Association of depressive and anxiety symptoms with blood pressure in first-episode, treatment-naïve patients with depression: a cross-sectional study

Abstract

Depressive and anxiety symptoms are common comorbidities in patients with depression, but their associations with blood pressure (BP) have not been well characterized in treatment-naïve patients. The objective of this cross-sectional investigation was to examine potential associations among depressive symptoms (HAMD-17), anxiety symptoms (HAMA), and blood pressure in first-episode, treatment-naïve (FETN) patients with depression. A total of 1,718 FETN patients with depression participated in this cross-sectional investigation. Depressive symptoms were evaluated through the Hamilton Depression Rating Scale (HAMD-17), while anxiety symptoms were evaluated via the Hamilton Anxiety Rating Scale (HAMA). Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) served as outcome variables. Multiple linear regression analyses were used for evaluate the relationships among HAMD, HAMA, as well as blood pressure, adjusting to control for demographic characteristics and clinical variables. Participants’ average age measured 34.87 ± 12.43 years, and 65.77% were] female. Mean HAMD-17 and HAMA scores were 30.30 ± 2.94 and 20.80 ± 3.47, respectively. Mean SBP and DBP were 119.48 ± 10.91 mmHg and 75.95 ± 6.74 mmHg, respectively. In the fully adjusted model including both variables simultaneously, HAMD-17 remained significantly correlated with both SBP (β = 0.80, 95% CI: 0.63, 0.98, p < 0.001) as well as DBP (β = 0.36, 95% CI: 0.24, 0.49, p < 0.001). HAMA showed no significant association regarding SBP (β = 0.13, 95% CI: − 0.02, 0.28, p = 0.079) while remained significantly associated for DBP (β = 0.15, 95% CI: 0.04, 0.26, p = 0.006). Among FETN patients presenting depression, depressive symptoms were independently correlated with SBP as well as DBP, while anxiety symptoms demonstrated a significant association only with DBP. These findings suggest that depressive and anxiety symptoms may have distinct associations with cardiovascular parameters in patients with depression.

Background

Major depressive disorder (MDD) is a leading cause of global disability, with an estimated lifetime prevalence of 16.2% worldwide and 6.8% in China¹. The disorder typically manifests with peak onset between late adolescence and young adulthood (15–30 years), affecting women approximately twice as often as men (female-to-male ratio of approximately 2:1). MDD frequently co-occurs with various medical conditions including hypertension, diabetes, obesity, and chronic pain syndromes, which can independently influence blood pressure regulation². The comorbidity rate between hypertension and MDD ranges from 20 to 30% globally. In China, individuals with major depression often experience substantial delays in seeking treatment, with a mean duration from illness onset to first treatment contact of 7.49 years³. Emerging evidence suggests that telomere length may represent a biological link connecting depression, hypertension, and accelerated aging. Meta-analysis of 38 studies (N = 34,347) demonstrated a significant negative association between depression and telomere length, with depression severity significantly correlating with shorter telomeres⁴. Similarly, telomere length has been inversely associated with hypertension, with each kilobase decrease in telomere length corresponding to a 1.4-fold increased risk of hypertension after controlling for age and gender⁵. The pathomechanism may involve chronic stress-induced cellular replication leading to accelerated telomere attrition, oxidative stress, and inflammation—processes common to both depression and hypertension⁶.

