TY - JOUR A1 - Drechsler, Christiane A1 - Ritz, Eberhard A1 - Tomaschitz, Andreas A1 - Pilz, Stefan A1 - Schönfeld, Stephan A1 - Blouin, Katja A1 - Bidlingmaier, Martin A1 - Hammer, Fabian A1 - Krane, Vera A1 - März, Winfried A1 - Allolio, Bruno A1 - Fassnacht, Martin A1 - Wanner, Christoph T1 - Aldosterone and cortisol affect the risk of sudden cardiac death in haemodialysis patients JF - European Heart Journal N2 - Background: Sudden cardiac death is common and accounts largely for the excess mortality of patients on maintenance dialysis. It is unknown whether aldosterone and cortisol increase the incidence of sudden cardiac death in dialysis patients. Methods and results: We analysed data from 1255 diabetic haemodialysis patients participating in the German Diabetes and Dialysis Study (4D Study). Categories of aldosterone and cortisol were determined at baseline and patients were followed for a median of 4 years. By Cox regression analyses, hazard ratios (HRs) were determined for the effect of aldosterone, cortisol, and their combination on sudden death and other adjudicated cardiovascular outcomes. The mean age of the patients was 66 ± 8 years (54% male). Median aldosterone was <15 pg/mL (detection limit) and cortisol 16.8 µg/dL. Patients with aldosterone levels >200 pg/mL had a significantly higher risk of sudden death (HR: 1.69; 95% CI: 1.06–2.69) compared with those with an aldosterone <15 pg/mL. The combined presence of high aldosterone (>200 pg/mL) and high cortisol (>21.1 µg/dL) levels increased the risk of sudden death in striking contrast to patients with low aldosterone (<15 pg/mL) and low cortisol (<13.2 µg/dL) levels (HR: 2.86, 95% CI: 1.32–6.21). Furthermore, all-cause mortality was significantly increased in the patients with high levels of both hormones (HR: 1.62, 95% CI: 1.01–2.62). Conclusions: The joint presence of high aldosterone and high cortisol levels is strongly associated with sudden cardiac death as well as all-cause mortality in haemodialysed type 2 diabetic patients. Whether a blockade of the mineralocorticoid receptor decreases the risk of sudden death in these patients must be examined in future trials. KW - mortality KW - kidney disease KW - cardiovascular events KW - sudden cardiac death KW - cortisol KW - aldosterone Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132562 VL - 34 ER - TY - JOUR A1 - Drechsler, Christiane A1 - Schmiedeke, Benjamin A1 - Niemann, Markus A1 - Schmiedeke, Daniel A1 - Krämer, Johannes A1 - Turkin, Irina A1 - Blouin, Katja A1 - Emmert, Andrea A1 - Pilz, Stefan A1 - Obermayer-Pietsch, Barbara A1 - Wiedemann, Frank A1 - Breunig, Frank A1 - Wanner, Christoph T1 - Potential role of vitamin D deficiency on Fabry cardiomyopathy JF - Journal of Inherited Metabolic Disease N2 - Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the vitamin D status and its association with LV mass and adverse clinical symptoms in patients with Fabry disease. 25-hydroxyvitamin D (25[OH]D) was measured in 111 patients who were genetically proven to have Fabry disease. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, BMI and season. Patients had a mean age of 40 ± 13 years (42 % males), and a mean 25(OH)D of 23.5 ± 11.4 ng/ml. Those with overt vitamin D deficiency (25[OH]D ≤ 15 ng/ml) had an adjusted six fold higher risk of cardiomyopathy, compared to those with sufficient 25(OH)D levels >30 ng/ml (p = 0.04). The mean LV mass was distinctively different with 170 ± 75 g in deficient, 154 ± 60 g in moderately deficient and 128 ± 58 g in vitamin D sufficient patients (p = 0.01). With increasing severity of vitamin D deficiency, the median levels of proteinuria increased, as well as the prevalences of depression, edema, cornea verticillata and the need for medical pain therapy. In conclusion, vitamin D deficiency was strongly associated with cardiomyopathy and adverse clinical symptoms in patients with Fabry disease. Whether vitamin D supplementation improves complications of Fabry disease, requires a randomized controlled trial. KW - Fabry patient KW - urinary protein excretion KW - hypertrophic cardiomyopathy KW - renal fibrosis KW - left ventricular mass KW - LV mass KW - diabetic mouse KW - septal hypertrophy KW - Fabry nephropathy KW - cardiac hypertrophy KW - cornea verticillata KW - enzyme