Direct Low-density Lipoprotein Research Articles

Specialized lipid profiles.

Individuals with abnormal blood lipids and lipoproteins are at increased risk for cardiovascular disease. With the development of effective dietary, behavioral, and pharmaceutical treatments to optimize blood lipoproteins, accurate clinical assessment of blood lipids and lipoproteins are essential for patient management and research. This article discusses the use of a variety of lipid analyses currently available. The use of traditional lipoprotein measurements, including Friedewald calculation of low-density lipoprotein (LDL) cholesterol and ultracentrifugation methods to measure blood lipoproteins, are discussed. Newer analytic techniques, including the vertical analytic profile, nuclear magnetic resonance, direct LDL measurement, LDL size determination, and triglyceride-rich lipoprotein remnants, are also described. Despite the development of a number of lipid and lipoprotein assays, lipoprotein analysis with a Friedewald- calculated LDL measurement remains the lipoprotein analysis performed in approximately 93% of clinical laboratories. It remains to be determined if the alternative lipid and lipoprotein assays currently available will become more widely utilized in the future.

Comparison of fasting and postprandial plasma lipoproteins in subjects with and without coronary heart disease

Plasma lipoprotein levels, including remnant-like particle (RLP) cholesterol and RLP triglycerides, were assessed in fasting (12 hours) and postprandial (PP) (4 hours after a fat-rich meal) states in 88 patients with coronary heart disease (CHD) and 88 controls. All lipoproteins were assessed by direct methods. We hypothesized that patients with CHD would have greater percent increases in their triglyceride levels, RLP cholesterol, and RLP triglycerides, in response to a fat-rich meal. In the fasting state, triglycerides, RLP cholesterol, RLP triglycerides, and low-density lipoprotein (LDL) cholesterol levels were all significantly higher in cases versus controls by 51%, 35%, 39%, and 40%, respectively. These levels were 57%, 37%, 64%, and 37% higher in the PP state, respectively. Mean high-density lipoprotein (HDL) cholesterol values were 27% lower in cases in both the fasting and PP states. After eating, triglycerides, RLP cholesterol, and RLP triglycerides increased 64%, 71%, and 290% in controls, respectively, whereas in cases these levels increased by 71%, 94%, and 340%, respectively (all p <0.0001). Percent increases in the PP state were not significantly different in cases versus controls. Following the fat-rich meal, LDL and HDL cholesterol decreased by 5% and 4% in controls, and by 7% and 6% in patients, with no significant difference in percent changes between groups. Fasting values correlated very highly with PP values for all parameters (all p <0.0001). Our data indicate that although patients with CHD have higher fasting and PP levels of triglycerides, RLP cholesterol, and RLP triglycerides than controls, the response (percent increase) to a fat-rich meal is comparable in both groups. Thus, a feeding challenge is not essential for assessment of these lipoproteins. Moreover, it is not necessary to obtain a fasting sample to assess direct LDL and HDL cholesterol.

Direct Method for the Measurement of Low-Density Lipoprotein Cholesterol Levels in Patients with Chronic Renal Disease: A Comparative Assessment

Background/Aim: This study was performed to comparatively evaluate the results obtained for low-density lipoprotein (LDL) cholesterol concentrations by either a newly described direct method or the Friedewald equation in subjects with and without chronic renal disease. Methods: Fasting plasma was obtained from a total of 169 subjects, 105 with normal renal function (including 53 hyperlipidaemic) and 64 with chronic renal disease (nephrotic syndrome and/or chronic renal failure; including 40 hyperlipidaemic patients), and analyzed for LDL cholesterol using the Friedewald equation and a direct LDL assay method. Results: The Friedewald equation and the direct LDL cholesterol assay correlated well with each other (r = 0.79–0.90 in all subjects with plasma triglyceride, TG, levels greater than or less than 4.0 mmol/l and with and without chronic renal disease and/or hyperlipidaemia, all p < 0.0001). The values for LDL cholesterol, however, tended to be higher with the direct measurement. This mean difference was trivial in hyperlipidaemic subjects with (8.5%) and without (7.1%) normal renal function (both p < 0.05), but could be clinically significant in those with TG >4.0 mmol/l (mean difference 18%, p < 0.001). Indeed, bias plots confirmed this observation of wider negative bias for Friedewald estimation in these moderately hypertriglyceridaemic subjects. Conclusion: For most routine laboratories the options immediately available for assessment of lipid levels are the Friedewald equation or the direct measurement. The Friedewald equation and the direct assay method for LDL cholesterol are about equally good for assessment of the LDL status in patients with chronic renal disease and plasma TG <4.0 mmol/l. Where there are restraints on laboratory budgets, it would appear appropriate that the more expensive direct assay method be restricted to cases in whom plasma TG >4.0 mmol/l or to patients who, for whatever reason, are unable to produce fasting samples.

