Publications by authors named "Jacek Rysz"

233 Publications

Are Nutraceuticals Beneficial in Chronic Kidney Disease?

Pharmaceutics 2021 Feb 6;13(2). Epub 2021 Feb 6.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.

Chronic kidney disease (CKD) is a worldwide health problem in which prevalence is constantly rising. The pathophysiology of CKD is complicated and has not been fully resolved. However, elevated oxidative stress is considered to play a vital role in the development of this disease. CKD is also thought to be an inflammatory disorder in which uremic toxins participate in the development of the inflammatory milieu. A healthy, balanced diet supports the maintenance of a good health status as it helps to reduce the risk of the development of chronic diseases, including chronic kidney disease, diabetes mellitus, and hypertension. Numerous studies have demonstrated that functional molecules and nutrients, including fatty acids and fiber as well as nutraceuticals such as curcumin, steviol glycosides, and resveratrol not only exert beneficial effects on pro-inflammatory and anti-inflammatory pathways but also on gut mucosa. Nutraceuticals have attracted great interest recently due to their potential favorable physiological effects on the human body and their safety. This review presents some nutraceuticals in which consumption could exert a beneficial impact on the development and progression of renal disease as well cardiovascular disease.
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http://dx.doi.org/10.3390/pharmaceutics13020231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7915977PMC
February 2021

The influence of cognitive-behavioral therapy on depression in dialysis patients - meta-analysis.

Arch Med Sci 2020 16;16(6):1271-1278. Epub 2020 Jan 16.

Department of Gerontology, Public Health and Didactics, National Institute of Geriatrics, Rheumatology and Rehabilitation, Warsaw, Poland.

Introduction: Depressive disorders are the most common mental health problem among patients undergoing dialysis. Furthermore, depression is an independent factor increasing the mortality and frequency of hospitalization in this group of patients, yet psychological intervention programs aimed at improving the mental health of dialysis patients have still not been developed. This meta-analysis aimed to assess the effects of cognitive-behavioral therapy on depressive symptoms in dialysis patients. The main hypothesis of this study is that cognitive-behavioral therapy is an effective psychological method of reducing the severity of depression symptoms among patients undergoing dialysis.

Material And Methods: A systematic search was conducted using Medline, PubMed, Web of Science, Scopus and Google Scholar. Data extraction was carried out by two independent researchers. The severity of depression symptoms in the included studies was measured by the Beck Depression Inventory. A random-effects model was used to estimate the pooled mean difference of these values between patients undergoing CBT and the controls.

Results: Four of the 1841 search results met the inclusion criteria with data from 226 patients who had undergone dialysis therapy due to renal disorders and psychological intervention based on cognitive-behavioral therapy. This therapy significantly reduced the level of depression symptoms in all studies included in the meta-analysis (mean difference = -5.3, = 0.001; 95% CI: -7.95 to -2.66).

Conclusions: The study showed that the use of psychological intervention based on cognitive- behavioral therapy was an effective method of decreasing the severity of depressive symptoms in hemodialyzed patients. For the sake of patient well-being, it seems reasonable to extend renal replacement therapy with psychological intervention such as cognitive-behavioral therapy.
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http://dx.doi.org/10.5114/aoms.2019.88019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7667424PMC
January 2020

Oxidative Stress in ESRD Patients on Dialysis and the Risk of Cardiovascular Diseases.

Antioxidants (Basel) 2020 Nov 3;9(11). Epub 2020 Nov 3.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-419 Łódź, Poland.

Chronic kidney disease is highly prevalent worldwide. The decline of renal function is associated with inadequate removal of a variety of uremic toxins that exert detrimental effects on cells functioning, thus affecting the cardiovascular system. The occurrence of cardiovascular aberrations in CKD is related to the impact of traditional risk factors and non-traditional CKD-associated risk factors, including anemia; inflammation; oxidative stress; the presence of some uremic toxins; and factors related to the type, frequency of dialysis and the composition of dialysis fluid. Cardiovascular diseases are the most frequent cause for the deaths of patients with all stages of renal failure. The kidney is one of the vital sources of antioxidant enzymes, therefore, the impairment of this organ is associated with decreased levels of these enzymes as well as increased levels of pro-oxidants. Uremic toxins have been shown to play a vital role in the onset of oxidative stress. Hemodialysis itself also enhances oxidative stress. Elevated oxidative stress has been demonstrated to be strictly related to kidney and cardiac damage as it aggravates kidney dysfunction and induces cardiac hypertrophy. Antioxidant therapies may prove to be beneficial since they can decrease oxidative stress, reduce uremic cardiovascular toxicity and improve survival.
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http://dx.doi.org/10.3390/antiox9111079DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693989PMC
November 2020

The Role of Metabolic Factors in Renal Cancers.

Int J Mol Sci 2020 Sep 30;21(19). Epub 2020 Sep 30.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.

An increasing number of evidence indicates that metabolic factors may play an important role in the development and progression of certain types of cancers, including renal cell carcinoma (RCC). This tumour is the most common kidney cancer which accounts for approximately 3-5% of malignant tumours in adults. Numerous studies indicated that concomitant diseases, including diabetes mellitus (DM) and hypertension, as well as obesity, insulin resistance, and lipid disorders, may also influence the prognosis and cancer-specific overall survival. However, the results of studies concerning the impact of metabolic factors on RCC are controversial. It appears that obesity increases the risk of RCC development; however, it may be a favourable factor in terms of prognosis. Obesity is closely related to insulin resistance and the development of diabetes mellitus type 2 (DM2T) since the adipocytes in visceral tissue secrete substances responsible for insulin resistance, e.g., free fatty acids. Interactions between insulin and insulin-like growth factor (IGF) system appear to be of key importance in the development and progression of RCC; however, the exact role of insulin and IGFs in RCC pathophysiology remains elusive. Studies indicated that diabetes increased the risk of RCC, but it might not alter cancer-related survival. The risk associated with a lipid profile is most mysterious, as numerous studies provided conflicting results. Even though large studies unravelling pathomechanisms involved in cancer growth are required to finally establish the impact of metabolic factors on the development, progression, and prognosis of renal cancers, it seems that the monitoring of health conditions, such as diabetes, low body mass index (BMI), and lipid disorders is of high importance in clear-cell RCC.
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http://dx.doi.org/10.3390/ijms21197246DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582927PMC
September 2020

Correction to: Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis.

