Angiopoietin-like proteins ANGPTL3 and ANGPTL8 have been shown to inhibit lipoprotein lipase, and thus regulate triglyceride level in the circulation. Whether the regulation of lipid metabolism by ANGPTLs is affected by the menopausal status remains unclear. We aimed to assess the relationships between serum ANGPTL3 and ANGPTL8 and atherogenic biomarkers in presumably healthy women during ageing. The study group included 94 women of whom 31 were premenopausal (PRE ≤ 40 years) and 37 were postmenopausal (POST ≥ 52 years). Atherogenic lipid and non-lipid biomarkers and ANGPTLs (ANGPTL3, ANGPTL8) were assayed in serum samples. TG/HDL-C index, non-HDL-cholesterol, remnant cholesterol concentrations, and BMI were calculated. Median levels of ANGPTL3 and concentrations of lipid biomarkers were significantly higher in POST comparing to PRE but ANGPTL8 levels were not different. In PRE, ANGPTL8 levels correlated significantly with TG and TG/HDL-C index while there were no correlations between ANGPTL3 and these biomarkers. In POST both ANGPTLs correlated with TG, sdLDL-C, and TG/HDL-C. ANGPTL8 and sd-LDL-C were the most significant predictors of early triglyceride elevation > 100 mg/dL (1.13 mmol/L) in the whole group and POST whereas the prediction power of ANGPTL3 was negligible in the whole group and non-significant in the subgroups. We demonstrated a significant positive correlation of ANGPTL3 with age category which predisposes to postmenopause. Despite the increase in ANGPTL3 level with ageing the ANGPTL3/ANGPL8 ratio was maintained. In conclusion, ANGPTL8 predicts the early triglyceride elevation better than ANGPTL3, especially in postmenopausal women. The association of ANGPTL3 with triglyceride levels is weaker than ANGPTL8 and depends on menopausal status. We suggest that the choice for the best efficient treatment of dyslipidemia with new inhibitors of angiopoietin-like proteins may depend on the menopausal status.

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.

Scientists have been trying to find the best parameter for laboratory assessment of the risk of cardiovascular diseases (CVD) for decades. Initially, the results of many studies indicated that the analysis of the lipid profile was sufficient to evaluate the risk of CVD. Further studies revealed that more precise laboratory prediction of cardiovascular risk requires quantification of atherogenic lipoproteins. Recently, angiopoietin-like proteins 3, 4 and 8 (ANGPTLs) have been described as important regulators of plasma lipoprotein metabolism and triglyceride homeostasis. Mutations in ANGPTL3 leading to loss of its function have been linked to decreased risk of CVD in humans. Among potential new targets for the management of dyslipidemia, ANGPTL3 may become a considerably promising one.

Disorders of lipid metabolism cause accelerated atherosclerosis and increase cardiovascular risk, which is why lipid profile screening, especially at a young age, should be widely applied. Aim. The aim of the study was to determine the cutoff points for non-fasting lipid parameters in presumably healthy children aged 9-11 years. Material and methods. The study was performed with the use of blood samples taken in non-fasting state from 289 school children of both sexes (152 girls and 137 boys). Routine lipid profile was assessed: TC, LDL-C, HDL-C, and triglycerides. Laboratory measurements were performed in serum samples using a biochemical autoanalyser. Results. In this study we determined the 97.5 percentile values for TC, LDL-C, and triglycerides and the 2.5 percentile values for HDL-C. The upper cutoffs for TC, LDL-C, and triglycerides were found to be 239 mg/dL, 163 mg/dL, and 284 mg/dL, respectively, and the lower cutoff for HDL-C was 37 mg/dL. Conclusions. The upper range of non-fasting total cholesterol was higher by about 30 mg/dL compared to fasting state for a similar age range; the cutoff points in non-fasting children for LDL-C and TG were also higher. The lower cutoff for HDL-C was similar compared to fasting state for the respective age range. The determination of the non-fasting cutoff values for routine lipid profile in the paediatric population is essential for the proper evaluation of the cardiovascular risk because using the reference values for adults may cause an incorrect interpretation of the laboratory results.