Arterial stiffness, its assessment, prognostic value, and implications for treatment.

Arterial stiffness has been known as a sign of cardiovascular risk since the 19th century. Despite this, accurate measurement and clinical utility have only emerged in recent times. Arterial stiffness and its hemodynamic consequences are now established as predictors of adverse cardiovascular outcome. They are easily and reliably measured using a range of noninvasive techniques, which can be used readily by risk assessment facilities or individual practitioners. The techniques described in this review are based on the pulsatility of the cardiovascular system, utilizing the timing of pulse travel along major arteries and the magnitude of wave reflection. These have enabled better understanding of the ill effects of arterial stiffening, not only on large arteries and the left ventricle, but also on tiny arteries in highly perfused organs such as brain and kidneys. Treatment options, which directly target the consequences of arterial stiffening, as opposed to arbitrary reduction of brachial blood pressure, have proved clinical superiority; optimal therapy entails use of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and calcium-channel blockers, as well as vasodilating β-blockers. Arterial stiffness will undoubtedly contribute to cardiovascular assessment and management in future clinical practice. Reviews such as this will hopefully increase awareness of the mounting evidence underlying this transition, and the relevant theory and methodology. As we begin the second decade of the 21st century, we are finally collectively coming to realize what pioneers such as Osler, Roy, Bramwell and Hill foresaw in the 19th and 20th centuries.

[1]  Thomas Young,et al.  I. The Croonian Lecture. On the functions of the heart and arteries , 1809, Philosophical Transactions of the Royal Society of London.

[2]  C. Roy,et al.  The Elastic Properties of the Arterial Wall , 1881, The Journal of physiology.

[3]  James Mackenzie,et al.  The Study of the Pulse, Arterial, Venous, and Hepatic, and of the Movements of the Heart , 1902, The Indian Medical Gazette.

[4]  T. Lewis,et al.  The factors influencing the prominence of the dicrotic wave , 1906, The Journal of physiology.

[5]  J. Mackenzie Principles of Diagnosis and Treatment in Heart Affections , 1916, Bristol Medico-Chirurgical Journal (1883).

[6]  A. Hill,et al.  VELOCITY OF TRANSMISSION OF THE PULSE-WAVE: AND ELASTICITY OF ARTERIES , 1922 .

[7]  Michael F. O'Rourke,et al.  Vascular Impedance of the Femoral Bed , 1966 .

[8]  M. G. Taylor,et al.  The input impedance of an assembly of randomly branching elastic tubes. , 1966, Biophysical journal.

[9]  E D Freis,et al.  Changes in the carotid pulse which occur with age and hypertension. , 1966, American heart journal.

[10]  M F O'Rourke,et al.  Pressure and flow waves in systemic arteries and the anatomical design of the arterial system. , 1967, Journal of applied physiology.

[11]  M Anliker,et al.  Dispersion and Attenuation of Small Artificial Pressure Waves in the Canine Aorta , 1968, Circulation Research.

[12]  W. Parmley,et al.  The contractile state of the heart as expressed by force-velocity relations. , 1969, The American journal of cardiology.

[13]  G A Ewy,et al.  The Dicrotic Arterial Pulse , 1969, Circulation.

[14]  T. Dawber,et al.  Characteristics of the Dicrotic Notch of the Arterial Pulse Wave in Coronary Heart Disease , 1973, Angiology.

[15]  A P Avolio,et al.  A comparative study of pulsatile arterial hemodynamics in rabbits and guinea pigs. , 1976, The American journal of physiology.

[16]  N. Westerhof,et al.  Aortic Input Impedance in Normal Man: Relationship to Pressure Wave Forms , 1980, Circulation.

[17]  Thomas Young, M.D. (1773-1829). , 1980, American heart journal.

[18]  D L McGee,et al.  Systolic blood pressure, arterial rigidity, and risk of stroke. The Framingham study. , 1981, JAMA.

[19]  J. Levenson,et al.  Effect of nitroglycerin on peripheral large arteries in hypertension. , 1982, British journal of clinical pharmacology.

[20]  J Melbin,et al.  Arterial tonometry: review and analysis. , 1983, Journal of biomechanics.

[21]  A P Avolio,et al.  Effects of aging on arterial distensibility in populations with high and low prevalence of hypertension: comparison between urban and rural communities in China. , 1985, Circulation.

[22]  M. O'Rourke,et al.  Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man. , 1986, Cardiovascular research.

[23]  L. Kuller,et al.  Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial. , 1988, Circulation.

[24]  Kiichi Sagawa,et al.  Effect of nitroglycerin on aortic impedance, diameter, and pulse-wave velocity. , 1988 .

