Annotated Abstracts of Journal Articles
2014, 1st Quarter
Annotations by Jeff Huffman, MD, FAPM
March 2014
ANNOTATION (Jeff Huffman)
The Finding: Despite moderate heterogeneity of individual studies, the comprehensive systematic review found rather clear connections between depression and adverse outcomes post-ACS. Based on this review and additional aspects of this association (e.g., plausible mechanism connecting depression and adverse outcomes), the committee concluded that depression should be considered a risk factor for adverse events after an ACS.
Strengths and Weaknesses: Strengths included a careful and comprehensive systematic review and consideration of multiple criteria required to reach risk factor status. The authors also carefully outlined and discussed sources of heterogeneity. Weaknesses of the review included inclusion only of articles in English, only considering post-ACS outcomes (rather than onset of cardiac illness or other conditions), and the inherent limitations and heterogeneity of the reviewed studies. With regard to the assignment as a risk factor, an important weakness was that the authors did not include the criterion that treatment/reduction of the risk factor leads to improved prognosis (not yet proven), and that it includes only a very specific condition rather than coronary artery disease overall.
Relevance: This article may prove somewhat controversial for the reasons above. However, at this point, there is little doubt that depression is linked to cardiac mortality after ACS, and while there has not yet been an adequately powered study proving that depression treatment leads to mortality reduction, there have been multiple studies showing depression care management of cardiac patients leads to improved health-related quality of life and function. Whether or not one can consider depression a “risk factor,” it is clearly important to address in post-ACS patients.
Background: Although prospective studies, systematic reviews, and meta-analyses have documented an association between depression and increased morbidity and mortality in a variety of cardiac populations, depression has not yet achieved formal recognition as a risk factor for poor prognosis in patients with acute coronary syndrome by the American Heart Association and other health organizations. The purpose of this scientific statement is to review available evidence and recommend whether depression should be elevated to the status of a risk factor for patients with acute coronary syndrome.
Methods and Results: Writing group members were approved by the American Heart Association’s Scientific Statement and Manuscript Oversight Committees. A systematic literature review on depression and adverse medical outcomes after acute coronary syndrome was conducted that included all-cause mortality, cardiac mortality, and composite outcomes for mortality and nonfatal events. The review assessed the strength, consistency, independence, and generalizability of the published studies. A total of 53 individual studies (32 reported on associations with all-cause mortality, 12 on cardiac mortality, and 22 on composite outcomes) and 4 meta-analyses met inclusion criteria. There was heterogeneity across studies in terms of the demographic composition of study samples, definition and measurement of depression, length of follow-up, and covariates included in the multivariable models. Despite limitations in some individual studies, our review identified generally consistent associations between depression and adverse outcomes.
Conclusions: Despite the heterogeneity of published studies included in this review, the preponderance of evidence supports the recommendation that the American Heart Association should elevate depression to the status of a risk factor for adverse medical outcomes in patients with acute coronary syndrome.
ANNOTATION (Jeff Huffman)
The Finding: PTSD symptoms one month after ACS were greater in patients with ongoing depression and in those who were evaluated at times of ED crowding, and there was a significant interaction such that depressed patients appeared to be more vulnerable to the PTSD-related effects of crowding.
Strengths and Weaknesses: The strengths of this work include a relatively careful and prospective design with serial systematic assessments of patients; this is also an interesting and novel field of study in cardiac psychiatry. Weaknesses include the use of a PTSD numerical scale (rather than an actual structured diagnostic interview), and a relatively small sample from a single site in this exploratory trial.
Relevance: This confirms two potential risk factors for development of PTSD post-ACS, and suggests a significant interaction: that depressed patients will be much more sensitive to the ED crowding effects that have been linked to subsequent PTSD. Clinicians may wish to be attentive to the possibility of PTSD in depressed post-ACS patients, especially those patients who had particularly serious medical courses (e.g., ICU admission) and/or who presented with ACS in chaotic environments.