Depressive and anxiety symptoms have been extensively documented as significant risk factors for cardiovascular disease, with mounting evidence suggesting that elevated blood pressure may serve as a crucial mediating pathway through which these psychiatric symptoms contribute to increased cardiovascular morbidity and mortality⁷. The co-occurrence of anxiety and depressive symptoms may exert synergistic effects on cardiovascular parameters, as anxiety frequently accompanies depression and independently influences blood pressure regulation through heightened sympathetic hypothalamic-pituitary-adrenal axis dysregulation and nervous system activation⁸. Recent Mendelian randomization analyses have provided compelling evidence for causal relationships between anxiety symptoms, depressive symptoms, and elevated blood pressure levels, suggesting that these associations extend beyond mere correlation⁹. However, empirical studies examining the associations between depressive and anxiety symptoms and blood pressure have yielded inconsistent results, creating considerable uncertainty in our understanding of these relationships. Cross-sectional investigations have reported mixed findings, with some studies demonstrating positive associations between depressive symptoms and blood pressure¹⁰, while others have found inverse relationships¹¹, and several have reported no significant relationships¹². Similarly, longitudinal studies have produced conflicting evidence, with some cohort studies showing that higher anxiety symptoms predict elevated blood pressure over time¹³, while others have documented inverse associations between depressive symptoms and blood pressure in prospective analyses¹⁴. For instance, a large-scale cohort study found that anxiety symptoms were positively associated with increased blood pressure (hazard ratio [HR] = 1.48; 95% CI, 1.03–2.12) over a 2-year observation period¹⁵, whereas another longitudinal investigation reported that depressive symptoms showed negative associations with both systolic blood pressure (SBP) as well as diastolic blood pressure (DBP)¹². Importantly, most previous studies have included patients receiving antidepressant or antihypertensive medications, potentially confounding the direct associations between psychiatric symptoms and blood pressure through pharmacological effects on both mood and cardiovascular parameters^12–16.

In contrast, examining first-episode, treatment-naïve (FETN) patients with depression provides a unique chance to explore the unconfounded associations among depressive and anxiety symptoms and blood pressure, eliminating the potential masking effects of psychotropic and antihypertensive medications¹⁷. Moreover, understanding these associations in the early stages of psychiatric illness may provide crucial insights for developing targeted cardiovascular risk stratification and prevention strategies, particularly given that the pathophysiological mechanisms underlying psychiatric-cardiovascular comorbidity may be most clearly observable before treatment initiation. Despite the theoretical foundation and emerging evidence from general populations, studies specifically focusing on FETN depression patients remain scarce, with limited investigations examining the relationships between psychiatric symptom severity and blood pressure parameters in this critical population. Therefore, simultaneous examination of both depressive and anxiety symptom associations with blood pressure in this unique population is essential to advance our understanding of psychiatric-cardiovascular relationships and inform early intervention strategies. Such investigation could potentially inform clinical practice by enabling early identification of patients at elevated cardiovascular risk and guiding the development of personalized intervention approaches that address both psychiatric symptoms and cardiovascular health concurrently¹⁸.

Our primary hypothesis posited that depressive and anxiety symptoms would demonstrate differential associations with blood pressure parameters, based on their distinct pathophysiological mechanisms—specifically, that anxiety symptoms would show stronger positive associations with blood pressure through direct sympathetic activation, while depressive symptoms might exhibit more complex or weaker associations given the mixed evidence regarding autonomic dysregulation in depression. Given the limited prior research in this specific population and the mixed findings from previous studies, we adopted an exploratory approach without predetermined assumptions about the direction or magnitude of these associations. The unique contribution of studying first-episode, treatment-naïve (FETN) patients lies in eliminating confounding effects of chronic illness progression, medication use, and treatment-related physiological changes that characterize treated or chronic populations. This approach allows us to examine the intrinsic relationships between psychiatric symptoms and cardiovascular parameters at illness onset, providing cleaner evidence for understanding the early pathophysiological mechanisms linking depression, anxiety, and blood pressure dysregulation.

Methods

Research design and participant selection

The present investigation employed a cross-sectional approach to examine participants systematically. Recruitment activities were conducted continuously within the mental health outpatient clinic of a general hospital located in Taiyuan city, Shanxi province, China, spanning between September 2016 through December 2018. All individuals attending outpatient services were systematically screened for potential study inclusion.

