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World J Psychiatry. Nov 19, 2026; 16(11): 122420
Published online Nov 19, 2026. doi: 10.5498/wjp.122420
Potential impact of generalized anxiety disorder on future hypertension risk: Investigating the role of psychophysiological stress pathways
Le-Rong Ouyang, Miao-Ling Zheng, Jin-Yi Hu, Qiu-Hong Li, Hu Xie, Xi Yang, Jian-Bin Xue, Xin-Yue Lin
Le-Rong Ouyang, Qiu-Hong Li, Licheng Community Health Service Center, Headquarters of Shenzhen Nanshan Medical Group, Shenzhen 518055, Guangdong Province, China
Le-Rong Ouyang, General Outpatient Clinic, Southern Medical University Shenzhen Hospital, Shenzhen 518101, Guangdong Province, China
Miao-Ling Zheng, Xi Yang, Department of Traditional Chinese Medicine, Nanshan Community Health Service Center, Headquarters of Shenzhen Nanshan Medical Group, Shenzhen 518055, Guangdong Province, China
Jin-Yi Hu, Department of Public Health, School of Public Health, Southern Medical University, Shenzhen 510515, Guangdong Province, China
Hu Xie, Department of Social Health Management, Headquarters of Shenzhen Nanshan Medical Group, Shenzhen 518052, Guangdong Province, China
Jian-Bin Xue, Department of Disease Prevention, Guangzhou Baiyun District Center for Disease Control and Prevention, Guangzhou 510440, Guangdong Province, China
Xin-Yue Lin, Cotton Ridge Community Health Service Center, Shenzhen Luohu Hospital Group, Shenzhen 518019, Guangdong Province, China
Co-first authors: Le-Rong Ouyang and Miao-Ling Zheng.
Author contributions: Ouyang LR and Zheng ML contributed equally to this work as co-first authors; Ouyang LR, Zheng ML, and Lin XY conceived and designed the study; Ouyang LR, Zheng ML, Li QH, Xie H, Yang X, Xue JB, and Lin XY were responsible for data acquisition; Ouyang LR, Zheng ML, Hu JY, and Xue JB performed the data analysis and interpretation; Ouyang LR and Zheng ML drafted the manuscript; Hu JY, Li QH, Xie H, Yang X, Xue JB, and Lin XY critically revised the manuscript for important intellectual content; Lin XY supervised the study and is the guarantor of this work. All authors have read and approved the final manuscript.
AI contribution statement: Portions of this manuscript were edited using AI tools solely for language refinement. The authors carefully reviewed and verified all AI-assisted outputs and take full responsibility for the scientific content of the manuscript.
Institutional review board statement: This study was reviewed by the Ethics Committee of the Medical Committee of Southern Medical University Shenzhen Hospital, No. NYSZYYEC2022K112R009.
Clinical trial registration statement: We would like to respectfully clarify that the present study was a prospective observational cohort study and did not involve prospective assignment of participants to any intervention. This study was approved by the institutional ethics committee before enrollment, and written informed consent was obtained from all participants.
Informed consent statement: All study participants or their legal guardians provided written informed consent before study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Xin-Yue Lin, MD, Cotton Ridge Community Health Service Center, Shenzhen Luohu Hospital Group, No. 2 Xinmian Road, Shenzhen 518019, Guangdong Province, China.
13410786720@163.com
Received: May 19, 2026
Revised: July 6, 2026
Accepted: July 31, 2026
Published online: November 19, 2026
Processing time: 162 Days and 21.7 Hours
BACKGROUND
Generalized anxiety disorder (GAD) may be associated with an increased risk of future hypertension through psychophysiological stress pathways; however, this association must be interpreted carefully, considering medication use, lifestyle factors, clinic-based selection, and limited temporal information provided by baseline biomarkers.
AIM
To explore the potential impact of GAD on future hypertension risk and preliminarily analyze the roles of psychophysiological stress-related pathways (neuroendocrine, sympathetic activation, and inflammatory response) in the same.
METHODS
This was a prospective, observational cohort study. A total of 300 outpatients and physical examination participants from January 2023 to December 2024 at Southern Medical University Shenzhen Hospital were included; no participants had hypertension at baseline. The participants were divided into a GAD group (n = 96) and a non-GAD group (n = 204) according to the DSM-5 diagnosis and the GAD-7 scale. Data on general information, lifestyle factors, dietary salt intake, physical activity, family history, psychotropic/hypnotic medication use, and sleep quality were collected. Early morning serum cortisol, C-reactive protein, interleukin-6, 24-hour ambulatory blood pressure, and heart rate variability parameters were obtained. All participants were followed up for 12 months and sustained new-onset hypertension was recorded. Multivariate and sensitivity analyses were performed to assess the association between GAD and hypertension, while mediation analysis was used as exploratory statistical decomposition rather than causal pathway confirmation.
RESULTS
All 300 participants completed the 12-month follow-up; 50 cases of new-onset hypertension were observed. Incident hypertension occurred in 36/96 (37.5%) participants in the GAD group, significantly higher than 14/204 (6.9%) in the non-GAD group. After adjusting for demographic factors, body mass index, smoking and alcohol use, sleep quality, baseline blood pressure, family history of hypertension, psychotropic/hypnotic medication use, physical activity, and dietary salt intake, GAD remained associated with a higher risk of new-onset hypertension in the expanded penalized model (adjusted odds ratio = 2.31, 95% confidence interval: 1.23-4.38). Replacing the dichotomous GAD status with a continuous GAD-7 score yielded a consistent association. Compared to the non-GAD group, the GAD group showed higher levels of cortisol, C-reactive protein, and interleukin-6, and heart rate variability (HRV) indices indicated impaired sympathovagal balance. Exploratory mediation analysis suggested that increased cortisol levels and a standardized HRV composite jointly explained 32.5% of the association between GAD and incident hypertension, while inflammatory markers showed borderline or positive indirect-effect trends.
CONCLUSION
GAD was associated with a higher 12-month risk of sustained new-onset hypertension in this clinic-based cohort; this association persisted after adjustment for common clinical, medication-related, and lifestyle confounders. Elevated cortisol levels and reduced HRV may statistically explain part of this association; however, mediation findings should not be interpreted as definitive causal pathways. Clinically, dynamic blood pressure monitoring, anxiety assessment, medication review, sleep management, and lifestyle interventions should be considered in patients with GAD.
Core Tip: This prospective observational cohort study suggests that generalized anxiety disorder (GAD) is associated with future hypertension risk in a clinic-based population without baseline hypertension. Among the 300 participants, the 12-month incidence of sustained new-onset hypertension was higher in the GAD group (37.5% vs 6.9%). This association persisted after expanded adjustment for clinical variables, psychotropic/hypnotic medication use, physical activity, and dietary salt intake (adjusted odds ratio = 2.31). Patients with GAD also showed higher cortisol, C-reactive protein, and interleukin-6 levels and impaired heart rate variability. Exploratory mediation analysis supported cortisol and heart rate variability as possible statistical links; however, causal interpretation requires longer-term studies with repeated biomarker measurements.
