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Journal of Behavioral Medicine, Vol. 26, No. 2, April 2003 (°

C 2003)

Age Differences in Symptoms of Depression

and Anxiety: Examining Behavioral
Medicine Outpatients
Jennifer H. Goldberg,1,4 James N. Breckenridge,2,3 and Javaid I. Sheikh2,3

Accepted for publication: September 24, 2002

This study examined whether symptoms of depression and concomitant anx-

iety differed between older and younger medical outpatients referred to a be-
havioral medicine clinic. In a sample of 178 male veterans aged 21–83 years,
older adults (≥60 years) reported lower overall depressive symptoms on the
Beck Depression Inventory (BDI) and anxiety symptoms on the State-Trait
Anxiety Inventory than did younger adults (<60 years). Depressive symptoms
were highly prevalent. Among older adults, 60.0% scored 10 or higher on BDI
and 33.8% scored 16 or higher. Among younger adults, 70.8% scored 10 or
higher on BDI, and 48.7% scored 16 or higher. The age difference in over-
all depressive symptoms was driven by cognitive–affective symptoms. While
older adults had lower cognitive–affective symptoms than did younger adults,
the two groups did not differ on somatic-performance symptoms. These results
suggest the importance of assessing cognitive–affective depressive symptoms
in both older and younger male medical outpatients.
KEY WORDS: medical patients; depression; anxiety; age.

1Stanford Center for Research in Disease Prevention, Stanford University School of Medicine,
Palo Alto, California.
2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine,
Stanford, California.
3VA Palo Alto Health Care System, Palo Alto, California.
4To whom correspondence should be addressed; e-mail: jennifer.goldberg@stanford.edu.

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C 2003 Plenum Publishing Corporation
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120 Goldberg, Breckenridge, and Sheikh

Elevated symptoms of depression and diagnosed depression have long

been observed among medical outpatients of all ages. Structured psychiatric
interviews have revealed that 5–10% of medical outpatients meet criteria
for major depression at a given time (Katon and Schulberg, 1992). Both di-
agnosed depression and symptoms of depression have been associated with
increased medical morbidity, mortality, health utilization, functional impair-
ment, and decreased quality of life (Bush et al., 2001; Ganzini et al., 1997;
Katon, 1996; Wells et al., 1989). Depression is prevalent among subgroups
of medical patients with the types of specific health problems addressed
by behavioral medicine psychological treatment including coronary heart
disease (Carney et al., 1995; Musselman et al., 1998), cancer (Newport and
Nemeroff, 1998; Spiegel, 1996), and chronic pain (Banks and Kerns, 1996).
Yet the interpretation of depression diagnoses and depressive symptoms can
be complicated in medical outpatients, including those referred for behav-
ioral medicine treatment, as specific somatic symptoms of depression (e.g.,
fatigue, loss of appetite) may be attributed to underlying medical conditions
rather than to a mood disorder.
The effects of age further complicate the interpretation of depression
diagnoses and depressive symptoms in these medical outpatients. Although
epidemiological studies have found lower rates of diagnosed major de-
pression and lower lifetime prevalence of major depression in older adults
than those in younger adults (e.g., Weissman et al., 1988), multiple stud-
ies of depressive symptoms using primarily the Center for Epidemiologic
Studies—Depression scale (CES-D; Radloff, 1997) have revealed higher
symptom rates in older adults than those younger adults (e.g., Fiske et al.,
1998; Kasl-Godley et al., 1998; Newmann, 1989). Specifically, several re-
cent studies have described higher rates of somatic symptoms and lower
rates of certain cognitive–affective symptoms in older adults than those in
younger adults although these results are not consistent across the litera-
ture (Fiske et al., 1998; Kasl-Godley et al., 1998). A study using the Beck
Depression Inventory (BDI) (Beck et al., 1961, 1979) to compare somatic
and cognitive–affective symptoms of depression among institutionalized
older adults, noninstitutionalized older adults, and young adults (college
students) found higher total BDI and higher BDI somatic symptoms among
both groups of older adults than those among younger adults, but no dif-
ferences between BDI cognitive–affective symptoms (Zemore and Eames,
1979). A subsequent study using the Zung Self-Rating Depression Scale
(Zung, 1965) to compare somatic and psychological symptoms of depres-
sion between community-dwelling (and presumably healthier) older adults
and young adults (college students) found higher somatic symptoms only
among older women than those among younger women and no age differ-
ences among the men (Berry et al., 1984). Age-related symptom differences
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Age Differences in Symptoms of Depression and Anxiety 121