Evaluation and Clinical Application of a Direct Low-Density Lipoprotein Cholesterol Assay in Normolipidemic and Hyperlipidemic Adults

This study examines the performance and clinical use of a commercial immunoseparation assay for low-density lipoprotein (LDL) cholesterol in a sample population of normolipidemic and hyperlipidemic adult volunteers. Using paired fasting and nonfasting samples, we compared the direct LDL assay with the β quantification method and the Friedewald calculation. Overall, the direct LDL assay correctly classified 82% and 60% of fasting and nonfasting subjects, respectively, into National Cholesterol Education Program risk groups. The Friedewald method correctly classified 84% of subjects. The fasting direct LDL assay has comparable positive and negative predictive values to the Friedewald method, except at an LDL cholesterol of 100 mg/dl. The nonfasting direct LDL assay demonstrates unacceptable positive predictive values when LDL cholesterol decreases to the 130 to 159 and ≥160 mg/dl categories. Overall, direct LDL assay demonstrates limitations in the nonfasting state and at the LDL cholesterol level of 100 mg/dl used for patients with established coronary heart disease.

A More Valid Measurement of Low-Density Lipoprotein Cholesterol in Diabetic Patients

PURPOSE: This study was conducted to determine if the direct low-density lipoprotein (LDL) cholesterol assay would provide a more valid measure of LDL cholesterol in diabetic patients compared with the Friedewald equation.PATIENTS AND METHODS: Fasting plasma from 148 diabetic patients, 40 with insulin-dependent diabetes (IDDM) and 108 with non-insulin-dependent diabetes (NIDDM) with triglyceride levels <400 mg/dL, were analyzed for LDL cholesterol using the Friedewald equation, the direct LDL assay, and beta-quantification. Forty-six diabetic patients with triglyceride levels ≥400 mg/dL were also studied to determine the validity of the direct LDL cholesterol assay with hypertriglyceridemia.RESULTS: The Friedewald equation and the direct LDL cholesterol assay correlated well with beta-quantification (r = 0.969 and r = 0.971, respectively) for LDL cholesterol determination in diabetic patients. Although the Friedewald equation in comparison with beta-quantification underestimated (8%) LDL cholesterol values in diabetic patients, the direct LDL cholesterol assay had a mean bias of <1%. Also, the underestimation by the Friedewald equation exceeded 10% for the triglyceride subgroup of 200 to 400 mg/dL. Furthermore, the accuracy of the direct LDL cholesterol assay was superior to the Friedewald equation since LDL cholesterol levels determined by the two methods coincided within ±10% of beta-quantification in 85% and 68% of diabetic patients, respectively (P = 0.0005). Similar results for both the Friedewald equation and the direct LDL cholesterol assay in comparison with beta-quantification were seen when diabetic patients were subgrouped into IDDM and NIDDM. Also, the direct LDL cholesterol assay appeared to provide a reliable estimate in patients with triglycerides ≥400 mg/dL.CONCLUSION: The results of our studies indicate that the direct LDL cholesterol assay is a more reliable and accurate method than the Friedewald formula for LDL cholesterol determination in diabetic patients and is more rapid and cost effective than the reference method.

Efficacy of Psyllium in Reducing Serum Cholesterol Levels in Hypercholesterolemic Patients on High- or Low-Fat Diets

To determine the efficacy of psyllium in reducing serum cholesterol levels in patients on high- or low-fat diets. Double-blind, placebo-controlled, 16-week parallel trial. The study included an 8-week baseline period and an 8-week treatment period. Healthy men and women, 21 to 70 years old, with primary hypercholesterolemia (total serum cholesterol > or = 5.7 mmol/L [220 mg/dL]). Thirty-seven participants followed a high-fat diet and 81 participants followed a low-fat diet. Participants were randomly assigned to either psyllium, 5.1 g twice a day, or placebo. Fasting lipid and apolipoprotein concentrations, including direct low-density lipoprotein (LDL) cholesterol quantification; nutritional analyses of 4 days of 7-day food records to monitor dietary compliance; and physical examinations, clinical chemistry and hematologic studies, and urinalysis to assess treatment safety. Psyllium recipients in both the high- and low-fat diet groups showed small but significant decreases (P < 0.05) in total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Total cholesterol and LDL cholesterol levels decreased 5.8% and 7.2%, respectively, in psyllium recipients on high-fat diets and 4.2% and 6.4%, respectively, in psyllium recipients on low-fat diets. No significant difference was seen in LDL cholesterol response when psyllium recipients on low- and high-fat diets were compared (P > 0.2). No significant reductions in lipid levels were observed in placebo recipients. Based on the National Cholesterol Education Program LDL cholesterol classification system, 39% of the psyllium recipients improved in LDL cholesterol classification (P < 0.0001) compared with 20.3% of placebo recipients (P > 0.2). Psyllium produces a modest but significant improvement in total cholesterol and LDL cholesterol levels in persons on either low-fat or high-fat diets. Psyllium, when added to a prescribed low-fat diet, may obviate the need for typical lipid-lowering medications or may prove to be a valuable adjunct to other treatments in patients with moderately elevated LDL cholesterol levels.