Download Survival Associated with Two Sets of Diagnostic Criteria

American Journal of Epidemiology
Copyright © 2004 by the Johns Hopkins Bloomberg School of Public Health
All rights reserved
Vol. 160, No. 7
Printed in U.S.A.
DOI: 10.1093/aje/kwh268
Survival Associated with Two Sets of Diagnostic Criteria for Congestive Heart
Failure
Gina D. Schellenbaum1, Thomas D. Rea2, Susan R. Heckbert1, Nicholas L. Smith1, Thomas
Lumley3, Veronique L. Roger4, Dalane W. Kitzman5, Herman A. Taylor6, Daniel Levy7, and
Bruce M. Psaty1,2,8
1
Department of Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, WA.
Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA.
3 Department of Biostatistics, Cardiovascular Health Research Unit, University of Washington, Seattle, WA.
4 Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, MN.
5 Section on Cardiology, Department of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC.
6 Department of Medicine, University of Mississippi Medical Center, Jackson, MS.
7 National Heart, Lung, and Blood Institute and the Framingham Heart Study, Framingham, MA.
8 Department of Health Services, Cardiovascular Health Research Unit, University of Washington, Seattle, WA.
2
Received for publication February 3, 2004; accepted for publication April 12, 2004.
Congestive heart failure (CHF) definitions vary across epidemiologic studies. The Framingham Heart Study
criteria include CHF signs and symptoms assessed by a physician panel. In the Cardiovascular Health Study, a
committee of physicians adjudicated CHF diagnoses, confirmed by signs, symptoms, clinical tests, and/or
medical therapy. The authors used data from the Cardiovascular Health Study, a population-based cohort study
of 5,888 elderly US adults, to compare CHF incidence and survival patterns following onset of CHF as defined
by Framingham and/or Cardiovascular Health Study criteria. They constructed an inception cohort of nonfatal,
hospitalized CHF patients. Of 875 participants who had qualifying CHF hospitalizations between 1989 and 2000,
54% experienced a first CHF event that fulfilled both sets of diagnostic criteria (concordant), 31% fulfilled only the
Framingham criteria (Framingham only), and 15% fulfilled only the Cardiovascular Health Study criteria
(Cardiovascular Health Study only). No significant survival difference was found between the Framingham-only
group (hazard ratio = 0.87, 95% confidence interval: 0.71, 1.07) or the Cardiovascular Health Study-only group
(hazard ratio = 0.89, 95% confidence interval: 0.68, 1.15) and the concordant group (referent). Compared with
Cardiovascular Health Study central adjudication, Framingham criteria for CHF identified a larger group of
participants with incident CHF, but all-cause mortality rates were similar across these diagnostic classifications.
follow-up studies; heart failure, congestive; prognosis; survival
Abbreviations: CHF, congestive heart failure; CI, confidence interval; FEV1, forced expiratory volume in 1 second; HR, hazard
ratio.
Congestive heart failure (CHF) is especially common
among older adults (1–3). Although a standard definition is
crucial to understanding the epidemiology of CHF, diagnostic criteria for CHF are difficult to define and apply in
population-based settings. No physical sign, blood assay, or
imaging test is definitive for the diagnosis of CHF. The
primary symptoms of CHF—shortness of breath, fatigue,
and swelling of the legs, ankles, or feet—are not specific to
CHF and are prominent in other medical conditions common
in older adults (2).
In 1971, the Framingham Heart Study published diagnostic criteria for CHF based on signs and symptoms
assessed and adjudicated by a physician panel (1). The
Cardiovascular Health Study defines CHF by using signs,
symptoms, clinical tests, and/or medical therapy via central
adjudication by a committee of physicians (4, 5). Differences
Correspondence to Gina D. Schellenbaum, 1730 Minor Avenue, Suite 1360, Seattle, WA 98101 (e-mail: [email protected]).
628
Am J Epidemiol 2004;160:628–635
Survival Associated with CHF Diagnostic Criteria 629
between these two sets of diagnostic criteria could affect
estimates of CHF incidence and prognosis.