Lipids Health Dis 2020 09 20;19(1):208. Epub 2020 Sep 20.

Department of Hypertension, Medical University of Lodz, Rzgowska, 281/289, 93-338, Łódź, Poland.

An amendment to this paper has been published and can be accessed via the original article.
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http://dx.doi.org/10.1186/s12944-020-01380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504830PMC
September 2020

The correlation between lipid metabolism disorders and the prostate cancer.

Curr Med Chem 2020 Aug 5. Epub 2020 Aug 5.

Department of Nephrology, Hypertension and Family Medicine; Medical University of Lodz, Zeromskiego 113, 90-549 Lodz. Poland.

Prostate cancer is second most common cancer affecting male population all over the world. The existence of a correlation between lipid metabolism disorders and cancer of the prostate gland has been widely known for a long time. According to hypotheses, cholesterol may contribute to prostate cancer progression as a result of its participation as a signalling molecule in prostate growth and differentiation via numerous biologic mechanisms including Akt signalling and de novo steroidogenesis. The results of some studies suggest that increased cholesterol levels may be associated with higher risk of more aggressive course of disease. The aforementioned alterations in the synthesis of fatty acids are a unique feature of cancer and, therefore, it constitutes an attractive target for therapeutic intervention in the treatment of prostate cancer. Pharmacological or gene therapy aimed to reduce the activity of enzymes involved in de novo synthesis of fatty acids, FASN, ACLY (ATP citrate lyase) or SCD-1 (stearoyl-CoA desaturase) in particular, may result in cells growth arrest. Nevertheless, not all cancers are unequivocally associated with hypocholesterolaemia. It cannot be ruled out that the relationship between prostate cancer and lipid disorders is not a direct quantitative correlation between carcinogenesis and the amount of the circulating cholesterol. Perhaps the correspondence is more sophisticated and connected to the distribution of cholesterol fractions, or even sub-fractions of e.g. HDL cholesterol.
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http://dx.doi.org/10.2174/0929867327666200806103744DOI Listing
August 2020

Pharmacogenomics of Hypertension Treatment.

Int J Mol Sci 2020 Jul 1;21(13). Epub 2020 Jul 1.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.

Hypertension is one of the strongest modifiable cardiovascular risk factors, affecting an increasing number of people worldwide. Apart from poor medication adherence, the low efficacy of some therapies could also be related to inter-individual genetic variability. Genetic studies of families revealed that heritability accounts for 30% to 50% of inter-individual variation in blood pressure (BP). Genetic factors not only affect blood pressure (BP) elevation but also contribute to inter-individual variability in response to antihypertensive treatment. This article reviews the recent pharmacogenomics literature concerning the key classes of antihypertensive drugs currently in use (i.e., diuretics, β-blockers, ACE inhibitors, ARB, and CCB). Due to the numerous studies on this topic and the sometimes-contradictory results within them, the presented data are limited to several selected SNPs that alter drug response. Genetic polymorphisms can influence drug responses through genes engaged in the pathogenesis of hypertension that are able to modify the effects of drugs, modifications in drug-gene mechanistic interactions, polymorphisms within drug-metabolizing enzymes, genes related to drug transporters, and genes participating in complex cascades and metabolic reactions. The results of numerous studies confirm that genotype-based antihypertension therapies are the most effective and may help to avoid the occurrence of major adverse events, as well as decrease the costs of treatment. However, the genetic heritability of drug response phenotypes seems to remain hidden in multigenic and multifactorial complex traits. Therefore, further studies are required to analyze all associations and formulate final genome-based treatment recommendations.
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http://dx.doi.org/10.3390/ijms21134709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369859PMC
July 2020

Serum NGAL, KIM-1, IL-18, L-FABP: new biomarkers in the diagnostics of acute kidney injury (AKI) following invasive cardiology procedures.

Int Urol Nephrol 2020 Nov 17;52(11):2135-2143. Epub 2020 Jun 17.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549, Lodz, Poland.

Purpose: The aim of this study was to assess the levels of selected markers in patients who underwent planned or emergency coronary angiography and to examine if they correlated with the occurrence of AKI.

Methods: The study included 52 patients who underwent planned or emergency coronary angiography and received contrast agent. Serum levels of markers (NGAL, L-FABP, KIM-1, IL-18) were analyzed in all patients using ELISA tests, at baseline, after 24 and 72 h from angiography.

Results: 9.62% of patients developed CI-AKI. No significant differences were observed between markers levels in patients who developed CI-AKI and those who did not. After 24 h, serum levels of IL-18 were higher in patients with CI-AKI, however, this difference was on the verge of significance. Increase in serum NGAL, KIM-1 and IL-18 was observed after 24 h. Serum levels of biomarkers were insignificantly higher in group with CI-AKI. Significant changes in levels in time (baseline vs. 24 h vs. 72 h) were observed only for NGAL [157.9 (92.4-221.0) vs. 201.8 (156.5-299.9) vs. 118.5 (73.4-198.7); p < 0.0001]. No significant correlations were observed between the decrease in eGFR or the increase in creatinine and biomarkers level.