A consecutive sampling method was utilized to identify eligible participants who fulfilled the diagnostic criteria for depression. The recruitment process yielded 1,718 qualified individuals (gender distribution: 588 males, 1,130 females) within an age spectrum of 18 to 60 years. These participants were systematically enrolled following comprehensive screening procedures at the psychiatric clinic within the general hospital setting.

Ethical clearance for this study was obtained from the Ethics Committee of the First Clinical Medical College at Shanxi Medical University (No: 2016-Y27), with the research protocol adhering strictly to the principles outlined in the Declaration of Helsinki and ensuring compliance with institutional guidelines and international ethical standards. Comprehensive information regarding the research aims, procedures, and potential implications was furnished to all prospective participants. Written informed consent was obtained from each individual prior to their inclusion in the study.

Inclusion and exclusion criteria

Participants were considered eligible for enrollment based on the following predetermined criteria: (1) individuals aged between 18 and 60 years of Han Chinese ethnicity; (2) presentation of an initial acute depressive episode at the time of study entry; (3) fulfillment of major depressive disorder diagnostic requirements according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR); (4) absence of any prior psychotropic medication exposure, including antidepressant or antipsychotic treatments; (5) current depressive symptomatology severity indicated by 17-item Hamilton Depression Rating Scale scores (HAMD-17) ≥ 24; (6) capacity to provide written informed consent and participate in comprehensive clinical evaluations.

Participants were systematically excluded from the study based on the following criteria: (1) presence of severe medical conditions including malignant neoplasms, type 2 diabetes mellitus, cardiovascular/cerebrovascular diseases, thyroid disorders, or benign prostatic hypertrophy (BPH) (n = 9); (2) documented record of substance dependency and abuse during the preceding six-month period, with tobacco smoking as the sole exception (n = 9); (3) current pregnancy status or breastfeeding period (n = 10); (4) manifestation of severe personality pathology; (5) evidence of any additional Axis I psychiatric disorders beyond major depressive disorder (n = 15); (6) established diagnosis of hypertension or concurrent use of antihypertensive medications; (7) acute clinical presentations that compromised interview reliability or assessment feasibility (n = 5); (8) inability to understand consent procedures or declining to complete consent documentation (n = 21). During the screening process, 78 individuals were deemed ineligible based on these predetermined exclusion criteria, with additional undocumented exclusionary factors accounting for the remaining cases (n = 9).

Sociodemographic and anthropometric data collection

Baseline demographic characteristics and general participant information were systematically gathered through administration of a purpose-designed structured survey instrument. The questionnaire captured essential variables including gender distribution, chronological age, educational attainment levels, and matrimonial status across all enrolled individuals.

Blood pressure (mmHg) was measured using automated oscillometric devices (Omron HEM-7121, Omron Healthcare Co., Ltd., Kyoto, Japan), which are validated according to international protocols and hold relevant medical device registration certificates in China. All measurements were conducted by trained nursing staff between 8:00–10:00 AM to minimize circadian variation. Participants were instructed to avoid caffeine, nicotine, and vigorous physical activity for at least 30 min prior to assessment. After resting quietly in a seated position for 5 min in a quiet environment, blood pressure was measured on the right arm supported at heart level, with feet flat on the floor and back supported. Appropriate cuff sizes were selected based on arm circumference. Three consecutive measurements were taken at 1-minute intervals, and the average of the second and third readings was recorded for analysis. All devices underwent regular calibration according to manufacturer specifications to ensure measurement consistency across the study period.

Clinical assessment procedures

Consensus diagnostic determination for major depressive disorder was established through independent evaluation by two certified psychiatrists utilizing the Chinese-language adaptation of the Modified Structured Clinical Interview for DSM-IV-TR criteria (SCID-I/P). Both clinicians possessed extensive clinical experience exceeding five years and underwent comprehensive pre-study training protocols for standardized assessment tool administration.

