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Original Investigation |

Costs for Heart Failure With Normal vs Reduced Ejection Fraction FREE

Lawrence Liao, MD; James G. Jollis, MD; Kevin J. Anstrom, PhD; David J. Whellan, MD; Dalane W. Kitzman, MD; Gerard P. Aurigemma, MD; Daniel B. Mark, MD; Kevin A. Schulman, MD; John S. Gottdiener, MD
[+] Author Affiliations

Author Affiliations: Duke Clinical Research Institute, Durham, NC (Drs Liao, Jollis, Anstrom, Mark, and Schulman); Jefferson Heart Institute, Philadelphia, Pa (Dr Whellan); Wake Forest University School of Medicine, Winston-Salem, NC (Dr Kitzman); University of Massachusetts Medical Center, Worcester (Dr Aurigemma); and University of Maryland School of Medicine, Baltimore (Dr Gottdiener).


Arch Intern Med. 2006;166(1):112-118. doi:10.1001/archinte.166.1.112.
Text Size: A A A
Published online

Background  Among the elderly population, heart failure (HF) with normal ejection fraction (EF) is more common than classic HF with low EF. However, there are few data regarding the costs of HF with normal EF. In a prospective, population-based cohort of elderly participants, we compared the costs and resource use of patients with HF and normal and reduced EF.

Methods  A total of 4549 participants (84.5% white; 40.6% male) in the National Heart, Lung, and Blood Institute Cardiovascular Health Study were linked to Medicare claims from 1992 through 1998. By protocol echo examinations or clinical EF assessments, 881 participants with HF were characterized as having abnormal or normal EF. We applied semiparametric estimators to calculate mean costs per subject for a 5-year period.

Results  There were 495 HF participants with normal EF (186 prevalent at study entry and 309 incident during the study period) and 386 participants with abnormal EF (166 prevalent and 220 incident). Participants with abnormal EF had more cardiology encounters and cardiac procedures. However, compared with abnormal EF participants, the 5-year costs for normal EF participants were similar in both the prevalent ($33 023 with abnormal EF and $32 580 with normal EF; P = .93) and incident ($49 128 with abnormal EF and $45 604 with normal EF; P = .55) groups. In models accounting for comorbid conditions, the costs with normal and abnormal EF remained similar.

Conclusions  Over a 5-year period, patients with HF and normal EF consume as many health care resources as those with reduced EF. These data highlight the substantial financial burden of HF with normal EF among the elderly population.

Figures in this Article

Heart failure (HF) affects nearly 5 million Americans, with over 500 000 new cases diagnosed each year.1 The burden of HF is greatest in the elderly population, with 80% of HF hospitalizations and 90% of HF-related deaths occurring among those 65 years and older.2,3 As a result, HF has become the single most frequent reason for hospitalization in the elderly.2,4

Within the heterogeneous HF population, many patients experience clinical HF with normal systolic function.5,6 In the elderly, HF with a normal ejection fraction (EF) (ie, diastolic HF) is more common than failure with a reduced EF (ie, systolic HF).7 Prognosis for normal EF patients may be better than for patients with abnormal EF.8 While the extent of systolic dysfunction has been related to costs and resource use, no studies have assessed the long-term costs of HF with normal EF.8,9 Because mortality and cardiovascular comorbidity appears to be lower in patients with HF and normal EF, we hypothesized that costs for these patients would be lower than for patients with HF and reduced EF.6 In a prospective, longitudinal cohort of elderly patients, we compared the long-term costs and resource use of patients with HF and normal and abnormal EF.

