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Correspondence: Ishwarlal Jialal, MD, PhD, Veterans Affairs Medical Center, UC Davis, Staff Physician, VA Medical Center, 10535 Hospital Way, Mather, CA 95655, USA (E-mail: [email protected]).
The hypertriglyceridemia waist (HTGW) phenotype is associated with visceral adiposity, metabolic syndrome, type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD). Since the cut points for abdominal obesity and hypertriglyceridemia, differ for different race groups, investigators have developed the product of triglycerides (TG) and waist circumference (WC) as the TG.WC index. We compared this TG.WC index to the TG:HDL-C ratio in the National Health and Nutrition Examination Survey (NHANES) study to predict metabolic syndrome (MetS) in African Americans (AAs).
Methods
Participants included 950 AAs and 2651 non-Hispanic Whites (NHWs) for comparison from the NHANES data set. Persons with diabetes, ASCVD and macro-inflammation were excluded. Fasting blood was obtained for lipids, insulin and CRP.
Results
In AAs and NHWs, both the TG.WC index and TG:HDL-C ratio were significantly increased in MetS patients. Also, both increased with increasing severity of MetS and correlated with all features of MetS, insulin resistance and inflammation. Receiver operating characteristic (ROC) curve analysis showed that discrimination with TG.WC for MetS was superior to the TG:HDL-C ratio especially in AAs.
Conclusions
TG.WC index is a superior biomarker to TG:HDL-C for predicting MetS in AAs despite their lower TG levels.
The issue of differential health outcomes based on race clearly pertains to the area of cardio-metabolic disorders.
It has been shown, using cut points for non-Hispanic whites (NHWs), that the hypertriglyceridemia waist (HTGW) phenotype, the simultaneous presence of increased waist circumference (WC) and hypertriglyceridemia, is strongly associated with cardio-metabolic risk, metabolic syndrome (MetS), type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD).
Hypertriglyceridemic waist phenotype and lipid accumulation product: two comprehensive obese indicators of waist circumference and triglyceride to predict type 2 diabetes mellitus in Chinese population.
Due to the wide variation in waist circumference criteria in different races, investigators have instead quantitatively defined the TG.WC index as the product of WC and TG, using both as continuous variables. This new TG.WC index classified patients for their cardio-metabolic risk like the original definition of the HTGW phenotype.
Screening for metabolic syndrome using an integrated continuous index consisting of waist circumference and triglyceride: a preliminary cross-sectional study.
MetS is a common global disorder comprising a cardio-metabolic cluster that predisposes to both type 2 diabetes mellitus (T2DM) and atherosclerotic cardiovascular disease (ASCVD).
Recently it was shown, using this large National Health and Nutrition Examination Survey (NHANES) data set, that the ratio of triglycerides (TG) to high-density lipoprotein cholesterol (HDL-C) (TG:HDL-C) ratio is a better biomarker of MetS in AAs compared to the CRP:HDL-C ratio, despite their lower TG and higher CRP levels.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
In an attempt to improve the assessment of cardio-metabolic disease risk in AAs, in the present report, we compared, the TG.WC index to the TG:HDL-C ratio in AAs and NHWs in the large NHANES study to determine which is the superior biomarker for MetS.
Methods
Data from the US general population National Health and Nutrition Examination Survey (NHANES) cycles from 2005 to 2018) (https://www.cdc.gov/nchs/nhanes/index.htm) collected by the Centers of Disease Control and Prevention (CDC),
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
was used for analysis. NHANES was approved by the National Center for Health Statistics institutional review board and written consent was obtained from all participants. The work described has been carried out in accordance with the Code of Ethics of the World Medical Association for experiments involving human subjects. As described previously, the data set was restricted to NHW and non-Hispanic AA participants of either sex aged 20-80 years.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
WC was measured to the nearest 0.1 cm by trained personnel at the level of the ilium following normal respiratory expiration. Controls (non-MetS) needed to have 2 or fewer features of MetS and not be on blood pressure medications. To minimize confounding by other variables and to better focus on MetS in a nascent stage, exclusion criteria included diabetes, smoking and macro-inflammation (defined by a hsCRP >10mg/L and or an increased total white blood cell count).
