Association between depression and cardiovascular disease: A review based on QT dispersion

Abstract

Depression is highly prevalent in the world and is related to the risk of developing cardiovascular disease (CVD) in previously cardiac healthy individuals. However, uncertainties remain on the pathophysiological mechanisms underlying the association between depression and CVD, including subclinical atherosclerosis. Depression-related dysfunctions in the autonomic nervous system and hypothalamic–pituitary– adrenal axis seem to play a role in the development of CVD. The effect of autonomic imbalance on the heart is commonly estimated by QT dispersion (QTD) values and heart rate variability analyses. Both are related to autonomic modulation. In addition, QTD also reflects ventricular repolarization abnormalities. Previous investigators have reported that QTD is higher in clinically healthy patients with anxiety as compared with controls. As there is an association between anxiety and the somatic symptoms of depression, this study aimed to conduct a systematic review and an exploratory meta-analysis of the available published literature related to QTD in depressed patients without cardiovascular disease. We performed a search of MEDLINE and EMBASE from January 1990 to December 2018. An all-fields search for index terms (‘‘depression’’ OR ‘‘depressive’’ OR ‘‘depressed’’) AND (‘‘QT dispersion’’ OR ‘‘QT interval’’) was done. We included all articles that evaluated and reported data about the relationship between QT dispersion on electrocardiogram and depression diagnosed by Diagnostic and Statistical Manual of Mental Disorders criteria in patients without CVD. For each study, effect sizes comparing the performance of depressive and control groups on each measure (crude QTD and heart rate-corrected QTD) were calculated as Cohen’s d. The percentage of the total variability in the set of effect sizes due to true heterogeneity was tested with the I statistic. After a systematic literature search, a total of 654 records was identified. Three articles were included in the final analysis, which encompassed 187 cardiac healthy subjects (91 depressed and 96 non-depressed). There were 141 (75.4%) women (73 in the non-depressed group, and 68 in the depressed group). Age means did not differ between depressed (48.1 years) and control groups (49.6 years). In all the studies, the values of crude QTD and heart rate-corrected QTD were significantly higher in depressed patients. For each one of the three studies, the values of crude and rate-corrected QTD in the depressed groups (Table 1) always exceeded 50 ms, which is known as the normal upper limit. In all the studies, the QTD measurements were significantly higher in the depressed patients. The aggregated standardized difference in the means was equal to 1.493 (standard error: 0.36; Z-value1⁄4 4.135, p< 0.001) for crude QTD. For heart rate-corrected QTD, the aggregated difference was1.685 (standard error: 0.386; Z-value1⁄4 4.294, p< 0.001). The I values for crude QTD and heart rate-corrected QT dispersion varied from 73% to 75%. Nahshoni et al. found autonomic nervous system disturbance and higher arrhythmia risk in depressed individuals without heart disease, but the patients were taking antidepressants. Tosu et al. showed that non-medicated patients with a first-time diagnosis of depression had significantly higher QTD compared with healthy volunteers, but patients with hypertension or diabetes, and smokers, were not excluded. Tolentino and Schmidt reported higher QTD in non-smoking, physically healthy depressed women who were not taking antidepressants. In addition, they found that QTD was intriguingly associated with depression severity: moderately depressed patients showed greater impairment in cardiac autonomic modulation (increased QTD) as compared with either severely depressed patients and non-depressed subjects. In a previous meta-analysis, somatic/affective depressive