High Blood Pressure
HIGH BLOOD PRESSURE
Although diastolic blood pressure is considered an important risk factor for cerebrovascular disease, congestive heart failure, and coronary heart disease, it is now clear that isolated systolic hypertension and elevated pulse pressure also play an important role in the development of these diseases, which are the major causes of cardiovascular morbidity and mortality among subjects over sixty-five years of age. The benefit of antihypertensive therapy in reducing the incidence of cardiovascular and cerebrovascular complications has been shown for systolic and systolo-diastolic hypertension. Essential hypertension (no discoverable organic cause) is the main cause of hypertension in the elderly population. In addition, secondary hypertension—especially that associated with kidney disease—is more common in older than in younger adults.
Definition of hypertension
Blood pressure is defined by two values: systolic (contraction of the heart), the highest value, and diastolic (dilation of the heart), the lower. "The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" (JNC-VI) and the World Health Organization/International Society of Hypertension Guidelines subcommittees have agreed that both systolic and diastolic blood pressure should be used to classify hypertension. Systolo-diastolic hypertension is diagnosed when systolic and diastolic blood pressure are over 160 and 90, respectively. Isolated systolic hypertension refers to systolic blood pressure over 160 and diastolic blood pressure under 90.
Misdiagnosis may be more frequent in the elderly due to various factors, including inappropriate length of the cuff due to obesity or very low weight, fluctuations in blood pressure due to postural hypotension, and/or anxiety (white coat effect). The difficulty of measuring blood pressure in elderly persons should encourage the development of ambulatory blood pressure measurement.
Ambulatory blood pressure measurement is most useful for identifying patients with white-coat hypertension, also known as isolated clinic hypertension, which is arbitrarily defined as a clinc blood pressure of more than 140 mmHg systolic or 90 mmHg diastolic in a patient with daytime ambulatory blood pressure below 135 mmHg systolic and 85 mmHg diastolic.
Blood pressure changes and hypertension
Both systolic and diastolic blood pressure increase with age. However, diastolic blood pressure increases with age until the age of fifty or sixty and then tends to remain stable or even decrease slightly, whereas systolic blood pressure rises progressively until the age of seventy or eighty. This combination of changes probably reflects stiffening of the blood vessels and reduced arterial elasticity and leads to a large increase in pulse pressure (the difference between the systolic and diastolic pressures) with aging (Burt et al.). In persons over eighty, a decrease in both diastolic and systolic blood pressure has been found in some studies, and may be due to poor health in this very frail population. The global prevalence of both diastolic and systolic hypertension in people over sixty-five is about 45 percent. Hypertension is more frequent in black than white persons, and in women than men. The prevalence of isolated systolic hypertension is about 7, 11, 18, and 25 percent in people aged sixty to sixty-nine, seventy to seventy-nine, eighty to eighty-nine, and over ninety, respectively. Isolated systolic hypertension is more frequent in women than men.
The mechanisms of hypertension in elderly persons involve an increase in thickness of aortic and large artery walls and a decrease in vessel elasticity, which raises systolic blood pressure. Hypertension also increases peripheral vascular resistance, because of the reduced elasticity of these arteries. In addition, it reduces the sensitivity of nerve endings stimulated by pressure changes, resulting in the impairment of postural reflexes, which makes elderly persons with hypertension prone to hypotension when standing erect. The vasoconstriction due to changes in the balance between beta-adrenergic vasodilatation and alpha-adrenergic vasoconstriction raises peripheral vascular resistance and blood pressure. Increased sodium intake and decreased sodium excretion induce sodium retention. In contrast to hypertension in younger adults, the reninangiotensin system is not thought to play a major role in hypertension in older adults.
Risk of hypertension
Hypertension stands out as the major risk factor for cardiovascular disease and mortality in elderly persons (Forette et al., 1982). Both systolic and diastolic blood pressure are involved, but with advancing age, systolic blood pressure has been identified as a better predictor of cardiovascular risk than diastolic blood pressure, in both men and women (Kannel and Gordon, 1978). Since at any given level of systolic blood pressure, mortality was found to increase as diastolic pressure decreased, pulse pressure must also be considered a risk factor (Staessen et al., 2000).
