The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Relationship Between Aortic Stiffening and Microvascular Disease in Brain and Kidney: Cause and Logic of Therapy
Abstract
A close relationship has been established between microvascular damage in brain and kidney and indices of age and hypertension (pulse pressure, aortic pulse wave velocity, and augmentation index). The mechanism of such association has not been established, nor has rationale for prevention and treatment of microvascular damage. A logical pathophysiological explanation can be offered on the basis of differential input impedance in the brain and kidney compared with other systemic vascular beds. Torrential flow and low resistance to flow in these organs exposes small arterial vessels to the high-pressure fluctuations that exist in the carotid, vertebral, and renal arteries. Such fluctuations, measurable as central pulse pressure, increase 3- to 4-fold with age. Exposure of small vessels to highly pulsatile pressure and flow explains microvascular damage and resulting renal insufficiency and intellectual deterioration, according to the mechanism established by Byrom >50 years ago. The logical approach to prevention and treatment requires reduction of central pulse pressure. Because the aorta and large arteries are not directly affected by drugs, this entails reduction of wave reflection by dilation of conduit arteries elsewhere in the body. This can be accomplished by regular exercise and by drugs such as nitrates, calcium channel blockers, angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers. The explanation given here accounts for greater and earlier vascular damage in diabetes mellitus (relative microvascular fragility) and is similar to that given for vascular changes of pulmonary hypertension caused by ventricular septal defects and other congenital vascular shunts.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The cited source says what the claim attributes to it.
In the citing paper
“Several pathways may link aortic stiffness to microvascular brain damage. They include endothelial dysfunction and oxidative stress,209 a mutually reinforcing remodeling of large and small vessels (ie, large-/small-artery cross talk),210 and exposure of small vessels to the high-pressure fluctuations of the cerebral circulation,211”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Laurent, S., Boutouyrie, P., Asmar, R., Gautier, I., Laloux, B., Guize, L., Ducimetiere, P., & Benetos, A. (2001) · Hypertension · doi:10.1161/01.hyp.37.5.1236 · Cited by 3,856
Hemodynamic Patterns of Age-Related Changes in Blood Pressure: The Framingham Heart Study
Franklin, S. S., Gustin, W., Wong, N. D., Larson, M. G., Weber, M. A., Kannel, W. B., & Levy, D. (1997) · Circulation · doi:10.1161/01.cir.96.1.308 · Cited by 2,321
Hypertension : pathophysiology, diagnosis, and management
Laragh, J. H., & Brenner, B. M. (1995) · Raven Press eBooks · Cited by 1,932
Aortic Stiffness Is an Independent Predictor of Primary Coronary Events in Hypertensive Patients
Boutouyrie, P., Tropeano, A., Asmar, R. G., Gautier, I., Bénétos, A., Lacolley, P. J., & Laurent, S. (2002) · Hypertension · doi:10.1161/hy0102.099031 · Cited by 1,745
McDonald's Blood Flow in Arteries: Theoretical, Experimental and Clinical Principles
Vlachopoulos, C., O'Rourke, M., & Nichols, W. W. (2011) · doi:10.1201/b13568 · Cited by 1,613
Self-citationArterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease
