Abstract-To elucidate mechanisms by which left ventricular (LV) hypertrophy (LVH) increases the risk of atherosclerotic heart disease, we sought to determine whether LVH is independently associated with coronary artery calcium (CAC) and serum C-reactive protein (CRP) levels in the general population. The Dallas Heart Study is a population-based sample in which 2633 individuals underwent cardiac MRI to measure LV structure, electron beam CT to measure CAC, and measurement of plasma CRP. We used univariate and multivariable analyses to determine whether LV mass and markers of concentric LV hypertrophy or dilation were associated with CAC and CRP. Increasing quartiles of LV mass indexed to fat-free mass, LV wall thickness, and concentricity, but not LV volume, were associated with CAC in both men and women (PϽ0.001). After adjustment for traditional cardiovascular risk factors and statin use, LV wall thickness and concentricity remained associated with CAC in linear regression (PϽ0.001 for each). These associations were particularly robust in blacks. LV wall thickness and concentricity were also associated with elevated CRP levels (Pϭ0.001 for both) in gender-stratified univariate analyses, although these associations did not persist in multivariable analysis. In conclusion, concentric LVH is an independent risk factor for subclinical atherosclerosis. LVH is also associated with an inflammatory state as reflected in elevated CRP levels, although this relationship appears to be mediated by comorbid conditions. These data likely explain in part why individuals with LVH are at increased risk for myocardial infarction. , whether determined by the ECG 1-9 or echocardiogram, 6 -8,10 -18 has been associated with various adverse cardiovascular outcomes, including mortality, myocardial infarction, and heart failure. Although there has been considerable speculation as to why LVH is such an important marker of risk, 19,20 the basic mechanisms that predispose patients with LVH to develop atherosclerotic heart disease (ASHD) are not known. Previous hypotheses have included abnormalities in the coronary vasculature 21-25 or platelets, 26 increased blood viscosity, 27 and a prothrombotic state. 28 In addition to these factors, which may contribute to reduced myocardial oxygen supply, myocardial oxygen demand is also increased in patients with LVH. 20 Another simple explanation for the association of LVH and ASHD is that LVH reflects target organ damage from concomitant risk factors, such as hypertension, thus providing a noninvasive barometer of the extent of ASHD. The association of LVH with atherosclerosis in other vascular territories, for example, the carotid artery, 29 supports this hypothesis. There are scant data as to whether LVH is associated with the burden of coronary atherosclerosis as estimated by coronary artery calcium (CAC). 30 -32 Yet another emerging hypothesis is that LVH itself is a low-level inflammatory state, as has been suggested recently from animal 33 and human studies. 34,35 If this is the case, one co...