Right ventricular infarction complicated by acute right-to-left shunting.
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Acute Disease↗
Biomedical subjects
K K Ho
Publications and source records attributed to K K Ho.
Effect of octreotide, a somatostatin analog, on sleep apnea in patients with acromegaly.
OBJECTIVE: To determine the effects of octreotide, a somatostatin analog, on the severity of sleep apnea and on growth hormone levels in patients with acromegaly. DESIGN: Open-label, prospective study. SETTING: Tertiary referral hospital. PATIENTS: 19 patients with active acromegaly. INTERVENTION: Octreotide in a 6-month, stepwise incremental dosage. MEASUREMENTS: Sleep studies and indices of hormonal activity (levels of insulin-like growth factor 1 [IGF-1] and growth hormone). RESULTS: A 50% decrease occurred in the respiratory disturbance index (baseline compared with 6 months, 39 events/h compared with 19 events/h; P = 0.0002), and a 40% decrease occurred in total apnea time (27.6% of total sleep time compared with 15.1%; P = 0.001). Indices of oxygen desaturation, sleep quality, and subjective sleepiness improved after 6 months of octreotide. A parallel decrease was noted in mean levels of growth hormone (40.0 micrograms/L compared with 9.1 micrograms/L; P = 0.003) and IGF-1 (107 nmol/L compared with 47 nmol/L; P = 0.0001). However, no correlation was noted between the decrease in the total amount of sleep time spent in apnea and the decrease in growth hormone levels (rho = -0.35; P > 0.2). The residual respiratory disturbance index after 6 months of treatment was similar in patients who improved, regardless of whether or not biochemical remission (IGF-1 < 35 nmol/L) occurred. CONCLUSIONS: Improvement in indices of sleep apnea severity occurs in association with octreotide treatment in patients with sleep apnea and acromegaly. However, sleep apnea may either persist despite normalization of growth hormone levels or may improve markedly even if there is only partial biochemical remission.
Acromegaly↗
ITT and IGF-I in the diagnosis of growth hormone deficiency in adults.
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Adolescent↗
Diagnosis of growth hormone deficiency in adults.
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Adolescent↗
Diagnosis of growth-hormone deficiency in adults.
There is no consensus as to the most appropriate method of diagnosing growth-hormone (GH) deficiency in adults. We have evaluated the relative diagnostic merits of measuring peak GH response to insulin-induced hypoglycaemia (insulin tolerance test), mean 24 h GH concentration derived from 20 min sampling, serum insulin-like growth factor I (IGF-I) concentrations, and serum IGF binding protein 3 (IGFBP-3) concentrations. These tests were undertaken in 23 patients considered GH deficient from extensive organic pituitary disease, and in 35 sex-matched normal subjects of similar age and body-mass index. Hypopituitary subjects had significantly lower stimulated peak GH, mean 24 h GH, IGF-I, and IGFBP-3 concentrations than normal subjects. The ranges of stimulated peak GH responses were clearly separated between the hypopituitary (< 0.2-3.1 ng/mL) and normal (5.3-42.5 ng/mL) groups, but mean 24 h GH, IGF-I, and IGFBP-3 concentrations overlapped. Mean 24 h GH concentrations were below assay sensitivity in 80% of hypopituitary subjects and 16% of normal subjects. 70% and 72%, respectively, of the IGF-I and IGFBP-3 values in hypopituitary subjects were within the range for normal subjects. We conclude that GH deficiency in adults is most reliably identified by stimulatory testing, and that IGF-I and IGFBP-3 are poor diagnostic tests of adult GH deficiency.
Adolescent↗
Further evidence that the failure to cleave the aminopropeptide of type I procollagen is the cause of Ehlers-Danlos syndrome type VII.