[25]  D. Fitchett,et al.  Effect of nitroglycerin on left ventricular hydraulic load. , 1988, The Canadian journal of cardiology.

[26]  C. Hayward,et al.  Noninvasive determination of age-related changes in the human arterial pulse. , 1989, Circulation.

[27]  M. O'Rourke,et al.  Arterial dilation and reduced wave reflection. Benefit of dilevalol in hypertension. , 1989, Hypertension.

[28]  A P Avolio,et al.  Nitroglycerin has more favourable effects on left ventricular afterload than apparent from measurement of pressure in a peripheral artery. , 1990, European heart journal.

[29]  A. Katz Cardiomyopathy of overload. A major determinant of prognosis in congestive heart failure. , 1990, The New England journal of medicine.

[30]  R. Virmani,et al.  Effect of aging on aortic morphology in populations with high and low prevalence of hypertension and atherosclerosis. Comparison between occidental and Chinese communities. , 1991, The American journal of pathology.

[31]  D. Fitchett,et al.  Noninvasive determination of aortic input impedance and external left ventricular power output: a validation and repeatability study of a new technique. , 1992, Journal of the American College of Cardiology.

[32]  M. Karamanoglu,et al.  An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. , 1993, European heart journal.

[33]  Michael F. O'Rourke,et al.  Arterial vasodilation : mechanisms and therapy , 1993 .

[34]  A. Katz The Cardiomyopathy of Overload: An Unnatural Growth Response in the Hypertrophied Heart , 1994, Annals of Internal Medicine.

[35]  N Westerhof,et al.  Haemodynamic basis for the development of left ventricular failure in systolic hypertension and for its logical therapy. , 1995, Journal of hypertension.

[36]  C H Chen,et al.  Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure. , 1996, Hypertension.

[37]  W. Nichols McDonald's Blood Flow in Arteries , 1996 .

[38]  R. Vasan,et al.  The progression from hypertension to congestive heart failure. , 1996, JAMA.

[39]  C. H. Chen,et al.  Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. , 1997, Circulation.

[40]  C. Hayward,et al.  Gender-related differences in the central arterial pressure waveform. , 1997, Journal of the American College of Cardiology.

[41]  A Change of Heart , 1997 .

[42]  B. Fetics,et al.  Estimation of Central Aortic Pressure Waveform by Mathematical Transformation of Radial Tonometry Pressure Data , 1998 .

[43]  M. Safar,et al.  Influence of body height on pulsatile arterial hemodynamic data. , 1998, Journal of the American College of Cardiology.

[44]  A. Mason A Century of Arterial Hypertension , 1998 .

[45]  D. Webb,et al.  Reproducibility of pulse wave velocity and augmentation index measured by pulse wave analysis , 1998, Journal of hypertension.

[46]  D. Kass,et al.  Parametric model derivation of transfer function for noninvasive estimation of aortic pressure by radial tonometry , 1999, IEEE Transactions on Biomedical Engineering.

[47]  S. Yusuf,et al.  Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. , 2000 .

[48]  D. Webb,et al.  The influence of heart rate on augmentation index and central arterial pressure in humans , 2000, The Journal of physiology.

[49]  S. Laurent,et al.  Local pulse pressure and regression of arterial wall hypertrophy during long-term antihypertensive treatment. , 2000, Circulation.

[50]  P. Ducimetiere,et al.  Aortic Stiffness Is an Independent Predictor of All-Cause and Cardiovascular Mortality in Hypertensive Patients , 2001, Hypertension.

[51]  M E Safar,et al.  Comparative effects of aging in men and women on the properties of the arterial tree. , 2001, Journal of the American College of Cardiology.

[52]  J. Blacher,et al.  Impact of Aortic Stiffness Attenuation on Survival of Patients in End-Stage Renal Failure , 2001, Circulation.

[53]  M. O'Rourke,et al.  Prospective Evaluation of a Method for Estimating Ascending Aortic Pressure From the Radial Artery Pressure Waveform , 2001, Hypertension.

[54]  D. Kass,et al.  Improved Arterial Compliance by a Novel Advanced Glycation End-Product Crosslink Breaker , 2001, Circulation.

[55]  M. E. Safar,et al.  Aortic Pulse Wave Velocity Predicts Cardiovascular Mortality in Subjects >70 Years of Age , 2001, Arteriosclerosis, thrombosis, and vascular biology.

[56]  M. O'Rourke,et al.  Quantification of glyceryl trinitrate effect through analysis of the synthesised ascending aortic pressure waveform , 2002, Heart.

[57]  J. Blacher,et al.  Central Pulse Pressure and Mortality in End-Stage Renal Disease , 2002, Hypertension.

