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Background: Cardiac isoform of alpha 2 macroglobulin (CA2M), a serum protein (182000Mr) has been used as a diagnostic molecular marker for cardiac manifestations in HIV and diabetic patients. This study investigates the reliability of CA2M as an early diagnostic marker for cardiac manifestations in HIV patients and factors that could possibly influence their levels., Methods: A total of 206 serum samples were analysed from HIV patients with cardiac diseases (68), with non-cardiac ailments (48), opportunistic infections (34) and without other co-morbidities (56). The immuno-cross-reactivity between human serum CA2M and anti-rat CA2M antibody was tested and quantified by sandwich enzyme linked immunosorbent assay (ELISA)., Results: The CA2M levels were high in HIV patients with cardiac diseases irrespective of the manifestations. The CA2M levels were not influenced by opportunistic infections, non-cardiac ailments and patient parameters like age, sex, duration of illness, past history of other co-morbidities., Conclusion: CA2M can be used as a reliable early diagnostic marker in HIV patients with cardiac manifestations. CA2M levels were not influenced by other patient parameters., (Copyright (c) 2009 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and New Zealand. Published by Elsevier B.V. All rights reserved.)