Mechanisms of Left Ventricular Hypertrophy in Hypertension: More than Just Blood Pressure

Abstract

Hypertension is associated with a constellation of cardiac structural and functional changes, including increased left ventricular (LV) mass, and LV systolic and diastolic dysfunction. (1) Of the several adverse changes in cardiovascular morphology and function that occur in association with hypertension, LV hypertrophy is an established and independent prognostic factor for major cardiovascular events, including sudden cardiac death, acute myocardial infarction, stroke, and congestive heart failure. (2-6) Furthermore, there is a wealth of literature which demonstrates that decrease of LV mass in hypertensive patients results in improved survival rates. (7) Pathological changes of the left ventricle during long-term exposure to chronic pressure overload include an increase in the size of the cardiomyocyte, alterations in the extracellular matrix with accumulation of fibrosis, and abnormalities of the intramyocardial coronary vasculature, including medial hypertrophy and perivascular fibrosis (8) (Figure). However, given the detrimental contribution of LV hypertrophy to survival and cardiovascular events, most attention has also been focused on other mechanisms which may explain the risk associated with LV hypertrophy, and on the beneficial effects of anti-hypertensive pharmacological treatment. (1, 9-11) The mechanisms responsible for progression to hypertrophy include not only a mere response to the mechanical stress from elevated blood pressure (BP), but also the influence of neurohormones, growth factors, and cytokines. (1,12) Specifically, among factors promoting the progression of LV pathological remodeling, secretion and production of vasoactive peptides (such as angiotensin II, endothelin-1 and norepinephrine) are increased during the process and play critical roles in the hypertrophic response to systemic hypertension. (1) Oxidative stress, heat shock proteins, calcineurin, and some kinases are also involved in the hypertrophic process. (13)