Blood Pressure Monitoring in Chronic Kidney Disease

Transcription

1 Blood Pressure Monitoring in Chronic Kidney Disease Aldo J. Peixoto, MD FASN FASH Associate Professor of Medicine (Nephrology), YSM Associate Chief of Medicine, VACT Director of Hypertension, VACT

2 American Society of Hypertension, Inc. (ASH) Disclosure of Relationships Over the past 12 months Aldo J. Peixoto, MD Grant/Research Support: Veterans Administration HSR&D Honoraria: American Society of Nephrology, Society of Critical Care Medicine, Novartis Other Support: International Society of Nephrology (Sister Renal Centers Program)

3 Educational Objectives 1. To review the profile of out-of-office BP in patients with CKD 2. To review the prognostic role of out-of-office BP in patients with CKD 3. To discuss possible treatment implications of the patterns of out-of-office BP to patients with CKD

4 Premises of this talk 1. ABPM (and HBP) bear closer relationships with of target organ damage in HTN than clinic BP. 2. ABPM (and HBP) are better predictors of hard outcomes in HTN than clinic BP. 3. Night-time BP is marginally better than daytime BP to predict hard outcomes in HTN. 4. ABPM (and home BP) are cost-saving in the diagnosis of HTN compared with clinic BP.

5 CKD-specific issues related to BP measurement

6 CKD-specific issues related to BP measurement Presence of AVF in CKD 4 patients

7 CKD-specific issues related to BP measurement Presence of AVF in CKD 4 patients Visit-to-visit variability of office BP is increased in CKD

8 Visit-to-visit variability (standard deviation) of SBP by egfr in NHANES III egfr, ml/min/1.73 m to 59 <45 P-trend Unadjusted SD 7.5 (5.3) 9.1 (5.4) 12.2 (7.4) <0.001 Model 1 0 (ref) 0.47 (0.78) 2.76 (1.28) <0.001 Model 2 0 (ref) 0.25 (0.74) 1.49 (1.21) Model 1 adjusted for age, race-ethnicity, and sex, mean SBP Model 2 adjusted for age, race-ethnicity, and sex, mean SBP across visits Courtesy: Paul Muntner, PhD

9 CKD-specific issues related to BP measurement Presence of AVF in CKD 4 patients Visit-to-visit variability of office BP is increased in CKD Masked and white coat effects are common in CKD

10 Prevalence of masked HTN, white coat HTN, and masked and WC effects in CKD N=980 in 6 studies Masked HTN = 8% [95%CI = ] White coat HTN = 18% [95% CI = ] M and WC effects (impact on control assessment) 40% controlled in the office, not at home 31% controlled at home, not in the office Bangash and Agarwal. CJASN 2009; 4:

11 Ambulatory BP is often uncontrolled in African-American patients with CKD and controlled office BP Pogue et al. Hypertension 2009; 53: 20-7

12 CKD-specific issues related to BP measurement Presence of AVF in CKD 4 patients Visit-to-visit variability of office BP is increased in CKD Masked and white coat effects are common in CKD Nocturnal HTN and non-dipping are the norm in CKD

13 Nocturnal hypertension is common in CKD and worsens with lower levels of renal function N = Farmer et al. Nephrol Dial Transplant 1997; 12:

14 Prevalence and profile of different dipping status in AASK All Subjects N=617 Dippers N=122 (20%) Non-Dippers N=253 (41%) Reverse Dippers N=242 (39%) Office BP 134/80 133/79 136/81 132/79 24h BP 137/81 131/78 137/82 139/82 Daytime BP 138/83 136/82 138/83 137/82 Night-time BP 134/77 116/67 132/76 146/84 Age = 60±10 years GFR = 44±16 ml/min Pogue et al. Hypertension 2009; 53: 20-7

15 Potential mechanisms responsible for nondipping in CKD Autonomic neuropathy Sympathetic overactivity Overactivity of the RAAS Sleep disordered breathing Decreased activity of vasodilatory and natriuretic systems, impaired natriuresis Decreased physical activity Interactions of renal function and proteinuria Peixoto and White. Kidney Int 2007; 71: 855 Agarwal, Peixoto, Santos and Zoccali. Blood Press Monit 2009; 14: 2-11