In the Cardiovascular Health Study, contemporary
elements of the Framingham criteria were collected for
cardiac hospitalizations of Cardiovascular Health Study
participants, and these data enable a direct comparison
between the Framingham criteria and the Cardiovascular
Health Study central adjudication approach. Given the low
survival rates among persons with CHF (1, 6–9), mortality
was chosen as an endpoint for comparing the two criteria.
The investigation compared survival following the diagnosis
of incident CHF by the Framingham criteria, Cardiovascular
Health Study adjudication, or both methods.
TABLE 1. Availability of Framingham Heart Study CHF* criteria
(%) among Cardiovascular Health Study participants in the
inception cohort at incident CHF hospitalization, the
Cardiovascular Health Study, United States, 1989–2000
Original Framingham criteria†
Present
Absent
Unknown
Bilateral moist rales
69
26
6
Paroxysmal nocturnal dyspnea
and/or orthopnea
52
39
10
Pulmonary edema by
radiography
54
34
11
Neck vein distention in the
semirecumbent position
28
61
12
Enlarging heart by radiography
Major criteria
56
30
14
MATERIALS AND METHODS
S3 gallop
8
70
22
Participants and setting
Hepatojugular reflux
3
69
29
Ankle edema
49
43
8
Pleural effusion
36
47
17
Hepatomegaly
1
81
18
Tachycardia (≥120 beats per
minute)
10
66
24
Dyspnea on exertion
39
22
40
6
38
56
The Cardiovascular Health Study is a prospective, population-based cohort study of 5,888 adults who were at least 65
years of age at baseline. Participants were recruited from a
random sample of Medicare-eligible residents from the four
study sites: Sacramento County, California; Washington
County, Maryland; Forsyth County, North Carolina; and
Allegheny County, Pennsylvania. Persons were eligible to
participate if they 1) had been sampled, or were living in the
household of a person sampled, from the Health Care
Financing Administration lists; 2) were at least 65 years of
age; 3) were not institutionalized; 4) expected to remain in
the area for 3 years; and 5) did not require a proxy respondent. All participants gave informed consent, all relevant
institutional committees on human research approved the
study, and the procedures followed were in accordance with
institutional guidelines. The study enrolled 57 percent of the
eligible persons contacted. The original cohort of 5,201
participants was recruited in 1989–1990; 687 additional
subjects, most of whom were African American, were
recruited in 1992–1993 by using similar methods.
Peripheral venous pressure
>16 cm H2O
Arm-to-tongue circulation time
≥25 seconds
Weight loss of ≥4.5 kg in 5 days
with treatment
Minor criteria
Night cough
33 1/3% decrease in vital
capacity
* CHF, congestive heart failure.
† A Framingham diagnosis of CHF requires either two major
criteria or one major and two minor criteria (12); autopsy evidence
was not considered because only nonfatal CHF cases were
included; four criteria were not available.
Data collection
Patient characteristics were assessed at baseline and
annual follow-up clinic visits (10). Prevalent CHF at baseline was ascertained through self-report, with medical record
verification; during follow-up, baseline CHF status was
updated by using information obtained during investigations
for incident events (11). All potential incident cardiovascular
events (CHF, myocardial infarction, angina, stroke, transient
ischemic attack) and deaths were adjudicated by the events
committee (4). Deaths were confirmed by review of medical
records and death certificates, as well as the Health Care
Financing Administration Medicare health care utilization
database for hospitalizations. The present investigation
includes morbidity and mortality through June 30, 2000.
Framingham diagnostic criteria
For all potential incident cardiovascular event hospitalizations, trained medical abstractors reviewed hospital records
for diagnostic information, including the Framingham CHF
Am J Epidemiol 2004;160:628–635
criteria. A Framingham diagnosis of CHF required either
two major criteria or one major and two minor criteria (table
1) (12). When no information was available about the presence of a Framingham criterion, this criterion was assumed
to be absent.
Cardiovascular Health Study diagnostic criteria
The events committee—a panel of physicians—adjudicated CHF by reviewing all pertinent data, including history,
physical examination, chest radiography report, and medication use. Physician diagnoses of CHF were confirmed by
documentation in the participants’ medical records of a
constellation of symptoms (i.e., shortness of breath, fatigue,
orthopnea, paroxysmal nocturnal dyspnea) and physical
signs (i.e., edema, pulmonary rales, gallop rhythm, displaced
left ventricular apical impulse) or by clinical findings such as
evidence of pulmonary edema on chest radiograph.
