Ambulatory Blood Pressure Measurement. Objectives of the Presentation. Methods of Measuring BP: Pros and Cons

Transcription

1 Ambulatory Blood Pressure Measurement William B. White, MD Professor of Medicine and Chief, Hypertension and Clinical Pharmacology Calhoun Cardiology Center University of Connecticut School of Medicine Farmington, Connecticut Immediate Past President, American Society of Hypertension Objectives of the Presentation To understand the 3 key forms of blood pressure measurement To assess the relations among clinic, home and 24 hour blood pressure To review the utility of ambulatory blood pressure in clinical practice To determine when to incorporate outof-office measurement in hypertension management Clinic Methods of Measuring BP: Pros and Cons Pros Ease of measurement Associated with clinical trial outcome data Cons Lack of reproducibility White-coat effect Masked hypertension Home (self) ABPM Inexpensive Empowers patient involvement in his/her own care Large number of measurements obtained Sleep measurements obtained Provides the ability to evaluate drug treatment effect Little outcome data Can cause patient anxiety Device variability Most expensive blood pressure method Inconvenient for patient to do repeatedly 1

2 Suggested Values for the Upper Limit of Normal Ambulatory Pressure Optimal Normal Abnormal Daytime < 130/80 < 135/85 > 140/90 Nightime < 115/65 < 120/70 > 125/75 24-hour < 125/75 < 130/80 > 135/85 Pickering TG and White WB. When and how to use self (home) and ambulatory blood pressure monitoring. J Am Soc Hypertens 2008; 2 (3): White Coat Hypertension 2

3 Cumulative hazard of stroke, % 2-year incidence of cardiovascular endpoints Ambulatory BP Predicts CV Morbidity Better than Clinic BP - Prospective Studies Author Year Population n Comments Perloff Referred 1076 Low risk if ABP < CBP Verdecchia Referred 1187 WCH at low risk Imai Population 1789 ABP & HBP predict, not CBP Redon Refractory 86 Low risk if ABP<CBP Khattar Referred 479 WCH at low risk (intraarterial) Staessen Syst-Eur 808 ABP gives better prediction Clement OvA 1963 Elevated ABP predicts events in treated hypertensives Sega General 2051 Home and ABP (systolic) best at predicting CV death 1 Perloff D et al. JAMA 1983;249: Verdecchia P et al. Hypertension 1994;24: Imai Y et al. Blood Press Monit 1996;1: Redon J et al. Hypertension 1998;31: Khattar RS et al. Circulation 1998;98: Staessen JA et al. JAMA 1999;282: Clement DA et al N Engl J Med 2003; in press (12 June) 8Sega R et al Circulation 2005; 111: Conventional, 24-h, Daytime and Night-time SBP as Predictors of Cardiovascular Endpoints Syst-Eur Night-time 24-h Daytime Conventional Systolic blood pressure (mmhg) Staessen JA et al. JAMA 1999;282: Time to Stroke Event According to Patient ABP Sub-Type 8 7 White-coat hypertension Ambulatory hypertension 6 5 Normotensive group Verdecchia P et al. Hypertension 2005;45:203-8 p = Time to stroke, year

4 Incidence of CV events (no./1000 person-yr) Masked Hypertension Factors Contributing to Masked Hypertension Factors that Lower Clinic Pressure Negative White Coat Effect Resting State Factors that Raise Ambulatory Pressure Stressful Environment Smoking Cigarettes Physical Activity White WB and Gulati V. Current Cardiology Reports 2015 ;17: in press Higher Ambulatory BP Measurements in Treated Hypertensives Predicts CV Risk / hr ambulatory systolic BP: <135 mmhg 135 mmhg <140 8/71 23/506 26/ Office systolic BP (mmhg) 19/271 67/ Clement DL, De Buyzere ML, De Bacquet DA, for the Office versus Ambulatory Pressure Study Investigators. Prognostic value of ambulatory blood-pressure recordings in patients with treated hypertension. N Engl J Med. 2003,348,