Depressive symptom severity was quantified using the Chinese version of the HAMD-17. This validated instrument comprises seventeen assessment items with differential scoring mechanisms: nine items utilize a five-point rating system spanning from 0 (symptom absence) to 4 (severe manifestation), while eight items employ a three-point scale ranging between 0 (absent) and 2 (symptom-specific severity descriptors). The cumulative scoring range extends from 0 to 52 points, with elevated scores corresponding to increased depressive symptom intensity. Previous research has demonstrated satisfactory psychometric properties for this instrument, establishing its widespread clinical utility within Chinese populations¹⁹.

Anxiety symptomatology was evaluated through administration of the Chinese version of the Hamilton Anxiety Rating Scale (HAMA)²⁰. This standardized instrument encompasses fourteen symptom-specific items assessed on a five-point Likert rating system ranging from 0 (complete absence) to 4 (severe symptom presentation), yielding cumulative scores spanning 0 to 56 points. The HAMA incorporates assessment of both psychological anxiety manifestations (including psychological distress and mental agitation) and somatic anxiety presentations (encompassing anxiety- associated physical symptoms).

Following intensive training procedures, inter- observer reliability values for both HAMA as well as HAMD total scores consistently exceeding 0.85 across repeated evaluations, ensuring measurement consistency. Additionally, assessing clinicians remained blinded to participants’ clinical status throughout the evaluation process to minimize potential bias and maintain assessment objectivity.

Statistical analysis

SPSS software version 25.0 was utilized for statistical analyses to examine the relationships between depressive symptoms, anxiety symptoms, and blood pressure parameters. Continuous data were reported as mean ± standard deviation (SD), while categorical data were displayed as frequencies and percentages (n, %). Baseline demographic as well as clinical characteristics were summarized through descriptive statistics. Multiple linear regression modeling was conducted to investigate the associations between HAMD-17 scores, HAMA scores, and blood pressure measurements (systolic and diastolic blood pressure). Five sequential modeling approaches were employed: Model 1 A examined the unadjusted association between HAMD-17 scores and blood pressure outcomes; Model 1B assessed the fully adjusted association between HAMD-17 scores and blood pressure outcomes, incorporating all covariates; Model 2 A investigated the unadjusted association between HAMA scores and blood pressure outcomes; Model 2B evaluated the fully adjusted association between HAMA scores and blood pressure outcomes; Model 3 simultaneously included both HAMD-17 and HAMA scores in the regression model to assess their independent associations with blood pressure outcomes while controlling for all demographic and clinical covariates. Variance Inflation Factor (VIF) analysis revealed that the VIF value for both HAMD-17 and HAMA in Model 3 was 1.62, which is substantially below the conventional threshold of 10 (and even below the more conservative threshold of 5) that indicates problematic multicollinearity. Categorical covariates (sex, marital status, education level) were not transformed into dummy variables in the regression models. While alternative coding approaches might provide additional methodological refinement, these variables served as adjustment factors rather than primary predictors of interest. Regression coefficients (β) with corresponding 95% confidence intervals (CI) were computed to determine the magnitude and direction of associations. Statistical significance was established at p < 0.05 (two-tailed).

Results

Baseline characteristics

A total of 1,718 FETN patients with depression were enrolled in this cross-sectional investigation. The baseline demographic profile of all patients is presented in Table 1. The average age of participants was 34.87 ± 12.43 years, comprising 588 (34.23%) male patients and 1,130 (65.77%) female patients. Most participants were married (70.78%), and nearly half had completed senior high school education (44.24%). The mean duration of illness was 6.31 ± 4.73 months. At baseline, the mean HAMD-17 score was 30.30 ± 2.94, and the mean HAMA score was 20.80 ± 3.47. The average SBP was 119.48 ± 10.91 mmHg, while the average DBP was 75.95 ± 6.74 mmHg.

Table 1.

Baseline characteristics of all patients.

