1. ARTERIAL STIFFNESS Dr.R.V.S.N.Sarma., M.D., M.Sc., (Canada) Consultant Physician and Chest Specialist

2. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings The Blood Vessels and the Cardiovascular System Figure 15-1: Functional model of the cardiovascular system

3. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Endothelium Elastic tissues Rebounds Evens flow Smooth muscles Fibrous tissue Tough Resists stretch Make Up of Bllod Vessels: Arteries and Arterioles Figure 15-2: Blood vessels

4. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Blood Pressure: Generated by Ventricular Contraction Figure 15-4: Elastic recoil in the arteries

5. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings More Blood Pressures: Pulse and Mean Arterial Pressures Figure 15-5: Pressure throughout the systemic circulation

6. Copyright © 2004 Pearson Education, Inc., publishing as Benjamin Cummings Factors Controlling MAP : The Driving Pressure for Blood Flow Figure 15-10: Factors that influence mean arterial pressure

7. Arterioles as a group have a greater cross sectional area than the large vessels. How can their resistance be greater?

8. r = 1 A= 3.14 Res=1 B and C in parallel have a combined resistance of 2 and a cross sectional area of 3.14 A r =.707 A= 1.57 Res=4 B C Resistance ~ ( r 4 ) Area ~ (r 2 ) Branching to smaller radius vessels increases resistance

9. The heart pumps in short spurts. The compliant aorta stores this energy during ejection and releases it during diastole so that flow into the periphery continues throughout the cardiac cycle

10. The bagpipe player blows into the bag in short spurts. That energy is stored in the bag and the air escapes through the pipes in a continuous stream thanks to the bag's compliance.

11. If the vessels were rigid pipes then all forward flow would have to occur during the ejection period which is only about 1/3 of the cardiac cycle. Blood pressure would have to be 3 times higher during that period to maintain the cardiac output.

12. Why is aortic pressure pulsatile? With each ejection the aortic volume increases by one stroke volume

13. If aortic compliance were to decrease, pulse pressure will increase.

14. Pulse pressure = stroke volume/compliance

15. Aging reduces aortic compliance Pulse pressure naturally increases with age Compliance =  volume/  pressure 120/80 Systolic hypertension >140

16. Mean and Pulse Pressure

17. Mean Arterial Pressure MAP = cardiac output x total resistance

18. Arterial Elasticity Stores Pressure and Maintains Flow

19. Factors Controlling Blood Pressure  Peripheral resistance  mean arterial pressure  Cardiac output  mean arterial pressure  Stroke volume  pulse pressure  Arterial compliance  pulse pressure  Heart Rate  pulse pressure  Blood Volume  arterial & venous

20. Conduits –To conduct blood to the organs and periphery Impedance matching –Minimise cardiac work –Minimise pulse pressure –Control flow according to demand What are arteries for?

21. What are arteries made of? Why do large arteries become stiffer with age (and disease)? Why are some people affected more than others? Questions Conduit arteries: large arteries near the heart and their main branches Why are conduit arteries distensible?

22. Arteries are distensible because: 80 100 120 1 sec The wheel has yet to evolve in the animal kingdom (bacteria have propellers) Therefore(?) the heart is a pulsatile pump. Its output consists of a pulse wave superimposed on a steady component.

23. Systolic pressure Diastolic pressure Mean Arterial Pressure Pulse pressure = systolic pressure - diastolic pressure 80 100 120 1 second Pressure [mmHg] Aortic pulse wave

24. MAP determined by resistance of peripheral arteries = Pd +1/3 PP Pulse pressure determined by elasticity of large arteries Pulse pressure = systolic pressure - diastolic pressure Systolic pressure Diastolic pressure Mean Arterial Pressure 80 100 120 1 second Pressure [mmHg]

25. The pulse is a wave of dilatation With thanks to Chris Martyn

26. Speed of the wave is related to the stiffness of the artery it is traveling in The stiffer the artery; the higher the wave speed Wave speed is proportional to the square root of arterial stiffness

27. Stress, strain and elastic modulus

28. Stress ( , sigma) –Force per unit area= (F/A) Strain ( , epsilon) –Change in length per unit length= (  L/L 0 ) Elastic (Young’s) modulus (E) –stress/strain=  F L0F L0 A LA L =

29. 2001000 Pressure (mmHg) Relative Radius 1.0 1.5 2.0 PP P RR R PP P RR R

30. 2.62.42.22.01.81.61.41.21.0 R/Ro 0 5 10 15 E inc [Nm -2 x 10 5 ] Variation of E inc with stretch

31. WHY THE ARTERY? Epidemiological studies have shown that: Cardiovascular disease is the first cause of morbidity and mortality in western countries. Cardiovascular morbidity and mortality are principally related to arterial pathology. Arterial wall alterations are usually associated with: age, smoking, diabetes, dyslipidemia and hypertension.

