Approved research

Understanding the Role of the Brain and Cardiovascular Factors in Hypertension-Affect Relationships

Lay summary

Hypertension is the leading single risk factor globally for disability and death. Its high global prevalence continues to rise with population growth and aging. Hypertension also often co-occurs in people with mood/affective disorders, which in turn increases their risk of developing cardiovascular disease. In spite of its immense relevance for public health, causes of the most common form of hypertension, essential hypertension, are largely unknown. Recently, psychosocial factors, including stress, anxiety, depression, and well-being, have gained increased attention as proposed risk factors for essential hypertension. However, evidence for a causal role of psychosocial factors in essential hypertension is inconclusive and the brain-body mechanisms underlying hypertension-affect interactions remain poorly understood. We aim to investigate to what extent changes in blood pressure (BP) relate to (subclinical) alterations in emotional processing and affect, and to what degree this relationship may be influenced by brain or cardiovascular factors. By conducting our research within a large population-based cohort, our results will be relevant for a comprehensive understanding of the multidirectional relationship between hypertension, mental health, the cardiovascular system, and the brain. Understanding the role of emotional factors in hypertension is vital to pave roads for appropriate and evidence-based prevention and intervention strategies in hypertension management, which will consequently also lower the risk of other chronic diseases, such as cardiovascular disease or stroke. Our main research questions (RQs) for the proposed project are: 1. Is elevated BP related to cross-sectional and longitudinal changes in affect? 2. Which brain structures or functions influence the relationship between BP and affect? 3. How is the relationship between BP and affect influenced by (secondary) vascular disease? 4. Are there potential sex differences in the relationships identified in RQs 1-3? In RQ1, we aim to test whether BP relates to self-reported affect (e.g. depression, anxiety). In RQ2, we aim to assess if brain responses to emotion (e.g. amygdala activity) relate to BP levels. Additionally, we will test whether the BP-affect relationship is influenced by brain structure (e.g. volume, vasculature) or brain function (resting-state fMRI) in regions associated with emotion and cardiovascular regulation (e.g. amygdala, medial-frontal regions). In RQ3, we aim to examine how the BP-affect relationship is influenced by vascular disease markers (e.g. cerebral white matter lesions, atherosclerosis). In RQ4, sex differences in the relationships identified in RQs 1-3 will be assessed. We estimate a duration of 24 months for the proposed research.

Scope extension, June 2024:

Cardio- and cerebrovascular diseases are significant burden global health (Roth et al., 2020). Interestingly, epidemiological studies have shown strong associations between mental health disorders such as anxiety, depression, and "somatic" vascular disorders (Ghoge et al., 2003; Burrage et al., 2018). Consistently, our previous study on UK Biobank data has demonstrated a link between elevated blood pressure, well-being, and cerebral processing of emotions and the potential role of this relationship in the development of hypertension, which is a significant risk factor for vascular diseases (Schaare et al., 2023). Considering these findings, we hypothesize that bilateral communication between the brain and the cardiovascular system is involved in the pathophysiology of mental and cardiovascular disorders. This study aims to identify neural and cardiovascular factors and markers of their interaction that contribute to the development of cardiac disorders and mental disorders over time. 

Our research questions:

1. Which brain areas mediate the link between cardiac disorders, cognitive impairment, and disorders of mental health?
2. Is there a link between functional and structural alterations in brain areas responsible for emotional processing and interoception and the development of cardiac disorders?
3. Could the combination of cognitive features and imaging findings serve as predictors for cardiac disorders?