Biomedical subjects

C S Williams

Publications and source records attributed to C S Williams.

At least 37 records · Page 2Linked to original sources

PubMed2000

Postnatal differentiation of efferent ductule epithelium in goats: a light microscopic and ultrastructural study.

Caprine efferent ductule epithelium contains ciliated and nonciliated cells. The latter cells are divided into three types: type II cells contain PAS-positive granules, type III cells contain PAS-negative vacuoles, and type I cells lack both granules and vacuoles (Goyal and Williams, Anat. Rec. 220:58-67). The objectives of this study are i) to determine when the epithelium differentiates into ciliated and nonciliated cells, ii) to determine when nonciliated cells acquire characteristics typical for type II and type III cells, and iii) to relate developmental changes in the epithelium with those in the testis. Testes and efferent ductules were examined at the light and electron microscopic levels in goats from 1-25 weeks of age. Efferent ductule epithelium contained ciliated and nonciliated cells as early as week 1. While ciliated cells were differentiated at week 1, differentiation of nonciliated cells did not occur until week > or =15. Differential features in ciliated cells included the presence of cilia at the apical border and an aggregation of mitochondria in the apical cytoplasm. Those in nonciliated cells included the presence of i) an endocytotic apparatus at week > or =15, ii) PAS-positive granules at week > or =15, and iii) PAS-negative vacuoles at week > or =25. The seminiferous tubules developed lumens at 12-15 weeks. Hence, while differentiation of ciliated cells occurred much before lumen formation in the seminiferous tubules, that of nonciliated cells coincided with, or occurred soon after, lumen formation, suggesting a role for testicular fluid contents in their differentiation. The goat efferent ductules can be characterized morphologically mature by 25 weeks.

Age Factors↗

PubMed2000

Dizziness among older adults: a possible geriatric syndrome.

BACKGROUND: In previous studies of dizziness, the prevalence of specific causes has varied widely and either no or multiple causes have been identified. Dizziness might be better considered a geriatric syndrome that results from impairment or disease in multiple systems. OBJECTIVE: To determine the predisposing characteristics and situational factors associated with dizziness. DESIGN: Population-based, cross-sectional study. SETTING: Community. PARTICIPANTS: Probability sample of 1087 community-living persons in New Haven, Connecticut, who were at least 72 years of age. MEASUREMENTS: Episodes of dizziness that occurred for at least 1 month; manifestations of dizziness; and predisposing demographic, medical, neurologic, sensory, and psychological characteristics. RESULTS: 261 participants (24%) reported dizziness; 56% of dizzy persons described several sensations and 74% reported several triggering activities. The adjusted relative risks for characteristics associated with dizziness were 1.69 (95% CI, 1.24 to 2.30) for anxiety, 1.36 (CI, 1.02 to 1.80) for depressive symptoms, 1.27 (CI, 0.99 to 1.63) for impaired hearing, 1.30 (CI, 1.01 to 1.68) for five or more medications, 1.31 (CI, 0.92 to 1.87) for postural hypotension, 1.34 (CI, 0.95 to 1.90) for impaired balance, and 1.31 (CI, 1.00 to 1.71) for past myocardial infarction. The adjusted relative risk for dizziness was 1.38 (CI, 1.27 to 1.49) for each additional characteristic. CONCLUSIONS: The association among characteristics in multiple domains (cardiovascular, neurologic, sensory, psychological, and medication-related) and dizziness, coupled with the multiplicity of sensations and triggering activities, suggests that dizziness may be a geriatric syndrome, similar to delirium and falling. If so, an impairment reduction strategy, proven effective for other geriatric syndromes, may be effective in reducing the symptoms and disabilities associated with dizziness.

Aged↗

PubMed2000

Transforming growth factor-beta1 enhances Ha-ras-induced expression of cyclooxygenase-2 in intestinal epithelial cells via stabilization of mRNA.

