Elevated plasma hepcidin concentrations are associated with an increased risk of mortality and nonfatal cardiovascular events in patients with type 2 diabetes: a prospective study.

BACKGROUND: The effect of plasma hepcidin concentrations on the long-term risk of developing adverse cardiovascular outcomes in people with type 2 diabetes mellitus (T2DM) is unclear. METHODS: We followed for a median of 55.6 months 213 outpatients with established T2DM (45.5% women, mean age 69 ± 10 years; BMI 28.7 ± 4.7 kg/m2; median diabetes duration 11 years). Baseline plasma ferritin and hepcidin concentrations were measured with an electrochemiluminescence immunoassay and mass spectrometry-based assay, respectively. The primary study outcome was a composite of all-cause mortality or incident nonfatal cardiovascular events (inclusive of myocardial infarction, permanent atrial fibrillation, ischemic stroke, or new hospitalization for heart failure). RESULTS: 42 patients developed the primary composite outcome over a median follow-up of 55.6 months. After stratifying patients by baseline hepcidin tertiles [1st tertile: median hepcidin 1.04 (IQR 0.50-1.95) nmol/L, 2nd tertile: 3.81 (IQR 3.01-4-42) nmol/L and 3rd tertile: 7.72 (IQR 6.37-10.4) nmol/L], the risk of developing the primary composite outcome in patients in the 3rd tertile was double that of patients in the 1st and 2nd tertile combined (unadjusted hazard ratio [HR] 2.32, 95%CI 1.27-4.26; p = 0.007). This risk was not attenuated after adjustment for age, sex, adiposity measures, smoking, hypertension, statin use, antiplatelet medication use, plasma hs-C-reactive protein and ferritin concentrations (adjusted HR 2.53, 95%CI 1.27-5.03; p = 0.008). CONCLUSIONS: In outpatients with T2DM, higher baseline hepcidin concentrations were strongly associated with an increased long-term risk of overall mortality or nonfatal cardiovascular events, even after adjustment for established cardiovascular risk factors, plasma ferritin concentrations, medication use, and other potential confounders.

Relationship between Helicobacter pylori infection and risk of metabolic dysfunction-associated steatotic liver disease: An updated meta-analysis.

BACKGROUND: Recent observational studies examining the association between Helicobacter pylori infection and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) have reported conflicting results. We performed a meta-analysis to quantify the magnitude of the association between H. pylori infection and the risk of MASLD. METHODS: We systematically searched three large electronic databases to identify eligible observational studies (published up to 30 November 2023) in which liver biopsy, imaging methods or blood-based biomarkers/scores were used for diagnosing MASLD. Data from selected studies were extracted, and meta-analysis was performed using common and random-effects modelling. Statistical heterogeneity among published studies, subgroup analyses, meta-regression analyses and publication bias were assessed. RESULTS: A total of 28 observational studies (24 cross-sectional and 4 longitudinal studies) were identified, including 231 291 middle-aged individuals of predominantly Asian ethnicity (~95%). Meta-analysis of cross-sectional studies showed that H. pylori infection was significantly associated with a small increase in the risk of prevalent MASLD (n = 24 studies; random-effects odds ratio 1.11, 95% CI 1.05-1.18; I2 = 63%). Meta-analysis of data from longitudinal studies showed that H. pylori infection was significantly associated with an increased risk of developing incident MASLD over a mean 5-year follow-up (n = 4 studies; random-effects odds ratio 1.20, 95%CI 1.08-1.33; I2 = 44%). Sensitivity analyses did not modify these results. The funnel plot did not reveal any significant publication bias. CONCLUSIONS: H. pylori infection is associated with a mildly increased risk of prevalent and incident MASLD. Further well-designed prospective and mechanistic studies are required to better decipher the complex link between H. pylori infection and the risk of MASLD.

Clinical risk factors and features on computed tomography angiography in high-risk carotid artery plaque in patients with type 2 diabetes.

BACKGROUND: High-risk carotid artery plaque (HPR) is associated with a markedly increased risk of ischemic stroke. The aims of this study were: 1) to examine the prevalence of HRP in a cohort of asymptomatic adults with type 2 diabetes (T2D); 2) to investigate the relationship between HRP, established cardiovascular risk factors and computed tomography angiography (CTA) profile; and 3) to assess whether the presence of HRP is associated with an increased risk of major adverse cardiovascular events (MACE). METHODS: This was a retrospective cohort study of T2D asymptomatic patients who underwent carotid endarterectomy (CEA) from January 2018 to July 2021. The carotid atherosclerotic plaque (CAP) was assessed for the presence of ulceration, the presence of lipids, fibrosis, thrombotic deposits, hemorrhage, neovascularization, and inflammation. A CAP presenting at least five of these histological features was defined as a HRP (Group A); in all other cases it was defined as a mild to moderate heterogeneous plaque and no-HRP (Group B). CTA features included the presence of rim sign consisting of thin peripheral adventitial calcification (<2 mm) and internal soft plaque (≥2 mm), NASCET percent diameter stenosis, maximum plaque thickness, ulceration, calcification, and intraluminal thrombus were recorded. Binary logistic regression with Uni- and Multivariate was used to evaluate possible predictors for HRP while multivariable Cox Proportional Hazards was used to assess independent predictors for MACE. RESULTS: One hundred eighty-five asymptomatic patients (mean age 73±8 years, 131 men), undergoing carotid endarterectomy, were included. Of these, 124 (67%) had HRP, and the 61 (33%) did not. Diabetic complications (OR 2.4, 95% CI: 1.1-5.1, P=0.01), NASCET stenosis ≥75% (OR 2.4, 95% CI: 1.2-3.7, P=0.02) and carotid RIM sign (OR 4.3, 95% CI: 3.9-7.3, P<0.001) were independently associated with HRP. However, HRP was not associated with a higher risk of MACE (freedom from MACE at 5 years: HRP 83.4% vs. non HRP 87.8%, P=0.72) or a reduction of survival (5-year survival estimates: HRP 96.4% vs. non HRP: 94.6%, P=0.76). CONCLUSIONS: A high prevalence of HRP (67%) was observed in asymptomatic and elderly T2D patients. Independent predictors of HRP were diabetic complications, NASCET stenosis ≥75% and carotid RIM sign (OR 4.3, 95% CI: 3.9-7.3, P<0.001). HRP was not associated with an increased risk of MACE during a mean follow-up of 39±24 years.