Characteristics and reference values of the atherogenic index of plasma in an adult population in China

To the Editor: The atherogenic index of plasma (AIP) is derived from the logarithmic conversion of the ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C). It comprehensively reflects plasma lipid homeostasis. AIP has been reported to be related to cardiovascular disease (CVD) in population-based studies,[1] and is regarded as a potential independent predictor for CVD risk in clinical practice. Currently, there are limited data on the characteristics of AIP values in China. We examined the differences in AIP values among ethnic groups based on multiethnic Chinese population data. The reference values of AIP in Chinese adults were established, and their variation tendencies according to age were identified. This study was based on the China National Health Survey (CNHS),[2] a large cross-sectional population-based survey from 2012 to 2017 in China. Fifty urban communities and 90 villages from the 11 provinces were selected as the survey areas in CNHS according to strata factors including geographical regions, distribution of minority populations, degree of urbanization, and level of socioeconomic development. The study was approved by the Bioethical Committee of the Institute of Basic Medical Sciences, the Chinese Academy of Medical Sciences, Beijing, China (No. 028-2013). Written informed consent was obtained from all participants. At the time when we conducted this study, data from three provinces were not available due to data cleaning. Hence, for this study, we applied and obtained 37,567 records of CNHS from eight localities, including the Yunnan, Hainan, Guizhou, Gansu, Shaanxi, and Heilongjiang provinces and the Xinjiang Uygur autonomous region and Inner Mongolia autonomous regions. Basic characteristics of the participants were collected. Included subjects are individuals aged from 20 to 80 years. Ineligible participants were excluded due to missing data on any among age, sex, body mass index, tobacco use, blood pressure, or medical records or due to self-reported neoplastic, respiratory, hepatic, renal, hematologic, or other non-cardiovascular chronic diseases that may significantly affect the laboratory tests. Basic characteristics of the participants were tabulated. AIP was calculated by common logarithm of TG/HDL-C. Subgroup analyses were conducted for the mean AIP values in different ethnic (Han, Uyghur, Yi, and Bouyei) and age groups. To obtain the reference AIP value of the adult population in China, the 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, and 97.5th percentiles of AIP were calculated according to sex and age. Statistical analyses were completed in R (version 4.0.2, 2020, https://www.R-project.org/). A two-sided P value <0.05 was regarded as statistically significant. The study flowchart is shown in Supplementary Figure 1, https://links.lww.com/CM9/B78. The final analysis included 30,236 participants (11,752 men and 18,484 women). Supplementary Table 1, https://links.lww.com/CM9/B78 shows the basic characteristics of the eligible participants grouped by sex. The mean age of the subjects was 48.39 ± 13.53 years, and 64.5% of the participants lived in northern China. The mean AIP of all participants was 0.01 ± 0.34, and the difference between men and women was noteworthy (0.10 ± 0.35 in men and −0.04 ± 0.31 in women, mean difference = 0.14, 95% confidence interval −0.15 to −0.13, P < 0.001). Mean AIP values in the population as grouped by age and ethnic group are shown in Supplementary Table 2, https://links.lww.com/CM9/B78. Among participants of all ages, the Han population had the highest AIP values, while the Bouyei population had the lowest AIP values. This was especially apparent in older age groups (age groups ranging from 50 to 80 years). The AIP values according to age group in different ethnic groups are shown in Supplementary Figure 2, https://links.lww.com/CM9/B78. Differences in male and female participants were also observed, and men had higher AIPs than women in most subgroups. According to the whole population analysis, the AIP values continued to rise from early adulthood and became stable in their 50s. Similar to the trend shown in the entire population, the later AIP values in women became stable, and the highest mean value was in the age group ranging from 60 to 69 years. In men, however, the highest mean value of AIP was found in the age groups ranging from 30 to 49 years. The AIP values of male participants rose in early adulthood, became stable for years, and began to fall slightly when the participants were aged ≥50 years. Notably, adult men had higher AIP values than women of the same age until the values became approximate in old age. Table 1 shows the age-specific distributions for AIP. In men aged 30 to 39 years, the reference values (2.5th–97.5th percentiles) were −0.45 to 0.94. For men in their 40s, the range was −0.50 to 1.00, and the values fell in −0.52 to 0.60 in men aged from 70 to 80 years. For women in their 20s, the reference values ranged from −0.64 to 0.38, while the values rose