Cardiovascular Disease in Dialysis Prof. Bancha Satirapoj, MD Division of Nephrology Department of Medicine Phramongkutklao Hospital and College of Medicine
Disclosure information ❖ Prof. Bancha Satirapoj, M.D. ❖ Scienti c Advisor/Honoraria: ❖ Astra Zeneca, Boehringer Ingelheim, LG Life Sciences, Janssen-Cilag, MSD, Novo Nordisk, Osotspa Taisho and Sano Aventis ❖ DISCLAIMER ❖ The view and opinions expressed in this presentation are those of the speaker, and do not re ect the o cial policy or position of Boehringer Ingelheim or any of its a liates or subsidiaries. iffifflfifif
Causes of death in patients with ESRD receiving hemodialysis, who died in 2018 55% 44% 2020 Annual Report USRDS: End-Stage Renal Disease in the United States
CKD with increased risk of sudden cardiac death among patients with coronary artery disease Pun PH, et al. Kidney Int 2009;76:652-8.
ACC/AHA and ESC Guideline ❖ All people with CKD be considered at increased risk for cardiovascular disease (1A) ❖ CKD = CAD risk equivalent ❖ CKD is not only a coronary risk equivalent for ascertainment of coronary risk but also a independent risk factor for the development and progression of CVD. (1A)
Histology of left ventricular wall Normal heart Patient with CKD Interstitial and perivascular brosis in the heart is a major determinant of diastolic dysfunction among patients with CKD and hypertension Tonelli M, et al. Circulation. 2016;133:518-536. fi
Cardiovascular diseases in CKD Artery Heart ❖ Increased wall thickness ❖ Altered cardiac geometry ❖ Arterial calci cation ❖ Myocardial brosis ❖ Arterial sti ness ❖ Left ventricular dysfunction ❖ Endothelial dysfunction ❖ Valvular disease esp. AS ❖ Arrhythmia & conduction defects Brenner & Rector’s the kidney 10th edition fifffi
Mediators of chronic kidney disease–associated myocardial and coronary artery changes Mathew RO, et al. Kidney Int 2017;91:797-807.
Mechanisms behind various cardiovascular abnormalities seen in various stages of CKD Wong MG, et al. European Heart Journal (2015) 36, 2988–2995
Volume overload CVS disease Pressure overload Increase wall stretch Left ventricular lling pressure Myocyte proliferation Enlarged wall & cavity Concentric hypertrophy Eccentric hypertrophy Impaired ventricular relaxation Impaired contractility Reduced compliance Reduced EF Diastolic dysfunction (50%) Systolic dysfunction (20%) Decrease GFR and proteinuria Activation of SNS, RAAS Malnutrition, In ammation Ca, PO4, PTH, Oxidative stress Valvular calci cation Uremic toxin Anemia Satirapoj B. Pocket Dialysis 2021 fiflfi
Cardiovascular Risks in CKD Traditional cardiovascular risk Nontraditional cardiovascular risk factors factors ❖ Old age ❖ Uremic toxins RAS activity ❖ Male gender ❖ Decreased GFR and albuminuria ❖ Diabetes ❖ Anemia ❖ Hypertension ❖ Abnormal Ca, PO4 and iPTH ❖ Dyslipidemia ❖ Vitamin D deficiency ❖ Smoking ❖ RAAS activation ❖ Physical inactivity ❖ SNS activation ❖ Psychosocial stress ❖ Inflammation and oxidative stress ❖ Family history of cardiovascular ❖ Malnutrition ❖ Extracellular fluid volume overload disease Satirapoj B. Pocket Dialysis 2021
Glycemic control in dialysis
Efficacy of MRA in Patients Who Require Dialysis: A Meta-analysis Ricks J, et al. Diabetes 2012;61:708-15.
Glycemic targets ❖ Individualized HbA1c target ranging from <6.5% to <8.0% in patients with diabetes and CKD not treated with dialysis (1C). KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD. Kidney Int 2020: 98, S1–S115.
GFR<15 Insulin DPP4-i TZD Sulfonyurea Avoid hypoglycemia GLPRA DPP4-i TZA KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD. Kidney Int 2020: 98, S1–S115.
BP control in dialysis
BP targets in hemodialysis patients Predialysis SBP and mortality in a large cohort of incident and prevalent hemodialysis patients Turner JM, et al. Kidney Int 2017;92:816-23.