16 Interactions between proteinuria, low GFR and circadian BP + CKD, + PROT No CKD, + PROT N = 336 elderly veterans 55% with CKD 34% DM2 36% GN 45% no CKD + CKD, no PROT No CKD, no PROT Agarwal et al. Nephrol Dial Transplant. 2009; 24:

17 Take Home Points (#1) Masked HTN effect is common in CKD out-of-office BP is a must for the evaluation of the patient. Nocturnal hypertension is a hallmark of the BP profile in advanced CKD ABPM may have special relevance.

18 Prognostic Implications of Different BP Measurements in CKD

19 ABPM improves the definition of hypertension-associated outcomes in CKD N = 217 males 42% DM, 92% on HTN Rx GFR 45 ml/min F/U 3.5 years 52 deaths, 36 ESRD Agarwal and Andersen. Kidney Int 2006; 69:

20 ABPM improves the definition of hypertension-associated outcomes in CKD HR for ESRD after adjustment for clinic BP = 2.2 [ ] Agarwal and Andersen. Kidney Int 2006; 69:

21 ABPM is an independent marker of risk of CV and renal events in CKD N = 436, GFR 43 ml/min, 37% DM F/U = 4.2 years Adjusted for age, sex, bmi, diabetes mellitus, CV disease, hemoglobin level, proteinuria, and GFR, and stratified for center Minutolo et al. Arch Intern Med 2011; 171:

22 Relationship between ambulatory BP and outcomes in CKD CV Events ESRD Minutolo et al. Arch Intern Med 2011; 171:

23 Hazard Ratios (HR) Relating Baseline BP Variables to Subsequent Renal Outcomes HR 95% CI P-value 24-hour SBP 1.24 ( ) <0.001 Nighttime SBP 1.17 ( ) <0.001 Daytime SBP 1.27 ( ) <0.001 Clinic SBP 1.28 ( ) <0.001 N = 617, baseline GFR 43.5 ml/min Renal endpoint = Doubling of serum Creat, ESRD or Death Results are adjusted by age, gender, baseline egfr, BMI and number of comorbid conditions, and are stratified by randomization group. Courtesy: Francis Gabbai, MD ASN 2009: manuscript under review

24 Hazard Ratios (HR) Relating Baseline BP Variables to Subsequent Cardiovascular Outcomes HR 95% CI P-value 24-hour SBP 1.31 ( ) <0.001 Nighttime SBP 1.23 ( ) <0.001 Daytime SBP 1.32 ( ) <0.001 Clinic SBP 1.23 ( ) <0.001 N = 617, baseline GFR 43.5 ml/min CV Endpoint: Hospitalized MI, CHF, stroke, revascularization or CV death Results are adjusted by age, gender and are stratified by randomization group. Courtesy: Francis Gabbai, MD ASN 2009: manuscript under review

25 =clinic SBP less than 130 mmhg; uncontrolled=clinic SBP more than 130 mmhg. NT SBP: night time SBP DT SBP: day time SBP Additive predictability for Renal outcomes of ABPM SBPs in models including clinic SBP Overall Controlled clinic SBP < 130 mmhg Uncontrolled clinic SBP > 130 mmhg Event (Rate) 200 (0.079) 65 (0.055) 135 (0.099) HR P-value HR P value HR P value 24-HR SBP Nighttime SBP Daytime SBP Courtesy: Francis Gabbai, MD ASN 2009: manuscript under review

26 Additive predictability for cardiovascular outcomes of ABPM SBPs in models including clinic SBP Overall Controlled clinic SBP < 130 mmhg Uncontrolled clinic SBP > 130 mmhg Event (Rate) 99 (0.040) 38 (0.033) 61 (0.045) HR P-value HR P value HR P value 24-HR SBP Nighttime SBP Daytime SBP Courtesy: Francis Gabbai, MD ASN 2009: manuscript under review

