Anxiety and depression are associated with heightened risk of incident deep vein thrombosis: Mediation through stress-related neural mechanisms.

Controversy exists as to whether anxiety and depression increase deep vein thrombosis (DVT) risk, and the mechanisms mediating potential links remain unknown. We aimed to evaluate the association between anxiety and depression and DVT risk and determine whether upregulated stress-related neural activity (SNA), which promotes chronic inflammation, contributes to this link. Our retrospective study included adults (N = 118 871) enrolled in Mass General Brigham Biobank. A subset (N = 1520) underwent clinical 18F-FDG-PET/CT imaging. SNA was measured as the ratio of amygdalar to cortical activity (AmygAC). High-sensitivity C-reactive protein (hs-CRP) and heart rate variability (HRV) were also obtained. Median age was 58 [interquartile range (IQR) 42-70] years with 57% female participants. DVT occurred in 1781 participants (1.5%) over median follow-up of 3.6 years [IQR 2.1-5.2]. Both anxiety and depression independently predicted incident DVT risk after robust adjustment (HR [95% CI]: 1.53 [1.38-1.71], p < .001; and 1.48 [1.33-1.65], p < .001, respectively). Additionally, both anxiety and depression associated with increased AmygAC (standardized beta [95% CI]: 0.16 [0.04-0.27], p = .007, and 0.17 [0.05-0.29], p = .006, respectively). Furthermore, AmygAC associated with incident DVT (HR [95% CI]: 1.30 [1.07-1.59], p = .009). Mediation analysis demonstrated that the link between anxiety/depression and DVT was mediated by: (1) higher AmygAC, (2) higher hs-CRP, and (3) lower HRV ( < .05 for each). Anxiety and depression confer an attributable risk of DVT similar to other traditional DVT risk factors. Mechanisms appear to involve increased SNA, autonomic system activity, and inflammation. Future studies are needed to determine whether treatment of anxiety and depression can reduce DVT risk.

Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution.

With a growing body of evidence that now links environmental pollution to adverse cardiovascular disease (CVD) outcomes, pollution has emerged as an important risk factor for CVD. There is thus an urgent need to better understand the role of pollution in CVD, key pathophysiological mechanisms, and to raise awareness among health care providers, the scientific community, the general population, and regulatory authorities about the CV impact of pollution and strategies to reduce it. This article is part 2 of a 2-part state-of-the-art review on the topic of pollution and CVD-herein we discuss major environmental pollutants and their effects on CVD, highlighting pathophysiological mechanisms, and strategies to reduce CVD risk.

Environmental Pollution and Cardiovascular Disease: Part 1 of 2: Air Pollution.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Over the past 50 years, there has been a substantial decline in the incidence of CVD and related mortality in high-income countries, largely due to the mitigation of modifiable risk factors such as smoking, hypertension, and diabetes. However, a significant burden of CVD remains in low- to middle-income countries, despite their lower prevalence of traditional risk factors; other environmental factors, particularly pollution, play a significant role in this attributable risk. Mounting evidence underscores a strong association between pollution and adverse health effects, including CVD. This article is part 1 of a 2-part state-of-the-art review and discusses air pollution and its adverse effects on CVD, highlighting pathophysiological mechanisms and methods to reduce air pollution and exposure to these pollutants.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity.

BACKGROUND: 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 ß: -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.

Radiology: Cardiothoracic Imaging Highlights 2023.

Radiology: Cardiothoracic Imaging publishes novel research and technical developments in cardiac, thoracic, and vascular imaging. The journal published many innovative studies during 2023 and achieved an impact factor for the first time since its inaugural issue in 2019, with an impact factor of 7.0. The current review article, led by the Radiology: Cardiothoracic Imaging trainee editorial board, highlights the most impactful articles published in the journal between November 2022 and October 2023. The review encompasses various aspects of coronary CT, photon-counting detector CT, PET/MRI, cardiac MRI, congenital heart disease, vascular imaging, thoracic imaging, artificial intelligence, and health services research. Key highlights include the potential for photon-counting detector CT to reduce contrast media volumes, utility of combined PET/MRI in the evaluation of cardiac sarcoidosis, the prognostic value of left atrial late gadolinium enhancement at MRI in predicting incident atrial fibrillation, the utility of an artificial intelligence tool to optimize detection of incidental pulmonary embolism, and standardization of medical terminology for cardiac CT. Ongoing research and future directions include evaluation of novel PET tracers for assessment of myocardial fibrosis, deployment of AI tools in clinical cardiovascular imaging workflows, and growing awareness of the need to improve environmental sustainability in imaging. Keywords: Coronary CT, Photon-counting Detector CT, PET/MRI, Cardiac MRI, Congenital Heart Disease, Vascular Imaging, Thoracic Imaging, Artificial Intelligence, Health Services Research © RSNA, 2024.

