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Depression and Risk of Heart Failure Among Older Persons With Isolated Systolic Hypertension
Jerome Abramson, PhD;
Alan Berger, MD;
Harlan M. Krumholz, MD, MPH;
Viola Vaccarino, MD, PhD
Arch Intern Med. 2001;161:1725-1730.
ABSTRACT
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Background Investigators have shown that depression is associated with an increased
risk of coronary heart disease in general and myocardial infarction in particular.
However, it is unknown whether depression, independent of its association
with myocardial infarction, is a risk factor for heart failure.
Methods This study examined whether depression was a predictor of incident heart
failure among 4538 persons aged 60 years and older with isolated systolic
hypertension who were enrolled in the Systolic Hypertension in the Elderly
Program (SHEP). Depression was defined as a score of 16 or more at baseline
on the Center for Epidemiological Studies Depression Scale (CES-D). The relationship
between depression and heart failure was assessed using Cox proportional hazards
regression.
Results The average follow-up was 4.5 years. Heart failure developed in 138
(3.2%) of 4317 nondepressed persons and in 18 (8.1%) of 221 depressed persons.
After controlling for age; sex; race; history of myocardial infarction, diabetes,
or angina; blood pressure; cholesterol levels; electrocardiographic abnormalities;
smoking; disability; and SHEP treatment group, depressed persons had more
than a 2-fold higher risk of developing heart failure compared with nondepressed
persons (hazard ratio, 2.59; 95% confidence interval, 1.57-4.27; P<.001). After additional adjustment for the occurrence of myocardial
infarction during follow-up, depressed persons remained at elevated risk of
heart failure (hazard ratio, 2.82; 95% confidence interval, 1.71-4.67; P<.001).
Conclusions Depression is independently associated with a substantial increase in
the risk of heart failure among older persons with isolated systolic hypertension.
This association does not appear to be mediated by myocardial infarction.
INTRODUCTION
INVESTIGATORS have shown that depression is associated with an increased
risk of developing coronary heart disease in general1-3
and myocardial infarction (MI) in particular.3-4
Studies5-8
have also shown that depression is a negative prognostic factor among persons
with established coronary heart disease. Less is known about the relationship
between depression and heart failure. One study9
reported an association between depression and higher death rates among persons
with existing heart failure. However, prior investigations have not addressed
whether depression predicts the onset of heart failure. Because depression
is associated with increased MI risk and because MI is a major risk factor
for heart failure, one would expect depression to be associated with an increased
risk of developing heart failure. In addition, however, depression has been
associated with excessive activation of the sympathetic nervous system,10-11 and heightened activation of this
system is thought to be one of the processes involved in the pathogenesis
of heart failure.12 As such, depression-induced
sympathetic nervous system activation represents a separate pathway, not necessarily
related to MI risk, by which depression could increase the risk of incident
heart failure. If a link were established between depression and increased
risk of heart failure, it would add to the growing evidence of depression's
negative impact on cardiovascular health. In the present study, we examined
whether depression was predictive of incident heart failure among older persons
with isolated systolic hypertension enrolled in the Systolic Hypertension
in the Elderly Program (SHEP).
METHODS
DESIGN AND PARTICIPANTS
SHEP was a randomized, double-blind, placebo-controlled, multicenter
clinical trial designed to test the efficacy of antihypertensive therapy in
reducing stroke incidence among older persons with isolated systolic hypertension.13 Major inclusion criteria were an age of 60 years
or older, a baseline systolic blood pressure (SBP) of 160 mm Hg or higher,
and a diastolic blood pressure (DBP) of less than 90 mm Hg. Major exclusion
criteria were a baseline SBP of 220 mm Hg or higher and a recent episode (6
months before baseline) of a major cardiovascular event such as MI or stroke.