The study population consisted of participants of the National Heart, Lung, and Blood Institute Cardiovascular Health Study (CHS), a prospective, community-based, epidemiologic, observational study of 5888 individuals 65 years and older from 4 communities (Sacramento County, California; Washington County, Maryland; Forsyth County, North Carolina; and Allegheny County, Pennsylvania).10,11 The CHS identified potential participants from a random sample of Medicare enrollment lists stratified by age group. Participants were followed by clinic visit on an annual basis through 1999. At 10 years, 95% of living CHS participants participated in follow-up. The study contacted participants (or designated surrogates) every 6 months to establish vital status and to screen for the occurrence of primary events and hospitalizations. The details of the CHS design and procedures have been previously reported.10

STUDY GROUP

We linked 4549 of the 5888 CHS participants to Medicare Part A and Part B claims from June 1992 through December 1998. Only subjects enrolled in traditional Medicare fee-for-service could be linked to claims. Of the 4549 participants successfully linked to claims data, 881 were characterized as having clinical HF according to prior CHS methods.12,13 Clinical HF was defined by hospitalization for HF or self-report of a physician diagnosis of congestive HF.7 These events were adjudicated by an expert panel who reviewed all pertinent data, including history, physical examination, chest radiography, and medications.13 As per CHS protocol, medical therapy (diuretic, digitalis, or vasodilator) for HF was also confirmatory evidence.13 Participants were further characterized as having “prevalent HF” if failure was documented before 1992 (start of claims availability) or “incident HF” if failure developed during follow-up. Either protocol CHS echocardiographic results or clinical studies of left ventricular function (echocardiography, nuclear, or catheterization data) were available for all subjects with HF to classify them as having abnormal EF (EF<50%) or normal EF (EF≥50%).

STATISTICAL ANALYSIS

Descriptive statistics comparing the systolic and normal EF groups were presented using percentages for categorical variables and means for continuous variables. For the baseline comparisons, nonparametric tests were used to calculate P values.

Costs were calculated from Medicare payments and discounted at 3% annually to account for the present value of money.14 The costs for the incident HF group were calculated beginning at the time of HF diagnosis as adjudicated by CHS events committee. Costs shown represent US dollars in the year 2000. Annual resource use, including procedures and physician encounters by specialty, was also compiled for each subject using Part B data. Because the Medicare standard analysis files divide separate costs for the Part B program into physician/provider and institutional outpatient costs, we maintained these categories in our analysis.

We applied semiparametric weighted estimators to calculate mean costs and resource use per participant for a 5-year period.15 This method inversely weights the uncensored observations by their estimated probability of not being censored and has been shown to perform well in finite samples, even with heavily censored data.16,17 Estimates of resource use and medical costs were adjusted for censoring because of the end of the study period or participants’ switching out of Medicare fee-for-service. The censoring distribution was modeled using Cox proportional hazards models. P values and confidence intervals (CIs) were calculated using robust standard error estimates.18P<.05 was considered statistically significant.

Semiparametric estimates of mean costs over time were calculated by grouping costs into 60 monthly intervals from the time of study entry.15 These estimates of mean costs reflect the fact that patients do not accumulate costs after death. While these costs reflect the experience of the group, they less accurately portray the costs of survivors. To account for costs while participants are alive, we also calculated conditional mean costs for participants having survived the monthly interval. For incident subjects, we also compared the medical costs and resource use in the year prior to the development of HF with those in subsequent years.

We developed covariate adjusted log-linear regression models to estimate the relationship between patient characteristics and their long-term medical costs. Costs were grouped into intervals and weighted using a Cox proportional hazards estimator for the censoring distribution. The estimated parameters in the log-linear model, when exponentiated, describe the proportional increase in costs due to a 1-unit increase of the factor. In these models, the patient’s costs for an interval were included only if they had survived the corresponding period. All analyses were performed using SAS software (version 8.2; SAS Institute Inc, Cary, NC). This study was approved by our institutional review board.

