Impact of Hypertriglyceridemia on Lipoprotein Function in Familial Combined Hyperlipidemia

Patients with familial combined hyperlipidemia (FCH) may have more severe pro-atherogenic changes in the presence vs absence of hypertriglyceridemia, according to a study published in Biomedicines.

In this observational study, patients with FCH were examined before and after statin treatment for dyslipidemia for ≥3 months (n=25). Patients were classified according to their triglyceride (TG) levels: fasting TG >2.26 mmol/L were (HTG group; n=12) and TG levels <2.25 mmol/L (NTG group; n=13). Normolipidemic and normoglycemic individuals constituted the control group (n=15). The lipid profiles, C-reactive protein (CRP) levels, and the qualitative characteristics of lipoproteins were assessed.

All lipid parameters were higher in patients with vs without FCH, with the exception of high-density lipoprotein-cholesterol (HDL-c) levels which were lower in patients in the HTG group. The levels of CRP and plasma apolipoprotein J and the activity of lipoprotein-associated phospholipase A2 (Lp-PLA2) were higher in patients with FCH vs control individuals. After treatment with statins, the increases in CRP and Lp-PLA2 were no longer observed.

Patients with FCH and HTG vs NTG were found to have more frequently altered lipoprotein composition, resulting in dysfunctional low- (LDLs; eg, smaller molecules, more prone to oxidation) and high-density lipoproteins (HDLs). HDLs in patients with FCH from both groups were found to be less anti-anti-inflammatory compared with those in control individuals.

Patients in the HTG group had lower Lp-PLA2 activity, compared with participants in the NTG group. Statin therapy was associated with a normalization of total cholesterol and LDL-c, but not of VLDL-c or HDL-c in patients with FCH.

Study limitations include its observational nature, the small sample size, and the prolonged statin treatment, which could have additional effects on lipoprotein function.

“The persistence of lipoprotein disorders following statin therapy is much more marked in patients with HTG,” noted the study authors. “These alterations could compromise lipoprotein functionality and contribute to the especially high residual risk in this subgroup of patients under treatment with statins only….[M]ore aggressive lipid-lowering therapies, including approaches targeting hypertriglyceridemia, should be considered when a phenotype of high TG levels is present in these patients.”

Reference

Puig N, Miñambres I, Benítez S, et al. Familial combined hyperlipidemia (FCH) patients with high triglyceride levels present with worse lipoprotein function than FCH patients with isolated hypercholesterolemia. Biomedicines. 2020;8(1):6