Charles K. Francis

Rationale and Design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Are newer types of antihypertensive agents, which are currently more costly to purchase on average, as good or better than diuretics in reducing coronary heart disease incidence and progression? Will lowering LDL cholesterol in moderately hypercholesterolemic older individuals reduce the incidence of cardiovascular disease and total mortality? These important medical practice and public health questions are to be addressed by the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a randomized, double-blind trial in 40,000 high-risk hypertensive patients. ALLHAT is designed to determine whether the combined incidence of fatal coronary heart disease (CHD) and nonfatal myocardial infarction differs between persons randomized to diuretic (chlorthalidone) treatment and each of three alternative treatments—a calcium antagonist (amlodipine), an angiotensin converting enzyme inhibitor (lisinopril), and an a-adrenergic blocker (doxazosin). ALLHAT also contains a randomized, open-label, lipid-lowering trial designed to determine whether lowering LDL cholesterol in 20,000 moderately hypercholesterolemic patients (a subset of the 40,000) with a 3-hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitor, pravastatin, will reduce all-cause mortality compared to a control group receiving “usual care.” ALLHATs main eligibility criteria are: 1) age 55 or older; 2) systolic or diastolic hypertension; and 3) one or more additional risk factors for heart attack (eg, evidence of atherosclerotic disease or type II diabetes). For the lipid-lowering trial, participants must have an LDL cholesterol of 120 to 189xa0mg/dL (100 to 129xa0mg/dL for those with known CHD) and a triglyceride level below 350xa0mg/dL. The mean duration of treatment and follow-up is planned to be 6 years. Further features of the rationale, design, objectives, treatment program, and study organization of ALLHAT are described in this article.

Coronary Revascularization and Cardiac Catheterization in the United States: Trends in Racial Differences

OBJECTIVESnWe sought to determine whether racial differences in rates of coronary artery bypass graft surgery (CABG), percutaneous transluminal coronary angioplasty (PTCA) and cardiac catheterization decreased after 1980.nnnBACKGROUNDnMany reports of racial differences in utilization of CABG have been published since 1982. However, changes in the relative utilization of revascularization over time have received little attention.nnnMETHODSnData from the National Hospital Discharge Survey were examined for the years 1980 through 1993. Estimated numbers of procedures performed in nonfederal U.S. hospitals were used to compute age-adjusted rates per 100,000 population by year and race for patients 35 to 84 years old.nnnRESULTSnIn patients 35 to 84 years old, the rate of CABG increased in blacks and whites between 1980 and 1993. Between 1986 and 1993, there was little change in the black/white ratio of age-adjusted rates (0.23 in 1980 through 1985 combined, 0.38 in 1986 and 0.43 in 1993). An apparent increase from 0.23 in 1980 through 1985 combined may have been due to sampling variation. Despite rapid increases in rates of PTCA in both races, no increase in the black/white ratio was noted (0.57 in 1993). However, the rate of inpatient cardiac catheterization increased more rapidly in blacks than in whites. This resulted in an increase in the black/white ratio of age-adjusted rates from 0.42 in 1980 to 0.91 in 1993.nnnCONCLUSIONSnRates of CABG, cardiac catheterization and especially PTCA increased between 1980 and 1993, a period during which racial disparities in the procedures became widely known. Despite apparent increases in the black/white ratio for inpatient cardiac catheterization, large racial disparities in the utilization of CABG and PTCA persist and require further evaluation and possible intervention.

