Cardiovascular Diseases in CKD

Transcription

1 1 Cardiovascular Diseases in CKD Hung-Chun Chen, MD, PhD. Kaohsiung Medical University Taiwan Society of Nephrology 1

2 2 High Prevalence of CVD in CKD & ESRD Foley RN et al, AJKD 1998; 32(suppl 3):S112-9

3 3 High CV Mortality in ESRD Foley RN et al, AJKD 1998; 32(suppl 3):S112-9

4 CKD Increased Risks of Death, CV Events & Hospitalization 4 Go AS et al, NEJM 2004;351:

5 5 Cardiorenal Syndrome Ronco C, Contrib Nephrol. 2010;164:33-8

6 Traditional and Nontraditional Risk Factors for CVD in CKD 6 Menon V et al, AJKD 2005;45:223-32

7 Our Findings of Some Nontraditional CV Risk Factors in CKD Patients 7 Cardiac structural changes Heeart Echo Parameters, Surface ECG P wave, bpep/bet (brachial pre-ejection period/ejection time) Framingham risk score Arterial stiffness bapwv (Pulse wave velocity) Four limb BP Volume status Metabolic changes: Hyperuricemia, Anemia, BMI

8 Increased LVMI & Decreased LVEF Correspond with CKD Stages in DM 8 LVMI LVEF LVH LVEF<55% A cross-sectional study enrolled 285 DM with CKD stages 3-5 Chen & Chen, Exp Diabetes Res 2012;2012:789325

9 ECG Parameters are Associated with Increased CV Events in CKD 9 LAD<4.7cm LVEF>55% LAD>4.7cm LVEF<55% HR 2.141, P=0.016 HR 2.007, P=0.028 N=505, Stage 3-5 Chen & Chen, NDT 2012;27:

10 10 Inappropriate LVM is Associated with Increased CV Events in CKD Appropriate LVM Log-rank P = Inappropriate LVM N=485, Stage 3-5 Chen & Chen, Hypertens Res. 2012;35:832-8

11 11 Concentric LVH is Associated with Progression to Dialysis in CKD Non-LVH Concentric LVH Eccentric LVH HR 2.03, P=0.049 A longitudinal study enrolled 415 stage 3-5 Pts Chen & Chen, CJASN 2011;6:2750-8

12 High UA & LVMI are Associated with Rapid Renal Progression & Dialysis 12 N=540, Stage 3-5, Follow 33.4m, Rapid progressor: egfr >-3/y Chen & Chen, Am J Hypertens 2013;26:243-9

13 Anemia & LVH are Associated with Renal Function Decline & CV Events 13 High Hb, LVH(-) Low Hb, LVH(-) High Hb, LVH(+) Low Hb, LVH(+) N=415, Stage 3-5 Chang & Chen, Am J Med Sci 2014; 347:183-9

14 14 High BMI better? Low BMI better?

15 15 Combination of Lower BMI & Higher LVMI is Associated with CV Events in CKD Parameters Unadjusted Multivariate adjusted (1) Multivariate adjusted (2) hazard ratio (95% CI) p hazard ratio (95% CI) p hazard ratio (95% CI) p Higher BMI and lower LVMI Lower BMI and LVMI Higher BMI and LVMI Lower BMI and higher LVMI ( ) ( ) ( ) ( ) ( ) ( ) ( ) ( ) < ( ) Multivariate model (1): adjusted for age, diabetes mellitus, hypertension, coronary artery disease, atrial fibrillation, systolic blood pressure, and pulse pressure. Multivariate model (2): model (1) + albumin, fasting glucose, log triglyceride, total cholesterol, hemoglobin, egfr, proteinuria, and ACEI and/or ARB use. N=523, Stage 3-5 Chen & Chen, Am J Med Sci :91-6

16 16 Combination of High LAD & Low Albumin is Associated with Renal Function Decline and Dialysis L LAD L LAD H LAD H LAD H Alb L balb H Alb L Alb N=395, Stage 3-5 Chen & Chen, Int J Med Sci 2013;10:575-84

17 17 12-Lead ECG P Wave The 12-lead ECG (P wave morphology, P wave dispersion, P wave duration) is a simple and cheap noninvasive clinical tool to access left atrial enlargement, left ventricular hypertrophy, and left ventricular diastolic dysfunction. Arch Intern Med 1989; 149: Furthermore, P wave parameters were independently associated with increased risks for atrial fibrillation and recurrent transient ischemic attacks. South Med J 2008; 101: Am J Cardiol 107: e911

18 18 High ECG P Wave Dispersion & Maximum P Wave Duration are Associated with Progression to Dialysis & Death Higher P Dispersion Higher Max P Duration N=439, Stage 3-5 Chen & Chen, PLoS One. 2014;9:e101962

19 19 Framingham Risk Score The Framingham Risk Score is a gender-specific algorithm used to estimate the 10-year cardiovascular risk. It contains age, sex, total and HDL cholesterol, BP, smoking.

