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      Severity of Depression, Anxious Distress and the Risk of Cardiovascular Disease in a Swedish Population-Based Cohort

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          Depression is known to be associated with cardiovascular diseases (CVD). This population-based cohort study aimed to determine the association between depression of varying severity and risk for CVD and to study the effect of concomitant anxious distress on this association.


          We utilized data from a longitudinal cohort study of mental health, work and relations among adults (20–64 years), with a total of 10,443 individuals. Depression and anxious distress were assessed using psychiatric rating scales and defined according to DSM-5. Outcomes were register-based and self-reported cardiovascular diseases.


          Overall increased odds ratios of 1.5 to 2.6 were seen for the different severity levels of depression, with the highest adjusted OR for moderate depression (OR 2.1 (95% CI 1.3, 3.5). Similar odds ratios were seen for sub-groups of CVD: ischemic/hypertensive heart disease and stroke, 2.4 (95% CI 1.4, 3.9) and OR 2.1 (95%CI 1.2, 3.8) respectively. Depression with anxious distress as a specifier of severity showed OR of 2.1 (95% CI 1.5, 2.9) for CVD.


          This study found that severity level of depression seems to be of significance for increased risk of CVD among depressed persons, although not in a dose-response manner which might be obscured due to treatment of depression. Further, we found a higher risk of CVD among depressed individuals with symptoms of anxious distress.

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          Most cited references 38

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          Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies.

          With negative treatment trials, the role of depression as an aetiological or prognostic factor in coronary heart disease (CHD) remains controversial. We quantified the effect of depression on CHD, assessing the extent of confounding by coronary risk factors and disease severity. Meta-analysis of cohort studies measuring depression with follow-up for fatal CHD/incident myocardial infarction (aetiological) or all-cause mortality/fatal CHD (prognostic). We searched MEDLINE and Science Citation Index until December 2003. In 21 aetiological studies, the pooled relative risk of future CHD associated with depression was 1.81 (95% CI 1.53-2.15). Adjusted results were included for 11 studies, with adjustment reducing the crude effect marginally from 2.08 (1.69-2.55) to 1.90 (1.49-2.42). In 34 prognostic studies, the pooled relative risk was 1.80 (1.50-2.15). Results adjusted for left ventricular function result were available in only eight studies; and this attenuated the relative risk from 2.18 to 1.53 (1.11-2.10), a 48% reduction. Both aetiological and prognostic studies without adjusted results had lower unadjusted effect sizes than studies from which adjusted results were included (P<0.01). Depression has yet to be established as an independent risk factor for CHD because of incomplete and biased availability of adjustment for conventional risk factors and severity of coronary disease.
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            Population-based study of first onset and chronicity in major depressive disorder.

            There are no studies of the natural history of major depressive disorder that lack prevalence and clinic biases. To estimate risk factors for first lifetime onset and parameters of chronicity following the first episode, including duration, recovery, and recurrence, and to search for predictors of each parameter. Prospective population-based cohort study with 23 years of follow-up. East Baltimore, Maryland, an urban setting. Probability sample of 3481 adult household residents in 1981, including 92 with first lifetime onset of major depressive disorder during the course of the follow-up, and 1739 other participants followed up for at least 13 years. Diagnostic Interview Schedule and Life Chart Interview. Female participants showed higher risk of onset of disorder, longer duration of episodes, and a nonsignificant tendency for higher risk of recurrence. Sex was not related to recovery. The median episode length was 12 weeks. About 15% of 92 individuals with first episodes did not have a year free of episodes, even after 23 years. About 50% of first episode participants recovered and had no future episodes. The evolution of the course was relatively stable from first to later episodes. Individuals with 1 or 2 short alleles of the serotonin transporter gene were at higher risk for an initial episode, but experienced episodes of shorter duration. There were few strong predictors of recovery or recurrence. Major depressive disorder is unremitting in 15% of cases and recurrent in 35%. About half of those with a first-onset episode recover and have no further episodes.
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              Depression and anxiety as predictors of 2-year cardiac events in patients with stable coronary artery disease.

              Anxiety and depression are associated with mechanisms that promote atherosclerosis. Most recent studies of emotional disturbances in coronary artery disease (CAD) have focused on depression only. To assess the 2-year cardiac prognostic importance of the DSM-IV-based diagnoses of major depressive disorder (MDD) and generalized anxiety disorder (GAD) and self-report measures of anxiety and depression and their co-occurrence. Two-year follow-up of 804 patients with stable CAD (649 men) assessed using the Beck Depression Inventory II (BDI-II), the anxiety subscale of the Hospital Anxiety and Depression Scale (HADS-A), and the Structured Clinical Interview for DSM-IV (masked to self-reports) 2 months after acute coronary syndromes. Major adverse cardiac events (MACEs) (cardiac death, myocardial infarction, cardiac arrest, or nonelective revascularization) in the 2 years after baseline. Of the 804 patients, 57 (7.1%) met the criteria for MDD and 43 (5.3%) for GAD (11 [1.4%] had comorbidity); 220 (27.4%) had elevated BDI-II scores (> or = 14), and 333 (41.4%) had elevated HADS-A scores (> or = 8), with 21.1% overlap. MDD (odds ratio [OR], 2.85; 95% confidence interval [CI], 1.62-5.01), GAD (OR, 2.09; 95% CI, 1.08-4.05), elevated BDI-II (OR, 1.75; 95% CI, 1.21-2.54), elevated HADS-A score (OR, 1.67; 95% CI, 1.18-2.37), and continuous standardized scores on the BDI-II (OR, 1.34; 95% CI, 1.11-1.62) and the HADS-A (OR, 1.38; 95% CI, 1.16-1.63) all predicted MACEs. After covariate control, only the P value associated with the continuous BDI-II score increased to above .10. Most of the risk associated with elevated symptoms was in patients with psychiatric disorders. However, patients with comorbid MDD and GAD or elevated anxiety and depression symptoms were not at greater MACE risk than those with only 1 factor. Anxiety and depression predict greater MACE risk in patients with stable CAD, supporting future research into common genetic, environmental, and pathophysiologic pathways and treatments.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                15 October 2015
                : 10
                : 10
                [1 ]Karolinska Institutet, Department of Public Health Sciences, Stockholm, Sweden
                [2 ]Department of Medicine, Aga Khan University, Karachi, Pakistan
                [3 ]Department of Community Health Sciences and Medicine, Aga Khan University, Karachi, Pakistan
                [4 ]Departments of Public Health and General Practice, Faculty of Medicine, Norwegian University of Science and Technology, Trondheim, Norway
                Chiba University Center for Forensic Mental Health, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: AA YF JM. Performed the experiments: AA YF RI IJ JM. Analyzed the data: AA. Contributed reagents/materials/analysis tools: JM YF. Wrote the paper: AA YF RI IJ JM. Approved the final version of the manuscript: AA YF RI IJ JM.


                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

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                Figures: 0, Tables: 2, Pages: 12
                Funding for the PART was provided by the Swedish Research Council (to YF, the Stockholm County Council (ALF) (to YF), the Karolinska Institutet Faculty Funds (to YF). The PhD student support was provided by Faculty development award, Aga Khan University, Karachi, Pakistan. None of the funding organizations have had any influence on the design and conduct of the study; the collection, management, analysis or interpretation of the data; or the preparation, review or approval of the manuscript.
                Research Article
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                Data are ethically restricted for patient privacy concerns. However, de-identified, participant level data can be obtained pending ethical approval. Please send requests for a minimal dataset to Dr. Yvonne Forsell, yvonne.forsell@ .



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