Rationale and study design of the prospective, longitudinal, observational cohort study “rISk strAtification in end-stage renal disease” (ISAR) study

BackgroundThe ISAR study is a prospective, longitudinal, observational cohort study to improve the cardiovascular risk stratification in endstage renal disease (ESRD). The major goal is to characterize the cardiovascular phenotype of the study subjects, namely alterations in micro- and macrocirculation and to determine autonomic function.Methods/designWe intend to recruit 500 prevalent dialysis patients in 17 centers in Munich and the surrounding area. Baseline examinations include: (1) biochemistry, (2) 24-h Holter Electrocardiography (ECG) recordings, (3) 24-h ambulatory blood pressure measurement (ABPM), (4) 24 h pulse wave analysis (PWA) and pulse wave velocity (PWV), (5) retinal vessel analysis (RVA) and (6) neurocognitive testing. After 24 months biochemistry and determination of single PWA, single PWV and neurocognitive testing are repeated. Patients will be followed up to 6 years for (1) hospitalizations, (2) cardiovascular and (3) non-cardiovascular events and (4) cardiovascular and (5) all-cause mortality.Discussion/conclusionWe aim to create a complex dataset to answer questions about the insufficiently understood pathophysiology leading to excessively high cardiovascular and non-cardiovascular mortality in dialysis patients. Finally we hope to improve cardiovascular risk stratification in comparison to the use of classical and non-classical (dialysis-associated) risk factors and other models of risk stratification in ESRD patients by building a multivariable Cox-Regression model using a combination of the parameters measured in the study.Clinical trials identifierClinicalTrials.gov NCT01152892 (June 28, 2010)

[1]  C. P. Hughes,et al.  A New Clinical Scale for the Staging of Dementia , 1982, British Journal of Psychiatry.

[2]  C. Mackenzie,et al.  A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. , 1987, Journal of chronic diseases.

[3]  J. Concato,et al.  Importance of events per independent variable in proportional hazards regression analysis. II. Accuracy and precision of regression estimates. , 1995, Journal of clinical epidemiology.

[4]  M. O'Rourke,et al.  Pulse wave analysis. , 1996, Journal of hypertension. Supplement : official journal of the International Society of Hypertension.

[5]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[6]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[7]  A. Levey,et al.  "U" curve association of blood pressure and mortality in hemodialysis patients. Medical Directors of Dialysis Clinic, Inc. , 1998, Kidney international.

[8]  J. Blacher,et al.  Impact of aortic stiffness on survival in end-stage renal disease. , 1999, Circulation.

[9]  A. Camm,et al.  Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction , 1999, The Lancet.

[10]  R. Elashoff,et al.  Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis. , 2000, The New England journal of medicine.

[11]  Frank E. Harrell,et al.  Regression Modeling Strategies: With Applications to Linear Models, Logistic Regression, and Survival Analysis , 2001 .

[12]  J. Blacher,et al.  Arterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease , 2001, Hypertension.

[13]  W Vilser,et al.  RETINAL VESSEL ANALYSIS - NEW POSSIBILITIES , 2002, Biomedizinische Technik. Biomedical engineering.

[14]  B.-U. Seifert,et al.  RETINAL VESSEL ANALYZER (RVA) - DESIGN AND FUNCTION , 2002, Biomedizinische Technik. Biomedical engineering.

[15]  G. Schmidt,et al.  Risk Stratification After Acute Myocardial Infarction by Heart Rate Turbulence , 2003, Circulation.

[16]  R. Klein,et al.  Relationships between age, blood pressure, and retinal vessel diameters in an older population. , 2003, Investigative ophthalmology & visual science.

[17]  R. Klein,et al.  Retinal vessel diameters and their associations with age and blood pressure. , 2003, Investigative ophthalmology & visual science.

[18]  R. Klein,et al.  Hypertensive Retinal Vessel Wall Signs in a General Older Population: The Blue Mountains Eye Study , 2003, Hypertension.

[19]  Francesco Locatelli,et al.  Effect of dialysis dose and membrane flux in maintenance hemodialysis. , 2003, The New England journal of medicine.

[20]  R. Klein,et al.  The prevalence and risk factors of retinal microvascular abnormalities in older persons: The Cardiovascular Health Study. , 2003, Ophthalmology.