Conclusion: Obtained results do not allow for the indication of efficient AKI biomarkers. Their further validation in large studies of CI-AKI patients is required.
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http://dx.doi.org/10.1007/s11255-020-02530-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575457PMC
November 2020

Biochemical markers in the prediction of contrast-induced acute kidney injury.

Curr Med Chem 2020 May 1. Epub 2020 May 1.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Zeromskiego 113, 90-549 Lodz. Poland.

For many years clinicians have been searching for "kidney troponin"- a simple diagnostic tool to assess risk of acute kidney injury (AKI). Recently, the rise in the variety of contrast-related procedures (contrast computed tomography [CT], percutaneous coronary intervention [PCI] and angiography) have resulted in increased number of contrast-induced acute kidney injuries (CI-AKI). CI-AKI remains important cause of overall mortality, prolonged hospitalization and it increases total costs of therapy. The consequences of kidney dysfunction affect the quality of life and they may lead to disability as well. Despite extensive worldwide research, there are no sensitive and reliable method of CI-AKI prediction. Kidney Injury Molecule 1 (KIM-1) and Neutrophil Gelatinase Lipocalin (NGAL) have been considered as kidney specific molecules. High concentrations of these substances before the implementation contrast-related procedures have been suggested to enable the estimation of kidney vulnerability to CI-AKI and they seem to have predictive potential for cardiovascular events and overall mortality. According to other authors, routine determination of known inflammation factors (e.g. CRP, WBC, neutrophil count) may be helpful in prediction of CI-AKI. However, the results of clinical trials provide contrasting results. The pathomechanism of contrast-induced nephropathy remains unclear. Due to its prevalence, the evaluation of the risk of acute kidney injury remains serious problem to be solved. This paper reviews pathophysiology and suggested optimal markers facilitating the prediction of contrast-induced acute kidney injury.
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http://dx.doi.org/10.2174/0929867327666200502015749DOI Listing
May 2020

The Influence of Inflammation on Anemia in CKD Patients.

Int J Mol Sci 2020 Jan 22;21(3). Epub 2020 Jan 22.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.

Anemia is frequently observed in the course of chronic kidney disease (CKD) and it is associated with diminishing the quality of a patient's life. It also enhances morbidity and mortality and hastens the CKD progression rate. Patients with CKD frequently suffer from a chronic inflammatory state which is related to a vast range of underlying factors. The results of studies have demonstrated that persistent inflammation may contribute to the variability in Hb levels and hyporesponsiveness to erythropoietin stimulating agents (ESA), which are frequently observed in CKD patients. The understanding of the impact of inflammatory cytokines on erythropoietin production and hepcidin synthesis will enable one to unravel the net of interactions of multiple factors involved in the pathogenesis of the anemia of chronic disease. It seems that anti-cytokine and anti-oxidative treatment strategies may be the future of pharmacological interventions aiming at the treatment of inflammation-associated hyporesponsiveness to ESA. The discovery of new therapeutic approaches towards the treatment of anemia in CKD patients has become highly awaited. The treatment of anemia with erythropoietin (EPO) was associated with great benefits for some patients but not all.
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http://dx.doi.org/10.3390/ijms21030725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036805PMC
January 2020

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease.

Int J Mol Sci 2020 Jan 17;21(2). Epub 2020 Jan 17.

Department of Nephrology, Hypertension and Family Medicine, Chair of Nephrology and Hypertension, Medical University of Lodz, 90-549 Lodz, Poland.

Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.
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http://dx.doi.org/10.3390/ijms21020601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014265PMC
January 2020

Selected cardiovascular risk factors in early stages of chronic kidney disease.

Int Urol Nephrol 2020 Feb 18;52(2):303-314. Epub 2020 Jan 18.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Żeromskiego 113, 90-549, Lodz, Poland.

Cardiovascular diseases, including hypertension, congestive heart failure, myocardial infarction, stroke and atherosclerosis, are common in patients with chronic kidney disease. Aside from the standard biomarkers, measured to determine cardiovascular risk, new ones have emerged: markers of oxidative stress, apoptosis, inflammation, vascular endothelium dysfunction, atherosclerosis, organ calcification and fibrosis. Unfortunately, their utility for routine clinical application remains to be elucidated. A causal relationship between new markers and cardiovascular diseases in patients with chronic kidney disease remains to be established. First of all, there is a lack of large, randomized trials. Moreover, most studies focus on patients with end-stage renal disease as well as on dialysed patients. In such patients, cardiovascular diseases are already present and advanced while early detection of cardiovascular disease risk factor in patients with early-stages of chronic kidney disease would allow more precise prognosis and, as a result, changes in treatment algorithm. In this article, we conduct a comprehensive review of literature for publications relating to cardiovascular risk factors in patients with early-stages of chronic kidney disease. Overall, there are many encouraging advances in detection of cardiovascular risk factors that are making the future more promising for patients suffering from chronic kidney disease.
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http://dx.doi.org/10.1007/s11255-019-02349-1DOI Listing
February 2020

Cholesterol Disturbances and the Role of Proper Nutrition in CKD Patients.

Nutrients 2019 Nov 18;11(11). Epub 2019 Nov 18.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.

