Depressive symptoms as risk factors for the onset of home hypertension: a prospective cohort study

Depression commonly co-occurs with somatic diseases and is associated with increased cardiovascular disease (CVD) risk and poorer prognosis. This is partly due to a higher prevalence of CVD risk factors among people with depressive symptoms (e.g., obesity, poor diet, inactivity, smoking, and poor adherence), as well as stress-related dysregulation of the autonomic nervous system and adrenocortical hormones. Hypertension (HT) is a key modifiable risk factor for CVD, and prior work suggests blood pressure can be influenced by depression, anxiety, stress, and personality traits; however, the relationship between depression and HT remains unclear. Because home blood pressure (BP) is more reproducible and predictive of CVD than office or research BP, this study investigated whether baseline depressive symptoms increase the risk of new-onset home HT among individuals with home normotension. The authors hypothesized a positive association and additionally compared associations using research BP versus home BP.

Prior studies on the depression–hypertension relationship have been inconsistent, with some reporting positive and others negative associations. A major limitation of much of the prior literature is reliance on office BP measurements, which may contribute to mixed findings. The authors previously reported a positive association between depressive symptoms and masked hypertension in normotensive individuals in a cross-sectional analysis, suggesting the importance of assessing home BP in people with depressive symptoms for early diagnosis and management. Current guidelines prioritize home BP monitoring and recommend treatment for masked hypertension. Home BP monitoring has advantages: measurement in a familiar environment, better reproducibility and predictive value for CVD, and availability of both morning and evening readings. Despite these insights, the causal relationship between depressive symptoms and home hypertension had not been established, motivating the present prospective cohort study.

Design and setting: Prospective cohort study using the Tohoku Medical Megabank Community-Based Cohort Study (TMM CommCohort) in Miyagi Prefecture, Japan. Baseline surveys were conducted from 2013 to 2016; a secondary survey occurred approximately 4 years later (June 2017 to March 2021). Ethical approval was obtained (Tohoku Medical Megabank Organization IRB: 2022-4-160), and written informed consent was collected. Participants: Inclusion required participation in type 2 baseline and secondary surveys; home BP measured on at least 3 days during both baseline and secondary periods; no home HT at baseline (SBP <135 mmHg and DBP <85 mmHg for morning and evening home BP and no antihypertensive treatment); and complete CES-D data at baseline. Exclusions at baseline included withdrawal (n=205), missing questionnaires (n=12), missing research or home BP or CES-D (n=344), cardiovascular disease history (n=495), and home or treated HT (n=4183). Of 5216 eligible at baseline, those not in the secondary survey (n=870) or lacking home BP at secondary (n=1264) were excluded, yielding 3082 participants for analysis. Assessment of depressive symptoms: The Center for Epidemiologic Studies Depression Scale (CES-D), Japanese version (20 items, 0–3 per item) was administered at baseline. A score ≥16 defined depressive symptoms, regardless of antidepressant use. Home blood pressure measurement: Participants used an upper-arm electronic device (HEM-7080IC, OMRON) to measure BP and heart rate at home every morning and evening for 2 weeks at baseline and for 10 days at secondary. Morning BP was measured seated within 1 hour of awakening after 1–2 minutes of rest, before breakfast and medications. Evening BP was measured seated 1–2 minutes before bedtime. Mean morning BP and mean evening BP were calculated separately and used for exclusion and outcome definitions. Average home BP (mean of morning and evening BP) was also calculated for covariate adjustment. Changes in research and home BP between baseline and secondary were evaluated. Research BP: At the Community Support Center, trained nurses measured seated BP twice (mean of two readings) after 1–2 minutes of rest using an electronic device (HEM-9000AI, OMRON). Research heart rate was also measured. Other measurements: Physical exams included height, weight, and BMI. Laboratory data included γ-GTP, HbA1c, LDL-C, HDL-C, triglycerides, creatinine; estimated daily sodium intake was derived via Tanaka’s method. Questionnaires captured smoking (never/former/current), drinking habit (any alcohol use; daily alcohol consumption calculated from type, frequency, amount), exercise (regular exercise defined as ≥1 time/week), medical history (HT, diabetes mellitus, dyslipidemia, stroke, heart failure, myocardial infarction), Athens Insomnia Scale (AIS; 8 items, 0–3 each; treated as continuous), and education (less than high school, high school, more than high school, or other). Contextual covariates included examination year, degree of house damage from the 2011 Great East Japan Earthquake (6-level scale), and examination season (winter defined as December–February). Outcomes: The primary outcome was new-onset home HT at the secondary survey, defined as meeting home HT criteria (SBP ≥135 mmHg or DBP ≥85 mmHg) for either morning or evening home BP, or being under treatment for HT. Morning HT and evening HT were defined by meeting these criteria in morning or evening measurements, respectively. Participants on antihypertensive treatment at follow-up were counted in both morning and evening HT regardless of BP values. Statistical analysis: Continuous data were summarized as mean±SD or median (IQR), categorical as number (%). Group comparisons (depressive symptoms vs none) used t-tests (Student’s or Welch’s), Mann–Whitney U, or chi-square tests as appropriate. Age- and sex-adjusted least squares means were calculated for BP and HR. Associations between depressive symptoms (exposure) and incident home HT (outcome) were assessed via multivariable logistic regression with odds ratios (OR) and 95% confidence intervals (CI), using complete case analysis across four models: Model 1 adjusted for age and sex; Model 2 added research heart rate, BMI, dyslipidemia, diabetes mellitus, eGFR, smoking status, alcohol consumption, urinary sodium-to-potassium ratio, AIS score, and regular exercise; Model 3 added education, house damage, and winter examination; Model 4 further adjusted for baseline BP (average SBP for home HT analysis, morning SBP for morning HT, or evening SBP for evening HT). Subgroup analyses stratified by age (≤56 vs >56 years), sex, BP pattern (normotension vs white coat hypertension), and drinking habit; interaction terms tested effect modification. Sensitivity analysis excluded participants who were on antihypertensive treatment at the secondary survey. Statistical significance was set at p<0.05. Analyses were performed using R 4.2.1 (Linux).