[58]  Omapatrilat Reduces Pulse Pressure and Proximal Aortic Stiffness in Patients With Systolic Hypertension: Results of the Conduit Hemodynamics of Omapatrilat International Research Study , 2002 .

[59]  Morris J. Brown,et al.  Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs , 2002, Journal of hypertension.

[60]  S. Anderson,et al.  Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance: An Integrated Index of Vascular Function? , 2002, Circulation.

[61]  M. Safar,et al.  Selective reduction of cardiac mass and central blood pressure on low-dose combination perindopril/indapamide in hypertensive subjects , 2004, Journal of hypertension.

[62]  Michael F O'Rourke,et al.  Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. , 2005, Hypertension.

[63]  M. Safar,et al.  Stiffness of Capacitive and Conduit Arteries: Prognostic Significance for End-Stage Renal Disease Patients , 2005, Hypertension.

[64]  M. O'Rourke,et al.  Benefit of glyceryl trinitrate on arterial stiffness is directly due to effects on peripheral arteries , 2005, Heart.

[65]  Alireza Khoshdel,et al.  Increased pulse wave velocity is not associated with elevated augmentation index in patients with diabetes , 2005 .

[66]  M. Caulfield,et al.  Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) , 2005, The Lancet.

[67]  Yasmin,et al.  Normal vascular aging: differential effects on wave reflection and aortic pulse wave velocity: the Anglo-Cardiff Collaborative Trial (ACCT). , 2005, Journal of the American College of Cardiology.

[68]  Hiroshi Miyashita,et al.  Noninvasive evaluation of the influence of aortic wave reflection on left ventricular ejection during auxotonic contraction , 2005, Heart and Vessels.

[69]  Kozo Hirata,et al.  Benefits from angiotensin-converting enzyme inhibitor ‘beyond blood pressure lowering’: beyond blood pressure or beyond the brachial artery? , 2005, Journal of hypertension.

[70]  Albert Hofman,et al.  Arterial Stiffness and Risk of Coronary Heart Disease and Stroke: The Rotterdam Study , 2006, Circulation.

[71]  Tine Willum Hansen,et al.  Prognostic Value of Aortic Pulse Wave Velocity as Index of Arterial Stiffness in the General Population , 2006, Circulation.

[72]  Alun D. Hughes,et al.  Differential Impact of Blood Pressure–Lowering Drugs on Central Aortic Pressure and Clinical Outcomes: Principal Results of the Conduit Artery Function Evaluation (CAFE) Study , 2006 .

[73]  Thomas H Marwick,et al.  Validation of a Generalized Transfer Function to Noninvasively Derive Central Blood Pressure During Exercise , 2006, Hypertension.

[74]  M. Safar,et al.  Arterial stiffness in hypertension , 2006 .

[75]  H. Struijker‐Boudier,et al.  Expert consensus document on arterial stiffness: methodological issues and clinical applications. , 2006, European heart journal.

[76]  G. Mancia,et al.  Central blood pressure measurements and antihypertensive therapy: a consensus document. , 2007, Hypertension.

[77]  M. O'Rourke,et al.  Mechanical factors in arterial aging: a clinical perspective. , 2007, Journal of the American College of Cardiology.

[78]  G. De Backer,et al.  Noninvasive (Input) Impedance, Pulse Wave Velocity, and Wave Reflection in Healthy Middle-Aged Men and Women , 2007, Hypertension.

[79]  A. Dominiczak,et al.  2007 Guidelines for the Management of Arterial Hypertension: The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC) , 2007, European heart journal.

[80]  Nikos Stergiopulos,et al.  Individualization of transfer function in estimation of central aortic pressure from the peripheral pulse is not required in patients at rest. , 2008, Journal of applied physiology.

[81]  B. Fernhall,et al.  Racial differences in central blood pressure and vascular function in young men. , 2008, American journal of physiology. Heart and circulatory physiology.

[82]  G. Bakris,et al.  Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. , 2008, The New England journal of medicine.

[83]  M. O'Rourke How stiffening of the aorta and elastic arteries leads to compromised coronary flow , 2008, Heart.

[84]  Riccardo Pini,et al.  Central but not brachial blood pressure predicts cardiovascular events in an unselected geriatric population: the ICARe Dicomano Study. , 2008, Journal of the American College of Cardiology.

[85]  Michael O'Rourke,et al.  Aortic dimensions and stiffness in normal adults. , 2008, JACC. Cardiovascular imaging.

[86]  Hirofumi Tanaka,et al.  Age-associated elongation of the ascending aorta in adults. , 2008, JACC. Cardiovascular imaging.

[87]  Bernet Kato,et al.  Increased wave reflection rather than central arterial stiffness is the main determinant of raised pulse pressure in women and relates to mismatch in arterial dimensions: a twin study. , 2009, Journal of the American College of Cardiology.