Dermal fibroblasts from a Chinese Ehlers-Danlos syndrome type VII patient synthesized approximately equal amounts of normal pro-alpha 2(I) chains of type I procollagen and abnormal ones with electrophoretic mobility of pN alpha 2(I) chains, in which the amino-propeptide (N-propeptide) was retained. Reverse-transcriptase PCR analysis of the proband's RNA showed outsplicing of the 54 base exon 6 in half of the pro-alpha 2(I) mRNAs. Exon 6 encodes 18 amino acids of the N-telopeptide which contains the procollagen N-proteinase cleavage site and a cross-link precursor lysine. Loss of these sequences would result in failure to cleave the amino-propeptide of pro-alpha 2(I) and the accumulation of pN-alpha 2(I) chains. Nucleotide sequencing analyses of the proband's COL1A2 gene showed the presence of a T to C transition at position +2 of intron 6 in one allele and the proband is heterozygous for the defect. This mutation which destroyed the consensus GT dinucleotide at the 5' splice donor site of the intron is responsible for the loss of exon 6 by exon skipping. Electron microscopic analysis of the patient's dermis showed the presence of abnormal collagen I fibrils of irregular diameter and circularity. This mutation in COL1A2 in an EDS VII patient is the first reported case in the Chinese population and is identical to one reported for another EDS-VII (Libyan) patient. The occurrence of an identical mutation in two probands of different ethnic origin is direct evidence that the mutant genotype is the cause of the EDS VII phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
Base Sequence↗
Challenges in comparing treatment outcome from a prospective with that of a retrospective study: assessing the merit of gentamicin therapeutic drug monitoring in pediatric oncology.
The objectives of this study were: (a) to assess whether treatment outcome with gentamicin in pediatric oncology patients could be improved by a pharmacy based therapeutic drug monitoring (TDM) service that included pharmacokinetic interpretation; and (b) to describe the challenges in comparing treatment outcome from a prospective to a retrospective study when the merit of gentamicin therapeutic drug monitoring (TDM) was assessed in pediatric oncology patients. Two groups of pediatric oncology patients, aged 1-18 years, received empiric gentamicin therapy for fever and for confirmed or suspected infection, with the same inclusion and exclusion criteria. Group 1 consisted of patients from a prospective gentamicin pharmacokinetic study with a formalized pharmacy-based TDM service (n = 52). Group 2 consisted of patients admitted to the oncology units who had gentamicin levels analyzed in the TDM Laboratory without the formalized TDM Service (n = 25). Gentamicin dosage adjustments were recommended based on three blood samples (one pre- and two postdose concentrations) collected between the third and sixth doses from each patient in the TDM group, utilizing pharmacokinetic principles and the Sawchuk-Zaske method. In the non-TDM group, dosage adjustments based on two routine blood samples (one pre- and post-gentamicin dose) were performed by physicians without the help of the formalized TDM Service. Multiple regression analysis showed that time periods (TDM, non-TDM), duration of neutropenia, intravenous methotrexate, and types of cancer, e.g., hematologic malignancy vs. solid tumor, had significant effects on duration of fever. Initial absolute neutrophil count, insertion of central venous line, intravenous cloxacillin administration, bacteriologic cultures, and initial post gentamicin levels > or = 5 mg/ml had no significant effects on the duration of fever. Mean duration of fever in the TDM group (2.8 +/- 2.4 days) was significantly shorter than that in the non-TDM group (9.0 +/- 8.8 days) (p < 0.001). Therapeutic serum concentrations were achieved more promptly in the TDM group, with significantly fewer patients requiring dose changes and fewer sets of serum concentrations required. One patient from each group had a > 100% increase in serum creatinine on day 5 compared to baseline. No apparent nephrotoxicity was observed in other patients. Although there was an association of shorter duration of fever with prompt achievement of therapeutic gentamicin serum concentrations with the TDM Service, there were several unresolved factors that affected duration of fever. A randomized prospective and controlled study would be required to substantiate the merit of TDM in shortening the duration of fever in pediatric oncology patients.(ABSTRACT TRUNCATED AT 400 WORDS)
Adolescent↗
Evaluating the potential cost-effectiveness of stenting as a treatment for symptomatic single-vessel coronary disease. Use of a decision-analytic model.
