Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature.

High levels of homocysteine (Hcy) have been linked with adverse cardiovascular outcomes, such as arrhythmias and stroke. In the context of paroxysmal atrial fibrillation (PAF), hyperhomocysteinemia has been demonstrated to be an independent predictor of future events. The aim of this report was to address the potential value of Hcy levels in predicting future paroxysms of atrial fibrillation (AF), as well as to identify the potential mechanisms of action. We searched PubMed and the Cochrane Database on 16 January 2022. Keywords used were homocysteine or hyperhomocysteinemia paired with a total of 67 different keywords or phrases that have been implicated with the pathogenesis of AF. We included primary reports of clinical and non-clinical data in the English language, as well as systematic reviews with or without meta-analyses. We placed no time constraints on our search strategy, which yielded 3748 results. Following title review, 3293 reports were excluded and 455 reports were used for title and abstract review, after which 109 reports were finally used for full-text review. Our review indicates that Hcy levels seem to hold a predictive value in PAF. Herein, potential mechanisms of action are presented and special considerations are made for clinically relevant diagnostic procedures that could complement plasma levels in the prediction of future PAF events. Finally, gaps of evidence are identified and considerations for future clinical trial design are presented.

Association Between Secondary Hyperparathyroidism and Body Composition in Pediatric Patients With Moderate and Advanced Chronic Kidney Disease.

Objective: This single center cross-sectional study aims to investigate the association between secondary hyperparathyroidism and body composition in pediatric patients with moderate (stage 3) and advanced (stage 4-5) chronic kidney disease (CKD). Methods: 61 patients (median age: 13.4 years) were included. Body composition indices, including lean tissue index (LTI) and fat tissue index (FTI), were measured using multi-frequency bio-impedance spectroscopy. Muscle wasting was defined as LTI adjusted to height-age (HA) z-score < -1.65 SD and high adiposity as FTI z-score > 1.65 SD. Serum mineral metabolism parameters, including serum intact parathormone (iPTH), calcium, phosphorus and 25-hydroxyvitamin D, as well as serum leptin were measured in each patient. In advanced CKD patients, the mean values of serum mineral laboratory parameters of the 6 months prior to body composition assessment were recorded, and alfacalcidol index, defined as weekly alfacalcidol dose (mcg/week) per pg/ml of iPTH × 1,000, was calculated. Results: In moderate CKD (31 patients), high iPTH (>90 ng/ml) was observed in 10 (32.3%) patients and was associated with higher FTI z-score (p = 0.022). Moreover, serum iPTH was negatively correlated to LTI HA z-score (rs = -0.486, p = 0.006), and positively correlated to serum leptin levels (rs = 0.369, p = 0.041). The positive correlation between FTI z-score and iPTH (rs = 0.393, p = 0.039) lost significance after adjustment for serum leptin. iPTH was positively associated with high adiposity (12 patients, 38.7%) after adjustment for the other mineral metabolism parameters (OR 1.023, 95% CI 1.002-1.045, p = 0.028). In advanced CKD (30 patients), no significant correlation was observed between iPTH and body composition indices and serum leptin levels. Eleven (36.7%) patients with muscle wasting presented lower alfacalcidol index (p = 0.017). Alfacalcidol index ≤ 24 was strongly associated with muscle wasting after adjustment for CKD stage and other mineral metabolism parameters (OR 7.226, 95% CI 1.150-45.384, p = 0.035). Conclusion: Secondary hyperparathyroidism is associated with high adiposity in moderate but not in advanced CKD, with leptin acting as a potential contributive factor. In advanced CKD, targeting higher alfacalcidol weekly dose per each unit of serum PTH seems beneficial for preventing muscle wasting.

Association between insulin growth factor-1, bone mineral density, and frailty phenotype in children with chronic kidney disease.

