The Cardiovascular Impact and Genetics of Pericardial Adiposity
Joel T Rämö1,2,3, Shinwan Kany1,2,4, Cody R Hou1,5
1Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Insights
Pericardial adipose tissue (PAT) is linked to cardiovascular diseases and type 2 diabetes. Genetic analysis reveals shared determinants with abdominal fat, highlighting PAT as an independent predictor.
Area of Science:
- Cardiovascular Disease Research
- Genetics and Genomics
- Medical Imaging Analysis
Background:
- Previous studies on pericardial adipose tissue (PAT) and cardiovascular diseases were limited by sample size and population selection.
- The genetic underpinnings of pericardial adipose tissue (PAT) remain largely unexplored.
- Large-scale population studies are needed to understand PAT's role in cardiovascular health.
Purpose of the Study:
- To evaluate the association between pericardial adipose tissue (PAT) and prevalent and incident cardiovascular diseases.
- To identify the genetic determinants of pericardial adipose tissue (PAT) in a large cohort.
- To explore the relationship between PAT, cardiovascular disease risk, and genetic factors.
Main Methods:
- A deep learning model quantified pericardial adipose tissue (PAT) from UK Biobank cardiac MRI scans.
- Cross-sectional and prospective associations of PAT with cardiovascular diseases were analyzed, controlling for covariates.
- Genome-wide association study (GWAS) and polygenic score (PGS) analysis were conducted in UK Biobank and FinnGen cohorts.
Main Results:
- Pericardial adipose tissue (PAT) positively correlated with age, BMI, and waist-to-hip ratio, and was higher in males.
- Elevated PAT was associated with prevalent heart failure, type 2 diabetes, coronary artery disease, and atrial fibrillation.
- PAT predicted incident heart failure and type 2 diabetes independently of BMI, with 5 novel genetic loci identified.
Conclusions:
- Pericardial adipose tissue (PAT) shares genetic determinants with abdominal adiposity.
- Pericardial adipose tissue (PAT) is an independent predictor of incident type 2 diabetes and heart failure.
- Genetic insights into PAT may offer new avenues for cardiovascular disease prevention and treatment.
Background:
While previous studies have reported associations of pericardial adipose tissue (PAT) with cardiovascular diseases such as atrial fibrillation and coronary artery disease, they have been limited in sample size or drawn from selected populations. Additionally, the genetic determinants of PAT remain largely unknown. We aimed to evaluate the association of PAT with prevalent and incident cardiovascular disease and to elucidate the genetic basis of PAT in a large population cohort.
Methods:
A deep learning model was trained to quantify PAT area from four-chamber magnetic resonance images in the UK Biobank using semantic segmentation. Cross-sectional and prospective cardiovascular disease associations were evaluated, controlling for sex and age. A genome-wide association study was performed, and a polygenic score (PGS) for PAT was examined in 453,733 independent FinnGen study participants.
Results:
A total of 44,725 UK Biobank participants (51.7% female, mean [SD] age 64.1 [7.7] years) were included. PAT was positively associated with male sex (β = +0.76 SD in PAT), age (r = 0.15), body mass index (BMI; r = 0.47) and waist-to-hip ratio (r = 0.55) (P < 1×10-230). PAT was more elevated in prevalent heart failure (β = +0.46 SD units) and type 2 diabetes (β = +0.56) than in coronary artery disease (β = +0.22) or AF (β = +0.18). PAT was associated with incident heart failure (HR = 1.29 per +1 SD in PAT [95% CI 1.17-1.43]) and type 2 diabetes (HR = 1.63 [1.51-1.76]) during a mean 3.2 (±1.5) years of follow-up; the associations remained significant when controlling for BMI. We identified 5 novel genetic loci for PAT and implicated transcriptional regulators of adipocyte morphology and brown adipogenesis (EBF1, EBF2 and CEBPA) and regulators of visceral adiposity (WARS2 and TRIB2). The PAT PGS was associated with T2D, heart failure, coronary artery disease and atrial fibrillation in FinnGen (ORs 1.03-1.06 per +1 SD in PGS, P < 2×10-10).
Conclusions:
PAT shares genetic determinants with abdominal adiposity and is an independent predictor of incident type 2 diabetes and heart failure.
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