Systolic Hypertension: A Guide to Optimal Therapy
Systolic Hypertension: A Guide to Optimal Therapy
Sustained control of hypertension reduces the morbidity and mortality of cardiovascular disease.1,2 A key message from the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines is that in persons 60 years or older, systolic hypertension is a more important risk factor for cardiovascular disease than diastolic hypertension.2 It is the component of blood pressure (BP) most likely to be "uncontrolled" in population studies.3 Systolic hypertension is defined as systolic blood pressure (SBP) of 140 mm Hg or higher and diastolic BP of less than 90 mm Hg.
The latest data from the National Health and Nutrition Examination Survey (NHANES) indicate that more than 50 million Americans have hypertension.4 Although awareness and control of hypertension have improved during the past 2 decades, about 30% of hypertensive Americans are unaware that they have hypertension, 40% are not receiving therapy, and 66% or more who are being treated have suboptimal control. Elderly patients are the ones most likely to have inadequately controlled BP (usually SBP).5 In this article, we review the pathophysiology of systolic hypertension as well as the most current treatment approaches.
The causes of essential hypertension include genetic factors, increased sympathetic nervous system activity, a variety of circulating humors, and vascular remodeling. Evidence for the role of genetic factors comes from the finding of a clustering of this condition in families.6 In addition, there is BP concordance among monozygotic twins and biological siblings compared with adopted siblings raised together.7,8 A few hypertensive disorders result from single gene mutations (eg, Liddle syndrome), but most cases of essential hypertension probably result from mutations of multiple genes in addition to environmental factors. Notably, persons with hypertension also tend to inherit diabetes and lipid disorders.9 Data from studies in families using ambulatory BP monitoring suggest that both systolic and diastolic hypertension patterns are inherited.10
Hypertension is often characterized by increased sympathetic nervous system activity. Evidence that an elevated heart rate correlates with the development of hypertension corroborates this finding.11 Increased sympathetic tone leads to elevated diastolic pressure, vascular remodeling, and likely end-organ damage, particularly left ventricular hypertrophy (LVH). Humoral factors, such as norepinephrine, angiotensin II, transforming growth factor b, and insulin-like growth factor, are implicated in the enhanced activation of the sympathetic nervous system. There is also evidence of increased sympathetic activity in the kidneys in hypertension.9
The vascular remodeling that occurs in hypertension leads to increased peripheral vascular resistance and increased pulse wave velocity. The arterial bed stores substrate-enriched blood and acts as a conduit for its delivery to systemic organs and tissues. Arterial mechanics depend on arterial stiffness, arterial wall thickness, and arterial diameter. Arterial stiffness is a measurable and important cardiovascular risk factor. Arteries stiffen as a consequence of the increased collagen deposition, fragmentation, and loss of elastin that occur with aging. This manifests clinically as elevated pulse wave velocity (PWV), the speed at which the pulse wave travels through the arterial bed.
In young persons, large, healthy arteries such as the aorta have low PWV values. This slower PWV enables the pulse wave to reflect back to the aorta in a timely manner to reduce the pressure load to the smaller peripheral arteries and at the same time reach the central circulation at an appropriate time in the cardiac cycle so as to augment coronary blood flow. Stiff arteries are characterized by increased PWV. Under these conditions, the reflected pulse wave increases the ventricular afterload and the ventricular systolic pressure, and thus puts a greater load on the heart (Figure). This process decreases diastolic pressure and jeopardizes coronary blood flow, which can eventually result in LVH, coronary ischemia, and heart failure. This helps explain why increased SBP heightens cardiovascular risk, particularly in elderly patients.
END-ORGAN MANIFESTATIONS OF UNCONTROLLED SYSTOLIC HYPERTENSION
The goal of therapy for hypertension is to reduce or prevent end-organ damage. The principal targets of hypertension include the heart, the cerebrovascular system, and the kidneys.
Cardiovascular disease. Coronary artery disease, heart failure, and LVH are often the result of long-standing hypertension. As discussed above, the vascular remodeling and arterial stiffness that occur with systolic hypertension lead to LVH, diastolic dysfunction and, eventually, diastolic heart failure. Diastolic heart failure is more prevalent than systolic heart failure among the elderly; its morbidity is comparable to that of systolic heart failure.12 Patients with diastolic heart failure are often diabetic or obese or have chronic renal disease.