Glomerular filtration rate estimation and mortality in an elderly population.

BACKGROUND: Few studies have addressed the link between minor renal dysfunction and mortality in the elderly. AIM: To compare three equations for estimated GFR (eGFR) in assessing renal dysfunction and predicting mortality in an elderly population. DESIGN: Longitudinal observational study. METHODS: We studied 441 people from the Jerusalem Seventy Year Olds Longitudinal Study who had measurements of serum creatinine, all of whom were aged 70 years at study initiation and were living in the community. GFR was estimated based on serum creatinine and using the Cockcroft-Gault (CG), the abbreviated Modification of Diet in Renal Disease (MDRD) and the Mayo Clinic equations. Twelve-year mortality was the main outcome measure. RESULTS: The prevalence of reduced eGFR was 51% using the CG, 34% using MDRD and 16% using the Mayo Clinic equation. eGFR dichotomized by the definition of CKD significantly predicted mortality only with the Mayo Clinic equation (hazard ratio 1.56, 95%CI 1.01-2.39). When eGFR was divided into quartiles and the lowest compared to the highest, all equations predicted mortality. Hazard ratios (95%CI) were 5.48 (1.27-23.65), 7.47 (2.74-20.3), and 7.375 (3.13-17.36), for CG, MDRD, and Mayo Clinic, respectively. DISCUSSION: Reduced eGFR was prevalent in this study group, and associated with mortality. This association was strongest using the Mayo Clinic equation.

Climbing Stairs, Handrail Use, and Survival.

BACKGROUND: Negotiating stairs is identified as a challenging task by older people, and using a handrail to climb stairs is a compensatory gait strategy to overcome mobility difficulties. We examine the association between handrail use to climb stairs at increasing ages, and long term survival. METHODS: Data were collected by the Jerusalem Longitudinal Study, which is a prospective study of a representative sample from the 1920-1921 birth-cohort living in West Jerusalem. Comprehensive assessment at home in 1990, 1998, and 2005, at ages 70 (n=446), 78 (n=897), and 85 (n=1041) included direct questioning concerning handrail use for climbing stairs. Mortality data were collected from age 70-90. RESULTS: The frequency of handrail use to climb stairs at ages 70, 78, 85 years was 23.1% (n=103/446), 41.0% (n=368/897), and 86.7% (n=903/1041) respectively. Handrail use was associated throughout follow-up with a consistent pattern of negative demographic, functional and medical parameters. Between ages 70-78, 70-90, 78-85, 78-90, and 85-90, survival was significantly lower among subjects using a handrail, with unadjusted mortality Hazard Ratios of HR 1.57 (95%CI, 1.01-2.42), HR 1.65 (95%CI, 1.27-2.14), HR 1.78 (95%CI, 1.41-2.25), HR 1.71 (95%CI, 1.41-2.06), and HR 1.53 (95%CI, 1.01-2.33) respectively. HR's remained significant at all ages after adjusting for sociodemographic factors (gender, education, marital, and financial status), and common medical conditions (ischemic heart disease, hypertension, diabetes, chronic pain), as well as between ages 78-85 and 78-90 after adjusting for functional covariables (self-rated health, physical activity, depression, BMI and ADL difficulties). CONCLUSION: Using a handrail to climb stairs is increasingly common with rising age, was associated with a negative profile of health parameters and is associated with subsequent mortality.

Moderate renal insufficiency at 70 years predicts mortality.