Most acute coronary syndrome (ACS) patients first present to the emergency department (ED). Patients who present to overcrowded EDs develop more posttraumatic stress disorder (PTSD) symptoms due to the ACS than do patients who present to less crowded EDs, but no research has indicated whether some patients may be more vulnerable to the effects of ED crowding than others. In an observational cohort study, we tested whether depressed patients developed more ACS-induced PTSD symptoms under conditions of ED overcrowding than patients who had never been depressed. We conducted psychiatric interviews for current and past depression in 189 ACS patients admitted through the ED within a week of hospitalization, and screened for PTSD symptoms 1 month later using the Impact of Events Scale-Revised. The sum of ED admissions for the 12 h prior to and 12 h after each participant’s admission was categorized into tertiles for analysis. In a 3 (ED crowding tertile) by 3 (never, past, current depression) analysis of covariance adjusted for demographic and clinical factors, we found significant effects for ED crowding, depression status, and their interaction (all p’s < .05). Mean PTSD scores were significantly higher (p = .005) for participants who were currently depressed and were treated during times of high ED crowding [25.38, 95% CI = 16.18-34.58], or had a history of depression [10.74, 95% CI = 6.86-14.62], relative to all other participants, who scored 5.6 or less. These results suggest that depressed ACS patients may be most vulnerable to the stress-inducing effects of ED crowding.
ANNOTATION (Jeff Huffman)
The Finding:
Patients diagnosed as depressed using the HADS just prior to ICD placement had greater all-cause mortality over the next ~4 years, though there was not an increased rate of appropriate ICD firing in patients with depression.
Strengths and Weaknesses: Strengths of the trial included the prospective design of the trial, the relatively long-term follow-up, a good sample of both depressed (n>100) and non-depressed participants, and high retention. A substantial weakness is the lack of data about the cause of mortality for these patients; there was also no detail on clinical or medication changes that occurred during the follow-up period. Finally, using the HADS on the day before ICD placement may have picked up transient distress rather than depression meeting full diagnostic criteria.
Relevance: These are interesting findings: depression is again linked to mortality in a cardiac cohort, but it is very interesting to note that in a cohort at high risk for ventricular arrhythmias, it did not appear that depressed patients had higher rates of these arrhythmias. So how did they die? Further study in this cohort is needed to identify the cause of death linked to depression in this high-risk cohort, but yet again this work signals a need to address depression in high-risk cardiac patients.
Objective: We examined whether depression is independently associated with implantable cardioverter defibrillator (ICD) therapy for ventricular tachyarrhythmias and mortality.
Methods: A cohort of 430 consecutive patients with a first-time ICD (79% men; mean [standard deviation] age = 57.8 [12.1] years) completed the Hospital Anxiety and Depression Scale 1 day before implantation. During follow-up, the ICD was interrogated at 3-month intervals. Cox proportional hazard regression analyses were used to examine the impact of depression on time to first appropriate ICD therapy and all-cause mortality during a median follow-up period of 3.8 years.
Results: Of all patients, 108 (25.1%) were depressed. Depression was not associated with time to first appropriate ICD therapy (unadjusted hazard ratio [HR] = 1.07, 95% confidence interval [CI] = 0.73-1.56). However, depression was associated with an increased risk for all-cause mortality (unadjusted HR = 2.18, 95% CI = 1.36-3.49). Depression remained independently associated with all-cause mortality (HR = 1.94, 95% CI = 1.06-3.54, p = .031), after adjusting for demographic and clinical characteristics. Patients who remained depressed during the first 3 months after implantation were at greatest risk for dying (HR = 2.88, 95% CI = 1.29-6.45, p = .010).
Conclusions: The current study showed that depression at the time of implant is not associated with time to first appropriate ICD therapy but almost doubled the risk for all-cause mortality in patients with an ICD. Patients with persistent depression during the first 3 months after implantation face the greatest risk of dying. Current evidence indicates that multifactorial interventions are likely to be the most successful in terms of reducing distress. Whether this translates into enhanced survival has yet to be determined.