Systolic, diastolic, and combined hypertension increase the risk of stroke. Data from the Framingham Study have shown that apart from this risk, elevated systolic blood pressure is a major risk factor for all cardiovascular diseases, including left ventricular hypertrophy, congestive heart failure, ischemic cardiopathy, and peripheral artery diseases. High midlife blood pressure has been shown to be a strong independent predictor of later cognitive impairment. However, some authors who studied very old patients reported a J curve profile with higher cognitive impairment in subjects with low blood pressure. The decrease in blood pressure may be due to pathological processes that also affect cognitive functioning or, alternatively, it may be a consequence of dementia. In addition, hypertension appears to be the strongest risk factor for vascular dementia and possibly for Alzheimer's disease.
A correlation between mortality and high blood pressure has been widely shown. This excess mortality is mainly correlated with systolic blood pressure (Kannel et al., 1976). However, in people over eighty years old, some authors have reported either no association between blood pressure and mortality or an inverse association, which disappears after adjustment for indicators of poor health.
Benefits of antihypertensive therapy
Several randomized, double-blind, placebo-controlled intervention studies have provided strong evidence in favor of treating hypertension in elderly patients. Reports of first outcome trials published in 1985 and 1991 that focused attention on systolo-diastolic hypertension showed a reduction in cardiovascular and cerebrovascular morbidity and mortality in patients over sixty-five years old (Amery et al.; Dahlöf et al.; Medical Research Council).
More recent trials have specifically addressed the problem of isolated systolic hypertension. A meta-analysis by Staessen et al. (2000) showed that in 15,693 patients with isolated systolic hypertension who were included in eight trials, antihypertensive treatment reduced stroke by 30 percent. Total mortality decreased by 13 percent, cardiovascular mortality by 18 percent, all cardiovascular complications by 26 percent, and coronary events by 23 percent. Treatment prevented strokes more effectively than it prevented coronary events.
An important finding in the investigation of systolic hypertension in Europe (Syst-Eur; Forette et al., 1998) was that in older people with isolated systolic hypertension, antihypertensive treatment that started with the calcium-channel blocker nitrendipine significantly reduced the incidence of dementia, from 7.7 to 3.8 per 1000 person-years. The incidence of Alzheimer's disease dropped even more after such treatment than that of vascular or mixed dementia. By contrast, in the Systolic Hypertension in the Elderly Program (SHEP), active treatment based on diuretics and beta-blockers failed to reduce the incidence of dementia significantly. These negative results argue against conferring protection simply by lowering blood pressure. In the mechanism of dementia prevention, calcium-channel blockers might have a neuroprotective effect. The potential importance of the Syst-Eur results for public health policies warrants confirmation by other trials.
Should very old people be treated?
The value of antihypertensive treatment is well established for patients age sixty years and over. The results are mixed for the oldest age group, eighty years and over. The European Working Party on High Blood Pressure in the Elderly Trial failed to demonstrate that antihypertensive treatment was significantly beneficial above the age of eighty (Amery et al.). In the STOP-Hypertension trial (Dahlöf et al.), this treatment resulted in a smaller reduction in the number of deaths from stroke, myocardial infarction, and other cardiovascular diseases in older than in younger patients. By contrast, in the SHEP trial the positive effect of active treatment, compared with placebo, on the relative risk of stroke increased with age, and reached its maximum in the group of patients age eighty years or older. In the Syst-Eur study, a significant reduction was found in morbidity, but not in mortality, in the oldest patients (Staessen et al., 1997). In a meta-analysis of data from 1,870 participants over age eighty, Gueyffier et al. suggested that treatment reduced the rates of stroke, major cardiovascular events, and heart failure by 30 percent. On the other hand, there was no reduction in mortality due to cardiovascular disease or in total mortality. The results of this meta-analysis, which were favorable for morbidity, argue against the existence of a threshold age beyond which hypertension should not be treated.
What should be the goal blood pressure ?
Although the benefit of treating hypertension in elderly subjects is now well established, controversy still exists regarding the goal blood pressure. Indeed, according to the J curve hypothesis, a major reduction in diastolic blood pressure to less than 65 mmHg might jeopardize appropriate blood flow in the brain, heart, and kidneys during the diastole, and might be associated with an increase in mortality. However, in the SHEP study low diastolic blood pressure did not increase mortality.
As an intermediate goal, most studies recommended either reducing systolic blood pressure to under 160 mmHg and diastolic pressure to under 90 mmHg, or reducing the initial systolic and diastolic blood pressures by 20 mmHg. The benefit of a larger decrease (≤140 mmHg) remains to be determined by the results of ongoing studies.
