Methods

Participants were hospitalized patients with ACS enrolled in the Prescription Usage, Lifestyle, and Stress Evaluation (PULSE) study, a prospective cohort study of the prognostic risk conferred by depression at the time of an ACS. Patients with unstable angina pectoris or acute ST-segment and non–ST-segment elevation myocardial infarction (MI) were recruited from the Columbia University Medical Center within 1 week of hospitalization for their ACS. Patients completed a structured psychiatric interview 3 to 7 days after discharge to ascertain their depression status, and they returned for a follow-up visit 1 month later. The present analyses include 472 participants who completed the self-report anergia questionnaire during the baseline (in-hospital) interview. Excluded from bivariate analyses were 28 participants with missing data on anergia at baseline. Data collection occurred from February 2009 through June 2010. The institutional review board of Columbia University approved this study, and all participants provided informed consent.

Using a questionnaire that has been included in previous studies, anergia was defined by participants’ binary responses (yes/no) to 7 items related to energy level. It was operationalized as the presence of the cardinal criterion “sits around a lot for lack of energy” and any 2 of the 6 following additional criteria: “recently not enough energy,” “felt slowed physically in the previous month,” “doing less than usual in the previous month,” “any slowness is worse in the morning,” “wakes up feeling tired,” and/or “naps (>2 hours) during the day.” Participants completed this questionnaire, which has acceptable internal reliability, face validity, and predictive validity for morbidity and mortality, during their in-hospital interview.

At baseline participants identified their ethnicity (Hispanic vs non-Hispanic), race (white vs black vs other), years of education, partner status, participation in regular exercise, and cigarette smoking status. Medical charts were used to ascertain previous cardiovascular disease and cardiac procedures (angina pectoris, MI, percutaneous coronary intervention, coronary artery bypass grafting, New York Heart Association heart failure class), previous cerebrovascular disease (stroke, transient ischemic attack), and other chronic medical conditions (respiratory diseases, liver diseases, rheumatologic diseases, and stomach ulcers). Age and gender were recorded for each patient. The Global Registry of Acute Coronary Events (GRACE) risk score was used to calculate 6-month mortality risk after ACS, and medical co-morbidities were assessed using the Charlson Co-morbidity Index.

Blood samples were collected from a subset of participants (n = 259), and serum concentrations of high-sensitivity C-reactive protein were determined using a high-sensitivity enzyme-linked immunoadsorbent assay. Left ventricular ejection fraction was assessed by electrocardiography, ventriculography, or nuclear stress testing. ACS type (unstable angina pectoris, ST-segment MI, non–ST-segment MI) was determined from chart review by study cardiologists. In-hospital hematocrit (percentage), thyroid-stimulating hormone, and serum creatinine at admission were ascertained from patient charts and used to determine anemia status, thyroid function, and estimated glomerular filtration rate, respectively. Probable chronic kidney disease was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m ² , and anemia was defined as a hematocrit level <36% for women and <39% for men.

Participants were evaluated for symptoms of depression at baseline based on their responses to the 21-item Beck Depression Inventory (BDI) and the 9-item Patient Health Questionnaire (PHQ-9). Symptoms of anxiety were determined based on participants’ responses to the Hospital Anxiety and Depression Scale—Anxiety subscale.

Three to 7 days after their discharge from the hospital, participants were telephoned and evaluated by a trained mental health professional for a depressive disorder using the Diagnostic Interview and Structured Hamilton (DISH), a gold-standard structured interview that was developed to screen cardiac patients for depressive disorders. The DISH is used to diagnose major and minor depression according to criteria in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Revision . Consistent with other studies of depression in patients with ACS, diagnostic criteria were modified such that participants received a diagnosis if they met the symptom criteria for a major or minor depressive episode for ≥7 days (instead of the usual 14 days) or if they reported taking antidepressant medication. Participants who did not complete the DISH but who met criteria for a major depressive or other depressive syndrome on the PHQ-9 according to a validated diagnostic algorithm were considered to have a current depressive disorder. Current and past depressive disorders were identified separately using time periods included in the DISH.

One month after their discharge from the hospital, participants returned for a follow-up visit during which they completed the Pittsburgh Sleep Quality Inventory, a measurement that has been used to identify subjects with poor sleep quality. Poor sleep quality was defined categorically as a global Pittsburgh Sleep Quality Inventory score >5, a cutoff with acceptable diagnostic sensitivity and specificity. Participants also completed a pain item from the 12-item Short Form Health Survey, which asks “how much did pain interfere with your normal work (… both work outside the home and housework).” Responses were provided on a 5-point scale (1 = “not at all” to 5 = “extremely”) and converted to T-scores using normative data. Higher T-scores indicate less pain.

The prevalence of anergia and its components was determined. To investigate associations of anergia with clinical–demographic measurements, we performed bivariate analyses comparing those with to those without anergia. Chi-square analyses with Fisher’s exact test were used for dichotomous variables and independent-samples t tests were used for continuous variables. A multivariable logistic regression model was estimated to ascertain which clinical–demographic variables were independently associated with anergia. This model included all variables that were significant at a p value <0.10 in bivariate analysis and any clinically relevant variables identified a priori (e.g., age, gender, race, and partner status). Multiple imputation using a fully conditional specification method was performed to account for missing data in the multivariable logistic regression model. Data are presented as odds ratios (ORs) and 95% confidence intervals (CIs). A 2-tailed p value <0.05 was considered statistically significant.

The PULSE study includes several measures of depression (BDI, PHQ-9, current depressive disorder, and previous depressive disorder), and a primary aim of the present analyses was to further elucidate the association of anergia with depression. Given that the strong intercorrelations among these depression measures would affect parameter estimates in any multivariable regression analyses that included them all simultaneously, we decided a priori to include current depressive disorder as the measure of depression in our multivariable model because it is based on the gold-standard DISH assessment for depression diagnosis. Sensitivity analyses were subsequently conducted in which we substituted the BDI and PHQ-9 for current depressive disorder in the multivariable model. Because history of several cardiovascular and noncardiac diseases is captured in the Charlson Co-morbidity Index score, we likewise made the a priori decision to include only the Charlson Co-morbidity Index score in our multivariable model.

Given the strong association between depression and anergia reported in a previous study and the strong resemblance of depressive symptoms and symptoms of anergia, we further sought to identify clinical–demographic factors that accompany anergia in those without a current depressive disorder. To do so, we performed bivariate analyses comparing those with to those without anergia in participants without a depressive disorder. Because the distribution of high-sensitivity C-reactive protein concentration was not normal, this variable was logarithmically transformed for all analyses. All analyses were performed in SPSS 18.0.

Results

Prevalence of the criteria used to identify participants with anergia in the PULSE cohort is presented in Table 1 . At least 1 complaint of anergia was reported by 79.9% of patients (n = 377) at baseline, and 32% of participants (n = 153) met criteria for anergia at baseline.

Clinical–demographic characteristics of participants, stratified by anergia status at baseline, are listed in Table 2 . Participants’ ages ranged from 26 to 96 years. The cohort included a multiethnic population of predominately non-Hispanic participants, although participants of Hispanic ethnicity constituted approximately 32% of the sample. Most participants were white, men, and partnered or married. The most common type of ACS with which participants presented to the hospital was unstable angina pectoris.

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