title: 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.
authors.affiliation: St Vincent's Clinic, University of New South Wales, VCCRI, Sydney, Australia. m.orourke@unsw.edu.au
authors.forename: Michael F
authors.initials: MF
authors.lastname: O'Rourke
authors.forename: Michel E
authors.initials: ME
authors.lastname: Safar
mesh_terms: D001011:Aorta / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply*; D003187:Compliance; D006801:Humans; D007668:Kidney / Q000098:blood supply*; D008833:Microcirculation; D014652:Vascular Diseases / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy