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Background: Fasting hypertriglyceridaemia has been reported to occur commonly in cigarette smokers and is thought to increase cardiovascular disease (CVD) risk in these individuals. More recently, it has been suggested that an increase in non-fasting triglycerides, rather than fasting hypertriglyceridaemia, is an independent CVD risk factor., Methods: In this study, we divided 24 smokers into insulin-resistant (IR) and insulin-sensitive (IS) groups by determining their steady-state plasma glucose concentrations during the insulin suppression test and compared fasting and daylong postprandial accumulation of total triglycerides and remnant lipoprotein (RLP) concentrations, before and after 3 months of pioglitazone (PIO) administration., Results: The two groups were similar in age, body mass index, race and gender distribution, but differed dramatically in insulin sensitivity. Baseline fasting and postprandial triglyceride, RLP cholesterol and RLP triglyceride concentrations were significantly higher in the IR smokers (p=0.01 to <0.01). Insulin resistance [corrected] and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p=0.05 to 0.01) [corrected] in PIO-treated IR smokers, without any significant increase in weight instead of insulin sensitivity and both fasting and postprandial triglyceride and RLP triglyceride levels decreased significantly (p = 0.05 to, 0.01) in PIO-treated IR smokers, without any significant increase in weight. [corrected], Conclusions: The postprandial accumulation of RLP particles is increased in the IR subset of smokers and is likely to contribute to the increased CVD risk in these individuals. Furthermore, PIO administration provides a possible therapeutic approach to decreasing postprandial lipaemia and CVD risk in IR smokers who are unwilling or unable to stop smoking.

Potentially atherogenic triglyceride-rich lipoprotein (TRL) remnants can be isolated and quantitated as remnant-like particles (RLP), using an immunoaffinity gel containing specific anti-human apolipoprotein A-I (apoA-I) and apoB-100 monoclonal antibodies. The aim of the present study was to determine the relationship between postprandial changes in RLP levels and changes in total serum triglyceride (TG) in patients with different forms of hypertriglyceridemia (HTG). Three groups of patients were selected, having similarly elevated serum TG levels: a) HTG with TRL remnant accumulation (i.e., type III patients, n = 15, TG: 3.8 +/- 0.2 mm), b) HTG with increased LDL (i.e., type IIb patients, n = 15, TG: 3.7 +/- 0.2 mm), and c) HTG without evidence of remnant or LDL accumulation (i.e., type IV patients, n = 15, TG: 3.9 +/- 0.3 mm). Ingestion of a 45-g fat meal caused a significant increase in serum TG (30;-50%) in all patients. Mean serum TG levels of the three groups were not significantly different at 4 or 6 h after the meal. RLP cholesterol (C) and TG levels increased after the meal in all patients, but these postprandial increases were also not significantly different among groups. Type III patients had significantly higher (P < 0.01) levels of RLP-C and RLP-apoE in the fasted and fed state, and also had significantly higher RLP-C-to-serum TG ratios (P < 0.001) compared with the other groups. These results indicate that 1) RLP-C and RLP-TG levels are significantly increased in the fed versus fasted state in patients with elevated fasting TG levels; 2) patients with different forms of HTG, but similar TG levels, have similar postprandial increases in RLP-C and RLP-TG; and 3) type III patients have significantly elevated levels of RLP-C and RLP-apoE in both the fed and fasted state.

Background: Familial type III hyperlipoproteinemia (HLP) is characterized by the presence of beta-migrating VLDL (beta-VLDL) and increased risk of cardiovascular disease. Assessment of plasma beta-VLDL is achieved by measuring the ratio of VLDL-cholesterol (VLDL-C) to total plasma triglycerides (TGs) or by detecting beta-VLDL in total VLDL. The objective of this study was to compare the clinical utility of the ratio of remnant-like particle-cholesterol (RLP-C) to total TGs with that of the current methods for diagnosing type III HLP., Methods: Detection of beta-VLDL by electrophoresis of VLDL was used to define type III HLP. Twenty-eight patients with type III HLP and 43 subjects lacking beta-VLDL were investigated. Fasting TG concentrations were >2.26 mmol/L in all subjects. Subjects were separated into three groups: group 1, serum total cholesterol 5.18 mmol/L and TGs between 2.26 and 9.04 mmol/L (n = 51); and group 3, TGs >9.04 mmol/L (n = 9)., Results: In group 2, a RLP-C-to-total TG molar ratio >/=0.23 (>/=0.10 when using mg/dL) and a VLDL-C-to-total TG molar ratio >/=0.69 (>/=0.30 when using mg/dL) correctly classified 94% and 90% of the subjects, respectively. The utility of the RLP-C-to-total TG ratio in diagnosing type III HLP decreased in patients in the other two groups., Conclusion: When used in an appropriate target population, the RLP-C-to-total TG ratio is a convenient and effective alternative to ultracentrifugal and electrophoretic methods for diagnosing type III HLP.