A total of n = 3541 individuals (2635 controls and 906 MetS) were identified in this study. The TG.WC index was calculated as the product of triglycerides (mmol/L) x waist circumference (cm).
SAS version 9.4 (SAS Institute, Cary, NC) was used for statistical analysis. Stratified by race, TG.WC index and TG:HDL-C ratio were expressed as median and interquartile ranges. The MetS and control groups were compared with the Wilcoxon Rank Sum test. Trend analysis of the ratios associated with increasing number of characteristics of MetS in subjects was evaluated using the Jonckheere-Terpstra (J-T) test. After combining the control and MetS groups, Spearman rank correlation coefficients were determined to assess the association between TG.WC index and TG:HDL-C ratio and metabolic variables. Logistic regression models were used to compute receiver operating characteristic (ROC) curves. Comparison of areas under correlated ROC curves and 95% confidence intervals (CI) for the ROC area under curve (AUC) for biomarkers and biomarker differences were determined. The Youden Index was defined as the maximum value of sensitivity + specificity - 1. Significance was defined as a 2-sided p value <0.05.
Results
In this study, the same cohort from the NHANES population in which the TG:HDL-C ratio was recently shown to be a valid biomarker of MetS in AAs was used.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
Briefly, the participants with MetS had significant differences in all cardio-metabolic features. In AAs the median WC, systolic BP, glucose, TG and HDL-C were significant different compared to controls, p < 0.0001: WC 109.5 cm vs 93.2 cm, systolic BP 136 mmHg vs 118 mmHg, glucose 112 mg/dl vs 95 mg/dl, TG 118 mg/dl vs 68 mg/dl and HDL-C 46 mg/dl vs 57 mg/dl. Also, HOMA-IR 1.83 vs 0.97 and hsCRP 2.9 mg/L vs 1.4 mg/L were significantly higher in AAs with MetS, p < 0.0001. As reported previously, AAs with MetS had lower TG levels (118 mg/dl vs 173 mg/dl, p < 0.001) and higher HDL-C levels (46 mg/dl vs 43 mg/dl, p = 0.0008) compared to NHWs.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
ratio and TG.WC index were significantly increased in patients with MetS compared to controls, p < 0.0001 (Fig. 1). Both ratios increased significantly with increasing severity (number of cardio-metabolic features) of MetS, using the J-T test for trend; p < 0.0001 for both. In both AAs and NHWs patients, the TG.WC index was significantly correlated with all five features of MetS, as well as with hsCRP and HOMA-IR (Table 1). The TG.WC index was significantly higher in NHWs (median and inter-quartile range) 211 (160–280) compared to AAs 155 (99–233) with MetS, p < 0.0001. The TG:HDL-C ratio was also significantly higher in NHWs compared to the AAs in both the MetS and control groups, as previously reported.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
Fig. 1A comparison of the TG.WC Index between MetS and controls in both races. Abbreviations: AAs, African Americans; MetS, metabolic syndrome; NHWs, non-Hispanic Whites; TG, triglycerides; WC, waist circumference.
ROC curve analyses for predicting MetS for the two indices is shown in Fig. 2. ROC-AUC (95% CI) for TG.WC for AAs and NHWs were excellent, according to the criteria of Hosmer and Lemeshow
: 0.82 with 95% confidence intervals (CI) between 0.79–0.86 and 0.86 with 95% CI of 0.85-0.88. The ROC-AUC for NHWs compared to AAs was significantly higher, p = 0.04. As reported recently
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
the ROC-AUC for TG:HDL-C was also significantly greater in NHWs compared to AAs, 0.85 (95% CI, 0.83-0.87) versus 0.79 (95% CI, 0.75-0.83) respectively, p = 0.004. In both the AA and NHW groups, the TG.WC index was a better predictor of MetS than the TG:HDL-C ratio, as shown in Fig. 2: in AAs 0.82 versus 0.79, AUC difference 0.03 (0.01, 0.05), p = 0.001; in NHWs 0.86 versus 0.85, AUC difference 0.01 (0.003, 0.02), p = 0.004. The improvement in the AUC by the TG.WC index for the NHWs group was smaller. The Youden index of TG. WC was computed to provide a practical cut point, it was 113 for AAs (sensitivity 0.78 and specificity 0.71) and 154 for NHWs (sensitivity 0.82 and specificity 0.77).