Carvedilol increases two-year survival in dialysis patients with dilated cardiomyopathy CV death All-cause hospital admission Cice G, et al. J Am Coll Cardiol 2003;41:1438-44.
Effect of amlodipine on CV events in hypertensive hemodialysis patients Mortality Mortality from any cause and CV event HR 0.53 (95% CI 0.31-0.93) primary endpoint was mortality from any cause. Secondary endpoint was a composite variable consisting of mortality from any cause, cardiac event including myocardial infarction, need for coronary angioplasty or coronary bypass surgery, ischemic stroke, peripheral vascular disease with the need for amputation or angioplasty. Tepel M, et al. Nephrol Dial Transplant 2008;23:3605-12.
Effects of ACEI and ARB on CV events and residual renal function in dialysis patients: a meta-analysis CV events Heart failure Liu Y, et al. BMC Nephrol 2017;18:206.
Efficacy of MRA in Patients Who Require Dialysis: A Meta-analysis Cardiovascular mortality in dialysis patients Quach K, et al. Am J Kidney Dis 2016;68:591-8.
Drug choices for HT in CKD vs ESKD on dialysis Sinha AD, et al. Clin J Am Soc Nephrol 2019: 14: 757–764.
Lipid control in dialysis
Dyslipidemia in advance CKD/dialysis ± LDL ↑TG ↑Small-dense LDL Large VLDL ↓ HDL-C Chronic Kidney Disease ↑Small-Dense Metabolic Syndrome Type 2 Diabetes HDL Keech AC et al, Lancet 2008; 371:117-25.
Atorvastatin in Type 2 Diabetics on Dialysis: 4D Study 1255 T2DM patients on dialysis 4D Study Relative Risk Reduction 8% (95% CI: 0.77-1.10, P=0.37) Atorvastatin had no signi cant e ect on the composite primary end point of CV death, nonfatal MI, and stroke in patients with diabetes receiving hemodialysis Wanner C et al. N Engl J Med 2005; 353:238-48 fffi
Rosuvastatin and CV Events in Patients Undergoing Hemodialysis (The AURORA Study) 2776 patients, 50 to 80 years of age, undergoing maintenance hemodialysis AURORA Study HR 0.96, P=0.59 The initiation of treatment with rosuvastatin lowered the LDL cholesterol level but had no signi cant e ect on the composite primary end points Fellström BC, et al: N Engl J Med 2009; 360(14):1395-407. ffif
Study of Heart and Renal Protection (SHARP) SHARP Study ❖ Subjects: ~9,000 patients with CKD (6,000 pre-dialysis, 3,000 on dialysis) ❖ Interventions: Simvastatin /ezetimibe combination vs. placebo Baigent C et al. Lancet. 2011;377:2181–2192.
Study of Heart and Renal Protection (SHARP) Risk ratio 0.83 (0.74 – 0.94) Baigent C et al. Lancet. 2011;377:2181–2192.
SHARP: Major Atherosclerotic Events by renal status at randomization Risk ratio 0.78 (0.67-0.91) Risk ratio 0.90 (0.75-1.08) Baigent C et al. Lancet. 2011;377:2181–2192.
Treatment goals for LDL-cholesterol Mach F, et al. Eur Heart J. 2020; 41(1):111-188.
Treatment goals for LDL-cholesterol It is recommended that a high-intensity statin is prescribed up to the highest tolerated dose to reach the goals set for the speci c level of risk Mach F, et al. Eur Heart J. 2020; 41(1):111-188. fi
Lipid management in patients with CKD CKD = High or very high risk CV Statin with ezetimibe Mach F, et al. Eur Heart J. 2020; 41(1):111-188.
Lipid management in patients with CKD Continue stains or ezetimibe at time of dialysis No initiate statin in dialysis without CV Mach F, et al. Eur Heart J. 2020; 41(1):111-188.
Aspirin is beneficial in patients with CKD Effect of Aspirin According to eGFR Category Effect of Aspirin on bleeding rates Aspirin therapy produces greater absolute reduction in major An increased risk of major bleeding appears to CV events and mortality in hypertensive patients with CKD be outweighed by the substantial bene ts. Jardine MJ, et al. J Am Coll Cardiol 2010;56:956-65. fi
Evidence-based modification of traditional risk factors to mitigate CV disease Gregg LP, et al. Am J Kidney Dis. 2018;72(5):728-744.