Chronic kidney disease (CKD) is a widespread disease with increasing prevalence in the modern society. Lipid disturbances are common in this group of patients. In most patients with CKD atherogenic dyslipidemia is observed. Dyslipidemia in patients with renal diseases increases the risk of cardiovascular diseases and it accelerates the progression of chronic kidney disease to its end stage. The amelioration of dyslipidemia and the lowering of oxidative stress, inflammatory processes, insulin sensitivity and remnant lipoproteins levels may lead to the reduction in cardiovascular burden. Nutritional interventions can strengthen the beneficial effect of treatment and they play an important role in the preservation of overall well-being of the patients with CKD since the aim of appropriate diet is to reduce the risk of cardiovascular events, prevent malnutrition, and hamper the progression of kidney disease. The management of dyslipidemia, regardless of the presence of chronic kidney disease, should be initiated by the introduction of therapeutic lifestyle changes. The introduction of diet change was shown to exert beneficial effect on the lipid level lowering that reaches beyond pharmacological therapy. Currently available evidence give the impression that data on dietary interventions in CKD patients is not sufficient to make any clinical practice guidelines and is of low quality.
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http://dx.doi.org/10.3390/nu11112820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6893650PMC
November 2019

Association of statin use and clinical outcomes in heart failure patients: a systematic review and meta-analysis.

Lipids Health Dis 2019 10 31;18(1):188. Epub 2019 Oct 31.

Department of Hypertension, Medical University of Lodz, Rzgowska, 281/289; 93-338, Łódź, Poland.

Background: The role of statins in patients with heart failure (HF) of different levels of left ventricular ejection fraction (LVEF) remains unclear especially in the light of the absence of prospective data from randomized controlled trials (RCTs) in non-ischemic HF, and taking into account potential statins' prosarcopenic effects. We assessed the association of statin use with clinical outcomes in patients with HF.

Methods: We searched PubMed, EMBASE, Scopus, Google Scholar and Cochrane Central until August 2018 for RCTs and prospective cohorts comparing clinical outcomes with statin vs non-statin use in patients with HF at different LVEF levels. We followed the guidelines of the 2009 PRISMA statement for reporting and applied independent extraction by multiple observers. Meta-analyses of hazard ratios (HRs) of effects of statins on clinical outcomes used generic inverse variance method and random model effects. Clinical outcomes were all-cause mortality, cardiovascular (CV) mortality and CV hospitalization.

Results: Finally we included 17 studies (n = 88,100; 2 RCTs and 15 cohorts) comparing statin vs non-statin users (mean follow-up 36 months). Compared with non-statin use, statin use was associated with lower risk of all-cause mortality (HR 0.77, 95% confidence interval [CI], 0.72-0.83, P < 0.0001, I = 63%), CV mortality (HR 0.82, 95% CI: 0.76-0.88, P < 0.0001, I = 63%), and CV hospitalization (HR 0.78, 95% CI: 0.69-0.89, P = 0.0003, I = 36%). All-cause mortality was reduced on statin therapy in HF with both EF < 40% and ≥ 40% (HR: 0.77, 95% Cl: 0.68-0.86, P < 0.00001, and HR 0.75, 95% CI: 0.69-0.82, P < 0.00001, respectively). Similarly, CV mortality (HR 0.86, 95% CI: 0.79-0.93, P = 0.0003, and HR 0.83, 95% CI: 0.77-0.90, P < 0.00001, respectively), and CV hospitalizations (HR 0.80 95% CI: 0.64-0.99, P = 0.04 and HR 0.76 95% CI: 0.61-0.93, P = 0.009, respectively) were reduced in these EF subgroups. Significant effects on all clinical outcomes were also found in cohort studies' analyses; the effect was also larger and significant for lipophilic than hydrophilic statins.

Conclusions: In conclusion, statins may have a beneficial effect on CV outcomes irrespective of HF etiology and LVEF level. Lipophilic statins seem to be much more favorable for patients with heart failure.
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http://dx.doi.org/10.1186/s12944-019-1135-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822388PMC
October 2019

Diabetes-induced Alterations in HDL Subfractions Distribution.

Curr Pharm Des 2020 ;26(27):3341-3348

Department of Nephrology, Hypertension and Family Medicine, WAM Teaching Hospital of Lodz, Zeromskiego 113, Lodz, 90-549, Poland.

Introduction: Diabetes mellitus (DM) due to its increasing prevalence and associated morbidity and mortality has become a serious public health problem. In DM, HDL may lose its beneficial features and become proatherogenic due to its altered biological activity thus increasing cardiovascular risk. The aim of this study was to assess the influence of the presence of diabetes mellitus type 2 and its duration on the distribution of HDL subfractions. Moreover, the effect of statin treatment on HDL subfraction share was analysed in this study.

Methods: The study group consisted of 50 patients with newly diagnosed DM and 50 persons with DM for longer than 10 years while the control group consisted of 50 healthy volunteers. HDL subfractions were analysed with the use of Lipoprint.

Results: We demonstrated progressive worsening of heart functioning and impairment of its structure in the course of diabetes mellitus. Moreover, we observed that HDL-6 subfraction and intermediate HDL fraction are lowest in the group with advanced DMt2 compared to the group with newly diagnosed DM and a healthy control group. Finally, the results of our study indicated the effect of statin treatment on HDL subfractions that seems not to be advantageous.

Conclusion: It seems that in patients with diabetes mellitus compromised antiatherogenic properties of HDL, as a result of oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein, increase cardiovascular risk.
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http://dx.doi.org/10.2174/1381612825666190227224246DOI Listing
January 2021

A systematic review and meta-analysis of clinical trials investigating the effects of flaxseed supplementation on plasma C-reactive protein concentrations.

Arch Med Sci 2019 Jan 30;15(1):12-22. Epub 2018 Dec 30.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland.