BACKGROUND: Glomerular filtration rate (GFR) diminishes with age. Kidney function in the elderly is often assessed by serum creatinine alone, although it is insensitive in this age group. Formulae for predicting GFR are not widely used. AIM: To study the effect of low predicted GFR on mortality. DESIGN: Longitudinal cohort study. SETTING: The community-based Jerusalem Seventy Year Olds Longitudinal Study. METHODS: We studied 445 subjects, all aged 70 years, using questionnaires, a medical examination with history-taking, and standard laboratory tests. Moderate renal insufficiency was defined as a predicted GFR of <60 ml/min, based on the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) equations. RESULTS: Predicted GFR was normally distributed, with a mean +/- SD of 62.4 +/- 15.27 ml/min. Predicted GFR was <60 ml/min in 221 (46%), most of whom had normal serum creatinine. Twelve-year mortality was 38.7% in these 221 vs. 27% in the other 204. The survival advantage was already evident after 3 years. Under Cox proportional hazard analysis using numerous common risk factors as independent variables, lower predicted GFR had a significant mortality risk (hazard ratio 2.108, 95%CI 1.43-3.12, p = 0.0002). DISCUSSION: In community-dwelling elderly people, moderate renal insufficiency as assessed using the CG equation is a strong and independent predictor of mortality. Most of these at-risk patients have 'normal' serum creatinine.

The siesta in the elderly: risk factor for mortality?

BACKGROUND: During the siesta, blood pressure declines like it does during night sleep. Because cardiovascular and cerebrovascular events cluster during the morning hours, when hemodynamic changes from nocturnal baseline are maximal, we hypothesized that an additional sleep period during the day (the siesta) may increase cardiovascular and cerebrovascular events, and thus mortality. METHODS: A prospective population-based cohort study of 455 70-year-old residents of Jerusalem, Israel, using self-reported siesta at baseline and 6 1/2 years of total mortality data. RESULTS: The prevalence of the practice of the siesta was 60.7%. It was more prevalent among men than women (68% vs 51%, P<.001) and in survivors of previous myocardial infarction than in those without previous myocardial infarction (78% vs 58%, P = .009). After 6 1/2 years of follow-up (1990-1996), 75 subjects died. For those who practiced the siesta, total mortality was 20% vs 11% for those who did not (P = .01; risk odds ratio, 2.0; 95% confidence interval, 1.1-3.4). In a multiple logistic regression model that included several lifestyle descriptors, risk factors, and diseases, the siesta remained predictive of mortality (P = .03; risk odds ratio, 2.1; 95% confidence interval, 1.1-3.9).

Effectiveness of combined nifedipine and propranolol treatment in hypertension.

The long-term antihypertensive effect of combined nifedipine and propranolol therapy was assessed in an open trial in 26 hypertensive patients (19 men, seven women, mean age 53 years). On propranolol alone (160 to 240 mg/day), the patients' average sitting blood pressure was 192 +/- 5/114 +/- 2 mm Hg. Propranolol was continued in a fixed dose and nifedipine was added in a dose that was gradually increased from 30 to 90 mg/day to achieve blood pressure (BP) values below 160/95 mm Hg. Twenty-two patients remained on the combined regimen for 14 to 30 weeks. Their BP decreased to 136 +/- 3/84 +/- 2 mm Hg on an average daily dose of 59.5 mg nifedipine. Seventeen of the 22 subjects were subsequently treated sequentially with propranolol alone, combined therapy, and nifedipine alone, to assess the relative efficacy of each mode of therapy. The combined regimen was found to be more effective than either drug alone. Side effects occurred in 13 of 26 patients. Four dropped out 4 to 11 weeks after starting nifedipine because of either intolerable flushing (2), allergic rash (1), or headache (1). Nine subjects experienced mild reactions that were well tolerated. It is concluded that the combined use of propranolol and nifedipine is effective in the long-term treatment of moderately severe hypertension and offers an alternative therapeutic approach that deserves further evaluation.

Calcium channel blockers in the management of hypertension in the elderly.

