Cardiovascular Remodeling in Essential Hypertension: LIFE Study
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 (R = 0.14, P < .05) and by magnetic resonance imaging (R = 0.32, P = .001) were associated with 24-hour systolic BP, whereas relative wall thickness was associated with plasma epinephrine (R = 0.12, P < .05) and aldosterone (R = 0.10, P < .05). Intima-media cross-sectional area/height was associated with 24-hour systolic BP (




= 0.40) and plasma epinephrine (



= 0.43) (adjusted R = 0.32, P < .001), whereas carotid distensibility was associated with 24-hour systolic BP (



= 0.40) and plasma angiotensin II (



= -0.41) (adjusted R = 0.30, P < .001). Media/lumen ratio in subcutaneous resistance arteries was associated with plasma epinephrine (R = 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.


Patients with essential hypertension often have cardiovascular changes, the severity of which do not always relate to the blood pressure (BP), suggesting that neurohormonal factors may contribute to the changes. Cardiac myocyte growth is believed to be primarily governed by loading conditions, whereas smooth muscle cell and fibroblast proliferation is primarily regulated by neurohumoral mechanisms. The importance of the renin-angiotensin system and the sympathetic nervous system in the development of vascular hypertrophy and remodeling has been discussed for many years. In addition, associations between left ventricular (LV) hypertrophy and peripheral vascular remodeling, as well as conduit artery hypertrophy and stiffness have been documented. Some data indicate that reversal of vascular changes can add to regression of LV hypertrophy in conjunction with BP reduction, but the possibility of any causality in these associations is still unclear. Treatment with low-dose angiotensin-converting enzyme inhibitors has, in rats, been demonstrated to induce regression of vascular remodeling without reduction in blood pressure, supporting the hypothesis that blocking the renin-aldosterone-angiotensin II system in humans may have beneficial effects on regression of cardiovascular remodeling above and beyond the effects of blood pressure reduction.

This study was undertaken to investigate the association of increased BP and various neurohormonal factors to cardiovascular hypertrophy and remodeling in patients with hypertension and electrocardiographic LV hypertrophy to sort out the relative importance of hemodynamic burden versus neurohormonal factors on cardiovascular hypertrophy and remodeling. Furthermore, we wanted to describe the relationship between LV hypertrophy and vascular hypertrophy, remodeling, and stiffness. LV mass was assessed by echocardiography, as well as by magnetic resonance imaging--combining the most clinically used method with the more accurate method.