Oncogenic ras induces the expression of cyclooxygenase-2 (COX-2) in a variety of cells. Here we investigated the role of transforming growth factor-beta (TGF-beta) in the Ras-mediated induction of COX-2 in intestinal epithelial cells (RIE-1). RIE-1 cells were transfected with an inducible Ha-Ras(Val12) cDNA and are referred as RIE-iRas cells. the addition of 5 mM isopropyl-1-thio-beta-D-galactopyranoside (IPTG) induced the expression of Ha-Ras(Val12), closely followed by an increase in the expression of COX-2. Neutralizing anti-TGF-beta antibody partially blocked the Ras-induced increase in COX-2. Combined treatment with IPTG and TGF-beta1 resulted in a 20-50-fold increase in the levels of COX-2 mRNA. The t1/2 of COX-2 mRNA was increased from 13 to 24 min by Ha-Ras induction alone. The addition of TGF-beta1 further stabilized the COX-2 mRNA (t1/2 > 50 min). Stable transfection of a luciferase reporter construct containing the COX-2 3'-untranslated region (3'-UTR) revealed that TGF-beta1 treatment and Ras induction each stabilized the COX-2 3'-UTR. Combined treatment with IPTG and TGF-beta1 synergistically increased the luciferase activity. Furthermore, a conserved AU-rich region located in the proximal COX-2 3'-UTR is required for maximal stabilization of COX-2 3'-UTR by Ras or TGF-beta1 and is necessary for the synergistic stabilization of COX-2 3'-UTR by oncogenic Ras and TGF-beta1.

3' Untranslated Regions↗

PubMed2000

Regulation of cyclooxygenase 2 expression in hepatocytes by CCAAT/enhancer-binding proteins.

BACKGROUND & AIMS: Expression of cyclooxygenase (COX)-2 in response to lipopolysaccharide (LPS) challenge has been analyzed in cultured fetal, neonatal, and adult hepatocytes and in hepatoma cell lines. METHODS: To study the mechanisms of LPS-dependent expression of COX-2 in these cells, the activity of the COX-2 promoter and the levels of CCAAT/enhancer-binding proteins (C/EBPs) were determined. RESULTS: COX-2 was induced in fetal hepatocytes, but this response declined rapidly after birth. This loss of inducibility of COX-2 paralleled the expression of C/EBP-alpha in neonatal hepatocytes. Transfection of fetal and adult hepatocytes with sequences corresponding to the 5'-flanking region of the rat COX-2 gene confirmed the absence of promoter activity in adult hepatocytes. Moreover, transient expression of C/EBP-alpha, but not C/EBP-delta, in the hepatoma cell line AT3F cells abolished the COX-2 promoter activity. Prolonged culture of adult hepatocytes restored the induction of COX-2 after complete disappearance of C/EBP-alpha. CONCLUSIONS: These results suggest that the presence of high levels of C/EBP-alpha is involved in the impairment of COX-2 expression in adult hepatocytes challenged with proinflammatory stimuli.

Age Factors↗

PubMed2000

Association of patients' perception of health status and exercise electrocardiogram, myocardial perfusion imaging, and ventricular function measures.

BACKGROUND: Patients' viewpoint of their health status is increasingly used as an important outcome measure of the success of treatments. Because clinicians rarely formally measure patients' health-related quality of life, the question arises whether noninvasive testing for ischemia can provide similar information regarding physical functioning and general health perception. METHODS: We measured physical functioning and general health status with the Medical Outcomes Study Short Form (SF-36) survey in 195 consecutive patients (68% male, mean age 55.6 +/- 11.1 years) referred for exercise testing with myocardial perfusion imaging. The survey was completed immediately before the exercise test. RESULTS: In the multivariate analysis, the strongest predictor of physical functioning and general health perception was metabolic equivalents. However, the best model, including demographic, clinical, and test variables, predicted only 14% of the variation in physical functioning and 10% of the variability in general health perception. CONCLUSIONS: The variation in physical functioning and general health perception, as measured by the SF-36, among patients referred for exercise testing is not predicted well by the results of the test. As expected, several test results are significantly associated with physical functioning and general health perception; however, there was substantial overlap among individual patients, suggesting that the parameters are poor surrogates for the actual assessment of the domains. If these domains are deemed important to tracking patient outcomes, then they should supplement the current assessments of these patients.

Adult↗

PubMed2000

Consequences of driving cessation: decreased out-of-home activity levels.

