Abstract

The MESA (Multi-Ethnic Study of Atherosclerosis) is an ongoing study of the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multi-ethnic cohort. It provides a valuable opportunity to examine the development and progression of CAC (coronary artery calcium), which is an important risk factor for the development of coronary heart disease. In MESA, about half of the CAC scores are zero and the rest are continuously distributed. Such data has been referred to as “zero-inflated data” and may be described using two-part models. Existing two-part model studies have limitations in that they usually consider parametric models only, make the assumption of known forms of the covariate effects, and focus only on the estimation property of the models. In this article, we investigate statistical modeling of CAC in MESA. Building on existing studies, we focus on two-part models. We investigate both parametric and semiparametric, and both proportional and nonproportional models. For various models, we study their estimation as well as prediction properties. We show that, to fully describe the relationship between covariates and CAC development, the semiparametric model with nonproportional covariate effects is needed. In contrast, for the purpose of prediction, the parametric model with proportional covariate effects is sufficient. This study provides a statistical basis for describing the behaviors of CAC and insights into its biological mechanisms.

Highlights

  • The MESA (Multi-Ethnic Study of Atherosclerosis) is an ongoing study of the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multi-ethnic cohort [1]

  • In MESA, CAC is measured with the Agatston score, which is the amount of calcium at each lesion scaled by an attenuation factor and summed over all lesions [3]

  • The MESA Study The MESA is a study of the characteristics of subclinical cardiovascular disease and the risk factors that predict progression to clinically overt cardiovascular disease or progression of the subclinical disease [1]. 6814 participants 45 to 84 years of age were recruited from six US communities from 2000 to 2002

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Summary

Introduction

The MESA (Multi-Ethnic Study of Atherosclerosis) is an ongoing study of the prevalence, risk factors, and progression of subclinical cardiovascular disease in a multi-ethnic cohort (http:// www.mesa-nhlbi.org/) [1]. It provides a valuable opportunity to investigate the development and progression of CAC (coronary artery calcium), which is an important risk factor for the development of coronary heart disease events [2]. In a relatively healthy cohort, such a mixture CAC distribution is commonly observed. The CAC has a ‘‘point mass at zero+continuous’’ distribution and is a special case of zero-inflated data. To describe nonzero CAC values, existing methods include generalized estimating equations [4], Tobit regression [5], zero-inflated normal model [6], quantile regression [7], and others. To describe zero versus nonzero CAC values, existing methods include logistic regression [5], relative risk regression, and others

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