[21]  Hude Quan,et al.  Adapting the Charlson Comorbidity Index for use in patients with ESRD. , 2003, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[22]  J. Cummings,et al.  The Montreal Cognitive Assessment, MoCA: A Brief Screening Tool For Mild Cognitive Impairment , 2005, Journal of the American Geriatrics Society.

[23]  S. Greenland,et al.  Reverse Epidemiology of Hypertension and Cardiovascular Death in the Hemodialysis Population: The 58th Annual Fall Conference and Scientific Sessions , 2005, Hypertension.

[24]  U. Rajendra Acharya,et al.  Heart rate variability: a review , 2006, Medical and Biological Engineering and Computing.

[25]  M. Malik,et al.  Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study , 2006, The Lancet.

[26]  Charles E McCulloch,et al.  Relaxing the rule of ten events per variable in logistic and Cox regression. , 2007, American journal of epidemiology.

[27]  J. Griffith,et al.  Subcortical cognitive impairment in dialysis patients , 2007, Hemodialysis international. International Symposium on Home Hemodialysis.

[28]  J. Mourad.  Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease. , 2008 .

[29]  E. W. Hancock,et al.  AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the , 2009, Journal of the American College of Cardiology.

[30]  E. W. Hancock,et al.  AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part V: electrocardiogram changes associated with cardiac chamber hypertrophy: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinic , 2009, Journal of the American College of Cardiology.

[31]  Zhi Huang,et al.  An improved comorbidity index for outcome analyses among dialysis patients. , 2010, Kidney international.

[32]  W. Zidek,et al.  Validation of the mobil-O-Graph: 24 h-blood pressure measurement device , 2010, Blood pressure monitoring.

[33]  T. Weber,et al.  A new oscillometric method for pulse wave analysis: comparison with a common tonometric method , 2010, Journal of Human Hypertension.

[34]  B. Imholz,et al.  Evaluation of the Mobil-O-Graph new generation ABPM device using the ESH criteria , 2010, Blood pressure monitoring.

[35]  R. Agarwal.  Blood Pressure and Mortality Among Hemodialysis Patients , 2010, Hypertension.

[36]  A. Nissenson,et al.  Prevalence and correlates of cognitive impairment in hemodialysis patients: the Frequent Hemodialysis Network trials. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[37]  S. Davies,et al.  End-stage renal disease: A new comorbidity index for estimating mortality risk in ESRD , 2010, Nature Reviews Nephrology.

[38]  Yang Qiu,et al.  Excerpts from the US Renal Data System 2009 Annual Data Report. , 2010, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[39]  Leopold Schmetterer,et al.  Use of the retinal vessel analyzer in ocular blood flow research , 2010, Acta ophthalmologica.

[40]  A. Ciocâlteu,et al.  [The impact of hemodialysis on retinal circulation]. , 2011, Oftalmologia.

[41]  Martin Schumacher,et al.  Competing Risks and Multistate Models with R , 2011 .

[42]  Siegfried Wassertheurer,et al.  Validation of a Brachial Cuff-Based Method for Estimating Central Systolic Blood Pressure , 2011, Hypertension.

[43]  W. Winkelmayer,et al.  The increasing prevalence of atrial fibrillation among hemodialysis patients. , 2011, Journal of the American Society of Nephrology : JASN.

[44]  J. Staessen,et al.  24-h ambulatory recording of aortic pulse wave velocity and central systolic augmentation: a feasibility study , 2012, Hypertension Research.

[45]  Siegfried Wassertheurer,et al.  Assessment of central haemomodynamics from a brachial cuff in a community setting , 2012, BMC Cardiovascular Disorders.

[46]  Richard J McManus,et al.  NICE hypertension guideline 2011: evidence based evolution , 2012, BMJ : British Medical Journal.

[47]  T. Wong,et al.  Retinal Vascular Caliber Measurements: Clinical Significance, Current Knowledge and Future Perspectives , 2012, Ophthalmologica.

[48]  Andreas Holzinger,et al.  Online and Offline Determination of QT and PR Interval and QRS Duration in Electrocardiography , 2012, ICPCA/SWS.

[49]  Junichiro Hayano,et al.  Nonlinear measures of heart rate variability and mortality risk in hemodialysis patients. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[50]  Siegfried Wassertheurer,et al.  Oscillometric estimation of aortic pulse wave velocity: comparison with intra-aortic catheter measurements , 2013, Blood pressure monitoring.