630 Schellenbaum et al.
on the date their matched case entered the analysis. For five
of the cases, no exact match could be found, so the age criterion was relaxed to find a match within 3 years.
Variable definitions
FIGURE 1. Inclusion diagram showing the formation of the congestive heart failure (CHF) inception cohort and diagnostic classifications for Cardiovascular Health Study (CHS) participants, United
States, 1989–2000. The “no qualifying CHF event” box includes participants without CHF and participants whose CHF events were disqualified: 70 who were not hospitalized, six for whom hospital
documentation was missing, 123 who died before hospital discharge,
and 152 whose events were procedure related.
Although ejection fraction was not available for all incident
CHF hospitalizations, when it was available it was considered part of the clinical picture. The diagnosis of CHF was
also confirmed if, in addition to having a physician diagnosis
of CHF, the participant was receiving medical therapy for
CHF, including diuretics, digitalis, angiotensin-converting
enzyme inhibitors, and beta-blockers.
Inception cohort
The CHF inception cohort included 875 participants who
survived to be discharged from the hospital between July 1,
1989, and June 30, 2000, following an incident, definite
episode of CHF (figure 1). CHF cases were classified into
three mutually exclusive groups: 1) concordant (fulfilled
both the Framingham and the Cardiovascular Health Study
criteria for CHF at the incident hospitalization), 2)
Framingham only (fulfilled only the Framingham criteria for
CHF), and 3) Cardiovascular Health Study only (fulfilled
only the Cardiovascular Health Study criteria for CHF).
Excluded from the inception cohort were participants with
probable or definite heart failure at baseline (n = 273), participants with incident CHF events that were procedure related
(n = 152) or were entirely managed outside of the hospital
(n = 70), or participants for whom hospital documentation
was unavailable (n = 6). Information on clinical conditions
and behavioral characteristics was taken from the annual
study visit immediately before the qualifying CHF hospitalization (an average of 8 months before the qualifying event),
unless otherwise noted.
To better understand the survival patterns of the three
diagnostic classifications, we created a comparison group
without CHF. A random sample of participants (N = 875)
who had not developed CHF were individually matched to
qualifying CHF cases by sex, age at baseline (year), and
recruitment cohort (recruited in 1989–1990 vs. 1992–1993).
Each of these participants without CHF entered the analysis
Treated hypertension was defined as use of antihypertensive medications and a self-reported history of hypertension.
Treated diabetes was defined as use of insulin or oral hyperglycemic agents. Abstracted hospital chart information was
used to classify the prevalence of chronic obstructive pulmonary disease during the qualifying CHF hospitalization. Selfreport was used to classify asthma status, as well as kidney
disease and heart valve problems. Atrial fibrillation was
defined as either self-reported history or electrocardiogram
evidence of atrial fibrillation at a Cardiovascular Health
Study clinic visit. A hospital discharge diagnosis of heart
failure was defined as any International Classification of
Diseases, Ninth Revision, code 428, 425, 402.91, 402.11,
402.01, or 398.91.
Body mass index calculations were based on annual weight
measurement and the most recent height measurement from
one of three visits at which height was measured. Forced
expiratory volume in 1 second (FEV1) was also measured
during only three visits. Percent predicted FEV1 was considered the measured FEV1 divided by the calculated FEV1 for
healthy persons of the same age, sex, and height (13).
Smoking behavior was reported at each annual visit for the 30
days before the visit, and alcohol consumption was calculated
from self-reported typical amounts and frequencies.
Statistical analysis
Kaplan-Meier curves, log-rank tests, and Cox proportional
hazards models with robust variance estimates were used to
examine differences in all-cause mortality among the CHF
diagnostic classifications and matched participants without
CHF. All p values were two-sided. The Kaplan-Meier curves
were truncated at 6 years of follow-up because of the small
sample size beyond that point: 358 participants
(Framingham only: 40, Cardiovascular Health Study only:
17; concordant: 67; no CHF: 234). The proportional hazards
assumption was tested and was not rejected for comparisons
of survival for the three CHF diagnostic classifications.
Restricted subgroup analyses were conducted to explore the
possibility that the survival differences might be observed in
a distinctive group only, such as those with conditions that
make a CHF diagnosis more difficult.
