Abstract 211: Apoptosis and Subclinical Atherosclerosis: Caspase-3 is Associated with Aortic Compliance and Coronary and Aortic Atherosclerosis in the Dallas Heart Study
Caspase-3, an apoptosis protease, is expressed in atherosclerotic plaques. However, plasma caspase-3 has not been examined as a measure of vascular dysfunction and atherosclerosis. We examined the relationship between plasma caspase-3 levels, aortic compliance, and atherosclerosis. Caspase-3 was measured in 3221 subjects from the Dallas Heart Study. Electron beam computed tomography measures of coronary calcium (CAC) (n=2466) and magnetic resonance imaging (MRI) measures of abdominal aortic wall thickness (AWT) (n=2271) and aortic compliance (AC) (n=2391) were obtained. Multivariate analyses were performed, adjusting for age, sex, ethnicity, body mass index (BMI), and traditional cardiovascular risk factors. A second model additionally adjusting for novel atherosclerotic risk biomarkers (osteoprotegerin (OPG), NT-pro-BNP, troponin I, monocyte chemoattractant protein-1 (MCP-1), and high- sensitivity C-reactive protein (hsCRP)) was also performed. Increasing levels of caspase-3 associate with cardiovascular risk factors, hs-CRP, MCP-1, and OPG (p<0.0001 for each). In univariable analysis, caspase-3 was associated with CAC (p<0.0001), AWT (p<0.002), and AC (p<0.0001). After multivariable adjustment, 4th quartile caspase-3 (compared to 1st quartile) was significantly associated with CAC (OR 1.7, 95%CI 1.2–2.3; p=0.003), AWT (p=0.013), and AC (p<0.0001). Adjustment for novel biomarkers did not attenuate these associations (Table 1⇓). Caspase-3 independently associates with CAC, AWT, and AC, suggesting a link between apoptosis and atherosclerosis. Caspase-3 levels may be useful in the evaluation of anti-apoptotic agents in cardiovascular disease.