Is cardiovascular remodeling in patients with essential hypertension related to more than high blood pressure? A LIFE substudy. Losartan Intervention For Endpoint-Reduction in Hypertension

Abstract

Background: Blocking the renin-aldosterone-angiotensin II system has been hypothesized to induce blood pressure-dependent as well as blood pressure-independent regression of cardiovascular hypertrophy. However, the relative influence of elevated blood pressure (BP) and various neurohormonal factors on cardiovascular remodeling in hypertension is unclear.

Methods: In 43 untreated patients with hypertension with electrocardiographic left ventricular hypertrophy, we measured relative wall thickness and left ventricular mass index by echocardiography and by magnetic resonance imaging (n = 32), intima-media cross-sectional area, and distensibility of the common carotid arteries by ultrasound, media/lumen ratio of isolated subcutaneous resistance arteries by myography, and median 24-hour systolic BP (n = 40), serum insulin, and plasma levels of epinephrine, norepinephrine, renin, angiotensin II, aldosterone, and endothelin.

Results: In multiple regression analyses, left ventricular mass index by echocardiography (R2 = 0.14, P <.05) and by magnetic resonance imaging (R2 = 0.32, P =.001) were associated with 24-hour systolic BP, whereas relative wall thickness was associated with plasma epinephrine (R2 = 0.12, P <.05) and aldosterone (R2 = 0.10, P <.05). Intima-media cross-sectional area/height was associated with 24-hour systolic BP (beta = 0.40) and plasma epinephrine (beta = 0.43) (adjusted R2 = 0.32, P <.001), whereas carotid distensibility was associated with 24-hour systolic BP (beta = 0.40) and plasma angiotensin II (beta = -0.41) (adjusted R2 = 0.30, P <.001). Media/lumen ratio in subcutaneous resistance arteries was associated with plasma epinephrine (R2 = 0.22, P <.01).

Conclusion: Apart from being associated with a high BP burden, cardiovascular remodeling was associated with high levels of circulating epinephrine, aldosterone, as well as angiotensin II, suggesting a beneficial effect above and beyond the effect of BP reduction when using antihypertensive agents blocking the receptors of these neurohormonal factors.