BACKGROUND: Coronary stenting appears to provide more predictable immediate results and lower rates of restenosis than conventional balloon angioplasty for selected lesion types, but its hospital costs are significantly higher. This study was designed to evaluate the potential cost-effectiveness of Palmaz-Schatz coronary stenting relative to conventional balloon angioplasty for the treatment of patients with symptomatic, single-vessel coronary disease. METHODS AND RESULTS: We developed a decision-analytic model to predict quality-adjusted life expectancy and lifetime treatment costs for patients with symptomatic, single-vessel coronary disease treated by either Palmaz-Schatz stenting (PSS) or conventional angioplasty (PTCA). Estimates of the probabilities of overall procedural success (PTCA, 97%; PSS, 98%), abrupt closure requiring emergency bypass surgery (PTCA, 1.0%; PSS, 0.6%), and angiographic restenosis (PTCA, 37%; PSS, 20%) were derived from review of the literature published as of September 1993. Procedural costs were based on the true economic (ie, variable) costs of each procedure at Boston's Beth Israel Hospital. On the basis of these data, coronary stenting was estimated to result in a higher quality-adjusted life expectancy than conventional angioplasty but to incur additional costs as well. Compared with conventional angioplasty, stenting had an estimated incremental cost-effectiveness ratio of $23,600 per quality-adjusted life year gained. Although the cost-effectiveness ratio for stenting changed with variations in assumptions about the relative costs and restenosis rates, it remained less than $40,000 per quality-adjusted year of life gained--and thus was similar to many other accepted medical treatments--unless the stent angiographic restenosis rate was > 23%, the angioplasty restenosis rate was < 34%, or the cost of stenting (including vascular complications) exceeded that of conventional angioplasty by more than $3000. The alternative strategy of secondary stenting (initial angioplasty followed by stenting only for symptomatic restenosis) was estimated to be both less effective and less cost-effective than primary stenting over a wide range of plausible assumptions and thus does not appear to be cost-effective when primary stenting is also an option. CONCLUSIONS: Decision-analytic modeling can be used to evaluate the potential cost-effectiveness of new coronary interventions. Our analysis suggests that despite its higher cost, elective coronary stenting may be a reasonably cost-effective treatment for selected patients with single-vessel coronary disease. Primary stenting is unlikely to be cost-effective for lesions with a low probability of restenosis (eg, < 30%) or for patients for whom the cost of stenting is expected to be much higher than usual (eg, because of a high risk of vascular complications). Given the sensitivity of the cost-effectiveness ratios to even modest variations in the relative restenosis rates and cost estimates, future studies will be necessary to determine more precisely the cost-effectiveness of coronary stenting for specific patient and lesion subsets.
Angioplasty, Balloon, Coronary↗
Body composition and energy expenditure in acromegaly.