Cardiovascular Risks in CKD Traditional cardiovascular risk Nontraditional cardiovascular risk factors factors ❖ Old age ❖ Uremic toxins RAS activity ❖ Male gender ❖ Decreased GFR and albuminuria ❖ Diabetes ❖ Anemia ❖ Hypertension ❖ Abnormal Ca, PO4 and iPTH ❖ Dyslipidemia ❖ Vitamin D deficiency ❖ Smoking ❖ RAAS activation ❖ Physical inactivity ❖ SNS activation ❖ Psychosocial stress ❖ Inflammation and oxidative stress ❖ Family history of cardiovascular ❖ Malnutrition ❖ Extracellular fluid volume overload disease Satirapoj B. Pocket Dialysis 2021
BMI with outcomes in patients with CKD U-shaped association with progression of CKD in 453,946 United States veterans with eGFR<60 ml/min per 1.73 m2 Lu JL, et al J Am Soc Nephrol. 2014;25:2088–96.
Hypoalbuminemia predict CKD mortality by inflammation ❖ Assessed at baseline in 822 patients: 523 incident dialysis patients, 212 prevalent HD and 87 prevalent PD patients Low serum-alb and high hsCRP Alves FC, et al. PLoS ONE 2018: 13(1): e0190410.
Protein carbamylation is associated with mortality in diabetic patients with end stage renal disease We strati ed 1,161 patients by C-Alb to see if differences in carbamylation altered the effects of atorvastatin on survival. Sudden cardiac death High C-Alb levels are associated with ongoing cardiac damage and sudden cardiac death Subjects were categorized into upper, middle, and lower tertiles according to serum C-Alb values measured at the outset of the study Drechsler C, et al. Kidney Int. 2015;87:1201–1208. fi
Carbamylated proteins related endothelial dysfunction and atherosclerosis Tonelli M, et al. Circulation. 2016;133:518-536.
High-efficiency postdilution online hemodiafiltration ❖ Multi-center, open-label, randomized controlled trial in which we assigned 906 chronic hemodialysis patients either to continue hemodialysis (n=450) or to switch to high-e ciency post-dilution OL-HDF (n=456). OL-HDF had a 30% lower risk of all-cause mortality (HR 0.70; 95%CI 0.53–0.92; P=0.01) High-ef ciency postdilution OL- HDF reduces all-cause mortality compared with conventional hemodialysis Maduell F, et al. J Am Soc Nephrol 2013;24:487-97. fiffi
Comparing patient mortality with hemodiafiltration and hemodialysis: RCT Canaud B, et al. Clin J Am Soc Nephrol. 2018; 13(9):1435-1443.
Patient survival depends on using a high convection volume Bene t in patients on delivered convection volume (>23 L per treatment or 68 L/wk) Canaud B, et al. Clin J Am Soc Nephrol. 2018; 13(9):1435-1443. fi
Effect of frequent nocturnal HD vs conventional HD on left ventricular mass and quality of life ❖ AFrteoqtuael notfn5o2ctpurantaiel nhetsmuodnidaleyrsgisoiimngprhoveemdoledftiavleynstirsicwulearremraescs,rureidteudce. d the need for BP medications, improved mineral metabolism, and quality of life. Culleton BF, et al. JAMA 2007;298:1291-9.
Changes in bone mineral parameters with mortality in hemodialysis patients The association of calcium The association of phosphate and i-PTH with all cause with all cause mortality was mortality was U-shaped J-shaped Lamina C, et al. Nephrol Dial Transplant 2020; 35(3):478-487.
FGF23 induces left ventricular hypertrophy Faul C, et al. J Clin Invest 2011;121:4393-408.
Soluble Klotho Protects against Uremic Cardiomyopathy Klotho-de cient CKD mice have aggravated cardiac brosis compared with WT mice Xie J, et al. J Am Soc Nephrol 2015;26:1150-60 fifi
Vascular calcification with attendant clinical consequences Nelson AJ, et al. J Am Coll Cardiol Basic Trans Science 2020;5:398–412 .
Medial and Intimal Calcification in CKD Rogers M, et al. J Am Heart Assoc. 2013; 2(5):e000481.
Putative mechanisms of Coronary artery disease in CKD Fujii H, et al. Clinical and Experimental Nephrology (2019) 23:725–732.
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