to −0.48 to 0.76 in women aged 50 to 59 years. The fluctuations of the 95th percentiles in both men and women were greater than the 5th percentiles [Supplementary Figure 3, https://links.lww.com/CM9/B78]. Our study showed that the AIP values varied with different subgroups of age, sex, and ethnic group in the Chinese adult population. The reference values of AIP fluctuated with increasing age and had different trends between men and women. AIP values increased progressively in men, reaching peak values between 40 and 49 years of age and declining thereafter. In women, the AIP values continued to increase until menopause (approximately the age of 50 years and older). As expected, the variations in AIP values with aging were similar to the previously reported TG trends in both men and women.[3] Age-relevant changes in AIP values indicate the importance of determining age-specific abnormalities in AIP because applying the same criteria for adults would underestimate the severity of plasma lipid homeostasis in younger individuals. More importantly, appropriate subgroup reference values of AIP are able to help us in the early detection of rising risk for related diseases, which is crucial for CVD prevention. In the ethnic group analysis, the AIP values of Hans and Uyghurs were found to be significantly higher than those in the other two populations. The Bouyei people had the lowest AIP values in both sexes, which was consistent with the body fat level results reported in a previous study.[4] These ethnic variations in AIP values could be explained by various genetic backgrounds, diverse lifestyles, and social-economic factors in these populations. Table 1 - Reference values of AIP percentiles in Chinese adult population. Percentile Age group (years) N 2.5th 5th 10th 25th 50th 75th 90th 95th 97.5th Whole population All 30,236 −0.55 −0.47 −0.39 −0.22 −0.02 0.22 0.45 0.60 0.75 20–29 3152 −0.62 −0.56 −0.48 −0.35 −0.18 0.04 0.27 0.43 0.54 30–39 4995 −0.57 −0.51 −0.42 −0.27 −0.08 0.18 0.43 0.60 0.74 40–49 7789 −0.54 −0.47 −0.38 −0.21 −0.01 0.22 0.45 0.61 0.78 50–59 7363 −0.49 −0.42 −0.33 −0.17 0.04 0.27 0.49 0.65 0.82 60–69 5079 −0.52 −0.43 −0.34 −0.18 0.02 0.25 0.46 0.62 0.74 70–80 1858 −0.50 −0.43 −0.35 −0.20 0.00 0.20 0.41 0.53 0.61 Men All 11,752 −0.51 −0.43 −0.32 −0.15 0.07 0.32 0.55 0.70 0.87 20–29 1226 −0.53 −0.46 −0.37 −0.23 −0.03 0.20 0.42 0.55 0.69 30–39 1893 −0.45 −0.37 −0.28 −0.11 0.13 0.38 0.62 0.77 0.94 40–49 2850 −0.50 −0.39 −0.28 −0.09 0.14 0.38 0.61 0.78 1.00 50–59 2820 −0.53 −0.43 −0.31 −0.13 0.10 0.34 0.58 0.72 0.89 60–69 2126 −0.55 −0.46 −0.36 −0.19 0.01 0.25 0.46 0.62 0.73 70–80 837 −0.52 −0.47 −0.38 −0.23 −0.03 0.18 0.39 0.51 0.60 Women All 18,184 −0.56 −0.49 −0.42 −0.26 −0.07 0.15 0.36 0.50 0.65 20–29 1926 −0.64 −0.59 −0.52 −0.40 −0.26 −0.08 0.11 0.24 0.38 30–39 3102 −0.60 −0.54 −0.46 −0.34 −0.17 0.02 0.24 0.36 0.48 40–49 4939 −0.56 −0.49 −0.41 −0.26 −0.08 0.11 0.33 0.45 0.59 50–59 4543 −0.48 −0.42 −0.34 −0.19 0.01 0.22 0.42 0.56 0.76 60–69 2953 −0.50 −0.41 −0.33 −0.17 0.03 0.26 0.47 0.61 0.74 70–80 1021 −0.46 −0.40 −0.33 −0.17 0.03 0.24 0.42 0.54 0.62 AIP: Atherogenic index of plasma. Adding AIP to conventional risk factors improved coronary artery disease risk discrimination in Asian Indians.[5] This affordable index is a promising alternative for effective cardiovascular risk estimation, especially in developing countries.[6] A major advantage of the current study on reference value establishment is that different areas, especially remote areas, and multiple ethnic groups in China were taken into consideration, making the samples more representative. This study may have some limitations. CNHS investigators did not acquire the local population size during the design of sampling process, and so we cannot address the sampling probability in the analysis. Discrete age group analyses may have influenced the clinical implications in assessing cardiovascular risk for certain individuals. Huge heterogeneity regarding living environment, health-related behaviors, diet, socio-economic factors, and other factors may exist in the same ethnic group, yet detailed information pertaining to these aspects was not collected in our cross-sectional survey, which was conducted in a relatively short period of time at each field survey site. In summary, the AIP value differs in different age, sex, and ethnicity subgroups in the Chinese adult population. Future studies and clinical practices concerning AIP may need to consider the reference values in different populations. Acknowledgments We thank all the local clinical and Center for Disease Control and Prevention staff who contributed their valuable efforts in collecting the data for this research project. We also thank Dr. Ke Xu (Department of Endocrinology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China), Dr. Dongping Ning (Department of Pediatrics, Linfen Central Hospital, Linfen, China), and Dr. Xianxian Yuan (Division of Endocrinology and Metabolism, Department of Obstetrics, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China) for their help in the data cleaning. Conflicts of interest None.