Brain Microbleeds, Amyloid Plaques, Intellectual Deterioration, and Arterial Stiffness
To the Editor:
The article by Henskens et al1 on brain microbleeds supports a view2 that cerebral microvascular disease in hypertensive patients is responsible for intellectual deterioration and is caused by abnormal flow pulsations extending into the small cerebral vessels as a consequence of aortic stiffening. The relationship between cognitive decline and aortic stiffness and pulse pressure, suspected previously on mechanistic grounds,2 has been confirmed by Waldstein et al3 for the Baltimore Longitudinal Study of Aging in the same issue of Hypertension. MRI studies have confirmed an association between cerebral white matter hyperintensities and high-flow pulsations in the cerebral vasculature and have referred to the former as caused by “pulse wave encephalopathy.”4 Histological studies have shown that the amyloid deposits characteristic of Alzheimer’s dementia can be attributed to previous microbleeds.5 Our own work2 suggests that microbleeds, white matter hyperintensities, and lacunar infarcts are caused by the damaging forces of high pulsatile pressure and flow in cerebral microvessels, as first pointed out by Byrom in Sydney, and by a similar mechanism in the pulmonary circulation of children with congenital left to right shunts, as pointed out by Edwards from the Mayo Clinic 50 years ago.
These mechanisms may help explain other recent findings. Increased circulating endothelial cell fragments in persons with aortic stiffening6 may be caused by such microvascular damage in brain and kidney.2 High C-reactive protein levels in older persons may be a consequence of inflammation caused by small vessel damage rather than a cause of large artery damage. Even the findings of highest value of nocturnal blood pressure in outcomes by Henskens et al1 and by Fagard et al7 in the same issue of Hypertension may be due in part to cerebral arteries being exposed to the highest blood pressure during sleep when persons are recumbent and the brain less protected from hydrostatic (gravitational) forces than when a person is erect or sitting.
The article by Henskens et al1 and others in the same issue of Hypertension provide more evidence to support a cerebral microvascular mechanism for intellectual deterioration in older persons with arterial stiffening.
M.F.O. is a founding director of AtCor Medical Pty Ltd, manufacturer of systems for analyzing the arterial pulse.
Henskens LHG, van Oostenbrugge RJ, Kroon AA, de Leeuw P, Lodder J. Brain microbleeds are associated with ambulatory blood pressure levels in a hypertensive population. Hypertension. 2008; 51: 62–68.
O’Rourke MF, Safar ME. Relationship between aortic stiffening and microvascular disease in brain and kidney: cause and logic of therapy. Hypertension. 2005; 46: 200–204.
Waldstein SR, Rice SC, Thayer JF, Najjar SS, Scuteri A, Zonderman AB. Pulse pressure and pulse wave velocity are related to cognitive decline in the Baltimore Longitudinal Study of Aging. Hypertension. 2008; 51: 99–104.
Henry-Feugeas MC, De Marco G, Idy-Peretti I, Godon-Hardy S, Fredy D, Schouman-Claeys E. age-related cerebral white matter changes and pulse-wave encephalopathy: observations with three-dimensional MRI. Magn Reson Imaging. 2005; 23: 145–165.
Wang JM, Huang YJ, Wang Y, Xu MG, Wang LC, Wang SH, Tao J. Increased circulating CD31+/CD42− microparticles are associated with impaired systemic artery elasticity in healthy subjects. Am J Hypertens. 2007; 20: 957–964.
Fagard RH, Celis H, Thijsh L, Staessen JA, Clement DL, De Buyzere ML, De Bacquer D. Daytime and nighttime blood pressure as predictors of death and cause-specific cardiovascular events in hypertension. Hypertension. 2008; 51: 55–61.