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.
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“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”
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Renal dysfunction increases the risk of recurrent stroke in patients with acute ischemic stroke
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“One result of increased arterial stiffness is transfer of cardiac flow pulsatility to the less compliant small blood vessels of the brain, resulting in increased mechanical stress on those vessels that eventually culminates in microhemmorhage (Henskens et al. 2008; Mitchell et al. 2011; O’Rourke and Safar 2005; Ohmine…”
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Older age and male sex are associated with higher cerebrovascular impedance
Sugawara, J., Tarumi, T., Xing, C., Liu, J., Tomoto, T., Pasha, E. P., & Zhang, R. (2020) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00396.2020 · Cited by 18
Sabra, D., Intzandt, B., Desjardins-Crépeau, L., Langeard, A., Steele, C. J., Frouin, F., Hoge, R. D., Bherer, L., & Gauthier, C. J. (2021) · PLoS ONE · doi:10.1371/journal.pone.0257815 · Cited by 17
Common Carotid Artery Flow Parameters Predict the Incidence of Hypertension
Sasaki, N., Maeda, R., Ozono, R., Nakano, Y., & Higashi, Y. (2021) · Hypertension · doi:10.1161/hypertensionaha.121.18080 · Cited by 18
Age-Associated Dysregulation of Integrin Function in Vascular Smooth Muscle
Ojha, K. R., Shin, S. Y., Padgham, S., Olmedo, F. L., Guo, B., Han, G., Woodman, C. R., & Trache, A. (2022) · Frontiers in Physiology · doi:10.3389/fphys.2022.913673 · Cited by 18
Wen, Q., Wright, A. M., Tong, Y., Zhao, Y., Risacher, S. L., Saykin, A. J., Wu, Y., Limaye, K. S., & Riley, K. J. (2023) · NMR in Biomedicine · doi:10.1002/nbm.5048 · Cited by 17
“7 This may result in microvascular insult to the brain, leading to ischemia and disruption of the blood – brain barrier, as well as a disruption to the vascular-driven clearance of waste proteins from the brain parenchyma.”
Ong, W., Ng, M. P.-E., Loke, S. Y., Jin, S., Wu, Y., Tanaka, K., & Wong, P. T.-H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0068335 · Cited by 18
“Arterial stiffness is a major determinant of increased systolic blood pressure, and is associated with lesions in intracranial arteries [8].”
BackgroundVasoregression: A Shared Vascular Pathology Underlying Macrovascular And Microvascular Pathologies?
Gupta, A., & Bhatnagar, S. (2015) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2015.0128 · Cited by 20
“These similarities were attributed to the hemodynamic similarities between the vascular beds in the brain and kidney (Mogi and Horiuchi, 2011; O’Rourke and Safar, 2005).”
Kinjo, Y., Ishida, A., Kinjo, K., & Ohya, Y. (2016) · Journal of Hypertension · doi:10.1097/hjh.0000000000000993 · Cited by 18
“The reflected wave returning from the lower body contributes substantially to the contour of the brachial pressure wave, being responsible for its secondary late systolic surge, whereas reflection from the upper limb has little effect on lower body pulse [19].”
BackgroundThe effect of an acute bout of resistance exercise on carotid artery strain and strain rate
Black, J. M., Stöhr, E. J., Stone, K. J., Pugh, C. J. A., Stembridge, M. R., Shave, R., & Esformes, J. I. (2016) · Physiological Reports · doi:10.14814/phy2.12959 · Cited by 18
“The increase in S-SR immediately post exercise may occur to buffer the elevated blood pressure associated with the onset of exercise, providing a smoother, more consistent flow (Kingwell 2002), and preventing damage to cerebral microvessels (O’Rourke and Safar 2005).”
BackgroundThe relationships between lipid ratios and arterial stiffness
Mulè, G., Nardi, E., Geraci, G., Schillaci, M. K., & Cottone, S. (2017) · Journal of Clinical Hypertension · doi:10.1111/jch.13030 · Cited by 18
Carotid Artery Stiffness and Cognitive Decline Among Women With or at Risk for HIV Infection
Huck, D. M., Hanna, D. B., Rubin, L. H., Maki, P. M., Valcour, V., Springer, G., Xue, X., Lazar, J., Hodis, H. N., Anastos, K., et al. (2018) · JAIDS Journal of Acquired Immune Deficiency Syndromes · doi:10.1097/qai.0000000000001685 · Cited by 18
The Utility of Cerebrovascular Reactivity MRI in Brain Rehabilitation: A Mechanistic Perspective
Krishnamurthy, V., Sprick, J. D., Krishnamurthy, L. C., Barter, J., Turabi, A., Hajjar, I. M., & Nocera, J. R. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.642850 · Cited by 20
“Thus, long term increases in pulsatile flow with arterial stiffness are thought to contribute to microvascular damage within the brain (O’Rourke and Safar, 2005).”
