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1 Ambulatory Arterial Stiffness Monitoring, As Good As Ambulatory Blood Pressure Monitoring? 이해영서울대학병원순환기내과

2 The Korean Society of Cardiology COI Disclosure Hae-Young Lee The authors have no financial conflicts of interest to disclose concerning the presentation 2017 Annual Spring Scientific Conference of the KSC in conjunction with KHRS, KSIC, KSE, and KSoLA

3 동맥경화검사 (Vascular biomarker) 가가져야할요건 효능 (Proof of concept) 심혈관사건 ( 기 ) 발생자와미발생자사이차이가있는가? 예후예측력 (Prospective validation) 코호트연구등에서사건발생예측력이증명되었나? 추가효능 (Incremental value) 기존의위험예측도에더한추가적인예측력이있는가? 검사효과 (Clinical utility) 검사결과로치료방침을바꿀만한가? 치료효과 (Clinical outcomes) 무작위검사에서검사에따른치료결정으로예후에차이를보았는가? 비용대비효과 검사의용이성 검사방법의통일성 인종 / 성별 / 연령에따른정상치보유

4 Operator-independent 동맥경화도검사 Carotid-femoral pulse wave velocity Brachial-ankle pulse wave velocity Central hemodynamics/wave reflections

5 Rationale of carotid-femoral PWV measurement Central Conduit Stiffness = Characteristic Impedence = Carotid- Femoral PWV Peripheral (muscular) Conduit Stiffness = Carotid- Brachial PWV = Carotid- Radial PWV

6 Pros and cons of brachial-ankle PWV Brachial-ankle PWV 의단점 혈관계가좁은하지의동맥을포함하므로 CfPWV 에비해큰값을가짐 ( 일본인만명을대상으로한연구에서 bapwv 값이 14.0 m/s 이상인경우 Framingham score 에의한심혈관위험도예측에서독립적인예측인자였음 ) 동일혈관이아닌상지 - 하지별개의혈관속도를인위적으로합친측정치 Elastic artery 인대동맥보다는 peripheral muscular artery 의경화도를주로반영? Brachial-ankle PWV 의장점 간편하고비침습적인방법 : 의복을착용한상태에서간편하게측정가능 혈압과 Ankle-brachial index 를동시에측정가능 말초소동맥의경화도반영하므로좌심실비대및기능저하의평가인자로서는 carotid-femoral PWV 보다잠재적우위성이있을가능성?

7 Noninvasive estimation of aortic blood pressure Noninvasive measurement underestimate actual SBP by ~4.5mmHg compared with gold standard invasive catheter measurement J of hypertension. 2016;34:

8 Indirect, non-invasive methods for estimating central pressure Radial arterial tonometry: SphygmoCor, HEM9000AI High-sensitivity cuff oscillometry: ARCsolver device incorporated in Mobil-O-Graph

9 중심동맥압이상완동맥압에비해경동맥비대 / 죽상경화예측에우월함 *Statistical comparison of central vs brachial correlation Roman MJ, Devereux RB. Hypertension. 2014;63:

10 중심동맥압이상완동맥압에비해좌심실질량 / 좌심실비대예측에우월함 *Statistical comparison of central vs brachial correlation Roman MJ, Devereux RB. Hypertension. 2014;63:

11 표적장기손상예측에대한중심동맥압평가의효용성 경동맥비대, 좌심실비대등심혈관질환미세손상지표와의상관관계가상완동맥보다높음 고혈압환자에서 Perindopril/Indapamide를이용해좌심실비대를호전시킨 REASON 연구에서는좌심실질량의감소정도가중심동맥압에서만유의하였음 심혈관사건발생의예측력이보고됨 중심동맥압중심의고혈압약제치료시 16% 의환자에서약제중지가가능했다는보고가있음 Randomized trial of guiding hypertension management using central aortic blood pressure compared with best-practice care: principal findings of the BP GUIDE study. Hypertension 2013; 62:

12 고혈압환자의위험도평가에중심동맥압이 Reclassification 효과가있음 Overlap in aortic SBP despite no overlap in brachial SBP, in healthy men and women (n = 5648). > 70% of individuals with high-normal BP had aortic SBP in common with individuals with stage 1 hypertension. Hypertension 2008;51:

