Lp(a) falls as triglycerides rise above 300 mg/dL, but only without diabetes, obesity or familial hypercholesterolaemia, in 5,275 Spanish lipid-clinic patients (Clin Investig Arterioscler 2024)

Original title: Influence of triglyceride concentration in lipoprotein (a) as a function of dyslipidemia

Clin Investig Arterioscler · 30 December 2023 · 6

Marco-Benedí V, Cenarro A, Laclaustra M, Calmarza P, Bea AM, Vila À, Morillas-Ariño C, Puzo J, Mediavilla Garcia JD, Fernández Alamán AI, Suárez Tembra M, Civeira F

In 5,275 subjects from the Spanish Society of Atherosclerosis lipid-clinic registry (mean age 53.0 years, 48% women), median Lp(a) was 55.0 nmol/L and median triglycerides 130 mg/dL. Lp(a) showed an inverse association with triglycerides once triglycerides exceeded 300 mg/dL, falling from a mean of 60.1 nmol/L below this threshold to 17.9 nmol/L above 1000 mg/dL. This inverse relationship was especially pronounced in subjects without diabetes or obesity (median Lp(a) 58.3 nmol/L at triglycerides <300 mg/dL versus 22.0 nmol/L at >1000 mg/dL, P<0.001), but was absent in subjects with diabetes, obesity, or familial hypercholesterolaemia. The findings suggest that severe hypertriglyceridaemia driven by hepatic VLDL overproduction suppresses Lp(a) formation, a mechanism that does not operate when triglycerides accumulate through impaired peripheral clearance.

Original abstract

Background: Recently, an inverse relationship between the blood concentration of lipoprotein(a) (Lp(a)) and triglycerides (TG) has been demonstrated. The larger the VLDL particle size, the greater the presence of VLDL rich in apoliprotein E and in subjects with the apoE2/E2 genotype, the lower Lp(a) concentration. The mechanism of this inverse association is unknown. The objective of this analysis was to evaluate the Lp(a)-TG association in patients treated at the lipid units included in the registry of the Spanish Society of Atherosclerosis (SEA) by comparing the different dyslipidemias.

Patients And Methods: Five thousand two hundred and seventy-five subjects ≥18 years of age registered in the registry before March 31, 2023, with Lp(a) concentration data and complete lipid profile information without treatment were included.

Results: The mean age was 53.0 ± 14.0 years, with 48% women. The 9.5% of subjects (n = 502) had diabetes and the 22.4% (n = 1184) were obese. The median TG level was 130 mg/dL (IQR 88.0-210) and Lp(a) 55.0 nmol/L (IQR 17.9-156). Lp(a) concentration showed a negative association with TG concentration when TG values exceeded 300 mg/dL. Subjects with TG > 1000 mg/dL showed the lowest level of Lp(a), 17.9 nmol/L, and subjects with TG < 300 mg/dL had a mean Lp(a) concentration of 60.1 nmol/L. In subjects without diabetes or obesity, the inverse association of Lp(a)-TG was especially important (p < 0.001). The median Lp(a) was 58.3 nmol/L in those with TG < 300 mg/dL and 22.0 nmol/L if TG > 1000 mg/dL. No association was found between TG and Lp(a) in subjects with diabetes and obesity, nor in subjects with familial hypercholesterolemia. In subjects with multifactorial combined hyperlipemia with TG < 300 mg/dL, Lp(a) was 64.6 nmol/L; in the range of 300-399 mg/dL of TG, Lp(a) decreased to 38. 8 nmol/L, and up to 22.3 nmol/L when TG > 1000 mg/dL.

Conclusions: Our results show an inverse Lp(a)-TG relationship in TG concentrations > 300 mg/dL in subjects without diabetes, obesity and without familial hypercholesterolemia. Our results suggest that, in those hypertriglyceridemias due to hepatic overproduction of VLDL, the formation of Lp(a) is reduced, unlike those in which the peripheral catabolism of TG-rich lipoproteins is reduced.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.