BackgroundArterial Stiffness, Kidney Function, and Chronic Kidney Disease Progression
Townsend, R. R., & Tomiyama, H. (2013) · Pulse · doi:10.1159/000354113 · Cited by 18
Yu, M., Yu, M.-K., Yu, M.-K., Lee, F., & Huang, W. (2010) · Pediatric Nephrology · doi:10.1007/s00467-010-1590-2 · Cited by 18
“Nowadays, there is evidence that baPWV not only has a similar efficiency to aortic PWV, but it can also examine global arterial stiffness, particularly small-vessel damage in the brain and kidney [31, 33 , 34].”
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Wei, F., Zhang, Z., Petit, T., Cauwenberghs, N., Gu, Y., Thijs, L., Raaijmakers, A., Jacobs, L., Yang, W., Allegaert, K., et al. (2016) · Hypertension Research · doi:10.1038/hr.2016.81 · Cited by 18
Coutinho, A. M., Coutu, J., Lindemer, E., Rosas, H. D., Rosen, B. R., & Salat, D. H. (2016) · NeuroImage · doi:10.1016/j.neuroimage.2016.11.021 · Cited by 18
“Also, due to anatomical and physiological similarities, the kidneys are sensitive to microvascular and ischemic damage in a similar way as brain tissue (Ikram et al., 2007; O'Rourke and Safar, 2005; Sedaghat et al., 2015a, 2015b).”
BackgroundLi, H., Cao, W., Zhang, X., Sun, B., Jiang, S., Li, J., Liu, C., Yin, W., Wu, Y. C., Liu, T., et al. (2018) · NeuroImage · doi:10.1016/j.neuroimage.2018.11.030 · Cited by 18
“Vascular aging could lead to small vessel dysregulation, which would change the blood flow and then influence renal and brain function (O'Rourke and Safar, 2005).”
Namasivayam, M. J., Adji, A. I., Lin, L., Hayward, C., Feneley, M. P., O’Rourke, M. F., Muller, D. W., & Jabbour, A. (2020) · Cardiovascular Engineering and Technology · doi:10.1007/s13239-020-00462-2 · Cited by 18
Self-citationNoninvasive arterial compliance estimation
Švec, D., & Javorka, M. (2021) · Physiological Research · doi:10.33549/physiolres.934798 · Cited by 17
“In case of decreased AC, this function might be insufficient and blood pressure pulsatility may promote increased target organ damage through excessive penetration of pulsatility into peripheral target organs such as kidney or brain (Chirinos 2012, O’Rourke and Safar 2005).”
BackgroundEpidemiology and Risk Factors for Stroke in Chronic Kidney Disease: A Narrative Review
Kourtidou, C., & Τζιόμαλος, Κ. (2023) · Biomedicines · doi:10.3390/biomedicines11092398 · Cited by 17
“The brain and kidneys are composed of low vascular resistance systems that allow continuous high-volume perfusion [34,35].”
BackgroundDrugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor
Liabeuf, S., Pešić, V., Spasovski, G. B., Mačiulaitis, R., Bobot, M., Farinha, A., Wagner, C. A., Unwin, R. J., Capasso, G., Bumblytė, I. A., et al. (2023) · Clinical Kidney Journal · doi:10.1093/ckj/sfad241 · Cited by 17
“On the other hand, it was noted that small-vessel disease in the brain is mirrored by small-vessel pathologies in other organs [ 27 ].”
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Macro- and microvascular alterations in patients with metabolic syndrome: sugar makes the difference
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Gu, Y., Petit, T., Wei, F., Thijs, L., Jacobs, L., Zhang, Z., Yang, W., Cauwenberghs, N., Knez, J., Struijker-Boudier, H. A. J., et al. (2015) · Hypertension Research · doi:10.1038/hr.2015.125 · Cited by 17
Quantification of near‐wall hemodynamic risk factors in large‐scale cerebral arterial trees
Ghaffari, M., Alaraj, A. M., Du, X., Zhou, X. J., Charbel, F. T., & Linninger, A. A. (2018) · International Journal for Numerical Methods in Biomedical Engineering · doi:10.1002/cnm.2987 · Cited by 17
Komnenov, D., Levanovich, P., Perecki, N., Chung, C. S., & Rossi, N. F. (2020) · Integrated Blood Pressure Control · doi:10.2147/ibpc.s257205 · Cited by 17
Vascular smooth muscle stiffness and its role in aging
Trache, A., Massett, M. P., & Woodman, C. R. (2020) · Current topics in membranes · doi:10.1016/bs.ctm.2020.08.008 · Cited by 17
Murai, S., Tanaka, S., Dohi, Y., Kimura, G., & Ohte, N. (2014) · Scientific Reports · doi:10.1038/srep03884 · Cited by 17
Arterial stiffness and renal function—a complex relationship
Salvi, P., & Parati, G. (2014) · Nature Reviews Nephrology · doi:10.1038/nrneph.2014.226 · Cited by 17
Tanaka, T., Shimizu, T., & Fukuhara, T. (2009) · Computerized Medical Imaging and Graphics · doi:10.1016/j.compmedimag.2009.04.007 · Cited by 17
“[8] O’Rourke MF, Safar ME.”
Background
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
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