Changes in drug treatment in the elderly between 1971 and 2000.

OBJECTIVE: To investigate changes in drug treatment among elderly men and women over a 29-year period between 1971 and 2000. METHODS: Drug consumption was investigated in five representative population samples of 70-year-olds born in 1901-1902 (n=973), 1906-1907 (n=1036), 1911-1912 (n=619), 1922 (n=449) and 1930 (n=506) and in three representative samples of 79- to 80-year-olds born in 1901-1902 (n=537), 1906-1907 (n=538) and 1915 (n=212). RESULTS: The proportion of 70-year-olds who used drugs increased from 60% to 79% in men and from 76% to 88% in women from 1972 to 2000. Among 80-year-olds, 21% of the men and 11% of the women were without drug treatment in 1980, compared with 7% in 1995. The average number of drugs among 70-year-olds on treatment increased during the observation period from 2.8 to 3.5 in men and from 2.8 to 4.0 in women. At age 79-80 years, the mean number of drugs was 3.3 in men and 4.0 in women in 1980 and 4.0 in men and 4.7 in women in 1995. The most common drugs were cardiovascular drugs, analgesics and drugs for diseases in the central nervous system. The most pronounced changes in the consumption of specific drugs were found for anti-ulcerative drugs (increased), digitalis (decreased), diuretics (decreased in women), anti-thrombotic drugs (increased), calcium/vitamin D (increased), insulin (increased in men aged 70 years), analgesics (increased), levaxin (increased in women), anti-depressants (increased in women aged 70 years) and oestrogen in women (increased). The treatment patterns for cardiovascular diseases changed during the observation period and the use of calcium antagonists, angiotensin converting enzyme inhibitors, beta-blockers and lipid-lowering drugs increased. CONCLUSION: The proportion of the population with drug treatment at ages 70 years and 79-80 years increased as did the average number of drugs among treated subjects between 1971 and 2000. Important differences in the treatment patterns for different diseases were observed.

Cerebral atherosclerosis as predictor of stroke and mortality in representative elderly population.

BACKGROUND AND PURPOSE: The aim of this study was to assess the relationship between cardiovascular risk factors, atherosclerotic disease in the carotid bifurcation, and the risk of stroke and mortality in a representative population sample. METHODS: One hundred forty-two men and women participated in a population study at ages 70 and 76 years. At age 78, extracranial and intracranial circulation was examined by means of duplex sonography and transcranial Doppler techniques. Mortality and hospitalization for stroke were analyzed over a 5-year follow-up period up to age 83 years. RESULTS: Carotid plaques were identified in 82% of the men and 79% of the women. Bilateral plaques were found in 57% of the men and 46% of the women, and stenosis resulting in >50% diameter reduction occurred in 28% of the men and 17% of the women. Carotid stenosis >75% was observed in 7 subjects (0.5%). Bilateral plaques at age 78 were correlated with systolic blood pressure and ischemic heart disease at age 70 years. The pulsatility index was 1.0 to 1.4 in 63% and > or =1.5 in 13% of the study population. The pulsatility index was correlated with systolic and diastolic blood pressure, serum cholesterol, and triglycerides. Men with bilateral carotid plaques at age 78 years had an increased risk of stroke or mortality during the 5-year follow-up period (74% bilateral plaques versus 21% unilateral or no plaques). This was not found in the women (33% versus 26%). CONCLUSIONS: Carotid atherosclerosis was prevalent in a majority of elderly subjects. Bilateral plaques were correlated with systolic blood pressure and ischemic heart disease at age 70 years and predicted the risk of stroke and mortality in men but not in women.

Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H-70 Study.