32. WHY THE ARTERY? Arterial alterations can be observed at early stages in both small and large arteries. Alterations of the arterial wall properties favor development of arterial lesions: Arteries constitute the target, the battleground and the common denominator of cardiovascular complications. – Kidneynephroangiosclerosis – Cerebralstroke – Coronaryangina, M.I. – Peripheralstenosis, aneurysm

33. WHY THE ARTERY? Cardiovascular morbidity and mortality are principally due to arterial lesions. Treatments differ by their effect on the arterial wall. The evaluation of cardiovascular prevention and its impact on the arterial wall is important as an intermediate marker Large therapeutic trials including arterial evaluation are required.

34. WHY PULSE WAVE VELOCITY? Arterial pathology is a major contributor to cardiovascular disease, morbidity and mortality. Most non-invasive methods to assess large arteries are ultrasound based: –Doppler velocity measurement –Echography –High resolution Echo-tracking Sophisticated, costly and reserved for a few clinical research labs.

35. WHY PULSE WAVE VELOCITY? Clinical assessment of large arteries requires a simple, practical method. Pulse wave velocity = Index of arterial stiffness Arterial stiffness will –Play a potential etiologic role in cardiovascular disease. –Help to recognize arterial changes. –Constitute an "early risk marker". –Be useful in assessing the arterial effects of drugs.

36. PULSE WAVE VELOCITY A simple method to assess arterial stiffness and distensibility. A long-established and widely used technique. Non-invasive, accurate and reproducible.

37. PULSE WAVE VELOCITY Principles L.V.E. generates a pulse wave which will propagate along the arterial walls at a certain speed. Propagation along the arterial tree Systole L.V. Blood = incompressible fluid Artery = elastic conduit }

38. PULSE WAVE VELOCITY The propagation velocity is determined by: –the elastic and geometric properties of the arterial wall –the characteristics of the arterial wall structure. Higher velocity = higher stiffness = lower distensibility. Principles

39. PULSE WAVE VELOCITY Intermittent cardiac output SystoleDiastole Large arteries store a part of the ejection volume during systole and restore it during diastole. Arterial Buffering function Continuous peripheral flow

41. PULSE WAVE VELOCITY The Complior® device

42. COMPLIOR Automatic Measurement (The Complior®) Transducer = large frequency band (0.1 - 100 Hz) Signal gain adjustment (manual or automatic) Acquisition frequency = 4 kHz Waveforms = entire exam stored in memory (signal data & parameters) Pedal for trigger acquisition Automatic detection and calculation of propagation delay between the 2 pulse waves

43. PULSE WAVE VELOCITY Plasma cholesterol Glycemia Smoking status Gender Atherosclerosis Genetic Factors Determining Factors Age Blood pressure +++From + to ++

44. ARTERIAL STIFFNESS Clinical Implications and Epidemiological Data Arterial StiffnessCardiovascular risk Compliance Distensibility PWV Pulse pressure Atherosclerosis LVH Systolic HT Stroke CHD

45. ARTERIAL DISTENSIBILITY Arterial distensibility in coronary heart desease (CHD). CHD n = 24 Normal n = 18 Systolic pressure (mmHg) Distensibility (cm² x dynes -1 ) 117+ 4 121 + 4NS 1.6 + 0.13.4 + 0.4P < 0.001 Stefanadis C et al. Am J Cardiol. 1987

46. PULSE WAVE VELOCITY Aortic P.W.V. is an independent determinant of L.V.H. 1.9 1.5 1.0 0.6 51015 r = 0.61 p < 0.001 PWV m/sec Left ventricular mass/volume = NT (normotensive) = HTA (Bouthier et al, Am Heart J 1985)