Fig. 2Comparison of receiver operating characteristic (ROC) area under the curves (AUC) between TG.WC index and TG:HDL-C ratio in AAs (p = 0.001) and NHWs (p = 0.004). Abbreviations: AAs, African Americans; HDL-C, high-density lipoprotein cholesterol; MetS, metabolic syndrome; NHWs, non-Hispanic Whites; TG, triglycerides; WC, waist circumference.
Given the disparities in health care, particularly in AAs, we decided to focus on how well current and new biomarkers of cardio-metabolic risk work in this group. In the present report, we tested the TG.WC index as a biomarker of MetS since it uses both measures as continuous variables. The original criteria for the HTGW phenotype were based on NHWs data in Canadians and not AAs and was shown to severely underestimate risk in AAs.
In the present report, we showed in both AAs and NHWs patients in this large cohort based on the US general population (NHANES) that the TG.WC index is superior to the well-known TG:HDL-C ratio in predicting MetS. In fact, the TG.WC index AUC compared to the TG:HDL-C AUC was significantly greater in AAs compared to the corresponding differences in NHWs. Furthermore, the TG.WC index correlated with all features of MetS, inflammation and insulin resistance and increased with increasing severity of MetS. Also, we provide the Youden index of 113 as a reasonable and practical decision point of increased cardio-metabolic risk in AAs. Despite the deficiencies in criteria to diagnose MetS in AAs based on their more favorable TG and HDL-C levels the most recent prevalence data (2011–2012) shows similar prevalence of MetS in NHWs and AAs of 37.4% and 35.5% respectively.
We believe our simple TG.WC index will facilitate early and greater diagnosis of MetS in AAs resulting in better management to forestall the sequalae of T2DM and ASCVD.
Some authors have used an index comprising 3 of the 5 features of MetS, glucose, TG and WC.
Since one needs 3 of the 5 features to sustain a diagnosis of MetS, we are unclear of the added value of this measure as a biomarker. Nonetheless in a Spanish population (n = 314), the TG.WC index was equivalent in predicting MetS compared to the TG.Glucose.WC index with similar ROC-AUC of 0.81 for both.
We strongly believe that biomarker research to define MetS should be confined to 2 or fewer features and metabolomics or proteomic biomarkers since 3 features define the syndrome and are cumbersome for clinical and research use.
Conclusions
In conclusion, in this study we show that the novel TG.WC index, using both as continuous variables instead of cut points defined for NHWs, is a superior measure of predicting MetS in African Americans than the more commonly used TG:HDL-C ratio. Furthermore, we provide a cut point using the Youden index of 113 to define cardio-metabolic risk in AAs. Thus, with a fasting lipid profile and tape measure one can assess cardio-metabolic risk at the bedside. In future studies, it will be instructive for investigators with other larger data sets comprising AAs to confirm our novel findings.
Source of funding
There was no funding for this research.
Declaration of Competing Interest
No conflicts of interest, financial or otherwise, are declared by any of the authors.
Acknowledgments
We thank the volunteers for participating in this study. We thank Maureen Samson from NIH for providing us access to the NHANES data.
References
Airhihenbuwa C.O.
Liburd L.
Eliminating health disparities in the African American population: the interface of culture, gender, and power.
Hypertriglyceridemic waist phenotype and lipid accumulation product: two comprehensive obese indicators of waist circumference and triglyceride to predict type 2 diabetes mellitus in Chinese population.
Screening for metabolic syndrome using an integrated continuous index consisting of waist circumference and triglyceride: a preliminary cross-sectional study.
A comparison of the ratios of C-reactive protein and triglycerides to high-density lipoprotein-cholesterol as biomarkers of metabolic syndrome in African Americans and non-Hispanic Whites.
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