Total and High Density Lipoprotein Cholesterol Ratio is Associated With Metabolic Syndrome Among Very Elderly in Chengdu, China

metabolic syndrome (MetS) is currently a major public health challenge worldwide. This study was to investigate the potential association between total and high density lipoprotein cholesterol ratio (THR) and MetS in very elderly population in Chengdu. totally 1056 very elderly (aged ≥ 80 years ) in Chengdu community were enrolled in this cross-sectional study. Geographic characteristics of participants were collected and laboratory measurement were performed. Metabolic syndrome (MetS) was dened according to Chinese and international diabetes federation (IDF) criteria respectively. Logistic analysis was used to investigate the potential association between THR and MetS. The receiver operating characteristic curve (ROC) analysis was used to evaluate the eciency of THR in predicting MetS. The both and IDF was (95%CI: and 0.727 (95%CI: 0.669-0.786, P<0.001) for predicting MetS according to Chinese and IDF criteria, respectively.


Introduction
Metabolic syndrome (MetS) is nowadays a big challenge worldwide, which is characterized by a cluster of several metabolic disorders, i.e. abdominal obesity, dyslipidemia, hypertension and dysregulation of glucose [1,2]. Despite unclear common pathophysiological mechanism, MetS has been recognized to increase the risk of diabetes mellitus (DM) and series arteriosclerotic cardiovascular disease(ASCVD), i.e. coronary heart disease, cardiovascular mortality [2,3], cognitive impairment [4] and all cause mortality [5]. Lifestyle modi cation and risk factors management are currently recommended to decrease the risk of subsequent cardiovascular diseases. Previous studies [6,7] have emphasized the importance of dyslipidemia as one component for the diagnosis of MetS and recent epidemiological study [8] has demonstrated that more than one-thirds Chinese adults in 2010 suffered from MetS, which was similar to the epidemiological situation in USA in 2014. Furthermore, the prevalence of MetS in Americans older than 60 years was 1.6 fold higher [9], which shows that MetS components are more likely to cluster together in older population. Dyslipidemia (hypertrigleicemiea and hypo-high density lipoproteinemia) is an important component for MetS, which plays a critical role in the progression from MetS to DM and ASCVD [6,7]. Some studies [10][11][12] have investigated the potential ability of total to high-density lipoprotein cholesterol (THR) and triglyceride to high-density lipoprotein cholesterol ratio to predict ASCVD in young and middle aged population, while few about very elderly has been reported until now.
Therefore, this study aimed to explore the potential association between THR and MetS among community very elderly population in Chengdu.

Study population
This study was designed to investigate cardiovascular and metabolic risk factors in general community very elderly (≥ 80 years old) in Chengdu, which locates in the southwest of China [13]. From 2013 to 2015, a representative sample of very elderly in community were recruited by using of a strati ed threestage cluster sampling design, which was described previously elsewhere [13]. Totally, 1056 very elderly from 20 residential communities were enrolled according to registration data from local government. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as re ected in a prior approval by the ethics committee of the second people's hospital of Chengdu. And all participants have given informed consent.

Demographic data collection and laboratory test
Well trained physicians and nurses were responsible for demographic data collecting (such as medical history, lifestyle, cardiovascular and metabolic risk factors) by a questionnaire-based face to face interview with a standardized questionnaire. The body mass index (BMI) was de ned as weight in kilograms divided by the square of the height in meters. Blood pressure (BP) were measured three times in a sitting position by using a standardized automatic electronic sphygmomanometer (HEM-7300, Omron Kyoto, Japan) according to the Chinese guideline [14] and average values were calculated and included in statistical analysis.

Diagnostic criteria of MetS
In this study, MetS were de ned according to the Chinese guideline for dyslipidemia management [15] and the Consensus Worldwide De nition from international diabetes federation (IDF) [16] respectively as follows: Chinese criteria : MetS should ful ll any three or more of the following items: abdominal obesity (waist circumference (WC) ≥ 90 cm in men and ≥ 85 cm in women) , fasting TG ≥ 150 mg/dL (1.7 mmol/L), fasting HDL-C < 40 mg/dL (1.0 mmol/L), FPG ≥ 110 mg/dL (6.10 mmol/L) or 2 hour blood glucose after glycemic load ≥ 140 mg/dL (7.80 mmol/L) or anti-diabetic treatment, and BP ≥ 130/85 mmHg or antihypertensive treatment.
IDF criteria : abdominal obesity with ethnic-speci c WC cut-points (≥ 90 cm for Chinese men and ≥ 80 cm for women) and ful lls two items of the following: TG ≥150 mg/dL (1.7 mmol/L) or treatment for hypertriglycerides, HDL-C <40 mg/dL (1.03 mmol/L) in men or <50 mg/dL (1.29 mmol/L) in women or treatment for low HDL-C, FPG ≥100 mg/dL (5.6 mmol/L) or previously diagnosed type 2 diabetes, and BP ≥130/85mmHg or treatment for hypertension.

