Friday, January 13, 2006

Central versus brachial blood pressure, it that a key to differences in efficacy of medications

The ASCOT trial which demonstrated that amlodipine plus perindopril was superior to a combination of atenolol and a thiazide in terms of reduction in cardiovascular and renal outcomes and overall mortality had an interesting substudy known as CAFE. The Conduit Artery Function Evaluation study investigated the role of central versus peripheral blood pressure in cardiovascular outcomes.The amlodipine-perindopril group had lower central pressures while brachial pressures differed little. Could the greater reduction in central pressure be the reason for the apparent better outcomes of the amlodipine-perindopril regimen? There are data that indicate that calcium channel blockers and ACE inhibitors lower central pressure while atenolol does not.These two data sets were not obtained with catheters in the aorta but rather estimated central aortic pressure with something called "radial applanation tonometry". There are data indicating that this is a reproducibbe technique and provides a good estimate of central aortic pressure.Arterial stiffness as quantitated by several parameters derived from this pulse wave study seem to correlate with coronary artery disease and may be considered a type of end organ damage to which various outcome data correlate. Internists have a tradition of being enamored with pathophysiology and having grown up medically with the imperative of striving to "reason in terms of pathophysiology", I continue to find it intellectually gratifying to find instances where the data seem to be "explained" by underlying pathophysiological observations and theories.Having said that, I realize the theories are provisional and subject to refutation as we continue to try and discern how things work. Still, the mantra of the ALLHAT devotees of "diuretics and beta-blockers are best" is becoming less and less convincing.See also DB"s Medical Rants for an important perspective on diuretics.

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