have not been well addressed in the medical outpatient population

(Alexopoulos, 1995).
Previous research has emphasized the importance of both age and co-
morbid anxiety symptoms in depression presentations. Many patients with
depressive symptoms also experience significant anxiety symptoms (Clark
and Watson, 1991). Depression and anxiety are common psychological dis-
orders in both older and younger adults with medical disorders (Hansen
et al., 2001; Nguyen et al., 2000; Silverstone, 1996) and frequently comorbid
in medical patients at both syndromal and subsyndromal levels. In addition
to patients with comorbid diagnosable depression and anxiety disorders, pri-
mary care physicians have reported a high incidence of patients who exhibit
symptoms of both depression and anxiety concurrently and are significantly
impaired, yet fail to meet criteria for either disorder (e.g., Katon and Roy-
Byrne, 1991; Liebowitz, 1993).
In this study, we characterized the prevalence of clinically significant
levels of depressive symptoms in both younger (21–59) and older (60–83)
male medical outpatients identified by their primary physicians at a Veterans
hospital and referred to a behavioral medicine clinic. The primary aim of
this study was to determine whether symptoms of depression and anxiety,
and specifically cognitive–affective versus somatic-performance symptoms
of depression, differed between the older and younger medical outpatients
referred to a behavioral medicine clinic for psychological treatment.

METHOD

Participants and Procedures

All available files from patients seen in the Behavioral Medicine Clinic
at a Veterans hospital during the 1980s were examined. These patients were
medical outpatients referred for psychological treatment by their primary
care providers primarily for pain, stress or anxiety management, or depres-
sion. The search identified a sample of 186 behavioral medicine patients who
had completed both BDI and the State-Trait Anxiety Inventory (STAI).
Both measures were frequently administered as part of routine assessment
and treatment during this time period.
Eight of these patients were female, and the remaining 178 were male.
Because the sample included so few women and numerous studies have
found increased rates of depression in women compared to men (e.g.,
Kaelber et al., 1995), with women scoring higher than men on measures
of depression including BDI (Beck et al., 1988), only the 178 male patients
were included in the analyses.
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122 Goldberg, Breckenridge, and Sheikh

Measures

BDI

BDI is a 21-item self-report questionnaire of depressive symptoms in a

4-point Likert format (0–3 scale) (Beck et al., 1961,1979). Total scores range
from 0 to 63 with higher scores indicating greater symptom severity. The
21 items assess cognitive, affective, somatic and performance symptoms of
depression over the past week. Beck and Steer (1987) have suggested that
BDI can be divided into two subscales: a cognitive–affective subscale con-
taining the first 13 items with a range of 0–39 and a somatic-performance sub-
scale consisting of the last 8 items with a range of 0–24. Cognitive–affective
symptoms include depressed mood, pessimism, sense of failure, lack of sat-
isfaction, guilt feelings, sense of punishment, self-dislike, self-accusation,
suicidal thoughts, crying, irritability, social withdrawal, and indecisiveness.
Somatic-performance symptoms include distortion of body image, work in-
hibition, sleep disturbance, fatigability, loss of appetite, weight loss, somatic
preoccupation, and loss of libido.
Beck and Steer (1987) suggest that an appropriate cutoff score for clin-
ically significant depressive symptoms on BDI varies depending on the pa-
tient population. In normal populations, total scores of 16 or more may
indicate depression although an actual diagnosis can only be made after
clinical assessment. Among depressed patients, scores of 10 or more are
considered indicative of at least mild dysphoria, with 10–15 reflecting mild
depression, 16–23 reflecting moderate depression, and 24–63 reflecting se-
vere depression (Beck and Steer, 1987; Gallagher, 1986; Katz et al., 1995;
Kendall et al., 1987). Studies of BDI in adults aged 60 and over suggest that
it is a useful screening instrument with, for example, 91% of those scoring 17
or greater being independently diagnosed with major depression and 81%
of those scoring 10 or less not meeting independent criteria for a depressive
disorder (Gallagher, 1986; Gallagher et al., 1983; Rapp et al., 1988; Zich et al.,
1990).