The association between blood pressure and dementia is debated. Results from population-based studies on blood pressure and dementia are inconclusive, and most are performed in subjects younger than 80 years of age. We examined the relation between blood pressure and dementia and the possible effect modification of this relation by age in a pooled dataset based on two prospective population-based studies. Subjects came from the Rotterdam study (n = 6,668), a longitudinal population-based study among subjects aged 55 years and over, and from the Gothenburg H-70 Study (n = 317), a study on subjects aged 85 years at baseline. Screening and diagnostic procedures for assessment of dementia were similar at baseline and follow-up and comparable between studies. We estimated relative risks of dementia using Cox proportional hazards regression analysis, adjusted for age, gender and study location. The average follow-up was 2.1 years. During this period, 196 subjects developed dementia. The risk of dementia decreased with increasing blood pressure level (per 10 mm Hg systolic blood pressure: RR = 0.93, 95% CI = 0.88-0.99; per 10 mm Hg diastolic blood pressure: RR = 0.89, 95% CI = 0.79-1.00). This association was confined to subjects who used anthypertensive medication. Persons who were demented at baseline had a stronger blood pressure decline during follow-up than those who were non-demented. This study suggests an inverse association between blood pressure and dementia risk in elderly persons on antihypertensive medication. Possibly, they may need higher blood pressure levels to maintain an adequate cerebral perfusion. Alternatively, lower blood pressure may be secondary to brain lesions in preclinical stages of dementia.

Haemodynamic and renal effects of felodipine in young and elderly subjects.

OBJECTIVE: To study the influence of age on renal and haemodynamic effects of the calcium antagonist felodipine. METHODS: Eight young (mean age 27 years) and eight elderly (mean age 75 years) healthy normotensive subjects were given felodipine intravenously for 120 min aiming at close to therapeutic plasma level concentration. Renal blood flow (RBF) and renal vascular resistance (RVR) was estimated from para-aminohippuric acid (PAH) clearance 51CrEDTA clearance was used to measure glomerular filtration rate (GFR) and used in the calculations of fractional excretion (FE) of electrolytes. Impedance cardiography was performed to assess stroke volume and for the calculation of cardiac output and ejection fraction. RESULTS: At the end of felodipine infusion, the concentration of felodipine was on average 10.0 nmol x l(-1) in young and 12.0 nmol x l(-1) in elderly subjects (NS). During felodipine infusion blood pressure (BP) decreased from 138/76 to 120/68 in elderly subjects. The BP in young subjects was 126/74 at basal and 125/70 after infusion of felodipine. The systemic and renal vascular resistance decreased to a similar extent in young and elderly subjects after felodipine infusion. Felodipine caused a decrease in systemic vascular resistance from 25.6 to 23.3 in elderly and from 23.8 to 21.8 in the young subjects. Mean values for RVR at baseline and during infusion of felodipine were significantly higher in the elderly (10.1-15.1) than in the young subjects (5.4-6.7). Felodipine reduced RVR by 10% in the young and by 12% in the elderly at the end of infusion. The young subjects had 31% higher GFR than the elderly subjects at the start of infusion. Felodipine infusion did not affect GFR. There were no effects on stroke volume and ejection fraction. An initial natriuretic effect was found after infusion of felodipine in the young subjects. The fractional excretion of all electrolytes tended to increase after both felodipine and placebo, more in the elderly than in the young subjects. CONCLUSION: The effects of felodipine on central and renal haemodynamics previously observed in young and middle-aged subjects also seem to exist in the elderly. Volume expansion seems to increase the excretion of electrolytes more in elderly than in young people, and therefore the effect of felodipine on natriuresis is more evident in young subjects.

Energy intake and expenditure: validation of a diet history by heart rate monitoring, activity diary and doubly labeled water.

