Depression and HIV infection: Risk factors for cardiovascular disease

Depression, a common mental health disorder, is associated with higher risk of cardiovascular disease (CVD). Adults with HIV infection are often burdened with depression. Although both depression and HIV infection are risk factors for CVD, previous studies have not explored how co-occurring depression and HIV are associated with CVD outcomes or underlying physiology. The aim of this dissertation was to (i) measure the risk of incident heart failure (HF) with co-occurring major depressive disorder (MDD) and HIV infection; (ii) measure biomarkers of inflammation, coagulation, monocyte activation, and metabolism with depression and HIV infection; and (iii) provide a comprehensive biomarker profile associated with symptoms of major depression in HIV+ and HIV- participants. We analyzed data from the Veterans Aging Cohort Study (VACS), a prospective study of HIV+ and HIV- veterans matched on age, sex, race/ethnicity, and geographical region. In a sample of 81,427 participants, we found that those with co-occurring HIV infection and MDD had significantly higher risk of incident HF compared to HIV- participants without MDD, after adjusting for covariates. In a subset of 2,099 participants, we determined that depression was associated with higher concentrations of interleukin-6 and soluble CD14 (biomarkers for inflammation and monocyte activation) in HIV- participants but not HIV+ participants. HIV+ participants had higher concentrations of glucose and triglycerides and lower concentrations of high-density lipoprotein cholesterol with depression. In a smaller sample with more extensive biomarker data, we found a significant association between depression and lower concentrations of vascular endothelial growth factor in HIV+ participants. Neither biomarker study supported the hypothesis that co-occurring depressive symptoms and HIV infection would interact and produce excessively high concentrations of these biomarkers. The findings from this dissertation are significant for public health research and practice. Depression is extremely common and is a risk factor for CVD. In the future, investigators must elucidate specific mechanisms driving CVD risk with depression and identify effective therapies for preventing depression-related CVD morbidity and mortality in both HIV- and HIV+ adults. Meanwhile, clinicians must remain vigilant in identifying and managing depressive symptoms, especially among those who are at heightened risk for CVD due to HIV infection

Clinical and structural risk factors predicting atrial fibrillation

Atrial fibrillation (AF) is associated with a high morbidity and mortality. Early identification of patients with AF may reduce morbidity and mortality. Current models predicting AF have limitations and focus on mainly clinical variables which are not always apparent in AF patients. Models focusing on pathophysiological mechanisms such as blood based biomarkers and ECG markers may be more accurate in identifying patients with AF. This study is based on the Birmingham and Black Country Atrial Fibrillation Registry (BBC-AF Registry) which recruited a cohort of 800 patients with and without AF. Blood based biomarkers and ECG markers were compared between the two groups of patients. The blood based biomarker analysis using a novel proteomics chip technique demonstrated that BNP and a novel biomarker, fibroblast growth factor 23 (FGF-23) were increased in AF patients and were also independently predictive of AF. In the ECG analysis, QT interval was increased in AF patients and independently predicted AF. A combined model using blood based biomarkers, ECG markers and clinical variables demonstrated that a simple model consisting of simple clinical variables, QT interval, BNP and FGF-23 had a good ability to predict AF and performed better than contemporary AF prediction models in the current literature

Bioregulatory systems medicine: an innovative approach to integrating the science of molecular networks, inflammation, and systems biology with the patient\u27s autoregulatory capacity?

Bioregulatory systems medicine (BrSM) is a paradigm that aims to advance current medical practices. The basic scientific and clinical tenets of this approach embrace an interconnected picture of human health, supported largely by recent advances in systems biology and genomics, and focus on the implications of multi-scale interconnectivity for improving therapeutic approaches to disease. This article introduces the formal incorporation of these scientific and clinical elements into a cohesive theoretical model of the BrSM approach. The authors review this integrated body of knowledge and discuss how the emergent conceptual model offers the medical field a new avenue for extending the armamentarium of current treatment and healthcare, with the ultimate goal of improving population health