Less than 5 percent of the data for variables in this analysis
were missing, except for the Framingham criteria. Of all
documented hospitalizations, no known values for any of the
Framingham diagnostic criteria were available for 15.5
percent. The Framingham diagnostic criteria were more
likely to all be missing at one of the clinics (Forsyth, North
Carolina: 20.1 percent), for the younger participants (less
than 75 years of age at the time of their hospitalized event:
32.6 percent), and early in the study (before the mean hospitalized event date, September 3, 1995: 29.7 percent). Nevertheless, among qualified hospitalizations classified as
incident, definite CHF by the Cardiovascular Health Study
Am J Epidemiol 2004;160:628–635
Survival Associated with CHF Diagnostic Criteria 631
criteria, data on all of the Framingham criteria were missing
for fewer than 2 percent. To address the missing data for
individual Framingham criteria, sensitivity analyses were
conducted by excluding participants for whom data were
missing for most or all of the Framingham criteria and by
using a multiple imputation program (NORM software) to
assign values for these missing data (14). The multiple imputation analysis used patient characteristics, clinical conditions, available Framingham criteria data, and outcome
information to fill in missing Framingham criteria values.
Survival analyses were conducted for each of 10 imputed
data sets (1,000 iterations each), and the results were recombined. As part of the recombination, the effective amount of
missing data was estimated to be approximately 2 percent
based on the variations between the 10 imputation analyses.
RESULTS
The mean age at CHF diagnosis was 80 years, and approximately 50 percent of participants with CHF were female and
85 percent were Caucasian. At their incident event, 31
percent fulfilled only the Framingham criteria for CHF, 15
percent fulfilled only the Cardiovascular Health Study
criteria, and 54 percent fulfilled both criteria (figure 1). In
general, the three groups defined by diagnostic classification
(Framingham only, Cardiovascular Health Study only, and
concordant) had similar demographic and clinical characteristics (table 2). The Framingham-only group was less likely
than the Cardiovascular Health Study-only group to reside in
Forsyth County, North Carolina, or have a discharge diagnosis code for heart failure. Compared with the other two
groups, the Framingham-only group was less likely to have a
history of myocardial infarction or treated diabetes and was
somewhat more likely to have a low body mass index, high
percent predicted FEV1, or prevalent clinical lung disease.
Of the original 875 participants in the three diagnostic
classification groups, 435 died during a median of 3.7 years
(range: 1 day to 10.6 years) of observation following hospital
discharge. No significant global difference in survival was
seen between the diagnostic classifications (log-rank test:
p = 0.36) (figure 2). Compared with those for the concordant
group, the all-cause mortality rates in the Framingham-only
group (hazard ratio (HR) = 0.87, 95 percent confidence
interval (CI): 0.71, 1.07) and the Cardiovascular Health
Study-only group (HR = 0.89, 95 percent CI: 0.68, 1.15)
were slightly but not significantly lower (table 3). The
Framingham-only and Cardiovascular Health Study-only
groups had similar survival patterns (HR = 1.02, 95 percent
CI: 0.76, 1.35). The survival patterns for the entire
Framingham (Framingham only plus concordant) and
Cardiovascular Health Study (Cardiovascular Health Study
only plus concordant) groups were similar, and the confidence interval excluded a moderate difference in mortality
between these groups (HR = 1.02, 95 percent CI: 0.94, 1.11).
Fewer than 45 percent of those in the Framingham-only,
Cardiovascular Health Study-only, and concordant groups
survived for at least 5 years. The survival pattern for 875
age- and sex-matched persons without CHF was significantly better than that for each of the CHF diagnostic classifications (p < 0.001). A higher proportion of the deaths in the
Am J Epidemiol 2004;160:628–635
Framingham-only group compared with the other two
groups were adjudicated to be noncardiovascular related
(Framingham only: 57 percent, Cardiovascular Health Study
only: 46 percent, concordant: 40 percent).
