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

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

Giovanni Civieri  1   2 , Shady Abohashem  1   3 , Simran S Grewal  1   3 , Wesam Aldosoky  1 , Iqra Qamar  1   3 , Erin Hanlon  1 , Karmel W Choi  4   5   6 , Lisa M Shin  7   8 , Rachel P Rosovsky  9 , Sandeep Chandra Bollepalli  10 , Hui Chong Lau  1   3 , Antonis Armoundas  10   11 , Antonia V Seligowski  1   4 , Sarah M Turgeon  12 , Roger K Pitman  8 , Francesco Tona  2 , Jason H Wasfy  3 , Jordan W Smoller  4   5   13   14 , Sabino Iliceto  2 , Jill Goldstein  4   14 , Catherine Gebhard  15   16   17 , Michael T Osborne  1   3 , Ahmed Tawakol  1   3
Affiliations

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

Giovanni Civieri et al. JACC Adv. .

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.

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Conflict of interest statement

Dr Osborne has received consulting fees from WCG Clinical for unrelated work; and is supported in part by NIH K23HL151909 and AHA 23SCISA1143491. Dr Tawakol’s institution has received grant support from Lung Biotechnologies for unrelated work. Dr Seligowski is supported in part by NIH MH125920. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.PerspectivesCOMPETENCY IN MEDICAL KNOWLEDGE: Important neuroimmune pathways underlie the association between anxiety, depression, and cardiovascular risk. Specific treatment of these pathways may reduce the cardiovascular risk associated with anxiety and depression. COMPETENCY IN PATIENT CARE: A close screening of cardiovascular risk factors should be performed in subjects with anxiety and depression. Younger female, although generally being at low risk of developing cardiovascular risk factors, are particularly susceptible to the cardiometabolic effects of anxiety and depression,

Figures

None
Graphical abstract
Figure 1
Figure 1
Study Design AmygAc = amygdalar to ventromedial prefrontal cortical activity ratio; AF = atrial fibrillation; AFL = atrial flutter; HFrEF = heart failure with reduced ejection fraction; HRV = heart rate variability; hs-CRP = high sensitivity C-reactive protein; MACE = major adverse cardiovascular event; MI = myocardial infarction; VT = ventricular tachycardia.
Central Illustration
Central Illustration
Anxiety and Depression are Associated With Accelerated Development of Cardiovascular Disease Risk Factors (A) Anxiety and/or depression are associated with an accelerated development of new CVDRFs. Increased stress-related neural activity, chronic inflammation, and sympathetic activity are associated with anxiety and/or depression, interact with each other, and might represent the mechanistic background of the association between psychiatric conditions and development of new CVDRF. Finally, the development of new CVDRF represents an important mediator in the relationship between anxiety, depression, and MACE. (B) Depression and/or anxiety significantly reduce the survival free from the development of new CVDRF (area between the curves=0.718 [95% CI: 0.627-0.807], P < 0.001). (C) Younger females suffer a significantly greater influence of anxiety and/or depression on the development of CVDRFs than other age and sex subgroups. Analyses are adjusted for the components of the primary model. Error bars represent 95% CI. ∗P < 0.05; anx/dep = anxiety and/or depression; CVDRF = cardiometabolic cardiovascular risk factor (hypertension, hyperlipidemia, and diabetes mellitus); ns = not significant; MACE = major adverse cardiovascular event.
Figure 2
Figure 2
Anxiety and Depression Influence the Timing of Development of CVDRFs Among subject (n = 27,048) who develop CVDRF, those with anxiety and/or depression develop them sooner than patients without. The presence of both conditions has a significant effect compared to the presence of only one. Time is expressed as mean time within each group, with error bars representing 95% confidence interval. ∗P < 0.05; HTN = hypertension; HLD = hyperlipidemia; DM = diabetes mellitus; CVDRF = cardiometabolic cardiovascular risk factor (hypertension, hyperlipidemia, diabetes mellitus); ns = non-significant.
Figure 3
Figure 3
Age and Sex Modify the Relationship Between Psychiatric Conditions and Neuro-immune Pathways (A) In younger participants, the presence of pre-existing anxiety and/or depression tends to determine a greater increase in AmygAc (P for interaction = 0.058). (B) Although younger females have the greatest relative increase in hs-CRP levels when pre-existing depression/anxiety is present, neither age nor sex significantly modified the impact of depression/anxiety on hs-CRP. (C) In younger participants, the presence of pre-existing anxiety and/or depression determined a significantly greater increase in HRV (P for interaction = 0.06). Among these, the effect is stronger in female (P for interaction = 0.037). Mean values of AmygAc, HRV, and CRP are reported. Error bars represent 95% CI. Age is divided according to the median age of each study cohort. ∗P < 0.05; anx/dep = anxiety and/or depression; AmygAc = amygdalar to ventromedial prefrontal cortical activity ratio; HRV = heart rate variability; hs-CRP = high sensitivity C-reactive protein; ns = not significant
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