In addition, persons with uncontrolled heart failure at baseline were excluded
from SHEP. Investigators randomized 4736 participants who met these criteria
to either stepped-care treatment or placebo. The drugs used for the active
treatment were chlorthalidone, 12.5 mg increased to 25 mg (step 1), and, if
necessary, atenolol, 25 or 50 mg (step 2). For persons whose baseline SBP
was more than 180 mm Hg, the goal was to reduce the SBP to below 160 mm Hg;
for persons whose baseline SBP was between 160 and 179 mm Hg, the goal was
a reduction of at least 20 mm Hg in SBP. Participants were followed up for
an average of 4.5 years. SHEP demonstrated that the active treatment resulted
in a significant reduction in the incidence of stroke.14
Additional details about the design and conduct of SHEP can be found elsewhere.13-14
Uncontrolled heart failure was one of the SHEP exclusion criteria. However,
compensated heart failure was not one of the exclusion criteria. According
to information gathered from extensive physical examinations made at baseline,
physicians determined that 16 SHEP participants had had compensated heart
failure within 1 year before the start of the study. These 16 persons were
excluded from our analyses. We additionally excluded 182 persons with missing
data on depression or any of the other variables used in our analyses. After
all exclusions, the sample size for the present study was 4538 persons.
ASCERTAINMENT OF DEPRESSION
At baseline, depression was assessed by the Center for Epidemiological
Studies Depression Scale (CES-D).15 The CES-D
is a 20-item self-report scale designed to measure depressive symptoms in
the general population. Each item assesses how frequently a participant experiences
a particular depressive symptom. A given item is scored on a 4-point scale
ranging from 0 to 3. Scores from the individual items are then summed to arrive
at a total CES-D score that can range from 0 to 60, with higher scores representing
higher levels of depressive symptoms. For those with 1 to 3 missing CES-D
items (n = 103), we imputed total CES-D scores by calculating the average
score on the nonmissing items and then multiplying this average score by 20.
Participants with more than 3 missing items on the CES-D were excluded from
our analyses. For purposes of this study, depression was defined as a score
of 16 or more on the CES-D at baseline. This score has been shown to provide
a reasonable approximation to a clinical diagnosis of depression.15-16
ASCERTAINMENT OF HEART FAILURE
The outcome in this study was fatal or nonfatal heart failure. Some
SHEP participants experienced multiple heart failure events during follow-up,
but we only considered the first event in our analyses. When a suspected cardiovascular
or cerebrovascular event occurred in SHEP, staff at participating centers
forwarded relevant clinical information (including electrocardiographic [ECG]
data, cardiac enzyme levels, chest x-ray reports, and death certificates or
autopsy reports) to a coordinating center so that a coding panel could adjudicate
diagnoses. The coding panel included 3 physicians, at least 1 of whom was
a cardiologist. For a diagnosis of heart failure, the coding panel required
1 of the following to be present: paroxysmal nocturnal dyspnea, dyspnea at
rest, orthopnea, or New York Heart Association classification III cardiac
disease. In addition, 1 of the following criteria also needed to be present:
rales, ankle edema (2+ or greater), tachycardia (heart rate of  120/min
after 5 minutes of rest), S3 gallop, jugular venous distension,
or radiographic evidence of heart failure.14
Diagnoses of heart failure were not made if the symptoms or signs listed herein
were due to pulmonary conditions such as pneumonia or chronic obstructive
pulmonary disease.
CONTROL VARIABLES
A number of baseline factors were included as control variables in our
analyses. These factors included age, sex, race (white vs nonwhite), history
of MI or angina as determined by a physician, self-reported history of diabetes,
SBP and DBP, total cholesterol and high-density lipoprotein cholesterol (HDL-C)
levels, and presence of ECG abnormalities. We also controlled for self-reported
smoking (current vs former or never), presence of any disability in activities
of daily living,17 and SHEP treatment status
(active treatment vs placebo).
Another control variable that we considered was the occurrence of MI
during follow-up. Of the MIs that occurred during follow-up, we only controlled
for those that happened before a heart failure event. As with heart failure,
a coding panel of 3 SHEP physicians diagnosed MIs during follow-up on the
basis of clinical information gathered by SHEP staff. A diagnosis of MI during
follow-up required the presence of typical symptoms associated with acute
MI and either typical ECG changes (including new Q waves) or enzyme levels
at least 1.25 times greater than normal.
