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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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“High pulse pressure leads to arterial stiffness (30); and kidney cells are passively perfused by pulsatile flow which can cause endothelial damage by disrupting small arteriolar vessels (31).”
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Features of hyperintense white matter lesions and clinical relevance in systemic lupus erythematosus
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“Indeed, it has been confirmed by other studies that proteinuria can indicate generalized endothelial dysfunction,([37]) which may cause fluid to leak into the WM.”
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“The two organs most vulnerable to pulse-induced damage are the brain and another high-blood-flow organ, the kidney (O’Rourke and Safar, 2005).”
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“These previous observations might explain why AASI has a more pronounced association with cerebral events than the 24-h PP (7, 14).”
BackgroundCardiovascular disease is preventable among women
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“Although there are certain common underlying risk factors causing the occurrence of WMHs and cerebral lacunar infarction [28, 29], we found no significant association between aortic arch PWV and WMHs after correction for confounding factors.”
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“Aortic stiffness may contribute to microvascular brain injury by exposing the small vessels to the high pressure fluctuations and flow in the cerebral circulation [6].”
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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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