[51]  C. Stefanadis,et al.  Non-invasive 24 hour ambulatory monitoring of aortic wave reflection and arterial stiffness by a novel oscillometric device: the first feasibility and reproducibility study. , 2013, International journal of cardiology.

[52]  Mahboob Rahman,et al.  Heart Rate Variability Is a Predictor of Mortality in Chronic Kidney Disease: A Report from the CRIC Study , 2013, American Journal of Nephrology.

[53]  T. Wong,et al.  Structural changes in the retinal microvasculature and renal function. , 2013, Investigative ophthalmology & visual science.

[54]  A. Davey,et al.  Kidney disease and cognitive function. , 2013, Contributions to nephrology.

[55]  Geoffrey A Head,et al.  European Society of Hypertension practice guidelines for ambulatory blood pressure monitoring. , 2014, Journal of hypertension.

[56]  J. Wi,et al.  Aortic pulse wave velocity predicts mortality in chronic kidney disease stages 2–4 , 2014, Journal of hypertension.

[57]  V. Liakopoulos,et al.  Evaluation of a Novel Brachial Cuff-Based Oscillometric Method for Estimating Central Systolic Pressure in Hemodialysis Patients , 2014, American Journal of Nephrology.

[58]  Hans Förstl,et al.  Variability of Cognitive Performance during Hemodialysis: Standardization of Cognitive Assessment , 2014, Dementia and Geriatric Cognitive Disorders.

[59]  U. Heemann,et al.  Aortic pulse wave velocity predicts mortality in chronic kidney disease stages 2–4 , 2014, Journal of hypertension.

[60]  Jürgen Floege,et al.  The Montreal Cognitive Assessment (MoCA) - A Sensitive Screening Instrument for Detecting Cognitive Impairment in Chronic Hemodialysis Patients , 2014, PloS one.

[61]  S. Rajagopalan,et al.  Relationship between heart rate variability and pulse wave velocity and their association with patient outcomes in chronic kidney disease , 2013, Clinical nephrology.

[62]  C. Kremser,et al.  Comparison of an Oscillometric Method with Cardiac Magnetic Resonance for the Analysis of Aortic Pulse Wave Velocity , 2015, PloS one.

[63]  Belinda Jim,et al.  Pathophysiologic and Treatment Strategies for Cardiovascular Disease in End-Stage Renal Disease and Kidney Transplantations , 2014, Cardiology in review.

[64]  P. Boutouyrie,et al.  Aortic-Brachial Stiffness Mismatch and Mortality in Dialysis Population , 2015, Hypertension.

[65]  Amit X Garg,et al.  Worldwide access to treatment for end-stage kidney disease: a systematic review , 2015, The Lancet.

[66]  R. Foley,et al.  United States Renal Data System public health surveillance of chronic kidney disease and end-stage renal disease , 2015, Kidney international supplements.

[67]  S. Cerutti,et al.  Advances in heart rate variability signal analysis: joint position statement by the e-Cardiology ESC Working Group and the European Heart Rhythm Association co-endorsed by the Asia Pacific Heart Rhythm Society. , 2015, Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology.

[68]  R. Agarwal.  Pro: Ambulatory blood pressure should be used in all patients on hemodialysis. , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[69]  V. Liakopoulos,et al.  Ambulatory recording of wave reflections and arterial stiffness during intra- and interdialytic periods in patients treated with dialysis. , 2015, Clinical journal of the American Society of Nephrology : CJASN.

[70]  Florian Kronenberg,et al.  Development and validation of a predictive mortality risk score from a European hemodialysis cohort , 2015, Kidney international.

[71]  C. Zoccali,et al.  Moderator's view: Ambulatory blood pressure monitoring and home blood pressure for the prognosis, diagnosis and treatment of hypertension in dialysis patients. , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[72]  M. Vidovich,et al.  Acute Exertion Elicits a H2O2-Dependent Vasodilator Mechanism in the Microvasculature of Exercise-Trained but Not Sedentary Adults , 2015, Hypertension.

[73]  A. Jardine.  Con: Ambulatory blood pressure measurement in patients receiving haemodialysis: a sore arm and a waste of time? , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[74]  Ambulatory aortic blood pressure, wave reflections and pulse wave velocity are elevated during the third in comparison to the second interdialytic day of the long interval in chronic haemodialysis patients. , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.