Prior infection with cytomegalovirus markedly increases the risk of restenosis following directional coronary atherectomy

Recent evidence suggests a potential role of cytomegalovinis (CMV) on the development of reetenosis: CMV DNA is present in restenosis lesions from atherectomy specimens, and a CMV immediate early gene protein (IE84) binds to and inhibits p53, gene product that can block cell cycle progression and initiate apoptosis. These pS3-mediated effects may contribute to increased SMC accumulation and thereby predispose to reatenosis. In the present prospective study, 68 consecutive pts undergoing directional coronary atberectomy (DCA) for symptomatic CAD were prospectively evaluated by measuring anti-CMV IgG and IgM antibodies (before DCA) to determine whether prior CMV exposure increases restenosis risk, as determined by a 6-month post-DCA angiogram. Anti-CMV antibody status was restudied 6-month post-DCA. Diabetes, hypercholesterolemia, hypertension, LAD lesion, and small vessel lesion (less than 3 mm in diameter), smoking, and unstable angina were also analyzed and compared with CMV status for potential risk to restenosis. To determine the specificity of CMV immunopositivity and restenosis, anti-hepatitis A antibody status was studied (seroposivity to hepatitis A has approximately the same frequency as seropositivity to CMV). Of the pts (n=47) with prior CMV exposure, 47% developed restenosis; in contrast, only 1496 pts without prior CMV exposure (n = 21) developed restenosis (p=0.01). In a multivariate analysis including other potential risk factors, the presence of positive anti-CMV IgG antibody titers conveyed an odds ratio of 10.3 for restenosis development, a value far above that associated with any other risk factor in this or prior studies. The strength and magnitude of the effect persisted after adjustment for all study covariates. There was no evidence of acute infection as anti-CMV IgG antibody titers did not increase over the 6-month time and anti-CMV IgM antibodies were negative in all pts. 41% of the pts were seropositive for hepatitis A virus. However, no association with restenosis was found. We conclude that prior infection with CMV is an independent strong risk factor for the development of restenosis following DCA. This prospectively determined link of CMV to restenosis raises new possibilities for risk assessment for patients undergoing angioplasty, and for therapeutic approaches designed to reduce the risk of restenosis.