**Authors and Affiliations**
Betsy J. Medina-Inojosa, M.Da; Jose R. Medina Inojosa, M.D.a,b; Zhuo Chen, M.D. Ph.D.a; Matthew M. Clark, Ph.D.c; Nazanin Rajai, M.D., M.P.H.a; Amir Lerman, M.D.a; Itzhak Zachi Attia Ph.D.a; Paul A. Friedman  M.D.a, Francisco Lopez-Jimenez, M.D., M.Sc.a
a Department of Cardiovascular Medicine, Mayo Clinic, Minnesota, USA.
b Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905
c Department of Psychology, Mayo Clinic, Rochester, MN, US.

**Background**
Depression is prevalent in almost half of patients with cardiovascular disease (CVD) and is associated with CVD and mortality. We used a previously developed artificial intelligence algorithm using ECG that predicts physiological age (ECG-Age) and it has been linked to increased total and CVD mortality and CVD risk factors. We hypothesized that depressive symptoms would be associated with physiologic aging, as measured by AI-ECG

**Methods**
A previously validated algorithm was applied to determine ECG-Age to 105,732 consecutive ECGs of individuals aged ≥18 who sought care at Mayo Clinic between June 2019 and January 2022 and completed the Patient Health Questionnaire-9 (PHQ-9) within a month of ECG. PHQ-9 ascertains severity and frequency of depressive symptoms with values from 0 - 27 and were categorized as (None≤4, Mild 5-9, Moderate 10-14, Moderately severe 15-19 and Severe ≥20). Delta-Age was defined as ECG-Age minus chronological age and accelerated aging was defined as a Delta-Age >1SD above the mean. Logistic regression analyses associated PHQ-9 scores with positive Delta-Age while adjusting for CVD risk factors

**Results**
Mean chronological age was 57±17 yr and mean ECG-Age 58±14 yr (R2 = 0.85, P < 0.0001), Delta-Age 0.71±9.40 yr, 58% women, average PHQ-9 5±6, 61% had none, 20% mild, 10 % moderate, 5%moderately severe and 4% had severe depressive symptoms. Delta-Age was 2.10 years higher in those with depressive symptoms, reflecting accelerated aging. Compared to those with no depressive symptoms, those with severe symptoms were 1.5 times more likely to have Delta-Age >1SD (OR 1.52 CI 95%1.73-1.33), independently of CV risk factors and the Charlson comorbidity index. Figure.  There is significant attenuation of the association once accounting for age, sex and standard CVD risk factors

**Conclusion**
Depressive symptoms are associated with physiologic aging, highlighting the role of depression in physiologic aging and the potential of preventive strategies in patients with depression and CVD



**Authors and Affiliations**
Betsy J. Medina-Inojosa, M.D^a^; Jose R. Medina Inojosa, M.D.^a,b^; Zhuo Chen, M.D. Ph.D.^a^; Matthew M. Clark, Ph.D.^c^; Nazanin Rajai, M.D., M.P.H.^a^; Amir Lerman, M.D.^a^; Itzhak Zachi Attia Ph.D.^a^; Paul A. Friedman  M.D.^a^, Francisco Lopez-Jimenez, M.D., M.Sc.^a^
a Department of Cardiovascular Medicine, Mayo Clinic, Minnesota, USA.
b Division of Epidemiology, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN 55905
c Department of Psychology, Mayo Clinic, Rochester, MN, US.

**Background**
Depression is prevalent in almost half of patients with cardiovascular disease (CVD) and is associated with CVD and mortality. We used a previously developed artificial intelligence algorithm using ECG that predicts physiological age (ECG-Age) and it has been linked to increased total and CVD mortality and CVD risk factors. We hypothesized that depressive symptoms would be associated with physiologic aging, as measured by AI-ECG

**Methods**
A previously validated algorithm was applied to determine ECG-Age to 105,732 consecutive ECGs of individuals aged ≥18 who sought care at Mayo Clinic between June 2019 and January 2022 and completed the Patient Health Questionnaire-9 (PHQ-9) within a month of ECG. PHQ-9 ascertains severity and frequency of depressive symptoms with values from 0 - 27 and were categorized as (None≤4, Mild 5-9, Moderate 10-14, Moderately severe 15-19 and Severe ≥20). Delta-Age was defined as ECG-Age minus chronological age and accelerated aging was defined as a Delta-Age >1SD above the mean. Logistic regression analyses associated PHQ-9 scores with positive Delta-Age while adjusting for CVD risk factors

**Results**
Mean** **chronological age was 57±17 yr and mean ECG-Age 58±14 yr (R2 = 0.85, P < 0.0001), Delta-Age 0.71±9.40 yr, 58% women, average PHQ-9 5±6, 61% had none, 20% mild, 10 % moderate, 5%moderately severe and 4% had severe depressive symptoms. Delta-Age was 2.10 years higher in those with depressive symptoms, reflecting accelerated aging. Compared to those with no depressive symptoms, those with severe symptoms were 1.5 times more likely to have Delta-Age >1SD (OR 1.52 CI 95%1.73-1.33), independently of CV risk factors and the Charlson comorbidity index. [Figure](https://drive.google.com/file/d/1DcwtraoMaMjgZjfwy7QFn6B2AhtiJ2lF/view?usp=drive_link).  There is significant attenuation of the association once accounting for age, sex and standard CVD risk factors

**Conclusion**
Depressive symptoms are associated with physiologic aging, highlighting the role of depression in physiologic aging and the potential of preventive strategies in patients with depression and CVD



Association Between Depressive Symptoms Severity and Physiological Age as Determined by Artificial Intelligence-ECG