The survival differences among the three main diagnostic
classifications were not materially affected by adjustment
for the patient characteristics and clinical conditions listed in
table 2. In subgroup analyses, Cox models comparing the
Framingham-only and Cardiovascular Health Study-only
groups with the concordant group suggested that survival
was similar across diagnostic classifications or was slightly
worse for the concordant group (figure 3). In addition,
restricting the analysis of the three main diagnostic classification groups to those with a discharge diagnosis of heart
failure did not change the mortality differences substantially
(Framingham only vs. concordant: HR = 0.94, 95 percent CI:
0.76, 1.17; Cardiovascular Health Study only vs. concordant: HR = 0.93, 95 percent CI: 0.71, 1.22).
In additional analyses, the Framingham CHF definition
was modified to require an International Classification of
Diseases, Ninth Revision, code for heart failure to emulate
the strategy used in several recent epidemiologic studies
(15–18). This approach slightly changed the sizes of the
groups (Framingham only: n = 216, Cardiovascular Health
Study only: n = 156, concordant: n = 447), but the hazard
ratios remained consistent with those from the main analysis
(Framingham only vs. concordant: HR = 0.94, 95 percent CI:
0.76, 1.17; Cardiovascular Health Study only vs. concordant: HR = 0.87, 95 percent CI: 0.68, 1.12). When the
Cardiovascular Health Study definition was modified to
include probable cases of CHF, the size of the Framinghamonly and Cardiovascular Health Study-only groups became
more similar (Framingham only: n = 238, Cardiovascular
Health Study only: n = 165, concordant: n = 495), and
survival among the diagnostic classification groups became
more similar (Framingham only vs. concordant: HR = 0.91,
95 percent CI: 0.74, 1.13; Cardiovascular Health Study only
vs. concordant: HR = 0.94, 95 percent CI: 0.75, 1.18).
Sensitivity analyses restricting the cohort to those participants for whom Framingham criteria information was
complete (n = 198) or nearly complete (no more than one
criterion missing: n = 272; no more than two criteria
missing: n = 358) revealed patterns of survival among the
diagnostic classifications similar to those seen in the entire
cohort. Multiple imputation analyses also were used to look
at the sensitivity of the findings to assumptions about
missing Framingham criteria data. In each of 10 imputations,
the Framingham-only group and the Cardiovascular Health
Study-only group had a slightly, but not significantly better
survival experience than the concordant group did. Hazard
ratios combining the imputation estimates (Framingham
only vs. concordant: HR = 0.84, 95 percent CI: 0.68, 1.01;
Cardiovascular Health Study only vs. concordant: HR =
0.88, 95 percent CI: 0.65, 1.12) were similar to those from
the main analysis.
DISCUSSION
In this investigation, the Framingham and Cardiovascular
Health Study methods of classification produced substan-
632 Schellenbaum et al.
TABLE 2. Patient characteristics by CHF* diagnostic classification† among Cardiovascular
Health Study participants in the inception cohort, United States, 1989–2000‡
Concordant
(n = 472)
Framingham
Heart Study only
(n = 272)
Cardiovascular
Health Study only
(n = 131)
Age in years at event (mean (SD*))
80.2 (6.1)
80.3 (6.0)
80.9 (6.5)
Female sex
51
52
50
Caucasian ethnicity
82
88
88
Forsyth, North Carolina
22
15
35
Sacramento, California
27
29
17
Washington, Maryland
24
29
27
Allegheny, Pennsylvania
27
28
21
ICD-9* code for heart failure
95
82
89
Myocardial infarction
23
16
23
Angina
34
32
35
Atrial fibrillation
21
25
21
Valve problems
17
18
15
Stroke
15
10
13
Transient ischemic attack
8
8
5
Asthma
10
13
8
Emphysema
9
10
8
COPD*
11
13
6
Kidney disease
11
7
8
Treated diabetes mellitus
22
14
15
Treated hypertension
59
57
50
Body mass index in kg/m2 (mean (SD))
27.4 (5.1)
26.1 (4.5)
26.8 (4.5)
Percent predicted FEV1* (mean (SD))
79.4 (24.0)
83.2 (23.9)
78.0 (17.9)
Never
41
44
56
Past
48
45
36
Current
10
11
8
None
65
60
68
<7
27
33
24
Clinic county and state
Prevalent clinical disease
Smoking status
No. of alcoholic drinks per week
7–<14
5
4
5
≥14
3
3
4
* CHF, congestive heart failure; SD, standard deviation; ICD-9, International Classification of
Diseases, Ninth Revision; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory
volume in 1 second.