Hypertension, cardiac disease, and compliance in minority patients

In minorities, as in the general population, hypertension is taken seriously because it is a risk factor for cardiovascular disease. Until recently, our understanding of the role that hypertension plays in the heart disease seen in minorities has been limited by a paucity of prospective data regarding the prevalence, natural history, and pathophysiology of the disease process in minority populations. In the last few years large-scale epidemiologic studies and well-controlled clinical studies alike have confirmed usually high rates of hypertension-related morbidity and mortality in minorities, particularly blacks and Hispanics. The severity of end-organ damage, both cardiac and renal, that is seen in these patients--especially when coupled with the severe cerebrovascular damage that is also more common in black and Hispanic hypertensives--mandate that more effective public health measures be taken to reduce the incidence of hypertension in these patient populations. Because hypertension is usually without significant clinical symptoms, noncompliance with drug therapy and high dropout rates are common in all patient populations. They are strikingly higher in inner-city populations, however, where illiteracy, poverty, homelessness, and high rates of chemical dependency combine to exacerbate an already serious problem in treating hypertensive patients. Inner-city patients are, increasingly, black and Hispanic patients, and these patients are more likely to be underinsured or uninsured, to be functionally illiterate in English, to be disinclined to seek health care, and to be less capable of following a prescribed regimen than the populace as a whole. The nature of the therapeutic regimen itself is probably the most important determinant of compliance, and compliance with drug therapy will be improved if the clinic chooses a simplified drug regimen and avoids drugs that produce intolerable side effects. Once-a-day--or, with transdermal clonidine, one-a-week--single-drug therapy may not be possible in all patients, but multiple drug therapy and multiple daily dosing schedules should be avoided wherever possible.

New Staging System of the Fifth Joint National Committee Report on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V) Alters Assessment of the Severity and Treatment of Hypertension

The fifth Joint National Committee report on the detection, evaluation, and treatment of high blood pressure (JNC-V) introduced a new system of blood pressure classification that incorporated systolic blood pressure (SBP) and established new diastolic blood pressure (DBP) cut points. With the previous JNC classification, subjects were classified according to DBP alone. In this study, our purpose was to assess the effect of the new staging system on the assessment of hypertension severity and to determine whether the new JNC-V staging system better identifies individuals at risk for hypertensive target-organ damage. We compared the assessment of hypertension severity using JNC-IV with that using JNC-V in 1158 subjects enrolled in the Harlem Hospital Hypertension Clinic database from 1975 to 1992. We used pretreatment DBP to classify subjects according to JNC-IV criteria. These subjects were reclassified into one of the four stages of JNC-V. The assessment of hypertension severity and prevalence of organ damage in subjects who remained in the same category of severity in both systems was compared with damage in subjects who were upstaged. With the JNC-V classification, 321 subjects remained in the same category, and 837 were upstaged. Six hundred and four subjects moved up because of the new cut points of DBP, and 275 were upstaged because of higher SBP. Upstaged subjects had more manifestations of hypertensive target-organ damage. With the new JNC-V classification system, hypertension is assessed as severe or very severe in more individuals than with JNC-IV. Subjects who are upstaged in JNC-V are more likely to have evidence of renal disease and other target-organ damage.

Improving compliance in an inner-city hypertensive patient population

Because hypertension is a silent disease process, compliance with therapy is always a problem. In the inner city, where socioeconomic factors such as poverty, illiteracy, and substance abuse raise additional barriers to effective health care, poor compliance with antihypertensive regimens can reach epidemic proportions--as it did in our clinic in the early 1970s. After identifying the major causes of poor compliance in our patients, we instituted measures that led directly to greatly improved compliance and control, among them the expansion of clinic hours, the expediting of laboratory services, and the training of nurse-therapists to assume many of the responsibilities of running the clinic. In recent years a number of new antihypertensive agents have been introduced, and these new drugs have afforded patients better blood pressure control through less complex drug regimens with fewer serious side effects. Indeed, we observed a strong correlation between patient compliance and the administration of agents with longer dosing intervals and improved side effects profiles. This observation led us to consider whether transdermal clonidine--which requires weekly, rather than daily, administration--might not be an especially effective means of controlling blood pressure in inner-city patients. To test this hypothesis, we enrolled 20 patients, all of them blacks, in a pilot study of this unique delivery system. Blood pressure was adequately controlled in all 18 patients who completed the study, and patients were uniformly enthusiastic about this alternative to daily dosing. As a result, compliance with this mode of therapy was excellent.