STAI

STAI is a self-report measure of anxiety in a 4-point Likert scale format

(1–4 scale) composed of two separate 20-item scales (Spielberger et al., 1970).
The first scale measures state anxiety, or how a respondent feels right now
(STAI-state, Form X-1), while the second scale measures trait anxiety, or
how a respondent generally feels (STAI-trait, Form X-2). Scores on each
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Age Differences in Symptoms of Depression and Anxiety 123

scale range from 20 to 80 with higher scores indicating greater levels of

anxiety.

Missing Data

Two patients were missing responses to one BDI item, two other pa-
tients were missing responses to one STAI-state item, and a fifth patient was
missing responses to two BDI items. These data points were interpolated us-
ing linear regression equations based on the other items from each patient’s
questionnaire and each patient’s age.

RESULTS

Sample Characteristics

These 178 male patients ranged in age from 21 to 83. The sample was
divided into younger adult (<60) and older adult (≥60) age groups for anal-
ysis consistent with previous literature (e.g., Gallagher et al., 1983). The
demographic and psychological characteristics of the sample by age group,
including their primary presenting complaint and ethnicity, are shown in
Table I.
A chi-square test revealed no significant differences in primary present-
ing complaint between the two age groups, χ 2 (6, N = 174) = 4.23, p = 0.65.
A chi-square test did reveal a significant difference in the rate of reporting
ethnicity between the two age groups, χ 2 (4, N = 178) = 11.59, p = 0.02,
although there was no difference in ethnicity between the two age groups
among those participants who reported an ethnicity, χ 2 (3, N = 161) = 3.85,
p = 0.28. One member of the older age group and 16 members of the
younger age group had not reported an ethnicity. To examine this differ-
ence more closely, several follow-up analyses were conducted. A chi-square
test between those 97 younger adults who had reported their ethnicity and
those 16 younger adults who had not reported their ethnicity revealed no
significant difference between the two groups in their primary presenting
complaint, χ 2 (6, N = 110) = 8.10, p = 0.23. Student’s t tests were con-
ducted to compare the 97 younger adults who had reported their ethnicity
and the 16 younger adults who had not reported their ethnicity on the depres-
sion and anxiety measures. The two groups did not differ on total BDI score,
the BDI cognitive–affective subscale, the STAI-state or the STAI-trait (all
ts < 0.9, all ps ≥ 0.4). However, the younger adults who did not report an
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124 Goldberg, Breckenridge, and Sheikh

Table I. Sample Characteristics by Age Group

Younger adults Older Adults Total Sample

(N = 113) (N = 65) (N = 178)
Variable M SD % M SD % Mean SD %

Demographic
Age 43.62 10.11 65.71 4.57 51.69 13.64
Sex (% male) 100.0 100.0 100.0
Ethnicity
Caucasian 69.9 90.8 77.5
African American 4.4 3.1 3.9
Hispanic 7.1 3.1 5.6
Asian/Pacific Islander 4.4 1.5 3.4
Unreported 14.2 1.5 9.6
Primary Presenting
Complaint
Pain 48.7 46.2 47.8
Anxiety/stress 17.7 24.6 20.2
Depression 8.8 7.7 8.4
Weight 5.3 1.5 3.9
Smoking 0.9 1.5 1.1
Serious medical 11.5 15.4 12.9
condition (e.g.
cancer, hypertension)
Other (e.g. sleep, 4.4 1.5 3.4
Type A)
Unreported 2.7 1.5 2.2
Psychological
BDI Total 15.67 9.05 12.98 7.89 14.69 8.72
BDI cognitive 8.64 6.00 5.92 5.29 7.65 5.88
affective
BDI somatic 7.04 3.91 7.06 3.44 7.04 3.74
performance
STAI-state 48.52 13.08 43.54 12.70 46.70 13.13
STAI-trait 48.07 10.21 44.29 9.43 46.69 10.08

ethnicity had significantly lower BDI somatic-performance subscale scores

(M = 4.94, SD = 3.57) than did those younger adults who reported an eth-
nicity (M = 7.38, SD = 3.87), t (111) = 2.36, p = 0.02, 95% CI = 0.39–4.49,
Cohen’s d = 0.49.