To investigate whether GH is a regulator of body composition and energy metabolism in adult life, we have compared body composition and resting energy expenditure (REE) in a cross-sectional study in 20 acromegalic and 20 normal subjects, pair-matched for sex, age, height, and weight. In a longitudinal study, 8 acromegalic patients were also studied before and after 12 weeks of treatment [n = 6 during octreotide (100 micrograms, 3 times/day); n = 2 after pituitary surgery], and 7 patients were studied 12 weeks after withdrawal of octreotide. REE was measured by indirect calorimetry and fat mass and fat-free soft tissue mass (FFSTM) by dual energy x-ray absorptiometry. A subgroup of 12 matched pairs of subjects and 7 treated patients had measurement of extracellular water (ECW) by 24Na dilution, which when subtracted from FFSTM provided an estimate of body cell mass (BCM). Fat mass was significantly reduced (25.4 +/- 2.2 vs. 29.7 +/- 2.7 kg; P = 0.007) and FFSTM increased (53.3 +/- 2.2 vs. 49.2 +/- 2.3 kg; P = 0.003) in acromegaly with ECW (25.6 +/- 1.6 vs. 21.1 +/- 0.9 L; P = 0.0003), but not BCM, significantly elevated. Treatment of acromegaly increased fat mass and reduced FFSTM [change (delta), -1.3 +/- 0.4 kg; P = 0.004]; the latter reflected a significant fall in ECW (delta, -2.2 +/- 0.4 L; P = 0.002), but not BCM. The opposite effect on body composition occurred after treatment withdrawal. REE was increased in acromegaly (1682 +/- 49 vs. 1540 +/- 45 Cal/24 h; P = 0.02) and significantly related to insulin-like growth factor-I (P = 0.02). REE was significantly reduced (delta, -154 +/- 17 Cal/24 h; P = 0.0001) with treatment and increased after treatment withdrawal (P = 0.003). In acromegaly, there is a reversible 1) reduction in fat mass; 2) increase in FFSTM, accounted for by an increase in ECW, but not BCM; and 3) increase in REE, which is dependent on disease activity. We conclude from these observations in acromegaly that GH is a regulator of energy metabolism and body composition.
Absorptiometry, Photon↗
Direct quantitation of growth hormone binding protein in human serum by a ligand immunofunctional assay: comparison with immunoprecipitation and chromatographic methods.
Current methods for measuring GH-binding protein (GHBP) are laborious, require separation of GHBP complex, and may be affected by endogenous GH content of the sample. Such methods estimate binding activity and GHBP concentration can only be obtained by Scatchard analysis. We have developed and validated a 2-site immunofunctional assay for the direct quantitation of GHBP in human serum employing a capture monoclonal antibody against GHBP and a polyclonal antibody against hGH. Results were compared with binding activity data and Scatchard-derived capacity estimates obtained by immunoprecipitation and gel chromatography procedures. Serum samples were obtained from 21 subjects with GH deficiency, 24 patients with acromegaly, and 56 normal subjects; 12 of whom were postmenopausal women who were studied before and during oral estrogen treatment. Using the immunofunctional assay, serum GHBP concentrations in normal subjects ranged from 0.14-3.28 nmol/L, was positively related to body mass index (BMI, P = 0.0004) and negatively related to age (P = 0.015). Women had significantly higher levels (0.99 +/- 0.12 vs. 0.63 +/- 0.09 nmol/L; P = 0.0191) than age and BMI-matched men. GHBP levels were not different between normal, acromegalic, or GH-deficient subjects. Oral estrogen therapy in postmenopausal women increased serum GHBP concentrations up to 5-fold. There was a significant nonlinear relationship between the immunofunctional assay measurements and binding activity by either immunoprecipitation (r = 0.84) or chromatographic (r = 0.73) methods; increase in GHBP concentrations was not reflected in proportionate increase in both activity assays. Estrogen-induced changes in circulating GHBP levels were greatest with the immunofunctional assay followed by Scatchard-derived values from immunoprecipitation and chromatographic methods. We conclude that ligand immunofunctional assay measurements of GHBP are higher but show good agreement with binding activity or Scatchard derived estimates from immunoprecipitation and chromatographic methods. This assay provides a direct and practical tool for rapid, accurate and sensitive estimation of GHBP concentration in serum.
Adult↗
Labial melanotic macule: a clinical, histopathologic, and ultrastructural study.
BACKGROUND: The labial melanotic macule (LMM) is a recently described pigmentary anomaly that may simulate malignant melanoma. OBJECTIVE: Our purpose was to define the LMM clinically, histologically, and immunohistochemically in a large group of patients. METHODS: We describe the clinical features of 36 LMMs in 29 patients (aged from 4 to 79 years, 4 male, 25 female) seen during the past 4 years. Histopathologic findings in 21 of these patients are discussed. Seventeen lesions were immunostained with HMB-45 monoclonal antibody, and electron microscopy was performed on eight lesions. RESULTS: The majority of patients were women and had solitary lesions on the lower lip with the mean age of onset of 30 years. Histologically prominent basilar hyperpigmentation accentuated at the tips of the rete ridges was present without atypia or nevoid formation. Immunohistochemical studies showed that all intralesional melanocytes were HMB-45 negative, supporting their benign nature. Ultrastructurally, numerous stage III and IV melanosomes clustered within basal keratinocytes and papillary dermal melanophages were found. CONCLUSION: The LMM is a clinically and histologically distinctive benign pigmentary anomaly.