Blacher, J., Guérin, A. P., Pannier, B., Marchais, S. J., & London, G. M. (2001) · Hypertension · doi:10.1161/hy1001.096358 · Cited by 1,416
Pauca, A. L., O’Rourke, M. F., & Kon, N. D. (2001) · Hypertension · doi:10.1161/hy1001.096106 · Cited by 1,179
Self-citationArterial stiffness, wave reflections, and the risk of coronary artery disease
Weber, T., Auer, J., O’Rourke, M. F., Kvas, E., Lassnig, E., Berent, R., & Eber, B. (2004) · Circulation · doi:10.1161/01.cir.0000105767.94169.e3 · Cited by 1,081
Self-citationAortic Stiffness Is an Independent Predictor of Fatal Stroke in Essential Hypertension
Laurent, S., Katsahian, S., Fassot, C., Tropeano, A., Gautier, I., Laloux, B., & Boutouyrie, P. (2003) · Stroke · doi:10.1161/01.str.0000065428.03209.64 · Cited by 1,058
Impact of Aortic Stiffness Attenuation on Survival of Patients in End-Stage Renal Failure
Guérin, A. P., Blacher, J., Pannier, B., Marchais, S. J., Safar, M. E., & London, G. M. (2001) · Circulation · doi:10.1161/01.cir.103.7.987 · Cited by 1,038
Self-citationAvolio, A. P., Chen, S. G., Wang, R. P., Zhang, C. L., Li, M., & OʼRourke, M. F. (1983) · Circulation · doi:10.1161/01.cir.68.1.50 · Cited by 965
Self-citationCentral Pulse Pressure and Mortality in End-Stage Renal Disease
Safar, M. E., Blacher, J., Pannier, B., Guérin, A. P., Marchais, S. J., Guyonvarc’h, P.-M., & London, G. M. (2002) · Hypertension · doi:10.1161/hy0202.098325 · Cited by 800
Self-citationAortic Pulse Wave Velocity Predicts Cardiovascular Mortality in Subjects >70 Years of Age
Meaume, S., Benetos, A., Henry, O. F., Rudnichi, A., & Safar, M. E. (2001) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/hq1201.100226 · Cited by 731
Self-citationRegulation of large cerebral arteries and cerebral microvascular pressure.
Faraci, F. M., & Heistad, D. D. (1990) · Circulation Research · doi:10.1161/01.res.66.1.8 · Cited by 616
Pulse Pressure Not Mean Pressure Determines Cardiovascular Risk in Older Hypertensive Patients
Blacher, J., Staessen, J. A., Girerd, X. J., Gąsowski, J., Thijs, L., Liu, L., Wang, J. G., Fagard, R. H., & Safar, M. E. (2000) · Archives of Internal Medicine · doi:10.1001/archinte.160.8.1085 · Cited by 580
Self-citationPrognostic Significance of Small-Artery Structure in Hypertension
Rizzoni, D., Porteri, E., Boari, G. E. M., Ciuceis, C. D., Sleiman, I., Muiesan, M. L., Castellano, M., Miclini, M., & Agabiti‐Rosei, E. (2003) · Circulation · doi:10.1161/01.cir.0000095031.51492.c5 · Cited by 494
Byrom, F. B. (1954) · The Lancet · doi:10.1016/s0140-6736(54)91821-8 · Cited by 416
Sutton‐Tyrrell, K., Newman, A. B., Simonsick, E. M., Havlik, R. J., Pahor, M., Lakatta, E. G., Spurgeon, H. A., Vaitkevicius, P. V., & for the Health ABC Investigators (2001) · Hypertension · doi:10.1161/01.hyp.38.3.429 · Cited by 389
Does Radial Artery Pressure Accurately Reflect Aortic Pressure?
Pauca, A. L., Wallenhaupt, S. L., Kon, N. D., & Tucker, W. Y. (1992) · CHEST Journal · doi:10.1378/chest.102.4.1193 · Cited by 337
Effect of different antihypertensive drug classes on central aortic pressure
Morgan, T. (2004) · American Journal of Hypertension · doi:10.1016/j.amjhyper.2003.09.012 · Cited by 330
Arterial Stiffness and Kidney Function
Safar, M. E., London, G. M., & Plante, G. E. (2004) · Hypertension · doi:10.1161/01.hyp.0000114571.75762.b0 · Cited by 327
Self-citationLondon, G. M., Asmar, R. G., O’Rourke, M. F., & Safar, M. E. (2004) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2003.07.039 · Cited by 323
Self-citationVascular impedance in studies of arterial and cardiac function.
