European Heart Journal (1997) 18, 1019-1023 Blood pressure and mortality in an older population A 5-year follow-up of the Helsinki Ageing Study S.-M. Hakala, R. S. Tilvis, and T. E. Strandberg Division of Geriatrics, Department of Medicine, University of Helsinki, Helsinki, Finland Objective Hypertension is an established risk factor of cardiovascular diseases, and in clinical studies its treatment has reduced cardiovascular complications in subjects up to 80 years of age. In the older age groups, prognostic data on blood pressure is sparse. We evaluated the prognostic significance of different blood pressure levels and the history of elevated blood pressure in an older population. Conclusion At the population level, among subjects aged 75 years and over, favourable 5-year survival is indicated by a high, but not a low, blood pressure. (Eur Heart J 1997; 18: 1019-1023) Results At 5 years, 240 subjects (40%) had died, 50% of them of cardiovascular disease. In crude analyses, an inverse relationship between both systolic and diastolic blood Key Words: Blood pressure, survival prognosis, elderly, hypertension. Introduction As the proportion of individuals over that age (and with a high prevalence of hypertension) is rapidly increasing in Western societies, it is important to elucidate the role of hypertension in this age group. There is evidence both from Finland'4' and in the United States'5' that older people with high blood pressure have a favourable survival prognosis. The purpose of our study was to extend these previous studies by investigating the prognostic value of blood pressure in those aged between 75 and 85 years at the population level. Recent reviews of several randomized trials have convincingly shown that older people benefit from treatment for elevated blood pressure'1>2'. Antihypertensive treatment has been shown to reduce the incidence of cardiovascular accidents, particularly strokes. In addition, the treatment of isolated systolic hypertension — considered earlier to be an innocuous phenomenon in the elderly — was shown to prevent cardiovascular complications in one study'3'. However, the studies have been selective, including mostly healthy elderly, and consequently, the results may not apply to the elderly at large. Furthermore, the trial evidence was mostly only up to 79 years. Revision submitted 2 July 1996, and accepted 8 July 1996. Correspondence: Professor Reijo S. Tilvis, MD, Division of Geriatrics, Department of Medicine, University of Helsinki, FIN-00290 Helsinki, Finland. 0195-668X/97/061019+05 $18.00/0 Methods Subjects The Helsinki Ageing Study is a population-based joint study of general and special health care in the City of Helsinki, Finland. It was planned to evaluate the prognostic significance of different clinical findings in the 1997 The European Society of Cardiology Downloaded from by guest on October 15, 2014 Design In the Helsinki Ageing Study random individuals 75, 80, and 85 years of age (n = 521) were evaluated at baseline using postal questionnaires, structured interviews, clinical examinations, laboratory investigations, and blood pressure measurements (supine, seated, standing). Date of death during a 5-year follow-up was verified using computerized registers, and thus the follow-up was 100% complete. The data were analysed using life-table analyses and Cox proportional hazards models. pressure and mortality was observed in all groups combined (P<001), and separately in the 80 and 85-year-old groups. However, a J-shaped link between diastolic blood pressure and mortality was found in the 75-year-old group. After controlling for age, gender and the presence of clinically significant diseases (in 72% of subjects) baseline blood pressure was associated with favourable 5-year survival. The risk ratios of systolic (per lOmmHg) and diastolic blood pressure (per 5 mmHg) were 0-90 (95% CI 0-85-0-96) and 0-92 (95% CI 0-86-0-99), respectively. Neither isolated systolic hypertension nor a history of hypertension treatment were associated with 5-year survival. 1020 S.-M. Hakala et al. Table 1 Helsinki Ageing Study population by gender and living conditions Age group (years) Gender Women Men Living conditions Home Nursing home Hospital 85 80 75 Random sample Studied clinically This study Random sample Studied clinically This study Random sample Studied clinically This study 190 84 168 71 143 58 192 74 155 57 126 48 201 54 156 44 115 31 248 20 6 216 17 6 186 11 4 217 39 10 172 30 10 153 16 5 169 64 22 126 52 22 107 29 10 Clinical evaluations and follow-up The cohorts were re-examined three times (in 1991, 1993 and 1994). The examinations included a postal questionnaire, a structured interview conducted by public-health nurses, a review of all available patient records, a thorough clinical structured examination carried out by general practitioners, comprehensive laboratory investigations, and echocardiogaphic examinations at entry161. The census status was examined annually until 31 December 1994 (5 years). overnight, but they had taken their regular medications. Blood pressure and heart rate were first measured while seated, followed by an electrocardiogram recording. After lying down for 5 min, the supine blood pressure, and after 1 min quiet standing, the standing blood pressure were measured. Seated blood pressure