replacement therapy Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132102 VL - 37 IS - 2 ER - TY - JOUR A1 - Drechsler, Christiane A1 - Kolleritz, Barbara A1 - Meinitzer, Andreas A1 - März, Winfried A1 - Ritz, Eberhard A1 - König, Paul A1 - Neyer, Ulrich A1 - Pilz, Stefan A1 - Wanner, Christoph A1 - Kronenberg, Florian T1 - Homoarginine and Progression of Chronic Kidney Disease: Results from the Mild to Moderate Kidney Disease Study JF - PLoS ONE N2 - Background: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD). Methods: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. Results: Study participants were at baseline on average 47 \(\pm\)13 years old and 65% were male. Mean \(\pm\) standard deviation of homoarginine concentrations were \(2.5 \pm 1.1 \mu mol/L\) and concentrations were incrementally lower at lower levels of GFR with mean concentrations of \(2.90 \pm 1.02 \mu mol/L\) (GFR. 90 ml/min), \(2.64 \pm 1.06 \mu mol/L\) (GFR 60-90 ml/min), \(2.52 \pm 1.24 \mu mol/L\) (GFR 30-60 ml/min) and \(2.05 \pm 0.78 \mu mol/L\) (GFR, 30 ml/min), respectively (p = 0.002). The age-and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (\(1.1 \mu mol/L\)) of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06). Conclusions: Homoarginine concentrations are directly correlated with kidney function and are significantly associated with the progression of CKD. Low homoarginine concentrations might be an early indicator of kidney failure and a potential target for the prevention of disease progression which needs further investigations. KW - risk KW - alkaline phosphatase KW - cardiovascular events KW - nictric-oxide KW - induced insulin-release KW - creatine synthesis KW - renal function KW - heart failure KW - rat kidney KW - L-arginine Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130979 VL - 8 IS - 5 ER - TY - JOUR A1 - Schneider, Andreas A1 - Schneider, Markus P. A1 - Scharnagl, Hubert A1 - Jardine, Alan G. A1 - Wanner, Christoph A1 - Drechsler, Christiane T1 - Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes JF - BMC Nephrology N2 - Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients. Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers. Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance. Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies. KW - type 2 diabetes KW - heodialysis patients Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-128695 VL - 14 IS - 67 ER - TY - JOUR A1 - Weidemann, Frank A1 - Sanchez-Nino, Maria D. A1 - Politei, Juan A1 - Oliveira, João-Paulo A1 - Wanner, Christoph A1 - Warnock, David G. A1 - Oritz, Alberto T1 - Fibrosis: a key feature of Fabry disease with potential therapeutic implications JF - Orphanet Journal of Rare Diseases N2 - Fabry disease is a rare X-linked hereditary disease caused by mutations in the AGAL gene encoding the lysosomal enzyme alpha-galactosidase A. Enzyme replacement therapy (ERT) is the current cornerstone of Fabry disease management. Involvement of kidney, heart and the central nervous system shortens life span, and fibrosis of these organs is a hallmark of the disease. Fibrosis was initially thought to result from tissue ischemia secondary to endothelial accumulation of glycosphingolipids in the microvasculature. However, despite ready clearance of endothelial deposits, ERT is less effective in patients who have already developed fibrosis. Several potential explanations of this clinical observation may impact on the future management of Fabry disease. Alternative molecular pathways linking glycosphingolipids and fibrosis may be operative; tissue injury may recruit secondary molecular mediators of fibrosis that are unresponsive to ERT, or fibrosis may represent irreversible tissue injury that limits the therapeutic response to ERT. We provide an overview of Fabry disease, with a focus on the assessment of fibrosis, the clinical consequences of fibrosis, and recent advances in understanding the cellular and molecular mechanisms of fibrosis that may suggest novel therapeutic approaches to Fabry disease. KW - Fabry KW - fibrosis KW - podocyte KW - Lyso-Gb3 KW - kidney KW - enzyme replacement therapy KW - alpha-galactosidase-A KW - focal semental glomerulosclerosis KW - cardiovascular magnetic-resonance KW - left-ventricular hypertrophy KW - biopsy findings