13 수축기혈압의변이폭은상완동맥과유사함

14 중심동맥압측정이정립되기위해해결되어야할과제 중심동맥압측정기기사이의측정치차이가큼 경동맥파형분석방식과비교해 Omron (HEM9000AI) 기기의중심동맥압측정치는 12mmHg 높게표시되고, Sphygmocor 기기의경우 7mmHg 낮게표시됨. 중심동맥압의정상치가정립되어있지않음 상완동맥압의 140/90 mmhg 에대해중심동맥압 125/90mmHg 수준이상응된다는보고가있는실정 연령 / 성별 / 신장 / 맥박등요인에따라상완동맥압, 중심동맥압의차이가영향받으나, 30% 의혈압차이의요인은아직설명되지않음. 표적장기손상에대한높은예측력이 개의맥박결과를평균해서오는정밀도에의한것이라는유보적견해도있음

15 ESC/ESH guideline 에서의 PWV, Central BP 의위치

16 Pulse wave analysis over 24 hours Simultaneous monitoring of peripheral BP Central arterial pressure Arterial stiffness in ambulatory conditions over the 24 h. Mobil-O-Graph PWA By I.E.M. GmbH BPLab By OOO Petr Telegin BPro By HealthSTATS International

17 Mobil-O-Graph PWA Obtains pulse waves with a conventional upper arm BP cuff. Following inflation to DBP level, acquiring the pulse waveform over 10 s through a high fidelity pressor sensor. After digitalization by 12-bit A/D converter, a three-stage signal processing used to confirm signal quality. Aortic pulse wave generated by means of a generalized transfer function (ARCSolver) to compute vascular parameters. ARCSolver method uses late systolic peak and a transfer function-like method. To estimate aortic PWV, this method utilizes parameters from PWA combined into a proprietary mathematical model, coupled with information on age and CAP

18 BPLab During a step-by-step deflation of an upper arm cuff, brachial pulse wave forms obtained from oscillograms, digitalized and stored. Signal processing performed using a special mathematical algorithm (Vasotens transfer function) CAP and AIx derived from the analysis of the reconstructed central pulse wave.

19 BPro Acquires the radial pressure waveform through automated radial tonometry (EVidence-Based blood Pressure tonometry) at a frequency of 60 Hz A single radial waveform averaged from individual waveforms recorded consecutively for 10 s per block of waveforms. From the radial waveform, estimating CAP using an N- point moving average method Accurately derive CAP and does not generate an aortic waveform.

20 Main features and validations of 24h devices Twenty-Four-Hour Ambulatory Pulse Wave Analysis in Hypertension Management: Current Evidence and Perspectives. Curr Hypertens Rep. 2016;18:72

21 Accuracy of 24h pulse wave analysis In most studies, measurements of PWV, CAP, and AIx were in accordance with the reference standard. Cuff-based method seems to be the most promising technique, given the fact that it is affordable, convenient, and easy-to-use. Oscillometric devices with autocalibration function can estimate central SBP with a very high degree of accuracy [test-reference difference and 95 % confidence interval: 0.77 ( 3.27, 1.73) mmhg]. All studies were performed in resting conditions.

22 24 시간동맥경화도측정의정확도 Comparing the Mobil-O-Graph with the gold standard SphygmoCor, mean difference in estimated aortic SBP of only 0.1mmHg and a difference in aortic Aix of 1.2%. An acceptable accuracy between PWV measured by the Mobil-O-Graph and PWV derived from the invasive intra-aortic catheter measurements Moderately higher PWV values in Mobil-O-Graph

23 Reproducibility of 24h pulse wave analysis Reproducibility or 24-h ambulatory CAP taken at least 1-week apart in 30 consecutive subjects. Acceptable reproducibility of both 24-h CAP (2.6 and 3.2 %) and 24-h brachial BP (2.7 and 3.3 %). Highly reproducible PWV and AIx, with average variation coefficients of 1.5 and 11.4 %, respectively, and intraclass correlation coefficients always >0.8. Reproducibility of a new interesting index, the Pulse Time Index of Norm (PTIN) Percentage of a 24-h period during which the PWV does not exceed the 10 m/s threshold Similar during the first and second recording, either in normotensives (86.5 vs %) or in HT pts (57.5 vs %) Excellent intraclass correlation coefficients (0.98 for normotensives and 0.95 for hypertensives)