[88]  Richard B Devereux,et al.  High central pulse pressure is independently associated with adverse cardiovascular outcome the strong heart study. , 2009, Journal of the American College of Cardiology.

[89]  J. Gardin,et al.  Racial differences in incident heart failure among young adults. , 2009, The New England journal of medicine.

[90]  M. Desai,et al.  Aortic stiffness is increased in hypertrophic cardiomyopathy with myocardial fibrosis: novel insights in vascular function from magnetic resonance imaging. , 2009, Journal of the American College of Cardiology.

[91]  Siegfried Wassertheurer,et al.  Noninvasive determination of carotid–femoral pulse wave velocity depends critically on assessment of travel distance: a comparison with invasive measurement , 2009, Journal of hypertension.

[92]  Edward G Lakatta,et al.  Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels. , 2009, The Medical clinics of North America.

[93]  K. Kario,et al.  Differential Effects Between a Calcium Channel Blocker and a Diuretic When Used in Combination With Angiotensin II Receptor Blocker on Central Aortic Pressure in Hypertensive Patients , 2009, Hypertension.

[94]  Pascal Verdonck,et al.  Amplification of the Pressure Pulse in the Upper Limb in Healthy, Middle-Aged Men and Women , 2009, Hypertension.

[95]  Thomas Weber,et al.  Determination of travel distance for noninvasive measurement of pulse wave velocity: case closed? , 2009, Hypertension.

[96]  R. Reneman,et al.  The dicrotic notch as alternative time-reference point to measure local pulse wave velocity in the carotid artery by means of ultrasonography , 2009, Journal of hypertension.

[97]  H. Kühl Hypertrophic cardiomyopathy, fibrosis, and aortic stiffness: an unidentified association unraveled by magnetic resonance imaging. , 2009, Journal of the American College of Cardiology.

[98]  Jamil Mayet,et al.  A meta-analysis of the mechanism of blood pressure change with aging. , 2009, Journal of the American College of Cardiology.

[99]  Kenji Takazawa,et al.  Flawed measurement of brachial tonometry for calculating aortic pressure? , 2009, Hypertension.

[100]  Alban Redheuil,et al.  Reduced Ascending Aortic Strain and Distensibility: Earliest Manifestations of Vascular Aging in Humans , 2010, Hypertension.

[101]  Eung Ju Kim,et al.  Differing effects of aging on central and peripheral blood pressures and pulse wave velocity: a direct intraarterial study , 2010, Journal of hypertension.

[102]  K. Shimada,et al.  Cross-sectional characterization of all classes of antihypertensives in terms of central blood pressure in Japanese hypertensive patients. , 2010, American journal of hypertension.

[103]  Hao-Min Cheng,et al.  Wave Reflection and Arterial Stiffness in the Prediction of 15-Year All-Cause and Cardiovascular Mortalities: A Community-Based Study , 2010, Hypertension.

[104]  W. Nichols,et al.  Pulse Wave Analysis of the Aortic Pressure Waveform in Severe Left Ventricular Systolic Dysfunction , 2010, Circulation. Heart failure.

[105]  M. O'Rourke,et al.  Central pressure and pulse wave amplification in the upper limb. , 2010, Hypertension.

[106]  Yasmin,et al.  Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors: ‘establishing normal and reference values’ , 2010, European heart journal.

[107]  W. Nichols,et al.  Changes in the central arterial pressure pulse with aging. , 2010, Journal of the American College of Cardiology.

[108]  M. O'Rourke,et al.  Pulse waveform characteristics predict cardiovascular events and mortality in patients undergoing coronary angiography , 2010, Journal of Hypertension.

[109]  M. O'Rourke,et al.  Clinical use of applanation tonometry: hope remains in Pandora's box. , 2010, Journal of hypertension.

[110]  M. O'Rourke,et al.  Aortic augmentation index and aging: mathematical resolution of a physiological dilemma? , 2010, Hypertension.

[111]  Aortic stiffness in hypertrophic cardiomyopathy. , 2010, Journal of the American College of Cardiology.

[112]  Christodoulos Stefanadis,et al.  Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. , 2010, European heart journal.

[113]  C. Vlachopoulos,et al.  Prediction of Cardiovascular Events and All-Cause Mortality With Arterial Stiffness , 2011 .

[114]  Michael J. Pencina,et al.  Arterial Stiffness and Cardiovascular Events: The Framingham Heart Study , 2010, Circulation.

[115]  Paolo Salvi,et al.  Pulse pressure amplification a mechanical biomarker of cardiovascular risk. , 2010, Journal of the American College of Cardiology.

[116]  Jeroen J. Bax,et al.  2007 ESH-ESC Guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). , 2007, Blood pressure.