There were 352 participants (186 with normal EF and 166 with abnormal EF) with prevalent HF at study entry. In this cohort, participants with normal EF were older (mean age, 78.9 years vs 77.6 years with abnormal EF; P = .08) and more likely to be female (61.2% vs 37.4% with abnormal EF; P<.001). The participants with abnormal and normal EF had similar rates of hypertension, diabetes, previous stroke or transient ischemic attack, and current smoking (Table 1). The participants with normal EF had better renal function (mean creatinine level, 1.20 vs 1.29 mg/dL [106.08 vs 114.04 μmol/L] with abnormal EF; P = .02) and a greater proportion of chronic obstructive pulmonary disease (21.0% vs 10.8% with abnormal EF; P = .02). The participants with abnormal EF had higher rates of coronary disease (79.5% vs 59.7% with normal EF; P<.001) and peripheral vascular disease (17.5% vs 8.1% with normal EF; P = .01). The mean follow-up in the prevalent HF cohort was 46.7 months (median, 50 months).

Table Graphic Jump LocationTable 1. Baseline Patient Demographics*

An additional 529 participants (309 with normal EF and 220 with abnormal EF) developed incident HF during the study period (Table 1). Similar to the prevalent group, participants with normal EF were older (mean age, 81.6 years vs 80.1 years with abnormal EF; P = .03) and less likely to be male (48.2% vs 62.3% with abnormal EF; P<.001). Participants with normal EF were less likely to have coronary disease (51.8% vs 71.4% with abnormal EF; P<.001) or angina at baseline (46.9% vs 66.4% with abnormal EF; P<.001). The mean follow-up in the incident HF group was 21.6 months (median of 16 months and maximum of 72 months of cost data).

COSTS AND RESOURCE USE
Prevalent HF

Participants with abnormal EF had more cardiology encounters (15.7 vs 9.8 with normal EF; P = .01) but participants with normal EF accounted for more long-term care encounters (7.1 vs 2.8 with abnormal EF; P = .01). There were no significant differences in primary care encounters, inpatient visits, outpatient visits, or emergency department visits. Cardiac procedure use was higher in participants with abnormal EF, with significantly more echocardiography (P = .02), right heart catheterization (P = .001), and other EP procedures (P = .04). Participants with abnormal EF had higher numbers of days in the intensive care unit compared with patients with normal EF, but this difference was not statistically significant (P = .11).

In the prevalent HF cohort, the mean cumulative costs for participants with normal EF were similar to the costs for participants with abnormal EF at 1 year ($9203 vs $9836; P = .72). This similarity persisted throughout the study period (5-year costs, $32 580 with normal EF vs $33 023 with abnormal EF) (Figure 1). The 5-year cost difference (95% CI, −$8484 to $9370; P = .93) was not significant. In the analysis conditional on survival, there were still no appreciable differences, though total costs in both groups increased (Figure 2). Within the cost subcategories (Part A, Part B physician/provider, and Part B institutional), costs with normal EF were similar to the costs with abnormal EF ($21 169, $8694, and $2718, respectively, for normal EF vs $22 085, $8244, and $2694, respectively, with abnormal EF).

Place holder to copy figure label and caption
Figure 1.

Mean costs with diastolic and abnormal ejection fraction (EF) in the incident and prevalent groups.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Mean costs conditional on survival with diastolic and abnormal ejection fraction (EF) in the incident and prevalent groups.

Graphic Jump Location
Incident HF

Participants with abnormal EF had more days in the intensive care unit (P = .04) and cardiology encounters (P = .02) but had fewer long-term care encounters (P = .01). As in the prevalent group, there were no significant differences in primary care encounters, inpatient visits, outpatient visits, or emergency department visits. Cardiac procedure use was greater in the participants with abnormal EF, with this group accounting for more echocardiograms (P = .02), left heart catheterizations (P = .05), and right heart catheterizations (P = .01) (Table 2).

Table Graphic Jump LocationTable 2. Five-Year Resource Use and Medical Costs*

In the incident cohort, the cumulative 5-year costs were similar for participants with normal and abnormal EF ($45 604 [95% CI, $37 989 to $53 219] with normal EF vs $49 128 [95% CI, $40 449 to $57 757] with abnormal EF; P = .55) (Table 2). These cost similarities (95% CI for difference, −$7985 to $15 032) persisted throughout the study period (Figure 1) even after restriction to survivors (Figure 2) and examining each yearly interval separately (Table 2). Part A and Part B physician/provider costs were higher in the group with abnormal EF, but Part B institutional costs were higher in the group with normal EF (Table 2). None of these differences was statistically significant.

