Pathophysiologic Mechanisms of Cardiovascular Disease in Patients With Bipolar Disorder

Bipolar disorder (BD) is a mental health condition characterized by periodic intense emotional states ranging between mania and depression. It has a strong association with comorbid cardiovascular disease (CVD), which contributes greatly to the mortality among this patient population. While a part of this association can be attributed to antipsychotic medication use, this systematic review highlights and offers a comprehensive analysis of other pathophysiological mechanisms that drive CVD in BD patients beyond pharmacologic and psychosocial factors. Through a systematic search of EMBASE, OVID, and Web of Science databases, a total of 282 full articles were screened, with 31 total studies being included. To avoid bias, four authors reviewed these articles and discussed conflicts until a consensus was reached. This systematic review thus synthesized the data into five broad categories of pathophysiological mechanisms: genetics, inflammatory markers, endothelial dysfunction, oxidative stress, and structural cardiovascular changes that contribute to CVD in the BD population. A further study into how these mechanisms are integrated in the BD population showed that there were 129 shared loci between BD and CVD, along with specific gene polymorphisms that are associated with cardiomyopathy and arrhythmias. Furthermore, elevated levels of inflammatory markers in BD patients contribute to atherogenesis via oxidative stress. In turn, increased atherogenesis leads to elevations in coronary calcium and left ventricular mass index, especially in male patients with BD. The elevations in inflammatory markers and changes in endothelial function appear to be associated with mood lability in BD patients. These findings further cement how fundamentally BD as an inflammatory condition contributes to the CVD burden in its population. This paper thus suggests proactive measures to be implemented in healthcare settings to assess the multiple pathophysiologic mechanisms responsible for the increased risk of CVD in BD patients. Further research in the realm of genetic biomarkers is vital to explicate the pathogenesis of CVD in BD patients.