In the oral session “Hypertension in the Elderly and Vascular Ageing”, Jan Staessen, MD (University of Leuven, Belgium), analyzed the issuelower blood pressure (BP) in middle-aged subjects and maintaining normotension at older age, when the control of the systolic BP is a prerequisite to prevent stroke and dementia.
Hypertension (HT) “affects over 30% of the world’s population” said Prof. Staessen, “and BP is the most powerful predictor of stroke”. Population mortality trends for stroke parallel those for HT. A systolic BP of 115 mmHg or higher explains 60% of the population-attributable risk of stroke. Worldwide, stroke causes 9% of all deaths and is the second most common cause of death after ischemic heart disease. “Two thirds of stroke deaths occur in developing nations” he noted.
“In placebo-controlled trials, antihypertensive treatment of middle-aged or older hypertensive patients with predominantly diastolic HT proved that a 5-6 mmHg decline in diastolic BP maintained over five years reduced the incidence of stroke by nearly 40%” told Dr. Staessen. In older patients with isolated systolic HT, antihypertensive treatment over four years lowered systolic BP on average by 10 mmHg and decreased fatal and nonfatal stroke by 30% in Western and Asian patients alike.
The recently published Hypertension in the Very Elderly Trial (HYVET) proved that lowering BP in very old patients (>/=80 years) with systolic (>/=160 mm Hg) or diastolic (90-109 mmHg) HT to less than 150 mmHg systolic and 80 mmHg diastolic reduced the incidence of fatal and nonfatal stroke by 30%, Staessen noted. Fatal stroke and all-cause mortality declined by 39 and 21%, respectively. The HYVET results definitely dispelled the suspicion that in the very elderly the benefit of BP lowering therapy in terms of stroke prevention might come at the cost of a higher mortality. To prevent one death, only 40 very elderly had to be treated for two years.
“Because of the aging of populations, the number of demented patients will increase twofold every 20 years to 81.1 million by 2040, with over 60% living in developing countries” said Staessen. Traditional teaching subdivides the dementia syndrome into neurodegenerative Alzheimer disease (AD), vascular dementia (VaD), and mixed variants. In spite of the vast literature on the dichotomy between AD and VaD, new emerging concepts highlight the role of cardiovascular risk factors in the pathogenesis of AD. HT is the major player in the pathogenesis of stroke, poststroke dementia, and VaD.
AD is the most common cause of dementia, contributing from 45% to over 75% of the cases in Asians and Caucasians, respectively. HT, especially when already present at middle age, adversely affects cognition later in life and predisposes to AD. “In very old adults, the association between impaired cognition and HT becomes more difficult to demonstrate, because systolic BP falls in the very old and after the onset of dementia” said Staessen.
The double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial demonstrated that the risk of dementia associated with systolic HT is reversible, he noted. Active treatment consisted of the calcium-channel blocker nitrendipine, which could be combined with enalapril, hydrochlorothiazide, or both add-on drugs. Median follow-up lasted only two years. The trial had to be stopped prematurely, because active treatment resulted in a 42% decrease in fatal and nonfatal stroke. In the substudy of dementia (n = 2418; mean age, 70 years), active treatment reduced systolic/diastolic BP by 8.3/3.8 mmHg and the incidence of dementia by 50% from 7.7 to 3.8 cases per 1000 patient-years. After the double-blind trial had been stopped in 1997, all patients were offered therapy with the same active medication. Median follow-up lengthened to 3.9 years. The number of dementia cases doubled from 32 to 64 (41 with Alzheimer’s disease). Immediate compared to delayed antihypertensive therapy reduced the risk of dementia by 55% (CI, 24-73%; p < 0.001) from 7.4 to 3.3 cases per 1000 patient-years.
The potential for prevention
In summary, absolute risk is higher in older than younger patients, so that for a similar relative risk reduction, the number of patient-years of treatment required to prevent one major cardiovascular event is substantially less in the elderly, in particular in the presence of additional risk factors, such as male sex or a history of previous cardiovascular complications, noted Staessen.
Recent HT guidelines favor a global approach with the use of charts for risk stratification based on additional risk factors, target organ damage, or associated conditions, such as diabetes mellitus or a history of cardiovascular or renal disease. This approach is justified on the basis that HT, hypercholesterolemia and smoking account for approximately 85% of the modifiable cardiovascular risk.
“Clinicians should be aware that similar proportional risk reductions across the age range translates into much higher absolute benefit in older than younger patients and that antihypertensive treatment should be embedded within the management of the global cardiovascular risk” said Staessen.
- Forette F, Seux ML, Staessen JA, Thijs L, Babarskiene MJ, Babeanu S, Bossini A, Fagard R, Gil-Extremerea B, Laks T, Kobalava Z, Sarti C, Tuomilehto J. Vanhanen H, Webster J, Yodfat Y, Birkenhäger WH, for the Syst-Eur Investigators. The prevention of dementia with antihypertensive treatment. New evidence from the Systolic Hypertension in Europe (Syst-Eur) Trial. Arch Intern Med 2002;162:2046-2052.
- Zhang H, Thijs L, Staessen JA. Blood pressure lowering for primary and secondary prevention of stroke. Hypertension 2006;48:187-195.
- Staessen JA, Richart T, Birkenhäger WH. Less atherosclerosis and lower blood pressure for a meaningful life perspective with more brain. Hypertension 2007;49:389-400.
- Staessen JA, Richart T, Verdecchia P. Reducing blood pressure in people of different ages. Absolute benefit increases with age and management of the overall cardiovascular risk. BMJ 2008;336:1080-1081.
- Beckett NS, Peters R, Fletcher AE, Staessen JA, Liu L, Dumitrascu D, Stoyanovsky V, Antikainen RL, Nikitin Y, Anderson C, Belhani A, Forette F, Rajkumar C, Thijs L, Banya W, Bulpitt CJ, for the HYVET Study Group. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-1898 .