CKD and CVD. Jamal Salameh, MD, FACP, FASN First Coast Nephrology

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1 CKD and CVD Jamal Salameh, MD, FACP, FASN First Coast Nephrology

An Epidemic of Kidney Disease Prevalence CKD stages 1-4 10% 1988-94 13% 1999-2004 Coresh, JAMA 298:2038, 2007 Stage 5: GFR <15 Stage 4: GFR 15 29 Stage 3: GFR 30 59 n=300,000 n=400,000 n=7,600,000

2 An Epidemic of Kidney Disease Prevalence CKD stages % % Coresh, JAMA 298:2038, 2007 Stage 5: GFR <15 Stage 4: GFR Stage 3: GFR n=300,000 n=400,000 n=7,600,000 Stage 2: GFR 60 89* n=5,300,000 n=5,900,000 Stage 1: GFR 90* Total=23 million USA Clinical Practice Guidelines for CKD Am J Kidney Dis. 2002;39(suppl 1):S17 S31. GFR = glomerular filtration rate (ml/min/1.73 m2); *with kidney damage

3 Scope of Disease: NHANES data Figure 1.1 (Volume 1) NHANES participants age 20 & older. USRDS Annual Data Report 2011 Fig 1.1, Vol 1

4 CKD and CVD CKD is an independent risk for all types of CVD In addition, CKD is associated c adverse outcomes in patients c CVD This includes an inc M/M in CAD, PCI, CABG, PTA, CHF, PVD and arrhythmias (not discussed) Both a decrease in GFR and Proteinuria independently increase risk of CVD

5 Albuminuria and GFR affect mortality and CKD outcomes KDIGO controversies conference KI 80:17-28, 2011

7 CKD predicts CV events: HOPE study Events per 1000 person years 40 n=908 All patients Patients taking placebo 30 Patients taking ramipril 20 n= Creatinine <124 µmol/l Creatinine 124 µmol/l HOPE=Heart Outcomes and Prevention Evaluation study Mann et al. Ann Intern Med 2001;134:

8 Age-standardised rate per 100 person years Rates of death and cardiovascular events rise as renal function declines 40 Death from any cause Cardiovascular events > <15 Estimated GFR (ml/min/1.73 m 2 ) Go et al et al. NEJM : 351(13):

9 Annual mortality (%) Cardiovascular Mortality Rates are Higher among Dialysis Patients >85 Age Dialysis: male Dialysis: female General population: male General population: female Adapted from Levey AS et al. Am J Kidney Dis 1998; 32:

10 CKD and CVD Spectrum of disease: -CAD (Angina/ACS) -CHF -CVA -PVD -SCD (Sudden Cardiac Death)

11 Prevalence of Co-morbidity and Level of GFR GFR GFR< <60 60 ml/min GFR 60 ml/min GFR % DM Any IHD CHF Stroke/ CVD TIA PVD

12 CKD and CAD Incidence/Severity of CAD inc c dec GFR In pts c CAD, CKD worsens prognosis Pattern of Diffuse Multivessel dz Incidence approaches or > 50% in ESRD pts M/M are Inversely assoc c Dec GFR Typical Risk Factors are common in CKD

13 Cardiovascular diseases in CKD patients Damage to the heart (Uremic cardiomyopathy) Damage to the arteries (Uremic arteriopathy)

14 CKD and CAD Typical Risks include: -Age (>55 M and >65 F) -Sex (Male) -Dyslipidemia (Inc LDL, Low HDL) -Smoking -FHx of CAD

15 CKD and CAD Traditional Risk Factors for CAD -HTN -DM -LVH -Sedentary Lifestyle -Menopause -Obesity

16 CKD Screening in the Primary Care Population: Who is At Risk National Kidney Foundation Kidney Disease Outcome Quality Initiative: NKF KDOQI Provides evidence-based clinical practice guidelines

17 CKD and CAD Non Traditional Risk Factors for CAD: -Albuminuria -Hyperhomocysteinemia -Anemia -Abnl Ca and PO4 metabolism-vasc Ca++ -ECF Overload -Inflammation -Lipoprotein abnormalities

Cardiovascular Disease in CKD : Multifactorial Pathogenesis Elevated PTH/ 2 HPT Duration of dialysis Dyslipidemia Oxidative stress Hypertension Diabetes Mellitus Genetics Cardiovascular Disease

18 Cardiovascular Disease in CKD : Multifactorial Pathogenesis Elevated PTH/ 2 HPT Duration of dialysis Dyslipidemia Oxidative stress Hypertension Diabetes Mellitus Genetics Cardiovascular Disease Exogenous vitamin D / deficit Chronic inflammation Hyperphosphatemia Smoking Increased homocysteine levels Elevated Ca P product Exogenous Ca intake Traditional risk factors Non Traditional risk factors

*** 83% 20% 0% Russo et al RIND TTG *Russo et al AJKD 2004 (CrCl =33

19 Prevalence of Vascular Calcification in CKD Patients New to Dialysis and Established Patients 100% 80% 60% 40% Stage 3-4 CKD * 40% ** 57% *** 83% 20% 0% Russo et al RIND TTG *Russo et al AJKD 2004 (CrCl =33 ml/min) **Spiegel D et al. Hemod Internat 2004: 8:265 ***Chertow et al KI 2002

20 Probability of Survival Probability of All-Cause Survival According to Calcification Status Calcification Score: 0 Calcification Score: 1 Calcification Score: Calcification Score: Calcification Score: Duration of Follow-Up (Months) *Comparison Between Curves Was Highly Significant (x2=42.66, P<0.0001) Source: Blacher A, et al. Hypertension: , October 2001

Relative Risk of Death* Serum Phosphorus and Mortality in Hemodialysis Patients 2.5 2 n = 40,538 P < 0.0001 1.68 2.03 1.5 1.50 1.25 1.42 1 1.00 1.

