PHYSIOLOGICAL PROFILE
It has long been assumed that in African Americans, plasma volume is expanded; however, the actual data on this are conflicting. Yet, there is little doubt regarding the fact that African Americans, particularly women, prominently manifest salt sensitivity. Salt sensitivity is an important intermediate BP phenotype for a multiplicity of reasons.
First, salt sensitivity has been linked to obesity in both Caucasians and African Americans. Although my focus is on hypertensive individuals, normotensive individuals also manifest salt sensitivity but to a lesser degree than among hypertensive individuals. I recently showed that the link of salt sensitivity with body size in African Americans was virtually all attributable to fat notlean body mass. Moreover, I and others have shown that the abnormal diurnal BP variation—an attenuation or absence of the nocturnal BP fall—has been linked to obesity and, in turn, to salt sensitivity. Salt sensitivity also increases BP medication requirements, although to a lesser degree for diuretics and calcium antagonists than for other drug classes. This makes attainment of ade- quate trough BP reductions—a surrogate marker of 24-h BP control—
perhaps more difficult in salt-sensitive patients. Salt-sensitivity has also been linked to a pattern of abnormal intrarenal hemodynamics (raised intraglomerular pressure, increased intrarenal vascular resistance and filtration fraction) that, if sustained over time, could lead to progressive renal injury.
African Americans are also noted for their tendency to manifest suppressed circulating renin levels as well as a lesser stimulation of circulating renin with provocative volume-depleting stimuli. Suppres- sion of circulating renin levels can be a marker for several physiologic and hemodynamic states, including high levels of dietary sodium intake, high levels of tissue angiotensin II in the juxtaglomerular cells of the renal afferent arteriole, high BP levels, and plasma volume expansion.
The totality of evidence, though largely circumstantial, points to a central role for the renin-aldosterone-kinin system in the pathogenesis of elevation and pressure-related TOD in African Americans.
Although it is beyond the scope of this chapter, several other patho- physiologic aberrations have been described in African Americans.
However, it is important for the reader to understand that these racial differences represent quantitative, not qualitative, differences. In addi- tion, within any racial or ethnic group, there is tremendous variation in the actual expression of any of the aforementioned physiologic traits.
Finally, whether racial/ethnic physiologic tendencies represent primary (genetic) or secondary phenomena, perhaps attributable to BP per se, remains speculative.
GENERAL THERAPEUTIC PRINCIPLES
The general therapeutic approach to hypertension does not vary significantly by race or ethnic group. Once the diagnosis of hypertension has been confirmed, the patient should undergo comprehensive history, physical, and laboratory examinations that focus on identifying the status of related target organs (brain, kidneys, and heart) that may have been damaged by hypertension and/or other coexisting cardiovascular conditions such as diabetes mellitus or hyperlipidemia. An assessment of patient well-being is extremely important.
Lifestyle modifications such as weight loss, salt and alcohol restric- tion, and increased physical activity are particularly useful, either alone or in combination with antihypertensive drug treatments, in lowering BP. Weight loss is particularly effective in lowering BP. Moreover, weight loss attenuates the pressure response to dietary sodium intake, which, in turn, lowers antihypertensive medication requirements to achieve a given BP level. Reducing sodium intake is also an important lifestyle change in hypertensive African Americans because the major- ity of hypertensive African Americans are salt sensitive. Thus, lowering sodium intake to approx 2 to 3 g (87–131 mmol/d) will augment the BP-lowering response of virtually all antihypertensive drug classes, particularly those with the renin-angiotensin-aldosterone-kinin system as their primary site of action. Appropriate levels of regular aerobic physical activity lower BP as well as contribute to the maintenance of normal body weight. African-American women, particularly those residing in the southeastern United States, are disproportionately over- weight compared with Caucasian women. In addition, many African- American women report low levels of physical activity. Nevertheless, hypertensive African Americans of both sexes will benefit from prudent initiation of the aforementioned lifestyle modifications. However, if the patient is unable to effectively adopt these lifestyle modifications, the practitioner should avoid the trap of allowing the patient’s lack of success to become a wedge to the patient-practitioner relationship.
Finally, there must be ample consideration and respect of individual preference, which may be deeply rooted in cultural tradition and beliefs.
THERAPEUTIC TARGETS
Appropriate therapeutic targets can be set only after comprehensive evaluation of the patient. The minimum therapeutic goal for those with uncomplicated hypertension is <140/90 mmHg. However, a minimum BP of <130/85 mmHg should be the therapeutic goal in hypertensive patients with renal insufficiency, diabetes mellitus, and/or CHF. When proteinuria exceeds 1 g/24 h, the appropriate BP target is even lower at <125/75 mmHg. Gradual attainment of these BP levels over many weeks to months is preferable to more rapid BP normalization if overmedication and treatment-related side effects are to be avoided.
African-American hypertensive patients will not infrequently be a can- didate for initiation of drug therapy at BP levels <140/90 mmHg because of their high prevalence of coexisting diabetes, renal insufficiency, and/
or CHF.
Likewise, a significant number of African Americans also will qualify for lower target BP levels well below 130/85 mmHg. Nevertheless, certain drugs may be preferred within a multidrug regimen. The avenues available to express such preference are highlighted in the Preferred Drug Therapies section. The practitioner should remember the low likelihood of achieving target BP in persons with JNC VI stage 3 hypertension with monotherapy.
