Optimizing Hypertension Control in Patients With Multiple Cardiovascular Risk Factors

The concept of risk factors for cardiovascular disease has evolved steadily over the past 60 years since the first epidemiologic studies were conducted. Following World War II, Ansel Keys' study of heart disease in US businessmen and his international comparisons of the relationship of heart disease to diet were the first to implicate hypercholesterolemia and dyslipidemia as risk factors.1,2 The Framingham Heart Study,3 begun in the 1940s, continues to provide useful data on cardiovascular risk factors such as hypertension, dyslipidemia, and diabetes and lifestyle factors such as smoking and high-fat and high-sodium diets. Despite epidemiologic evidence, clinical recommendations for treatment of risk factors have evolved more slowly, following the development of medications and the demonstration through randomized clinical trials that interventions which improve blood pressure or lipid levels lead to fewer cardiovascular events. Hypertension has not always been viewed as a cardiovascular risk factor. In the 1930s and 1940s, hypertension was considered essential for the perfusion of vital organs and therefore remained untreated. Although the first generally utilized antihypertensive agent, reserpine, became available in 1949, the debate about whether to treat hypertension continued for some years. During the past several decades, many other classes of drugs have been developed, and today there are more than 300 individual or combination antihypertensive agents available to the clinician. As knowledge of the etiology of hypertension has evolved, so has therapy—from dietary modifications first suggested in the 1920s to pharmacologic agents such as hydralazine, chlorothiazide, and β-blockers in the late 1950s. More recently, calcium channel block-ers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers have been added to the armamentarium of hypertension therapy. The disagreement over the importance of treating hypertension continued into the 1970s, highlighted by a major debate at an American College of Physicians meeting in 1971. Partially in response to the ongoing debate within the medical community, the National Blood Pressure Education Program was established in 1972. This program established the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC), which published its first guidelines in 1977 with the goal of providing clinical practice guidelines to manage hypertension.4 The JNC guidelines have evolved during the past 30 years, incorporating data demonstrating an increase in the risk of cardiovascular and renal disease, including stroke, ischemic heart disease and heart failure associated with levels of blood pressure previously considered normal, or mild hypertension.4–11 For example, the JNC I (1977) and II (1980) guidelines made little mention of systolic blood pressure (SBP) goals, reflecting the commonly held but erroneous belief that high diastolic blood pressure (DBP) was more accurate in predicting risk.4,5 In the middle and late 1980s, data from observational studies revealed that SBP was a better indicator than DBP of cardiovascular disease risk, particularly in older people. The report of the Multiple Risk Factor Intervention Trial (MRFIT)12 noted that once SBP exceeded 160 mm Hg, the mortality rate from coronary heart disease increased significantly, regardless of the DBP. During this same period, JNC III (1984) and IV (1988) changed guidelines to indicate that an SBP between 140 mm Hg and 160 mm Hg was borderline hypertension.6,7 Later, JNC V (1993) labeled this level of SBP stage 1 hypertension.8 Signalling a new emphasis, the term Prevention was added to JNC's full name by the time JNC VI was released (1997).9 The current JNC 7 guidelines, published in 2003,10 contain an important distinction from the recommendations in JNC VI. A new classification of prehypertension was introduced, which encompasses patients with SBP values ranging from 120 mm Hg to 139 mm Hg and/or DBP values ranging from 80 mm Hg to 89 mm Hg. This range was previously considered normal to high-normal BP. The previous category of optimal BP (<120/80 mm Hg) is now considered normal BP.10 The JNC goal for people with prehypertension is to lower BP to normal levels with lifestyle changes, if possible. In addition, one recent study establishes the benefit of treating individuals with prehypertension.13 Another classification change in JNC 7 is the combination of what previously was divided into stage 2 and stage 3 hypertension into a single category (stage 2) for all people with SBP ≥160 mm Hg or DBP ≥100 mm Hg. The revision acknowledges that cardiovascular risk above these levels is substantial and advocates the same aggressive therapy for these patients.10 Dr Cohen's article in this supplement discusses the JNC guidelines, as well as recommendations from other groups that focus on hypertension. Additionally, it features trials published since JNC 7 that impact the treatment of hypertension. The progressive understanding of the role of hypertension as a risk factor for heart attack, stroke, chronic kidney disease, and congestive heart failure, as well as recommendations for more aggressive BP lowering, has led to a decrease in deaths related to cardiovascular disease over the past century. Cardiovascular disease deaths peaked in the mid-1950s and then declined approximately 60% until the mid-1990s because of increased awareness of cardiovascular risk factors among physicians and the public, resulting in better control of dyslipidemia, hypertension, and smoking.3 In the early 1990s, it was reported that hypertension preceded the development of congestive heart failure in 91% of cases.14 Although the death rate from cardiovascular disease declined from 1993 to 2003 by 22.1%, cardiovascular disease still accounted for 37.3% of all deaths in 2003, and 1 in 3 adults in the United States had some form of cardiovascular disease.15 In addition, the age-adjusted death rate related to hypertension increased 29.3%, and the actual number of deaths rose 56.1% from 1999 to 2003.15 Hypertension has been strongly associated with an increased incidence of stroke and ischemic heart disease.15 Dr Levine's article in this supplement highlights several of the extensive clinical trials that indicate a link between lowering blood pressure and reducing cardiovascular events, especially in patients with other cardiovascular risk factors and comorbidities such as the metabolic syndrome, diabetes, dyslipidemia, and kidney disease. The coexistence of hypertension with one or more of these other factors (referred to as risk-factor clustering) has an additive effect on cardiovascular outcomes. As a result, treatment guidelines recommend lower BP goals for patients with risk factors such as diabetes and kidney disease. Increased physician education and public awareness of recommended BP goals, coupled with lifestyle changes, may prevent the development of comorbidities and reduce the risk of cardiovascular events in patients with multiple cardiovascular risk factors.