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Hypertension Isolated Systolic Hypertension in the Elderly Sheldon Tobe, MD, FRCP(C), Assistant Professor of Medicine, Nephrology, University of Toronto; Division Director Nephrology, Sunnybrook & Women’s College Health Sciences Centre,Toronto, ON. Sudha Cherukuri, MD, DNB(Nephrology), Clinical Fellow, University of Toronto, Toronto, ON. Isolated systolic hypertension (ISH) is a common disorder in the elderly. Several studies have shown a constant positive and graded association between the level of systolic blood pressure and subsequent mortality from cardiovascular disease and stroke. ISH is defined as an elevated systolic pressure above 160mmHg and a diastolic pressure below 90mmHg. Arterial stiffening is the main cause of increasing systolic pressure in the elderly.The finding of high systolic blood pressure with diastolic below 90mmHg is a marker of higher cardiovascular risk and an indication to follow this patient more closely.The placebo-controlled SHEP and Syst-Eur trials have demonstrated that the treatment of ISH with diuretics or long-acting calcium channel blockers results in a marked reduction in cardiovascular events and stroke. Key words: hypertension, isolated systolic hypertension, clinical trials, drug therapy, elderly. Introduction Incidence Hypertension is an established risk factor for cardiovascular disease morbidity and mortality. Results of prospective epidemiological studies in different population groups indicate a constant positive and graded association between the level of systolic blood pressure and subsequent mortality from cardiovascular disease and stroke—especially with advancing age—irrespective of the level of diastolic blood pressure. This disorder is primarily seen in older patients. Data from the Framingham Heart Study have shown that the systolic pressure rises and the diastolic pressure falls after the age of 60 years in both the normotensive and untreated hypertensive subjects (Figure 1).4 ISH rises in prevalence from 8% in individuals aged 70 and older to 25% in those 80 and older.5 The elevation in pulse pressure in this setting is primarily due to diminished arterial compliance. In the group 50 years and older with either untreated or inadequately treated hypertension, 80% have isolated systolic hypertension.6 Definition Isolated systolic hypertension (ISH) is defined as an elevated systolic pressure above 160mmHg and a diastolic pressure that is below 90mmHg (Table 1).1 The MRFIT study demonstrated that as well as a graded, increased risk with higher systolic blood pressure, there was a particularly high risk for those with the highest systolic blood pressure and the lowest diastolic blood pressure.2 This was recently confirmed by a prospective study of over 9,000 people with hypertension 65 years and older followed for an average of 10.6 years.3 Importance ISH is associated with a two- to four-fold increase in the risk of myocardial infarction, left ventricular hypertrophy, stroke and cardiovascular mortality.7 The peak systolic pressure promotes the development of heart failure and atherosclerosis by increasing cardiac work and predisposing to vascular endothelial injury. related aortic stiffening.8 The ascending and descending aorta dilate with age, with the aortic diameter increasing by 15–35% from age 20–80. Histological changes occurring with normal aging include distorted normal orientation of the laminar unit, fracturing and fragmentation of the elastin fibres and increased collagen content of the vessel wall. These changes influence the aortic pulse, systemic pressure and ventricular performance. In addition, age-related changes occur in the arterial pulse. Left ventricular ejection creates a pressure wave that travels the length of the aorta to the periphery at a faster rate than blood flow. The velocity of the pressure wave is termed the pulse wave velocity.9 The pulse wave velocity is measured by recording the pulse wave at two sites, usually the carotid and femoral arteries. It is calculated as the distance from the carotid to the femoral artery divided by the time required for the pulse wave to travel this distance. With normal aging, the speed with which the pulse moves along the aorta markedly increases (Figure 2). In older subjects, the faster pulse wave velocity and wave reflection result in the reflected wave traveling back to the heart to reach the ascending aorta in late systole rather than early diastole. This causes an elevation in the systolic blood pressure and a fall in the diastolic blood pressure (wider pulse pressure). Normally, the reflected wave arriving back in early diastole results in Table 1 Classification of Hypertension According to WHO/ISH Category Systolic