Race or ethnicity is not an appropriate criterion on which to base the selection of antihypertensive drug therapy for individual patients.
A widespread clinical perception has been that`-blockers and angioten- sin-converting enzyme (ACE) inhibitors are ineffective in African- American hypertensive patients. Concern has been raised that the cur- rently marketed angiotensin II receptor antagonists are also ineffective hypotensive agents in African Americans. However, careful consider- ation of the published data, particularly regarding the ACE inhibitors and`-blockers, is that at low doses these agents are less effective in lowering BP in African Americans relative to Caucasians. Moreover, among African Americans, when used as monotherapy these agents also appear to be less effective than diuretics and calcium antagonists for lowering BP. On the other hand, the data are relatively persuasive that uptitration of ACE inhibitors into the upper part of their dosing range results in a substantial narrowing or obliteration of racial BP response differentials, and also improves the BP-lowering response of these agents relative to that obtained with calcium antagonists and diuretics.
Dietary sodium intake attenuates the magnitude of BP lowering with virtually all antihypertensive drug classes. The attenuation of the BP- lowering effect can be overcome, at least in part, by several strategies:
(1) reduce the sodium intake, (2) uptitrate the drug dose, or (3) add a diuretic. Perhaps one major reason that diuretics and calcium antago- nists have been widely perceived as the most effective antihypertensive monotherapy for the African-American hypertensive patient is because their BP lowering efficiency is less attenuated than other drug classes in the setting of usual (physiologically high) amounts of dietary sodium.
It is reasonable to give an adequately dosed antihypertensive agent about 6 wk to fully manifest its BP-lowering effect at a given dose.
When a therapeutic trial of sufficient duration has been given to a drug and BP remains uncontrolled, the practitioner must decide whether to substitute or add another drug from a different therapeutic class. When BP levels are in the high JNC VI stage 2 range (170–179/105–109 mmHg), strong consideration should be given to adding a second anti- hypertensive agent as opposed to substituting another drug.
PREFERRED DRUG THERAPIES
African Americans and Native American Indians will not infre- quently have coexisting cardiovascular-renal conditions for which selected drug therapies should be preferred. For example, both diabetic and nondiabetic renal insufficiency represents conditions for which ACE inhibitors have proven benefit. Thus, the practitioner can show preference for an ACE inhibitor by initiating therapy with an ACE, pushing the dose into the upper therapeutic range, and adding a second agent from a different class when monotherapy with the ACE inhibitor fails to achieve the BP goal. Even when monotherapy with the ACE inhibitor has been ineffective in reaching the BP goal, the added agent will manifest a steeper dose-response curve when prescribed concur- rently with the ACE than when taken at the same dose as monotherapy.
It has been repeatedly shown that African Americans with CHF have ACE inhibitors prescribed less often than their Caucasian counterparts.
A similar scenario can be construed for a `-blocker or long-acting calcium antagonist to be a preferred drug class in hypertensive African Americans with symptomatic coronary ischemia. _1 Antagonists are particularly useful, either alone or in combination, in diabetic persons because these agents improve insulin sensitivity, and they also have a
favorable effect on all lipoprotein fractions. A key concept regarding a preferred drug dose is that it should not be abandoned solely because of inadequate BP lowering.
CONCLUSION
The ultimate goal of antihypertensive drug therapy in African Americans is to improve patient well-being as well as to prevent pres- sure-related complications such as stroke, cognitive dysfunction, heart failure, renal insufficiency, and myocardial infarction. Patient character- istics that may attenuate the BP response to various antihypertensive drugs—renal function, obesity, sodium intake—are disproportionately prevalent in African Americans. However, when treating an individual patient, race is an inadequate criterion on which to base drug selection.
African Americans will require combination drug therapy more often than their Caucasian counterparts to achieve their target BP. Neverthe- less, the benefits of successful BP treatment to goal or lower levels will confer tremendous benefit, to both patient well-being and overall cardiovascular health in this high-risk population.
SUGGESTED READINGS
Flack JM, Neaton JD, Daniels B, Esunge P (1993) Ethnicity and renal disease: lessons from multiple risk factor intervention trial and the Treatment of Mild Hypertension Study.Am J Kidney Dis21(4) (Suppl. 1):31–40.
Flack JM (1988) Therapy of hypertension in primer on kidney diseases. In: Greenberg, A, ed. Cheung AK, et al., assoc. ed).Primer on Kidney Diseases,2nd ed., San Diego: Academic, pp 506–516.
Flack JM, Staffileno B (1998) Hypertension in Blacks. In: Johnson R, ed.Comprehen- sive Clinical Nephrology,London: Mosby International.
Ooi WL, Budner NS, Cohen H, Madhavan S, Alderman MH (1989) Impact of race on treatment response and cardiovascular disease among hypertensives.Hyperten- sion14(3):227–234.
Weir MR, Hall PS, Behrens MT, Flack JM (1997) Salt and blood pressure responses to calcium antagonism in hypertensive patients.Hypertension30(3) (Pt. 1):422–427.
Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (1997) The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med157:2413–2446.