The upper limits of normal blood pressure have been considered to be 139mmHg systolic and 89mmHg diastolic for adults, but these values are not necessarily applicable to the elderly. This report presents blood pressure values of healthy persons aged 65 to 94 and estimates the upper limits of normal blood pressure in the elderly based on follow-up studies. The Blood Pressure Subgroup of the Study on Reference Values of Laboratory Tests in Elderly Subjects defined inclusion criteria for the healthy elderly as follows: (1) persons aged 65 to 94, (2) persons not complicated with cardiovascular diseases, (3) persons capable of living and walking freely, (4) persons without dementia, (5) persons without anemia, liver disease, renal failure, diabetes mellitus on drug treatment, lung disease, valvular disease or marked arrhythmias, (6) persons without neuromotor disease. The subgroup collected 2008 persons who fulfilled the criteria. Of the 2008 persons, 663 were not taking antihypertensive drugs, had body weight within an average Body Mass Index±standard deviation and had no abnormalities on ECG. The 663 persons were considered to be a group of most the normal elderly. Blood pressure values in this group were 133.3±18.9/77.0±10.6mmHg for males (N=318) and 134.3±18.7/75.7±10.2mmHg for females (N=345). Follow-up studies carried out by some members of the Blood Pressure Subgroup suggested that the upper limits of the normal blood pressure were 140 to 159mmHg systolic and 80 to 89mmHg diastolic for the elderly.

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The characteristics of plasma glucose in individuals aged over 65 years was investigated by analysis of age dependent changes of fasting and post glucose (75g) load values in population based studies and some follow-up studies. Institutional differences were surveyed in central laboratory of institutions which joined this study and found that differences were the range of +3.0-3.5% from the mean glucose levels between 100-400mg/dl. Therefore plasma glucose values around cutoff level should be confirmed by repeated determinations for reaching final diagnosis. The reference interval of plasma glucose does not differ in an age-dependent manner. We may use the reference interval proposed by the Committee of Diagnostic Criteria of Diabetes Mellitus of Japan Diabetes Society for adult individuals. Cases of diabetes diagnosed before 65 years old should be judged by the adult criteria. However, those who were not diabetic before age 65 and were found to be hyperglycemic after that age can be diagnosed classifying as follows: (1) Diabetes should be diagnosed in individuals with a fasting plasma glucose of 140mg/dl or more and 2 hours after glucose (75g) of 240mg/dl or more. Those with some symptoms suggesting diabetes and either 140mg/dl more or fasting or 240mg/dl or more 2 hours post 75g glucose load can also be diagnosed as diabetes. (2) Those who are not included in the above mentioned criteria but have plasma glucose values either equal or more than 120mg/dl fasting or equal or more than 200mg/dl at 2 hours post glucose load (75g) can be classified as “questionable diabetes mellitus”. (3) Borderline glucose intolerance of this age group can be applicable to those who have borderline criteria and are not included in “questionable diabetes mellitus”. (4) Those who have “questionable diabetes mellitus” should be observed every 3 months, because they are a highly likely to develop diabetes mallitus and possibly will have diabetic complications in future. However, even though they may develop diabetes mellitus soon, the marked symptoms due to diabetic complications may begin from age 80 years or more. Thus this new criteria may be valid by compromizing avoidance of big incomvenience of lifestyle change due to diabetes and possibility of development of late diabetic complications in far future.

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Plasma lipids (cholesterol, triglyceride and HDL-cholesterol) were evaluated in order to estimate desirable values in the aged. Plasma lipids were determined by 6 multicenters among aged people with clinically uneventful backgrounds since the values measured by the different institutions were found acceptable and comparable. Plasma cholesterol level was mostly 200mg/dl less in males and 210mg/dl or more in females. Plasma cholesterol levels increase after menopause. HDL-cholesterol was also higher in females than in males over 60 years of age. Triglyceride was around 100mg/dl or less in both sexes and tended to decrease with aging. There were no significant differences in the plasma lipid levels among the cohorts. To observe the angiographical changes in the coronary arteries, 102 patients were followed for 1 or 2 years. Progression was frequently observed in the subjects with a cholesterol level of over 220mg/dl. These results indicate that even in the aged, plasma cholesterol level below 220mg/dl is considered to be desirable to minimize vascular events.