values were also registered by physicians. The group of healthy elderly Of the subjects, 126 were assigned to a group of healthy elderly, if their subjective health was good or moderate (scale: good, moderate, bad, very bad), if they had normal exercise tolerance according to the examining physicians (NYHA I)[9], and if they were free from diabetes, dementia, cancer, emphysema, and if they had no symptoms of cardiovascular (except high blood pressure) or cerebrovascular disorders. Statistical evaluation Data were analysed with Biomedical Data Processing (BMDP 1988) system"01. Life-table analyses and Cox proportional hazards regression models were used for survival analyses. Clinical criteria Hypertension was denned as a past diagnosis of hypertension with medication, or current blood pressure over 160/95 mmHg. Isolated systolic hypertension was defined as supine systolic blood pressure over 160 mmHg and diastolic less than 90 mmHg (with or without treatment). Clinical criteria for dementia and major depression were those of DSM-IH-R17'. Angina pectoris was diagnosed according to the criteria of Rose'81. The presence of other diseases was based either on data from hospital patients' records or the present clinical examination. Blood pressure measurements These were performed by specially trained nurses between 0800h and lOOOh. The subjects had fasted Eur Heart J, Vol. 18, June 1997 Results At 5 years, 240 subjects (40%) had died, 50% of them from cardiovascular diseases. Life-table analyses of all age groups showed an inverse relationship between total mortality and both systolic (/><0001) and diastolic blood pressure (/><0-001). Separate analyses of different age groups are shown in Fig. 1. In general, the associations were inverse between blood pressure and 5-year mortality. However, in the 75-year-old group, the association between diastolic blood pressure and mortality was J-shaped. After controlling for age, gender and the presence of clinically significant diseases (in 72% of subjects), baseline blood pressure was associated with beneficial Downloaded from by guest on October 15, 2014 older population at large. From the Helsinki Census Register, random cohorts of individuals alive in July 1988 and born in 1904, 1909 and 1914 (300 in each group, 11 -2% of total population of 8035) were invited to join the study in September 1989. Of these cohorts, 795 were still alive and living in the City of Helsinki. Altogether 144 (181%) refused to participate leaving 651 (81 -9%) people to be examined clinically until April 1990. The gender distribution of the study population equalled that of the total population. Three measurements of blood pressure were completed in 521 subjects (80%) (Table 1). Seventy-one of the study participants were in homes for the elderly. Blood pressure and mortality <120 Syst 121-140 °Hc blood 141-160 161-180 1021 >180 Downloaded from by guest on October 15, 2014 Figure 1 Percentage 5-year survival of three birth cohorts using baseline blood pressure levels from the population-based Helsinki Ageing Study. (There were no subjects in the 80-year-old group with diastolic blood pressure > 100 mmHg). 5-year survival (Table 2). The results were similar irrespective of whether the sample had been taken with the subjects supine, standing or seated. Neither the presence of isolated systolic hypertension at baseline, nor a history of hypertension treatment was significantly associated with 5-year survival. Exclusion of early deaths (during first 2 years) did not materially alter the results either. Eur Heart J, Vol. 18, June 1997 1022 S.-M. Hakala et al. Table 2 Adjusted risk ratios for five- year mortality of different blood pressure measurements Measurement Systolic, per lOmmHg supine standing sitting mean Diastolic, per 5 mmHg supine standing sitting mean Risk ratio 95% confidence interval 0-92 0-93 0-90 0-90 0-87-O-97 0-89-0-98 0-85-0-95 0-85-0-96 0-93 0-94 0-94 0-92 0-88-0-99 0-89-0-99 0-89-1 00 0-86-0-99 The risk ratios were calculated using the Cox regression model, in which age, gender and presence of diseases (yes/no) were forced in. Discussion Eur Heart J, Vol. 18, June 1997 This study was supported by the Ragnar Ekberg Foundation. References [1] Mulrow CD, Cornell JA, Herrera CR, Kadri A, Farnett L, Aguilar C. Hypertension in the elderly. Implications and generalizability of randomized trials. JAMA 1994; 272: 1932-8. [2] Lever AF, Ramsay LE. Treatment of hypertension in the elderly. J Hypertens 1995; 13: 571-9. [3] 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). JAMA 1991; 265: 3255-64. [4] Manila K, Haavisto M, Rajala S, Heikinheimo R. Blood pressure and five year survival in the very old. BMJ 1988; 296: 887-9. [5] Langer RD, Ganiats TG, Barrett-Connor E. Paradoxical survival of elderly men with high blood pressure. BMJ 1989: 298: 1356-8. [6] Lindroos M, Kupari M, Heikkila J, Tilvis R. Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample. J Am Coll Cardiol 1993; 21: 1220-5. [7] American Phychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd edn, revised, DSM-III-R. Washington DC: American Psychiatric Association. 