Introduction: Many experimental and clinical trials have suggested that flaxseed might be a potent antihypertensive, but the evidence concerning the effects of flaxseed supplements on plasma C-reactive protein (CRP) concentrations has not been fully conclusive. We assessed the impact of the effects of flaxseed supplementation on plasma CRP concentrations through a systematic review of literature and meta-analysis of available randomised controlled trials (RCTs).

Material And Methods: The literature search included EMBASE, ProQuest, CINAHL, and PUBMED databases up to 1 February 2016 to identify RCTs investigating the effect of flaxseed supplements on plasma CRP concentrations. Meta-analysis was performed using a random-effects model, and effect size was expressed as weighed mean difference (WMD) and 95% confidence interval (CI).

Results: Meta-analysis of 17 selected RCTs with 1256 individuals did not suggest a significant change in plasma CRP concentrations following supplementation with flaxseed-containing products (WMD: -0.25 mg/l, 95% CI: -0.53, 0.02, = 0.074). The effect size was robust in the leave-one-out sensitivity analysis. Subgroup analysis did not suggest any significant difference in terms of changing plasma CRP concentrations among different types of flaxseed supplements used in the included studies, i.e. flaxseed oil (WMD: -0.67 mg/l, 95% CI: -2.00, 0.65, = 0.320), lignan extract (WMD: -0.32 mg/l, 95% CI: -0.71, 0.06, = 0.103) and ground powder (WMD: -0.18 mg/l, 95% CI: -0.42, 0.06, = 0.142).

Conclusions: The meta-analysis of RCTs did not show a significant change in plasma CRP concentrations following supplementation with various flaxseed products. Large, well-designed studies should be still performed to validate the current results.
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http://dx.doi.org/10.5114/aoms.2018.81034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348364PMC
January 2019

Embracing the polypill as a cardiovascular therapeutic: is this the best strategy?

Expert Opin Pharmacother 2018 Dec 9;19(17):1857-1865. Epub 2018 Oct 9.

a Department of Nephrology, Hypertension and Family Medicine , Medical University of Lodz , Lodz , Poland.

Introduction: Cardiovascular disease (CVD) is an important cause of mortality and morbidity worldwide. CVD morbidity and mortality are associated with significant financial costs related to hospitalization, medication, and lost productivity. The concept of the 'polypill' for the reduction of cardiovascular risk was proposed in 2000. A polypill is a fixed combination of drugs in a single tablet or capsule. The initial polypill consisted of three different classes of antihypertensive drugs (each at half dose), in addition to aspirin, a statin, and folic acid. The challenge today is to produce polypills containing drugs with established efficacy and complementary actions. Areas covered: The authors provide their expert perspectives on the polypill and consider the randomized clinical trials that have evaluated the safety, efficacy, adherence, and cost-effectiveness of polypills. Expert opinion: The polypill makes prescribing easier by reducing the need for complex treatment algorithms and dose titration. It also appears to be cost-effective. However, there are several issues that need to be addressed before the polypill can be used routinely. A single polypill formulation may not be suitable for all patients. It may be necessary to develop several types of polypill to meet the needs of different patient groups.
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http://dx.doi.org/10.1080/14656566.2018.1532501DOI Listing
December 2018

Association between phenotypic familial hypercholesterolaemia and telomere length in US adults: results from a multi-ethnic survey.

Eur Heart J 2018 10;39(40):3635-3640

Cardiometabolic Service, Department of Cardiology, Royal Perth Hospital, School of Medicine, University of Western Australia, 35 Stirling Highway, Crawley, WA, Australia.

Aims: Familial hypercholesterolaemia (FH) accelerates atherosclerotic cardiovascular disease (ASCVD) and accordingly is the most potent hereditary cause of premature coronary heart disease. The association between telomere length (TL), a biological index of ageing, and FH has not been hitherto investigated. We addressed this question using data from the US National Health and Education National Surveys (NHANES, 1999-2002).

Methods And Results: We included individuals, who had TL measurements (with quantitative polymerase chain reaction method) and a phenotypic diagnosis of FH based on the Dutch Lipid Clinic Network (DLCN) criteria. Sample weights were applied for unequal probabilities of selection, non-response bias, and oversampling by complex sample analysis. The adult prevalence of FH in NHANES was 0.43% [95% confidence interval (95% CI) 0.33-0.57]. The frequencies of probable FH (mean DLCN score: 6.2) and definite FH (mean DLCN score: 8.9) were 0.42% (95% CI 0.32-0.48) and 0.03% (95% CI 0.02-0.06), respectively. Subjects with FH had a higher prevalence of non-communicable diseases (hypertension, diabetes 2 type, and obesity) and early atherosclerosis (2.9% in overall population vs. 42.2% in FH). Overall, the mean TL in the non-FH population was 1.09 (95% CI 1.06-1.12) (T/S ratio) and 1.09 (95% CI 1.03-1.12) [(T/S ratio) for total FH]. Telomere length adjusted for age, sex, race, and body mass index was shorter in FH compared with healthy subjects (FH 0.89, 95% CI 0.84-0.93 vs. healthy: 1.05, 95% CI 0.97-1.11 T/S ratio; P < 0.001). Subjects with longer TL (highest quartile) had 12% less chance of having FH compared with those with TL in the lowest quartile (Q1, 95% CI 0.78-0.93).

Conclusions: These preliminary data suggest an association between TL, an index of biological age, and the presence of FH, the most common inherited cause of premature ASCVD. Given our relatively low sample size, the findings need confirmation in larger studies.
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http://dx.doi.org/10.1093/eurheartj/ehy527DOI Listing
October 2018

Biomarkers, myocardial fibrosis and co-morbidities in heart failure with preserved ejection fraction: an overview.

