The association between serum triglyceride to high-density lipoprotein cholesterol ratio and sarcopenia in community adults: positive or negative?

The serum triglyceride to high-density lipoprotein cholesterol(TG/HDL) ratio has been identied to be positively correlated with a higher risk of sarcopenia in elderly Korean males in previous study. In this study, we aimed to discover the association between TG/HDL ratio and sarcopenia in Chinese community adults, including males and females.


Introduction
Age-related loss of muscle mass and function, termed "sarcopenia", has aroused a great interest all over the world, including China. [1][2][3][4][5] In 2014, the Asian Working Group for Sarcopenia(AWGS) proposed the de nition of the sarcopenia, in which age related loss of muscle mass, plus low muscle strength, and/or low physical performance were essential diagnostic components. [5] In 2019, AWGS de ned "possible sarcopenia" as either low muscle strength or low physical performance only. It is increasingly prevalent in the community, with 5.5-25.7% prevalence of sarcopenia.[6-8] Sarcopenia has become a public health problem, along with the accelerated aging of population.
So far the mechanisms underlying the sarcopenia hasn't been elaborated completely,many factors, such as aging, frailty, malnutrition, cachexia, in ammation and hormonal changes, has been regarded as causes of sarcopenia. [9][10][11][12][13][14][15] Serum lipid pro les are simple laboratory parameters that commonly tested clinically, including fasting serum triglyceride(TG) and cholesterol. Tae-Ha et al. demonstrated that TG to high-density lipoprotein(HDL) cholesterol ratio(TG/HDL) was positively correlated with an increased prevalence risk of sarcopenia in elderly Korean males. [16] Given this nding, we aimed to discover the association between TG/HDL and occurrence of sarcopenia in Chinese community adults, including males and females, and we found the opposite result.

Study population
This cross-sectional study included Chinese community adults participating in regular medical examinations at the First A liated Hospital of Wenzhou Medical University from May 2016 to August 2017. We included individuals who were 18 years or older and who had bioelectrical impedance analysis(BIA) and serum lipid pro les measures. Exclusion criteria for the study were: (1) individuals younger than 18 years old; (2)individuals with a history of stroke, thyroid disease, chronic kidney disease, chronic liver disease or malignant tumor; (3) individuals taking medicine for dyslipidemia.
A total 2613 subjects were enrolled in the study. All data concerning the demographic and clinical characteristics were reviewed and analyzed in accordance with the Declaration of Helsinki. The study was approved by the institutional review board(IRB) of The First A liated Hospital of Wenzhou Medical University and consent was waived by the IRB, given the cross-sectional nature of this study.

Data collection
We collected the data in regard to the health examinations for community adults, included questionnaires containing lifestyle factors and medical histories, and anthropometric, BIA, blood and biochemical measurements.
Lifestyle behaviors were evaluated, including alcohol consumption and smoking. Heavy drinks were de ned as alcohol drinking > 140 g/week for males and > 70 g/week for females. Smoking status was strati ed as 3 types: never(an individual who has never smoked), past(an individual who smoked in the past and abandoned for 2 years at least) and current smokers(an individual who smokes currently and last for 6 months at least).
[18] Hyperuricemia was de ned as a self-reported history of the disease, or serum uric acid(UA) above 7.0 mg/dl in males and above 6 mg/dl in females. [19] After 8-h overnight fasting, the height and weight were measured on the morning. The body mass index(BMI) was calculated as follows: BMI(kg/m 2 ) = weight(kg) / the square of the height(m 2 ).
Overweight was de ned as BMI equal to or more than 25 kg/m 2 .

Statistical analysis
Continuous variables were presented as medians(ranges), while categorical variables were presented as frequencies(percentages). We applied receiver operating characteristics(ROC) curves to evaluate the accuracies of the TG, HDL and TG/HDL ratio for sarcopenia diagnosis. Based on Youden index and area under curve(AUC), we selected the optimal indicator and grouping according to cutoff of the selected indicator(TG/HDL ratio low and high groups). In order to compare the differences between 2 groups, we performed the χ 2 test for categorical variables, and Mann-Whitney test for continuous variables. To weigh the effects of variables on the prevalence of sarcopenia, we applied univariable and multivariable logistic regression analysis. The variables with p value < 0.1 in univariable logistic regression analysis were brought into the subsequent multivariable analysis. Because frequency of sarcopenia distributed unevenly in different population, we also applied subgroup analyses according to different confounding factors. To further identi ed the correlation between TG/HDL ratio and prevalence of sarcopenia, individuals were strati ed by quartiles(Q1: ≤1.72, Q2: 1.72-2.86, Q3: 2.86-4.85 and Q4: >4.85), and prevalence of sarcopenia were compared by χ 2 test.
All analyses were conducted with R version 3.6.1(https://www.r-project.org/). All statistical tests were 2sided, and signi cance level was de ned as p value < 0.05.