5 Change from baseline SBP (mmhg) IDACO Total Mortality and CV Events by Category of the Night:Day Ratio of SBP 10 Total Mortality 10 CV Events Incidence (%) < P< P< Years of Follow-Up Adjusted for cohort, sex, age, body mass index, smoking and drinking, cholesterol, history of CV disease, diabetes mellitus, AH treatment, and 24-hour SBP. Boggia J et al. Lancet. 2007;370: Therapeutic Considerations for 24- Hour BP Monitoring Assessment of time of dosing Evaluation of differences according to pharmacodynamics and/or kinetics Influence of the circadian variation of physiologic factors Removal of all or most observer biases in clinical trials Comparison of 2 antihypertensive therapies in the same class Time after dosing (h) P<0.005 Valsartan 160 mg Telmisartan 80 mg P<0.05 P<0.001 P< P values are for Telmisartan vs Valsartan comparison Lacourcière Y and White WB. Blood Press Monit 2004:9;

6 Use of Ambulatory Blood Pressure in Hypertension Management Office Blood Pressure >140/90 mmhg in Low-risk Patients (no target organ disease) >130/80 mmhg in High-risk Patients (target organ disease, diabetes) Self-Monitored BP <130/80 mmhg Self-Monitored BP 130/80 mmhg Perform Ambulatory BP Monitoring 24-hour BP <130/80 mmhg 24-hour BP 130/80 mmhg Follow up with nondrug Initiate Antihypertensive Therapy therapy on a 6-12 month basis Repeat ambulatory BP Perform ambulatory blood-pressure monitoring measurement every one to two years 24-hour BP <130/80 mmhg 24 hour BP 130/80 mmhg White WB. N Engl J Med. 2003;348: Maintain present therapy Follow up with an ABPM every two years Change antihypertensive therapy to improve control (target <130/80 mmhg) Follow up with ABPM every two years TREATED Key Clinical Scenarios for Out-of- Office Blood Pressure Monitoring Ruling out White-Coat Hypertension (or White-Coat Effect) Concern that Masked Hypertension might be present Determination if Nocturnal Hypertension is Significant Evaluation of Complex Drug Therapy Highly variable blood pressures in the medical care environment (within visit and visit-to-visit) White WB, Blood Pressure Monitoring in Cardiovascular Medicine and Therapeutics, 3 rd Edition, Springer Science

7 7/11/2016 VuMedi July 11, 2016 HYPERTENSION MANAGEMENT IN CORONARY ARTERY DISEASE Clive Rosendorff, MD, PhD, DScMed, FACC, FRCP(Lond). Professor of Medicine (Cardiology), Icahn School of Medicine at Mount Sinai, New York, NY, USA and James J. Peters VA Medical Center, Bronx, NY, USA Total Coronary 300 Blood Flow (ml/min) 200 P1 A1 Coronary Event Rate Diastolic B.P (mm Hg) Rosendorff, In Hypertension, A Companion to Braunw ald s Heart Disease Ed. Black & Elliott, Elsevier 2013; years old SPRINT- Major Inclusion Criteria Systolic blood pressure : mm Hg (treated or untreated) Additional cardiovascular disease (CVD) risk Clinical or subclinical CVD (excluding stroke) Chronic kidney disease (CKD), defined as egfr 20 <60 ml/min/1.73m 2 Framingham Risk Score for 10-year CVD risk 15% Age 75 years 1

8 7/11/2016 SPRINT - Primary Outcome MI, ACS, Stroke, HF, CV death Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89) Standard (319 events) Intensive (243 events) Median follow-up = 3.26 years) Number Needed to Treat (NNT) to prevent a primary outcome = 61 Number of Participants SPRINT Primary Outcome and its Components Event Rates and Hazard Ratios Intensive No. of Events Rate, %/year Standard No. of Events Rate, %/year HR (95% CI) P value Primary Outcome (0.64, 0.89) All MI (0.64, 1.09) Non-MI ACS (0.64, 1.55) All Stroke (0.63, 1.25) All HF (0.45, 0.84) CVD Death (0.38, 0.85) < J Am Coll Cardiol 2015;65(18): ; Circulation. 2015;131:e435-e470. Hypertension. 2015;65: ; J Amer Soc Hypertens. 2015;9:

9 7/11/2016 Summary of BP Goals BP Goal, mm Hg Condition Class/Level of Evidence <150/90 Age > 80 y IIa/B <140/90 CAD I/A ACS IIa/ HF IIa/ <130/80 Reasonable CAD,ACS,HF IIb/C Post-MI, stroke, TIA, carotid art. dis., PAD, AAA. Rosendorff et al. J Am Coll Cardiol 2015;65(18): BP Goal, mm Hg Summary of BP Goals Condition Class/Level of Evidence <150/90 Age > 80 y IIa/B <140/90 CAD I/A ACS HF <130/80 Reasonable CAD,ACS,HF Post-MI, stroke, TIA, carotid art. dis., PAD, AAA. IIa/ IIa/ IIb/C POST-SPRINT SBP <120 mm Hg If tolerated: 1. BP lowered slowly 2. No increasing myocardial ischemia 3. No orthostatic hypotension, dizziness, or syncope 4. In ACS: Hemodynamically stable 5. In HF: No worsening HF symptoms or signs. SUMMARY 1. BP Goals: Lower is better for stroke AHA/ACC/ASH HT and CAD: <140/90; <130/80 reasonable 2015 SPRINT: SBP < For primary prevention of CAD: ACEI/ARB or CCB or diuretic, or combination. β-blockers not protective. 3. For established CAD, stable angina and ACS: β-blocker plus ACEI/ARB plus diuretic. Add DHP CCB if needed. Non-DHP CCB effective in angina instead of β-b, but not if HF. 4 For Ischemic Heart Failure: β-blocker plus ACEI/ARB plus diuretic plus aldosterone antagonist. Hydralazine/isosorbide 3

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11 SBP 95 th % Recent Advances in Pediatric Hypertension Definition Evaluation Target Organ Damage Treatment Targets Prevention Blood Pressure Levels for Boys by Age and Height Percentile Systolic BP (mmhg) Diastolic BP (mmhg) Age BP Percentile of Height Percentile of Height (Year) Percentile 5th 10th 25th 50th 75th 90th 95th 5th 10th 25th 50th 75th 90th 95th 12 50th th th th The fourth report; Pediatrics 2004 Prevalence of systolic hypertension - boys BMI < 85th 85th < BMI <95th BMI > 95th yr 6-10 yr yr yr Falkner, J Peds, 2006 Age grouping 1

12 Definition of Hypertension Hypertension average SBP and/or DBP that is greater than or equal to the 95th percentile for sex, age, and height on 3 or more occasions. Prehypertension average SBP or DBP levels that are greater than or equal to the 90th percentile, but less than the 95th percentile. Adolescents with BP levels greater than or equal to 120/80 mmhg should be considered prehypertensive. The fourth report; Pediatrics 2004 Prevalence of Childhood Hypertension Based on BP >95 th % predicted prevalence of pediatric hypertension is 5% (single BP measurement). With repeat measurement the prevalence had been expected to be 1-3% Data from screening >20,000 high school students (3 BP measurements) found 3.2% prevalence. (McNiece, J. Peds 2007) Analysis of data from electronic medical records of >14,000 well children with repeat BP measurements found 3.5 % prevalence of hypertension and approximately 3.5% prevalence of prehypertension. (Hansen, JAMA, 2007) High School Student BP Screening: McNiece et al 2007 Prevalence of High BP at First Screening Final Adjusted Prevalence of HTN Pre-hypertensive 9.5% Stage 1 8.4% Stage 2 1% Stage 1 2.6% Pre-hypertensive 15.7% Stage 2 0.6% Normotensive 81.1% Normotensiv 81.1% McNiece, J Peds