Arch Med Sci 2018 Jun 11;14(4):890-909. Epub 2018 Jun 11.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland.

The prevalence of heart failure with preserved ejection fraction (HFpEF) is steadily increasing. Its diagnosis remains difficult and controversial and relies mostly on non-invasive echocardiographic detection of left ventricular diastolic dysfunction and elevated filling pressures. The large phenotypic heterogeneity of HFpEF from pathophysiologic al underpinnings to clinical manifestations presents a major obstacle to the development of new therapies targeted towards specific HF phenotypes. Recent studies suggest that natriuretic peptides have the potential to improve the diagnosis of early HFpEF, but they still have significant limitations, and the cut-off points for diagnosis and prognosis in HFpEF remain open to debate. The purpose of this review is to present potential targets of intervention in patients with HFpEF, starting with myocardial fibrosis and methods of its detection. In addition, co-morbidities are discussed as a means to treat HFpEF according to cut-points of biomarkers that are different from usual. Biomarkers and approaches to co-morbidities may be able to tailor therapies according to patients' pathophysiological needs. Recently, soluble source of tumorigenicity 2 (sST2), growth differentiation factor 15 (GDF-15), galectin-3, and other cardiac markers have emerged, but evidence from large cohorts is still lacking. Furthermore, the field of miRNA is a very promising area of research, and further exploration of miRNA may offer diagnostic and prognostic applications and insight into the pathology, pointing to new phenotype-specific therapeutic targets.
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http://dx.doi.org/10.5114/aoms.2018.76279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6040115PMC
June 2018

The Role of Nutraceuticals in Statin Intolerant Patients.

J Am Coll Cardiol 2018 07;72(1):96-118

Biomedical Department of Internal Medicine and Medical Specialties, University of Palermo, Palermo, Italy.

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.
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http://dx.doi.org/10.1016/j.jacc.2018.04.040DOI Listing
July 2018

Impact of Vitamin D on the Cardiovascular System in Advanced Chronic Kidney Disease (CKD) and Dialysis Patients.

Nutrients 2018 Jun 1;10(6). Epub 2018 Jun 1.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 90-549 Lodz, Poland.

In patients suffering from chronic kidney disease (CKD), the prevalence of cardiovascular disease is much more common than in the general population. The role of vitamin D deficiency had been underestimated until a significant association was found between vitamin D therapy and survival benefit in haemodialysis patients. Vitamin D deficiency is present even in the early stages of chronic kidney disease. The results of experimental studies have revealed the relationship between vitamin D deficiency and impairment of cardiac contractile function, higher cardiac mass and increased myocardial collagen content. Experimental models propose that intermediate end points for the relationship between vitamin D deficiency and higher risk of cardiovascular disease comprise diminished left ventricular hypertrophy (LVH), enhanced left ventricular diastolic function, and decreased frequency of heart failure. Multiple observational studies have demonstrated an association between the use of active vitamin D therapy in patients on dialysis and with CKD and improved survival. However, there are also many studies indicating important adverse effects of such treatment. Therefore, large randomized trials are required to analyze whether supplementation of vitamin D may affect outcomes and whether it is safe to be used in CKD patients.
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http://dx.doi.org/10.3390/nu10060709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6024710PMC
June 2018

Cholesterol Subfraction Analysis in Patients with Acute Coronary Syndrome.

Curr Vasc Pharmacol 2019 ;17(4):365-375

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland.

Background: There is a close relationship between lipid metabolism disorders and atherosclerosis. Guidelines focus on lowering Low-Density Lipoprotein Cholesterol (LDL-C) levels. However, it should be kept in mind that LDL and High-Density Lipoprotein (HDL) consist of subfractions which can affect the progression of atherosclerosis.

Objective: We assessed the concentration of LDL and HDL subfractions in patients with Acute Coronary Syndromes (ACS). The influence of the presence of type 2 diabetes mellitus on LDL and HDL subfractions was also analyzed.

Methods: The study group consisted of 127 patients (62 men, 65 women) with ACS. All patients had coronary angiography and coronary angioplasty and stenting when necessary. Medical history was collected during 12 months of follow-up. HDL and LDL subfraction distribution was measured using Lipoprint (Quantimetrix).

Results: No differences in LDL nor HDL subfractions were observed between ST-Segment Elevation Myocardial Infarction (STEMI), Non-ST-Segment Elevation Myocardial Infarction (NSTEMI) and unstable angina (UA) patients. However, those with restenosis and the necessity of repeated revascularization had higher levels of intermediate-density lipoprotein C (IDL-C) (p=0.055) and LDL3 (p=0.048) as compared with the patients without, while the level of IDL A (IDLA) was lower than in the latter group (p=0.036). In diabetic patients, the percentage share of HDL10 and small-dense HDL was significantly higher while the share of HDL1 (small-dense) (p=0.028), HDL4 (intermediate density) (p=0.052) and HDL5 (intermediate density) (p=0.060) were lower than in patients without DM.

Conclusion: Patients with multi-vessel CAD disease had higher levels of LDL3 subfraction and IDL-C and a lower proportion of IDLA.
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http://dx.doi.org/10.2174/1570161116666180601083225DOI Listing
May 2020

Established and potential echocardiographic markers of embolism and their therapeutic implications in patients with ischemic stroke.

Cardiol J 2019 2;26(5):438-450. Epub 2018 May 2.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland.