24 Clinical studies based on Mobil-O-Graph Significantly lower systolic CAP than peripheral SBP either during the day (124.1 ± 15.7 vs ± 16.3 mmhg) or during the night (114.4 ± 14.5 vs ± 15.2 mmhg). Nocturnal fall in systolic CAP was lower than peripheral SBP fall 24-h central and brachial SBP were superior to conventional office BP in predicting BP-related cardiac damage (LVH and LV diastolic dysfunction) 24-h ambulatory central SBP was also more closely associated with LVH than 24-h brachial SBP (r = 0.51 vs. r = 0.40). Ambulatory PWV provides additional information to cfpwv regarding the association of arterial stiffness with the retinal vessel calibers.

25 Novel findings following 24 hour pulse wave analysis PWV decreases from day to night (0.7 m/s), whereas AIx increases (2.3 %). Ambulatory AIx significantly declined after highintensity interval training, but not after moderate continuous training. Strong relationship of 24-h BP variability with CAP and arterial stiffness, which is largely independent from the average 24-h BP level. Good correlation (r = 0.72) between PTIN (Pulse Time Index of Norm) and LVMI, indicating that PTIN may represent an interesting marker of end organ damage in hypertension.

26 Outcome-Based Evidence for 24-h PWA: the VASOTENS Registry VASOTENS (Vascular health ASssesment Of The hypertensive) Registry. International, multicenter, observational, non-randomized, prospective study, approximately 2000 subjects referred to 20 hypertension clinics worldwide for routine diagnostic evaluation and follow-up of hypertension of any severity or stage will be recruited. Each subject will be submitted every 6 to 12 months to an ABPM performed with a BPLab monitor, with simultaneous assessment of brachial BP, PWV, CAP, and Aix. Subjects will be followed up for a minimum of 2 years.

27 Current advantages of PWA assessment over 24 h Easy-to-use (particularly cuff-based techniques) Techniques are largely operator-independent Evaluation in daily life conditions Repeated and prolonged measurement Evaluation of the effect of activity vs. sleep Evaluation of antihypertensive treatment Affordability: in most cases devices are cheaper than those used for monitoring at rest Potentially useful for early screening of arterial damage in many conditions (e.g. arterial hypertension, diabetes, at high CV risk, etc.)

28 Current limitations of PWA assessment over 24 h Accuracy Validation studies performed only at rest No standardized validation protocols Lack of non-invasive reference gold standard Intra-arterial validation studies not feasible Validation is device-dependent: generalization not possible Possible artifacts due to the dynamic conditions Limited information on reproducibility in ambulatory conditions No reference values in ambulatory conditions Lack of outcome-based validation (no long-term prospective data) Limited clinical evidence

29 요약및결론 24-h PWA appears to be a potentially promising tool for evaluating vascular function, structure, and damage in daily life conditions and promoting early screening in subjects at risk. 24시간동맥경화도측정계의경우 Gold standard 동맥경화도측정계와비교해 acceptable한정확도를보인다. Accuracy and quality of the evidence collected so far seems to be strongly device-dependent and results could not be considered interchangeable between devices. Long-term follow-up (outcome) studies, such as the VASOTENS Registry, are needed to show the predictive value of the parameters provided by the various devices and to answer the many technical and clinical questions still open.

한국성인에서초기황반변성질환과 연관된위험요인연구

한국성인에서초기황반변성질환과 연관된위험요인연구 한국성인에서초기황반변성질환과 연관된위험요인연구 - - i - - i - - ii - - iii - - iv - χ - v - - vi - - 1 - - 2 - - 3 - - 4 - 그림 1. 연구대상자선정도표 - 5 - - 6 - - 7 - - 8 - 그림 2. 연구의틀 χ - 9 - - 10 - - 11 -