As seen in Figure 1 and Figure 2, development of incident HF resulted in a sharp initial increase in medical costs (to $24 882 with normal EF and $25 503 with abnormal EF) that stabilized by the third year following diagnosis. The paroxysm of costs in the year of diagnosis produced a greater than 200% increase in costs for participants with HF compared with the mean costs in the year prior to HF diagnosis (Table 3). This sharp increase in costs spread across all cost subcategories but was most pronounced in Part A costs. Greater costs were also reflected in greater resource use in both the systolic and normal EF groups. As shown in Table 3, costs for participants differed neither in the year prior nor in the year after HF incidence.

Table Graphic Jump LocationTable 3. Comparison of Preincident and Postincident Heart Failure (HF) Costs and Resource Use*

By year 3, the mean annual costs for participants with normal and abnormal EF had decreased markedly to $4471 and $6300, respectively. However, when only survivors were examined, the year 3 mean costs for both groups were higher ($8376 for normal EF and $12 346 for abnormal EF) and remained higher than the prediagnosis costs out to year 5 ($7632 for normal EF and $11 182 for abnormal EF).

REGRESSION MODELS

In the regression model for costs in the prevalent HF group, there was no significant difference between normal and abnormal EF (Table 4). The relative 5-year cost of abnormal EF was 3% higher than for normal EF and statistically not significantly different (P = .87). The strongest predictor of higher costs was New York Heart Association class IV HF (77% increase compared with class I or II patients; P = .01). Costs for black participants were lower (P = .01), whereas costs for renal insufficiency (creatinine level ≥1.4 mg/dL [≥123.76 μmol/L]) were higher (P = .07).

Table Graphic Jump LocationTable 4. Regression Model for the Prevalent Heart Failure (HF) Population

Similar results were seen in the regression model for the incident HF group (Table 5). In this population, abnormal EF costs over 5 years were comparable to normal EF costs. Overall adjusted abnormal EF costs were 4% lower than normal EF costs (P = .82). Unlike the prevalent HF group, the strongest predictors of higher costs in the incident group were creatinine level ≥1.4 mg/dL (≥123.76 μmol/L) (P = .006) and coronary disease (P = .02). Each decade increase in age reduced costs by approximately 25% (P<.001). Costs for black participants were the same in both groups (P = .99).

Table Graphic Jump LocationTable 5. Regression Model for the Incident Heart Failure (HF) Population

In the regression models for prevalent and incident failure that were also conditional on survival, the costs for normal and abnormal EF remained similar. In the prevalent group, abnormal EF costs were 7% higher (P = .73). In the incident group, abnormal EF costs were 1% lower (P = .94).

To our knowledge, this is the first study to compare the long-term health care costs of patients with HF and normal and abnormal EF. In a population of community-dwelling elderly participants, the costs for normal EF were similar to the costs for abnormal EF. These costs remained similar over 5 years even after adjustment for comorbid illnesses and examination conditional on survival. The study findings were consistent in both prevalent and incident HF groups. These data highlight the financial impact of normal EF in HF and underscore the need for attention to this common but underappreciated disease.

PREVIOUS WORK

Despite the high prevalence of HF with normal EF among the elderly population, the long-term costs for this condition were not previously known. Patients with HF represent a heterogeneous population and are likely to have differences in resource use. Using clinical criteria for diagnosis, a large percentage of patients with clinical HF actually have normal EF.5 It is estimated that up to 74% of patients with HF have normal EF.8 In 1998, Dauterman and colleagues8 reviewed 24 series studying the prevalence of diastolic failure (normal EF) and found a median study prevalence of 36%. In a community-based outpatient population of elderly patients with HF from the Cardiovascular Health Study, almost 55% had normal EF by echocardiogram.7 These patients represent a distinct group from those with abnormal EF and have different clinical features, care patterns, and prognosis. Dauterman and colleagues8 reviewed 9 studies assessing the mortality of HF with normal EF and found that prognosis in these patients is better than in patients with abnormal EF. While the extent of systolic dysfunction has been related to cost, no studies have specifically assessed the long-term costs with normal EF.8,9 Philbin and colleagues19 examined the hospitalizations of 1291 patients with HF and found that the length of stay and hospital charges were similar for patients with and without a normal EF. Our study results suggest that the in-hospital findings of Philbin et al19 extend through long-term follow-up to 5 years. With additional follow-up, it is possible that costs for the 2 groups may diverge.