Left ventricular systolic performance during upright bicycle exercise in patients with essential hypertension

Left ventricular performance was evaluated at rest and during maximal upright bicycle exercise in 51 patients with chronic essential hypertension. Twenty-eight of these patients had no clinical or electrocardiographic evidence of coronary artery disease and comprise the primary study population. The remaining 23 patients had coronary artery disease and represent a comparison group. First-pass radionuclide angiocardiograms were obtained at rest and during maximal upright bicycle exercise, allowing evaluation of global left ventricular ejection fraction and regional wall motion. At the time of the radionuclide studies, all patients were hypertensive, defined as a diastolic blood pressure 90 mm Hg or greater and/or a systolic blood pressure 140 mm Hg or greater with the patient at rest and sitting. In the primary study group, the left ventricular functional response to upright bicycle exercise was normal in 26 of 28 patients. Left ventricular ejection fraction averaged (+/- standard error) 65 +/- 2 percent at rest and increased significantly to 76 +/- 2 percent with exercise (p less than 0.001). Regional wall motion was normal both at rest and during exercise in all patients. Seventeen patients had electrocardiographic evidence of left ventricular hypertrophy, and 14 were receiving propranolol therapy. The left ventricular functional response also was normal in these subgroups. In contrast to the nearly uniform normal left ventricular responses noted in the patients with hypertension alone, the group with concomitant coronary artery disease had a markedly higher incidence of abnormal left ventricular reserve (19 of 23 versus two of 28, p less than 0.001) during exercise. Thus, in most patients with essential hypertension but without concomitant coronary artery disease, left ventricular reserve during exercise was normal. Hypertension, even with left ventricular hypertrophy, should not be viewed as the cause for an abnormal left ventricular response to exercise in a patient undergoing diagnostic exercise radionuclide angiocardiography.

Hypertension and cardiac disease in minorities.

Despite recent advances in both prevention and treatment, cardiovascular disease remains the leading cause of mortality in the United States. One of the major modifiable risk factors for cardiovascular disease, hypertension, is a leading cause of stroke, kidney disease, and diseases of the heart and coronary circulation. Essential hypertension is the most common cause of systemic blood pressure elevation and it responds readily to both pharmacologic and non-pharmacologic treatment. More patients visit physicians and receive prescriptions for the treatment of hypertension than for any other medical disorder. Nevertheless, more than a million Americans die each year from the direct or indirect effects of hypertension. Over the last two decades, significant progress has been made in reducing mortality from cardiovascular disease. Through public health programs like the National High Blood Pressure Education Program, increasing numbers of hypertensive patients have been detected, treated and controlled. As a result, the number of deaths from stroke, kidney disease, and coronary artery disease has declined significantly. For both blacks and Hispanics, however, the decreases in cardiovascular mortality have been less striking. Many factors could account for this disparity, among them the availability of health care facilities in minority neighborhoods, and the health-care-seeking behavior of the patients themselves. Understanding epidemiologic and pathophysiologic data regarding differences between blacks, Hispanics, and non-Hispanic whites will help reduce hypertension-related morbidity and mortality.

Research in Coronary Heart Disease in Blacks: Issues and Challenges

Research on coronary heart disease (CHD) has contributed to the decline in cardiovascular disease morbidity and mortality during the past three decades. However, life expectancy and rates of illness and death from CHD have not improved for blacks as for whites. Blacks have not experienced the full benefit of research advancements for a variety of reasons, including insufficient scientific data, lack of research focused on minority populations, and limited access to health care resources and technology. In order to address these disparities in prevention, diagnosis, treatment, and outcomes of CHD in blacks, the National Heart Lung, and Blood Institute convened a Working Group on Research in Coronary Heart Disease in Blacks. In its deliberations, the working group identified 10 priority research areas, which are treatment, epidemiology (data collection and analysis), evaluation of chest pain and diagnosis of CHD, prevention and behavior, risk factors, genetics, vascular biology, left ventricular hypertrophy, coronary microvasculature, and sudden cardiac death.