Age (years)	Mean + SD, N (%)
	34.87 ± 12.43
Sex
Male	588 (34.23%)
Female	1130 (65.77%)
Marital status
Single	502 (29.22%)
Marriage	1216 (70.78%)
Education
Junior high school	413 (24.04%)
Senior high school	760 (44.24%)
College	449 (26.14%)
Postgraduate	96 (5.59%)
Duration of illness (months)	6.31 ± 4.73
HAMD	30.30 ± 2.94
HAMA	20.80 ± 3.47
Systolic blood pressure (mmHg)	119.48 ± 10.91
Diastolic blood pressure (mmHg)	75.95 ± 6.74

HAMD-17: Hamilton Depression Rating Scale 17-item; HAMA: Hamilton Anxiety Rating Scale.

Association between depressive and anxiety symptoms and SBP

Multivariable regression modeling investigating the associations among HAMD, HAMA, as well as SBP are displayed in Table 2. In the unadjusted model (Model 1 A), HAMD demonstrated a significant positive correlation with SBP (β = 1.05, 95% CI: 0.88, 1.22, p < 0.001). After controlling for sex, age, education, marital status, and duration of illness (Model 1B), this association remained significant but was slightly attenuated (β = 0.90, 95% CI: 0.76, 1.04, p < 0.001). When examining HAMA separately (Model 2 A), a significant positive correlation with SBP was observed (β = 0.66, 95% CI: 0.52, 0.81, p < 0.001), which persisted after controlling for covariates (Model 2B: β = 0.55, 95% CI: 0.43, 0.67, p < 0.001). In the final model including both HAMD and HAMA simultaneously (Model 3), HAMD remained significantly associated with systolic blood pressure (β = 0.80, 95% CI: 0.63, 0.98, p < 0.001), while the association for HAMA was not statistically significant (β = 0.13, 95% CI: -0.02, 0.28, p = 0.079). Among the covariates, age showed a strong positive association with SBP (all p < 0.001), while marital status (all p = 0.002) and duration of illness (all p < 0.05) also demonstrated significant positive associations with SBP across all models.

Table 2.

Linear regression for the systolic blood pressure in different models.

	Model 1				Model 2				Model 3
	A		B		A		B
	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P
HAMD	1.05 (0.88, 1.22)	< 0.001	0.90 (0.76, 1.04)	< 0.001	–	–	–	–	0.80 (0.63, 0.98)	< 0.001
HAMA	–	–	–	–	0.66 (0.52, 0.81)	< 0.001	0.55 (0.43, 0.67)	< 0.001	0.13 (− 0.02, 0.28)	0.079
Age			0.45 (0.40, 0.50)	< 0.001			0.45 (0.40, 0.50)	< 0.001	0.45 (0.40, 0.50)	< 0.001
Sex			− 0.23 (− 1.07, 0.62)	0.600			− 0.33 (− 1.19, 0.54)	0.456	− 0.25 (− 1.10, 0.60)	0.562
Marital status			1.81 (0.64, 2.98)	0.002			1.85 (0.65, 3.04)	0.002	1.82 (0.66, 2.99)	0.002
Education			0.25 (− 0.28, 0.77)	0.352			0.26 (− 0.27, 0.80)	0.333	0.25 (− 0.27, 0.78)	0.343
Duration of illness			0.10 (0.01, 0.19)	0.029			0.13 (0.04, 0.23)	0.004	0.10 (0.01, 0.19)	0.026

HAMD-17: Hamilton Depression Rating Scale 17-item; HAMA: Hamilton Anxiety Rating Scale.