IMPLICATIONS

The similarity in costs between patients with normal and abnormal EF gives credence to the growing acknowledgment that HF with normal EF deserves more attention from clinicians, researchers, and policy makers. As a convenient common metric for illness morbidity, higher costs reflect more hospitalizations, clinic visits, and procedures. These data demonstrate that patients with normal and abnormal EF experience a comparable number of health care events. While many clinical trials have examined treatments for HF with abnormal EF, very few have considered interventions for patients with HF and normal EF. With the aging of the population, HF with normal EF will account for a growing proportion of HF patients and, consequently, a larger share of health care resources.

STRENGTHS

The study design has several important strengths. First, the rich clinical data available in the CHS allowed us to rely on clinical information rather than claims data for identification of HF and comorbid illnesses. Second, the longitudinal design of this data set enabled the description of long-term costs of HF. In particular, it permitted the examination of long-term costs following incident HF, which, to our knowledge, has not been previously described. It also permitted the accounting of costs for these patients prior to the diagnosis of HF. Third, these cost data included Part B and outpatient claims, which allowed a full accounting of medical costs for the study population.

LIMITATIONS

This work has several limitations. First, since the CHS cohort included only participants who were 65 years or older, our findings should be cautiously extended to younger patients with HF. In addition, because CHS excluded institutionalized, seriously ill or frail persons, this cohort is imperfectly representative of elderly patients.12 Second, our study was limited by our dependence on Medicare claims data for costs. Claims are available only for patients with traditional Medicare fee-for-service coverage and exclude medical costs not covered by Medicare, such as outpatient medications, and nonmedical costs of HF such as lost earnings. While nonmedical costs have significant patient and societal consequences, there is no clear method to assess them within the scope of this study. To help account for patients without complete Medicare fee-for-service claims, we applied increased weight to those individuals with complete data. The amount of weight depended on the patient covariates, ie, those from California received higher weight. Thus, participants crossing over to managed care were represented by participants with claims data having similar covariates. Third, this study relied on the clinical definitions of HF that have been used by the CHS steering committee because there are no uniformly accepted clinical criteria to use instead.8 Lacking a uniformly accepted gold standard, we used existing CHS categorizations that have been used in numerous previous publications.7,13,20 Fourth, our study lacked data to definitively assess diastolic function for all participants. However, more than half of the patients with normal EF had abnormal mitral Doppler E/A ratios (<0.75 or >1.5 at rest). Fifth, we cannot exclude differences between patients with normal and abnormal EF smaller than our study was powered to detect. Finally, our data come from the period between 1992 and 1998 and may imperfectly reflect contemporary experience.

In conclusion, over a 5-year period, patients with HF and normal EF consume as many health care resources as those with abnormal EF. These data highlight the financial importance of normal EF among the elderly population and suggest that additional research efforts should be spent on this common but underappreciated form of HF.

Correspondence: Lawrence Liao, MD, Box 3850, Duke University Medical Center, Durham, NC 27710 (liao0002@mc.duke.edu).

Accepted for Publication: June 23, 2005.

Financial Disclosure: None.

Funding/Support: The Cardiovascular Health Study was funded by contracts N01-HC-85079-85086 and N01-HC-15103 from the National Heart, Lung, and Blood Institute, Bethesda, Md. This work was supported by a grant from the American Heart Association, Dallas, Tex.