Calcium channel blockers seem to be particularly suitable for elderly hypertensive patients since these agents do not cause salt and fluid retention, postural hypotension, sedation, depression, or biochemical abnormalities. Moreover, their use is compatible with several common diseases of old age, such as diabetes, obstructive lung disease, and peripheral vascular disease. We recently conducted a study in 21 patients (average age, 79 +/- 2 years) who completed an eight-week trial with 20-mg nifedipine tablets taken twice daily. Mean blood pressure decreased from 191 +/- 2/96 +/- 2 mm Hg to 151 +/- 4/80 +/- 3 mm Hg. In 15 patients (71 percent), blood pressure decreased to less than or equal to 160/90 mm Hg; in four additional patients (19 percent), diastolic blood pressure decreased by 15 to 25 percent. Thus, there was a sustained lowering of blood pressure in 90 percent of the participants receiving nifedipine monotherapy. A review of recent studies in elderly hypertensive patients revealed similarly favorable results with calcium channel blockers given alone or in combination with other agents. The accumulating data suggest that these compounds may offer a useful new approach to the treatment of hypertension in old age. However, in these studies, the number of patients and the duration of follow-up need to be extended to confirm the favorable impression obtained thus far.

The effects of physical activity on mortality in the Jerusalem 70-Year-Olds Longitudinal Study.

OBJECTIVE: To study the association between physical activity and mortality in older men and women. DESIGN: A community-based cohort study: the Jerusalem 70-Year-Olds Longitudinal Study. PARTICIPANTS: A systematically selected and representative sample of all residents of the western part of Jerusalem born in 1920-1921: 456 subjects, 25% of the total population. MEASUREMENTS: An extensive social and medical profile was developed by extensive interview and physical and ancillary examination. Medical diagnoses were established and subjects reported their level of regular physical activity. RESULTS: Unadjusted mortality at 6-year follow-up was significantly greater for subjects reporting no regular exercise than for those walking as little as 4 hours weekly (23.4% vs 9.9%, odds ratio (OR) = 2.77; 95% confidence interval (CI), 1.64-4.69). The significance of these benefits was demonstrated for males as well as for females (30.28% vs 12.14%, P < .001, 16.19% vs 6.86%, P = .036, respectively). Logistic regression analysis demonstrated the survival advantage to be independent of gender, smoking, subjective economic hardship, or preexisting medical conditions (hypertension; diabetes; coronary artery, cerebrovascular, renal, and respiratory diseases; anemia; and malignancy). Increased regularity of activity correlated with declining mortality. The odds ratios for mortality compared to the sedentary group were 0.73 (CI, 0.33-1.62) for those doing sports activity at least twice weekly, 0.41 (CI, 0.19-0.91) for those walking at least 4 hours weekly, 0.14 (CI, 0.04-0.50) for those exercising daily, and 0.40 (CI, 0.22-0.72) for all levels of physical activity combined. CONCLUSIONS: These results suggest that regular physical activity confers increased survival in the aged. It is proposed that older people be encouraged to engage in regular, moderate physical activity.

Decreased hospital utilization by older adults attributable to a home hospitalization program.

OBJECTIVE: To evaluate the cost effectiveness of a short-term home health care program for older people, Home Hospitalization (HH), compared with the alternative of regular ambulatory care with general or geriatric hospitalization as necessary. SETTING: Our HH was initiated in November 1991 to serve Jerusalem residents. Program staff included physicians, nurses, and paramedical professionals. Other medical/hospital services were provided nonselectively by the general medical personnel of the various hospitals in Jerusalem. STUDY DESIGN: Patients over the age of 65 were either referred to the HH program (study group, n = 36,500) or to routine medical care (control group; n = 9000) depending on their Sick Fund assignment. Hospital utilization rates per enrollee were studied prospectively and compared both between the two groups and with hospitalization rates in the year before the initiation of the program. RESULTS: During the first 26 months of operations, the HH program cared for 741 older persons for a total of 37,290 days' care at an average daily costs of $30.06 (1992) and $23.64 (1993). Annual general hospitalization rates per person declined in the study group from 2.80 days in the 1991 baseline period to 2.65 days in 1992 and to 2.54 days in 1993. Hospitalization rates in the control group increased from 2.62 in 1991 to 2.70 days/member and 2.71 days/member in 1992 and 1993, respectively. Annual geriatric hospitalization rates declined considerably in the study group from the 1991 baseline of 1.49 to 1.34 (1992) to 1.33 (1993). The control group experienced a small decrease from 1.64 (1991) to 1.58 (1992) and then a rise to 1.68 days per member in 1993. For the 26-month duration of the program, estimated savings of 20,773 general hospital days ($5.54 million) and 8486 geriatric hospital days ($0.98 million) exceeded its costs ($0.97 million), providing a cost/benefit ratio of 5.7/1. In addition, patient satisfaction was high. CONCLUSION: The HH program provided a cost effective substitute for care in a geriatric or general hospital for Jerusalem's elderly.