O’Rourke, M. F. (1982) · Physiological Reviews · doi:10.1152/physrev.1982.62.2.570 · Cited by 285
Self-citationVascular Structural and Functional Changes in Type 2 Diabetes Mellitus
Schofield, I. S., Malik, R. A., Izzard, A. S., Austin, C., & Heagerty, A. M. (2002) · Circulation · doi:10.1161/01.cir.0000041432.80615.a5 · Cited by 284
Staessen, J. A., Li, Y., Thijs, L., & Wang, J. (2005) · Hypertension Research · doi:10.1291/hypres.28.385 · Cited by 246
Pulmonary Arterial Pulse Wave Velocity and Impedance in Man
Milnor, W. R., Conti, C. R., Lewis, K. B., & O’Rourke, M. F. (1969) · Circulation Research · doi:10.1161/01.res.25.6.637 · Cited by 238
Self-citationO'Rourke, M. F. (1967) · Cardiovascular Research · doi:10.1093/cvr/1.4.313 · Cited by 220
Self-citationPulmonary Vascular Impedance in the Dog
Bergel, D. H., & Milnor, W. R. (1965) · Circulation Research · doi:10.1161/01.res.16.5.401 · Cited by 217
Effect of glyceryl trinitrate on peripheral arteries alters left ventricular hydraulic load in man
YAGINUMA, T., Avolio, A. P., O’Rourke, M. F., Nichols, W. W., MORGAN, J. J., Roy, P., BARON, D., Branson, J., & Feneley, M. P. (1986) · Cardiovascular Research · doi:10.1093/cvr/20.2.153 · Cited by 183
Self-citationDiabetes, pulse pressure and cardiovascular mortality: the Hoorn Study
Schram, M. T., Kostense, P. J., van Dijk, R. A. J. M., Dekker, J. M., Nijpels, G., Bouter, L. M., Heine, R. J., & Stehouwer, C. D. A. (2002) · Journal of Hypertension · doi:10.1097/00004872-200209000-00017 · Cited by 178
Hirata, K., Vlachopoulos, C. V., Adji, A. I., & O’Rourke, M. F. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000160211.56103.48 · Cited by 165
Self-citationThe Lewis A. Conner Memorial Lecture
Edwards, J. E. (1957) · Circulation · doi:10.1161/01.cir.15.2.164 · Cited by 159
Regional, segmental, and temporal heterogeneity of cerebral vascular autoregulation
Baumbach, G. L., & Heistad, D. D. (1985) · Annals of Biomedical Engineering · doi:10.1007/bf02584248 · Cited by 119
Verhave, J. C., Fesler, P., du Cailar, G., Ribstein, J., Safar, M. E., & Mimran, A. (2005) · Hypertension · doi:10.1161/01.hyp.0000158843.60830.cf · Cited by 99
Self-citationThe causation of acute arterial necrosis in hypertensive disease
Byrom, F. B., & Dodson, L. F. (1948) · The Journal of Pathology and Bacteriology · doi:10.1002/path.1700600302 · Cited by 95
Epicardial Coronary Artery Compliance in the Dog
DOUGLAS, J. E., & Greenfield, J. C. (1970) · Circulation Research · doi:10.1161/01.res.27.6.921 · Cited by 91
Pulse pressure is associated with age and cardiovascular disease in type 1 diabetes
Schram, M. T., Chaturvedi, N., Fuller, J., & Stehouwer, C. D. A. (2003) · Journal of Hypertension · doi:10.1097/00004872-200311000-00012 · Cited by 90
The Hypertensive Vascular Crisis. An Experimental Study.
(1970) · Annals of Internal Medicine · doi:10.7326/0003-4819-72-5-770_8 · Cited by 81
Peripheral Pulse Pressure, Large Arteries, and Microvessels
Safar, M. E. (2004) · Hypertension · doi:10.1161/01.hyp.0000135448.73199.75 · Cited by 74
Self-citationEffects of Isosorbide Mononitrate and AII Inhibition on Pulse Wave Reflection in Hypertension
Stokes, G. S., Barin, E. S., & Gilfillan, K. L. (2003) · Hypertension · doi:10.1161/01.hyp.0000049622.07021.4f · Cited by 72
Outcome beyond blood pressure control?