Acknowledgment: We thank Nicholas Smith, PhD, Anita Chen, MS, and Judith A. Stafford, MS, for their assistance with data preparation.

American Heart Association, 2001 Heart and Stroke Statistical Update.  Dallas, Tex American Heart Association2001;
Schulman  KAMark  DBCaliff  RM Outcomes and costs within a disease management program for advanced congestive heart failure. Am Heart J 1998;135S285- S292
PubMed Link to Article
Haldeman  GACroft  JBGiles  WHRashidee  A Hospitalization of patients with heart failure: national hospital discharge survey, 1985 to 1995. Am Heart J 1999;137352- 360
PubMed Link to Article
Croft  JBGiles  WHPollard  RACasper  MLAnda  RFLivengood  JR National trends in the initial hospitalization for heart failure. J Am Geriatr Soc 1997;45270- 275
PubMed
Gaasch  WH Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA 1994;2711276- 1280
PubMed Link to Article
Hogg  KSwedberg  KMcMurray  J Heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 2004;43317- 327
PubMed Link to Article
Kitzman  DGardin  JGottdiener  JS  et al.  Importance of heart failure with preserved systolic function in patients ≥65 years of age. Am J Cardiol 2001;87413- 419
PubMed Link to Article
Dauterman  KWMassie  BMGheorghiade  M Heart failure associated with preserved systolic function: a common and costly clinical entity. Am Heart J 1998;135S310- S319
PubMed Link to Article
Berry  CMurdoch  DRMcMurray  JJV Economics of chronic heart failure. Eur J Heart Fail 2001;3283- 291
PubMed Link to Article
Fried  LPBorhani  NOEnright  PL  et al.  The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991;1263- 276
PubMed Link to Article
Tell  GSFried  LPHermanson  BManolio  TANewman  ABBorhani  NO Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol 1993;3358- 366
PubMed Link to Article
Mittelmark  MBPsaty  BMRautaharju  PM  et al.  Prevalence of cardiovascular diseases among older adults. Am J Epidemiol 1993;137311- 317
PubMed
Psaty  BMKuller  LHBild  D  et al.  Methods of assessing prevalent cardiovascular disease in the cardiovascular health study. Ann Epidemiol 1995;5270- 277
PubMed Link to Article
Gold  MRSiegel  JERussell  LBWeinstein  MC Cost-Effectiveness in Health and Medicine.  Oxford, England Oxford University Press1996;
Lin  DY Regression analysis of incomplete medical cost data. Stat Med 2003;221181- 1200
PubMed Link to Article
Bang  HTsiatis  AA Estimating medical costs with censored data. Biometrika 2000;87329- 343
Link to Article
Eisenstein  ELPeterson  EDJollis  JG  et al.  Evaluating the potential “economic attractiveness” of new therapies in patients with non-ST elevation acute coronary syndrome. Pharmacoeconomics 2000;17263- 272
PubMed Link to Article
Hernan  MABrumback  BRobins  JM Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 2000;11561- 570
PubMed Link to Article
Philbin  EFRocco  TA  JrLindenmuth  NWUlrich  KJenkins  PL Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors. Am J Med 2000;109605- 613
PubMed Link to Article
Aurigemma  GPGottdiener  JSShemanski  LGardin  JKitzman  D Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly. J Am Coll Cardiol 2001;371042- 1048
PubMed Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

Mean costs with diastolic and abnormal ejection fraction (EF) in the incident and prevalent groups.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Mean costs conditional on survival with diastolic and abnormal ejection fraction (EF) in the incident and prevalent groups.