Nifedipine in the treatment of hypertension in the elderly.

The effect of nifedipine monotherapy, retard tablets, 20 mg bid, was evaluated in 23 hypertensive patients, mean age, 79 +/- 2 years. Twenty-one patients completed an eight-week study. Blood pressure (BP) decreased to 160/90 mm Hg in 15 patients; in four additional patients diastolic BP dropped by 15% to 28%. In a subset of five patients with isolated systolic hypertension, a significant reduction in systolic BP was noted. Side effects were relatively mild and only two patients discontinued the study. The results suggest that nifedipine monotherapy offers an alternative, logic, therapeutic approach to hypertension in the elderly.

The cyclic AMP second messenger system in man: the effects of heredity, hormones, drugs, aluminum, age and disease on signal amplification.

The intracellular effects of a number of hormonal signals are mediated by the cyclic AMP second messenger system in man and the ubiquitous distribution of hormone-stimulated adenylate cyclase suggests the importance of this enzyme complex in normal aging and pathophysiological states. Various vectors including heredity, endogenous catecholamines, steroid hormones, and drugs affect the activity of hormone-stimulated adenylate cyclase in man. The effect of heredity was studied using lymphocytes obtained from monozygotic twin pairs and age and sex-matched sib pairs. Only for forskolin-stimulated activity is a significant proportion of individual variance attributable to heredity, suggesting the relative stability of the catalytic subunit. Beta-adrenergic and prostaglandin E-1 activity are "state" characteristics and their activities are controlled by environmental parameters. A significant reduction in isoproterenol-stimulated cyclic AMP accumulation between the menses and luteal phase of the menstrual cycle is observed in lymphocytes obtained from 11 female subjects. The lowest level of beta-adrenergic receptor activity is associated with the highest levels of progesterone and estradiol hormone levels in blood. Lithium at therapeutic concentrations markedly inhibits adenylate cyclase activity in platelet membranes. Moreover, marked individual differences are observed in sensitivity to lithium as determined by Dixon plot derived Ki values for 9 normal, healthy subjects. Human adenylate cyclase obtained from platelets and lymphocytes is activated by micromolar amounts of aluminum in the presence of NaF. Irreversible activation of adenylate cyclase by aluminum is suggested as a possible mechanism of this metal's neurotoxicity. The biochemical basis for the age-associated decline in beta-adrenergic responsiveness in man is discussed. Several investigations suggest a deficit at two levels in the adenylate cyclase complex: an impaired coupling of the receptor/N protein subunits and an additional lesion distal to the receptor at the level of N/C coupling. Perfusion studies with salbutamol suggest that the decline in beta-adrenergic sensitivity is general and not restricted to lymphocytes. Possible abnormalities in cyclic AMP signal amplification and recognition in various disease states is discussed. Increased prostaglandin E-1-stimulated cyclic AMP accumulation is observed in lymphocytes obtained from patients with Alzheimer's disease compared to age-matched controls and correlated with severity of the disease state.(ABSTRACT TRUNCATED AT 400 WORDS)

A prospective comparison of the use of nasogastric and percutaneous endoscopic gastrostomy tubes for long-term enteral feeding in older people.