Adolescent↗
Economics of elective coronary revascularization. Comparison of costs and charges for conventional angioplasty, directional atherectomy, stenting and bypass surgery.
OBJECTIVES: This study was designed to evaluate more closely the true in-hospital costs of elective revascularization by directional coronary atherectomy and intracoronary stenting and to compare these costs with those of the traditional revascularization alternatives (i.e., conventional balloon angioplasty and coronary artery bypass surgery). BACKGROUND: Previous studies have suggested that total hospital charges for directional coronary atherectomy or intracoronary stenting are significantly higher than those for conventional angioplasty. However, hospital charges do not necessarily reflect true economic costs, and their use may provide misleading data with regard to cost-effectiveness. METHODS: We analyzed in-hospital charges from the itemized hospital accounts of 300 patients undergoing elective angioplasty, directional atherectomy, Palmaz-Schatz coronary stenting or bypass surgery between January 1, 1990 and December 31, 1991. Costs were then derived by adjusting itemized patient accounts for department-specific cost/charge ratios. Catheterization laboratory costs were based on actual resource consumption, and daily room costs were adjusted for the intensity of nursing services provided. RESULTS: Length of hospital stay was similar for atherectomy (2.3 +/- 1.5 days) and conventional angioplasty (2.6 +/- 1.7 days) but significantly longer for stenting (5.5 +/- 2.6 days, p < 0.05). Total costs were also significantly higher for coronary stenting ($7,878 +/- $3,270, median $6,699, p < 0.05) than for angioplasty ($5,396 +/- $2,829, median $4,753) or atherectomy ($5,726 +/- $2,716, median $4,986). However, length of stay, resource consumption (laboratory and radiologic testing, drugs, blood products, for example) and total costs for bypass surgery were still greater than for any of the percutaneous interventional procedures. CONCLUSIONS: In contrast to previous studies utilizing only hospital charges, the in-hospital costs of angioplasty and directional coronary atherectomy were similar. Although the cost of coronary stenting was approximately $2,500 higher than that of conventional angioplasty, the magnitude of this difference was smaller than the $6,300 increment previously suggested on the basis of analysis of hospital charges. These findings reflect the inherent discrepancies between cost-based and charge-based methodologies and may have important implications for future studies evaluating the relative cost-effectiveness of newer coronary interventions.
Aged↗
The epidemiology of heart failure: the Framingham Study.
Congestive heart failure has become an increasingly frequent reason for hospital admission during the last 2 decades and clearly represents a major health problem. Data from the Framingham Heart Study indicate that the incidence of congestive heart failure increases with age and is higher in men than in women. Hypertension and coronary heart disease are the two most common conditions predating its onset. Diabetes mellitus and electrocardiographic left ventricular hypertrophy are also associated with an increased risk of heart failure. During the 1980s, the annual age-adjusted incidence of congestive heart failure among persons aged > or = 45 years was 7.2 cases/1,000 in men and 4.7 cases/1,000 in women, whereas the age-adjusted prevalence of overt heart failure was 24/1,000 in men and 25/1,000 in women. Despite improved treatments for ischemic heart disease and hypertension, the age-adjusted incidence of heart failure has declined by only 11%/calendar decade in men and by 17%/calendar decade in women during a 40-year period of observation. In addition, congestive heart failure remains highly lethal, with a median survival time of 1.7 years in men and 3.2 years in women and a 5-year survival rate of 25% in men and 38% in women.
