Because China is large and exhibits regional diversity in individual lifestyle, height, and weight, a multicenter study was conducted to more accurately ascertain pediatric coronary artery diameter reference values. The present study is the largest such multicenter Chinese pediatric study to date, and includes coronary artery measurement data from six regions in Northern and Southern China.
Study findings demonstrate that coronary artery diameters of a healthy Chinese pediatric population increase non-linearly with an increase in BSA, and differ significantly from those of a healthy North American pediatric population. Specifically, Chinese pediatric coronary artery diameters are larger at lower BSA ranges, but smaller at higher BSA ranges, than those of North American children. In addition, relative to the D method, the SZ method mean reference value-predictive regression model exhibits lower Z scores at lower BSA ranges and higher Z scores at higher BSA ranges. This suggests that the SZ method may be more accurate than the D method in the Chinese pediatric population.
Previous studies suggested the existence of a linear correlation between equal variance of coronary artery diameter and BSA13–17. However, multiple larger studies have found a non-linear correlation between coronary artery diameter and BSA in healthy pediatric populations2–9, 19. Coronary artery diameter standard deviation from the mean differs within distinct BSA ranges, resulting in population-inappropriate linear regression methods introducing bias during Z score calculation. Therefore, researchers have sought to identify regression models able to more accurately represent the non-linear relationship between coronary artery diameter mean and standard error. Specifically concerning heteroscedastic non-linear relationships, prior studies have evaluated the goodness of fit of various regression models, including quadratic, cubic polynomial, logarithmic, exponential, and square root2–9.
In the present study, an exponential regression model exhibited the best fit (based on maximum R2 and minimum RSE and AIC) and the standard test of normality was therefore applied to model residuals and Z scores. Results indicate that the model performs reliably. The present study therefore contributes to establishment of Chinese pediatric coronary artery diameter reference values, and provides data which may help overcome the lack of universality associated with single-center studies.
Up to 25 BSA calculation methods are available, including the Stevenson, Haycock, and Du Bois EF formula10,11,18,20. The American Society of Echocardiography guidelines for quantitative pediatric echocardiography recommends use of the Haycock formula when calculating Z scores for cardiovascular structure measurements 21,22. The Haycock formula may also be a better estimator of BSA for smaller children 4,22, although different BSA formulae do not result in different model Z scores in the present study. However, the Stevenson formula is commonly used within the Chinese healthcare system. Therefore, in order to determine the impact of formula choice on model Z scores, the present study derived regression models from a single original dataset (using BSA calculated via either the Stevenson or Haycock formulae), and compared resultant Z scores. Because Z scores did not differ significantly, either BSA formula is appropriate for use in quantitative evaluation of echocardiography data in a Chinese pediatric population. The present study ultimately incorporated the Haycock formula into the SZ method regression model. This is consistent with the approach of the D method, which also uses the Haycock formula, and facilitates comparison of these two methods.
In comparing Z scores resulting from the SZ and D methods, it was found that the SZ method produced Z scores closer to zero. This indicates that the SZ method may be more suitable than the D method for use in the Chinese pediatric population. Furthermore, predicted coronary artery diameter mean values and standard deviations differed between North American and Chinese pediatric populations, and the predicted mean value curve provided by the D method had a higher gradient than that provided by the SZ method. When BSA is low, predicted mean values for North American children were lower than those for Chinese children, and when BSA is high, predicted mean values for North American children were higher than those for Chinese children. This indicates that using predictive regression models based on North American pediatric reference values may over- or underestimate coronary artery measurement Z scores in the Chinese pediatric population, which would negatively impact CAD diagnosis and treatment.
We suggest that the D method regression model used for the North American pediatric population is unsuitable for use in the Chinese pediatric population. Factors such as region and race should be taken into account when incorporating automatic calculation functions into echocardiographic equipment and when selecting predictive regression models for clinical applications. The SZ method regression model established during the present study may be more suitable for use in the Chinese pediatric population.
However, we acknowledge certain study limitations. For example, determination coefficients (R2 values) are marginally lower than those determined by previous studies, especially for the RCA4,9. Determination coefficients for the LCA, LAD artery, and RCA obtained using the D method were higher than those obtained using the SZ method. Two possible reasons may account for this observation: differences between multiple participating study sites, or an unbalanced cohort gender ratio. Furthermore, coronary artery diameters were too small to avoid errors in measurement when enlarging images, and it is challenging to ensure inter-site consistency during a multicenter study. Mitigation strategies for such limitations should be considered when designing future studies.