To elucidate the clinical significance of lipoprotein (a) [Lp(a)] in the elderly, 48 patients with Lp (a) of 35mg/dl or more [the high Lp (a) group] and 97 patients with Lp (a) less than 20mg/dl [the low Lp (a) group] were enrolled to investigate their outcome for five years. At registration, they were all examined by brain computerized tomography (CT) for cerebrovascular diseases, B-mode ultrasonography (US) for carotid lesions, ECG for myocardial ischemia, and Doppler arteriography for the ankle pressure index (API). They were followed up completely to study survival rates, cause of death, and morbidity rates of vascular events, including occurrence of stroke, myocardial infarction, and aortic aneurysm as well as progression of the stage in arteriosclerosis obliterans. The mean age of the high Lp (a) group was 78.1, whereas that of the low Lp (a) group was 76.8. Baseline clinical findings revealed no difference in age or gender between the two groups, although a previous history of stroke, abnormal CT and US findings, and low API were more frequent in the high Lp (a) group than in the low Lp (a) group. In the high Lp (a) group [vs. the low Lp (a) group], 18 patients (vs. 21 patients) died within five years, which resulted in a cumulative mortality rate of 37.5% (vs. 21.6%) and an annual mortality rate of 9.4% (vs. 4.8%). Based on log-rank analysis, the survival rate of the high Lp (a) group was significantly lower than that of the low Lp (a) group. The most common causes of death were vascular events and pneumonia, more than half of them were aspiration pneumonia complicated with stroke. Ten patients in the high Lp (a) group had vascular events (vs. 8 patients). The morbidity rate of vascular events, most of which were cerebral infarction, was higher in the high Lp (a) group (annual morbidity rate 5.5%) than in the low Lp (a) group (1.8%). These findings suggested that serum Lp (a) concentration, genetically determined and remaining consistent throughout life, had influenced vascular wall damage over a long time with age, therefore, a high Lp (a) level might promote atherothrombosis. In the elderly, therefore, high Lp (a) level, resulting in symptomatic vascular lesions with organ dysfunction, is a distinct and independent poor prognostic risk factor.
Arotinolol hydrochloride with α-and β-receptor blocking action, developed in Japan, is mainly used for the treatment of hypertension. The study population consisted of 42 outpatients with essential hypertension with a blood pressure greater or equal to 160/96mmHg, 10 men and 32 women, with a mean age of 77.5 year. The patients received 10mg arotinolol hydrochloride daily for 24 weeks which was taken orally twice a day. We evaluated the changes of blood pressure, heart rate and chief complaints of patients before and every 4 weeks during treatment and the renal function before, 12 weeks after and 24 weeks after, the administration of arotinolol hydrochloride. Blood pressure and heart rate decreased significantly after 4 weeks of treatment with arotinolol hydrochloride (p<0.05). However, no significant changes were found in blood urea nitrogen, serum creatinine, serum albumin, β2-microglobuline, NAG or creatinine clearance during the 24 weeks of treatment. These results indicate that arotinolol hydrochloride has antihypertensive effects without renal dysfunction in elderly patients with essential hypertension.
Recent developments in molecular biological techniques allowed us to examine the genetic risk factors responsible for essential hypertension. The candidate gene approach revealed that several gene polymorphisms increase the relative risk for hypertension. Most genetic studies, however, examined only young subjects but not elderly ones. To examine the importance of gene polymorphisms in elderly hypertension, we carried out a case-control study and compared the odds ratio for hypertension between young (<60) and elderly (≥60) subjects. The participants of this study were recruited from the outpatients of Osaka University Medical School with informed consent. We examined the following polymorphisms as candidates: the angiotensinogen (AGT/M235T), angiotensin converting enzyme (ACE I/D), angiotensin II type 1 (AT1/A1166C) and type 2 (AT2/C3123A) receptors, alpha-adducin (adducin/Gly460Trp), methylenetetrahydrofolate reductase (MTHHR/C677T), and apolipoprotein (apoE/epsilon 4, apoE/T-491A). In young subjects, the AGT/T235 allele significantly increased the odds ratio for hypertension but not in elderly subjects. In young males, the AT2/A3123 allele was also associated with hypertension but not in females or in elderly subjects. Other associations between polymorphism and hypertension did not reach a significant level. To sum up, it was revealed that some polymorphisms increase the susceptibility for hypertension but others do not, which suggests that there is heterogeneity in the genetic involvement of polymorphism due to aging.
