Associations between mental health, blood pressure and the development of hypertension

Abstract

Multiple studies have reported a link between mental health and high blood pressure with mixed or even contradictory findings. Here, we resolve those contradictions and further dissect the cross-sectional and longitudinal relationship between mental health, systolic blood pressure, and hypertension using extensive psychological, medical and neuroimaging data from the UK Biobank. We show that higher systolic blood pressure is associated with fewer depressive symptoms, greater well-being, and lower emotion-related brain activity. Interestingly, impending hypertension is associated with poorer mental health years before HTN is diagnosed. In addition, a stronger baseline association between systolic blood pressure and better mental health was observed in individuals who develop hypertension until follow-up. Overall, our findings offer insights on the complex relationship between mental health, blood pressure, and hypertension, suggesting that-via baroreceptor mechanisms and reinforcement learning-the association of higher blood pressure with better mental health may ultimately contribute to the development of hypertension.

Fig. 1. Schematic overview of study design, outcome and predictor variables and analyses.

Our study included UK Biobank data (i) from the complete baseline assessment, which was conducted between 2006–2010, and (ii) from the ongoing 10-year follow-up visit which has started in 2014 and included brain magnetic resonance imaging (MRI). Our follow-up visit sample consisted of those participants whose data had been released by February 2020. In addition, a sub-sample of the baseline cohort participated in an online mental health follow-up assessment in 2016. We defined mental health variables (depressive symptoms, well-being) at baseline and follow-up as outcomes. Systolic blood pressure (SBP), hypertension diagnosis (HTN), and number of prescribed antihypertensive medications at baseline and follow-up were the main predictors in all models. Finally, we assessed the relationship of the main predictors with emotion-related brain function (i.e., BOLD fMRI response in Hariri task) at follow-up visit.

Fig. 2. Cross-sectional associations with mental health outcomes at initial assessment.

Forest plot shows standardized beta estimates and 95% confidence intervals for predictors of interest (systolic blood pressure, diagnosed hypertension (HTN), and number of antihypertensives) as well as covariates. There were N = 303,771 participants with data for current depressive symptoms and N = 129,876 participants with data for well-being (after exclusion of missing values). Source data are provided as a Source Data file.

Fig. 3. Longitudinal associations with mental health outcomes at follow-up assessment.

Forest plot shows standardized beta estimates and 95% confidence intervals for predictors of interest at baseline (systolic blood pressure, diagnosed hypertension (HTN), and number of antihypertensives) as well as covariates. There were N = 28,021 participants with data for current depressive symptoms and N = 29,966 participants with data for well-being (after exclusion of missing values). Source data are provided as a Source Data file.

Fig. 4. Association between mental health and systolic blood pressure at initial assessment moderated by hypertension status at follow-up (i.e., approximately 10 years later).

A Across all participants (excluding those with HTN and use of antihypertensives and missing data, N = 25,579), systolic blood pressure increased from baseline to follow-up. B People who developed hypertension until follow-up (i.e., received a hypertension diagnosis or started taking antihypertensives) until the follow-up assessment (dark blue colour) already showed higher systolic blood pressure levels at initial assessment, despite not having been diagnosed at this timepoint, yet. C No significant difference between groups in depressive symptoms at baseline (top, N = 24,202), but when controlling for SBP, HTN developers showed more depressive symptoms (bottom, N = 24,202). D No significant difference between groups in well-being at baseline (top, N = 9,444), but when controlling for SBP, HTN developers showed lower well-being (bottom, N = 9444). E Participants who developed hypertension (dark blue colour) had a steeper negative slope for the relationship between blood pressure and depressive symptoms than those participants who stayed non-hypertensive (light blue colour). F Similar trend for well-being in the expected opposite direction. Data in A are presented as mean values +/− SD. Data in C and D are presented as mean values +/− SEM. Data in E and F show individual data points with size of points representing density and regression lines with 95% confidence intervals. Source data are provided as a Source Data file.

Fig. 5. Association between systolic blood pressure and emotion-related brain function at follow-up.

Left column (violin plots with boxplots presenting the median, lower and upper hinges corresponding to the 25th and 75th percentiles and lower/upper whiskers extending from the hinge to the smallest/largest value no further than 1.5 * IQR from the hinge) shows group differences in Hariri task activity by hypertension status (HTN) at follow-up/imaging visit (N = 26,697): BOLD fMRI activity to emotional faces was lower in the amygdala (HTN z = 1.134; no HTN z = 1.249; two-sided t = 9.797; degrees of freedom = 15,129; 95% CI [0.091, 0.137]; p < 0.001) and in significant regions resulting from whole-brain analyses (HTN z = 2.322; no HTN z = 2.592; two-sided t = 14.528; degrees of freedom = 14,888; 95% CI [0.233, 0.306]; p < 0.001) in people with HTN compared to normotensives. Middle column shows negative correlations between blood pressure and BOLD fMRI activation in the faces>shapes contrast of the Hariri task in amygdala mask and whole-brain mask. The colour gradient represents the density of data points. Right column shows the same, but grouped by HTN at follow-up. Dark blue colours represent people who became hypertensive from baseline to follow-up. Light blue colours represent participants who stayed normotensive. The negative correlation between systolic blood pressure and emotion-related activity was flattened in participants who had developed hypertension. Source data are provided as a Source Data file.