Anxiety and Depression Associated With Increased Cardiovascular Disease Risk Through Accelerated Development of Risk Factors

Giovanni Civieri; Shady Abohashem; Simran S Grewal; Wesam Aldosoky; Iqra Qamar; Erin Hanlon; Karmel W Choi; Lisa M Shin; Rachel P Rosovsky; Sandeep Chandra Bollepalli; Hui Chong Lau; Antonis Armoundas; Antonia V Seligowski; Sarah M Turgeon; Roger K Pitman; Francesco Tona; Jason H Wasfy; Jordan W Smoller; Sabino Iliceto; Jill Goldstein; Catherine Gebhard; Michael T Osborne; Ahmed Tawakol

doi:10.1016/j.jacadv.2024.101208

Anxiety and Depression Associated With Increased Cardiovascular Disease Risk Through Accelerated Development of Risk Factors

JACC Adv. 2024 Aug 14;3(9):101208. doi: 10.1016/j.jacadv.2024.101208. eCollection 2024 Sep.

Authors

Giovanni Civieri^{1

2}, Shady Abohashem^{1

3}, Simran S Grewal^{1

3}, Wesam Aldosoky¹, Iqra Qamar^{1

3}, Erin Hanlon¹, Karmel W Choi^{4

5

6}, Lisa M Shin^{7

8}, Rachel P Rosovsky⁹, Sandeep Chandra Bollepalli¹⁰, Hui Chong Lau^{1

3}, Antonis Armoundas^{10

11}, Antonia V Seligowski^{1

4}, Sarah M Turgeon¹², Roger K Pitman⁸, Francesco Tona², Jason H Wasfy³, Jordan W Smoller^{4

5

13

14}, Sabino Iliceto², Jill Goldstein^{4

14}, Catherine Gebhard^{15

16

17}, Michael T Osborne^{1

3}, Ahmed Tawakol^{1

3}

Affiliations

¹ Cardiovascular Imaging Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
² Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University of Padua, Padua, Italy.
³ Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
⁴ Department of Psychiatry, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Psychiatric & Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁶ Center for Precision Psychiatry, Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
⁷ Department of Psychology, Tufts University, Medford, Massachusetts, USA.
⁸ Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Charlestown, Massachusetts, USA.
⁹ Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
¹⁰ Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
¹¹ Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
¹² Neuroscience Program, Amherst College, Amherst, Massachusetts, USA.
¹³ Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
¹⁴ Innovation Center on Sex Differences in Medicine (ICON-X), Massachusetts General Hospital, Boston, Massachusetts, USA.
¹⁵ Department of Nuclear Medicine, University Hospital Zurich, Zurich, Switzerland.
¹⁶ Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.
¹⁷ Department of Cardiology, University Hospital Inselspital Bern, Bern, Switzerland.

Abstract

Background: Prior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD).

Objectives: The authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved.

Methods: Using a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed.

Results: Among 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83], P < 0.001) and with a shorter time to their development (β = -0.486 [95% CI: -0.62 to -0.35], P < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055], P < 0.05). Neuro-immune pathways contributed to the development of CVDRFs (P < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression.

Conclusions: Anxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk.

Keywords: amygdala; cardiometabolic; mental health; neuro immune; prevention; sex differences.

Grants and funding

K23 HL151909/HL/NHLBI NIH HHS/United States