Association between depressive and anxiety symptoms and DBP

Similarly, linear regression analyses for DBP are displayed in Table 3. In the crude model (Model 1 A), HAMD demonstrated a significant positive correlation with DBP (β = 0.52, 95% CI: 0.41, 0.62, p < 0.001). This correlation remained significant after controlling for demographic variables as well as covariates (Model 1B: β = 0.47, 95% CI: 0.37, 0.57, p < 0.001). When examining HAMA independently (Model 2 A), a significant positive association with DBP was observed (β = 0.37, 95% CI: 0.28, 0.46, p < 0.001), which persisted after covariate adjustment (Model 2B: β = 0.34, 95% CI: 0.25, 0.42, p < 0.001). In the final model including both variables simultaneously (Model 3), HAMD maintained its significant association with DBP (β = 0.36, 95% CI: 0.24, 0.49, p < 0.001), while HAMA also remained significantly associated (β = 0.15, 95% CI: 0.04, 0.26, p = 0.006). Among the covariates in Table 3, marital status demonstrated a significant positive association with DBP across all models (all p < 0.001).

Table 3.

Linear regression for the diastolic blood pressure in different models.

	Model 1				Model 2				Model 3
	A		B		A		B
	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P	β (95% CI)	P
HAMD	0.52 (0.41, 0.62)	< 0.001	0.47 (0.37, 0.57)	< 0.001	–	–	–	–	0.36 (0.24, 0.49)	< 0.001
HAMA	–	–	–	–	0.37 (0.28, 0.46)	< 0.001	0.34 (0.25, 0.42)	< 0.001	0.15 (0.04, 0.26)	0.006
Age			0.11 (0.07, 0.14)	< 0.001			0.11 (0.07, 0.14)	< 0.001	0.10 (0.07, 0.14)	0.225
Sex			− 0.36 (− 0.98, 0.27)	0.260			− 0.42 (− 1.05, 0.21)	0.189	− 0.39 (− 1.01, 0.24)	0.225
Marital status			2.28 (1.42, 3.14)	< 0.001			2.30 (1.43, 3.12)	< 0.001	2.29 (1.43, 3.15)	< 0.001
Education			− 0.13 (− 0.52, 0.25)	0.498			− 0.12 (− 0.51, 0.24)	0.535	− 0.13 (− 0.51, 0.26)	0.514
Duration of illness			− 0.01 (− 0.07, 0.06)	0.910			0.01 (− 0.05, 0.08)	0.711	− 0.01 (− 0.07, 0.06)	0.947

HAMD-17: Hamilton Depression Rating Scale 17-item; HAMA: Hamilton Anxiety Rating Scale.

Discussion

This cross-sectional investigation examined the relationships between depressive and anxiety symptoms with blood pressure in FETN patients with depression, a unique population that offers valuable insights into the unconfounded relationships between psychiatric symptoms and cardiovascular parameters. Our findings revealed that depressive symptoms, as measured by HAMD-17 scores, were independently correlated with both systolic and diastolic blood pressure, with significant positive associations observed even after adjusting for demographic and clinical variables. In contrast, anxiety symptoms showed a more selective association pattern, demonstrating a significant association only with DBP but not with SBP when both symptom domains were examined simultaneously. These differential association patterns suggest that depressive and anxiety symptoms may exert distinct influences on cardiovascular parameters in patients with depression.

Our findings regarding the positive association between depressive symptoms and blood pressure are consistent with several recent studies that have reported similar relationships. Notably, a large-scale cohort study by Qi et al. demonstrated how depressive symptoms showed positive correlations with elevated blood pressure susceptibility, with Mendelian randomization analyses providing evidence for causal relationships¹⁵. Furthermore, a comprehensive genetic analysis by Cai et al. found significant causal effects between depressive symptoms and blood pressure parameters, supporting the biological plausibility of our observed associations¹⁰. However, our results contrast with some previous investigations that reported inverse associations between depressive symptoms and blood pressure. For instance, studies by Bhat et al. in young adults and Huang et al. in middle-aged populations found negative correlations between depression scores and systolic blood pressure^11,12. These discrepant findings may be attributed to substantial methodological heterogeneity across studies, encompassing variations in study populations (clinical samples versus general population), study designs (cross-sectional versus longitudinal), and measurement instruments (various depression and anxiety scales). Additionally, the inclusion of patients receiving antidepressant or antihypertensive medications in previous studies may have confounded the direct associations through pharmacological effects. Our study’s focus on FETN patients eliminates these potential confounding effects, providing clearer insights into the natural associations between psychiatric symptoms and blood pressure. Regarding anxiety symptoms, the literature has been more limited and equally inconsistent. While some studies have reported positive associations between anxiety symptoms and blood pressure¹³, others have found no significant relationships or even inverse associations²¹. Our findings of a selective association between anxiety symptoms and DBP, but not SBP, add to the complex literature and suggest that anxiety could exert more targeted influences on certain blood pressure parameters.