22 Relative Risk of Death* Serum Phosphorus and Mortality in Hemodialysis Patients n = 40,538 P < < >9 Serum Phosphorous Concentration (mg/dl) *Multivariable Adjusted Block G, J Am Soc Neph 15: , 2004

23 CKD and CAD

24 CKD and CAD

25 CKD and CAD Treatment: -ASA -Clopidogrel -B Blockers -ACE I/ARB s -Statins (not much data in ESRD x SHARP) -PCI -CABG (Conflicting data re PCI vs CABG)

26 CKD and CHF CHF Increases c Declining GFR CHF is Leading CV condition in CKD Common etiologies are Pressure/Volume XS Myocardial Interstitial Fibrosis (RAAS/SNS/Endothelin/ADH/TGF/IL1/TNF..)

27 Synergistic effect of CKD, CHF and Anemia as risk factors for Death 2 yr mortality (n~ 200,000 5% Medicare sample) % Collins, Adv studies in Med 2003

28 CKD and CHF

29 CKD and CHF Treatment: -Na restriction -Diuretics (usually higher doses) and UF -ACE I/ARB s -BB (Carvedilol, Metoprolol, Bisoprolol) -Anemia Tx -Ca and Phos Tx to prevent Calcifications

30 CKD and CVA Independent risk for ICH and Ischemic-RR=1.4 ESRD pts have a 5-10 risk of age match population to equal approx 4%/year Most CVA ischemic 87% in CHOICE study (enrolled 78% ESRD pts and rest CKD 5) Approximately 33% during or just p HD Mortality approx 35%, much higher than non HD population, compared to 12% for CKD only

31 CKD and CVA Treatment: -Tx HTN -Antiplatelets -Statin rx (controversy in ESRD x SHARP) -CEA in ipsilateral high grade dz

32 CKD and PVD CKD independent risk factor for PVD NHANES reported prevalence of 24% in CKD Other studies report 7% to 48% prevalence Worse stage/gfr yields worse dz High rate traditional risk factors in CKD pts Nontraditional risk factors abound too

33 CKD and PVD Treatment: -Antiplatelets -Smoking cessation -Plavix not studied in CKD population -Cilostazol helped in ESRD pts -Statins (as discussed prior) -PTA vs Bypass (ESRD pts may?? do better c PTA)

34 CKD and SCD SCD defined as sudden death, unexpected within an hour of Sx onset Accounts for 25% of death in ESRD pts Annual rate of 5.5% per year Survival is quite poor at 3-11% at 6 mos SCD incrementally increases c decreasing GFR ESRD pts die from SCD > ACS CKD pts die from ACS > SCD

35 Epidemiology of SCD : CKD populations CKD stages 3-5 (not dialysis) SCD risk by HR of 1.1 for every 10ml/min decline in egfr Event rate 0.8% per yr in non-dialysis CKD In non-diabetic dialysis patients, rate is 7% in 1 st yr of RRT SCD risk is > for HD than PD patients during 1 st 6 months of dialysis, but equalizes thereafter CKD 10 0 General Dialysis event rate per 1000 yrs

36 Karnik JA et al (Kidney International 2001:60: ) : Characteristics associated with arrest on hemodialysis Monday or Tuesday (greatest risk last 12 hrs before dialysis) Low potassium dialysate Older age Diabetic Catheter for access

37 CKD and SCD In ESRD pts Inc in SCD p long interhd periods Causes (?Hyperkalemia,?Fluid XS,?Low K/Ca baths) High prevalence of CMO, LVH, Hyperkalemia, Fluid Overlad and Long QT Treatment: BB and AICD all not studied well

38 Prevalence of LVH (%) Prevalence of Left Ventricular Hypertrophy in Relation to Creatinine Clearance n = p <0.003 (trend analysis) <25 Dialysis Creatinine clearance (ml/min) Patients with diabetes = 24% Adapted from Levin A et al. Am J Kidney Dis 1999; 34:

39 CKD and CVD In Conclusion there is paucity of data here ESRD pts are usually excluded from trials and have a high mortality over a short time frame complicating our ability to study and recruit these most vulnerable pts Thus the Txs for non ESRD pts should be used for ESRD pts and further work is needed

5 (Volume 1) CKD patients are receiving most of their care from their PCP Medicare

40 Cumulative probability of a physician visit at month 12 after CKD diagnosis, by dataset & physician specialty: all CKD Figure 3.5 (Volume 1) CKD patients are receiving most of their care from their PCP Medicare (age 66 & older) & MarketScan & Ingenix i3 (age 50 64) patients with CKD identified in USRDS Annual Data Report 2011

41 One Year Mortality Rate Timely Referral Leads to Reduced Mortality In a Recent Study of 300 Medicare Beneficiaries, the Risk of Death in the First Year on Dialysis Was Reduced by 48% For Early Referral Patients Compared to Late Referral Patients. 2 Several Other Studies Shown Below Confirm This. Early Referral Late Referral 40% 30% 20% Impact of Timing of Referral to 5 Nephrologist on Mortality 90 Day Mortality 3 3% 13% 6 Month Mortality 4 13% 31% 1 Year Mortality 5 6% 39% 1 Year Mortality 2 22% 41% 2 Year Mortality 6 56% 69% 10% 0% < 1 month 1-4 mos > 4 mos Timing of Referral to Nephrologist (Time Prior to Start of Dialysis) 2

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

Cardiovascular Disease in CKD. Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center Cardiovascular Disease in CKD Parham Eftekhari, D.O., M.Sc. Assistant Clinical Professor Medicine NSUCOM / Broward General Medical Center Objectives Describe prevalence for cardiovascular disease in CKD