Population characteristics
A total of 2613 individuals were enrolled in our analysis, with a median age of 48 years (range: Optimal cutoff of TG/HDL ratio and association between TG/HDL ratio and clinicopathological factors As pre-processing, ROC curves were utilized to evaluate the performances of TG, HDL, and TG/HDL ratio, and to discover corresponding cut-offs for sarcopenia diagnosis. As Fig. 1 showed, the cutoffs for TG(mg/dl), HDL(mg/dl), and TG/HDL ratio were 138.502 mg/dl(sensitivity: 0.718; speci city: 0.481), 42.719 mg/dl(sensitivity: 0.776; speci city: 0.439) and 2.775(sensitivity: 0.671; speci city: 0.546) respectively.
There were 1266 subjects with low TG/HDL ratio(< 2.775) and 1347 subjects with high(TG/HDL ratio ≥ 2.775). The association between TG/HDL ratio and clinical variables were summarized in Table 1.

Subgroup analyses
There were confounding factors existing in this study, including age and overweight, as Table 2 showed.
In addition, gender might be a confounding factor, as Chung et al. proposed that TG/HDL ratio was associated with sarcopenia in elderly Korean males.
[16] Thus, in our study, we chose these 3 factors and conducted further subgroup analyses, which was displayed in Fig. 2.
In age < 65 subgroup, more subjects were diagnosed with sarcopenia in TG/HDL low group than in Correlation between TG/HDL ratio and prevalence of sarcopenia Individuals were strati ed by quartiles into Q1, Q2, Q3 and Q4 groups, respectively. Figure 3 displayed the prevalence of sarcopenia of each group. The prevalence of sarcopenia decreased signi cantly as TG/HDL ratio increased(p < 0.001): 22.6% of Q1, 15.0% of Q2, 10.3% of Q3 and 7.4% of Q4, respectively.

Discussion
In the study, we discovered that TG/HDL ratio was negatively related with prevalence of sarcopenia in Chinese community adults. In the previous research by Tae-Ha et al, higher TG/HDL ratio was positively associated with a higher risk of sarcopenia in elderly Korean men, which was accompanied by the status of insulin resistance.
[16] Compared to the study by Tae-Ha et al, we enrolled a wider group of people, including males and females, with an average age of 48 years(range: 18-91). It might be nationality and gender differences that caused the yield totally different results.
In subgroup analyses, TG/HDL ratio remained the independent association with the risk of sarcopenia in males and females, with the age < 65 years old. But TG/HDL did not show the signi cantly association with sarcopenia in individuals with the age ≥ 65 years old, which was inconsistent with the previous study by Tae-Ha et al. [16] It was speculated that there might be a uctuant association between TG/HDL ratio and frequency of sarcopenia with age. In our study, the proportion of subjects over 65 was 8.8%. A further study enrolling more old people is required in the future.
Lipid pro le is an easy and economic parameter, which is widely used clinically. As a part of lipid pro le, medium-chain TG was veri ed to be a potential nutrient for sarcopenia in a randomized controlled trial. It was because medium-chain TG could activate the ghrelin to increase muscle function. [20] In addition, plasma TG generated from omega 3 fatty acid attenuate muscle loss, which was reviewed by Stella et al. [21] As an important member of lipid pro le, HDL was identi ed to be negatively associated with muscle strength improving.[22-24] Based on these research ndings, the negative correlation between TG/HDL ratio and sarcopenia should be considered. Thus, appropriate supplement of fatty foods might be bene cial to muscle mass and muscle strength, but supplementing to what degree required more further studies.
This study had some limitations. Primarily, because it was a cross-sectional study, a causality could not be developed. Secondly, due to the lack of data, we didn't take new de nition of sarcopenia into consideration, which proposed utilizing the existence of low muscle mass and low muscle strength for the diagnosis of sarcopenia [1]. Thirdly, many of the subjects enrolled in our study were younger than 65, and the population was Chinese community adults without any severe diseases. Thus, it might be restrictive to apply to the older and critical patients. Last, cutoff of TG/HDL ratio was de ned by ROC curve with a restrictive sensitivity of 0.671 and speci city of 0.546. Therefore, the cutoff of 2.775 was for reference of grouping individuals by TG/HDL ratio only.
In conclusion, our study indicated that low TG/HDL ratio was a promising risk marker for sarcopenia. Further prospective studies, with a larger sample size and more comprehensive data, are required to validated the association between TG/HDL ratio and the frequency of sarcopenia.   Figure 1 Receiver operating characteristic(ROC) curve analyses of the TG, HDL and TG/HDL ratio in sarcopenia status.