Statistical analysis
All statistical analysis were performed by using SPSS software (Version 22.0, SPSS Inc, Chicago, IL).
Continuous variables are expressed as mean ± standard deviation and requencies are presented as percentages. Statistical comparison of continuous variables between groups was conducted using ANOVA or Kruskal-Wallis test, whereas x 2 test was applied to compare frequencies. Multiple logistic regression models were used to evaluate the potential association between THR and MetS. The receiver operating characteristic curve (ROC) analysis was used to evaluate the e ciency of THR in predicting MetS according to different criterion. A two-sided P value < 0.05 was considered statistically signi cant.

Baseline characteristics
Totally, there were 1056 participants enrolled in this study and 1038 of them were included in the nal statistical analysis. In this study population, more very elderly women suffered from MetS and participants with MetS were younger, more likely to smoke and drink currently. And they had relatively higher WC, body weight, BP, FPG, non-HDL-C, serum uric acid, total and high density lipoprotein cholesterol ratio (THR) and lower eGFR.

Logistic regression analysis for MetS risk
The logistic analysis found that THR was associated with the increased risk of MetS both according to the Chinese criteria (odds ratio (OR): 3.211, 95% con dence interval (

Dyslipidemia and MetS
It is well known that MetS is a cluster or combination of several metabolic abnormalities without fully understood pathogenesis currently [17]. Genetic variants in MetS are associated especially with glucose metabolism or lipid metabolism. And genetic susceptibility may exist within adipose tissue, in insulin signaling pathways, and in regulation of individual components of MetS. Insulin resistance or hyperinsulinaemia may contribute to obesity-and DM related hypertension and possibly also promote dyslipidaemia in MetS. Obesity, lifestyle, chronic in ammation and circadian rhythm disturbances may also contribute to the genesis of MetS [18]. Dyslipidaemia in MetS is mainly characterized by highly atherogenic small dense low-density lipoprotein and small triglyceride-rich dense high-density lipoprotein particles [7]. One recent study has identi ed more than thirty new lipids contributing to key metabolic risk factors, i.e. obesity, dyslipidemia and dysglycemia in Framingham heart study [19]. Triglyceride could result in endothelial dysfunction and foam cells formation by accelerating the oxidation of LDL-C. While in contrast, HDL-C play an antiatherosclerosis role through transporting excess cholesterol to liver. Therefore, hypertrigleicemiea and hypo-high density lipoproteinemia play an important role in the pathogenesis in MetS. A previous study has reported that hypertrigleicemiea with a prevalence of 10.8% is the main type of lipid disorders in Chinese older than 60 years [20], especially in older women, which is in accordance with the result of our previous study [13]. In the present study, all levels of LDL-C, TC and TG, WC and BMI were higher in participated very elderly than the mean level in Chinese adults, while FBG was similar to which in general adults [8,13]. Especially, the prevalence of abdominal obesity and hypertrigleicemiea was also higher in this very elderly population than which in general Chinese adults and middle aged population in this area [13] and the prevalence of hypercholesterolaemia (35.8%) is notably higher than that of hypertrigleicemiea (21.6%). Aside from high prevalence of hypertension, these dramatic characteristics of components above contribute signi cantly to the relatively high prevalence of MetS in this very elderly population.

THR and MetS
Among very elderly participants in this study, TC level and THR were signi cantly higher and HDL-C level was signi cantly lower in participants with MetS. Previous studies [10,11,21,22] have already demonstrated that TC/HDL and TG/HDL ratio are associated with MetS in general population. This current study has also investigated that there is an association between THR and MetS either according to Chinese or IDF criteria in very elderly population. However, statistical analyses have demonstrated that THR has a higher ROC and larger ORs for MetS prediction according to Chinese criteria than IDF criteria. And interestingly, in this very elderly population, more very elderly women were found to suffer from MetS according to both criteria, which is different from the results of a previous study in young and middle aged Chinese [20]. Although the main differences of MetS de nition between Chinese and IDF criteria are the criteria of WC and HDL cholesterol cut points, the prevalence of abdominal obesity, hypercholesterolaemia and hypertrigleicemiea in this very elderly women were higher than which in young and middle aged women, which may be one of the potential explanation for the difference for predicting MetS according to different criterion.
Our study has also suggested that the ability of THR for predicting of MetS is similar to which of FPG, although it is inferior to which of TG in this very elderly population. TG and FPG abnormalities are important components of MetS according to different criterion. Except for these direct measured parameters for MetS diagnosis, THR might be a reliable indirect measured parameter for MetS predicting before the absolute increase of directly measured lipid parameters become apparent.

Conclusions
In conclusion, The main nding of this study is that THR is associated with the increase risk of MetS and it may be a simple predictor of MetS among very elderly population in Chengdu. According to the high prevalence of abdominal obesity, dyslipidemia and glucose abnormality in this study and the oil rich local daily food style, proper lifestyle modi cation, especially dietary changes are still needed to be emphasized in the prevention of MetS and ASCVD in very elderly, although the life expectancy in this population is short.
Several limitations should be considered in this study. First, this cross-sectional study could not describe any causality. Second, the study population in this study is very elderly in southwest of China, whether current ndings could be generalized to younger population or other very elderly population in other area of China needs further clari cation from further longitudinal prospective studies.