Cardiovascular Disease in CKD. Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center

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1 Cardiovascular Disease in CKD Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center

2 Objectives Describe prevalence for cardiovascular disease in CKD population Review key physiological mechanisms Left ventricular hypertrophy Coronary Artery Disease Sudden Cardiac Death in CKD Discuss therapeutic strategies

3 CKD Stages Clinical Geriatrics 2011;19(4):34-39

4 Rates of Acute Myocardial Infarction by CKD Status Jan. 1 pt. prev. Medicare pts. age 66 & older; first AMI event in 2007 or USRDS 2012 Annual Data Report: Cardiovascular disease and CKD

5 Probability of Death Following Acute Myocardial Infarction in CKD USRDS 2012 Annual Data Report: Cardiovascular disease and CKD

6 Lancet 2013; 382:

7 Unique Cardiac Risk Factors in CKD Nature Rev Nephrol. 2009; 5:

8 Cardiovascular Disease and CKD Left Ventricular Hypertrophy Coronary Artery Disease Sudden Cardiac Arrest

9 Nat Review Nephrol. 2011; 7:

10 Left Ventricular Hypertrophy and CKD Independent association with mortality. Up to 45% of CKD 1-4 patients have LVH. Up to 80% of ESRD patients have LVH. Kidney International. 2011; 80(6): Circulation. 2007; 116: 85-97

11 LVH and CKD Physiology Physiology: o Pressure Overload Concentric hypertrophy of left ventricle Vascular Calcification Reduced arterial compliance HTN (Renin-Aldosterone) o Volume Overload Dilated cardiomyopathy Anemia of CKD Oxidative stress Circulation. 2007; 116: 85-97

12 Clinical Consequences of LVH Myocardial infarction Intra-dialytic hypotension More frequent angina Heart Failure Sudden Cardiac Arrest Fatal Arrhythmia Prolonged QTc interval Increased Premature Ventricular Contractions Nature Rev Cardiology. 2009; 6:

13 Anemia and LVH in CKD Independent risk factor for the development and progression of LVH in CKD Cardiomyopathy and LVH: Effects of reduced oxygen delivery to the myocardium Anemia-related increased cardiac output and reduced systemic vascular resistance Increased oxidative stress Activation of the sympathetic nervous system Am Soc Nephrology 2009; 20:2651. Semin Nephrol Jul;26(4):

14 Cardio-Renal-Anemia Semin Nephrol Jul;26(4):

15 CKD Risk Factors for Coronary Disease Nature Rev Cardiol. 209; 6:

16 Definition of Albuminuria Normal albumin excretion < 30 mg/day Microalbuminuria 30 and 300 mg/day Macroalbuminuria is above 300 mg/day Brenner and Rector: The Kidney th edition.

17 Albuminuria and Cardiac Disease Independently associated with CVD outcome and all-cause mortality. Direct mechanism poorly understood Endothelial dysfunction and inflammation Increased atherosclerosis in peripheral vasculature. Circulation. 2004;110(1):32. Circulation. 2007; 116: Nature Rev Cardiology. 2009; 6:

18 Microalbuminuria and CVD: HOPE Trial Degree of albuminuria Clin J Am Soc Nephrol 2007; 2:

19 Macroalbuminuria and CVD: RENAAL Trial Circulation 2004;110:

20 Bone Mineral Disorder in CKD Increased arterial vascular calcification via PTH Advanced Arteriosclerosis in 50-90% in CKD 4 and 5 Increased cardiomyopathy and LVH Independent associations between increased CAD and PVD with mortality. Am J Kid Disease. 2010; 58:

21 Bone Mineral Disorder in CKD J Am Board Fam Med. 2009;22(5):

22 Hyperparathyroidism and CVD AJKD. In press, June 2013 [E pub ahead of print]

23 Coronary atherosclerosis in CKD Stages CKD 1-2 CKD 3 CKD 3b ***Arrows show calcified plaques CKD 4-5 Am. J. Kidney Dis. 2010; 55: 21 30

24 Arteriosclerosis and Atherosclerosis

25 Sudden Cardiac Death Approximately 50% of ESRD patients die from a CVD cause. Risk increases with duration of time on dialysis Duration of time since last dialysis Sudden cardiac death constitutes >60% of CVD mortality in ESRD. Nature Rev Cardiol 2011; 7: Circulation 2007; 116: 85-97

26 Rates Sudden Cardiac Death by GFR Kidney International 2009; 76:

27 J Am Soc Neph. 2012;23:

28 Inflammation, CKD and CVD Inflammatory state with CKD: 30-50% patients elevated Interleukins, TNF and inflammatory markers. Uremic toxins promote inflammation and oxidative stress. Progressive oxidative endothelial dysfunction. Circulation. 2007; 116: 85-97

29 Clinical Practice Guidelines for Diagnosis of CAD in ESRD Evaluation for CAD should occur at initiation of dialysis electrocardiogram (ECG) Echocardiogram ESRD patients with LV systolic function (EF<40%) should be evaluated for CAD If positive, exercise or pharmacological stress or nuclear imaging tests KDOQI Clinical Practice Guidelines for Cardiovascular Disease in Dialysis Patients

30 Troponin and Diagnostic Utility in CKD Elevated troponin common without clinical evidence of myocardial damage. LVH, endothelial dysfunction, impaired renal excretion. Serial elevations are more prognostic for CAD. Identifies a subgroup of CKD population: poor survival long term high risk of cardiac death despite being asymptomatic. Circulation Nov 15;112(20): Kidney International 2006; 69:

31 Mortality and Revascularization in CKD J Am Coll Cardiol. 2009;53(23):

32 PCI versus CABG in CKD PCI Preferred over medical therapy alone Higher rate of coronary re-stenosis Barrier = advanced vascular calcification in CKD CABG Improved coronary vessel patency Greater relief angina Some studies suggest improved survival over PCI Hemodialysis Int. 2011; 15: S30-36 J Kidney Dis. 2007; 22: Curr Opin Cardiol. 2007; 22:

33 Focus on Prevention Recognize importance of LVH ACE-I, ARB, or Aldosterone inhibitors Control HTN with goal BP <130/80 Treatment of Albuminuria ACE-I, ARB or Aldosterone inhibitors Treatment of Anemia in CKD Goal Hg Treatment of Hyperparathyroidism in CKD Controlling volume to avoid CHF in CKD Monitor electrolytes and dietary measures in CKD

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