OBJECTIVES: Increasing age, socioeconomic factors, and declining function and health have been linked to driving cessation, but little is known about the consequences of stopping driving. This study was designed to test the hypothesis that driving cessation leads to a decline in out-of-home activity levels. METHODS: In 1989 a survey of driving practices was administered to surviving noninstitutionalized members of the New Haven Established Populations for Epidemiologic Studies of the Elderly (EPESE) cohort. Of 1,316 respondents, 502 were active drivers as of 1988, 92 had stopped driving between 1982 and 1987, and 722 never drove or stopped before 1982. Information on sociodemographic and health-related variables came from in-home EPESE interviews in 1982, 1985, and 1988, and from yearly phone interviews. Activity was measured at all three in-home interviews, and an activity measure was created based on self-reported participation in nine out-of-home activities. A repeated measures random-effects model was used to test the effect of driving cessation on activity while controlling for potential confounders. RESULTS: Driving cessation was strongly associated with decreased out-of-home activity levels (coefficient-1.081, standard error 0.264, p < .001) after adjustment for sociodemographic and health-related factors. DISCUSSION: The potential consequences of driving limitations or cessation should be taken into account when advising older drivers and developing alternative transportation strategies to help maintain their mobility.

Activities of Daily Living↗

PubMed2000

Goals in geriatric assessment: are we measuring the right outcomes?

Previous evaluative studies of outpatient geriatric assessment have focused on a limited set of outcomes related to functioning, health services utilization, and costs. The purpose of this study was to identify important goals for care as described by patients and family caregivers being cared for in this setting. Using a cross-section of 226 consecutive sets of patients and their primary family caregivers, physicians, and case managers, goals of care for individual patients were coded from open-ended interview responses. The most common categories of goals expressed by family caregivers were obtaining education and referrals (57.5%) and improving social and family relationships (53.0%). The process of establishing and meeting such goals should be explicitly included in the design of future evaluations of outpatient geriatric assessment.

Activities of Daily Living↗

PubMed2000

Artificial formula induces precocious maturation of the small intestine of artificially reared suckling rats.

BACKGROUND: The artificially reared rat model was used successfully to study the effect of nutrition during the early postnatal period on growth and development of the neonate. Overgrowth and morphologic changes of the gastrointestinal tract are known consequences of artificial rearing. The major goal of our study was to elucidate whether artificial rearing-enhanced gut development is caused by artificial diet or by gastrostomy and the artificial rearing technique itself. METHODS: Suckling rats at day 8 of age underwent intragastric cannulation and were machine fed either a cow's milk-based artificial rat's milk substitute or pooled rat's milk for 4 days. Dam-fed littermates served as a control. RESULTS: Body growth did not differ in the three experimental groups. In rats receiving rat's milk substitute, small intestinal wet weight was approximately 60% greater than in rats fed rat's milk or control rats. Additionally, the entire small intestine was approximately 20% longer in the rat's milk substitute group. Morphologically, rat's milk substitute-fed pups demonstrated significantly greater intestinal villus length and crypt depth compared with rat's milk-fed or control rats. Jejunum and midjejunum of the rat's milk and control groups did not differ in these parameters. Intestinal sucrase activity of rat's milk substitute-fed rats was significantly elevated compared with rat's milk-fed rats or control animals. CONCLUSIONS: These results indicate that cow's milk-based formula, not gastrostomy or artificial feeding technique, is a principal cause of the small intestine overgrowth and precocious maturation of some intestinal functions observed in artificially reared sucklings.

Animals↗

PubMed2000

Environmental hazards and the risk of nonsyncopal falls in the homes of community-living older persons.

BACKGROUND: Identifying and eliminating environmental hazards in the home has high face validity but little empirical support for fall prevention. OBJECTIVE: The objective of this study was to determine whether environmental hazards increase the risk of nonsyncopal falls in the homes of community-living older persons. RESEARCH DESIGN: This was a prospective cohort study. PARTICIPANTS: The study included 1,088 men and women from a probability sample of 1,103 persons > or =72 years of age. MEASURES: A room-by-room assessment for 13 potential trip or slip hazards was completed at baseline and 1 year later by a trained research nurse using a standard instrument. Falls were ascertained monthly for 3 years using a fall calendar and follow-up phone calls. RESULTS: The numbers of participants with a nonsyncopal fall (by room) were as follows: 88 (kitchen), 144 (living room), 41 (hallway), 136 (bedroom), and 59 (bathroom). The risk of a nonsyncopal fall was significantly elevated for only 1 of the 13 trip or slip hazards. For exposure to > or =1 hazards per room, the relative risks adjusted for age, gender, and housing type were 0.91 (95% CI, 0.58-1.43) for the kitchen, 1.30 (95% CI, 0.92-1.83) for the living room, 1.73 (95% CI, 0.93-3.22) for the hallway, 1.29 (95% CI, 0.90-1.84) for the bedroom, and 0.57 (95% CI, 0.32-1.00) for the bathroom. No consistent association was found between the 13 trip or slip hazards and nonsyncopal falls, even after participants were categorized by impairments in vision, balance/gait, and cognition. CONCLUSIONS: Our findings do not support an association between environmental hazards and nonsyncopal falls.