Most trials have been run with diuretics and beta-blockers as first-line drugs. Since the 1980s, the efficacy and safety of these two classes of drugs have been demonstrated in elderly subjects (Amery et al.; SHEP; Dahlöf et al.; MRC). The benefit of calcium-channel blockers (Staessen et al. 1997; Hansson, Lindholm, Ekbom et al.) and angiotensin-converting-enzyme inhibitors (Hansson, Lindholm, Niskanan et al.) has been shown for the prevention of cardiovascular and cerebrovascular complications in older patients.
Because age- and disease-associated factors affect the metabolism and distribution of pharmacologic agents, antihypertensive therapy should be given at low doses, which should be increased gradually. However, despite alterations in metabolism, most elderly patients tolerate medication without a significant increase in adverse events compared to younger patients or control groups. First-line treatment should consist of diuretics or beta-blockers (JNC-VI). In isolated systolic hypertension, diuretics and calcium-channel blockers are recommended (SHEP; Staessen et al., 1997).
Concomitant diseases may influence the choice of therapy. In patients with coronary artery disease, beta-blockers may be useful, but peripheral artery disease, heart failure, or obstructive bronchopathy may limit their use in elderly persons. In older patients with coronary artery disease, use of calcium-channel blockers may be discussed. In cardiac dysfunction and congestive heart failure, prescription of diuretics, angiotensin-converting-enzyme inhibitors, or both is an appropriate initial choice. In older adults, fixed-dose combination therapy has the advantage of increasing compliance, reducing the cost of antihypertensive therapy, and achieving a higher response rate.
Older hypertensive patients can also benefit from nonpharmacologic interventions designed to lower blood pressure (JNC-VI), including weight control, reduction of excessive alcohol consumption, cessation of smoking, and increased exercise. Any reduction of sodium intake in elderly people should be cautious because it can reduce food intake.
Management of hypertension
Despite the evidence that treatment is beneficial in terms of reducing morbidity and mortality, hypertension is still poorly controlled in elderly persons. Both in the United States and in Europe, less than 30 percent of patients on hypertensive drugs attain the JNC-VI goal blood pressure (<140 and <90 mmHg) (JNC-VI; Burt et al.). Achieving the goal is relatively easy for diastolic blood pressure, but much harder for systolic blood pressure. Moreover, the new indication of pulse pressure as the most powerful risk factor must now lead doctors to consider systolic rather than diastolic blood pressure when determining treatment goals. Consequently, the development of drugs that lower systolic blood pressure more effectively should be promoted (Staessen et al., 2000). Blacher et al. have emphasized the need for randomized trials with anti-hypertensive drugs that act differently on the pulsatile component of blood pressure. These authors suggested that vasopeptidase inhibitors and nitric oxide donors might increase the distensilibility of large arteries and reduce pulse pressure.
See also Heart Disease; Stroke; Vascular Disease.
Amery, A.; BirkenhÄger, W.; Brixko, P.; Bulpitt, C.; Clement, D.; Deruyttere, M.; De Shaepdryver, A.; Dollery, C.; Fagard, R.; Forette, F.; Forte, J.; Hamdy, R.; Henry, J. F.; Joossens, J. V.; Leonetti, G.; Lund-Johanssen, P.; O'Malley, K.; Petrie, J.; Trasser, T.; Tuomilehto, J.; and Williams, B. "Mortality and Morbidity Results from the European Working Party on High Blood Pressure in the Elderly Trial." Lancet 1, no. 8442 (1985): 1349–1354.
Blacher, J.; Staessen, J. A.; Girerd, X.; Gazowsky, J.; Thijs, L.; Liu, L.; Wang, J. G.; Fagard, Robert; and Safar, Michel. "Pulse Pressure Not Mean Pressure Determines Cardiovascular Risk in Older Hypertensive Patients." Archives of Internal Medicine 160 (2000): 1085–1089.
Burt, V. L.; Whelton, P.; Roccella, E. J.; Brown, C.; Cutler, J. A.; Higgins, M.; Horan, M. J.; and Labarthe, D. "Prevalence of Hypertension in the U.S. Adult Population: Results from the Third National Health and Nutrition Examination Survey, 1988–1991." Hypertension 25 (1995): 305–313.
