Peripheral arterial disease (PAD) has a strong relationship with inflammation. However, it is unclear whether the dietary inflammatory potential is associated with PAD. We aimed to address this knowledge gap. The dietary inflammatory index (DII) was obtained using a 24-h dietary recall interview for each individual. Logistic regression models and restricted cubic spline were performed to assess the relationship of DII with the prevalence of PAD. In addition, Spearman correlation analysis and subgroup analysis were also undertaken. In total, 5840 individuals from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) were enrolled in our study. Participants in higher DII quartile tended to have higher rates of PAD. The increase in DII scores showed a positive association with PAD after fully multivariate adjustment (OR (odds ratios) = 1.094, 95% confidence interval (CI): 1.022–1.171). The multivariable-adjusted OR and 95% CI of the highest DII index quartile compared with the lowest quartile was 1.543 (95% CI: 1.116–2.133). Subgroup analysis demonstrated that the positive association between DII and PAD was persistent across population subgroups. In conclusion, we report that a proinflammatory dietary pattern is related to a higher risk of developing PAD among US adults.

Life’s Simple 7 (LS7) is the American Heart Association’s (AHA) proposal for a healthy lifestyle, also known as cardiovascular health (CVH) metrics. However, the association between CVH metrics and the severity of hepatic steatosis and liver fibrosis detected by transient elastography is unknown. We performed a cross-sectional study using the data from the 2017–2018 National Health and Nutrition Examination Survey (NHANES) cycle. The controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) were used to evaluate the severity of hepatic steatosis and liver fibrosis and to define NAFLD, advanced liver fibrosis, and cirrhosis. A total of 2679 participants were included. Multivariate linear regression analysis revealed that per 1-unit increase in the CVH metric, CAP and LSM decreased by 8.565 units and 0.274 units, respectively. In the multivariate logistic regression analysis, the risk of NAFLD, advanced liver fibrosis, and cirrhosis were 7, 10, and 6 times higher in the poor CVH group than in the ideal CVH group. Subgroup analysis indicated that CVD patients and non-Hispanic whites could benefit more from ideal CVH. In conclusion, adherence to ideal CVH metrics, as proposed by the AHA, can significantly reduce the risk of hepatic steatosis and liver fibrosis.

Statin therapy plays an important role in stabilizing and regressing coronary artery plaques. Omega-3 supplements also have anti-inflammatory and antioxidant effects on coronary plaques. However, the effect of omega-3 supplementation on the basis of statin therapy on the stability and composition of plaques, is still unclear. We searched for randomized controlled trials published prior to November 2020 in the PubMed, Embase and Cochrane databases. Finally, eight studies using different imaging techniques to evaluate coronary atherosclerotic plaque, including optical coherence tomography (OCT), coronary CT angiography (cCTA) and intravascular ultrasound (IB-IVUS), met our inclusion criteria. We pooled data extracted from the included studies using the standardized mean difference (SMD) or mean difference (MD) of the random effects model. Compared with statin treatment alone, the combined treatment further delayed the progression of total plaque volume [SMD -0.36, 95% confidence interval (CI) -0.64 to -0.08, p = 0.01] and fiber content (SMD -0.40, 95% CI -0.68 to -0.13, p = 0.004). The plasma high-sensitivity C-reactive protein (hs-CRP) level of patients in the combination treatment group was significantly lower than that of the patients in the statin treatment group alone (SMD -0.30, 95% CI -0.59 to -0.01, p = 0.04). In addition, the combined use of omega-3 further increases the fibrous cap thickness (FCT) of the plaque with an MD of 29.45 μm. There were no significant differences in plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or lipid content in plaques between the two groups. Omega-3 combined with statins is superior to the statin treatment group in stabilizing and promoting coronary plaque regression and may help to further reduce the occurrence of cardiovascular events.

Obesity is a major health issue and a risk factor for venous thromboembolic disease. Plasminogen activator inhibitor 1 (PAI-1), encoded by the gene SERPINE1, is a negative regulator of fibrinolysis and has been associated with obesity. The liver, which senses obesity-induced metabolic stress, is a key determinant of circulating PAI-1 levels. However, the mechanisms underlying the increased PAI-1 expression in obesity are unclear. This study investigated the upstream regulation of PAI-1 and its role in fibrinolysis and deep vein thrombosis (DVT). Compared with lean mice, diet-induced obesity mice presented significantly shorter fibrinolysis times and larger venous thrombi, largely due to increased hepatocyte expression of PAI-1. A publicly available single-cell RNA sequence data set from the livers of individuals with obesity suggested that increased PAI-1 expression may be related to reduced hepatocyte farnesoid X receptor (FXR) signaling. FXR activation also suppressed Serpine1 mRNA and PAI-1 protein expression levels in both mice and primary mouse hepatocytes (MPHs), but a decrease in PAI-1 in MPHs of Fxr-null mice after FXR activation was not observed. Both Fxr-null mice and Fxrfl/fl mice with AAV8-TBG-Cre exhibited significantly elevated plasma PAI-1, resulting in further impaired fibrinolysis and increased DVT burden. Dual-luciferase reporter assays and chromatin immunoprecipitation suggested that FXR activation directly represses Serpine1 transcription. Importantly, tropifexor treatment of obese mice lowered plasma PAI-1 levels and further alleviated fibrinolysis and the DVT load. These findings suggest that targeting FXR in hepatocytes may improve fibrinolysis and reduce DVT risk.