Prevalence and Severity of Depressive Symptoms

The BDI scores for the total sample are summarized in Table I. The
term “depressive symptoms” has been used because diagnosed depression
was not confirmed with standardized clinical interviews and diagnosis. For
the total sample, the average BDI scores ranged from 0 to 38 (Mdn = 14;
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Age Differences in Symptoms of Depression and Anxiety 125

Fig. 1. Beck Depression Inventory ranges by age group.

M = 14.69; SD = 8.72). Scores of 10 or higher, suggesting at least mild

levels of dysphoria, were observed in 66.9% of the population, with 23.6%
scoring between 10 and 15 suggesting a mild level of depressive symptoms,
and 43.3% scoring 16 or higher (27.0% scoring 16–23 suggesting a moderate
level of depressive symptoms, and 16.3% scoring 24 or higher suggesting
more severe depressive symptoms).
BDI scores by age group are also summarized in Table I. For younger
adults, the average BDI scores ranged from 1 to 38 (Mdn = 15; M = 15.67;
SD = 9.05). For older adults, the average BDI scores ranged from 0 to 38
(Mdn = 12; M = 12.98; SD = 7.89).
BDI ranges by age group are summarized in Fig. 1. Scores of 10 or
higher were observed in 70.8% of the younger adults, with 48.7% scoring 16
or higher. Scores of 10 or higher were observed in 60.0% of the older adults,
with 33.8% scoring 16 or higher. A chi-square test comparing the percentage
of older and younger adults in the asymptomatic (BDI, less than 10), mild
dysphoric (BDI, 10–15), and the moderate depression (BDI, 16 or higher)
categories did not reach significance, χ 2 (2, N = 178) = 3.83, p = 0.15.

Age Group Differences in Anxiety and Depressive Symptoms

Levene’s test for equality of variances was not significant for BDI total
score, the BDI cognitive–affective subscale, the BDI somatic-performance
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126 Goldberg, Breckenridge, and Sheikh

subscale, STAI-state or STAI-trait measures, indicating homogeneity of vari-

ance between the older and younger adults. Kilmogorov–Smirnov tests of
normality indicated that there were non-normal distributions for the BDI
cognitive–affective subscale for both the younger and older adults, the BDI
somatic-performance subscale for the younger adults, and the STAI-state
data for the older adults ( ps < 0.05). However, kurtosis was greater than
±1 only for BDI somatic-performance subscale for the older adults.
Student’s t-tests comparing the two age groups revealed that the older
adults have significantly lower levels of most depression and anxiety symp-
toms than do the younger adults, including total BDI scores, t(176) = 2.00,
p < 0.05, 95% CI = 0.03–5.35, Cohen’s d = 0.32; BDI cognitive–affective
subscale scores, t(176) = 3.03, p < 0.01, 95% CI = 0.95–4.48, Cohen’s
d = 0.48; STAI-state scores, t (176) = 2.47, p < 0.02, 95% CI = 1.01–8.96,
Cohen’s d = 0.39; and STAI-trait scores, t (176) = 2.44, p < 0.02, 95%
CI = 0.73–6.83, Cohen’s d = 0.38 (see Table I). The t test comparing the two
age groups yielded no significant differences in BDI somatic-performance
subscale scores, t (176) = 0.05, p = 0.96.

Exploratory Data Analyses

A multivariate analysis of variance (MANOVA) was used to investigate

differences in BDI depressive symptoms between the two age groups. For
depressive symptoms, this analysis found a main effect for age group, F (1,
9.5, N = 77) = 2.85, p < 0.001. Table II presents the univariate F tests for
the individual BDI items and effect sizes for significant F tests. Because these
univariate analyses were exploratory and tested different depressive symp-
toms, no alpha-level corrections (e.g., Bonferroni corrections) for multiple F
tests were made. The older adults reported significantly lower levels of sense
of failure, lack of satisfaction, self-dislike, self-accusation, crying, irritability,
social withdrawal, and distortion of body image than did the younger adults.
The older adults also reported significantly higher levels of loss of libido than
did the younger adults.