DahlÖf, B.; Lindholm, L. H.; Hansson, L.; ScherstÉn, B.; Ekbom, T.; and Wester, P. O. "Morbidity and Mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension)." Lancet 338 (1991): 1281–1285.
Forette, F.; De la Fuente, X.; Golmard, J. L.; Henry, J-F.; and Hervy, M-P. "The Prognostic Significance of Isolated Systolic Hypertension in the Elderly. Results of a Ten-Year Longitudinal Survey." Clinical Experimental Hypertension A4 (1992): 1177–1191.
Forette, F.; Seux, M-L.; Staessen, J. A.; Thijs, L.; BirkenhÄger, W. H.; Barbaskiene, M-R.; Babeanu, S.; Bossini, A.; Gol-Extremera, B.; Girerd, X.; Laks, T.; Lilov, E.; Moisseyev, V.; Tuomilehto, J.; Vanhannen, H.; Webster, J.; Yodfat, Y.; and Fagard, R. "On Behalf of the Syst-Eur Investigators. Prevention of Dementia in Randomized Double-Blind Placebo-Controlled Systolic Hypertension in Europe (Syst-Eur) Trial." Lancet 352 (1998): 1347–1351.
Gueyffier, F.; Bulpitt, C.; Boissel, Jean-Pierre; Schron, Eleanor; Ekbom, Tork; Fagard, Robert; Casiglia, Edoardo; Kerlikowske, K.; and Coope, J. "Antihypertensive Drugs in Very Old People: A Subgroup Meta-Analysis of Randomised Controlled Trials." Lancet 353 (1999): 793–796.
Guidelines Subcommittee, World Health Organization-International Society of Hypertension. "Guidelines for the Management of Hypertension." Journal of Hypertension 17 (1999): 151–183.
Hansson, L.; Lindholm, L. H., Niskanen, L.; Lanke, J.; Hedner, T.; Niklason, A.; LuomanmÄki, K.; DalhÖf, B.; de Faire, U.; MÖrlin, C.; Karlberg, B. E.; Wester, P. O.; and BjÖrk, J-E. "Effect of Angiotensin-Converting-Enzyme Inhibition Compared with Conventional Therapy on Cardiovascular Morbidity and Mortality in Hypertension: The Captopril Project (CAPPP) Randomised Trial." Lancet 353 (1999): 611–616.
Hansson, L.; Lindholm, L. H.; Ekbom, T.; DahlÖf, B.; Lanke, J.; ScherstÉn, B.; Wester, P. O.; Hedner, Thomas; and de Faire, Ulf. "Randomised Trial of Old and New Anti-hypertensive Drugs in Elderly Patients: Cardiovascular Mortality and Morbidity the Swedish Trial in Old Patients with Hypertension-2 Study." Lancet 354 (1999): 1751–1756.
Kannel, W. B., and Gordon, T. "Evaluation of Cardiovascular Risk in the Elderly: The Framingham Study." Bulletin of the New-York Academy of Medicine 54 (1978): 573–591.
MRC Working Party. "Medical Research Council Trial of Treatment of Hypertension in Older Adults: Principal Results." British Medical Journal 304 (1992): 405–412.
SHEP Cooperative Research Group. "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)." Journal of the American Medical Association 265 (1991): 3255–3264. "The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure." (JNC VI) Archives of Internal Medicine 157 (1997): 2413–2446.
Staessen, J. A.; Fagard, R.; Thijs, L.; Celis, H.; Arabidze, G. G.; BirkenhÄger, W. H. Bulpitt, C.; de Leeuw, W.; Dollery, C. T. Fletcher, A. E.; Forette, F.; Leonetti, G.; Nachev, C.; O'Brien, E. T.; Rosenfeld, J.; Rodicio, J. L.; Tuomilehto, J.; and Zanchetti, A. "Randomised Double-Blind Comparison of Placebo and Active Treatment for Older Patients with Isolated Systolic Hypertension." Lancet 350 (1997): 757–764.
Staessen, J. A.; Gazowski, J.; Wang, J. G.; Thijs, L.; Den Honde, E.; Boissel, J-P.; Coope, John; Ekbom, Tork; Gueyffier, FranÇois; Liu, L.; Kerlikowske, K.; Pocock, S.; and Fagard, R.. "Risks of Untreated and Treated Isolated Systolic Hypertension in the Elderly: Meta-Analysis of Outcome Trials." Lancet 355 (2000): 865–872.