Differential Impact of Biologic Therapy on Heart Function Biomarkers in Rheumatoid Arthritis Patients: Observational Study on Etanercept, Adalimumab, and Tocilizumab.

BACKGROUND: Rheumatoid arthritis (RA) represents the most frequent form of inflammatory arthritis, affecting approximately 1% of the population worldwide. The introduction of novel therapeutic strategies targeting proinflammatory cytokines (TNF-α and interleukin-6) revolutionized the treatment of RA. This kind of treatment, although effective in a substantial portion of patients, may potentially cause many side effects. Among them, cardiovascular safety is one of the main concerns. OBJECTIVES: In the present study, we investigated the impact of treatment with anti-TNF-α and anti-IL-6 agents on heart function and levels of heart function biomarkers. METHODS: To measure this, we used cardiac function biomarkers, such as NT-pro Brain Natriuretic Peptide, mid regional pro-Atrial Natriuretic Peptide, Galectin-3, and Heart-Type Fatty Acid-Binding Protein and compared them to patients treated with methotrexate as well as healthy controls. RESULTS: Patients treated with biologics were characterized by low disease activity or were in remission. The disease activity in these groups was significantly lower than in the methotrexate group. All patients recruited for the study were characterized by normal heart function measured using echocardiography (EF>50%). With the exception of MR-proANP between tocilizumab and adalimumab (median: 1.01 vs. 0.49 nmol/L, p<0.05), we failed to observe any significant differences in biomarkers levels between groups treated with biologics. Contrary to this, patients on MTX showed higher NT-proBNP levels compared to adalimumab and healthy controls (p<0.05 for both). Striking differences have been shown in regard to H-FABP. The levels of these biomarkers were elevated in all biologics and the methotrexate group compared to healthy controls. CONCLUSION: As this biomarker reflects potential heart injury, we suggest that heart damage proceeds in a continuous manner in RA patients despite effective treatment and attainment of remission/low disease activity. This finding, however, should be verified in a larger cohort of RA patients to ascertain if the routine assessment of H-FABP may be useful for the detection of patients with RA who are at risk of development of heart damage.

Factors affecting vitamin D status in outpatients with abdominal aortic aneurysm and peripheral artery disease- a single centre study.

BACKGROUND AND AIMS: Vitamin D (VD) deficiency is considered an important risk factor for the development of atherosclerosis and aortic aneurysms. The deficiency is claimed to enhance degeneration and remodeling of collagen and elastin fibers in the artery wall, leading to its weakening and progressive dilatation. This study aimed to assess vitamin D status, in outpatients with abdominal aneurysms (AAA) and peripheral artery disease (PAD) not treated with VD, and factors affecting serum 25-OH-D levels. METHODS AND RESULTS: This cross-sectional study involved 59 outpatients with AAA and 150 with PAD. AAA was defined as local dilation of the aorta diameter >30 mm in imaging. None of the patients was prescribed VD containing medicines. Serum 25-OH, iPTH, phosphorus and calcium levels were assessed in all study participants. VD status was categorized according to commonly used cut-offs for serum 25-OH-D (<20 ng/mL - deficiency, <30 ng/mL -insufficiency). Serum 25-OH-D levels were similar in patient with AAA and PAD [1-3Q: 26.2 (18.8-37.6) vs 21.8 (15.9-31.4) ng/mL; p = 0.30], with deficiency noted in 25.4% with AAA and 41.8% with PAD (p < 0.05). Multiple regression analysis revealed that VD deficiency was explained by past stroke episodes [OR = 2.80 (95%CI: 1.22-6.41)]. Secondary hyperparathyroidism was diagnosed in 1.7% of patients with AAA and 1.9% with PAD. CONCLUSIONS: The frequency of VD deficiency in outpatient with AAA is not greater than in those with PAD. Past stroke episode is associated with an increased occurrence of VD deficiency in both outpatients with AAA and PAD other than sun exposure and diet.

Severity of Vitamin D Deficiency Predicts Mortality in Ischemic Stroke Patients.

BACKGROUND: Vitamin D (VD) deficiency is considered an independent risk factor for death due to cardiovascular events including ischemic stroke (IS). We assessed the hypothesis that decreased levels of 25-hydroxyvitamin D (25-OH-D) are associated with increased risk of mortality in patients with IS. METHODS: Serum 25-OH-D, intact parathyroid hormone (iPTH), and intact fibroblast growth factor 23 (iFGF23) levels were assessed in serum of 240 consecutive patients admitted within the 24 hours after the onset of IS. Mortality data was obtained from the local registry office. RESULTS: Only three subjects (1.3%) had an optimal 25-OH-D level (30-80 ng/mL), 25 (10.4%) had a mildly reduced (insufficient) level, 61 (25.4%) had moderate deficiency, and 151 (62.9%) had a severe VD deficiency. 20% subjects had secondary hyperparathyroidism. The serum 25-OH-D level was significantly lower than that in 480 matched subjects (9.9 ± 7.1 vs. 21.0 ± 8.7 ng/mL). Of all the patients, 79 (32.9%) died during follow-up observation (44.9 months). The mortality rates (per year) were 4.81 and 1.89 in a group with and without severe VD deficiency, respectively (incidence rate ratio: 2.52; 95% CI: 1.44-4.68). There was no effect of secondary hyperparathyroidism and iFGF23 levels on mortality rates. Age, 25 - OH - D < 10 ng/mL, and functional status (modified Rankin scale) were significant factors increasing the risk of death in multivariable Cox proportional hazard regression test. CONCLUSIONS: Severe VD deficiency is an emerging, strong negative predictor for survival after IS, independent of age and functional status. VD supplementation in IS survivals may be considered due to high prevalence of its deficiency. However, it is uncertain whether it will improve their survival.