OBJECTIVE: To validate a diet history (DH). DESIGN: Energy intake (EI) estimated by a diet history (DH) was validated against total energy expenditure (TEE) measured by doubly labeled water (DLW) (n = 12) used as reference, by heart rate monitoring (HR) and by an activity diary (AD). SETTING: Department of Geriatric Medicine, Göteborg University, Vasa Hospital, Gothenburg, Sweden. SUBJECTS: 20 healthy free-living elderly subjects (73 years) from the gerontological and geriatric population studies, Gothenburg, Sweden (H70). RESULTS: Mean value for EI was 9.02 (s.d. 2.30), for TEE by HR was 9.66 (s.d. 2.25) MJ/d, and for TEE by AD was 9.40 (s.d. 2.08) MJ/d. In the 12 individuals measured with DLW, EI was 8.62 (s.d. 2.06), TEE by DLW was 9.90 (s.d. 1.43) MJ/d, TEE by HR was 8.94 (s.d. 1.96) MJ/d, and TEE by AD was 9.24 (s.d. 2.15)MJ/d. Mean difference between DH and DLW was 1.28 (s.d. 2.17) MJ (NS) and the DH/DLW ratio was 0.88. Four subjects were identified as under-reporters and one as an over-reporter. CONCLUSION: The DH slightly underestimated EI compared to the HR, but was in concordance with the AD. Compared to DLW, DH underestimated EI by 12%. On group level, the DH method gave comparable values to HR and AD. The DH was not valid for ranking of individuals. Compared to DLW, the HR method seemed to perform somewhat better than the AD for detection of under- and over-reporters.

A population-based study on blood pressure and brain atrophy in 85-year-olds.

In the general population, mean systolic and diastolic blood pressure increases up to age 75 years but decreases thereafter. The brain has a role in blood pressure regulation; it is not clear whether the cerebral changes that occur with aging contribute to the decline in blood pressure in the very elderly. We examined a population-based sample of 484 85-year-old persons (344 nondemented and 140 demented, 61 with Alzheimer's disease, 65 with vascular dementia, and 14 with other types of dementia) with a neuropsychiatric examination and blood pressure measurements. Dementia was diagnosed according to the criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders, edition 3, revised. Brain atrophy was measured by CT of the brain. In the nondemented group, frontal (r=-0.18, P=0.037) and parietal (r=-0.23, P=0.008) cortical atrophy and bifrontal ratio (r=-0.20, P=0.013) were associated with lower systolic blood pressure, and frontal (r=-0.23, P=0.010) and parietal (r=-0.24, P=0.008) cortical atrophy and bifrontal ratio (r=-0.23, P=0.006) with lower diastolic blood pressure. Systolic blood pressure was lower in subjects with Alzheimer's disease and vascular dementia, and diastolic blood pressure was lower in those with vascular dementia compared with the nondemented. Systolic (r=-0.27, P<0.0001) and diastolic (r=-0.10, P=0.020) blood pressure was negatively correlated to dementia severity. In the demented subjects, frontal cortical atrophy was correlated to lower diastolic blood pressure (r=-0.21, P=0.043). Our findings suggest that age-related changes in brain structure may contribute to the decrease in blood pressure in the very elderly and that low blood pressure in dementia disorders is mainly a secondary phenomenon.

15-year longitudinal study of blood pressure and dementia.

BACKGROUND: Vascular causes of dementia may be more common than supposed. Vascular factors may also have a role in late-onset Alzheimer's disease, but the role of hypertension in the development of dementia is unclear. METHODS: As part of the Longitudinal Population Study of 70-year-olds in Göteborg, Sweden, we analysed the relation between blood pressure and the development of dementia in the age intervals 70-75, 75-79, and 79-85 years in those non-demented at age 70 (n = 382). The sample was followed up for 15 years and examined repeatedly with a comprehensive investigation, including a psychiatric and physical examination. a FINDINGS: Participants who developed dementia at age 79-85 had higher systolic blood pressure at age 70 (mean 178 vs 164 mm Hg, p = 0.034) and higher diastolic blood pressure at ages 70 (101 vs 92, p = 0.004) and 75 (97 vs 90, p = 0.022) than those who did not develop dementia. For subtypes of dementia, higher diastolic blood pressure was recorded at age 70 (101, p = 0.019) for those developing Alzheimer's disease and at age 75 (101, p = 0.015) for those developing vascular dementia than for those who did not develop dementia. Participants with white-matter lesions on computed tomography at age 85 had higher blood pressure at age 70 than those without such lesions. Blood pressure declined in the years before dementia onset and was then similar to or lower than that in non-demented individuals. INTERPRETATION: Previously increased blood pressure may increase the risk for dementia by inducing small-vessel disease and white-matter lesions. To what extent the decline in blood pressure before dementia onset is a consequence or a cause of the brain disease remains to be elucidated.