DISCUSSION

This study investigated whether symptoms of depression and anxiety,

and specifically cognitive–affective versus somatic-performance symptoms
of depression, differed between the older and younger medical outpatients
referred to a behavioral medicine clinic for psychological treatment. We
found that depressive symptoms were prevalent in this group as a whole
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Age Differences in Symptoms of Depression and Anxiety 127

Table II. Comparison of Beck Depression Inventory Items by Age Group

Younger adults Older adults

(N = 113) (N = 65)
Effect size
Item M SD M SD F(1, 176) (Cohen’s d)

Lower in older adults than

younger adults
Sense of failure 0.52 0.76 0.29 0.58 4.48∗ 0.34
Lack of satisfaction 0.96 0.74 0.72 0.60 4.99∗ 0.36
Self-dislike 0.69 0.76 0.40 0.58 7.14∗∗ 0.43
Self-accusation 0.89 0.86 0.49 0.69 10.36∗∗ 0.51
Crying 0.66 0.99 0.28 0.72 7.64∗∗ 0.44
Irritability 0.92 0.72 0.65 0.67 6.27∗ 0.39
Social withdrawal 0.59 0.75 0.32 0.53 6.49∗ 0.42
Distortion of body image 0.60 0.89 0.34 0.71 4.14∗ 0.33
Higher in older adults than
younger adults
Loss of libido 0.69 0.89 1.08 1.05 6.84∗ 0.40
No significant difference
between groups
Depressed mood 0.64 0.80 0.43 0.64 3.15 na
Pessimism 0.66 0.82 0.58 0.75 0.41 na
Guilt feelings 0.36 0.71 0.29 0.58 0.47 na
Sense of punishment 0.47 1.00 0.43 0.95 0.06 na
Suicidal thoughts 0.42 0.58 0.31 0.50 1.86 na
Indecisiveness 0.83 0.90 0.72 0.82 0.65 na
Work inhibition 1.27 1.09 1.32 0.95 0.13 na
Sleep disturbance 1.26 0.96 1.34 1.00 0.29 na
Fatigability 1.07 0.83 1.29 0.63 3.46 na
Loss of appetite 0.50 0.76 0.43 0.66 0.43 na
Weight loss 0.67 1.06 0.38 0.72 3.80 na
Somatic preoccupation 0.97 0.82 0.88 0.78 0.59 na
∗p < 0.05; ∗∗ p < 0.01.

as would be expected of a group referred for psychological treatment in

a behavioral medicine clinic. Among the younger adults, 70.8% scored 10
or higher on BDI, and 48.7% scored 16 or higher. Older adults had lower
but still significant rates; 60.0% scored 10 or higher on BDI and 33.8%
scored 16 or higher. Epidemiological studies have found greater rates of
depressive symptoms in older adults than in younger adults but lower rates
of diagnosed depression in older adults than those in younger adults (e.g.,
Fiske et al., 1998; Kasl-Godley et al., 1998; Newmann, 1989; Weissman et al.,
1988). In the current study, however, differences between the two groups
in the percentage of patients with different levels of symptoms were not
statistically significant.
Older adults reported lower levels of depressive symptoms on BDI and
anxiety symptoms on the STAI than did younger adults. Interestingly, the dif-
ference in depression scores was driven by cognitive–affective symptoms of
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128 Goldberg, Breckenridge, and Sheikh

depression. Older adults reported lower scores on total cognitive–affective

symptoms than did younger adults and lower scores on individual cognitive–
affective symptoms including sense of failure, lack of satisfaction, self-dislike,
self-accusation, crying, irritability, social withdrawal, and distortion of body
image. In contrast, total somatic-performance symptoms did not differ be-
tween the two age groups. The two groups differed on only one somatic-
performance symptom, with the older adults scoring higher on loss of libido
than the younger adults. These findings differed from an earlier study using
BDI that found higher total BDI and higher BDI somatic symptoms among
older adults than those among younger adults, but no differences between
BDI cognitive–affective symptoms (Zemore and Eames, 1979). However,
this earlier study selected a very different sample comparing older adults
in nursing homes or on nursing home wait-lists with college students. Many
researchers have argued that findings of elevated somatic symptoms in older
adults may be due to age-related changes and increasing rates of physical
disorders compared to physically healthier younger samples. Indeed, among
older adults, depressive disorders are more prevalent among older medical
patients than among community samples (Koenig and Blazer, 1992).
Several other studies have also examined symptom differences in med-
ical patient populations. One study of depressive symptoms among medical
outpatients with or without diagnosed minor depressive disorder found sim-
ilar symptom profiles between the older and younger patients (Oxman et al.,
1990). Looking to studies of medical inpatients, no differences in somatic
symptoms between older and younger inpatients have also been reported,
paralleling the results of the current study (Koenig et al., 1993). Similar to the
results of epidemiological studies, lower rates of major depressive disorder
and greater minor depression have also been reported in older male veteran
medical inpatients than in young male veteran medical inpatients (Koenig
et al., 1991). This finding, however, was not replicated in the current study.
This study had several important limitations. The patient sample in-
cluded only male veterans, and the majority of the patients were Cau-
casian. Differences between ethnic groups were not examined because of the
small number of patients who identified themselves as African American,
Hispanic, and Asian American. It will be important to replicate these studies
in female and multicultural populations.
While the older and younger age groups in this study did not differ in
their primary referral problem, other health data, for example more infor-
mation about the health conditions of these patients, were unavailable. It is
possible that the current results reflect the impact of differing health condi-
tions and/or medication profiles between the two age groups. The findings
in this study may also reflect an age bias in who is referred for behavioral
medicine treatment. Furthermore, although both older and younger adults
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Age Differences in Symptoms of Depression and Anxiety 129

