Development and Validation of a Nomogram to Predict CAC Progression Based on the MESA and the CARDIA Study

Abstract

Background: This study aimed to develop and validate a nomogram for individually predicting coronary artery calcium (CAC) progression.

Methods: The Multi-Ethnic Study of Atherosclerosis (MESA) cohort with 5486 participants (47.3% male, mean [SD] age 61.9 [10.2] years) were included, who were randomly assigned into the training set, or the internal validation set at a 7:3 ratio. A separate cohort of 2447 participants (44.6% male, a mean [SD] age of 40.4 [3.5] years) from the Coronary Artery Risk Development in Young Adults (CARDIA) study served as the external validation set. Baseline clinical characteristics, findings on physical examination, and laboratory profiles were assessed. CAC progression was the primary outcome measure. A nomogram was established based on the least absolute shrinkage and selection operator (LASSO)-derived Cox regression model. The discrimination and calibration ability of this nomogram was evaluated by Hosmer–Lemeshow test and calibration curves in the training and validation cohorts.

Findings: Sixty-one features were reduced to 10, which were age, male gender, smoking status, waist circumference, systolic blood pressure, fasting glucose, lipid abnormalities, antihypertensive medication, and glucose-lowering medication and lipid-lowering medication use. The nomogram model showed a good discrimination in the training set (C-statistics: 0.682; 95% CI, 0.665-0.699), and application in the validation sets also gave good discrimination (C-statistics for the internal validation: 0.664; 95% CI, 0.638-0.690; for the external validation: 0.750; 95% CI, 0.729-0.771), which was better than the Framingham Risk Score model (C-statistics: 0.677; 95% CI, 0.663-0.691 vs. 0.658; 95% CI, 0.644-0.672, P<0.001). Calibration test yielded a high consistency between prediction and observation. Decision curve analysis demonstrated the clinical usefulness of the nomogram for predicting the risk of CAC progression.

Interpretation: This study presents a nomogram that may be used to facilitate individualized prediction of CAC progression and should help better focus on primary prevention of cardiovascular disease in clinical practice.

Funding: This work was supported by grants from National Natural Science Foundation of China (NSFC) [82170457, 81900379, 81870315, 81970683], Guangdong Basic and Applied Basic Research Foundation [2020A1515110313], and Yat-sen Start-up Foundation [YXQH202014]. The MESA study was supported by contracts N01-HC-95159 through N01-HC-95167 from the National Heart, Lung, and Blood Institute (NHLBI). The CARDIA study is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (grants HHSN268201800005I and HHSN268201800007I), Northwestern University (grant HHSN268201800003I), University of Minnesota (grant HHSN268201800006I), and Kaiser Foundation Research Institute (grant HHSN268201800004I), of the United States. The authors report no conflicts of interest. (9) Clinical trial registration number: The CARDIA trial was registered at clinicaltrials.gov as NCT00005130. The MESA trial was registered at clinicaltrials.gov as NCT00005487.

Declaration of Interest: The authors report no conflicts of interest.

Ethical Approval: All participants provided informed consent and the study protocol was approved by the Institutional Review Boards at each participating institution.

Keywords: Coronary artery calcium progression, Nomogram, Risk factors, Cardiovascular disease