KW - agalsidase-beta KW - natural-history data KW - cardiac energy metabolism KW - randomized controlled trial Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124773 SN - 1750-1172 VL - 8 IS - 116 ER - TY - JOUR A1 - Dörhöfer, Lena A1 - Lammert, Alexander A1 - Krane, Vera A1 - Gorski, Mathias A1 - Banas, Bernhard A1 - Wanner, Christoph A1 - Krämer, Bernhard K. A1 - Heid, Iris M. A1 - Böger, Carsten A. T1 - Study design of DIACORE (DIAbetes COhoRtE) - a cohort study of patients with diabetes mellitus type 2 JF - BMC Medical Genetics N2 - Background: Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE). Methods: DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro-and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e. g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness. Discussion: DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies. KW - chronic kidney-disease KW - stage renal-disease KW - glomerular-filtration-rate KW - genome-wide association KW - blood-glucose control KW - genetics KW - serum creatinine KW - cardiovascular disease KW - replacement therapy KW - United States KW - risk factors KW - diabetes mellitus type 2 KW - diabetic nephropathy KW - end stage renal disease KW - cardiovascular morbidity KW - diabetes complications KW - epidemiology Y1 - 2013 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122040 SN - 1471-2350 VL - 14 IS - 25 ER - TY - JOUR A1 - Locatelli, Francesco A1 - Spasovski, Goce A1 - Dimkovic, Nada A1 - Wanner, Christoph A1 - Dellanna, Frank A1 - Pontoriero, Giuseppe T1 - The effects of colestilan versus placebo and sevelamer in patients with CKD 5D and hyperphosphataemia: a 1-year prospective randomized study JF - Nephrology Dialysis Transplantation N2 - BACKGROUND: This study compared the effects of short-term titrated colestilan (a novel non-absorbable, non-calcium, phosphate binder) with placebo, and evaluated the safety and efficacy of colestilan over 1 year compared with sevelamer, in patients with chronic kidney disease (CKD) 5D. METHODS: This prospective multicentre study comprised a 4-week phosphate binder washout period, a 16-week short-term, flexible-dose, treatment period (including a 4-week placebo-controlled withdrawal period) and a 40-week extension treatment phase. RESULTS: At Week 16 (the end of the 4-week placebo-controlled withdrawal period), serum phosphorus level was 0.43 mmol/L (1.32 mg/dL) lower with colestilan than placebo (P < 0.001; primary end point). Serum LDL-C level was also lower with colestilan than with placebo (P < 0.001). Both colestilan and sevelamer produced significant reductions from baseline in serum phosphorus levels (P < 0.001), maintained for 1 year, and the proportion of patients achieving target levels of ≤1.78 mmol/L (5.5 mg/dL) or ≤1.95 mmol/L (6.0 mg/dL) at study end were similar (65.3 and 73.3%, respectively, for colestilan, and 66.9 and 77.4%, respectively, for sevelamer). Serum calcium level remained stable in the colestilan group but tended to increase slightly in the sevelamer group (end-of-study increase of 0.035 mmol/L over baseline). Both binders produced similar reductions from baseline in LDL-C level (P < 0.001), and responder rates after 1 year, using a target of <1.83 mmol/L (70 mg/dL) or <2.59 mmol/L (100 mg/dL) were similar in both groups (50.7 and 85.3% for colestilan and 54.0 and 80.6% for sevelamer). Colestilan was generally well tolerated. CONCLUSIONS: Colestilan is effective and safe for the treatment of hyperphosphataemia in patients with CKD 5D, and affords similar long-term phosphorus and cholesterol reductions/responder rates to sevelamer. KW - chronic kidney disease KW - colestilan KW - hyperphosphataemia KW - placebo KW - sevelamer Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-121114 VL - 29 IS - 5 ER - TY - JOUR A1 - Wagner, Martin A1 - Ashby, Damien R. A1 - Kurtz, Caroline A1 - Alam, Ahsan A1 - Busbridge, Mark A1 - Raff, Ulrike A1 - Zimmermann, Josef A1 - Heuschmann, Peter U. A1 - Wanner, Christoph A1 - Schramm, Lothar T1 - Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease JF - PLoS One N2 - Background Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels. Methods 249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003–2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models. Results Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05). Conclusions