† Unless otherwise noted, all values are expressed as percentages.
‡ COPD prevalence was assessed during the qualifying hospitalization; other clinical
conditions, body mass index, smoking status, and alcohol consumption were assessed at the
annual visit immediately before the qualifying CHF event; and percent predicted FEV1 was
calculated from the most recent FEV1 measurement before the qualifying hospitalization, one of
three visits at which FEV1 was measured.
tially different incidence estimates: use of the Framingham
criteria resulted in an incidence estimate approximately 23
percent greater compared with the Cardiovascular Health
Study criteria. The four Cardiovascular Health Study sites
differed with respect to the proportions in the Cardiovascular
Health Study-only and Framingham-only groups, possibly
reflecting differences in populations, documentation
patterns, or medical practice or missing data on the
Am J Epidemiol 2004;160:628–635
Survival Associated with CHF Diagnostic Criteria 633
FIGURE 2. Kaplan-Meier survival curves by congestive heart failure (CHF) diagnostic classification, the Cardiovascular Health Study (CHS),
United States, 1989–2000. Survival estimates for the CHF inception cohort diagnostic classifications, and a group of age- and sex-matched CHS
participants without CHF, are compared from the date of hospital discharge (participants without CHF entered on the date that their matched CHF
case was discharged from the hospital). Survival curves were truncated at 6 years because of the small sample size beyond this point.
mortality rate observed in the present study was higher than
the rate reported among prevalent CHF cases in the Cardiovascular Health Study (9), probably because of differences
in mean age, inclusion criteria, and survival bias.
Among those classified as having CHF according to the
Framingham criteria alone, the signs and symptoms that
make up the Framingham criteria may sometimes have been
due to noncardiac conditions. Alternatively, the
Framingham-only group may include persons with heart
failure who did not meet the Cardiovascular Health Study
criteria, perhaps because their condition was ambiguous,
atypical, or accompanied by comorbidities that complicated
the adjudication for CHF. This possibility is supported by
findings that participants who fulfilled the Framingham
criteria but not the Cardiovascular Health Study criteria had
more pulmonary disease and obesity, had a lower prevalence
of diabetes mellitus and myocardial infarction, included a
lower proportion with a hospital discharge diagnosis of heart
failure, and included a lower proportion of cardiovascular
deaths compared with the Cardiovascular Health Study-only
Framingham criteria components. Even though the diagnostic criteria classified different persons as having CHF,
each diagnostic classification was associated with a similarly
poor prognosis in this group of older adults. For each of the
CHF diagnostic classifications, mortality rates were higher
than those for age- and sex-matched participants without
CHF.
Several studies of CHF have used modified versions of the
Framingham criteria similar to the methods used in the
present analysis (15–18). Such studies excluded up to 18
percent of physician-identified cases (15) because of a lack
of sufficient, documented Framingham diagnostic criteria. In
the present analyses, 22 percent of cases classified as CHF
by the Cardiovascular Health Study events committee did
not fulfill the Framingham criteria, and 37 percent of cases
classified as CHF by the Framingham criteria did not meet
the Cardiovascular Health Study definition. Survival in these
elderly, community-dwelling adults with CHF was poor;
fewer than 45 percent survived for 5 years, a finding
congruent with other reports of older adults (6–9). The
TABLE 3. Survival estimates by CHF* diagnostic classification: Kaplan-Meier and Cox proportional hazards
model estimates, the Cardiovascular Health Study, United States, 1989–2000
95%
CI*
p
value
0.87
0.71, 1.07
0.19
0.89
0.68, 1.15
0.36
Deaths
(no.)
Person-years
(no.)
Mortality
rate/year
5-year
survival (%)
Hazard
ratio
Concordant
272
1,345
0.20
38
1.00
Framingham Heart
Study only
140
794
0.18
44
71
397
0.18
40
Cardiovascular Health
Study only
* CHF, congestive heart failure; CI, confidence interval.
