Investigation of the bidirectional association between cardiovascular diseases and depression

Abstract

Background: Cardiovascular diseases (CVDs) are the leading cause of disability and mortality globally. Although there has been substantial medical advancement in treating and managing CVDs, surviving CVD patients are at a greater risk of mortality and morbidity. Thus, preventative approaches aiming to identify, manage and control CVD risk factors remain the highest priority. Depression is a leading cause of disability worldwide, and it has been considered a relevant emergent, non-classical risk factor for the onset and poor prognosis of CVDs. Several systematic reviews have been published on this subject, providing evidence that depression is associated with an increased risk of CVD incidence. However, these reviews were limited by incorporating poor study designs and by focusing predominantly on a single CVD outcome. This previously fragmented investigation masked the overall picture of how strongly depression impacts each CVD subtype. At the same time, hypertension is one of the biggest risk factors for CVD; hence, the management and control of hypertension is of the utmost importance. Hypertensive patients mainly rely on antihypertensive treatment with a high dosage regimen and/or a combination of several antihypertensive drugs for the long term to control blood pressure and to consequently prevent the development or complication of CVD. Emerging evidence has investigated the effect of antihypertensive drugs in relation to depression onset, though the exact relationship remains unclear. Given that both hypertension and depression are risk factors for CVD, it becomes important that therapeutic agents to control blood pressure not have deleterious effects toward triggering depressive disorders, as both conditions will have a relevant big impact on patient’s health particularly those at high CVD risk. Objectives: This thesis has two main objectives: (1) updating the evidence of the association between depression and the risk of major subtypes of CVDs and (2) to investigate the association between exposure to antihypertensive drugs and risk of depression incident. Method: For the first objective, I conducted a systematic review and meta-analyses. Depression in the review referred to depressive symptoms or clinical depression and main outcomes of interest were incidence of fatal/non-fatal coronary heart diseases (CHD), heart failure (HF) and stroke, each measured as a single endpoint and reported as hazard ratio (HR) and 95% confidence interval (CI). The results for the systematic review were divided into three main results chapters based on the main outcomes (4-6). For the second objective, a secondary analysis of existing data held in the Glasgow Blood Pressure Clinic (GBPC) was conducted. Exposure was antihypertensive drugs which involves the five major classes including calcium channel blocker (CCB), beta-blocker (BB), angiotensin converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) and thiazide diuretic (TZD). The primary outcome was depression as indicated by the first prescription of antidepressants drug. Main findings of this analysis are presented in chapter 7. Results: Chapter 4 evaluated the relation between depression and risk of stroke. The meta-analysis included 19 studies enrolling 3,154,290 participants, with an average follow-up of 11.2 years. The pooled estimated risk revealed that baseline depression is associated with a 22% (HR = 1.22, 95% CI, 1.11-1.33) increased risk of developing first-ever stroke, with evidence of substantial statistical heterogeneity between studies (I2 = 67%). The magnitude of risk presented in this study is more modest than that previously reported in past systematic reviews for stroke outcomes. Sensitivity analyses were carried out to assess for a possible reverse causality (i.e. depression manifested as an acute sickness response to a subclinical stroke). This w