From hypertension to heart failure: breaking the chain of cardiovascular disease

The hazards of untreated hypertension are starkly illustrated by the case of former President Franklin D. Roosevelt, who died of a cerebral stroke in 1945.1 Over the 10 years preceding his death, Roosevelt had increasingly severe high blood pressure (BP), which culminated in malignant hypertension. His physician recorded BP as high as 260/150 mm Hg in the later stages of the disease, and of 300/190 mm Hg right after Roosevelt suffered his stroke. Because of the complete lack of effective antihypertensive treatment at that time, however, Roosevelt's highly qualified physicians were helpless to lower his BP and thereby delay or possibly prevent this outcome. The President's arteries were found postmortem to be severely diseased, and it is now believed that Roosevelt had untreated symptomatic heart failure (HF) throughout the last years of his life.1,2 The consequences of untreated hypertension in terms of cardiovascular (CV) complications were thus clearly demonstrated in this famous case. Today, HF is a major public health problem in the United States (US). An estimated 4.9 million Americans have HF. Each year 550,000 new cases are diagnosed, and HF deaths increased 145% between 1979 and 2000, according to latest statistics gathered by the American Heart Association.3 The annual number of hospitalizations due to HF has nearly doubled in the last decade, and HF is the most common Medicare diagnosis-related group.3 Hypertension is well known to be strongly associated with HF. A 1955 study that followed 500 subjects with untreated hypertension until death found that HF was the most common primary cause of mortality (22%), was a contributing cause in 38% of deaths, and accounted for 50% of all CV complications.2,4 A more recent study in more than 5000 Framingham Heart Study hypertensive participants without HF, encompassing a mean 14.1 years of follow-up and a total of 72,422 person-years of observation, showed that hypertension was antecedent to HF in 91% of cases.5 This study also found that the level of risk for HF increased with increasing age and with increasing severity of hypertension5 (Fig. 1). Furthermore, the survival data after diagnosis of HF in this study are grim: the median survival was 1.37 years in men and 2.48 years in women, and the 5-year survival rate was 24% in men and 31% in women.5 Fortunately, antihypertensive treatment significantly reduces the risk of HF. In major studies in elderly subjects with hypertension, including the Systolic Hypertension in the Elderly Program (SHEP) and Swedish Trial in Old Patients with Hypertension (STOP-Hypertension), antihypertensive therapy reduced the risk of HF by 35% to 54%.6,7,8,9 Reviews of studies in general hypertensive populations have also shown that hypertension treatment reduces HF risk by about 50%, in addition to significant risk reductions for other CV disease outcomes10,11 (Fig. 2). These data help to highlight the important role of hypertension in the progressive chain of CV events that lead to HF and cardiac death. Cardiovascular risk factors such as hypertension, dyslipidemia, obesity, diabetes, and smoking can lead to left ventricular hypertrophy or myocardial infarction (MI), which lead in turn to progressive left ventricular dysfunction and eventually to symptomatic HF.12 The purpose of this paper is to explicate the role of hypertension in the development of HF and to examine the therapeutic value of β-blockers (βB) at each stage along the CV disease continuum. This special publication of the American Journal of Hypertension is based on a symposium presented at the Eighteenth Annual Scientific Meeting of the American Society of Hypertension, which was held May 14–17, 2003, in New York City. The four articles in this supplement share in written format the information and concepts presented at this meeting. In his presentation, Henry R. Black, MD, discusses the high prevalence of HF and reviews the role of hypertension in its development.13 He also analyzes the results of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), showing that βB were the drugs most commonly added to the treatment regimens in all three arms of the trial.14 Importantly, reductions in risk for HF were seen with thiazide diuretic–based therapy in ALLHAT across all subgroups, including those of ethnicity, age, gender, and diabetes. George L. Bakris, MD, addresses the role of βB in diabetic renal disease.15 He presents data showing that diabetes is the most common cause of end-stage renal disease, and also shares disturbing survey findings that the use of cardioprotective drugs declines as kidney disease worsens (ie, in those who need them the most). Dr. Bakris also discusses results from major trials including ALLHAT and the United Kingdom Prospective Diabetes Study (UKPDS), showing that both diabetic and nondiabetic hypertensive patients require an average of two to three antihypertensive agents to reach target systolic BP goals. In concluding, Dr. Bakris notes that angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, βB, calcium channel blockers, and diuretics have all been shown in clinical trials to reduce CV events in individuals with kidney disease. In his presentation, Jan N. Basile, MD, addresses some of the main issues in optimizing antihypertensive therapy in clinical practice. Dr. Basile begins by reviewing the poor control rates of high BP worldwide.16 He presents data showing that multidrug therapy is necessary for most patients to reach BP goals and discusses the recommendations of the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) for selection of antihypertensive agents for patients with uncomplicated hypertension and those with compelling indications. He also addresses data supporting the use of βB for both primary and secondary prevention to reduce CV morbidity and mortality in patients with hypertension, patients post-MI, and those with HF. Dr. Basile concludes with a review of the data illustrating that βB reduce the risks of sudden cardiac death. John B. Kostis, MD, provides an update on the management of systolic and diastolic dysfunction.17 Dr. Kostis reviews data on the increasing prevalence and economic burden of HF and the current epidemiologic factors that may extend this trend, such as the rising proportion of elderly individuals in the US. Dr. Kostis discusses how HF develops from either long-standing hypertension or an acute MI, and the central role of ventricular remodeling in the development and progression of HF. He discusses the importance of treating all CV risk factors including hypertension, and explains the valuable therapeutic role of βB at all stages along the CV continuum. Dr. Kostis concludes by reviewing clinical trial data demonstrating the effectiveness of βB in reducing morbidity and mortality in patients with HF, including major subgroups such as diabetic individuals, women, elderly patients, and those with advanced stages of HF. Although significant advances have been made in hypertension management, the continued poor rates of high BP control and the rising prevalence of HF indicate that optimizing cardioprotective therapies is of the greatest urgency. β-Blockers have a remarkably broad spectrum of recommended uses in both primary and secondary prevention of CV disease. We trust that this supplement will help to clarify the important role of βB in optimizing strategies for cardioprotection.