Staessen, J. A. (2003) · European Heart Journal · doi:10.1016/s0195-668x(02)00797-2 · Cited by 49
Dementia and antihypertensive treatment
ger, W. B., Forette, F. O., & Staessen, J. A. (2004) · Current Opinion in Nephrology & Hypertension · doi:10.1097/00041552-200403000-00011 · Cited by 21
Blood pressure and outcomes in clinical trials
Williams, B., & Lacy, P. S. (2005) · Journal of Hypertension · doi:10.1097/01.hjh.0000160201.28287.92 · Cited by 6
Research works printed but not linked: 15
- 10.1161/hyp.39.3.735 · DOI
- 10.1161/hyp.39.1.10 · DOI
- 10.1161/hyp.38.4.938 · DOI
- 10.1161/hyp.37.5.1236 · DOI
- 10.1161/atvb.21.12.2046 · DOI
- 10.1161/hyp.38.3.429 · DOI
- SHEP Cooperative Research Group. Prevention of stroke by antihypertensive drug therapy in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991; 365: 3255–3264.
- 10.1161/hyp.38.4.932 · DOI
- 10.1161/res.16.5.401 · DOI
- 10.1161/res.25.6.637 · DOI
- 10.1161/res.27.6.921 · DOI
- 10.1161/res.66.1.2403863 · DOI
- 10.1161/circ.96.1.308 · DOI
- 10.1161/circ.103.7.987 · DOI
- 10.1161/circ.15.2.164 · DOI
Cited by
Sorted by citations
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Hypertension · doi:10.1161/hyp.0000000000000065 · Cited by 7,391
Whelton, P. K., Carey, R. M., Aronow, W. S., Casey, D. E., Collins, K. J., Dennison Himmelfarb, C., DePalma, S. M., Gidding, S., Jamerson, K. A., Jones, D. W., et al. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2017.11.006 · Cited by 6,616
Expert consensus document on arterial stiffness: methodological issues and clinical applications
Laurent, S., Cockcroft, J., Van Bortel, L., Boutouyrie, P., Giannattasio, C., Hayoz, D., Pannier, B., Vlachopoulos, C., Wilkinson, I., Struijker-Boudier, H., et al. (2006) · European Heart Journal · doi:10.1093/eurheartj/ehl254 · Cited by 6,077
“Another explanation is given by the differential input impedance in the brain compared with other systemic vascular beds.(108) Torrential flow and low resistance to flow in these organs expose small arterial vessels to the high-pressure fluctuations that exist in the carotid and vertebral arteries, and that increase t…”
BackgroundGorelick, P. B., Scuteri, A., Black, S. E., DeCarli, C., Greenberg, S. M., Iadecola, C., Launer, L. J., Laurent, S., Lopez, O. L., Nyenhuis, D., et al. (2011) · Stroke · doi:10.1161/str.0b013e3182299496 · Cited by 3,811
2024 ESC Guidelines for the management of elevated blood pressure and hypertension
McEvoy, J. W., McCarthy, C. P., Bruno, R. M., Brouwers, S., Canavan, M. D., Ceconi, C., Christodorescu, R. M., Daskalopoulou, S. S., Ferro, C. J., Gerdts, E., et al. (2024) · European Heart Journal · doi:10.1093/eurheartj/ehae178 · Cited by 2,298
Metadata
- Authors
- O’Rourke, M. F., & Safar, M. E.
- Affiliations
- UNSW Sydney (AU)
- Venue
- Hypertension
- Published
- 2005-07
- Volume
- 46
- Issue
- 1
- Pages
- 200-204
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2103868761
- Cited by
- 1,279
- References
- 43
- Citations by year
- 2026: 33 · 2025: 65 · 2024: 56 · 2023: 50 · 2022: 62 · 2021: 73 · 2020: 74 · 2019: 67 · 2018: 98 · 2017: 67 · 2016: 84 · 2015: 80 · 2014: 91 · 2013: 59 · 2012: 63
- FWCI
- 19.37
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Nephrology › Renal and Vascular Pathologies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- aortic stiffness, microangiopathy, central pulse pressure, aortic pulse wave velocity, augmentation index, input impedance, wave reflection, aging, renal failure, cognitive decline, diabetes mellitus, vascular fragility, nitrate, calcium channel blockers, ACE inhibitors, angiotensin receptor blockers, physical activity
- MeSH terms
- Aorta, Brain, Compliance, Humans, Kidney, Microcirculation, Vascular Diseases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