27 Home vs. Clinic BP and risk of renal endpoints in CKD Risk per SD of Home Systolic BP N = 217 * adjusted for age, race, diabetes mellitus, log protein/creatinine ratio, estimated Modification of Diet in Renal Disease glomerular filtration rate, serum albumin, hemoglobin, and angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use. Agarwal. Kidney Int 2006; 69:

28 Home vs. ABPM vs. Clinic and cardiovascular risk in CKD N=217 Cardiovascular outcomes were defined as a composite outcome of myocardial infarction, stroke or death. Agarwal and Andersen. Am J Nephrol 2006; 26:

29 Nocturnal HTN and baseline target organ damage in the AASK Cohort Study Lowest Middle Highest Nsbp <126 Nsbp Nsbp >141 P N=215 N=202 N=200 Echo LVH 57% 70% 81% < Prot/Cr ratio 0.17± ± ±1.05 < Prot/Cr > % 30% 43% < Non-dippers = 41% Reverse dippers = 39% Pogue et al. Hypertension 2009; 53: 20-7

30 Nocturnal hypertension is associated with worse outcomes in CKD -1.3% Unadjusted P< % N = 322 patients referred for ABPM 137 dippers, 185 non-dippers Median follow-up = 3.2 years Davidson et al. Arch Intern Med 2006;166:846-52

31 Nocturnal hypertension and ESRD risk in older men with CKD N = 217 Follow-up = 3.5 years 52 deaths, 36 ESRD Agarwal and Andersen. Kidney Int 2006; 69:

32 Lack of independent effect of circadian BP rhythm on mortality or ESRD NON-DIPPERS v. DIPPERS HR 95% CI P All-cause mortality Unadjusted Adjusted for 24h SBP Adjusted for age, 24h SBP End-stage renal disease Unadjusted Adjusted for 24h SBP Adjusted for age, 24h SBP N = 322 (179 with CKD), Follow-up for up to 8.7 years 116 deaths (60.4/1,000 pt-years, full cohort), 57 ESRD (69.2/1,000 pt-years, CKD cohort) Agarwal et al. Am J Nephrol 2009; 30:

33 Dipping status and outcomes in 4 Italian cohorts Adjusted for age, sex, body mass index, diabetes mellitus, CV disease, hemoglobin level, proteinuria, glomerular filtration rate, and 24-h mean BP. Minutolo et al. Arch Intern Med 2011; 171:

34 Take Home Points (#2) ABPM is stronger predictor than clinic BP of renal and CV events and death in CKD patients. ABPM is better than home BP to predict CV risk in CKD. Home BP is better than clinic BP to predict renal endpoints in CKD. The independent prognostic role of dipping status and nocturnal HTN in CKD remains uncertain.

35 Therapeutic Implications of BP monitoring in CKD

36 Treatment Opportunities ABPM and home have been used to guide the treatment of essential HTN.

37 Treatment Opportunities ABPM and home have been used to guide the treatment of essential HTN. ABPM targets were successfully used in the ESCAPE trial. Wuhl et al. N Engl J Med 2009; 361: 1369

38 Treatment Opportunities ABPM and home have been used to guide the treatment of essential HTN. ABPM targets were successfully used in the ESCAPE trial. Home telemedicine is effective in clinical trials in essential HTN.

39 Telemonitoring and self-management result in better BP control in patients with uncontrolled HTN BP Decline 6 months 12 months Intervention (N=234) 12.9/ /7.5 Control (N=246) 9.2/ /4.8 Difference 3.7/ /2.7 Median = 152 readings/year 74% obtained >90% of expected readings 8% did not complete basic training 12% ceased monitoring during the study McManus et al. Lancet 2010; 376:

40 Web communication under pharmacist supervision improves BP control N = 730 at 12 months Usual Care HBP/Web HBP/Web/Ph armd Adjusted delta SBP Adjusted delta DBP % reaching target 31% 36% 56% Anti-HTN drugs (baseline 1.6) Adjusted RR Ref All comparisons significant for UC vs. HW and H/W vs. HW/PharmD Green et al. JAMA 2008; 299:

