Abstract 16270: Genetic Susceptibility to Stress Associates With Higher Amygdalar Activity and Greater Myocardial Infarction Risk

Introduction and Hypothesis: Chronic psychological stress is strongly linked to cardiovascular disease (CVD) risk. Metabolic activity of the amygdala, a stress-associated brain center, robustly associates with high inflammation and CVD risk. We hypothesized that a validated polygenic risk score for neuroticism (nPRS), a broad trait measure of vulnerability to stress, independently associates with 1) heightened amygdalar activity (AmygA) and 2) increased myocardial infarction (MI) risk Methods: Individuals (N=14349; median age (IQR): 64 (52, 74) yrs, 46%male) were identified from the Partners Biobank where genome wide nPRS and principle components of ancestry (PCI) were calculated. Using validated 18 FDG PET/CT imaging methods, AmygA was measured (N=995) as a target-to-background-ratio in individuals with clinical PET/CT imaging. MI was adjudicated using International Classification of Diseases (ICD) diagnoses. Traditional CVD risk factors * and psychiatric history were obtained using ICD codes and questionnaires. Independent t-tests and linear and logistic regression were employed Results: A total of 1708 (12%) individuals experienced MI. nPRS associated with AmygA (standardized β [95% CI]: 0.07 [0.01, 0.13], p=0.02 Fig A ) after adjustment for age, sex, and 10 PCI. It remained significant after additional adjustment for psychiatric history (p=0.02). AmygA also predicted MI in an adjusted model (OR: 1.50, p=0.006 * ). Importantly, after adjustment for age, sex, and 10 PCI, nPRS significantly associated with MI incidence (standardized OR [95% CI]: 1.12 [1.05, 1.17], p<0.001 Fig B ) and remained significant after additional adjustment for CVD factors (p=0.006*) and psychiatric history (p=0.007) Conclusions: These findings show for the first time that a genetic susceptibility to stress (high nPRS) associates with greater stress-related neurobiological activity, and MI risk. Further, these findings suggest nPRS may serve as a novel risk marker for MI

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Abstract 17030: Stress-Related Neurobiological Activity Contributes to the Link Between Cardiovascular Polygenic Risk Score and Myocardial Infarction

Circulation ◽

10.1161/circ.142.suppl_3.17030 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Taimur Abbasi ◽

Shady Abohashem ◽

Tawseef Dar ◽

Ahmed Ghoneem ◽

Nicki Naddaf ◽

...

Keyword(s):

Risk Score ◽

International Classification Of Diseases ◽

Polygenic Risk Score ◽

Cvd Risk ◽

Dna Variation ◽

Polygenic Risk ◽

Inherited Susceptibility ◽

Classification Of Diseases ◽

Brain Center ◽

Fdg Pet Ct

Introduction: A polygenic risk score for coronary artery disease (PRS CAD ) integrates information from many sites of DNA variation into a single metric of inherited susceptibility. Heightened metabolic activity of the amygdala (AmygA), a stress-associated brain center, associates with increases in leukopoietic activity, atherosclerosis and CVD risk. We hypothesized that genes included in the PRS CAD link to MI in part by encoding for heightened stress-associated neurobiological activity. Accordingly, we tested whether CVPRS associates with heightened AmygA as a contributing factor linking high CVPRS and CVD events. Methods: Individuals (N=16821, median age (IQR): 63 (52, 74) years, 46% male) were identified from the Partners Biobank where genome-wide PRS CAD and principle components of ancestry (PCI) were calculated. Using validated 18 FDG-PET/CT imaging methods, AmygA was measured in individuals with prior clinical imaging (N=854). MI incidence was derived using International Classification of Diseases (ICD) diagnoses. Traditional CVD risk factors and psychiatric history were obtained using ICD codes and questionnaires and were used for covariable adjustments. Linear and logistic regression were employed. Results: A total of 2046 (12.1%) participants experienced an MI. PRS CAD associated with increased AmygA after adjusting for age and sex (β [95% confidence interval (CI)]: 0.099 [0.015, 0.183], p=0.021) as well as increased MI incidence (odds ratio (OR) [95% CI]: 1.208 [1.120, 1.302], p<0.001) ( Table 1, Figure 1 ). Concurrently, AmygA associated with increased MI incidence in adjusted analyses (OR [95% CI]: 1.451 [1.061, 1.983], p=0.003). Conclusion: High PRS CAD associates with higher AmygA and AmygA in-turn associates with MI. These findings suggest increased stress-related neurobiological activity may contribute to the link between PRS CAD and MI.

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Integrated FDG PET-CT imaging improves staging in malignant pleural mesothelioma

Nuklearmedizin ◽

10.3413/nukmed-0091 ◽

2007 ◽

Author(s):

Stefan Krüger ◽

S. Pauls ◽

Felix M. Mottaghy ◽

Andreas K. Buck ◽

Hubert Schelzig ◽

...

Keyword(s):

Malignant Pleural Mesothelioma ◽

Fdg Pet ◽

Ct Imaging ◽

Pleural Mesothelioma ◽

Pet Ct ◽

Fdg Pet Ct

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Dual Time F-18 FDG PET/CT Imaging in the Diagnosis of Renal Cell Cancer

Current Medical Imaging Formerly Current Medical Imaging Reviews ◽

10.2174/157340561002140715103316 ◽

2014 ◽

Vol 10 (2) ◽

pp. 134-139 ◽

Cited By ~ 2

Author(s):

Savas Karyagar ◽

Zehra Koc ◽

Sevda Karyagar ◽

Tamer Ozulker ◽

Cevat Topal ◽

...

