3.6 BLOOD PRESSURE REDUCTION IS THE MAIN DETERMINANT OF THE DE-STIFFENING EFFECT OF ANTIHYPERTENSIVE TREATMENT: A META-REGRESSION ANALYSIS AND COMPARISON WITH ACUTE MODULATION OF TRANSMURAL PRESSURE

Abstract

Background: Pulse wave velocity (PWV) is independent predictor of cardiovascular outcomes. Antihypertensive treatment reduces PWV, but it is unknown whether this results from an unloading of stiffer elements in the arterial wall or a structural change in the wall. Methods: To distinguish between these effects we performed a systematic review and meta-regression analysis of effects of different drug classes and durations of antihypertensive treatment on the relationship between reduction in PWV and that in mean arterial pressure (MAP). We compared this to the variation in PWV during an acute modulation of aortic transmural pressure (TMP) by respiratory manoeuvres, simulating a change in MAP in patients with essential hypertension. Results: We identified 99 trials on 6,703 hypertensive individuals in total (average age and treatment duration were 56 ± 9.4 years and 21.6 ± 17.9 weeks, respectively). Reduction in PWV was strongly associated with that in MAP, PWV falling by 0.7 m/s per 10 mmHg fall in MAP (95% CI 0.5 – 0.86 m/s, p < 0.001). However, reduction in PWV was independent of drug class or duration of treatment. Change in PWV during respiratory manoeuvres was related to TMP with a similar relation to that observed in the meta-regression analysis: 0.94 m/s per 10 mmHg change in TMP (95% CI 0.34 – 1.54 m/s, p<0.001). Conclusion: Antihypertensive treatment reduces PWV mainly by an unloading effect on the arterial wall, at least over the short term. There is little evidence for a treatment-specific effect. It may be possible to predict effects of antihypertensive treatment on reduction of PWV and pulse pressure by modulating transmural pressure.