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      Should Global Burden of Disease Estimates Include Depression as a Risk Factor for Coronary Heart Disease?

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          Abstract

          The 2010 Global Burden of Disease Study estimates the premature mortality and disability of all major diseases and injuries. In addition it aims to quantify the risk that diseases and other factors play in the aetiology of disease and injuries. Mental disorders and coronary heart disease are both significant public health issues due to their high prevalence and considerable contribution to global disease burden. For the first time the Global Burden of Disease Study will aim to assess mental disorders as risk factors for coronary heart disease. We show here that current evidence satisfies established criteria for considering depression as an independent risk factor in development of coronary heart disease. A dose response relationship appears to exist and plausible biological pathways have been proposed. However, a number of challenges exist when conducting a rigorous assessment of the literature including heterogeneity issues, definition and measurement of depression and coronary heart disease, publication bias and residual confounding. Therefore, despite some limitations in the available data, it is now appropriate to consider major depression as a risk factor for coronary heart disease in the new Global Burden of Disease Study.

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          Global mortality, disability, and the contribution of risk factors: Global Burden of Disease Study.

          Prevention and control of disease and injury require information about the leading medical causes of illness and exposures or risk factors. The assessment of the public-health importance of these has been hampered by the lack of common methods to investigate the overall, worldwide burden. The Global Burden of Disease Study (GBD) provides a standardised approach to epidemiological assessment and uses a standard unit, the disability-adjusted life year (DALY), to aid comparisons. DALYs for each age-sex group in each GBD region for 107 disorders were calculated, based on the estimates of mortality by cause, incidence, average age of onset, duration, and disability severity. Estimates of the burden and prevalence of exposure in different regions of disorders attributable to malnutrition, poor water supply, sanitation and personal and domestic hygiene, unsafe sex, tobacco use, alcohol, occupation, hypertension, physical inactivity, use of illicit drugs, and air pollution were developed. Developed regions account for 11.6% of the worldwide burden from all causes of death and disability, and account for 90.2% of health expenditure worldwide. Communicable, maternal, perinatal, and nutritional disorders explain 43.9%; non-communicable causes 40.9%; injuries 15.1%; malignant neoplasms 5.1%; neuropsychiatric conditions 10.5%; and cardiovascular conditions 9.7% of DALYs worldwide. The ten leading specific causes of global DALYs are, in descending order, lower respiratory infections, diarrhoeal diseases, perinatal disorders, unipolar major depression, ischaemic heart disease, cerebrovascular disease, tuberculosis, measles, road-traffic accidents, and congenital anomalies. 15.9% of DALYs worldwide are attributable to childhood malnutrition and 6.8% to poor water, and sanitation and personal and domestic hygiene. The three leading contributors to the burden of disease are communicable and perinatal disorders affecting children. The substantial burdens of neuropsychiatric disorders and injuries are under-recognised. The epidemiological transition in terms of DALYs has progressed substantially in China, Latin America and the Caribbean, other Asia and islands, and the middle eastern crescent. If the burdens of disability and death are taken into account, our list differs substantially from other lists of the leading causes of death. DALYs provide a common metric to aid meaningful comparison of the burden of risk factors, diseases, and injuries.
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            Impact of Psychological Factors on the Pathogenesis of Cardiovascular Disease and Implications for Therapy

            Recent studies provide clear and convincing evidence that psychosocial factors contribute significantly to the pathogenesis and expression of coronary artery disease (CAD). This evidence is composed largely of data relating CAD risk to 5 specific psychosocial domains: (1) depression, (2) anxiety, (3) personality factors and character traits, (4) social isolation, and (5) chronic life stress. Pathophysiological mechanisms underlying the relationship between these entities and CAD can be divided into behavioral mechanisms, whereby psychosocial conditions contribute to a higher frequency of adverse health behaviors, such as poor diet and smoking, and direct pathophysiological mechanisms, such as neuroendocrine and platelet activation. An extensive body of evidence from animal models (especially the cynomolgus monkey, Macaca fascicularis) reveals that chronic psychosocial stress can lead, probably via a mechanism involving excessive sympathetic nervous system activation, to exacerbation of coronary artery atherosclerosis as well as to transient endothelial dysfunction and even necrosis. Evidence from monkeys also indicates that psychosocial stress reliably induces ovarian dysfunction, hypercortisolemia, and excessive adrenergic activation in premenopausal females, leading to accelerated atherosclerosis. Also reviewed are data relating CAD to acute stress and individual differences in sympathetic nervous system responsivity. New technologies and research from animal models demonstrate that acute stress triggers myocardial ischemia, promotes arrhythmogenesis, stimulates platelet function, and increases blood viscosity through hemoconcentration. In the presence of underlying atherosclerosis (eg, in CAD patients), acute stress also causes coronary vasoconstriction. Recent data indicate that the foregoing effects result, at least in part, from the endothelial dysfunction and injury induced by acute stress. Hyperresponsivity of the sympathetic nervous system, manifested by exaggerated heart rate and blood pressure responses to psychological stimuli, is an intrinsic characteristic among some individuals. Current data link sympathetic nervous system hyperresponsivity to accelerated development of carotid atherosclerosis in human subjects and to exacerbated coronary and carotid atherosclerosis in monkeys. Thus far, intervention trials designed to reduce psychosocial stress have been limited in size and number. Specific suggestions to improve the assessment of behavioral interventions include more complete delineation of the physiological mechanisms by which such interventions might work; increased use of new, more convenient "alternative" end points for behavioral intervention trials; development of specifically targeted behavioral interventions (based on profiling of patient factors); and evaluation of previously developed models of predicting behavioral change. The importance of maximizing the efficacy of behavioral interventions is underscored by the recognition that psychosocial stresses tend to cluster together. When they do so, the resultant risk for cardiac events is often substantially elevated, equaling that associated with previously established risk factors for CAD, such as hypertension and hypercholesterolemia.
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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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                Author and article information

                Journal
                BMC Med
                BMC Medicine
                BioMed Central
                1741-7015
                2011
                3 May 2011
                : 9
                : 47
                Affiliations
                [1 ]Queensland Centre for Mental Health Research, Cnr Ellerton Drive and Wolston Park Rd, Wacol, Qld 4074, Australia
                [2 ]School of Population Health, University of Queensland, Herston Road, Herston, Qld, 4006, Australia
                [3 ]School of Psychology and Griffith Health Institute, Griffith University, Parklands Drive, Southport, Qld 4215, Australia
                Article
                1741-7015-9-47
                10.1186/1741-7015-9-47
                3101124
                21539732
                f8bf5c44-e470-44e0-9cb4-c7e4b03ade5d
                Copyright ©2011 Charlson et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 February 2011
                : 3 May 2011
                Categories
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                Medicine
                Medicine

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