20 Framingham Risk Score (FRS) in HD: Intermediate Risk Pts have Higher Mortality Rate 20 N=201, Follow 4.4±1.5y Huang & Chen, Nephrology 2013;18:510-5

21 FRS in CKD: ECG Parameters Increased FRS Predictive Power for CV Events 21 Parameters Cardiovascular events FRS AUCs Change in c- statistic FRS + albumin FRS + hemoglobin FRS + egfr FRS + proteinuria FRS + LA diameter > 4.7 cm FRS + LVH FRS + LVEF < 50% Chen & Chen, PLoS One 2013;8:e60008

22 Colin VP System

23 VP ABI, bapwv, bpep/bet 1.ABI/API (Ankle Brachial Pressure Index) Lower extremity artery stenosis Arteriosclerosis Arterial stiffness 2. PWV (Pulse Wave Velocity) Artery stiffness 3. bpep/bet(brachial pre-ejection period/brachilal ejection time) Systolic time interval (STI)

24 24 Good Correlation Between Brachial and ECG Systolic Time Interval (STI) R=0.708, P<0.001 PEP/ET(Pre-ejection period/ejection time): STI N=849, General Chen & Su, PLoS One 2013;8:e55840

25 Higher bpep/bet is Associated with Higher LVMI and Lower LVEF in CKD 25 r = 0.360, P < r = , P < bpep/bet(brachial pre-ejection period/brachilal ejection time): STI N=243, Stage 3-5 Chen & Su, NDT 2011;26:

26 26 bpep/bet is Associated with Increassed CV Events in CKD N=242, Stage 3-5 Chen & Chen, Circ J 2010 ;24;74:

27 27 Both ABI<0.9 & 1.3 are Associated with Overall and CV Mortality in HD and CKD ABI ABI ABI<0.9 ABI<0.9 ABI 1.3 ABI 1.3 Overall Survival Cardiovascular Survival N=69, Stage 3-5, HDN=231 Chen & Chen, Nephrology 2010;15:294-9

28 Either ABI<0.9 or 1.3 is Associated with LVH in CKD 28 N=684, Stage 3-5 Su & Chen, PLoS One 2012;7(9):e44732

29 29 High bapwv is Associated with Rapid Renal Function Decline and Progression to Dialysis and Death in CKD bapwv below Median bapwv above Median egfr Slope Combined end point-free Survival bapwv: brachial artery Pulse Wave Velocity (Arterial stiffness) N=145, Stage 3-5, Follow 14m Chen & Chen, CJASN 2011;6:724-32

30 High bapwv and High bpep/bet are Associated with Rapid Renal Function Decline and Progression to Dialysis in CKD L bapwv L bapwv H bapwv H bapwv L bpep/bet H bpep/bet L bpep/bet H bpep/bet N=243, Stage 3-5 Chen & Chen, Hypertens Res 2012;35:

31 31 Four-Limb BP High BP is an established modifiable risk factor for cardiovascular disease and mortality. However, the association between BP and cardiovascular risk weakens in the elderly. J Hypertens 24: , 2006 A major confounding factor is atherosclerotic PAD. When PAD is present in subclavian and brachial arteries, arm BP cannot be accurately measured, and HT therefore cannot be timely diagnosed and properly managed in clinical practice. Lane D et al, J Hypertens 20: , 2002

32 32 Interarm BP Difference National Institute for Health and Clinical Excellence (NICE) clinical guideline for hypertension a difference of < 10 mmhg can be regarded as normal a difference of > 20 mmhg between arms is unusual occur in less than 4% of people usually associated with underlying vascular disease

33 33 Interarm BP Difference is associated with PAOD and LVH N=1120 Su & Chen, PLoS One 2012;7:e41173

34 Interleg BP Difference Predicts Overall and CV Mortality in HD 34 Normal Interleg BP D. Normal Interleg BP D. log-rank P<0.001 log-rank P<0.001 Interleg Diffe. of SBP 15mmHg or DBP 10mmHg Interleg Diffe. of SBP 15mmHg or DBP 10mmHg Overall Survival N=110, Follow up 4.4±1.5y Cardiovascular Survival Chen & Chen, CJASN 2012;7:

