Genetic and biochemical analyses in dyslipidemic patients undergoing LDL apheresis.

OBJECTIVE: Familial hypercholesterolemia (FH) can be due to mutations in LDLR, PCSK9, and APOB. In phenotypically defined patients, a subset remains unresponsive to lipid-lowering therapies and requires low density-lipoprotein (LDL) apheresis treatment. In this pilot study, we examined the genotype/phenotype relationship in patients with dyslipidemia undergoing routine LDL apheresis. DESIGN: LDLR, APOB, and PCKS9 were analyzed for disease-causing mutations in seven patients undergoing routine LDL apheresis. Plasma and serum specimens were collected pre- and post-apheresis and analyzed for lipid concentrations, Lp(a) cholesterol, and lipoprotein particle concentrations (via NMR). RESULTS: We found that four patients harbored LDLR mutations and of these, three presented with xanthomas. While similar reductions in LDL-cholesterol (LDL-C), apolipoprotein B, and LDL particles (LDL-P) were observed following apheresis in all patients, lipid profile analysis revealed the LDLR mutation-positive cohort had a more pro-atherogenic profile (higher LDL-C, apolipoprotein B, LDL-P, and small LDL-P) pre-apheresis. CONCLUSION: Our data show that not all clinically diagnosed FH patients who require routine apheresis have genetically defined disease. In our small cohort, those with LDLR mutations had a more proatherogenic phenotype than those without identifiable mutations. This pilot cohort suggests that patients receiving the maximum lipid lowering therapy could be further stratified, based on genetic make-up, to optimize treatment.

Comparison of two point of care devices for capillary lipid screening in fasting and postprandial adults.

OBJECTIVES: The aim of this study was to assess the performance of two point of care (POC) devices for capillary lipid screening in fasting and post-prandial adults. DESIGN AND METHODS: Fasting and post-prandial capillary whole blood samples collected from 57 adult donors were analyzed simultaneously on Cholestech LDX Lipid Profile (Alere San Diego, Inc., San Diego, CA) cassettes and CardioChek Lipid Panel (Polymer Technology Systems, Indianapolis, IN) strips. Paired serum samples were collected from the same donors and analyzed with CDC-certified methods for total cholesterol, high density lipoprotein cholesterol (HDL-C) and non-blanked triglycerides. Non-HDL-C (total cholesterol minus HDL-C) and low density lipoprotein cholesterol (LDL-C) were calculated. Mean bias between capillary whole blood and serum laboratory lipids was calculated. RESULTS: HDL-C measurements were not affected by triglyceride content on either device. However, both devices exhibited significant variability in triglyceride measurement relative to the reference method. Compared to reference methods, Cholestech was more accurate than CardioChek for non-HDL-C while CardioChek was more accurate for HDL-C. Among the calculated cardiovascular risk parameters (LDL-C and non-HDL-C), Cholestech-calculated non-HDL-C exhibited the least average bias in both fasting and postprandial samples. CONCLUSIONS: The optimal approach to capillary lipid screening may be to use Cholestech non-HDL cholesterol; as it exhibited little bias relative to CDC reference methods in both fasting and postprandial samples, facilitating lipid screening in non-fasting adults.