Diastolic (mmHg) (mmHg) Pathogenesis Isolated systolic hypertension ≥140 One factor which may play a pivotal role in the pathogenesis of ISH is age- Subgroup: borderline 140–149 <90 <90 www.geriatricsandaging.ca 27 Isolated Systolic Hypertension pressure for coronary perfusion much like the effect of intra-aortic balloon counterpulsation, and its loss due to increased arterial stiffness will lead to reduced diastolic coronary perfusion and increased systolic work. Therefore, age-related aortic stiffening contributes to the prevalence of isolated systolic hypertension in the elderly and to a greater risk of cardiac ischemia. Age-related changes leading to ISH have important physiologic associations. In multiple studies, the systolic blood pressure and pulse pressure are stronger risk factors for cardiovascular disease in older subjects than the mean arterial pressure or the diastolic pressure.10 Treatment that lowers blood pressure in patients with isolated systolic hypertension is associated with significant reduction in cardiac and cerebrovascular events.11 Treatment The SHEP (Systolic Hypertension in the Elderly) trial was the first to demonstrate that people with ISH could not only benefit from therapy, but were also a much higher risk group than previously thought.12 Although 15 years later it is hard to believe that it used to be ethical to treat elderly ISH patients with a placebo, the state of knowledge at the time was such that this was reasonable. In this study, 4,736 patients with ISH were randomized to either active antihypertensive therapy with diuretic or placebo, with the aim to reduce systolic blood pressure by at least 20mmHg or to a level below 160mmHg. Achieved blood pressures were 143/68mmHg in the treatment group compared to 155/72mmHg in the placebo arm. At four to five years, the incidence of stroke was reduced from 8.2% in the placebo group to 5.2% in the treated group (a 36% relative risk reduction and a 3% absolute risk reduction, with a number needed to treat of only 33 for the outcome stroke). A similar reduction was noted in cardiac events as well. The Syst-Eur trial, which randomized 4,695 patients with ISH to placebo or nitrendipine—a dihydroperidine calcium channel blocker—also demonstrated a risk reduction equivalent to that found in the SHEP trial for both stroke and cardiovascular mortality.11,13 One issue that is frequently raised in the treatment of ISH is what happens if the diastolic blood pressure falls too low. However, we know from placebocontrolled trials such as SHEP and Syst- Figure 1 Patterns of Age-related Changes in Blood Pressure Group 1 (SBP < 120) Group 2 (SBP 120–139) Systolic 140 80 120 70 100 60 30 30 Age (years) Franklin SS et al. Circulation 1997;96:308-315. 28 GERIATRICS & AGING • February 2003 • Vol 6, Num 2 Choice of Therapy Based on the results of the SHEP and Syst-Eur trials, low-dose thiazide therapy is the preferred initial therapy for ISH. Hydrochlorothiazide at 12.5 or 25mg has the advantage of low cost, efficacy and proven benefit. The Syst-Eur trial demonstrated the safety and efficacy of long-acting dihydropyridine calcium antagonists for the treatment of ISH (Figure 3). It is recommended that all people older than 65 years have their blood pressure taken at least annually if they are normotensive, and every three to six months if their high blood pressure has been controlled. The finding of high systolic blood pressure with diastolic below 90mmHg is a marker of higher cardiovascular risk, and this patient must be followed more closely. Recently ambulatory blood pressure monitoring has been found to be a better predictor of adverse outcomes in older patients with widened pulse pressure and ISH. Home monitoring with an approved device may be a better way to monitor therapy and eliminate a white coat effect. Prevention Prevention of age-related aortic changes is possible with both lifestyle changes and drug therapy. Modifying lifestyle factors to lower blood pressure—such as weight loss, regular aerobic exercise, diet with low sodium content, cessation of smoking, moderation of alcohol intake and management of dyslipidemia and blood sugar control—will help to protect the vascular tree. Future –3 35 4 –3 40 9 – 45 44 –4 50 9 –5 55 4 –5 60 9 – 65 64 –6 70 9 –7 75 4 –7 80 9 –8 4 90 Age (years) Diastolic 100 160 –3 35 4 –3 40 9 – 45 44 –4 50 9 –5 55 4 –5 60 9 – 65 64 –6 70 9 –7 75 4 –7 80 9 –8 4 Blood Pressure (mmHg) 180 Group 3 (SBP 140–159) Group 4 (SBP 160+) Eur that treatment of these patients is better than no treatment at all. In a meta-analysis of clinical trials with a total of 15,693 people with ISH, active treatment reduced total mortality by 13%, all stroke by 30% and all coronary events by 23%.11 The clinical utility of measuring