Key result
Serum ANGPTL8 strongly discriminates hypertriglyceridemia in women with an AUC of ~0.83, outperforming men.
Why the study?
ANGPTL3 and ANGPTL8 regulate lipoprotein lipase and may reflect cardiovascular risk, prompting assessment of their gender-specific relationships with atherogenic lipid biomarkers and obesity in non-diabetic adults.
Do the associations of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and hypertriglyceridemia differ by sex and obesity status in non-diabetic adults?
Cross-Sectional (n=238)
Do the associations of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and hypertriglyceridemia differ by sex and obesity status in non-diabetic adults?
Answers are grounded in this paper and cite their sources.
Demonstrates distinct sex-specific associations where ANGPTL8 strongly predicts hypertriglyceridemia in women while ANGPTL3 is more closely linked to atherogenic lipids in men, suggesting sex differences should be considered when developing ANGPTL-targeted lipid-lowering therapies.
Hypertriglyceridemia is an independent risk factor for coronary artery disease. Lipoprotein lipase (LPL) plays an essential role in the metabolism of triglyceride-rich lipoproteins (TRLs). Angiopoietin-like proteins ANGPTL3 and ANGPTL8 are shown to be important regulators of LPL activity. Increased concentrations of these proteins may reflect cardiovascular risk, and the treatment of patients with dyslipidemia with ANGPTLs inhibitors may decrease this risk. We assessed the gender-specific relationships of serum ANGPTL3 and ANGPTL8 with atherogenic lipid biomarkers and obesity in non-diabetic adults. The study comprised 238 participants aged 25-74 [122 with triglycerides (TG) <150 mg/dL (<1.7 mmol/L) and 116 with hypertriglyceridemia]. Total cholesterol, HDL-cholesterol, LDL-cholesterol, TG, C-reactive protein (CRP), glycated hemoglobin, apolipoprotein B, small dense LDL-C (sd-LDL-C), ANGPTL3, and ANGPTL8 were measured. Non-HDL-cholesterol, remnant cholesterol (remnant-C) concentrations, and body mass index (BMI) were calculated. Results: Women and men did not differ in terms of age, CRP levels, the percentage of obese subjects, and concentrations of atherogenic lipid biomarkers, except higher TG in males and higher ANGPTL3 concentrations in females. Positive correlations of both ANGPTLs with TG, remnant-C, and sdLDL-C levels were found in females. In males, only ANGPTL3 correlated positively with atherogenic biomarkers, but there were no correlations with ANGPTL8. Concentrations of ANGPTL3 were higher in obese men, whereas ANGPTL8 levels were higher in obese women. In women alone, ANGPTL8 showed very good discrimination power to identify subjects with hypertriglyceridemia (AUC = 0.83). Contrary to this, ANGPTL3 was a better discriminator of hypertriglyceridemia (AUC = 0.78) in male subjects. Regression models, adjusted for age, sex, and BMI showed a weak but significant effect of ANGPTL8 to increase the risk of hypertriglyceridemia. Conclusions: In females, ANGPTL8 is more strongly associated with TRLs metabolism, whereas in males, ANGPTL3 plays a more important role. We suggest sex differences be taken into consideration when applying new therapies with angiopoietin-like proteins inhibitors in the treatment of dyslipidemia.
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Murawska et al. (2021) conducted a cross-sectional in Hypertriglyceridemia and dyslipidemia in non-diabetic adults (n=238). Serum ANGPTL3 and ANGPTL8 concentrations vs. Triglycerides <150 mg/dL vs. hypertriglyceridemia (TG ≥150 mg/dL), stratified by sex and obesity was evaluated on Discrimination of hypertriglyceridemia (TG ≥150 mg/dL) by serum ANGPTL8 and ANGPTL3 (AUC 0.83 (ANGPTL8 in females) vs AUC 0.54 (ANGPTL8 in males), p=<0.0001). Serum ANGPTL8 discriminated hypertriglyceridemia well in women (AUC 0.83) compared to men (AUC 0.54, p<0.0001), whereas ANGPTL3 was a better discriminator in men (AUC 0.78).
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