Accidental Falls↗

PubMed2000

Health, functional, and psychological outcomes among older persons with chronic dizziness.

OBJECTIVE: The recommended clinical strategy for a health condition should depend both on the known causes of and outcomes associated with the condition. The aim of this study was to determine the range of adverse outcomes associated with chronic dizziness. DESIGN: Population-based prospective cohort study. SETTING AND PARTICIPANTS: A probability sample of 1087 persons, age 72 and older, living in the community. MEASUREMENTS: The following were measured: chronic dizziness, death, hospitalizations, falls, syncope, basic and instrumental activities of daily living, depressive symptoms, self-rated health, falls self-efficacy, and social activities. RESULTS: Of the 1087 participants, 261 (24%) reported chronic dizziness. Over 1 year of follow-up, chronic dizziness was not associated with mortality, hospitalization for any reason, or change in basic or instrumental activities of daily living, but was associated with risk of falling (unadjusted relative risk [RR] 1.35; 95% confidence interval [CI] 1.06-1.72) and with experiencing syncope (RR 2.31; 95% CI 1.24-4.30). After adjustment for baseline level, chronic dizziness also was associated with worsening of depressive symptoms, self-rated health, falls efficacy, and social activities. The relationship remained significant, after adjustment for potential confounding factors, for self-rated health (T-statistic -2.95, P = .003) and falls efficacy (T-statistic -2.68; P = .008), and was of marginal significance for depressive symptoms (T-statistic -1.73; P = .085). CONCLUSIONS: These results suggest that the goals of care for older persons with chronic dizziness should be redirected from solely identifying and treating discrete diseases--an often expensive and unrewarding task--toward reducing the symptoms of chronic dizziness and alleviating the resulting physical, psychological, and social disability.

Accidental Falls↗

PubMed2000

Secretion of insulin-like growth factor-II into bile of rats of different ages.

Bile from rats of different ages (suckling 10-12 days; weanling 30-33 days, and adult 60-70 days) was collected and studied for the presence of immuno- and receptor-assayable insulin-like growth factor-II (IGF-II) concentrations. Concentrations of RIA IGF-II in bile were highest in suckling rats (230 +/- 38 ng/ml) and lowest in adults (47 +/- 7 ng/ml). These concentrations were approximately twice those of the bile IGF-I concentration in sucklings, as measured in a previous study. Selected bile samples were also assayed using a competitive binding assay with a crude preparation of adult rat liver membranes bearing the IGF-II receptor. These studies confirmed the presence of receptor- (as well as immuno-) active IGF-II in bile. Since bile flow rates increased dramatically after the suckling period, bile delivery rates of IGF-II were normalized as picograms per gram body weight per hour. When such calculations were done, bile IGF-II delivery rates to the small intestine were highest in sucklings and weanlings in comparison to adult rats. Thus non-enterically derived (milk- and bile-borne) IGF-II delivery to the suckling small intestine can be approximated at roughly 1 microg/day. Unlike IGF-I, intravenously injected IGF-II could not be detected in suckling bile, suggesting a predominantly hepatic origin. From this study we conclude that there exists a significant delivery of receptor-active IGF-II to the gastrointestinal tract of rats of all ages.

Aging↗

PubMed2000

Host cyclooxygenase-2 modulates carcinoma growth.

Cyclooxygenase-2 (COX-2; Ptgs2) acts as a tumor promoter in rodent models for colorectal cancer, but its precise role in carcinogenesis remains unclear. We evaluated the contribution of host-derived COX-1 and COX-2 in tumor growth using both genetic and pharmacological approaches. Lewis lung carcinoma (LLC) cells grow rapidly as solid tumors when implanted in C57BL/6 mice. We found that tumor growth was markedly attenuated in COX-2(-/-), but not COX-1(-/-) or wild-type mice. Treatment of wild-type C57BL/6 mice bearing LLC tumors with a selective COX-2 inhibitor also reduced tumor growth. A decrease in vascular density was observed in tumors grown in COX-2(-/-) mice when compared with those in wild-type mice. Because COX-2 is expressed in stromal fibroblasts of human and rodent colorectal carcinomas, we evaluated COX-2(-/-) mouse fibroblasts and found a 94% reduction in their ability to produce the proangiogenic factor, VEGF. Additionally, treatment of wild-type mouse fibroblasts with a selective COX-2 inhibitor reduced VEGF production by 92%.