35 35 Interankle SBP Difference is Associated with a 25% Decline in egfr Interankle SBP D. 6mmHg log-rank p = Interankle SBP D. 6mmHg N=1445, Stage 3-5, Follow 3.1y Chen & Chen, Nephrology 2016;21:379-86

36 Overhydration is Associated with Progression to RRT in CKD 36 N=472, Stage 4-5, Follow 17.3m Tsai & Chen, AJKD 2014;63:68-75

37 Overhydration is Associated with Overall and CV Mortality in CKD 37 Entire Cohort N=478 HS<7% N=239 HS 7% N=239 P-value Patient-year of follow-up <0.001 Combined outcomes per 100 patient-year (95%CI) 8.6 ( ) 4.4( ) 14.3( ) <0.001 Cardiovascular morbidity per 100 patient-year (95%CI) 6.7( ) 3.0( ) 11.5( ) <0.001 Death per 100 patient-year (95%CI) 3.3( ) 1.4( ) 5.8( ) Data are expressed as number (percentage) for categorical variables and median (25 th, 75 th percentile) for continuous variables, as appropriate. Abbreviations: HS, relative hydration status P-value was measured by comparisons between participants with HS 7% and those with HS<7%. N=478, Stage 4-5, Follow 23.2m Tsai & Chen, CJASN 2015;10:39-46

38 38 Heart Rate Variability (HRV) Heart rate variability (HRV) is used to evaluate the cardiovascular autonomic neuropathy. HRV is defined as variations of both instantaneous heart rate and R-R intervals of ECG. HRV may provide a simple and noninvasive way in assessing the activities of the autonomic nervous system. HRV has been categorized into high-frequency (HF) and low-frequency (LF) ranges. Normalized LF(LF%) is considered to mirror the sympatho-vagal balance or to reflect sympathetic modulation.

39 39 Some HRV Parameters Increased in Patients without Peripheral Artery Disease (PAD) in HD HRV parameters (frequency domain) Without PAD With PAD Before HD After HD Before HD After HD LF (ms 2 ) 2.5 ± ± ± ± 0.6 HF (ms 2 ) 2.3 ± ± 0.4 * 1.6 ± ± 0.7 LF% (nu) 42.2 ± ± 2.0 * 35.3 ± ± 3.4 HF% (nu) 33.0 ± ± ± ± 1.9 LF/HF 0.22± ± 0.10 * ± ± 0.16 N=161 HD Chen & Chen, PLoS One 2015;10:e

40 LF%(Normalized Low Frequency for HRV) Predicts Overall and CV Survival in HD 40 p = p = Overall Survival N=182 HD, Follow 35.2m Cardiovascular Survival Chen & Chen, Sci Rep 2016;6:20597

41 41 Cholesterol Iseki K et al, Kidney Int 2002; 61 :

42 Cholesterol is Associated with Renal Outcomes in CKD 42 Renal replacement therapy Rapid renal progression Unadjusted Adjusted Unadjusted Adjusted Total cholesterol HR (95% CI) HR (95% CI) OR (95% CI) OR (95% CI) Quintile (1.10, 1.61)* 1.23 (1.01, 1.49)* 1.12 (0.86, 1.46) 1.06 (0.79, 1.42) Quintile Quintile (0.74, 1.10) 1.08 (0.88, 1.33) 1.05 (0.81, 1.38) 1.17 (0.87, 1.57) Quintile (0.95, 1.39) 1.25 (1.02, 1.52)* 1.18 (0.90, 1.54) 1.20 (0.89, 1.61) Quintile (1.13, 1.64)* 1.35 (1.11, 1.65)* 1.98 (1.53, 2.55)* 1.36 (1.01, 1.83)* *p < 0.05; **p < compared to quintile 2 N=3,303, Stage 3-5, Follow 2.8y Chen & Chen, PLoS One 2013;8:e55643

43 Proteinuria Modify the Relationship Between Lipid Profile and Mortality in CKD 43 TC & TC/HDL-- Overall mortality if UPr<1g/D TC/HDL-- Overall mortality if UPr 1g/D N=3,303, Stage 3-5, Follow 2.8y Chen & Chen, CJASN 2013 ;8:

44 4 4 Summary Cardiovascular diseases are common in CKD, and CKD has been recognized as a major risk factor for CVD. Many nontraditional risk factors also contribute to CVD and should not be missed. We should recognize patients at risk and provide early prevention and treatment.

45 Thank you for your attention