STATISTICAL ANALYSIS
The first step in the analysis was to examine bivariate associations
between the dichotomous depression variable under study and the baseline control
variables. The t test was used for continuous control
variables and the  2 test was used for categorical control
variables. We used a series of Cox proportional hazards regression models
to examine the association between baseline depression and subsequent risk
of heart failure after adjusting for baseline control variables. Time to first
heart failure event was the outcome of interest in these Cox models. The proportional
hazards assumption was checked by including a time-dependent covariate representing
the interaction between depression and follow-up time. A nonsignificant P value for this covariate (P>.20)
was taken as evidence that the proportional hazards assumption had been satisfied.
Age, SBP, DBP, total cholesterol level, and HDL-C level were entered as continuous
variables in the Cox models. Other control variables were entered according
to the categories noted herein.
We also performed a number of additional analyses. First, we examined
the association of depression with heart failure after adjusting for MI events
that occurred subsequent to baseline. This analysis was accomplished by running
a Cox model that included a time-dependent covariate for the occurrence of
MI during follow-up. Second, we considered the possibility that the relationship
between depression and heart failure varied according to sex and SHEP treatment
group, respectively. To assess this possibility, we ran models that included
appropriate interaction terms. Third, because SHEP participants completed
the CES-D scale every 6 months during follow-up, we were able to assess how
updated CES-D values were related to heart failure risk. To do this, we ran
a model that included a time-dependent CES-D variable. Fourth, some investigators
have noted that depressive symptoms exert a graded effect on cardiovascular
outcomes.4, 18 To evaluate this
possibility, we divided baseline CES-D scores into 3 levels: low (0-7), medium
(8-15), and high (16). We then included these levels in a Cox model with
the 0 to 7 group as the referent group. These levels were chosen because they
were thought to represent clinically meaningful differences in CES-D scores,
with the highest group being consistent with clinically diagnosed depression.
RESULTS
Of the 4538 persons included in this study, 4317 were free of depression
at baseline, and 221 were depressed according to the CES-D. Persons who were
depressed were significantly less likely to be male (P<.001)
and more likely to be nonwhite (P<.001) (Table 1). Depressed persons had significantly
higher SBP readings (P = .01) and higher HDL-C levels
(P<.01), but there were no significant differences
in history of MI or diabetes.
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Table 1. Baseline Characteristics According to Baseline Depression
Level*
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During follow-up, heart failure events occurred in 138 (3.2%) of the
4317 nondepressed persons and in 18 (8.1%) of the 221 depressed persons. The
crude relative risk indicated that depressed persons were significantly more
likely than nondepressed persons to develop heart failure during follow-up
(relative risk, 2.55; 95% confidence interval [CI], 1.59-4.08; P<.001). Table 2 shows
that after adjustment for demographic factors (model 1), the association between
depression and heart failure incidence was still strong and significant (hazard
ratio [HR], 2.68; 95% CI, 1.63-4.42; P<.001).
In model 2, which additionally adjusted for history of MI, diabetes, and angina;
SBP and DBP; lipid levels; ECG abnormalities; current smoking; and treatment
status, depression continued to be a predictor of increased heart failure
risk (HR, 2.59; 95% CI, 1.57-4.27; P<.001). In
both of these models, the time-dependent interaction between depression and
follow-up time was not significant (P>.60), suggesting
that the proportional hazards assumption was satisfied. Thus, the effect of
depression on heart failure risk was fairly constant during the study and
was not confined to a particular period, such as the early part of the follow-up.
To further verify that depression was not simply associated with early heart
failure events (therefore suggesting that depression assessed at baseline
might be secondary to subclinical heart failure), we refitted model 2 after
excluding heart failure events that occurred within the first year of follow-up.