Animals↗

PubMed2000

Milk-borne epidermal growth factor modulates intestinal transforming growth factor-alpha levels in neonatal rats.

Epidermal growth factor (EGF) is present in milk from various mammalian species, but its physiologic function in neonatal development remains unclear. Transforming growth factor-alpha (TGF-alpha) is a peptide structurally related to EGF, and its presence is detected in the developing small intestine of rats. The purpose of the present study was to examine the effect of milk-borne EGF on endogenous production of EGF and TGF-alpha in the small intestine of suckling rats. Neonatal rats were fed via gastrostomy either growth factor-free rat milk substitute (RMS) or RMS supplemented with EGF (100 ng/mL of RMS) from 8 to 12 d of age. Artificially reared rats were then compared with their dam-fed littermates. Animals fed the EGF-deficient diet RMS had markedly increased EGF and TGF-alpha mRNA levels in duodenum and ileum compared with dam-fed controls and significantly elevated total intestinal content of TGF-alpha peptide. Intestinal EGF content and EGF serum levels were significantly decreased in the RMS group compared with controls. The addition of EGF to the RMS diet normalized TGF-alpha mRNA levels in the duodenum and ileum, EGF mRNA levels in the ileum, and total intestinal TGF-alpha content and EGF serum levels to the levels measured in dam-fed littermates. Motility studies showed that enteral administration of EGF did not affect stomach emptying and intestinal transit. These studies indicate that exogenous milk-borne EGF modulates endogenous production of TGF-alpha in developing small intestine. It is likely that neither TGF-alpha nor EGF are solely responsible for small intestinal overgrowth of artificially reared neonatal rats.

Animals↗

PubMed2000

Do ethanol and metronidazole interact to produce a disulfiram-like reaction?

OBJECTIVE: To obtain and evaluate evidence about the supposed disulfiram-like interaction between metronidazole and ethanol. DATA SOURCES: MEDLINE search from January 1964 to June 1999, using the terms metronidazole, ethanol, and drug reaction. DATA SYNTHESIS: The manufacturer's warnings include a disulfiram-like reaction between metronidazole and ethanol. However, review of reports published between 1969 and 1982 produced no convincing evidence that this reaction exists. Six case reports involving eight patients were evaluated. CONCLUSIONS: Four of the eight cases were serious, including one death, but the authors of all the reports presumed the metronidazole-ethanol reaction to be an established pharmacologic fact. None provided evidence that could justify their conclusions.

Alcohol Deterrents↗

PubMed1999

The role of cyclooxygenases in inflammation, cancer, and development.

The cyclooxygenase (COX) enzymes catalyze a key step in the conversion of arachidonate to PGH2, the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases. Prostaglandins play critical roles in numerous biologic processes, including the regulation of immune function, kidney development, reproductive biology, and gastrointestinal integrity. There are two COX isoforms, which differ mainly in their pattern of expression. COX-1 is expressed in most tissues, whereas COX-2 usually is absent, but is induced by numerous physiologic stimuli. Surprisingly, disruption of Cox1 (Ptgs1) in the mouse did not result in gastrointestinal abnormalities. cox-2 (Ptgs2) null mice show reproductive anomalies and defects in kidney development. Epidemiologic, animal, and human data indicate that NSAIDs, inhibitors of cyclooxygenase, are chemopreventive for colon cancer. COX-2 is overexpressed in 50% of benign polyps and 80-85% of adenocarcinomas. Offspring from cox-2 null by Apcdelta716 matings exhibit an 86% reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth. The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/ or immune function.

Animals↗

PubMed1999

Heat shock cognate 70 mutations in sporadic breast carcinoma.