41 Blood pressure (mmhg) Effectiveness of home telemedicine for HTN N=107 HT, 107 controls HBPT Control 137±18 134±17 132±17 133±15 132±16 133±18 132±15 133±14 74±12 73±11 71±12 73±11 70±12 72±13 71±12 72±11 Δ SBP Diff 3.6 [-2.0, 9.2] P=0.21 Δ DBP Diff 0.5 [-3.5, 4.5] P=0.81 Uncontrolled HT 33%, C 38% P= [-2.4, 8.0] P= [-2.3, 3.7] P=0.64 HT 31%, C 37% P= [-2.3, 4.8] P= [-2.6, 3.1] P=0.88 HT 30%, C 31% P=0.51 Baseline 3 months 6 months 12 months

42 Treatment Opportunities ABPM and home have been used to guide the treatment of essential HTN. ABPM targets were successfully used in the ESCAPE trial. Home telemedicine is effective in clinical trials in essential HTN. No data in CKD. Chronopharmacologic approaches may improve outcomes in essential HTN and in CKD.

43 Bedtime administration of valsartan is associated with decreased albuminuria in HTN night/day ratio vs. proteinuria (R=0.22, P=0.03) AM valsartan = 102 PM valsartan = 98 3-month study Hermida et al. Hypertension 2005; 46: 960-8

44 Non-dipping can be reverted pharmacologically in CKD with potentially beneficial effects Drug shift to PM improves dipping Drug shift to PM lowers proteinuria N = 32 Age = years egfr = ml/min PER = mg/day Minutolo et al. Am J Kidney Dis 2007; 50:

45 Cardiovascular outcomes with bedtime antihypertensive administration in patients with early CKD N=661, PROBE design, single center GFR 65 ml/min, 33% DM, 7% previous CVD 66% non-dippers at baseline Either all drugs on awakening or 1 or more at bedtime Bedtime agents: ACEi: ramipril or spirapril ARB: valsartan, telmisartan, olmesartan CCB: amlodipine or nifedipine GITS End-of-study BP: lower at night 123/63 vs 117/65 (P<0.001) End-of-study non-dippers: 41% vs 71% (P<0.001) Hermida et al. JASN 2011; 22:

46 Cardiovascular outcomes with bedtime antihypertensive administration in patients with early CKD N=661, PROBE design, single center F/U 5.4 years, 139 events Hazard Ratios 0.31 [0.21 to 0.46] 0.28 [0.13 to 0.61] Hermida et al. JASN 2011; 22:

47 Differential relationship between achieved clinic and sleep BP and outcomes in MAPEC Quintiles of achieved SBP Hermida et al. JASN 2011; 22:

48 CV events/1,000 person-years Potential risks: increased risk of stroke in extreme dippers with mild CKD N=811, F/U=41 months Adjusted* Hazard Ratios: ED = 2.59 [ ] ND = 1.83 [ ] ED = 165 (21%), D = 343 (42%), ND = 303 (37%) *Adjusted for age, sex, BMI, smoking, DM, hyperlipidemia, antihypertensive treatment, egfr, 24h SBP Ishikawa et al. J Clin Hypertens 2008; 10:

49 Potential effects of manipulation of nocturnal BP in CKD How much is too much? Minutolo et al. Arch Intern Med 2011; 171:

50 Take Home Points (#3) Treatment strategies that incorporate outof-office BP are feasible in CKD. Their efficacy and safety remain to be confirmed, especially as it pertains to bedtime medication dosing.

51 American Society of Hypertension, Inc. (ASH) Disclosure of Relationships Over the past 12 months Aldo J. Peixoto, MD Grant/Research Support: Veterans Administration HSR&D Honoraria: American Society of Nephrology, Society of Critical Care Medicine, Novartis Other Support: International Society of Nephrology (Sister Renal Centers Program)