Geriatric medical care can be viewed as general medical care for the elderly. We conducted a survey of members of the Japanese Society of General Medicine who belong to a university hospital, on their views of geriatric medicine/medical education. The questionnaires consisted of six categories of items about: (1) the physician's career; (2) whether the physician performs geriatric research in his/her laboratory; (3) whether the physician has an interest in geriatric medicine or medical education; (4) the physician's views on geriatric medicine or medical education; (5) of what pre- and post-graduate medical education on geriatric medicine should consist, from the physician's point of view; and (6) the physician's ideas about geriatric medicine/medical education in view of general medicine. Out of the 181 questionnaires sent, 96 (53%) people replied, of whom 51 (53.1%) were members of a Department of General Medicine, 57 (60%) were teaching staff, 46 (48.4%) had experience in home medical care such as home visits, and 17 (18.1%) belonged to the Japanese Society of Geriatric Medicine. Seventy-six respondents (85.4%) had an interest in geriatric medicine/medical education. Of the respondents, 96.8% recognized the need for pre- and post-graduate medical education concerning geriatrics. Some members of the Japanese Society of General Medicine who answered the questionnaire see geriatric medicine as entirely general medicine, and also that geriatric medicine is important, necessary and special. In addition, they see that the field of geriatric medicine is not yet developed in regard to geriatric medical care and education. Most respondents could not specify which section in a medical university is responsible for teaching the fields of basic and social medicine. This result shows that it may be difficult to incorporate pre-graduate geriatric medical education into the curriculum. As part of the pre-graduate curriculum of medical education on geriatrics, a practical exercise such as inspection of a geriatric hospital and geriatric home was considered most desirable by the respondents. Out of nine items, the top three most important aspects of post-graduate medical education on geriatrics for clinical and social medicine, were (1) studying the medical care and welfare of the elderly, (2) assessing the impaired life function of the elderly, and (3) studying pharmaco- therapy. Out of 6 items, the top three most important aspects of a practical exercise in post-graduate medical education in geriatrics were (1) providing general care to the elderly, (2) giving rehabilitation guidance and (3) providing psychological support for the elderly. Furthermore, 20 of the respondents (22.5%) have performed geriatric medical research on either the activities of daily life of the elderly or living wills, both of which seem to reflect the health and life of elderly people.
An 86-year-old man had a history of hypertension and had been treated with calcium antagonist but no medications that could reduce heart rate. As a 12-lead electrocardiogram showed sinus bradycardia, complete right bundle branch block and left anterior fascicular hemiblock on his first visit to our hospital on January 1998, he was admitted to our hospital for further examination and treatment. A 24-hour Holter electrocardiogram demonstrated a total number of 74, 182 heartbeats per day with pauses (>2.0sec) of 187/day. Overdrive atrial pacing study and His bundle electrogram revealed a prolonged corrected sinus node recovery time (5, 820msec at a stimulation rate of 130/min) and H-V conduction time (80msec) with normal A-H conduction time, respectively. We diagnosed these abnormalities as sick sinus syndrome (Rubenstein II). His activity of daily living score was 30 points by the Barthel index on the day of admission. Oral administration of orciprenaline sulfate (30mg/day), a β-adrenoceptor agonist, was initially chosen rather than implantation of a cardiac pacemaker to increase his heart rate since he did not have any symptoms due to bradycardia and he did not give us an informed consent for the implantation. Orciprenaline sulfate, however, failed to increase total heartbeats (73, 079/day). Then, oral cilostazol (100mg/day), a phosphodiesterase III inhibitor, was administered. After two weeks of the regimen total heart beats were increased (85, 642/day) with no pauses. The increase in heart rate resulted in the improvement of his activity of daily living (Barthel index: 55 points). Cilostazol could be the first line medication for elderly patients with bradyarrhythmia in whom implantation of cardiac pacemaker is not absolutely indicated.
Five elderly patients (≥65y) with cerebral infarction induced by dehydration during a heat wave were described to clarify the relationship between dehydration and stroke in the aged. When the daily maximum temperature exceeded 30°C every day for two weeks, 6 patients with acute stroke came to our hospital. Five of them were patients with cerebral infarction aged 73-89 (the elderly group) and one was a 52-year-old woman with putaminal hemorrhage. As control groups, patients with ischemic stroke during the period 4 weeks before and after, but excluding the heat wave period, which consisted of an elderly control group (n=7) and a young control group (n=5), were also studied retrospectively with regard to clinical findings and neuroimaging. The incidence of cerebral infarction in the elderly group was higher in the heat wave period among all three groups. Atherothrombotic, lacunar, and cardioembolic infarctions were seen in 1, 2 and 2 cases, respectively. The onset in the elderly group was characteristic as all occurred before noon and were related to exercise. Physical examination at arrival revealed decreased skin turgor and dry tongue. A high BUN/creatinine ratio (≥25) and elevated fibrinogen (>400mg/dl) was frequently noted, although high hematocrit (≥45) was not seen. According to clinical findings, dehydration was diagnosed and they were infused with fluid, resulting in the improvement of skin turgor and tongue moisture. These findings indicated that dehydration due to excess perspiration due to the heat wave induced cerebral infarction in the elderly. It suggests that water intake on awakening in summer is important to prevent dehydration and ischemic stroke because elderly people are especially susceptible to those conditions in the morning.
A 82-year-old woman was admitted because of dehydration and chronic renal failure. Although her renal function was improved by hydration, granulocytopenia (granulocyte number 645/mm3) occurred. Treatment with a relatively high dose of H2 blocker for one month before admission may have caused the granulocytopenia. To prevent possible infection in the patient, we administered 75g of granulocyte-colony stimulating factor (G-CSF) for 5 consecutive days but 4 days after commencement of administration of G-CSF, pain in both knee joints suddenly appeared. Synovial fluid aspiration revealed granulocytosis (10, 400/mm3) and deposition of calcium pyrophosphate dihydrate in the knee joints. The level of G-CSF in the synovial fluid was increased in the joints (700pg/ml), compared with the serum concentration (62pg/ml). Furthermore, the concentrations of interleukin-6 and interleukin-8 were markedly increased in the synovial fluid. The results indicated that her pseudogout exacerbation by G-CSF was at least in part explained by the increased production of cytokines in the knee joints. Because the prevalence of pseudogout and gout is overwhelming in the elderly, the possibility of GCSF induced exacerbation of joint pain should be carefully considered in elderly patients.