OBJECTIVE: To compare the indications for and the outcome of long-term enteral feeding by nasogastric tube (NGT) with that of percutaneous endoscopic gastrostomy (PEG) tube. DESIGN: A prospective, multicenter cohort study. SETTING: Acute geriatric units and long-term care (LTC) hospitals in Jerusalem, Israel. PARTICIPANTS: 122 chronic patients aged 65 years and older for whom long-term enteral feeding was indicated as determined by the treating physician. Patients with acute medical conditions at the time of tube placement were excluded. MEASUREMENTS: We examined the indications for enteral feeding, nutritional status, outcome and complications in all subjects. Subjects were followed for a minimum period of six months. RESULTS: Although the PEG patients were older and had a higher incidence of dementia, there was an improved survival in those patients with PEG as compared to NGT (hazard ratio (HR)=0.41; 95% confidence interval (CI) 0.22-0.76; P=0.01). Also, the patients with PEG had a lower rate of aspiration (HR=0.48; 95% CI 0.26-0.89) and self-extubation (HR=0.17; 95% CI 0.05-0.58) than those with NGT. Apart from a significant improvement in the serum albumin level at the 4-week follow-up assessment in the patients with PEG compared to those with NGT (adjusted mean 3.35 compared to 3.08; F=4.982), nutritional status was otherwise similar in both groups. CONCLUSION: In long-term enteral feeding, in a selected group of non-acute patients, the use of PEG was associated with improved survival, was better tolerated by the patient and was associated with a lower incidence of aspiration. A randomized controlled study is needed to determine whether PEG is truly superior to NGT.

Alzheimer's disease: isoproterenol and prostaglandin E1-stimulated cyclic AMP accumulation in lymphocytes.

Reduced lymphocyte beta-adrenergic receptor activity was observed in patients with Alzheimer's disease and in aged controls; a parallel decline in lymphocytic prostaglandin E1 receptor activity was seen in the aged controls. In the Alzheimer patients, however, such lymphocytic prostaglandin E1 receptor activity was significantly raised and correlated with a rating scale for severity of dementia.

Isoelectric focusing of human platelet phospholipase C: evidence for multimolecular forms.

Polyacrylamide gel isoelectric focusing was employed to characterize phospholipase C activity in the supernatant fraction after disruption of human platelets. Three bands of enzyme activity were detected on focused gels: a major band of activity (B) and two additional bands (A,C) were consistently identified. The isoelectric points of the three bands were in the range of pH 7.5-8.0. Phospholipase C activity was assayed using both phosphatidylinositol and phosphatidylinositol-4-monophosphate. The prominent B band was active against both substrates and no evidence for substrate preference towards phosphoinositides was obtained. These data suggest that isozyme forms of cystolic phospholipase C are present in human platelet supernatant and suggest the possibility of functional and structural differentiation of the various forms of the enzyme.

Age related decline in aluminum-activated human platelet adenylate cyclase: post-receptor changes in cyclic AMP second messenger signal amplification in normal aging and dementia of the Alzheimer type.

Low, micromolar concentrations of aluminum (in the presence of NaF) were shown to strongly activate human platelet adenylate cyclase and provided a useful probe for evaluating cyclic AMP second messenger function distal to the receptor: The effect of normal aging and disease state on second messenger activity in man was studied by measurements of the aluminum-activated enzyme. A significant decline in aluminum-stimulated platelet adenylate cyclase activity in older, healthy subjects was observed. An age-associated decline in NaF-stimulated cyclic AMP synthesis was also demonstrated for normal, non-demented subjects. These findings suggest an age-associated lesion at the level of the guanine nucleotide regulatory protein/catalytic subunit of the adenylate cyclase complex. However, for patients with Alzheimer's disease no such decline in platelet adenylate cyclase activity was detected, and increased sensitivity to both aluminum and NaF was demonstrated.

Acute desensitization of lymphocyte beta-adrenergic-stimulated adenylate cyclase in old age and Alzheimer's disease.

The effect of prior incubation with a single concentration of isoproterenol (10(-4) M) for 2 hours at 37 degrees C on isoproterenol-stimulated cyclic AMP accumulation in intact lymphocytes from young, old and subjects with Alzheimer's disease was studied. In lymphocytes from all three subjects groups prior incubation of cells with isoproterenol resulted in a significant reduction of cyclic AMP accumulation upon subsequent stimulation with isoproterenol.

Limited fluctuations in T lymphocyte parameters in the human as a marker of aging.

