Left ventricular hypertrophy: the next treatable, silent killer?

AN INCREASE IN THE MASS OF LEFT VENTRICULAR muscle is intimately associated with most chronic diseases of the heart. Classically, left ventricular hypertrophy, which represents an extreme increase in left ventricular mass, has been thought to represent a reaction to pressure or volume overload. In the short run, increases in left ventricular mass may be beneficial by allowing the heart to compensate for increased wall stress and potential hemodynamic compromise; in the long run, left ventricular hypertrophy is harmful. Although the development of left ventricular hypertrophy has been related to a number of conditions, including obesity, diabetes, prior myocardial infarction, aortic stenosis, and regurgitant valvular heart disease, hypertension may well be the condition about which the most is known. Data from the Framingham Heart Study have shown that even mild increases in blood pressure are associated with increased left ventricular mass. Furthermore, left ventricular hypertrophy associated with hypertension appears to be reversible—ie, a long-term reduction of blood pressure has been shown to be associated with reductions in left ventricular mass. Some data have suggested that specific types of drugs, such as angiotensin-converting enzyme receptor blockers or calcium blockers, may be more effective than others in reducing increased left ventricular mass associated with hypertension, whereas other reports suggest that the specific drug used to reduce blood pressure may not be that important. For more than 30 years, it has also been recognized that left ventricular hypertrophy is a risk factor for premature death and cardiovascular events. A landmark article from the Framingham Heart Study published in 1970 reported that left ventricular hypertrophy, as noted on the electrocardiogram, is associated with a mortality rate that is as high as having a Q-wave myocardial infarction. Although subsequent studies have confirmed the strong association between electrocardiographic left ventricular hypertrophy and cardiovascular risk, it has also been recognized that the electrocardiogram may be relatively insensitive for detecting prognostically important increases in left ventricular mass. With the advent of echocardiography, milder increases in left ventricular mass could be easily detected. Additional data from the Framingham Study, as well as data from Cornell University and the Cardiovascular Health Study, among others, have demonstrated that a strong gradient exists between increased echocardiographic left ventricular mass and increased cardiovascular risk. Despite the wealth of literature linking electrocardiographic and echocardiographic left ventricular mass to increased cardiovascular risk, left ventricular hypertrophy is often not thought of as a “standard” or “classic” risk factor. One explanation is that left ventricular hypertrophy— similar to, for example, increased carotid intimal-medial thickness detected by ultrasound—may be considered in the category of subclinical disease—intermediate on the continuum from standard risk factors to clinically manifest cardiovascular disease. However, another reason may be that relatively little data are available on the impact that reversing left ventricular hypertrophy has on outcomes. In contrast, a wealth of literature now shows that reduction of blood pressure, levels of cholesterol and blood glucose, and use of tobacco are associated with important clinical benefits. Observational data have suggested that a decrease in left ventricular mass with treatment for hypertension is associated with a better outcome. However, prospective and systematic clinical trial data have been meager. In this issue of JAMA, 2 reports systematically document that changes in left ventricular mass in the setting of a trial of hypertension treatment have been correlated with longterm cardiovascular outcome. Okin and colleagues report on more than 9000 patients who were enrolled in the LIFE hypertension trial. This randomized trial involved a comparison of losartan-based therapy with atenolol-based therapy. Although the degree of blood pressure reduction was similar with the 2 drugs, losartan was associated with a greater reduction in left ventricular mass and a variety of cardiovascular outcomes. In the current study reported by Okin et al, patients enrolled in the trial had electrocardio-