47. Relationship between arterial stiffness and number of atheromatous vessels Common carotid artery 0 10 20 30 N0-VD1-VD2-VD3-VD Stiffness index  * * adapted from Hirai et al. VD: vessel disease Abdominalaorta 0 10 20 30 N0-VD1-VD2-VD3-VD Stiffness index (  * * *

48. AORTIC PWV AND DISTENSIBILITY IN STROKE PATIENTS AND CONTROL SUBJECTS adapted from Lehmann 0 5 10 15 controlsstroke Aortic PWV (m/s) 0 5 10 controlsstroke Aortic distensibility ( Arbitrary unit ) *** ** 8.2 4.9 9.4 13.8 Carotid Radial PWV Carotid Femoral PWV

49. ARTERIAL DISTENSIBILITY IN PATIENTS WITH ABDOMINAL AORTIC ANEURYSM (AAA) 5 10 15 20 25 NormotensivesHypertensivesAAANormotensivesHypertensivesSupra-aneurysmAneurysm Arterial distensibility ( Kpa -1. 10 -3 ) AAA * * CAROTIDAORTA * adapted from Boutouyrie et al.

50. CAROTID-RADIAL PWV IN DIABETIC SUBJECTS 4 6 8 10 12 14 16 1 to 1011 to 2021 to 3031 to 4041 to 5051 to 60 Age (years) Carotid-radial PWV (m/sec) Healthy Diabetics adapted from Woolam et al

51. PULSE WAVE VELOCITY P.W.V. in normotensives and borderline hypertensives. HT = Borderline hypertensives NT = Normotensives 10 9 8 7 6 5 70 90 110 130 Mean Blood Pressure (mmHg) Carotid-Femoral PWV (m/s) (Girerd et al, J of Hyper, 1989)

52. 13 14 15 NoUnilateralBilateral 13 14 15 12345 PWV AND ATHEROSCLEROSIS INDICATORS Values are adjusted for age, sex, mean BP and pulse rate Quintiles of carotid artery wall thickness Plaques in carotid artery Carotid-femoral PWV (m/s) p < 0.001p = 0.001

53. PWV AND ATHEROSCLEROSIS INDICATORS Values are adjusted for age, sex, mean BP and pulse rate 13 13.5 14 14.5 12345 Quintiles of ankle-brachial pressure index Carotid-femoral PWV (m/s) p = 0.02 13 14 15 16 no mild moderatesevere Calcified plaques in the aorta Carotid-femoral PWV (m/s) p < 0.001

54. CONCLUSION Arterial stiffness must be taken into consideration in clinical practice. The Complior system is an accurate device to assess the arterial stiffness using pulse wave velocity measurements. The examination procedure is simple, and the method is accurate and reproducible.

57. Which is important ? SBP or DBP

69. The Impact of the Early Wave Reflection This earlier return to the heart of the reflected pressure wave (due to stiffening of the arteries) changes the aortic root pressure waveform, … with 3 key clinical implicationsThis earlier return to the heart of the reflected pressure wave (due to stiffening of the arteries) changes the aortic root pressure waveform, … with 3 key clinical implications Central pulse pressure increases... increasing risk of stroke and renal failureCentral pulse pressure increases... increasing risk of stroke and renal failure LV Load increases…. increasing LV mass, and accelerating progress towards LV hypertrophy and heart failureLV Load increases…. increasing LV mass, and accelerating progress towards LV hypertrophy and heart failure Coronary artery perfusion pressure in diastole reduces…. increasing risk of myocardial ischemiaCoronary artery perfusion pressure in diastole reduces…. increasing risk of myocardial ischemia  PP Increased Central Pulse Pressure Increased LV Load Decreased Coronary Artery Perfusion Pressure in Diastole

80. Treatment of Arterial Stiffness Currently approved drugs for arterial stiffness ACEi, ARBs Nitrates Diuretics Statins Aspirin Certain beta blockers Certain Ca channel blockers

81. Treatment of Arterial Stiffness Promising Drugs Endopeptidase inhibitors (Omiprilait) PDE inhibitors (Sildenafil group) Methyl Xanthines (with better safety window) NO donors (novel drugs avoiding tolerance) Drugs breaking AGE cross links (ALT 711)

82. PulseMetric Brachial Artery Distensibility, SVR, CO, LV dP/dt Uses Oscillometric BP cuff

83. Sphygmocor Pulse Wave Velocity & Augmentation Index Uses Arterial tonometer (radial)