We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define “high risk” populations in CKD. KW - diabetes mellitus KW - inflammation KW - type 2 diabetes KW - hemoglobin KW - chronic kidney disease KW - anemia KW - ferritin KW - proteinuria Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125514 VL - 10 IS - 4 ER - TY - JOUR A1 - Warnock, David G. A1 - Ortiz, Alberto A1 - Mauer, Michael A1 - Linthorst, Gabor E. A1 - Oliveira, João P. A1 - Serra, Andreas L. A1 - Maródi, László A1 - Mignani, Renzo A1 - Vujkovac, Bojan A1 - Beitner-Johnson, Dana A1 - Lemay, Roberta A1 - Cole, J. Alexander A1 - Svarstad, Einar A1 - Waldek, Stephen A1 - Germain, Dominique P. A1 - Wanner, Christoph T1 - Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation JF - Nephrology Dialysis Transplantation N2 - Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of 1 mg/kg/2 weeks for at least 2 years. Patients were categorized into quartiles based on slopes of estimated glomerular filtration rate (eGFR) during treatment. Multivariate logistic regression analyses were used to identify factors associated with renal disease progression. Results. Men within the first quartile had a mean eGFR slope of –0.1 mL/min/1.73m2/year, whereas men with the most rapid renal disease progression (Quartile 4) had a mean eGFR slope of –6.7 mL/min/1.73m2/year. The risk factor most strongly associated with renal disease progression was averaged urinary protein:creatinine ratio (UP/Cr) ≥1 g/g (odds ratio 112, 95% confidence interval (95% CI) 4–3109, P = 0.0054). Longer time from symptom onset to treatment was also associated with renal disease progression (odds ratio 19, 95% CI 2–184, P = 0.0098). Women in Quartile 4 had the highest averaged UP/Cr (mean 1.8 g/g) and the most rapid renal disease progression: (mean slope –4.4 mL/min/1.73m2/year). Conclusions. Adults with Fabry disease are at risk for progressive loss of eGFR despite enzyme replacement therapy, particularly if proteinuria is ≥1 g/g. Men with little urinary protein excretion and those who began receiving agalsidase beta sooner after the onset of symptoms had stable renal function. These findings suggest that early intervention may lead to optimal renal outcomes. KW - proteinuria KW - enzyme replacement therapy KW - alpha galactosidase KW - Fabry disease KW - genetic renal disease Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124697 VL - 27 IS - 3 ER - TY - JOUR A1 - Fruchart, Jean-Charles A1 - Davignon, Jean A1 - Hermans, Michael P. A1 - Al-Rubeaan, Khalid A1 - Amarenco, Pierre A1 - Assmann, Gerd A1 - Barter, Philip A1 - Betteridge, John A1 - Bruckert, Eric A1 - Cuevas, Ada A1 - Farnier, Michel A1 - Ferrannini, Ele A1 - Fioretto, Paola A1 - Genest, Jacques A1 - Ginsberg, Henry N. A1 - Gotto Jr., Antonio M. A1 - Hu, Dayi A1 - Kadowaki, Takashi A1 - Kodama, Tatsuhiko A1 - Krempf, Michel A1 - Matsuzawa, Yuji A1 - Núñez-Cortés, Jesús Millán A1 - Monfil, Calos Calvo A1 - Ogawa, Hisao A1 - Plutzky, Jorge A1 - Rader, Daniel J. A1 - Sadikot, Shaukat A1 - Santos, Raul D. A1 - Shlyakhto, Evgeny A1 - Sritara, Piyamitr A1 - Sy, Rody A1 - Tall, Alan A1 - Tan, Chee Eng A1 - Tokgözoğlu, Lale A1 - Toth, Peter P. A1 - Valensi, Paul A1 - Wanner, Christoph A1 - Zambon, Albertro A1 - Zhu, Junren A1 - Zimmet, Paul T1 - Residual macrovascular risk in 2013: what have we learned? JF - Cardiovascual Diabetology N2 - Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R(3)i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R(3)i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R(3)i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptor alpha agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R(3)i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk. KW - phospholipid fatty acids KW - term fenofibrate therapy KW - cardiovascular munster procam KW - residual cardiovascular risk KW - atherogenic dyslipidaemia KW - type 2 diabetes KW - therapeutic options KW - high denisty lipoprotein KW - randomized controlled-trial KW - coronary artery disease KW - type-2 diabetes mellitus KW - triglyceride-rich lipoproteins KW - alpha/delta agonist GFT505 KW - placebo-controlled trial Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117546 SN - 1475-2840 VL - 13 IS - 26 ER -