Am J Epidemiol 2004;160:628–635
634 Schellenbaum et al.
FIGURE 3. Subgroup hazard ratios and 95% confidence intervals for Framingham-only and Cardiovascular Health Study (CHS)-only
congestive heart failure cases compared with the concordant group, the CHS, United States, 1989–2000. In each subgroup, survival of the
Framingham-only and CHS-only groups was compared with the concordant group (reference) by using Cox proportional hazards models.
and concordant groups. These comorbid conditions would
themselves affect survival.
Since there is no “gold standard” for defining CHF, it was
not possible to determine which criteria “correctly” classified CHF. Given the greater number of cases identified by
using the Framingham criteria, these criteria may have classified participants without CHF as CHF cases more often
than the Cardiovascular Health Study method did. Alternatively, the Cardiovascular Health Study events committee
may have excluded CHF cases more often than the
Framingham criteria did. The relative value of these and
other methods for classifying persons with respect to CHF
depends, in part, on the goals of a particular study. Explicit
diagnostic criteria, such as the Framingham CHF criteria,
may be well suited to comparisons across study populations
or over time; central adjudication, as used by the Cardiovascular Health Study, offers the advantage of considering all
available information and may be more specific, which can
be important in studies of etiology. Indeed, as medical practice evolves, as it did during the course of this study, the relative utility of diagnostic criteria may change.
The findings of this analysis are strengthened by sensitivity analyses indicating that the survival analysis results are
robust to multivariate adjustment, restriction to subgroups,
and missing data assumptions: the Framingham criteria were
assumed to be missing because they were absent (main analysis) or missing at random (multiple imputation analysis).
Moreover, the approach used in the present analysis to assess
Framingham CHF criteria is similar to that used by other
studies attempting to find CHF cases by using the
Framingham criteria as recorded in medical records.
Considerable amounts of missing data for the Framingham
criteria may have resulted in incomplete identification of cases
meeting these criteria. The number of CHF cases that would
have fulfilled the Framingham criteria, and the difference in
incidence estimates between the two methods, may have been
Am J Epidemiol 2004;160:628–635
Survival Associated with CHF Diagnostic Criteria 635
underestimated in this analysis. Furthermore, the present application of the Framingham criteria was not exactly the same as
in the Framingham Heart Study. In that study, the Framingham
CHF criteria are applied by using central adjudication by
a panel of physicians that considers all hospitalizations
with a cardiovascular element. To avoid misclassification,
Framingham Heart Study investigators adjudicated CHF cases
and excluded those for whom the symptoms and signs of CHF
may have been due to another disease process. However, this
investigation has taken the approach, used in several recent
studies (15–18), of using contemporary components of the
Framingham criteria without adjudication. Although the
Framingham Heart Study investigators have also proposed
diastolic heart failure criteria (19), these criteria were not
included in the present investigation. Patients with diastolic
heart failure were included in these analyses, but diastolic heart
failure was not considered a separate condition.
The older age of Cardiovascular Health Study participants
may have limited this investigation’s ability to examine
survival differences between the two sets of diagnostic
criteria. However, in the general population, approximately
80 percent of CHF patients are at least 65 years of age (20).
The generalizability of this study is limited by the participation rate of 57 percent at baseline in the Cardiovascular
Health Study, and the results may not be generalizable to
ethnicities that were not represented in the Cardiovascular
Health Study cohort. Finally, because of data availability
issues, we considered only those hospitalized cases of incident CHF that were not procedure related. Diagnosis and
prognosis may differ for outpatients, younger populations,
and other groups of CHF patients excluded from this study.
For the complex syndrome of CHF, no uniform diagnostic
definition has emerged. The method chosen to define CHF
cases is likely to affect the observed incidence or prevalence
of CHF. In contrast, the current study suggests that survival
may be similar for these two diagnostic approaches. Whether
this finding applies to other classification approaches or populations requires additional investigation. Diagnostic criteria
for CHF should be chosen with care during the design phase
of a study, and differences between diagnostic criteria should
be considered when interpreting the available literature.
ACKNOWLEDGMENTS
This research was supported by contracts N01-HC-8507986, Georgetown Echo RC-HL35129, JHU MRI RCHL15103, HL43201, and 1-T32-HL07902 from the National
Heart, Lung, and Blood Institute and by grant AG09556 from
the National Institute on Aging. For a full list of Cardiovascular Health Study investigators and institutions, refer to the
following Internet website: http://www.chs-nhlbi.org.
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