In this refitted model, depression was still strongly associated with an increased
risk of heart failure (HR, 2.54; 95% CI, 1.39-4.66; P
= .002). Figure 1 shows the adjusted
probability of surviving free of heart failure, according to baseline depression
status.
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Table 2. Depression as a Predictor of Heart Failure in Multivariate
Cox Models*
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Adjusted survival curves showing the probability of surviving free
of heart failure (nonfatal or fatal) according to baseline score on the Center
for Epidemiological Studies Depression Scale (CES-D). Curves are adjusted
for age; sex; race; history of myocardial infarction, diabetes, or angina;
blood pressure; cholesterol levels; electrocardiographic abnormalities; disability;
smoking; and Systolic Hypertension and the Elderly Program treatment status.
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In additional analyses, we found no evidence that the association between
depression and heart failure was mediated by incident MI. We ran a fully adjusted
Cox model (adjusting for all of the variables in model 2 of Table 2) that included a time-dependent covariate for incident MI.
In this model, incident MI was an overwhelmingly strong risk factor for heart
failure (HR, 22.68; 95% CI, 15.92-34.49; P<.001).
Nevertheless, the model showed that depression was still associated with a
significant increase in the risk of heart failure; the association actually
appeared slightly stronger than in previous models (HR, 2.82; 95% CI, 1.71-4.67; P<.001).
The association between depression and heart failure did not vary significantly
according to sex or treatment status. A fully adjusted Cox model that included
a term for the interaction between depression and sex showed that the effect
of depression was somewhat lower in women compared with men, but the interaction
was not significant (for women: HR, 2.05; 95% CI, 1.05-4.00; for men: HR,
3.68; 95% CI, 1.76-7.70; P = .25 for the interaction
between depression and sex). A fully adjusted model that included a term for
the interaction between depression and treatment group indicated that the
effect of depression in the placebo and treatment groups was similar (for
the placebo group: HR, 2.67; 95% CI, 1.45-4.92; for the treatment group: HR,
2.45; 95% CI, 1.04-5.76; P = .92 for the interaction
between depression and treatment).
To determine the role of depression over time on heart failure risk,
a dichotomous CES-D variable (<16 vs 16) was modeled as a time-dependent
variable, which took into account longitudinal assessments of the CES-D throughout
the follow-up. This variable proved to be a significant predictor of heart
failure, even after full adjustment for all of the control variables (HR,
2.00; 95% CI, 1.21-3.31; P = .007). However, the
effect was somewhat smaller than it was for the baseline dichotomous CES-D
variable. We also used the follow-up CES-D scores to calculate change in CES-D
scores from baseline. When modeled as a time-dependent covariate, we found
that a change (increase) in CES-D scores from baseline was a risk factor for
heart failure. However, baseline depression remained a significant predictor
of heart failure (HR, 3.12; 95% CI, 1.76-5.52; P<.001),
even when the increase in CES-D score from baseline and other variables were
accounted for.
Finally, we examined whether CES-D scores exerted a graded effect on
the risk of heart failure. As noted earlier, we trichotomized baseline CES-D
scores as 0 to 7 (n = 3697), 8 to 15 (n = 620), and 16 or higher (n = 221).
After adjustment for all of the control variables, we found that those in
the 8 to 15 group did not have a higher risk of heart failure compared with
those in the 0 to 7 group (HR, 0.75; 95% CI, 0.46-1.22; P = .24). However, those in the 16 or higher group had a significantly
higher risk of heart failure compared with the subjects in the 0 to 7 group
(HR, 2.46; 95% CI, 1.48-4.07; P<.001).
COMMENT
The main finding of this study was that depression, as indicated by
a score of 16 or more on the CES-D, was associated with a substantial and
significant increase in the risk of developing heart failure during follow-up
among older persons with isolated systolic hypertension enrolled in SHEP.