1987. [8] Rose GA. Chest pain questionnaire. Milbank Mem Fund Q 1965: 43: 32-39. Downloaded from by guest on October 15, 2014 In the extensive field of hypertension and its treatment, the present study makes an important contribution for three reasons. First, the Helsinki Ageing Study was initially planned to evaluate the risk of different clinical conditions in the elderly. Therefore, special emphasis has been paid to the representativeness of the population sample. A second important feature — which also differentiates the study from most other studies in the elderly — is the age (birth) cohort approach. Consequently, it is possible to recognize possible differences inside the elderly population. This approach was useful in the present study where associations between blood pressure and mortality were not consistent until 80 years onwards. Third, our data can be seen to be reliable, as different methods of blood pressure measurement gave consistent results. The number of deaths was also sufficiently large to draw reliable conclusions. The inverse association between blood pressure and mortality seems to be at odds with well-known adverse effects of hypertension in young and middleaged populations'"1. The earlier finding in many studies in the elderly has been a J-shaped or U-shaped relationship between blood pressure and mortality. However, several former studies have found an inverse relationship, both in persons over 85 years'41 and around 78 years'51. This and the J-shape have usually been attributed to the effect of co-morbidity. The individuals with serious diseases have also low (or recently lowered) blood pressure and increased risk of death. Indeed, the recent study of Glynn et a/.'121 showed that after adjustment for serious diseases and exclusion of deaths during the first 3 years of follow-up, lower blood pressure did predict better survival. The age of their population, however, started from 65 years with the mean age less than 75 years. In the present study, the relationship tended to be inverse after 75 years, thus pinpointing the transition of high blood pressure from 'bad' to 'good' at 80 years of age. The statistical control for diseases, or exclusion of early deaths did not alter the major relationship. However, we do not believe that these procedures are sufficient to totally exclude recidual confounding by diseases associated with ageing. Thus, the lowering of blood pressure is evidently one sign of 'senile devitalization' preceding death. Also the lack of effect of antihypertensive treatment tends to support this. Recent reviews have shown that generally the treatment of hypertension benefits the elderly up to 80 years'121. Studies in persons over 80 years are sparse, but the Swedish STOP-hypertension study suggested benefit over the whole age range of 70-84 years with baseline blood pressure > 180/90 mmHg'131. However, no reports describe the benefit, specifically in the group over 80 years, which only constituted 16% of the study population. In general, participants in trials are very selective. For example, our cohorts were screened in order to find participants for the SYST-EUR trial of isolated hypertension, only 4% were found eligible. Not a single participant was eligible for the Hypertension in the Very Elderly Trial (HYVET, [14]). Overall, previous data and the present results suggest that starting antihypertensive medication after 80 years is problematic. Those with the lowest blood pressure are at increased risk of death, and as compared to them, those with highest values are not. Thus, at the individual level the finding of very old persons at true risk due to their hypertension is difficult, and the start of medication requires very individual assessments of benefits and risks. On the other hand, in contrast to some other studies'15il6], we found no association between antihypertensive drug use and subsequent mortality in our study. Blood pressure and mortality [9] Criteria Committee, New York Heart Association Inc. Diseases of the heart and blood vessels. Nomenclature and criteria for diagnosis, 6th edn. Boston: Little, Brown and Co.; 1964: 114. [10] Dixon WJ, ed. BMDP. Statistical Software. University of California Press, London 1988. [11] MacMahon S, Peto R, Cutler J et al. Blood pressure, stroke, and coronary heart disease: I effects of prolonged differences in blood pressure. Lancet 1990; 335: 765-74. [12] Glynn RJ, Field TS, Rosner B, Hebert PR. Taylor JO, Hennekens CH. Evidence for a positive linear relation between blood pressure and mortality in elderly people. Lancet 1995; 345: 825-9. [13] Dahlof B, Lindholm LH, Hansson L, Schersten B, EkbomT, Wester P-O. Morbidity and mortality in the Swedish Trial in 1023 Old Patients with Hypertension (STOP-Hypertension). Lancet 1991; 338: 1281-5. [14] Bulbitt CH, Fletcher AE, Amery A et al. The hypertension in the very elderly trial (HYVET): Rationale, methodology and comparison with previous trials. Drugs & Aging 1994; 5: 171-83. [j5] Seeman T, Mendes de Leon A, Berkman L, Ostfeld A. Risk factors for coronary heart disease among older men and women: a prospective study of community-dwelling elderly. Am J Epidemiol 1993; 138: 1037^12. McCallum J, Simons J. [16] s i m o n s LA Friediander Y, R i s k f a c t o r s f o r c o r o n a r y h e a r t d i s e a s e i n t h e prospective Dubbo Study of Australian elderly. Atherosclerosis 1995; 117: 107-18 Downloaded from by guest on October 15, 2014 Eur Heart J, Vol. 18, June 1997
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