Substantial evidence indicates that triglyceride-rich lipoprotein remnants are atherogenic. Additional research has, however, been limited by available methods for separation and quantification of remnants. We have evaluated an immunoseparation assay developed to measure cholesterol in remnant-like particles (RLP-C). This method uses monoclonal antibodies to human apolipoproteins B-100 and A-I to remove most of the apolipoprotein B-100-containing lipoproteins (namely LDL and nascent VLDL) and apolipoprotein A-I-containing lipoproteins (namely chylomicrons and HDL), leaving behind a fraction of triglyceride-rich lipoproteins, including chylomicron and VLDL remnants, both of which are enriched in apolipoprotein E. Cholesterol in the unbound fraction is measured with a sensitive enzymatic assay. The RLP-C concentration was highly correlated with total triglyceride-rich lipoproteins (sum of VLDL-cholesterol and IDL-cholesterol) separated by ultracentrifugation and by polyacrylamide gel electrophoresis (r = 0.86 and 0.76, respectively). The within-run and run-to-run imprecision (CV) of the assay was approximately 6% and 10%, respectively. The assay was not affected by hemoglobin up to 5000 mg/L (500 mg/dL), bilirubin up to 342 mmol/L (20 mg/dL), glucose up to 67 mmol/L (1200 mg/dL), or ascorbic acid up to 170 mmol/L (3.0 mg/dL). In 726 subjects (men, n = 364; women, n = 362) in the US, the 75th percentiles of RLP-C concentration were 0.17 mmol/L (6.6 mg/dL) and 0.23 mmol/L (8.8 mg/dL) in sera obtained after overnight fasting or randomly, respectively. A group of 151 patients from nine US centers and one Canadian center with coronary artery atherosclerosis established by angiography had higher median RLP-C concentrations than 302 gender- and age-matched controls (P <0.05). We conclude that the RLP-C assay compares favorably to ultracentrifugation and electrophoresis and provides a convenient and economical approach to measure triglyceride-rich lipoprotein remnants in routine clinical laboratories.

Cholesterol and triglyceride standardization procedures have been used extensively and continuously since the 1950s. Definitive and Reference Methods, as well as primary and secondary standards, have been developed and maintained as the basis for evaluating the accuracy of results by various methods in many laboratories. But, although standardization efforts for apolipoprotein A-I and B measurements have been reported in detail in the scientific literature, much less has been reported in the area of total and lipoprotein cholesterol and triglyceride standardization efforts. Standardized cholesterol and triglyceride concentrations, determined in multiple large epidemiological and clinical studies, have been instrumental to the National Cholesterol Education Program panels that have assessed the lipoprotein values associated with risk of coronary disease, and have determined the cutpoints that are now used extensively by physicians to guide diagnosis and treatment of individual patients.

Background: In order to assess accuracy of a newly developed, noninstrumented, self-administered fingerstick test that measures cholesterol levels in whole blood, the AccuMeter Cholesterol Self-Test was evaluated for home-use by untrained consumers in a multicenter study., Methods: A total of 486 untrained adult volunteers of varying age, occupation, and educational background were recruited at four sites. Participants received written instructions provided in the kit, access to a telephone "800" number for additional help, and, if necessary, a short instructional video available to consumers on request. Fingerstick cholesterol results obtained by untrained volunteers were compared with paired venous serum results obtained by the Abell-Kendall cholesterol reference method. After application of exclusion criteria, 79.0% (384/486) of subjects had AccuMeter fingerstick results available for comparison with the reference method., Results: Results obtained with the AccuMeter test correlated well with the Abell-Kendall results (r = 0.91). There was a mean overall bias for the AccuMeter of -0.116 +/- 0.528 mmol/liter (-2.2%), with a mean absolute bias of 0.398 +/- 0.367 mmol/liter (7.6%). Biases at the National Cholesterol Education Program cutpoints of 5.20 and 6.20 mmol/liter were -2.2 and -2.5%, respectively. Subjects with high-risk total cholesterol values (> or = 6.20 mmol/liter) were correctly classified 80.0% of the time, with an additional 18.8% placed in the borderline category (5.20-6.20 mmol/liter); 1.2% were inappropriately placed in the desirable category. No subjects were placed in the high-risk category by the AccuMeter test if they had a desirable cholesterol value by the reference method, while 9.8% were placed in this category if they were in fact borderline., Conclusions: This test appears to be a useful addition to available options in the effort to increase awareness of cholesterol as a heart disease risk factor. A large portion of untrained consumers were able to perform the AccuMeter Cholesterol Self-Test and obtain comparable results to the reference method. This test for the first time allows consumers to determine their own cholesterol values, with a reasonably good degree of accuracy.

Current interest in coronary heart disease and cholesterol has led to the development of a new generation of compact analysis systems designed for fingerstick whole blood measurement. Since reliable classification of patients based on national cut-points for serum cholesterol concentration requires accurate results, the question whether results from fingerstick capillary specimens are equivalent to those from conventional venous-derived serum specimens, the basis for the national cut-points, is germane. Earlier studies in the literature are contradictory, with fingerstick differences ranging from 9% low to 6% high. We developed guidelines for reliable fingerstick collection and, following these guidelines, achieved results that were comparable to results derived from concurrently collected venous serum specimens. Results measured either by an accurate, standardized enzymatic assay or by the AccuMeter, a new noninstrumented device, were in close agreement with serum results, ie, within 1% and 1.7%, respectively, suggesting that fingerstick measurements are appropriate for identifying individuals with elevated cholesterol levels and monitoring their treatment.