To our knowledge, no previous studies have systematically examined these relationships in medication-naïve patients with first-episode depression, making our findings particularly valuable for understanding unconfounded psychiatric-cardiovascular associations at illness onset. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis commonly observed in depressive disorders leads to chronic elevation of cortisol levels, which can contribute to sodium retention, increased vascular resistance, and subsequent blood pressure elevation¹⁶. Additionally, depression is associated with enhanced activation of the sympathetic nervous system, which elevates heart rate, cardiac contractility, along with peripheral vasoconstriction, all of these factors contributing to increased blood pressure⁹. Furthermore, depression may activate inflammatory cascades, resulting in release of inflammatory mediators including interleukin-6 and tumor necrosis factor-α, both of which can facilitate endothelial dysfunction and impair vascular reactivity⁸. From a behavioral perspective, depressive symptoms may also influence blood pressure through modifications in lifestyle factors, including reduced physical activity, altered sleep patterns, and changes in dietary habits, although these factors may be less pronounced in our treatment-naïve population. In contrast, the selective association of anxiety symptoms with diastolic blood pressure suggests different underlying mechanisms. Anxiety is characterized by acute and chronic stress responses that primarily affect the sympathetic nervous system, leading to increased peripheral vascular resistance, which predominantly influences diastolic blood pressure²². The cognitive-emotional-physiological feedback loops inherent in anxiety disorders may create sustained states of physiological arousal, with heightened attention to bodily sensations and threat-related stimuli contributing to persistent sympathetic activation⁷. Moreover, anxiety-related alterations in emotional regulation and autonomic nervous system function may specifically impact diastolic blood pressure through their effects on peripheral vascular tone and resistance¹⁸. The non-significant SBP-HAMA association in Model 3 (β = 0.13, p = 0.079) suggests that when both symptom domains are considered simultaneously, depressive symptoms capture the primary variance related to systolic elevation, whereas anxiety retains independent predictive value specifically for diastolic parameters. This pattern indicates partially separable cardiovascular effects that warrant further investigation in prospective FETN cohorts.

Several demographic and clinical variables emerged as significant covariates in our regression models. Notably, age demonstrated positive associations with both SBP and DBP, consistent with established physiological aging processes that affect vascular compliance and arterial stiffness. Marital status showed positive associations with both SBP and DBP, with married participants exhibiting higher blood pressure values compared to unmarried participants. Duration of illness demonstrated a positive association with SBP but not with DBP. Age, in particular, represents a well-established risk factor for both depression and hypertension, and older individuals may have higher likelihood of being married and experiencing longer illness duration. The complex interrelationships among these demographic and clinical variables, their independent contributions to blood pressure regulation, and potential mediating or moderating effects on the depression-anxiety-blood pressure pathway warrant dedicated investigation in future studies. Additionally, given potential gender differences in pathomechanisms linking psychiatric symptoms and cardiovascular parameters, future research with adequately powered gender-stratified analyses would provide valuable insights into sex-specific biological pathways.