parameters of arterial stiffness beyond the pulse pressure have not yet been determined. However, in the future serial Isolated Systolic Hypertension Left ventricular ejection creates pressure wave through aorta to periphery Pressure (mmHg) Pressure wave reflected back in early diastole Normal Diastole Faster pulse wave velocity causes reflected wave to travel back to heart in late systole rather than early diastole Ventricles contract Normal Systole Figure 2: The Pathogenesis of Isolated Systolic Hypertension Pressure (mmHg) Increased systolic pressure To counteract reflected pressure wave, cardiac muscle must contract harder in systole, thereby increasing systolic blood pressure With Aging www.geriatricsandaging.ca 29 Isolated Systolic Hypertension Figure 3 Treatment Algorithm for Isolated Systolic Hypertension: Target < 140mmHg Lifestyle modifications Low-dose thiazide Long-acting dihydropyridine calcium channel blocker Neither alpha- nor beta-blockers are indicated as first-line monotherapy for ISH due to the results of ALLHAT and other trials Combination Effective two-drug combination CONSIDER – Nonadherence? – Secondary hypertension? – Interfering drugs or lifestyle? – White coat effect? } (Add ACE-I or beta-blocker) Combination Triple or quadruple therapy measurements of arterial tonometry and pulse wave velocity to assess the effects of therapeutic interventions will provide more specific, clinically important information unavailable from the measurement of blood pressure alone. The focus of ISH treatment is to bring down the systolic blood pressure. In the future, ISH may no longer remain a separate entity in clinical practice guidelines, as treatment of high blood pressure will be initiated if blood pressure in the uncomplicated patient is greater than 140 systolic and/or 90 diastolic. Therefore, having a separate category for those with systolic pressure greater than 160 and diastolic less than 90 will be redundant. Today, however, there are a large number of treatment trials involving patients with ISH that help guide treatment in this higher risk group of hypertensives. Conclusion In summary, ISH is associated with a higher risk of cardiovascular disease and mortality. Wider pulse pressure in ISH is a marker of loss of vascular elasticity associated with hardening of the arteries. Treatment of ISH has been proven to be beneficial. The goal should be to bring the systolic blood pressure down to 140mmHg, or at least by 20mmHg. Multiple medications may be 30 GERIATRICS & AGING • February 2003 • Vol 6, Num 2 required. Because patients with ISH are at high risk, they should be assessed for multiple cardiovascular risk reduction strategies. ◆ No competing financial interests declared. References 1. Chalmers J, MacMahon S, Mancia G, et al. 1999 World Health Organization: International Society of Hypertension guidelines for the management of hypertension. Guidelines sub-committee. Clin Exp Hypertens 1999;21:1009-60. 2. Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med 1992;152:56-64. 3. Glynn RJ, Chae CU, Guralnik JM, et al. Pulse pressure and mortality in older people. Arch Intern Med 2000;160:2765-72. 4. Franklin SS, Gustin W, Wong ND, et al. Hemodynamic patterns of age-related changes in blood pressure. The Framingham Heart Study. Circulation 1997;96:308-15. 5. Gasowski J, Wang JG, Staessen JA. Clinical trials in isolated systolic hypertension. Curr Hypertens Rep 1999;1:387-93. 6. Franklin SS, Jacobs MJ, Wong ND, et al. Predominance of isolated systolic hypertension among middle-aged and elderly U.S. hypertensives: analysis based on National Health and Nutrition Examination Survey (NHANES) III. Hypertension 2001;37:869-74. 7. Franklin SS. Is there a preferred antihypertensive therapy for isolated systolic hypertension and reduced arterial compliance? Curr Hypertens Rep 2000;2:2539. 8. Dart AM, Kingwell BA. Pulse pressure—a review of mechanisms and clinical relevance. J Am Coll Cardiol 2001;37:975-84. 9. London GM, Guerin AP, Pannier B, et al. Large artery structure and function in hypertension and end-stage renal disease. J Hypertens 1998;16:1931-8. 10. Blacher J, Staessen JA, Girerd X, et al. Pulse pressure not mean pressure determines cardiovascular risk in older hypertensive patients. Arch Intern Med 2000;160:1086-9. 11. Staessen JA, Gasowski J, Wang JG, et al. Risks of untreated and treated isolated systolic hypertension in the elderly: meta-analysis of outcome trials. Lancet 2000;355:865-72. 12. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA 1991;265:3255-64. 13. Staessen JA, Thijs L, Gasowski J, et al. Treatment of isolated systolic hypertension in the elderly: further evidence from the systolic hypertension in Europe (Syst-Eur) trial. Am J Cardiol 1998;82:20R-22R.