Wilson's Disease and Cardiac Myopathy

Donald J. Grandis, Gregory Nah, Isaac R. Whitman, Eric Vittinghoff, Thomas A. Dewland, Jeffrey E. Olgin, Gregory M. Marcus

Wilson's disease is a well-characterized disorder known to cause liver and brain disease due to abnormal copper deposition. Data regarding copper infiltration of the heart is conflicting, and the risk of heart disease has not been well described. We aimed to determine whether Wilson's disease is associated with cardiac myopathy, clinically evident in the atria as atrial fibrillation (AF) and in the ventricles as heart failure (HF). We longitudinally assessed 14.3 million patients in the California Healthcare Cost and Utilization Project database from 2005 through 2009 for diagnoses of Wilson's disease, AF, HF, and covariates using International Classification of Diseases-9th Edition codes. Cirrhosis and appendicitis diagnoses were assessed for positive and negative validation, respectively. We identified 463 patients with Wilson's disease. As expected in validation analyses, patients with Wilson's disease had a threefold greater risk of cirrhosis (hazard ratio [HR] 2.85, 95% confidence interval [CI] 2.81 to 2.90, p <0.0001) and no increased risk of appendicitis (HR 0.24, 95% CI 0.04 to 1.71, p = 0.16). Patients with Wilson's disease exhibited a 29% higher risk of AF after adjusting for age, gender, race, income, hypertension, diabetes, renal disease, hyperlipidemia, obesity, coronary disease, and obstructive sleep apnea (HR 1.29, 95% CI 1.15 to 1.45, p <0.0001). After adjusting for the same covariates, patients with Wilson's disease had a 55% higher risk of incident HF (HR 1.55, 95% CI 1.41 to 1.71, p <0.0001). Patients with Wilson's disease have an increased risk of AF and HF, supporting the need for careful surveillance for heart disease. These findings also suggest that the role of copper metabolism in heart disease should be more broadly investigated.