Vascular compliance as a novel cardiovascular risk factor

1. Vascular compliance as a novel cardiovascular risk factor Dr Ian B. Wilkinson Senior Lecturer & BHF Research Fellow University of Cambridge

5. Hypertension and the Arterial Waveform F.A. Mohamed 1874

6. “ These persons appear to pass through life pretty much as others do and generally do not suffer from their high blood pressure except in their petty ailments upon which it imprints itself… As age advances the enemy gains accession of strength … the individual has now passed forty years, perhaps fifty of age, his lungs begin to degenerate, he has a cough in the winter time, but by his pulse you will know him … Alternatively headache, vertigo, epistaxis, and a passing paralysis, a more severe apopleptic seizure, and then the final blow…” F.A. Mahomed, 1879

7. Riva Rocci and Korotkoff, ~1905

8. “ When you can measure what your are speaking about, and can express it in numbers, you know something about it; but when you cannot measure it, when you cannot express it in numbers, your knowledge is of a meagre and unsatisfactory kind.” Lord Kelvin, 1891

9. Actuary Data Relating Blood Pressure to Mortality 1935-1954 Metropolitan Life Insurance Company 1961

10. Modern Techniques for Assessing Arterial Stiffness

11. Arterial Stiffness: a definition • Stiffness: the resistance of an elastic body to deflection by an applied force. • The stiffness E of a body that deflects a distance δ under an applied force F is:

12. Elastic Bodies unstretched spring x 2x F 2F Hooke’s Law: Fspring = -kx Spring constant k It takes twice as much force to stretch a spring twice as far

13. Schematic Diagram of a Large Artery Smooth muscle cells Elastic lamellae Endothelium Lamellar subunit

14. Why Have Elastic Arteries Diastole Systole DV Reduces peak pressure Maintains diastolic pressure Smoothes blood flow Improves efficiency

15. Effect of Arterial Stiffening • Systolic pressure •  Diastolic pressure Systolic hypertension Heart failure Myocardial ischaemia  Shear stress  Risk  NO production Arterial remodelling  Arterial stiffness Cyclical stress

16. Effect of Aortic Stiffening on Blood Pressure Saeki et al. Circ Res 1995;76:132-141

17. Indices of Arterial Stiffness Mackenzie and Wilkinson. QJM 1999;95:67

18. Pulse Wave Velocity Elastic Stiff

19. Measuring PWV

20. ApplanationTonometry of the Carotid Artery

21. Does stiffness matter…..?

22. Pulse Pressure and Aortic PWV Haynes et al. Am Heart J 1936;4:385

23. Isolated Systolic Hypertension is Associated with Increased Aortic Stiffness169 untreated subjects, 114 controls P<0.001 Yasmin et al. ATVB 2004;25:372

24. Aortic PWV Predicts the Risk of Developing Hypertensionn=499, 4.9 year follow-up Najjar et al. JACC 2008;51:377

25. Relationship Between Left Ventricular Mass and Aortic Stiffness in Dialysis Patients Barenbrock et al. KI 1994;45:1397

26. Aortic PWV and Cardiovascular Risk Blacher. Hypertension 1999;33:1111

27. PWV and Mortality in End-Stage Renal Failuren=241; mean age 51; 6 year follow up Blacher et al. Circulation 1999;99:2434

28. The Independent Predictive Value of Arterial Stiffness Consensus Statement: Eur Heart J 2006; 27:2588

29. Predictive Value of Aortic PWV for Stroke Death in Hypertensivesn=1715; 8 yr follow up; mean age 51 years Laurent S Stroke 2003; 34:1203

30. Predictive Value of Aortic PWV for Stroke Death in Hypertensivesn=1715; 8 yr follow up; mean age 51 years Laurent S Stroke 2003; 34:1203

31. Predictive Value of Aortic PWV and PP for Stroke Death After Correcting for Other Risk Factorsn=1715; 8 yr follow up; mean age 51 years Laurent S Stroke 2003; 34:1203

32. Predictive Value of Aortic PWV & Blood PressureDanish Monica Study n=1,678, 9.4yr follow-up, 154 events Hansen et al., Circulation 2006; 113: 664-70

33. Predictive Value of Aortic PWV & Blood PressureDanish Monica Study n=1,678, 9.4yr follow-up, 154 events Hansen et al., Circulation 2006; 113: 664-70

34. Predictive Value of Aortic PWV & Blood PressureDanish Monica Study n=1,678, 9.4yr follow-up, 154 events Hansen et al., Circulation 2006; 113: 664-70

35. Addition of Novel Biomarkers Does not Improve Risk Prediction Wang et al NEJM 2006;355:25

36. Aortic PWV Improves Risk Prediction Boutouyrie et al Hypertension 2002;39:10

37. Arterial Stiffness and Response to TreatmentPWV and Mortality in End-Stage Renal Failure Guerin et al. Circulation 2001

38. “Only in the case of young children do we find that the elasticity of the arteries is so perfectly adapted to the requirements of the organism as it is in the case of the lower animals” Roy: 1880

39. Age and Aortic Pulse Wave Velocity: UK Bramwell & Hill. Lancet 1922

40. Age and Pulse Wave Velocity Aortic McEniery et al JACC 2005;46:1753

42. x Number of cycles Cyclical stress Arterial Stiffening Elastin Fatigue = = x Pulse pressure Heart rate

43. Relationship Between Rate Pressure Product and aPWV in the Caerphilly Study McEniery et al Caerphilly Data

44. Comparison of Aortic PWV in urban and Rural Chinese Communities Avolio et al. Hypertension 1985; 71:202

45. Blood Pressure in !Kung Bushmen in Northern Botswana Truswell et al. Am Heart J 1972;84:5

46. Factors Influencing Arterial Stiffness Zieman et al ATVB 2005;25:932

47. Arterial Calcification

48. Relationship Between Age and Thoracic Aortic Calcium Content in Man Media Adventitia Elliot et al. Calcif Tissue Int 1994;54:268

49. Multi Slice CT Quantification of Aortic Calcification

50. aPWV and Abdo Calcification McEniery et al Caerphilly Data