13 Estimated Prevalance of Prehypertension-Hypertension in childhood Relative to BMI Percentile Tu et al; Hypertension 2011 Update of Pediatric Hypertension Guidelines are Underway New BP tables based on normal weight children and adolescents. Simplified BP tables Consideration of prevention strategies Ambulatory Blood Pressure Monitoring Useful in the evaluation of White-coat hypertension Detection of masked hypertension Target organ injury risk Apparent drug resistance Drug-induced hypotension Provides additional BP information in Chronic kidney disease Diabetes Autonomic dysfunction ABPM should be performed by clinicians experienced in its use and interpretation. 3

14 Association of Risk Factors with Vessel Pathology % of Aorta with Fatty 20 Streaks or 4 Number of Risk Factors Berenson et al, N Engl J Med 1998 Effects of Obesity and High BP On left ventricular mass in adolescents Falkner J Peds 2013 Vascular Stiffness in Adolescents According to Blood Pressure Status Urbina J of Clinical Hypertension

15 SHIP AHOY Determine the BP threshold for target organ damage. Determine the metabolic phenotype and hemodynamic phenotype associated with target organ damage. Explore genetic/epigenetic changes associated with target organ damage. Underway and Funded by AHA What About Salt? Yang Pediatrics 2012 online 5

16 DASH CAMP Controlled feeding study on adolescents to assess the effect of DASH diet (with and without low salt) on BP. Sponsored by NIH/NHLBI Beginning in

17 Systolic Blood Pressure Trajectories from Childhood to Early Adulthood. Theodore et al, Hypertension, 2015 Number to Remember 120/80 mm Hg 7

18 7/11/2016 Optimal Device Trial Design for Hypertension Therapy Michael A. Weber, MD State University of New York Downstate College of Medicine Speaker Disclosures I disclose that I am a Consultant for: Ablative Solutions, Astellas, Boston Scientific, Eli Lilly, Medtronic, Novartis, ReCor Rationale for Renal Denervation Action of renal nerves is to: Stimulate renin release Increase sodium reabsorption Increase central sympathetic outflow Thus, ablating renal nerves will reduce BP by: Decreasing activity of renin-angiotensin system Enhancing natriuresis Decreasing systemic sympathetic activity 1

19 Office SBP (mm Hg) Change in SBP at 6 Months (mmhg) 7/11/2016 Symplicity 3: RDN vs. Sham in Treatment Resistant HTN Δ = (95% CI, to 2.12) P=0.26* 200 Δ = -14.1±23.9 P<0.001 Δ = -11.7±25.9 P< mm Hg 180 mm Hg 166 mm Hg 168 mm Hg 100 Baseline 6 Months 50 0 (N=364) (N=353) (N=171) (N=171) Denervation Sham *P value for superiority with a 5 mm Hg margin; bars denote standard deviations Symplicity HTN 3: Explaining An Unexpected Result - Sham procedure design raised question: Did previous uncontrolled trials produce misleading data? - Compelling issues of: renal nerve anatomy catheter design operative technique - Patients with Treatment resistant Hypertension -- a poorly defined clinical entity driven largely by inaccurate diagnosis and poor medication compliance SYMPLICITY HTN-3 Procedure: Distribution of interventions 0 Office Ambulatory Home n=68 n=236 n=62 n=17 n=66 n=253 n=19 n=248 n= (-17.2, -11.2) (-21.6, -10.6) (-35.5, -13.1) P= (-8.2, -4.3) -8.2 (-9.3, -5.2) (-11.2, -4.2) (-12.2, -4.2) (-21.3, -3.3) (-21.1, 0.4) P=0.58 P= Four-quadrant ablations 1 Four-quadrant ablation (either right or left) 2 Four-quadrant ablations (both sides) Baseline SBP (mmhg) 0 Four-quadrant ablations Four-quadrant ablations Four-quadrant ablations Kandzari et al. Eur Heart J. 2015;36:

