The relationship between L-arginine/ADMA ratio and coronary collateral development in patients with low glomerular filtration rate

Background: It is yet to be established which factors are responsible for differences among patients with the same degree of coronary artery disease in terms of coronary collateral development (CCD). Methods: Patients who had a greater than or equal to 95% stenosis in at least one epicardial coronary artery were classified into two groups according to their glomerular filtration rate (GFR) level. Afterwards, the degree of CCD was evaluated according to their plasma concentration of asymmetric dimethylarginine (ADMA) and GFR levels. Results: Rentrop grade 2&#8211;3 was found more frequently in patients with GFR > 60 mL/min than in patients with GFR < 60 mL/min (68.6% vs 41.4%, p = 0.032). Then we divided patients into four groups according to their GFR levels and Rentrop grades; whereas we did not find any significant difference for L-arginine or ADMA levels (respectively p = 0.629 and p = 0.076), we did find a statistically significant difference between groups for L-arginine/ /ADMA ratio (p = 0.003) and this statistically significant difference was evident between patients with GFR 60 mL/min and Rentrop 2&#8211;3 (1.23 vs 1.69, p < 0.001). Multivariate logistic regression analysis revealed that L-arginine/ADMA ratio was the only variable which had a significant effect on CCD (OR = 1.016; 95% CI 1.001&#8211;1.031, Wald = 4.565; p = 0.033). Conclusions: These results showed that CCD was poor in patients with GFR < 60 mL/min, presumably because of the adverse effect of decreased L-arginine/ADMA ratio on endothelial cells and angiogenesis. (Cardiol J 2012; 19, 1: 29&#8211;35

Wpływ testosteronowej terapii zastępczej na stężenia witaminy D i FGF-23 w hipogonadyzmie wrodzonym

Introduction: Patients with hypogonadism are at increased risk of cardiac and metabolic diseases and osteoporosis. Vitamin D and Fibroblast growth factor-23 (FGF-23) play role in the regulation of bone mineral metabolism and endothelial functions. Low vitamin D levels are reported in hypogonadism, while there is no data about the effect of testosterone replacement therapy (TRT). We investigated the effect of TRT on vitamin D and FGF-23 levels along with endothelial functions and insulin resistance in hypogonadal patients. Material and methods: Patients with congenital hypogonadotrophic hypogonadism (CHH) (n=32, age 20.6 ±1.58 years) were enrolled. TRT was implemented in transdermal form. The demographic parameters, FGF-23, 25(OH)D3, Asymmetric dimethylarginine (ADMA) and homeostatic model assessment of insulin resistance (HOMA-IR) levels were measured both before and after TRT. Results: After a follow-up period of 3.63±1.33 months, ADMA and FGF-23 levels were significantly increased (p=0.03 and p=0.005 respectively), while the 25(OH)D3 and HOMA-IR index were not significantly changed. The body mass index and waist circumference levels of the patients were also increased (p&lt;0.001 and p=0.02) along with a significant decrease in the HDL cholesterol levels (p=0.006). Conclusions: The results show that a short term TRT increases plasma FGF-23 and ADMA levels, in young, treatment naive patients with CHH. Whether this is an early implication of TRT related adverse effects in this very young and treatment naïve population of CHH is not clear. Future prospective studies are required to find out the long-term effects of TRT on cardio-metabolic morbidity and mortality in this specific population.  Wstęp: U chorych z hipogonadyzmem występuje zwiększone ryzyko chorób sercowych I metabolicznych oraz osteoporozy. Witamina D i czynnik wzrostu fibroblastów-23 (FGF-23) uczestniczą w regulacji metabolizmu kostnego i czynności śródbłonka. Istnieją doniesienia na temat niskiego stężenia witaminy D w hipogonadyzmie, natomiast brakuje danych dotyczących wpływu testosteronowej terapii zastępczej (TRT) na to stężenie. Autorzy zbadali wpływ TRT na stężenia witaminy D i FGF-23 oraz na czynność śródbłonka i poziom insulinooporności u chorych z hipogonadyzmem. Materiał i metody: Do badania włączono chorych z wrodzonym hipogonadyzmem hipogonadotropowym (CHH) (n = 32, wiek 20,6 ± 1,58 roku). Chorzy otrzymywali TRT w postaci przezskórnej. Przez rozpoczęciem leczenia i po jego zakończeniu u chorych zebrano dane demograficzne, zmierzono stężenia FGF-23, 25(OH)D3 i asymetryczej dimetyloargininy (ADMA) oraz określono wskaźnik insulinooporności HOMA-IR. Wyniki: Po okresie obserwacji trwającym 3,63 ± 1,33 miesiąca stwierdzono istotne zwiększenie stężeń ADMA i FGF-23 (odpowiednio p = 0,03 i p = 0,005), natomiast stężenie 25(OH)D3 i wskaźnik HOMA-IR nie zmieniły się istotnie. Ponadto zaobserwowano u chorych zwiększenie wskaźnika masy ciała i obwodu pasa (p &lt; 0,001 I p = 0,02) oraz istotne zmniejszenie stężenia cholesterol frakcji HDL (p = 0,006). Wnioski: Wyniki badania pokazują, że krótkotrwałe stosowanie TRT u młodych chorych z CHH, uprzednio nieleczonych, powoduje zwiększenie osoczowego stężenia FGF-23 i ADMA, lecz nie wpływa na stężenie witaminy D. Nie jest jasne, czy jest to wczesny efekt działań niepożądanych TRT w tej grupie bardzo młodych pacjentów z CHH. Konieczne są dalsze prospektywne badania w celu ustalenia długookresowego wpływu TRT na chorobowość i śmiertelność w związku z chorobami sercowymi i metabolicznymi w tej szczególnej populacji

