Key result
Familial hypercholesterolemia subjects had significantly higher cholesterol in triglyceride-rich lipoproteins, including VLDL and IDL, revealing a tri-modal distribution according to the number of LDL receptor mutations.
Why the study?
Does the number of LDL receptor mutations modulate the quantity and quality of TG-rich lipoprotein fractions (VLDL and IDL) in patients with familial hypercholesterolemia?
Observational (n=375)
No
Does the number of LDL receptor mutations modulate the quantity and quality of TG-rich lipoprotein fractions (VLDL and IDL) in patients with familial hypercholesterolemia?
Absolute Event Rate: 16.8% vs 8.3%
p-value: p=<0.0001
Familial hypercholesterolemia is associated with quantitative and qualitative abnormalities in triglyceride-rich lipoproteins (VLDL and IDL) that worsen with the number of LDL receptor mutations.
May refine FH phenotyping by mutation burden; leaves open causal links to TG-rich lipoprotein abnormalities.
OBJECTIVES: It is well known that familial hypercholesterolemia (FH) is a common inherited disorder that can markedly elevate the level of plasma LDL cholesterol. However, little data exists regarding the clinical impact of the plasma triglyceride (TG)-rich lipoprotein fraction, including VLDL and IDL, in FH. Thus, we assessed the hypothesis that the mutations in the LDL receptor modulate lipoprotein metabolism other than the LDL fraction. DESIGN AND METHODS: We investigated plasma lipoprotein with a one-step ultracentrifugation method for 146 controls (mean age=61.4±17.1 yr, mean LDL cholesterol=92.7±61.2 mg/dl), 213 heterozygous mutation-determined FH subjects (mean age=46.0±18.0 yr, mean LDL cholesterol=225.1±61.2 mg/dl), and 16 homozygous/compound heterozygous mutation-determined FH subjects (mean age=26.9±17.1 yr, mean LDL cholesterol=428.6±86.1 mg/dl). In addition, we evaluated cholesterol/TG ratio in each lipoprotein fraction separated by ultracentrifugation. RESULTS: In addition to total cholesterol and LDL cholesterol levels, VLDL cholesterol (19.5±10.4, 25.2±19.3, 29.5±21.4 mg/dl, respectively) and IDL cholesterol (8.3±3.7, 16.8±11.5, 40.0±37.3 mg/dl, respectively) exhibited a tri-model distribution according to their status in LDL receptor mutation(s). Moreover, the ratios of cholesterol/TG of each lipoprotein fraction increased significantly in heterozygous FH and homozygous/compound heterozygous FH groups, compared with that of controls, suggesting that the abnormality in LDL receptor modulates the quality as well as the quantity of each lipoprotein fraction. CONCLUSIONS: Our results indicate that cholesterol in TG-rich lipoproteins, including VLDL and IDL, are significantly higher in FH subjects, revealing a tri-modal distribution according to the number of LDL receptor mutations.
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Tada et al. (2015) conducted an observational in Familial hypercholesterolemia (n=375). Heterozygous familial hypercholesterolemia vs. Controls was evaluated on IDL cholesterol (p=<0.0001). Familial hypercholesterolemia subjects had significantly higher cholesterol in triglyceride-rich lipoproteins, including VLDL and IDL, revealing a tri-modal distribution according to the number of LDL receptor mutations.
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