This association was observed after controlling for a number of factors, including
age; sex; race; history of MI, diabetes, or angina; SBP and DBP; total cholesterol
and HDL-C levels; ECG abnormalities; smoking; disability; and SHEP treatment
status. Others have reported that the prevalence of depression is higher in
persons with heart failure19 and that depression
is associated with an increased risk of death among persons with existing
heart failure.9 To our knowledge, our investigation
is the first study to establish an independent association between depression
and the subsequent development of heart failure.
In addition to the main result noted, we conducted a number of additional
analyses. First, we found that baseline depression was associated with a higher
risk of heart failure, even when the occurrence of MI during follow-up was
controlled for. Second, we failed to find evidence that the association between
depression and heart failure significantly varied according to sex. This is
in contrast to some prior studies of depression and cardiovascular outcomes,
which have reported significant interactions between depression and sex.18, 20 Third, we failed to observe a graded
association between depressive symptoms and heart failure. Instead, our findings
suggested that depressive symptoms increase heart failure risk only when those
symptoms reach a sufficiently high level (ie, a level considered an approximation
of a clinical diagnosis of depression). Other studies, however, have reported
graded associations between depression and cardiovascular outcomes such as
coronary heart disease.4, 18 Fourth,
we analyzed how depression levels during follow-up were related to heart failure
risk. An earlier study of the SHEP data reported that a change (increase)
in the CES-D score from baseline, modeled as a time-dependent covariate, was
associated with a higher risk of MI and stroke.21
We found that this time-dependent covariate was also associated with increased
heart failure risk, although baseline depression continued to predict heart
failure when this time-dependent covariate was accounted for. We also found
that a time-dependent dichotomous (<16 vs 16) depression variable was
associated with higher heart failure risk, but the association was somewhat
weaker than it was for the baseline dichotomous depression variable. Thus,
compared with updated measures of depression over time, a single measure of
depression at baseline in SHEP was as good or better at predicting heart failure.
What could account for the association between depression and increased
heart failure risk observed in this study? One possible explanation for our
findings is that, before baseline, heart failure in a subclinical or compensated
stage led to depression, and then the subclinical disease later manifested
itself as clinical disease during follow-up. Such a sequence of events would
make it seem as if depression led to heart failure when in fact the opposite
would be true. If this were the case, one might expect that the relation between
baseline depression and subsequent heart failure would primarily appear during
the early part of the follow-up period. However, our results indicated that
the effect of depression was not confined to the early part of follow-up but
was, instead, relatively constant throughout the study. Thus, our results
do not appear to be attributable to a scenario in which subclinical heart
failure led to depression.
A second possible explanation is that high-level depressive symptoms
led to MI events and that the latter subsequently led to heart failure. In
theory, this explanation seems plausible because there is evidence that depression
may increase the risk of MI,4 and MI is, in
turn, a major risk factor for heart failure. However, we found that depression
predicted increased heart failure risk after controlling for a history of
MI and the occurrence of MI during follow-up. Thus, MI does not appear to
mediate the association we observed between depression and increased heart
failure risk.
Factors known to differ between depressed and nondepressed persons at
baseline may provide a third possible explanation for our findings. For example,
we found that depressed persons were significantly more likely to be female
and nonwhite. We also found that depressed persons had higher SBP levels and
greater limitations in activities of daily living at baseline. After controlling
for these factors though, we still found a strong association between depression
and a higher risk of heart failure. Thus, unless there was residual confounding
due to imprecise control of these factors, such factors do not appear to account
for our results.
Fourth, our results may be due to factors that we did not have any information
about. We did not, for example, have any information on the duration of systolic
hypertension or the duration of medical therapy before baseline. Compliance
with medication regimens is another important factor that was not included
in our analyses. Evidence indicates that depressed persons may be less likely
to comply with medical advice,22 and such noncompliance
could be a potential explanation for our results. Finally, we did not have
information on sympathetic nervous system activity in our study. Depressed
persons tend to show heightened activation of the sympathetic nervous system.10-11 In addition, heightened activation
of this system is believed to play an important role in the pathogenesis of
heart failure.12, 23-25
Thus, depression-induced sympathetic nervous system activation is a plausible
physiological pathway that could account for our findings.