Keyword(s):

Renal Cell Cancer ◽

Fdg Pet ◽

Renal Cell ◽

Cell Cancer ◽

Ct Imaging ◽

Pet Ct ◽

Fdg Pet Ct

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Editorial (Thematic Issue: From Nuisance to State-of-the-Art: FDG-PET/CT Imaging of Infection and Inflammation)

Current Molecular Imaginge ◽

10.2174/221155520303150826121337 ◽

2015 ◽

Vol 3 (3) ◽

pp. 180-181

Author(s):

Poul Flemming Hoilund-Carlsen ◽

Soren Hess

Keyword(s):

Fdg Pet ◽

State Of The Art ◽

Ct Imaging ◽

Thematic Issue ◽

Pet Ct ◽

Infection And Inflammation ◽

Imaging Of Infection ◽

Fdg Pet Ct

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FDG-PET/CT Imaging of Infected Bones and Prosthetic Joints

Current Molecular Imaginge ◽

10.2174/2211555204666150619153219 ◽

2015 ◽

Vol 3 (3) ◽

pp. 225-229 ◽

Cited By ~ 2

Author(s):

Sandip Basu ◽

Thomas C. Kwee ◽

Soren Hess

Keyword(s):

Fdg Pet ◽

Ct Imaging ◽

Prosthetic Joints ◽

Pet Ct ◽

Fdg Pet Ct

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FDG PET/CT imaging of desmoplastic small round cell tumor: findings at staging, during treatment and at follow-up

Pediatric Radiology ◽

10.1007/s00247-015-3315-y ◽

2015 ◽

Vol 45 (9) ◽

pp. 1308-1315 ◽

Cited By ~ 15

Author(s):

Austin Ostermeier ◽

M. Beth McCarville ◽

Fariba Navid ◽

Scott E. Snyder ◽

Barry L. Shulkin

Keyword(s):

Fdg Pet ◽

Ct Imaging ◽

Cell Tumor ◽

Round Cell ◽

Round Cell Tumor ◽

Small Round Cell Tumor ◽

Small Round Cell ◽

Pet Ct ◽

Fdg Pet Ct

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Quantitative analysis of myocardial metabolic heterogeneity is superior to visual assessment for the detection of active cardiac sarcoidosis by F-18 FDG PET-CT imaging

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa356.345 ◽

2021 ◽

Vol 22 (Supplement_1) ◽

Author(s):

M Malik ◽

M Yazdani ◽

SM Gould ◽

E Reyes

Keyword(s):

Fdg Pet ◽

Cardiac Sarcoidosis ◽

Visual Assessment ◽

Ct Imaging ◽

Myocardial Inflammation ◽

Fdg Uptake ◽

Pet Ct ◽

Metabolic Heterogeneity ◽

Fdg Pet Ct

Abstract Funding Acknowledgements Type of funding sources: None. Background Myocardial inflammation may occur in the context of a multisystem disease such as sarcoidosis, adversely affecting prognosis. A definitive diagnosis of cardiac sarcoidosis (CS) is essential to implementing life-saving treatment but this is complicated by the invasive nature of endomyocardial biopsy (EMB) and its low accuracy. Positron emission tomography (PET) assists in diagnosis, which relies on visual interpretation of myocardial F-18 FDG uptake. The value of quantitative analysis and its application to clinical practice remain uncertain. Purpose To investigate the power of quantitative F-18 FDG PET-CT imaging analysis for detecting CS in patients with suspected disease. Methods All patients underwent F-18 FDG PET-CT after a 24-hour low-carbohydrate diet and 15-hour fasting as part of their diagnostic work-up for suspected cardiac inflammation. Cardiovascular magnetic resonance acted as gatekeeper to PET-CT in 8 of every 10 scans. Myocardial F-18 FDG uptake was assessed qualitatively and quantitatively using both manually drawn regions of interest and automatic polar maps to measure global and segmental standardised F-18 FDG uptake values (SUV). The coefficient of variation (CoV) was calculated to determine uptake heterogeneity. To confirm diagnosis, follow-up data regarding disease progression, further testing and treatment were collected. To allow for sufficient follow-up time, the first 40 consecutive patients from a prospective registry (n= 214; Sep 2017-Jun 2020) were included. Results A comprehensive clinical picture was obtained successfully in 37 patients (median [IQR], 17 [13.5] months) and a final diagnosis of CS reached in 7 (disease prevalence, 19%). EMB was performed in 2 patients only while 3 underwent PPM/ICD implantation. Significant predictors of CS were fulfilment of Japanese Ministry of Health and Welfare criteria (Wald, 6.44; p = 0.01) and left ventricular dysfunction (Wald 6.72; p = 0.01). Qualitative F-18 FDG PET-CT had a high negative (95%) but low positive (45%) predictive value for CS (sensitivity, 83%; specificity, 77%). F-18 FDG SUV CoV was the strongest imaging predictor (Wald, 6.77; p = 0.009) and was significantly higher in CS than non-CS (CoV median [quartiles], 0.26 [0.21, 0.36] and 0.12 [0.11, 0.14] respectively; p = 0.004). As per ROC curve analysis (AUC, 0.84), a CoV threshold of 0.20 was highly specific (93%) and sensitive (86%) for CS. Conclusion In a referring population with a low prevalence of cardiac sarcoidosis, F-18 FDG PET-CT imaging is sensitive for the detection of myocardial inflammation with active disease unlikely in patients with a negative scan. Quantitative evaluation of metabolic heterogeneity within the myocardium provides a strong, independent marker of active disease and should be considered alongside visual assessment.

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