Circulating interleukin-32 levels are associated with arterial hypertension in individuals at risk of nafld

Background Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic comorbidities such as arterial hypertension and increased risk of cardiovascular disease (CVD), but the mechanism remains unclear. We recently reported that Interleukin-32 (IL32) is strongly upregulated and secreted in patients with severe NAFLD, correlating with liver damage. Accumulating evidence suggests that IL32 affects endothelial function and may contribute to CVD. Aim To examine the relationship between circulating IL32 and metabolic comorbidities in healthy individuals with metabolic risk factors for NAFLD. Methods IL32 plasma levels were measured by Human IL-32 DuoSet ELISA (R&D Systems) in the prospective Liver-Bible cohort 2020 (n=949, age 53.9±6.4 years, 83.3% males). Inclusion criteria were age 40-65 and ≥3 among: BMI≥25 Kg/m2, glucose≥100mg/dl, triglycerides≥150mg/dl, HDL<45/55 mg/dl in M/F, impaired blood pressure control (systolic/diastolic>130/80mmHg). Multivariable generalized linear models were used to analyse the independent determinants of log normalized IL32 levels. Results Among participants, 470 (49.5%) had NAFLD (CAP≥275), 20 (2.1%) liver stiffness measurement (LSM)≥8. Of these, 31.4% showed low circulating IL32 (<10pg/mL); median IL32 concentration was 559 pg/mL (IQR: 6258-4936 pg/mL). High circulating levels of IL32 were associated with female sex (p=.0498), as well as impaired blood pressure control (p=.0007), detected in 68.9% of participants. Notably, IL32 levels were correlated with systolic but not diastolic blood pressure (p=.017), while the use of some antihypertensive agents including beta-blockers and ace-inhibitors was inversely associated (p=.047 and p=.029 respectively). Among other liver disease predictors, plasma IL32 resulted inversely correlated with HbA1c (p=.051), but not with fasting insulin, circulating lipids and ferritin/CRP. The independent determinants of circulating IL32 levels are shown in the Table 1. Conclusion Results suggest a potential cross-talk between IL32 and CVD in individuals with metabolic risk factors. Additional studies are warranted to examine the possible role of IL32 as therapeutic target to reduce NAFLD comorbidities. Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic comorbidities such as arterial hypertension and increased risk of cardiovascular disease (CVD), but the mechanism remains unclear. We recently reported that Interleukin-32 (IL32) is strongly upregulated and secreted in patients with severe NAFLD, correlating with liver damage. Accumulating evidence suggests that IL32 affects endothelial function and may contribute to CVD. To examine the relationship between circulating IL32 and metabolic comorbidities in healthy individuals with metabolic risk factors for NAFLD. IL32 plasma levels were measured by Human IL-32 DuoSet ELISA (R&D Systems) in the prospective Liver-Bible cohort 2020 (n=949, age 53.9±6.4 years, 83.3% males). Inclusion criteria were age 40-65 and ≥3 among: BMI≥25 Kg/m2, glucose≥100mg/dl, triglycerides≥150mg/dl, HDL<45/55 mg/dl in M/F, impaired blood pressure control (systolic/diastolic>130/80mmHg). Multivariable generalized linear models were used to analyse the independent determinants of log normalized IL32 levels. Among participants, 470 (49.5%) had NAFLD (CAP≥275), 20 (2.1%) liver stiffness measurement (LSM)≥8. Of these, 31.4% showed low circulating IL32 (<10pg/mL); median IL32 concentration was 559 pg/mL (IQR: 6258-4936 pg/mL). High circulating levels of IL32 were associated with female sex (p=.0498), as well as impaired blood pressure control (p=.0007), detected in 68.9% of participants. Notably, IL32 levels were correlated with systolic but not diastolic blood pressure (p=.017), while the use of some antihypertensive agents including beta-blockers and ace-inhibitors was inversely associated (p=.047 and p=.029 respectively). Among other liver disease predictors, plasma IL32 resulted inversely correlated with HbA1c (p=.051), but not with fasting insulin, circulating lipids and ferritin/CRP. The independent determinants of circulating IL32 levels are shown in the Table 1. Results suggest a potential cross-talk between IL32 and CVD in individuals with metabolic risk factors. Additional studies are warranted to examine the possible role of IL32 as therapeutic target to reduce NAFLD comorbidities.