20 7/11/2016 Our View of Renal Nerve Distribution Has Changed Renal nerves may have a positional bias on radial distance from arterial lumen: distal nerves are closer Distal Proximal Prior concept Uniform radial distribution Distal Proximal Current concept Non-uniform radial distribution Sakakura K, et al., JACC 2014; 64: Lessons Learned Cannot get reliable results when an inconsistent technique is applied to an ill-defined clinical condition Solution Optimize catheter designs to ensure full circumferential effects Establish rigorous standards of procedural technique: should we go beyond main renal artery? Study carefully defined hypertensive populations Use trial designs that effectively measure the effects of treatment on high blood pressure Methods for Renal Denervation CATHETER-BASED (within renal arteries) Radio-frequency ablation Ultrasound energy Delivery of neurolytic agent through renal artery wall EXTERNAL Focused ultrasound energy 3

21 7/11/2016 Investigational Device: Vessix Renal Denervation System Balloon-based technology 4-7 mm diameters Helical pattern of bipolar RF electrodes All electrodes are activated simultaneously 30 second treatment time Temperature-control algorithm for energy delivery at 68 C One button operation 7F compatible (Vessix Reduce Catheter) * Vessix System is an investigational device and not available for sale in the US. Which Populations to Study Start with uncomplicated patients with Stage 1 or 2 hypertension: Untreated systolic BPs mmhg WHY? Because analogous to testing a new hypertension drug -- we are studying the efficacy of RDN, from a regulatory point of view, for the first time in human hypertension Focused Protocols for Renal Denervation: Patients Initially Off Drugs Patient Selection Randomization (Blinded to patients and observers) Primary BP Efficacy Endpoint Long-term BP Efficacy Endpoint ABPM ABPM ABPM No BP meds at baseline (any previous meds D/C d) Renal Denervation Patients w ith inclusion BP* confirmed by clinic and ABPM measurements Sham Procedure Systematic addition of drugs needed to achieve BP control 4-Week Run-in Period 8-Week Initial Treatment Period 4-Month Continuing Treatment Period Clinic systolic BP mmhg and ABPM systolic BP mmhg Can be extended with careful patient ov ersight From: Weber/ Kirtane/ Mauri/Townsend/Kandzari/Leon. CCI/ Clin Cardiol/JCH 2015; In press 4

22 7/11/2016 Renal Denervation: Traditional Protocol for Combined Hypertension Treatments Patient Selection Randomization (Blinded to patients and observers) Primary BP Efficacy Endpoint ABPM ABPM No BP meds at baseline (any previous meds D/C d) Renal Denervation + Placebo Patients w ith inclusion BP* confirmed by clinic and ABPM measurements Sham Procedure + Active Drug Renal Denervation + Active Drug 4-Week Run-in Period 8-Week Treatment Period * Clinic systolic BP mmhg and ABPM systolic BP mmhg Can be extended with carful patient ov ersight Strictly-defined single or combination drug regimen Weber/Kirtane/Mauri/Townsend/Kandzari/Leon. JCH/CLC/CCI 2015 In press Indications for Renal Denervation (1) (Looking to the Future) Indication Comment 1.Treatment-resistant hypertension (TRH) 2. Patients with poor drug compliance 3. Systolic hypertension in the elderly SNS=sympathetic nervous system Weber MA. TCT Meetings, 2015 Condition poorly defined True TRH is rare No consistent evidence that RDN superior to expert drug therapy Improved RDN studies are ongoing Improvement in long term BP control could justify cost of intervention SNS is a factor Condition responds well to drugs RDN could simplify care if ablation energy can cross atherosclerotic renal artery walls Indications for Renal Denervation (2) (Looking to the Future) Indication Comment 4. Hypertension in young adults High SNS activity often characterizes this condition Early evidence for left ventricular changes, arterial stiffness etc. RDN could potentially improve lifelong natural history of hypertension 5. Hypertension associated with CKD 6. Atrial fibrillation and heart failure Early evidence that RDN can reduce rate of loss of renal function These indications already being studied independently of hypertension SNS=sympathetic nervous system; CKD=chronic kidney disease Weber MA. TCT Meetings,