Several limitations should be acknowledged in the interpretation of our results. First, this study’s cross-sectional methodology prevents determining causality in the associations between depressive and anxiety symptoms and blood pressure parameters. While our findings suggest associations between psychiatric symptoms and cardiovascular parameters, prospective research is necessary for determine the chronological sequence and directionality of these relationships. Furthermore, the present investigation was performed at one institution, potentially restricting the applicability of our findings to wider populations of FETN patients with depression across different healthcare settings and geographic regions. Additionally, while our sample of 1,718 participants provides adequate statistical power for detecting the observed associations, larger multi-institutional studies could strengthen the robustness and generalizability of these results. Second, methodological limitations in our measurement approaches should be considered. Blood pressure measurements were obtained during single clinical visits rather than through ambulatory blood pressure monitoring, which may not capture the full variability in blood pressure patterns and could be influenced by white-coat hypertension or other situational factors. The assessment of depressive and anxiety symptoms relied on clinician-administered rating scales (HAMD and HAMA), which, despite their established validity and reliability, may introduce subjective elements in symptom evaluation and could be influenced by inter-rater variability. Moreover, several potential confounding variables were not controlled for in our analyses, including body mass index, physical activity levels, dietary habits, sleep quality, substance use, family history of cardiovascular disease, and specific comorbid medical conditions, all of which could influence both psychiatric symptoms and blood pressure parameters. Third, limitations related to population representativeness should be acknowledged. The recruitment of participants from a single psychiatric hospital may introduce selection bias, as patients seeking treatment at specialized mental health facilities may differ systematically from those in community settings or primary care environments. Cultural and socioeconomic factors specific to our study population could restrict the applicability of results to different demographic groups, particularly given that cultural factors can influence both the expression of psychiatric symptoms and health-seeking behaviors. Forth, the MDD patients included in this study were quite severe in their depression, with the 17-item HAMD scores greater than or equal to 24, and the mean HAMA is above 20, so the results of this study may not be extrapolated to less severely affected patients. Additionally, socioeconomic variables such as income, employment status, and access to healthcare resources, which were not comprehensively assessed in this study, may moderate the relationships between psychiatric symptoms and cardiovascular parameters.

Conclusions

This cross-sectional study of 1,718 FETN patients with depression demonstrates that depressive symptoms are independently associated with both SBP and DBP, while anxiety symptoms show a selective association only with diastolic blood pressure, suggesting distinct cardiovascular effects of these psychiatric symptom domains. These findings highlight the importance of routine blood pressure monitoring in psychiatric assessments and support the implementation of integrated care models that address both psychiatric and cardiovascular health concurrently. The study’s focus on treatment-naïve patients provides valuable insights into the natural associations between psychiatric symptoms and blood pressure parameters without medication confounding effects. Future longitudinal studies incorporating comprehensive biological assessments are needed to establish causal relationships and elucidate underlying pathophysiological mechanisms, while intervention studies should examine whether treating psychiatric symptoms leads to blood pressure improvements, ultimately informing precision medicine approaches for optimizing cardiovascular disease prevention strategies in patients with depression.

Author contributions

Study Design: Xiangyang Zhang, Junjun Liu. Investigation: Qi Qian, Lu Wang, Baomei Zhang, Fulin Shen, Jie Qian, Lulu Ye. Analysis and interpretation of data: Qi Qian, Junjun Liu. Drafting of the manuscript: Qi Qian, Lu Wang, Baomei Zhang. Critical revision of the manuscript: Xiangyang Zhang. Approval of the final version for publication: Junjun Liu, Xiangyang Zhang.

Funding

This work was supported by the Medical Science and Technology Development Foundation, Nanjing Department of Health (Nos. YKK21216, YKK20184, YKK22264). The funding sources of this study had no role in study design, data collection and analysis, decision to publish, or preparation of the article.

Data availability

The datasets used and/or analysed during the current study available from the corresponding author on reasonable request.

Declarations

Competing interests

The authors declare no competing interests.

Ethics approval and consent to participate

Ethical approval for this study was granted by the Ethics Committee of the First Clinical Medical College at Shanxi Medical University (No: 2016-Y27).

Consent for publication

Written informed consent for publication was obtained from all participants.