The present study had a number of strengths. Heart failure events were
ascertained prospectively according to rigorous criteria, and all diagnoses
were confirmed by a panel of 3 physicians. In addition, all subjects underwent
an extensive medical examination at baseline, which allowed accurate assessment
of medical history and health status. Thus, we were able to control for a
number of other potential risk factors for heart failure, such as MI, blood
pressure, cholesterol levels, and smoking.
However, this study also had some weaknesses. Our measure of depression
was based on a CES-D score of 16 or more. The CES-D is a scale that assesses
depressive symptoms, and a score of 16 or more on the CES-D is not necessarily
equivalent to a clinical diagnosis of depression. Clinical diagnoses may have
provided a more precise method of measuring our exposure of interest. However,
previous studies15-16 have indicated
that a score of 16 or more on the CES-D is a reasonable approximation of a
clinical diagnosis of depression. The CES-D is one of the most commonly used
depression scales in epidemiologic studies because it is shorter and easier
to administer in population studies than are structured clinical interviews
for mental disorders used in clinical settings. In this respect, our study
follows the approach of previous epidemiologic studies2, 18, 20
that have linked depression to an increased risk of coronary heart disease.
A second weakness of our study was that our study population was a select
group of people who all had isolated systolic hypertension and had agreed
to participate in a clinical trial. Isolated systolic hypertension is fairly
common among elderly persons though,26 so our
results may have fairly broad applicability. Nevertheless, future studies
should confirm our findings in more general, community-based settings. A third
weakness was that our results were based on a relatively small number of events
(n = 18) in the depressed group. Although this did not prevent us from detecting
a significant association for the main effect of depression, it may have precluded
detection of significant interactions between depression and other variables,
such as sex. A fourth weakness is that we did not have information on whether
the heart failure events were due to systolic or diastolic ventricular dysfunction,
and, therefore, we were unable to determine the association between depression
and these different subtypes of heart failure.
In summary, our results indicate that depression is associated with
an increased risk of heart failure among older persons with isolated systolic
hypertension. This association is not explained by demographic characteristics,
baseline health status and medical history, or MI risk. This study adds to
the growing evidence that depression increases the risk of adverse cardiovascular
events.
AUTHOR INFORMATION
Accepted for publication January 11, 2001.
Corresponding author and reprints: Jerome Abramson, PhD, Emory Center
for Outcomes Research, Emory West, 1256 Briarcliff Rd NE, Suite 1 N, Atlanta,
GA 30306 (e-mail: jerome{at}ecor.cardio.emory.edu).
From the Department of Medicine, Division of Cardiology, Emory University
School of Medicine, Atlanta, Ga (Drs Abramson and Vaccarino); Division of
Cardiology and Epidemiology, University of Minnesota, Minneapolis (Dr Berger);
and Department of Epidemiology and Public Health and Section of Cardiovascular
Medicine, Yale University School of Medicine, New Haven, Conn (Dr Krumholz).
REFERENCES
| |
1. Anda R, Williamson D, Jones D, et al. Depressed affect, hopelessness, and the risk of ischemic heart disease
in a cohort of U.S. adults. Epidemiology. 1993;4:285-294.
ISI
| PUBMED
2. Ferketich AK, Schwartzbaum JA, Frid DJ, Moeschberger ML. Depression as an antecedent to heart disease among women and men in
the NHANES I study. Arch Intern Med. 2000;160:1261-1268.
FREE FULL TEXT
3. Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang NY, Klag MJ. Depression is a risk factor for coronary artery disease in men: the
Precursors Study. Arch Intern Med. 1998;158:1422-1426.
FREE FULL TEXT
4. Barefoot JC, Schroll M. Symptoms of depression, acute myocardial infarction, and total mortality
in a community sample. Circulation. 1996;93:1976-1980.
FREE FULL TEXT
5. Frasure-Smith N, Lesperance F, Juneau M, Talajic M, Bourassa MG. Gender, depression, and one-year prognosis after myocardial infarction. Psychosom Med. 1999;61:26-37.