PTSD increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways.

While posttraumatic stress disorder (PTSD) is known to associate with an elevated risk for major adverse cardiovascular events (MACE), few studies have examined mechanisms underlying this link. Recent studies have demonstrated that neuro-immune mechanisms, (manifested by heightened stress-associated neural activity (SNA), autonomic nervous system activity, and inflammation), link common stress syndromes to MACE. However, it is unknown if neuro-immune mechanisms similarly link PTSD to MACE. The current study aimed to test the hypothesis that upregulated neuro-immune mechanisms increase MACE risk among individuals with PTSD. This study included N = 118,827 participants from a large hospital-based biobank. Demographic, diagnostic, and medical history data collected from the biobank. SNA (n = 1,520), heart rate variability (HRV; [n = 11,463]), and high sensitivity C-reactive protein (hs-CRP; [n = 15,164]) were obtained for a subset of participants. PTSD predicted MACE after adjusting for traditional MACE risk factors (hazard ratio (HR) [95 % confidence interval (CI)] = 1.317 [1.098, 1.580], ß = 0.276, p = 0.003). The PTSD-to-MACE association was mediated by SNA (CI = 0.005, 0.133, p < 0.05), HRV (CI = 0.024, 0.056, p < 0.05), and hs-CRP (CI = 0.010, 0.040, p < 0.05). This study provides evidence that neuro-immune pathways may play important roles in the mechanisms linking PTSD to MACE. Future studies are needed to determine if these markers are relevant targets for PTSD treatment and if improvements in SNA, HRV, and hs-CRP associate with reduced MACE risk in this patient population.

Beyond symptoms: Unlocking the potential of coronary calcium scoring in the prevention and treatment of coronary artery disease.

Coronary Artery Disease (CAD) represents a persistent global health menace, particularly prevalent in Eastern European nations. Often asymptomatic until its advanced stages, CAD can precipitate life-threatening events like myocardial infarction or stroke. While conventional risk factors provide some insight into CAD risk, their predictive accuracy is suboptimal. Amidst this, Coronary Calcium Scoring (CCS), facilitated by non-invasive computed tomography (CT), emerges as a superior diagnostic modality. By quantifying calcium deposits in coronary arteries, CCS serves as a robust indicator of atherosclerotic burden, thus refining risk stratification and guiding therapeutic interventions. Despite certain limitations, CCS stands as an instrumental tool in CAD management and in thwarting adverse cardiovascular incidents. This review delves into the pivotal role of CCS in CAD diagnosis and treatment, elucidates the involvement of calcium in atherosclerotic plaque formation, and outlines the principles and indications of utilizing CCS for predicting major cardiovascular events.

Lack of leisure time physical activity and variations in cardiovascular mortality across US communities: a comprehensive county-level analysis (2011-2019).

OBJECTIVES: To investigate the associations between county-level proportions of adults not engaging in leisure-time physical activity (no LTPA) and age-adjusted cardiovascular mortality (AACVM) rates in the overall US population and across demographics. METHODS: Analysing 2900 US counties from 2011 to 2019, we used the Centers for Disease Control and Prevention (CDC) databases to obtain annual AACVM rates. No LTPA data were sourced from the CDC's Behavioural Risk Factor Surveillance System survey and county-specific rates were calculated using a validated multilevel regression and poststratification modelling approach. Multiple regression models assessed associations with county characteristics such as socioeconomic, environmental, clinical and healthcare access factors. Poisson generalised linear mixed models were employed to calculate incidence rate ratios (IRR) and additional yearly deaths (AYD) per 100 000 persons. RESULTS: Of 309.9 million residents in 2900 counties in 2011, 7.38 million (2.4%) cardiovascular deaths occurred by 2019. County attributes such as socioeconomic, environmental and clinical factors accounted for up to 65% (adjusted R2=0.65) of variance in no LTPA rates. No LTPA rates associated with higher AACVM across demographics, notably among middle-aged adults (standardised IRR: 1.06; 95% CI (1.04 to 1.07)), particularly women (1.09; 95% CI (1.07 to 1.12)). The highest AYDs were among elderly non-Hispanic black individuals (AYD=68/100 000). CONCLUSIONS: Our study reveals a robust association between the high prevalence of no LTPA and elevated AACVM rates beyond other social determinants. The most at-risk groups were middle-aged women and elderly non-Hispanic black individuals. Further, county-level characteristics accounted for substantial variance in community LTPA rates. These results emphasise the need for targeted public health measures to boost physical activity, especially in high-risk communities, to reduce AACVM.