Hypertension mediated the effects of pericardial adipose tissue on cardiovascular diseases

ABSTRACT Background Although previous studies have presented a relevance between pericardial adipose tissue (PAT) and cardiovascular diseases (CVDs), the precise role of PAT in CVDs remains uncertain. Methods In the Mendelian randomization (MR) research, we extracted instrumental variants significantly correlated with PAT to assess its effects on CVDs. Inverse-variance weighted model was elected as the leading MR analytical method. F-statistic was utilized to assess the intensity of instrumental variants and avert weak-tool bias. Numerous sensitivity analyses were adopted to confirm the credibility of outcomes. The mediated effect of hypertension between PAT and CVDs was estimated in 2-step MR analysis. Results The MR research demonstrated genetically determined PAT was remarkably correlated with greater risks of cardiovascular disease (OR 1.15; 95% CI 1.09--1.22, P=1.32*10 -6 ), heart failure (OR 2.62; 95% CI 1.28--5.34, P=0.008), coronary heart disease (OR 3.53; 95% CI 1.55--8.06, P=0.003), ischemic heart disease (OR 2.31; 95% CI 1.14--4.67, P=0.020), ischemic stroke (OR 3.18; 95% CI 1.63--6.20, P=0.001), and venous thromboembolism (OR 1.02; 95% CI 1.00--1.04, P=0.015). And the correlation was partially mediated by hypertension. Results were verified by sensitivity analysis. Conclusions Genetic determined PAT was remarkably correlated with additional risks of diverse CVDs. Identified as a mediator, hypertension had a significant influence on the causal association. The correlation between PAT and CVDs deserves further exploration. NOVELTY AND RELEVANCE What Is New? This was the first Mendelian randomization research to detect the potential causal relationship of genetically determined PTA on multiple CVDs risks and confirm the mediating effect of hypertension on the causal association. What Is Relevant? The MR research not only estimated the causal effect of PAT on hypertension but also identified the mediating role of hypertension between PAT and CVDs. Clinical/Pathophysiological Implications? This study revealed PAT promoted CVDs progression and hypertension played an intermediary role, which indicated that PAT might serve as a potential therapeutic target and antihypertensive drugs could be conjunctly used to provide cardiovascular benefits. especially for people with obesity, because they had more PAT accumulation.