Cardiovascular Mortality: General Population vs ESRD Dialysis Patients

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1 Cardiovascular Mortality: General Population vs ESRD Dialysis Patients Annual CVD Mortality (%) >85 Age (years) GP Male GP Female GP Black GP White Dialysis Male Dialysis Female Dialysis Black Dialysis White RN Foley, PS Parfrey, and MJ Sarnak; Clinical epidemiology of cardiovascular disease in chronic renal disease AJKD, (5):S112-S119

2 % of Death Causes of death in ESRD Patients 60% 51% 56% USRDS 40% 20% 21% 14% 0% 3% 3% Cardiovascular Infection Malnutrition Courtesy Peter Stenvinkel, MD

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4 Dyslipidemia PTH Dialysis vintage Oxidative stress AGE GFR AHT DIABETES ATHEROSCLEROSIS Vascular CALCIFICATION Endothelial dysfunction Chronic inflammation Genetic predisposition smoking Phosphate Homocysteine Exogenous Vit D Ca x P Pathogenesis of cardiovascular disease in CKD

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6 Risk increase Atherothrombosis is a Systemic Disease: Increase for Myocardial Infarction and Stroke as a Function of ABI 2.5 Measurement 1 x Ankle-brachial index (ABI) index 1. Dormandy JA, Creager MA. Cerebrovasc Dis 1999; 9(suppl 1): 14.

7 Medial calcifications Intimal calcifications Medicalcosis = Monckeberg Intimal = atherosclerosis

8 Intimal Calcification Medial Calcification Femoral Artery Pelvic Arteries Medial Calcification Mixed Calcification London et al., Nephrol Dial Transplant 2003; 18:

9 Calcification Status & Cardiovascular Survival in ESRD London et al., Nephrol Dial Transplant 2003; 18:

10 Frequency of calcified aortic arch* 100 % ABI<0.9 ABI ABI>1.3 Série * x-ray radiography

11 Atherosclerosis: causes Traditional risk factors Older age Hypertension Male gender Elevated LDL and Decreased HDL cholesterol Diabetes mellitus Tobacco use Psychosocial stress Family history of CVD Non-traditional risk factors ECF overload Anemia Abnormal mineral metabolism Malnutrition Inflammation/Infection Thrombogenic factors Oxidative stress Proteinuria Uremic toxins

12 Goodman, Am J Kidney Dis, 2004 Two types of risk factors

13 Biomarkers of vascular calcification Promoters Inhibitors - High blood glucose levels Circulating inhibitors - High LDL Cholesterol - fetuin A - Low HDL Cholesterol - bone morphogenic protein -7 - Uremic serum - PTHrP - Hyperphosphatemia - HDL - Increased CaxP product - Magnesium - High intake of Vitamin D - High ipth levels - Hypercalcemia Locally acting inhibitors - Elevated leptin levels - TNF α - Matrx Gla protein - TGFβ - Osteopontin - AGEs - Pyrophosphate - Oxidised lipids - Osteoprotegerin ( OPG)

14 Distribution of 83 HD patients according to CV risk and ABI % < >1.3 ABI no risk cv risk At least one cv complication: LVH; MI; stroke; Heart failure

15 Mechanisms of vascular calcifications Established general favouring conditions age +++ male gender hypertension diabetes mellitus vitamin D intoxication

16 Mechanisms of vascular calcifications Established favoring conditions linked to CKD severe 2ary hyperparathyroidism low bone turnover (hypopth, Al) high-dose active vitamin D metabolites high serum P or Ca; high Ca x P product excessive oral calcium intake duration of dialysis

17 Vascular calcification Moe, S. M. et al. J Am Soc Nephrol 2008;19:

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19 Vascular calcifications Ectopic calcification in the vessel wall is very common in ESRD Localization arterial calcifications atheromatous (intima, subintima) medial (media) arteriolar calcifications calcific uremic arteriolopathy ( calciphylaxis )