The Influence of α-Lipoic Acid and Garlic Administration on Biomarkers of Oxidative Stress and Inflammation in Rabbits Exposed to Oxidized Nutrition Oils.

We hypothesized that addition of substances with antioxidant activity could decrease the concentrations of biomarkers of oxidative stress and inflammatory process, thus inhibiting nonalcoholic steatohepatitis development. We investigated the influence of α-lipoic acid (ALA) and garlic administration on the development of adverse changes in rabbit liver and serum under oxidative stress conditions induced with HFD from oxidized oils. We determined 8-hydroxy-2'-deoxyguanosine (8 OHdG) and malondialdehyde (MDA) in liver homogenates, total oxidant status (TOS), lipid peroxides (LOO) and tumor necrosis factor alpha (TNFα) in blood serum, and TNFα and IL-1α genes expression in liver. The results indicate that the intake of dietary ALA and garlic was significantly associated with decreases of 8 OHdG and MDA levels in rabbits' liver tissue as well as TOS and LOO levels in rabbits' serum. Similarly, TNFα and IL-1α gene expressions were suppressed due to ALA and garlic supplementation. The histopathological analysis confirmed that HFD results in liver disorder leading to steatosis. This adverse effect of HFD was ameliorated by the supplementation of ALA and garlic. The obtained results indicate a beneficial effect of ALA and garlic administration by reducing the oxidative stress intensity and the levels of some proinflammatory cytokines in rabbits fed HFD.

Fibroblast growth factor 23 (FGF23) and early chronic kidney disease in the elderly.

BACKGROUND: Better biomarkers of CKD reflecting responses to decreased glomerular filtration rate (GFR) are needed. We determined the value of estimated GFR (eGFR) as a threshold for the increase of plasma cFGF23 (C-terminal) and intact fibroblast growth factor-23 (iFGF23) (intact) concentrations in the course of chronic kidney disease (CKD) and compared this eGFR value with values related to increased serum intact parathyroid hormone (iPTH) or phosphorus concentrations in an elderly population. METHODS: We measured plasma iFGF23, cFGF23, serum phosphorus, calcium, albumin, creatinine, urea, cystatin C, iPTH and vitamin 25-OH-D3 in 3780 population-based study participants aged ≥ 65 years. RESULTS: Serum phosphorus concentrations hardly increased until mean eGFR reached 47.3 ± 4.7 mL/min/1.73 m(2) but then increased exponentially. Similarly, both iPTH and iFGF23 increased slightly in early CKD but then increased exponentially when eGFR reached 55.0 ± 4.2 mL/min/1.73 m(2) for iPTH and 51.6 ± 5.7 mL/min/1.73 m(2) for iFGF23. The departure point for exponential increases in cFGF23 preceded those for iPTH and iFGF23 and occurred at a mean eGFR of 57.7 ± 7.8 mL/min/1.73 m(2). The prevalence of increased iFGF23 occurred at a remarkably higher eGFR value than that of cFGF23 across the CKD stages. CONCLUSIONS: The increase in cFGF23 preceded both the increase in iPTH and iFGF23 as eGFR declined. Increased plasma iFGF23 level did not precede the rise in serum iPTH concentrations and did not occur before stage-3 CKD in elderly persons. However, cFGF23 was not an early marker of CKD in the elderly subjects.

Substance P and intensity of pruritus in hemodialysis and peritoneal dialysis patients.

BACKGROUND: Uremic pruritus is a common complication in patients undergoing dialysis. The pathophysiological mechanisms of pruritus in patients with end-stage renal disease remain unknown. Neuropeptides, including substance P, are postulated to play an important role in the pathogenesis of pruritus. The aim of this study was to evaluate the role of substance P in uremic pruritus in patients on hemodialysis and peritoneal dialysis. MATERIAL/METHODS: We included 197 patients with end-stage renal disease: 54 on continuous ambulatory peritoneal dialysis and 143 on hemodialysis. Substance P, calcium, phosphorus, iron, ferritin, CRP, albumin, hemoglobin, Ca×P product, and iPTH level were determined in all participants. The correlation between these parameters and self-reported itching was evaluated in patients on hemodialysis in comparison with peritoneal dialysis patients. RESULTS: The incidence of itching was similar in hemodialysis and peritoneal dialysis patients. No differences in substance P level between the 2 groups were found. There was no correlation between substance P level and the incidence or intensity of pruritus in dialyzed patients. CONCLUSIONS: This study demonstrates that substance P does not play any important role in pruritus in hemodialysed and peritoneal dialyzed patients. However, further studies are necessary to assess the exact role of neuropeptides in uremic pruritus.