- Cohort: 3082 participants (mean age 54.2 years; 80.9% female); 729 (23.7%) had depressive symptoms at baseline (CES-D ≥16). Follow-up was approximately 3.5–4 years. - Incidence by depressive symptoms: Home HT developed in 124/729 (17.0%) with depressive symptoms and 388/2353 (16.5%) without; morning HT in 93 (12.8%) vs 347 (14.7%); evening HT in 81 (11.1%) vs 205 (8.7%). Antihypertensive treatment at follow-up: 15 (2.1%) with depressive symptoms vs 40 (1.7%) without. - Multivariable logistic regression (Model 4): Depressive symptoms were associated with higher odds of incident home HT (OR 1.37, 95% CI 1.02–1.84, p=0.034) and evening HT (OR 1.66, 95% CI 1.17–2.36, p=0.005), but not morning HT (OR 1.18, 95% CI 0.86–1.61, p=0.304). - BP changes and levels: Age- and sex-adjusted morning and evening SBP, and evening DBP at follow-up were significantly higher in participants with depressive symptoms; research BP showed no significant group difference. Change in evening BP from baseline to follow-up was larger with depressive symptoms (evening SBP +1.6 vs +0.6 mmHg; evening DBP +1.3 vs +0.6 mmHg). - Subgroups: Elevated odds associated with depressive symptoms were evident for women and non-drinkers (home and evening HT). Among those with baseline normotension, depressive symptoms were related to incident evening HT. In normotensive participants, the OR for hypertension based on research BP was 1.47 (95% CI 0.99–2.14).

The study addressed whether depressive symptoms predict future development of home-determined hypertension among adults with baseline home normotension. Using prospective data with standardized home BP monitoring, depressive symptoms independently increased the risk of incident home HT, with the effect particularly pronounced for evening hypertension. This pattern aligns with the notion that depressive symptomatology and associated stress pathways may affect circadian BP regulation, autonomic balance, and behavioral routines later in the day. The findings were robust across multiple covariate adjustments and largely consistent in subgroup analyses by age, sex, baseline BP pattern, and drinking habit, underscoring the relevance of depressive symptoms as a risk marker for hypertension that may not be captured by clinic measurements. Clinically, the results support the utility of home BP monitoring in individuals with depressive symptoms to enable earlier detection and management of hypertension, potentially improving cardiovascular risk profiles. The lack of a significant association with morning HT, despite higher adjusted morning SBP, suggests differential diurnal effects or behaviors influencing evening BP, meriting further investigation.

In this prospective cohort of Japanese adults with baseline home normotension, depressive symptoms were associated with increased risk of incident home hypertension, especially evening hypertension. These findings highlight the value of home BP monitoring for people with depressive symptoms to facilitate early diagnosis and management. Future research should determine whether targeted home BP monitoring and integrated management of depressive symptoms improve long-term cardiovascular outcomes, and clarify mechanisms underlying stronger evening BP associations.