Cardiogenic strokes comprised 11% of all strokes and 25% of ischemic strokes. An accurate identification of the cause of stroke is necessary in order to prepare an adequate preventive strategy. In this review the confirmed and potential causes of embolic strokes are presented, which can be detected in echocardiography in the context of present treatment guidelines and gaps in evidence. There remains a need for further studies assessing the meaning of potential cardiac sources of embolism and establishment of rules for optimal medical prevention (antiplatelet therapy [APT] vs. oral anticoagulation [OAC]) and interventional procedures to reduce the incidence of ischemic strokes. Currently available data does not provide definitive evidence on the comparative benefits of OAC vs. APT in patients with cryptogenic stroke or embolic stroke of undetermined source. There is a lack of antithrombotic treatment scheme in the time between stroke and the completed diagnosis of potential sources of thromboembolism.
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http://dx.doi.org/10.5603/CJ.a2018.0046DOI Listing
July 2020

Novel drugs for heart rate control in heart failure.

Heart Fail Rev 2018 07;23(4):517-525

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Zeromskiego 113, 90-549, Lodz, Poland.

In patients with heart failure, increased sympathetic activity is associated with a positive chronotropic stimulation leading to accelerated resting heart rate. Elevated heart rate (HR) is a risk factor for cardiovascular events, both in the general population and in patients with heart failure. Ivabradine is a pure HR-lowering agent, and it does not affect myocardial contractility, blood pressure, intracardiac conduction, or ventricular repolarization. In clinical trials such as BEAUTIFUL, CARVIVA HF, SHIFT, and INTENSIFY in patients with systolic left ventricular dysfunction, heart rate reduction with ivabradine brought positive outcomes. However, the results of the recent meta-analysis are rather neutral. In a diabetes mouse model of heart failure with preserved ejection fraction (HFpEF), selective heart rate reduction by I inhibition improved vascular stiffness, left ventricular (LV) contractility, and diastolic function. However, EDIFY (Effect of ivabradine in patients with heart rate with preserved ejection fraction) trial show that the use of ivabradine in patients with HFpEF is not supported. The further clinical trials investigating the use of ivabradine in heart failure should be carried out.
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http://dx.doi.org/10.1007/s10741-018-9696-xDOI Listing
July 2018

Prosarcopenic Effects of Statins May Limit Their Effectiveness in Patients with Heart Failure.

Trends Pharmacol Sci 2018 04 1;39(4):331-353. Epub 2018 Mar 1.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland; Cardiovascular Research Centre, University of Zielona-Gora, Zielona-Gora, Poland. Electronic address:

Some studies using small doses of statins revealed significant benefits for patients with chronic heart failure (HF). However, the results of large randomized studies did not confirm these advantages. Along with the primary effect of cholesterol lowering, statins have many ancillary actions that may be relevant for body wasting. In this context, the fear of muscle-related side effects needs to be put into clinical context and assessed appropriately before statins are either withheld or withdrawn in patients with sarcopenia (muscle wasting). Some of the mechanistic bases of statin-mediated muscle dysfunction correspond with mechanisms of sarcopenia observed in HF with reduced ejection fraction patients, connected with insulin-like growth factor 1, inflammation, the ubiquitin-proteasome pathway, apoptosis, and myostatin. Here we present the hypothesis of potential prosarcopenic properties of statins as a possible explanation of the lack of effectiveness of these drugs in HF patients.
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http://dx.doi.org/10.1016/j.tips.2018.02.003DOI Listing
April 2018

Clinical and prognostic usefulness of soluble urokinase plasminogen activator receptor in hemodialysis patients.

Int Urol Nephrol 2018 Feb 8;50(2):339-345. Epub 2018 Jan 8.

Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, Lodz, Poland.

Purpose: Considering its prognostic usefulness and the relationship with chronic kidney disease, we analyzed the clinical utility of soluble urokinase plasminogen activator receptor (suPAR) in end-stage renal disease patients undergoing hemodialysis treatment. We focused on the association between suPAR levels and clinical outcomes, especially those related to cardiovascular events and mortality as well as the effect of hemodialysis on the protein levels.

Methods: We enrolled 64 patients. Blood samples for laboratory tests were collected before and after the midweek hemodialysis. The concentration of suPAR was assessed using suPARNostic ELISA, ViroGates.

Results: Spearman rank analyses showed a positive association between suPAR and creatinine, cystatin C, galectin 3, N-terminal prohormone of brain natriuretic peptide and troponin T (p < 0.05). In ROC analysis, the suPAR concentration equal to 11.5 ng/mL was established to be the cutoff value for the prediction of mortality in the analyzed patients. Simultaneous analysis of creatinine and suPAR increased the predictive value of the latter-the area under curve increased to 0.84 (95% CI 0.70-0.94, p < 0.0001). Logistic regression analysis revealed that increase in the suPAR level was associated with the increase in odds ratio for death by 1.3 (95% CI 1.1-1.6, χ = 8.2, p = 0.004). In multivariable analysis, the prediction power of suPAR appeared to be stronger after including creatinine (p = 0.0005).

Conclusions: Elevated suPAR levels provide independent information on mortality risk in patients undergoing hemodialysis. The protein appears not to cross the dialysis membrane; thus, blood collection before the second hemodialysis session seems to give reliable information on the suPAR level for clinical interpretation.
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http://dx.doi.org/10.1007/s11255-017-1778-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811576PMC
February 2018

[Complications of endoscopic retrograde cholangiopancreatography].

Pol Merkur Lekarski 2017 Dec;43(258):272-275

WAM University Hospital, Medical University of Lodz, Poland: Gastrointestinal Endoscopy Laboratory.