BACKGROUND: This cohort study investigates the association between insulin growth factor-1 (IGF-1), bone mineral density, and frailty phenotype in children with chronic kidney disease (CKD). METHODS: Forty-six patients (median age 14.5 years) were prospectively enrolled. Frailty phenotype was defined as the presence ≥ 3 of the following indicators: suboptimal growth/weight gain (body mass index height age < 5th percentile or height < 3rd percentile or loss of ≥ 10 percentiles/year in at least one parameter), low muscle mass (lean tissue mass height age < 5th percentile or loss of ≥ 10 percentiles/year), general fatigue reported by parent or child, and C-reactive protein > 3 mg/l. Lumbar bone mineral apparent density (LBMAD) was measured by dual-energy X-ray absorptiometry, body composition by bioimpedance spectroscopy, and IGF-1 by enzyme-labeled chemiluminescent immunometric assay. RESULTS: Frailty phenotype (seven patients) was more frequent in advanced CKD (estimated glomerular filtration rate < 30 ml/min/1.73m2) (p = 0.014). IGF-1 and LBMAD z-scores were lower in patients with suboptimal growth/weight gain (14 patients) (p = 0.013, p = 0.012), low muscle mass (nine patients) (p = 0.001, p = 0.009), and general fatigue (eight patients) (p < 0.001, p = 0.004). IFG-1 and LBMAD z-scores were associated with frailty phenotype (OR 0.109, 95% CI 0.015-0.798 and OR 0.277, 95% CI 0.085-0.903) after adjustment for CKD stage. IGF-1 z-score was associated with LBMAD < 5th percentile (six patients) (OR 0.020, 95% CI 0.001-0.450) after adjustment for CKD stage. The association between LBMAD and frailty phenotype lost significance after adjustment for IGF-1. CONCLUSION: Frailty phenotype is more frequent in advanced pediatric CKD. IGF-1 is negatively associated with frailty phenotype and interferes in the association between frailty and LBMAD.

Association between relative fat mass, uric acid, and insulin resistance in children with chronic kidney disease.

INTRODUCTION: This cross-sectional study investigates the association between insulin resistance (IR) and serum uric acid (sUA) and relative fat (RFM) and lean mass (RLM) profiles in children with chronic kidney disease (CKD). MATERIAL AND METHODS: RLM and RFM were assessed by bioimpedance spectroscopy in 41 children and adolescents. Normal weight obesity (NWO) was defined as normal height-age body mass index and RFM >85th percentile, according to age and sex. Homeostatic model assessment of insulin resistance (HOMA-IR) level >95th percentile, according to sex and pubertal stage, and sUA >7 mg/dl were used to define IR and hyperuricemia, respectively. RESULTS: High RFM (15 patients) and NWO (7 patients) were associated with higher HOMA-IR in total (p < 0.001) and normal-weight patients (p = 0.004), respectively. RFM was positively and RLM negatively correlated to HOMA-IR (rs = 0.500, p = 0.001 and rs = -0.539, p < 0.001, respectively) and sUA (rs = 0.370, p = 0.017 and rs = -0.325, p = 0.038, respectively), while sUA was positively correlated to HOMA-IR (rs = 0.337, p = 0.031). Hyperuricemia (16 patients) was positively associated with higher RFM and HOMA-IR (p = 0.001 and p = 0.010, respectively). The correlation between sUA and HOMA-IR lost significance after adjustment for RFM. In logistic regression analysis, a 5% increase in RFM was associated with IR (11 patients) independently of the age, sex, sUA, and CKD stage in both total (OR 2.174, 95% CI 1.115-4.225) and normal-weight (OR 3.504, 95% CI 1.110-11.123) patients. CONCLUSION: Children with high RFM, including those presenting NWO, are at risk for IR regardless of CKD stage. RFM is probably the mediator of the link between sUA and IR.

High serum ferritin is associated with worse outcome of patients with decompensated cirrhosis.

BACKGROUND: Studies in patients with decompensated cirrhosis showed a correlation between serum ferritin levels and patients' prognosis. Besides, red blood cell distribution width (RDW) and mean platelet volume (MPV) have been associated with the severity of hepatic function. The aim of this study was to evaluate the prognostic impact of serum ferritin and RDW/MPV in the outcome [survival, death, or liver transplantation (LT)] of patients with stable decompensated cirrhosis. METHODS: Consecutive adult patients with stable decompensated cirrhosis admitted to our department between September 2010 and February 2016 were included. Serum ferritin, RDW and MPV were recorded in every patient. They were followed up and their outcome (alive, death, or LT) was evaluated. RESULTS: 192 consecutive patients with stable decompensated cirrhosis (142 men, age 54.2±12 years); at the end of follow up [12 (range: 1-64) months] 62 patients remained alive and 130 died or underwent LT. In multivariate analysis, serum ferritin (HR 1.001, 95%CI 1.00-1.002, P=0.005) and GFR (HR 0.96, 95%CI 0.92-0.99, P=0.035) were the only independent factors significantly associated with the outcome. Ferritin had low discriminative ability (AUC: 0.61) to the outcome yielding a sensitivity and specificity of 85.3% and 44.2%, respectively, at the best cut-off point (>55 ng/mL), while patients with ferritin >55 ng/mL (n=145) had a worse outcome compared to those with ferritin ≤55 ng/mL (n=47) (log rank P=0.001). RDW and MPV were not associated with the outcome. CONCLUSION: High serum ferritin, but not RDW/MPV, is associated with worse outcome in patients with established decompensated cirrhosis. However, further studies are needed to elucidate better this issue.