Graphic Jump Location

Tables

Table Graphic Jump LocationTable 1. Baseline Patient Demographics*
Table Graphic Jump LocationTable 2. Five-Year Resource Use and Medical Costs*
Table Graphic Jump LocationTable 3. Comparison of Preincident and Postincident Heart Failure (HF) Costs and Resource Use*
Table Graphic Jump LocationTable 4. Regression Model for the Prevalent Heart Failure (HF) Population
Table Graphic Jump LocationTable 5. Regression Model for the Incident Heart Failure (HF) Population

References

American Heart Association, 2001 Heart and Stroke Statistical Update.  Dallas, Tex American Heart Association2001;
Schulman  KAMark  DBCaliff  RM Outcomes and costs within a disease management program for advanced congestive heart failure. Am Heart J 1998;135S285- S292
PubMed Link to Article
Haldeman  GACroft  JBGiles  WHRashidee  A Hospitalization of patients with heart failure: national hospital discharge survey, 1985 to 1995. Am Heart J 1999;137352- 360
PubMed Link to Article
Croft  JBGiles  WHPollard  RACasper  MLAnda  RFLivengood  JR National trends in the initial hospitalization for heart failure. J Am Geriatr Soc 1997;45270- 275
PubMed
Gaasch  WH Diagnosis and treatment of heart failure based on left ventricular systolic or diastolic dysfunction. JAMA 1994;2711276- 1280
PubMed Link to Article
Hogg  KSwedberg  KMcMurray  J Heart failure with preserved left ventricular systolic function. J Am Coll Cardiol 2004;43317- 327
PubMed Link to Article
Kitzman  DGardin  JGottdiener  JS  et al.  Importance of heart failure with preserved systolic function in patients ≥65 years of age. Am J Cardiol 2001;87413- 419
PubMed Link to Article
Dauterman  KWMassie  BMGheorghiade  M Heart failure associated with preserved systolic function: a common and costly clinical entity. Am Heart J 1998;135S310- S319
PubMed Link to Article
Berry  CMurdoch  DRMcMurray  JJV Economics of chronic heart failure. Eur J Heart Fail 2001;3283- 291
PubMed Link to Article
Fried  LPBorhani  NOEnright  PL  et al.  The Cardiovascular Health Study: design and rationale. Ann Epidemiol 1991;1263- 276
PubMed Link to Article
Tell  GSFried  LPHermanson  BManolio  TANewman  ABBorhani  NO Recruitment of adults 65 years and older as participants in the Cardiovascular Health Study. Ann Epidemiol 1993;3358- 366
PubMed Link to Article
Mittelmark  MBPsaty  BMRautaharju  PM  et al.  Prevalence of cardiovascular diseases among older adults. Am J Epidemiol 1993;137311- 317
PubMed
Psaty  BMKuller  LHBild  D  et al.  Methods of assessing prevalent cardiovascular disease in the cardiovascular health study. Ann Epidemiol 1995;5270- 277
PubMed Link to Article
Gold  MRSiegel  JERussell  LBWeinstein  MC Cost-Effectiveness in Health and Medicine.  Oxford, England Oxford University Press1996;
Lin  DY Regression analysis of incomplete medical cost data. Stat Med 2003;221181- 1200
PubMed Link to Article
Bang  HTsiatis  AA Estimating medical costs with censored data. Biometrika 2000;87329- 343
Link to Article
Eisenstein  ELPeterson  EDJollis  JG  et al.  Evaluating the potential “economic attractiveness” of new therapies in patients with non-ST elevation acute coronary syndrome. Pharmacoeconomics 2000;17263- 272
PubMed Link to Article
Hernan  MABrumback  BRobins  JM Marginal structural models to estimate the causal effect of zidovudine on the survival of HIV-positive men. Epidemiology 2000;11561- 570
PubMed Link to Article
Philbin  EFRocco  TA  JrLindenmuth  NWUlrich  KJenkins  PL Systolic versus diastolic heart failure in community practice: clinical features, outcomes, and the use of angiotensin-converting enzyme inhibitors. Am J Med 2000;109605- 613
PubMed Link to Article
Aurigemma  GPGottdiener  JSShemanski  LGardin  JKitzman  D Predictive value of systolic and diastolic function for incident congestive heart failure in the elderly. J Am Coll Cardiol 2001;371042- 1048
PubMed Link to Article

Correspondence

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