Coronary heart disease at 70, 75 and 79 years of age: a longitudinal study with special reference to sex differences and mortality.

In a population study of 70-year-old people in Göteborg, Sweden, a representative sample of 449 men and 524 women was followed for nine years. The prevalence of coronary heart disease (CHD) at age 70 was about 30% in both sexes and did not change up to age 79. Myocardial infarction appeared twice as often in men as in women at age 70 but angina pectoris and ST-T changes on ECG showed no sex difference. Myocardial infarction and probable ischaemia on ECG increased significantly between ages 70 and 79 in both sexes. Half of the men with angina pectoris had a history of myocardial infarction and/or probable ischaemia on ECG criteria compared with 23% of the women. The mortality rate was twice as high in men as in women irrespective of CHD. When CHD was present at age 70 the nine-year mortality was doubled. CHD was shown to be a strong independent risk factor for death also in this age group.

Overtreatment of hypertension in the elderly?

In a representative population sample of 619 70-year-old people, 26% were taking antihypertensive treatment. Twenty per cent (n = 32) of them showed no signs of cardiovascular disease and had a blood pressure of less than 175/95 mmHg. Treatment was withdrawn in 25 of the 32 patients. Casual blood pressure, blood pressure during isometric exercise and left ventricular morphology and function were studied repeatedly over 2 years, using non-invasive methods. A significant increase in mean systolic and diastolic blood pressures was observed in the 14 patients who completed the study. No change was observed with respect to left ventricular morphology and left ventricular diastolic function. A statistically significant decrease in left ventricular fractional shortening, but no clinical signs of congestive heart failure were observed. Withdrawal of antihypertensive treatment in elderly patients free from signs of cardiovascular disease may thus be attempted without harmful effects on cardiovascular function.

Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects.

The pharmacokinetics and antihypertensive effects of felodipine, a new dihydropyridine calcium channel blocker, were studied in elderly hypertensive patients, 67 to 79 years of age and in young healthy subjects, 20 to 34 years of age following oral administration of 5 mg twice daily to steady-state. A single intravenous dose of 3H-felodipine (0.04mg) was given together with the oral dose on the study day. Cmax (17 nmol/L), Cmin (5 nmol/L) and AUC (82 nmol/L.h) were 3 times higher in the elderly than in the young subjects. Systemic availability was about 15% in both groups. Plasma clearance (CL) was reduced from 56.1 L/h in the young to 25.4 L/h in the elderly. There was no effect of age on the volume of distribution at steady-state (Vss). Reduced hepatic blood flow and enzyme activity or increased gut wall metabolism are possible reasons for the altered pharmacokinetics in the elderly. Blood pressure was reduced in the elderly from 190/99 to 177/91 mm Hg 12 hours after 5mg felodipine during twice daily dosage. The effect on blood pressure correlated with plasma concentrations of felodipine.

Blood pressure and mortality in old age. Eleven years' follow-up of a 70-year-old population.

The association between blood pressure levels and mortality up to 11 years has been studied in two representative samples of men and women (1951 people in total) from the longitudinal population study 'seventy-year-old people in Göteborg, Sweden'. We found a significant association between systolic blood pressure (SBP) and mean arterial pressures (MAP) and mortality after 6 years when data from both sexes were pooled. After 11 years, the mortality in the 10% of subjects who had the highest blood pressures at the age of 70 (greater than or equal to 190/105 for men and greater than or equal to 200/105 for women) was 30% higher among the men and 50-60% higher among the women than in the 75% of subjects with the lowest blood pressures. There was no difference between SBP and diastolic blood pressure (DBP) in this respect. A significant association between blood pressure and mortality remained when background factors such as treatment for hypertension, heart failure, coronary heart disease (CHD), diabetes, cholesterol, body mass index (BMI) and smoking habits were kept constant.