Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity
abstract
This abstract is available on the publisher's site.
Access this abstract now Full Text Available for ClinicalKey SubscribersBACKGROUND
The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood.
OBJECTIVES
This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression.
METHODS
Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygAC). CVD events were ascertained from electronic health records.
RESULTS
A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygAC (standardized β: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygAC reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023).
CONCLUSIONS
PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression.
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Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity
J Am Coll Cardiol 2024 Apr 23;83(16)1543-1553, H Zureigat, MT Osborne, S Abohashem, K Mezue, C Gharios, S Grewal, A Cardeiro, N Naddaf, G Civieri, T Abbasi, A Radfar, W Aldosoky, AV Seligowski, MM Wasfy, JS Guseh, TW Churchill, RP Rosovsky, Z Fayad, A Rosenzweig, A Baggish, RK Pitman, KW Choi, J Smoller, LM Shin, A TawakolFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Physical activity – why does it reduce CV risk?
We always tell patients that they need to do 150 minutes of exercise per week to reduce their risk of a cardiovascular (CV) event. Traditionally, we think it helps your heart stay in shape, which is true; however, the full benefit of physical activity (PA) may not stop at your heart.
This study looked at the effects of PA on the brain, particularly the neural network responsible for stress-related activities in the brain. The amygdala is the region that detects potential threats and the ventromedial prefrontal cortex (vmPFC) inhibits and regulates these "stress" centers.
The authors used data from the Mass General Brigham (MGB) Biobank, and the first question they asked was whether PA had a beneficial effect on CVD event reduction. And, in the 50,000-plus patients database, the patients who did the recommended exercises had a 19.8% reduction in 10-year CVD events compared with patients who did not do PA (HR, 0.802; 95% CI, 0.719–0.896; P < .001). So, PA is good.
Then the authors focused on the 774 patients who underwent 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography. These scans can measure the activity in different brain regions, and, hence, we can see whether physical activities affect the stress-related centers in the brain. With exercise, the activity of the amygdala was reduced, which means that there were fewer stress-related activities in the brain. However, there was more activity in the VMPFc, which inhibits stress-related activities in the brain. So, this lowers stress-related activities as well.
The PET scans effectively showed that PA turns off stress activity in the brain. This means that the activity of the hypothalamic–pituitary–adrenal axis is also reduced, and this has a great impact on the CV system. There were also reductions in inflammatory marker levels and coronary artery calcium scores.
Now, the final component is to look at patients with and without depression. We know that the activity of the amygdala is higher in patients with depression. Could PA have an even greater effect in patients with depression?
The authors compared 258 patients with a history of depression with 486 without a history of depression. They found a larger reduction in the rate of CV events with PA among the patients with a history of depression. The CV event reduction was twice as much as those without depression. In addition, a clear dose–response effect was observed, with further reductions in the risk of CVD events with more PA. Therefore, doing more than the recommended activity levels actually further reduced the CVD risk among patients with a history of depression. However, patients without depression did not have any extra benefit beyond the recommended activity levels. So, for patients with a history of depression, the more the PA the better.
This study has shown clearly that PA reduces stress-related activities in the brain. This is particularly useful in patients with a history of depression where these stress regions like the amygdala are overactive and the reduction with exercise has a profound effect on reducing CVD events.
We can tell patients that PA is good for their hearts and also good for their brains.
Recommended physical activity: (>150 minutes per week of moderate-intensity PA; >500 MET-min/wk)
Physical activity (PA) is associated with a lower risk of cardiovascular disease (CVD) as well as reduced incidence and symptoms of stress-related syndromes (such as anxiety and depression). As chronic stress and depression are associated with increased CVD risk in part via stress-related neural activity (SNA),1 this study tested whether PA 1) was associated with reductions in SNA, 2) decreased CVD risk in part via reductions in SNA, and 3) had a greater effect on CVD risk in individuals with depression.
Individuals enrolled in the Mass General Brigham Biobank completed a health behavior survey that assessed the average time spent per week on each of several activities during the preceding year. Individuals were followed for up to 10 years after enrollment. Diagnoses of depression and CVD were derived from ICD codes. Clinical 18F-FDG PET/CT imaging was performed in a subset of patients, enabling the assessment of SNA as the ratio of amygdalar-to–ventromedial prefrontal cortical metabolic activity.
Overall, 50,359 individuals (median age, 60 years; male, 40.1%) completed the PA questionnaire and were included in the study. Individuals who achieved the PA levels recommended by the guidelines had lower SNA; these differences remained significant in models adjusted for age, sex, socioeconomic and lifestyle factors, genetic influences (related to stress syndromes), and major medical comorbidities. Moreover, dose-dependent reductions in SNA were observed across the quintiles of PA. The reductions in SNA were driven by significant increases in prefrontal activity and a trend toward reductions in amygdalar activity.
Individuals meeting the PA guidelines had a 23.5% reduction in the 10-year risk of CVD. Mediation analysis suggests that reductions in SNA partially mediate the cardiovascular benefit of PA on CVD. As a follow-up to that observation, the investigators tested the hypothesis that individuals with higher SNA (eg, those with depression) may experience greater CVD risk reductions from PA. Notably, they observed that the benefits of PA on CVD were more than twice as great among individuals with pre-existing depression. Moreover, in subjects without pre-existing depression, CVD risk reduction plateaued after the third quintile of PA. In contrast, among individuals with pre-existing depression, there were additional reductions in CVD risk through the highest quintile of PA.
Overall, this study demonstrated that PA is associated with dose-dependent reductions in SNA and that this impact on SNA may partially mediate the cardiovascular benefit of PA on CVD risk. Moreover, individuals with pre-existing depression derive substantially greater CVD risk reduction from PA and continue to benefit even at higher levels of PA compared with individuals without depression. Altogether, these findings provide additional insights into the mechanisms underlying the benefits of PA and may inform individualized exercise prescriptions.
Reference