Adult↗
Background and radiation-induced 8-hydroxy-2'-deoxyguanosine in gamma-irradiated Escherichia coli.
The DNA base damage product, 8-hydroxy-2'-deoxyguanosine (7-hydro-8-oxo-2'-deoxyguanosine, or 8-OHdG) was measured in 2'-deoxyribonucleoside digests of DNA from irradiated E. coli or model DNA using HPLC separation and electrochemical detection (LCED). The LCED technique enabled the specific quantitation of 25 fmol of 8-OHdG (signal: noise ratio = 4:1) among a variety of DNA base lesions within the sample. A radiation dose-yield relationship for 8-OHdG was observable in cells that were rapidly lysed after irradiation using a chloroform-saturated, sarkosyl and EDTA solution at 4 degrees C (Tilby and Loverock 1983). The observed yield of 8-OHdG was 7.05 +/- 0.27 pmol J-1 and was against a background of 120 8-OHdG per E. coli genome. This yield translates to an average of 12 additional 8-OHdG lesions per genome at the mean lethal dose. The low radiochemical yield and high background suggests that factors other than the toxicity of 8-OHdG per se--such as its participation in clusters of base lesions (e.g. Ward 1985)--must contribute significantly to cell killing. Although exposure of DNA to phenol mixtures has often been reported to increase 8-OHdG, we found that a more significant effect of phenol mixtures was the potentiation of the radiochemical yields of 8-OHdG in model DNA from 5.26 +/- 0.48 to 158 +/- 12.2 nmol J-1. Other factors, such as the exposure of dried 2'-deoxyribonucleoside digests to ambient humidity in the presence of buffer components, were shown to contribute more significantly to the background of 8-OHdG.
8-Hydroxy-2'-Deoxyguanosine↗
Different modes of growth hormone (GH) administration do not change GH binding protein activity in man.
OBJECTIVE: Studies in rodents have shown GH binding protein (GHBP) levels to be dependent on the mode of GH administration. The aim is to determine whether GHBP levels in man are also modulated by the pattern of GH administration. PATIENTS: Six GH deficient subjects participated in a randomized study in which 2 IU GH were administered either as (i) a continuous 24-hour infusion, (ii) two intravenous boluses or (iii) eight intravenous boluses every 3 hours. In a second study, six normal men received a single subcutaneous injection of 0.2 U/kg GH and GHBP activity was measured over 24 hours. Control data were obtained from an untreated group of six age-matched normal men. MEASUREMENTS: GHBP activity was measured by immunoprecipitation using a monoclonal antibody that recognizes the human GHBP, and expressed as percentage specific binding of 125I-GH in 50 microliters of serum. RESULTS: GHBP activity was not significantly different between the GH deficient and normal subjects. GHBP activity did not rise significantly during GH administration with each of the three intravenous patterns of delivery nor were there any significant differences between treatments. In the second study, GHBP activity did not change significantly following subcutaneous GH injection nor did results differ from untreated normal controls. CONCLUSIONS: The level of GHBP in man is not dependent on GH secretory status or altered by short-term GH treatment or the mode of administration. These findings stand in contrast to GH treatment effects in rodents and suggest that GH regulation of GHBP may be different between species.
Adult↗
Effects of different oral oestrogen formulations on insulin-like growth factor-I, growth hormone and growth hormone binding protein in post-menopausal women.