The Effect of Corrected Inflammation, Oxidative Stress and Endothelial Dysfunction on Fmd Levels in Patients with Selected Chronic Diseases: A Quasi-Experimental Study.

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels

FRI0547 The Effect of Corrected Inflammation, Oxidative Stress and Endothelial Dysfunction on Fmd Levels in Patients with Selected Chronic Diseases: A Quasi-Experimental Study.

While the pathophysiology of chronic disorders varies there are three basic mechanisms - inflammation, oxidative stress and endothelial dysfunction - that are common in many chronic diseases. However, the failure of these mechanisms to work synchronously can lead to morbidity complicating the course of many chronic diseases. We analyzed data of 178 patients from cohorts with selected chronic diseases in this quasi-experimental study. Endothelial dysfunction was determined by flow-mediated dilatation (FMD) and asymmetric dimethylarginine (ADMA) levels. Serum ADMA, high sensitive C-reactive protein (hs-CRP), serum PTX3, malondialdehyde (MDA), Cu/Zn-superoxide dismutase (Cu/Zn-SOD), glutathione peroxidase (GSH-Px) levels and FMD were studied in baseline and after 12 weeks of Morinda citrifolia (anti-atherosclerotic liquid- AAL), omega-3 (anti-inflammatory capsules- AIC) and extract with Alaskan blueberry (anti-oxidant liquid- AOL). Stepwise multivariate regression analysis was used to evaluate the association of FMD with clinical and serologic parameters. Serum ADMA, MDA, PTX3, hsCRP and albumin levels, and proteinuria were significantly decreased while CuZn-SOD, GSH-Px and FMD levels were significantly increased following AAL, AIC and AOL therapies. The FMD was negatively correlated with serum ADMA, MDA, PTX3, and hsCRP levels and positively correlated with CuZn-SOD and eGFR levels. ADMA and PTX3 levels were independently related to FMD both before and after AAL, AIC and AOL therapies. Our study shows that serum ADMA, MDA, PTX3 levels are associated with endothelial dysfunction in patients with selected chronic diseases. In addition, short-term AAL, AIC and AOL therapies significantly improves a number of parameters in our cohort and can normalize ADMA, PTX3, hsCRP and MDA levels

Hormonal changes in hemodialysis patients: Novel risk factors for mortality?

Patients with end-stage renal disease undergoing dialysis commonly experience derangements in the hypothalamic-pituitary-gonadal axis together with alterations at the level of synthesis and clearance of many hormones. This hormonal imbalance, even if asymptomatic, has recently been associated with increased mortality in these patients. In this review, we summarize observational and mechanistic evidence linking hormonal alterations at the level of the thyroid and sex-hormone systems with this mortality risks