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure of the diagnosis and treatment of biliary and pancreatic diseases. ERCP combines both endoscopic and radiologic imaging. Despite the fact that it is widely considered as relatively safe and useful procedure when performed by an experienced endoscopist, ERCP may potentially result in complications due to its invasive nature. These complications vary in severity and include post-ERCP pancreatitis, cholangitis, hemorrhage and perforations of the gastrointestinal tract. Therefore, the selection of patients and their appropriate preparation before the procedure as well as the careful consideration of indications are highly required.
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December 2017

Cytisine - From the Past to the Future.

Curr Pharm Des 2018 ;24(37):4413-4423

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Zeromskiego 113, Lodz 90-549, Poland.

Introduction: Neuronal nicotinic acetylcholine receptors are ligand-gated ion channel receptors, distributed throughout central nervous system, as well as in peripheral ganglia and some non-neuronal cells. Cytisine, a qulinolizidine alkaloid, could be considered a high affinity ligand of those receptors. It is a partial agonist of β2*-containing receptors and a full agonist of α7 and β4*-containing receptors.

Current Indication: At present, pharmacodynamic properties of cytisine are leveraged only in a few European countries where it is available as medicinal product (Desmoxan and Tabex) indicated in the pharmacotherapy of nicotine addiction. Cytisine mimics the influence of nicotine on α4β2* receptors, but with higher affinity and lower activity. It lowers rewarding and reinforcing effects of nicotine in smoking persons and reduces withdrawal symptoms and craving in quitting ones.

Potential Indications: The results of non-clinical studies suggest that cytisine could affect ethanol consumption, has an antidepressant and neuroprotective effect and could be useful in reducing body mass and preventing weight gain. Although there is a lack of research on cytisine in the treatment of areca nuts usage, the preliminary data suggest its usefulness. The combination of cytisine and Trolox C was selected as a possible effective treatment for type 2 diabetes. Though these drugs alone are not effective, their theoretical usefulness was confirmed in animal models.

Summary: Treatment with cytisine is an effective, cost-efficient, affordable and well tolerated nicotine addiction therapy. Potential new indications for cytisine include the treatment of alcoholism, areca nuts usage, Parkinson's disease, an autonomic-system failure. Further studies are necessary.
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http://dx.doi.org/10.2174/1381612825666181123124733DOI Listing
November 2019

Telomere attrition, kidney function, and prevalent chronic kidney disease in the United States.

Oncotarget 2017 Oct 8;8(46):80175-80181. Epub 2017 Sep 8.

Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland.

Background: Telomere length is an emerging novel biomarker of biologic age, cardiovascular risk and chronic medical conditions. Few studies have focused on the association between telomere length (TL) and kidney function.

Objective: We investigated the association between TL and kidney function/prevalent chronic kidney disease (CKD) in US adults.

Methods: The National Health and Nutrition Examination Survey (NHANES) participants with measured data on kidney function and TL from 1999 to 2002 were included. Estimated glomerular filtration rate (eGFR) was based on CKD Epidemiology Collaboration (CKD-EPI) equation. Urinary albumin excretion was assessed using urinary albumin-creatinine ratio (ACR). We used multivariable adjusted linear and logistic regression models, accounting for the survey design and sample weights.

Results: Of the 10568 eligible participants, 48.0% (=5020) were men. Their mean age was 44.1 years. eGFR significantly decreased and ACR significantly increased across increasing quarters of TL (all <0.001). The association between TL and kidney function remained robust even after adjusting for potential confounding factors, but the association between TL and ACR was only borderline significant (β-coefficient= -0.012, =0.056).

Conclusion: The association of kidney function with a marker of cellular senescence suggests an underlying mechanism influencing the progression of nephropathy.
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http://dx.doi.org/10.18632/oncotarget.20706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5655188PMC
October 2017

The role and function of HDL in patients with diabetes mellitus and the related cardiovascular risk.

Lipids Health Dis 2017 Oct 30;16(1):207. Epub 2017 Oct 30.

Department of Nephrology Hypertension and Family Medicine, Medical University of Lodz, Żeromskiego 113, Łódź, 90-549, Poland.

Background: Diabetes mellitus (DM) is a major public health problem which prevalence is constantly raising, particularly in low- and middle-income countries. Both diabetes mellitus types (DMT1 and DMT2) are associated with high risk of developing chronic complications, such as retinopathy, nephropathy, neuropathy, endothelial dysfunction, and atherosclerosis.

Methods: This is a review of available articles concerning HDL subfractions profile in diabetes mellitus and the related cardiovascular risk. In this review, HDL dysfunction in diabetes, the impact of HDL alterations on the risk diabetes development as well as the association between disturbed HDL particle in DM and cardiovascular risk is discussed.

Results: Changes in the amount of circulation lipids, including triglycerides and LDL cholesterol as well as the HDL are frequent also in the course of DMT1 and DMT2. In normal state HDL exerts various antiatherogenic properties, including reverse cholesterol transport, antioxidative and anti-inflammatory capacities. However, it has been suggested that in pathological state HDL becomes "dysfunctional" which means that relative composition of lipids and proteins in HDL, as well as enzymatic activities associated to HDL, such as paraoxonase 1 (PON1) and lipoprotein-associated phospholipase 11 (Lp-PLA2) are altered. HDL properties are compromised in patients with diabetes mellitus (DM), due to oxidative modification and glycation of the HDL protein as well as the transformation of the HDL proteome into a proinflammatory protein. Numerous studies confirm that the ability of HDL to suppress inflammatory signals is significantly reduced in this group of patients. However, the exact underlying mechanisms remains to be unravelled in vivo.

Conclusions: The understanding of pathological mechanisms underlying HDL dysfunction may enable the development of therapies targeted at specific subpopulations and focusing at the diminishing of cardiovascular risk.
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http://dx.doi.org/10.1186/s12944-017-0594-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663054PMC
October 2017