FREE FULL TEXT
6. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction: impact on 6-month survival. JAMA. 1993;270:1819-1825.
FREE FULL TEXT
7. Frasure-Smith N, Lesperance F, Talajic M. Depression and 18-month prognosis after myocardial infarction. Circulation. 1995;91:999-1005.
FREE FULL TEXT
8. Barefoot JC, Helms MJ, Mark DB, et al. Depression and long-term mortality risk in patients with coronary artery
disease. Am J Cardiol. 1996;78:613-617.
FULL TEXT
|
ISI
| PUBMED
9. Murberg TA, Bru E, Svebak S, Tveteras R, Aarsland T. Depressed mood and subjective health symptoms as predictors of mortality
in patients with congestive heart failure: a two-years follow-up study. Int J Psychiatry Med. 1999;29:311-326.
FULL TEXT
|
ISI
| PUBMED
10. Gold PW, Goodwin FK, Chrousos GP. Clinical and biochemical manifestations of depression: relation to
the neurobiology of stress (part 2). N Engl J Med. 1988;319:413-420.
ABSTRACT
11. Chrousos GP, Gold PW. The concepts of stress and stress system disorders: overview of physical
and behavioral homeostasis. JAMA. 1992;267:1244-1252.
FREE FULL TEXT
12. Packer M. New concepts in the pathophysiology of heart failure: beneficial and
deleterious interaction of endogenous haemodynamic and neurohormonal mechanisms. J Intern Med. 1996;239:327-333.
FULL TEXT
|
ISI
| PUBMED
13. Borhani NO, Applegate WB, Cutler JA, et al. Systolic Hypertension in the Elderly Program (SHEP). I: rationale and
design. Hypertension. 1991;17(suppl II):2-15.
14. SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons
with isolated systolic hypertension: final results of the Systolic Hypertension
in the Elderly Program (SHEP). JAMA. 1991;265:3255-3264.
FREE FULL TEXT
15. Radloff LS. The CES-D Scale: a self-report depression scale for research in the
general population. Appl Psychol Meas. 1977;1:385-401.
FULL TEXT
16. Roberts RE, Vernon SW. The Center for Epidemiologic Studies Depression Scale: its use in a
community sample. Am J Psychiatry. 1983;140:41-46.
FREE FULL TEXT
17. Katz S, Ford AB, Moskowitz RW, Jackson BA, Jafine NW. Studies of illness in the aged: the index of ADL: a standardized measure
of biological and psychosocial function. JAMA. 1963;185:914-919.
18. Mendes de Leon CF, Krumholz HM, Seeman TS, et al. Depression and risk of coronary heart disease in elderly men and women:
New Haven EPESE, 1982-1991. Arch Intern Med. 1998;158:2341-2348.
FREE FULL TEXT
19. Havranek EP, Ware MG, Lowes BD. Prevalence of depression in congestive heart failure. Am J Cardiol. 1999;84:348-350.
FULL TEXT
|
ISI
| PUBMED
20. Penninx BW, Guralnik JM, Mendes de Leon CF, et al. Cardiovascular events and mortality in newly and chronically depressed
persons >70 years of age. Am J Cardiol. 1998;81:988-994.
FULL TEXT
|
ISI
| PUBMED
21. Wassertheil-Smoller S, Applegate WB, Berge K, et al. Change in depression as a precursor of cardiovascular events: SHEP
Cooperative Research Group (Systolic Hypertension in the Elderly). Arch Intern Med. 1996;156:553-561.
FREE FULL TEXT
22. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment:
meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000;160:2101-2107.
FREE FULL TEXT
23. Pepper GS, Lee RW. Sympathetic activation in heart failure and its treatment with  -blockade. Arch Intern Med. 1999;159:225-234.
FREE FULL TEXT
24. Kaye DM, Lefkovits J, Jennings GL, Bergin P, Broughton A, Esler MD. Adverse consequences of high sympathetic nervous activity in the failing
human heart. J Am Coll Cardiol. 1995;26:1257-1263.