Heat Shock Cognate 70 (HSC70) is a constitutively expressed molecular chaperone, functions of which regulate the structure, subcellular localization, and turnover of cell proteins. It is also a component of the centrosome facilitating rearrangements during mitotic/meiotic spindle formation and cytoplasmic microtubule organization. We localized HSC70 to 11q23.3, a region deleted in 40% of sporadic breast and other cancers. Sequencing demonstrated mutation in the NH2-terminal ATPase domain of HSC70 in 2 of 15 sporadic breast carcinomas examined. In both cases, mutation was coincident with allelic imbalance, suggesting that HSC70 is a target of somatic mutation and deletion in a fraction of breast carcinomas.

Adenosine Triphosphatases↗

PubMed1999

Postnatal differentiation of the ductus deferens, tail of the epididymis, and distal body of the epididymis in goats occurs independently of rete testis fluid.

Observations from extratesticular rete-ligated, mature goats indicated that epithelial morphology in the tail of the epididymis can be maintained without any input from testicular fluid (Goyal et al., Acta Anat., 1994;150: 127-135). Hence, the objective of this study was to determine whether the tail of the epididymis and/or other regions of the male excurrent ducts can differentiate prior to the appearance of lumen in the seminiferous tubules, which is an indicator for the onset of seminiferous tubular fluid secretion. Based on age and scrotal circumference (SC), 20 male goats were divided into four groups of five animals each: 1-4 weeks (SC, 6.5-7.5 cm), 7-10 weeks (SC, 8.5-11.0 cm), 12-15 weeks (SC, 11.0-14.0 cm), and 15-25 weeks (SC, 16.0-19.0 cm). Tissues were collected from the testis, six regions of the epididymis (proximal, middle and distal head; proximal and distal body; and tail), and the ductus deferens, and were processed for light and electron microscopic examination. Changes in epithelial height and cytological features associated with absorption (microvilli, pinocytotic and coated vesicles) and protein secretion (RER, Golgi body) were used as markers for differentiation. Differentiation of all of these features was comparable to that observed in the 15-25-week-old animals in the ductus deferens by > or = 1 week, in the tail of the epididymis by > or = 7 weeks, in the distal body of the epididymis by > or = 12 weeks, and in the proximal body of the epididymis and all three regions of the head of the epididymis by > or = 15 weeks. Seminiferous tubules developed lumens between 12 and 15 weeks. In conclusion, epithelial differentiation in the ductus deferens, tail of the epididymis, and distal body of the epididymis follows a time-dependent, spatial, ascending order and is achieved before lumen formation in the seminiferous tubules. Conversely, epithelial differentiation in all three regions of the head and the proximal body of the epididymis occurs simultaneously and after lumen formation in the seminiferous tubules.

Age Factors↗

PubMed1999

Risk factors for heart failure in the elderly: a prospective community-based study.

PURPOSE: The risk factors for the development of heart failure are not clearly defined, particularly for older adults. We undertook the current investigation to examine the associations of traditional cardiovascular risk factors, comorbidity, and psychosocial factors with the risk of heart failure during 10 years of follow-up in a community-based elderly population. SUBJECTS AND METHODS: We evaluated 1,749 subjects, 65 years of age or older, free of heart failure, myocardial infarction, and angina at baseline, who were participating in the New Haven, Connecticut cohort of the Established Population for Epidemiologic Studies of the Elderly program. Cox proportional hazards regression models were used to determine risk ratios (RR) and 95% confidence intervals (CI). RESULTS: During 13,811 person-years of follow-up, 173 subjects developed incident heart failure, as confirmed by chart review. Five factors were independent predictors of heart failure: male sex (RR = 1.7; CI, 1.3 to 2.4), older age (RR = 1.9; CI, 1.3 to 2.7 for age 75 to 84 years, RR = 3.0; CI, 1.7 to 5.5 for age 85 years and older, compared with < or = 74 years), diabetes (RR = 2.9; CI, 2.0 to 4.3), pulse pressure > or = 70 mm Hg (RR = 2.3; CI, 1.3 to 4.3, compared with <50 mm Hg), and body mass index > or = 28 kg/m2 (RR = 1.6; CI, 1.0 to 2.4, compared with <24 kg/ m2). Myocardial infarction occurred during follow-up in 8% of the cohort and was also an important predictor of heart failure (RR = 21; CI, 15 to 31). CONCLUSIONS: Age and traditional cardiovascular risk factors are associated with the development of heart failure in the elderly. Preventive strategies should focus on the management of diabetes, blood pressure, and weight, in addition to the prevention and management of myocardial infarction.

Aged↗