OBJECTIVE: Insulin like growth factor-I (IGF-I) levels in post-menopausal women are reduced by oral administration of the synthetic oestrogen ethinyl oestradiol but increased by transdermal delivery of 17 beta-oestradiol. Since these oestrogen types are different, the aim of this study was to clarify whether reduction in IGF-I is a specific effect of ethinyl oestradiol or common to other oral oestrogen formulations. DESIGN: Randomized cross-over study comparing one month of treatment with ethinyl oestradiol (20 micrograms), conjugated equine oestrogen (1.25 mg Premarin) and oestradiol valerate (2 mg). SUBJECTS: Six healthy post-menopausal women, age 60.3 +/- 5.6 years. MEASUREMENTS: Mean 24 hour GH (from hourly sampling), IGF-I, GH binding protein (GHBP), pituitary (LH, FSH) and hepatic function (SHBG and angiotensinogen) were measured. RESULTS: All three oestrogen formulations resulted in a significant reduction in IGF-I levels compared to baseline and significant elevations of GH and GHBP (P < 0.05). The percentage increase in GH during oestrogen treatment was significantly related to the percentage decrease in IGF-I levels (P = 0.04). All three oestrogen formulations resulted in significant suppression of LH and FSH and induction of the hepatic proteins, SHBG and angiotensinogen (P < 0.05). GHBP increased in parallel with other hepatic proteins. CONCLUSIONS: Reduction in IGF-I levels is an intrinsic effect of oral oestrogen therapy and increased GH levels may occur as a result of reduced feedback inhibition by IGF-I. Since GHBP activity is not changed by transdermal oestrogen, we conclude that the liver is a major source of circulating GHBP and that GHBP is an oestrogen sensitive protein.
Aged↗
Aging and growth hormone.
Detailed studies of the ontogeny of growth hormone (GH) secretion have shown unequivocally that GH is produced throughout life but secretion declines progressively to about 20% of that in puberty. These changes are accounted for in part by changes in central neuro-endocrine function, nutritional factors and by changes in sex steroid milieu. Mean 24-hour GH concentrations in the normal elderly are frequently below the limit of assay detectability where values are indistinguishable from matched adults with organic GH deficiency. The notion that diminished GH action may account for the undesirable changes in body composition and function in the elderly is supported by beneficial findings of GH treatment in GH-deficient adults. Preliminary results of GH treatment in the normal elderly suggest beneficial effects on body composition but a high incidence of side-effects. Questions addressing cost, benefit, dosage, safety and tolerance need to be critically addressed before GH can be considered for use in the aging.
Aging↗
Survival after the onset of congestive heart failure in Framingham Heart Study subjects.
BACKGROUND: Relatively limited epidemiological data are available regarding the prognosis of congestive heart failure (CHF) and temporal changes in survival after its onset in a population-based setting. METHODS AND RESULTS: Proportional hazards models were used to evaluate the effects of selected clinical variables on survival after the onset of CHF among 652 members of the Framingham Heart Study (51% men; mean age, 70.0 +/- 10.8 years) who developed CHF between 1948 and 1988. Subjects were older at the diagnosis of heart failure in the later decades of this study (mean age at heart failure diagnosis, 57.3 +/- 7.6 years in the 1950s, 65.9 +/- 7.9 years in the 1960s, 71.6 +/- 9.4 years in the 1970s, and 76.4 +/- 10.0 years in the 1980s; p < 0.001). Median survival after the onset of heart failure was 1.7 years in men and 3.2 years in women. Overall, 1-year and 5-year survival rates were 57% and 25% in men and 64% and 38% in women, respectively. Survival was better in women than in men (age-adjusted hazards ratio for mortality, 0.64; 95% CI, 0.54-0.77). Mortality increased with advancing age in both sexes (hazards ratio for men, 1.27 per decade of age; 95% CI, 1.09-1.47; hazards ratio for women, 1.61 per decade of age; 95% CI, 1.37-1.90). Adjusting for age, there was no significant temporal change in the prognosis of CHF during the 40 years of observation (hazards ratio for men for mortality, 1.08 per calendar decade; 95% CI, 0.92-1.27; hazards ratio for women for mortality, 1.02 per calendar decade; 95% CI, 0.83-1.26). CONCLUSIONS: CHF remains highly lethal, with better prognosis in women and in younger individuals. Advances in the treatment of hypertension, myocardial ischemia, and valvular heart disease during the four decades of observation did not translate into appreciable improvements in overall survival after the onset of CHF in this large, unselected population.
Age Factors↗