Rationale and design for the CARDIOVIT Study (Cardiovit, Atherosclerotic vascular disease and hypeRhomocysteinemia:an epiDemiological study in Indians, additionally evaluating the effect of Oral VITamin supplementation)

Abstract

ABSTRACTBackground and rationale: Atherosclerotic vascular disease (AVD), including coronary heart disease (CHD), is on the rise in India. Mortality due to CHD is estimated to be 40% higher in Indian Asians compared with Europeans. Hyperhomocyst(e)inaemia (hypertHcy) is emerging as a novel independent risk factor for AVD. Moreover, there is increasing evidence of its association with CHD in subjects of Indian origin possibly because of inadequate folic acid and B12 status. However, there is a lack of epidemiological data on its prevalence in Indians. A need to evaluate the optimum dose of folic acid required to reduce plasma homocyst(e)ine (tHcy) also exists.Objectives and methods: The CARDIOVIT study, divided into two stages, is designed to determine the prevalence and relevance of hypertHcy in Indian subjects and also evaluate the tHcy-lowering effect of a marketed multivitamin formulation (Cardiovit). Stage I is a cross-sectional epidemiological study to estimate the prevalence of hypertHcy in a randomly selected population in South India. We planned to screen 2000 subjects between 25 and 64 years of age for established risk factors; plasma tHcy levels will be estimated and the correlation of AVD with established risk factors, plasma tHcy and nutritional factors was evaluated. Subjects having tHcy levels > 12 µmol/L are recruited in Stage II; a randomized, three-arm, double-blind, double-dummy, placebo-controlled, parallel-group, comparative study designed to evaluate the tHcy-lowering effect of a multivitamin formulation containing 300 µg folic acid, 1 µg vitamin B12 and 1.5 mg vitamin B6, along with Vitamins A, C, E and selenium. Subjects will be randomized into three groups (n = 64 completed subjects each) and receive either two placebos, or one placebo and multivitamin, or two multivitamin tablets for 6 weeks. Serum vitamin B12, serum and red cell folate are estimated at baseline and at 6 weeks. Descriptive, univariate analysis, multiple logistic regression model and appropriate statistical tests will be used to analyse the prevalence of hypertHcy, association with risk factors of AVD, efficacy and safety of the multivitamin formulation and other data per protocol.† Cardiovit is a registered trademark of Emil Pharmaceutical Industries Ltd, Dist Thane, Maharashtra State, India and marketed by Pfizer Ltd, Mumbai, IndiaConclusions: CARDIOVIT is one of the first and largest studies in India to provide insight into the prevalence of hypertHcy, its association with AVD and conventional risk factors and the role of multivitamins in reducing it.