ABSTRACT
25. Cohn JN, Levine TB, Olivari MT, et al. Plasma norepinephrine as a guide to prognosis in patients with chronic
congestive heart failure. N Engl J Med. 1984;311:819-823.
ABSTRACT
26. The sixth report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-2446.
FREE FULL TEXT
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J Am Coll Cardiol 2009;53:1440-1447.
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Mental Disorders, Quality of Care, and Outcomes Among Older Patients Hospitalized With Heart Failure: An Analysis of the National Heart Failure Project
Rathore et al.
Arch Gen Psychiatry 2008;65:1402-1408.
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Depressive Symptoms, Health Behaviors, and Risk of Cardiovascular Events in Patients With Coronary Heart Disease
Whooley et al.
JAMA 2008;300:2379-2388.
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Heterogeneity in Randomized Controlled Trials of Long Chain (Fish) Omega-3 Fatty Acids in Restenosis, Secondary Prevention and Ventricular Arrhythmias
Jenkins et al.
J. Am. Coll. Nutr. 2008;27:367-378.
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Prevention of Heart Failure: A Scientific Statement From the American Heart Association Councils on Epidemiology and Prevention, Clinical Cardiology, Cardiovascular Nursing, and High Blood Pressure Research; Quality of Care and Outcomes Research Interdisciplinary Working Group; and Functional Genomics and Translational Biology Interdisciplinary Working Group
Schocken et al.
Circulation 2008;117:2544-2565.
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Challenges for Consultation-Liaison Psychiatry in the 21st Century
Strain and Blumenfield
Psychosomatics 2008;49:93-96.
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Depressive Symptoms and Heart Failure Stages
Azevedo et al.
Psychosomatics 2008;49:42-48.
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Relationship of Depression to Death or Hospitalization in Patients With Heart Failure
Sherwood et al.
Arch Intern Med 2007;167:367-373.
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Sleep disturbances independently predict heart failure in overweight middle-aged men
Ingelsson et al.
Eur J Heart Fail 2007;9:184-190.
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Prevalence of Depressive Symptoms Among Patients With Chronic Cough
Dicpinigaitis et al.
Chest 2006;130:1839-1843.
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Depression in Heart Failure: A Meta-Analytic Review of Prevalence, Intervention Effects, and Associations With Clinical Outcomes
Rutledge et al.
J Am Coll Cardiol 2006;48:1527-1537.
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Depression and cardiovascular disease: healing the broken-hearted.
Whooley
JAMA 2006;295:2874-2881.
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Reflections on Depression as a Cardiac Risk Factor
Frasure-Smith and Lesperance
Psychosom. Med. 2005;67:S19-S25.
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Depression increasingly predicts mortality in the course of congestive heart failure
Junger et al.
Eur J Heart Fail 2005;7:261-267.
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Depressive Symptoms Are Related to Higher Ambulatory Blood Pressure in People With a Family History of Hypertension
Grewen et al.
Psychosom. Med. 2004;66:9-16.
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Depressive symptoms are the strongest predictors of short-term declines in health status in patients with heart failure
Rumsfeld et al.
J Am Coll Cardiol 2003;42:1811-1817.
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Increased Coronary Events in Depressed Cardiovascular Patients: 5-HT2A Receptor as Missing Link?
Schins et al.
Psychosom. Med. 2003;65:729-737.
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Cytokines in Depression and Heart Failure
Pasic et al.
Psychosom. Med. 2003;65:181-193.
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Depression and Cardiac Morbidity 5 Years After Coronary Artery Bypass Surgery
Borowicz et al.
Psychosomatics 2002;43:464-471.
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Depression and Heart-Failure Risk in the Elderly: Report from SHEP
Journal Watch Cardiology 2001;2001:7-7.
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Confirming the Link Between Depression and Heart Failure
JWatch Psychiatry 2001;2001:5-5.
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