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A total of 161 atherosclerotic plaques from 50 aortas in elderly autopsy cases were pathomorphologically investigated to clarify the pathogenesis of atherosclerotic plaque with central depression. Atherosclerotic plaques with central depression, with well defined borders were employed for this study, ulcerated plaques being excluded. Pathomorphological findings showed that plaques with central depression could be divided into four groups according to their derivation respectively; (a) fused lesion of multiple fibrous plaque, (b) regressing lesion of plaque, (c) healing lesion of ulcerated atheromatous plaque, (d) mixed type. Finally, it was suggested that atherosclerotic regression may cause some central depression in the atheromatous plaques.

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To clarify the effect of the calcium antagonist Nifedipine and the ACE inhibitor Enalapril on cardiac autonomic activity, power spectral analysis of heart rate variability (PSA) was conducted in 39 elderly patients with essential hypertension (mean age: 63:±11 years) before and after treatment. Twenty patients were treated with 10-20mg of Nifedipine (N group) and 19 with 5mg of Enalapril (Egroup) for 3 months. β-blocker (Atenolol 12.5mg) was added to Nifedipine in 12 patients of the N group for 1 month, and the modified effect of Atenolol on cardiac autonomic activity was also evaluated. Blood pressures were significantly reduced in both N and E groups after the treatment. The low frequency component (LF) in PSA, which was considered to be a quantitative marker of cardiac sympathetic activity, increased significantly and the high frequency component (HF), which was a marker of cardiac parasympathetic activity, significantly decreased with increase of PNA levels in N group after the treatment. However, the LF decreased significantly after addition of Atenolol. On the other hand, there was little significant change in LF and PNA in E group. These results suggest that Nifedipine increased cardiac sympathetic activity and that Enalapril had little influence on the cardiac sympathetic tone, while both antihypertensive agents significantly reduced blood pressure itself.

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We investigated the rate of development of dementia in 84 neurologically normal elderly subjects living in an old-age home (30 subjects, mean 77.2 years) or their own home 954, 73.7) prospectively. We examined cerebral blood flow (CBF), Hasegawa's scale (HS) and Kohs' block design test 6 to 9 years before this study (1991). HS and Kohs' IQ were significantly lower in the old-age home group than that in their own home group at that time. However, there were no demented subjects. Mortality was 21%, and we confirmed 9 dementia and 6 stroke cases during the period of observation. Twenty-seven percent of the old-age home group showed dementia in 1991. This rate was significantly higher than that for the elderly living in their own home (6.7%). Occurrence of stroke was also significantly higher in the former group than in the latter group. The subjects who developed stroke during observation showed a high incidence of dementia. Mean CBF measured on the first examination was significantly lower in dementia cases with stroke than in dementia cases without it. We performed MRI in 4 demented cases in 1991 (Fig. 1). Two cases showed no significant lesions and the other cases showed cerebral infarction which could cause dementia. These results indicate that life style and social environment may have significant effect on aging of the brain and on development of dementia in the elderly.

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It has common knowledge that the advent of H₂-blockers has radically changed the treatment of peptic ulcer. We reviewed 26, 667 endoscopic examinations, 5, 800 consecutive autopsies and 134 consecutive patients operated for peptic ulcer over an 18-year period to evaluate the effects of H₂-blockers on the treatment of peptic ulcer in the elderly (≥60 years of age). The number of operations for peptic ulcer in the elderly markedly declined after H₂-blocker therapy was introduced. This is mainly due to decreased operative indications for gastric bleeding as a result of conservative treatment. However, the incidence of perforating ulcers has hardly changed even after the introduction of H₂-blockers. More than 90% of these cases were non-diagnosed or non-treated ulcers and 50% of them were NSAID- or steroid-treated, which is characteristic in the elderly. We conclude that patients to be treated by anti-inflammatory drugs should be screened by endoscopy, and should be given anti-ulcer drugs prophylactically if necessary.