Analysis of T lymphocytes was performed on SENIEUR protocol selected young and old individuals. Parameters examined were phenotype and reactivity to phytohemagglutinin (PHA) measured under standard and limiting dilution conditions. Blood samples were drawn twice, at an interval of one month, to establish the stability of values measured. The results showed no statistically significant difference as in proportion of CD4(+) and CD8(+) cells between the young and old peripheral blood samples. Standard proliferative responses to PHA were reduced in the old. Limiting dilution analyses revealed a reproducible, pronounced decrease in the frequency of precursors of PHA-reactive T lymphocytes in the old. Twice repeated determinations showed fluctuations in the above parameters in the young, whereas in the old the values were lower and less fluctuating. This observation was not associated with any change in the clinical status of the elderly subjects during the one-year follow up period.

Home hospitalization in the spectrum of community geriatric care.

The Home Hospitalization Programme was initiated in Jerusalem in 1991 to provide intensive medical care at home in order to prevent or shorten hospitalizations. The programme was based upon regular home visits by physicians, and nursing assessment to determine the need for regular nursing care. Primary-care physicians and nurses were renumerated by a global monthly fee, and were on 24-h call in addition to their periodic visits. Patients were recruited by senior geriatric physicians from acute hospital wards, as well as from the community, at the family doctor's request. Ancillary services available to the home hospitalization team included laboratory and electrocardiographic testing, specialty consultations, physical occupational or speech therapy, social work and home help up to 3 h daily. Monthly visits by a senior physician provided oversight and further consultation. Home hospitalization grew out of the continuing care division of the Clalit Sick Fund, a health maintenance organization providing umbrella medical insurance and ambulatory care. The programme grew synergistically with the other facilities of continuing care to encompass a network of comprehensive services to acute, subacute and chronic patients both at home and in institutional settings. In 4 years this network succeeded in establishing the focus of subacute intensive care in the community, achieving high levels of patient and family satisfaction, as well as striking economic advantages. In its first 2 years of operation home hospitalization saved S4 million due to reduced hospital utilization, and preliminary data for the subsequent 2 years indicated that this trend continued. Home hospitalization became the hub of a far-reaching system of supportive, intensive and humane care in the community.

Frailty, cognitive impairment and mortality among the oldest old.

INTRODUCTION: Both frailty and cognitive impairment are increasingly prevalent with advancing age. Nonetheless among the oldest old their relationship is poorly described. This study examines the association between frailty status and cognitive impairment at age 85 and their impact on 5-year mortality. METHODS: A representative sample of 840 community dwelling people from the Jerusalem Longitudinal Cohort Study was comprehensively assessed at age 85. Frailty was defined according to the "phenotype of frailty", as including at least three of the following: weight loss, slowness, weakness, exhaustion and low physical activity levels. Pre frailty was defined as 1-2/5 criteria. Cognitive impairment was assessed according to the Mini Mental State Examination (MMSE). Mortality data was collected from age 85-90. RESULTS: A total of 164 (19.5%) were frail, 470 (56%) were pre frail and 206 (24.5%) were not frail, with prevalence of MMSE≤24 being 53.3%, 15%, and 7.4% respectively. A uniform pattern of increased adverse health, affective, disease and functional measures were associated with frailty status. Frailty status was significantly associated with cognitive impairment, with an Odds Ratios of 3.77 (95%CI 1.42-9.99) for MMSE≤24 after adjustment for socio demographic, medical mood and functional covariates. Among frail, pre frail and non frail subjects, 5-year mortality was 44.5%, 20.4%, 13.6% respectively. Mortality among frail subjects with or without cognitive impairment was 54.2% vs. 54.9%, p=0.9). Adjusting together for frailty, MMSE, education and gender, the Hazards ratio for 5-year mortality for frailty was 3.861 (95%CI 2.4-6.2), and for MMSE≤24 was 1.25 (95%CI 0.87-1.78). CONCLUSIONS: Among the oldest old, frailty status was significantly associated with cognitive impairment; after adjustment, frailty alone was predictive of subsequent mortality.