were medical outpatients, older adults may have had different expectations
regarding their physical symptoms or may have made different social com-
parisons to their peer group. In addition, the symptom differences seen in
this study may be driven by age cohort effects and could also reflect selec-
tive mortality with, for example, less healthy people more likely to die out
over time resulting in a skewed older sample. These mechanisms should be
further investigated in future studies. Symptom presentation may also differ
in specific medical populations. Future studies may want to investigate age
differences in outpatients referred for psychological support with specific
medical disorders such as chronic pain and cardiovascular disease.
Although CES-D (Radfloff, 1977) has been primarily used in epidemio-
logical studies of depressive symptoms, BDI (Beck et al., 1961,1979) is widely
used by health practitioners as a screening instrument and an assessment of
the severity of depressive symptoms, and is widely used in depression re-
search (Beck and Steer, 1987; Perez-Stable et al., 1990). Investigations of
BDI with specific medical outpatient populations have found that in some
populations, medical patients report elevated somatic symptoms compared
to nonpatients. For example, studies with both AIDS patients and stroke pa-
tients have suggested that because of the prevalence of somatic symptoms
in these populations, the nonsomatic symptoms of BDI were best at discrim-
inating patients with depression (Kalichman et al., 2000; Stein et al., 1996).
Similarly, studies of medical inpatients have found elevations on somatic
BDI items (Emmons et al., 1987) and on some affective items but not on
cognitive items (Clark et al., 1998) compared to psychiatric inpatients. In the
BDI manual, Beck and Steer (1987) suggest that cognitive–affective items
may be especially useful with medical patients whose symptoms may be mis-
taken for depression. Because this study was conducted with patient data
from the 1980s, it used the original self-report BDI as a measure of depres-
sive symptoms. A more recently revised version of BDI, BDI-II, has been
constructed that matches DSM-IV major depressive disorder criteria more
closely than original BDI (Arnau et al., 2001; Beck et al., 1996). Another
version of BDI, the BDI-PC, has also been developed for use with primary
care patients (Beck et al., 1997; Steer et al., 1999). This version includes only
cognitive–affective items, a technique that is supported by the current study.
These current findings suggest that depressive symptoms are
highly prevalent in medical outpatients referred for behavioral medicine
treatment. Addressing even mild overall depressive symptoms (BDI 10+)
may be particularly important, especially among older medical outpatients.
Furthermore, in this particular medical outpatient population cognitive–
affective symptoms of depression appear more likely to differentiate older
and younger adults than do somatic symptoms. These findings are consistent
with research on elderly male inpatients (Clark and Steer, 1994; Rapp and
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130 Goldberg, Breckenridge, and Sheikh

Vrana, 1989) and with a general sample of medical inpatients (Cavanaugh

et al., 1983) supporting the use of the cognitive–affective subscale of the
BDI, or nonsomatic symptoms, for detecting depression. While somatic-
performance symptoms cannot be ignored, for behavioral medicine medical
outpatients targeting cognitive–affective symptoms and associated anxiety
symptoms in treatment may be especially important even in the face of con-
comitant somatic or medical complaints.

ACKNOWLEDGMENTS

This research was supported by an NIH-NHLBI Training Grant No.

5T32 H107034.

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