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Progression of atherosclerotic lesion of the carotid artery is suggested to induce the development of cerebrovascular events. We evaluate the risk factors related to carotid artery, wall thickness by ultrasonography. A total of 159 patients, who had received no medication for hypertension or hyperlipidemia were enrolled in this study. The wall thickness of carotid artery was evaluated as an intima-media (IM) complex measured by B-mode ultrasonography with a 7.5MHz probe. Simple regression analysis demonstrated significant correlation between the IM complex and both age and systolic blood pressure, but not with fasting levels of plasma glucose, hemoglobin A_1c, total and HDL cholesterol, triglyceride or gender. Stepwise regression analysis showed age and systolic blood pressure contribute to IM thickness (r=0.623). However, in patients aged 60 or over, blood pressure did not contribute to the IM wall thickness. Smoking was not a risk factor for IM thickness, but the Brinkman Index (daily consumption of cigarettes x years smoking) was significantly higher in patients with plaques in the carotid artery than those without it. These results suggest that high blood pressure is a risk factor for mild atherosclerotic lesions of the carotid artery for those aged under 60. Smoking may contribute to the formation of plaque, which may consequently lead to the ischemic cerebrovascular disease.

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To evaluate long-term efficacy of pravastatin, we administered this HMG-CoA reductase inhibitor at a mean dose of 9.9mg/day to 208 aged patients with serum levels of total cholesterol (TC) over 220mg/dl (mean±SD aged of 70±7 years; 62 males and 146 females) for 12 months. The mean serum value of TC significantly decreased from the basal level of 265mg/dl to 216mg/dl in the 3rd month, and this decrease was maintained throughout the observation period. Similar change was observed in the serum level of low density lipoprotein-cholesterol (LDL-C). Although the mean serum level of high density lipoprotein-cholesterol (HLC-C) in all patients did not change significantly, the HDL-C level in 34 patients with a HDL-C level below 40mg/dl significantly increased from the 3rd month. The mean serum level of triglyceride (TG) in all patients significantly decreased from the 3rd month, and this decrease in the TG was more prominent in 101 aged patients with TG levels higher than 150mg/dl. In 168 aged patients on 10mg/day of pravastatin thoughtout the period, there were significant negative correlations between the ratio of the decrease in TC in basal serum and each of the basal serum TC levels (r=-0.345, p<0.001) and age of the subjects (r=-0.208, p=0.007). These results indicate that long-term administration of pravastatin is effective treatment for lipid metabolism even in aged patients.

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To evaluate left ventricular diastolic filling properties in elderly hypertensive case with left ventricular hypertrophy (LVH), we investigated the influence of postural change from a supine to sitting position on transmitral flow velocity profile as assessed by pulsed Doppler echocardiography in 12 normotensives (N group) and 24 hypertensives, aged 65 to 80 years. Hypertensive subjects were divided into two groups on the basis of left ventricular mass index (LVMI): 12 hypertensives without LVH (H1 group; LVMI<130g/m²); 12 hypertensives with LVH (H2 group; LVMI>130g/m²). Peak early filling velocity (E), peak atrial filling velocity (A) and the E/A ratio were similar in the three groups in the supine position. The postural change decreased E and A in N and H1 groups. On the other hand, the change decreased E, but not A in the H2 group. The E/A ratio was decreased in the H2 group compared with both the N and H1 group in the sitting position. As a result, the sitting position increased atrial contribution to diastolic filling in the H2 group. These observations indicate that a reduction in preload changes the transmitral flow velocity profile in elderly hypertensives with left ventricular hypertrophy. The Doppler alterations may be related to impaired left ventricular diastolic function.

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The basal part of the interventricular septum may easily become hypertrophic because it is exposed to strong hemodynamic stress compared to the other portions of the left ventricle. We measured the end-diastolic interventricular wall thickness both at the base and in the midsection by 2D echocardiography in 122 normotensives, and examined whether the basal thickness increases with age. The basal thickness (B) increased with age in both sexes. In males the thickness averaged 10.1mm in the 50-59 age group, 10.2m in those aged 60-69 and 11.4mm (p<0.01) in those 70 or older compared to 9.4mm in those aged 49 or younger. In females it was 8.1mm (p<0.05) in the 50-59 age group, 8.3mm (<0.05) in those aged 60-69 and 10.0mm (p<0.01) in those 70 or older compared to 6.8mm in those 49 or younger. Concerning the midwall thickness (M), there were no significant changes among the respective age groups in either sex. As a result, a close correlation was found between the B/M ratio, a new and simple index for basal hypertrophy, and age (R=0.46, p<0.01 in males and R=0.43, p<0.01 in females). Comparison of the B/M ratio between the two age groups 49 or younger and 70 or older was as follows; 1.08 vs 1.30 (p<0.01) in males and 1.01 vs 1.27 (p<0.01) in females. Increase of basal hypertrophy in the aged was clearly indicated by the B/M ratio.

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