myocardial infarction myocardial infarction sudden death sudden death 60 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- gary at first to use trial-and-error m&hods, 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 Qidemiologic surveys indicate that average life expectancy is reduced with even slight elevations of sys- tolic 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 Kg 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. `$' 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