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The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, and calculated non-HDL cholesterol (=total - HDL cholesterol) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDL cholesterol is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDL cholesterol shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDL cholesterol decline poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDL cholesterol or apolipoprotein B, especially in patients with mild-to-moderate hypertriglyceridemia (2-10 mmol/L). Non-HDL cholesterol includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apolipoprotein B measurement can detect elevated LDL particle numbers often unidentified on the basis of LDL cholesterol alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20-100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Apolipoprotein B (apoB) plasma levels reflect the concentration of proatherogenic lipoproteins very low-density lipoprotein and low-density lipoprotein (LDL), whereas non-high-density lipoprotein cholesterol (non-HDL-C) levels reflect the concentration of cholesterol transported by these particles., Methods and Results: The aim of our study was to compare apoB, non-HDL-C, LDL cholesterol (LDL-C), and other lipid markers as predictors of coronary heart disease (CHD) in a nested case-control study among 18 225 participants in the Health Professionals Follow-up Study. Among men who were free of diagnosed cardiovascular disease at the time of blood collection, 266 had nonfatal myocardial infarction or fatal CHD during 6 years of follow-up. Through the use of risk set sampling, control subjects were selected at a 2:1 ratio and matched with regard to age, date of blood collection, and smoking status. After adjustment for matching factors, the relative risk of CHD in the highest quintile compared with the lowest quintile was 2.76 (95% confidence interval [CI], 1.66 to 4.58) for non-HDL-C, 3.01 (95% CI, 1.81 to 5.00) for apoB, 1.81 (95% CI, 1.12 to 2.93) for LDL-C, 0.31 (95% CI, 0.18 to 0.52) for HDL-C, 2.41 (95% CI, 1.43 to 4.07) for triglycerides (all P trend <0.001), and 1.42 (95% CI, 0.86 to 2.32, P trend =0.19) for lipoprotein(a). When non-HDL-C and LDL-C were mutually adjusted, only non-HDL-C was predictive of CHD. When non-HDL-C and apoB were mutually adjusted, only apoB was predictive; the relative risk was 4.18 (95% CI, 1.30 to 13.49; P trend =0.02) for apoB compared with 0.70 (95% CI, 0.21 to 2.27; P trend =0.72) for non-HDL-C. Triglycerides added significant information to non-HDL-C but not to apoB for CHD risk prediction., Conclusions: Although non-HDL-C and apoB were both strong predictors of CHD in this male cohort, more so than LDL-C, the findings support the concept that the plasma concentration of atherogenic lipoprotein particles measured by apoB is more predictive in development of CHD than the cholesterol carried by these particles, measured by non-HDL-C.

Context: Current guidelines for cardiovascular risk detection are controversial with regard to the clinical utility of different lipid measures, non-high-density lipoprotein cholesterol (non-HDL-C), lipid ratios, apolipoproteins, and C-reactive protein (CRP)., Objective: To directly compare the clinical utility of total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, non-HDL-C, apolipoproteins A-I and B(100), high-sensitivity CRP, and the ratios of total cholesterol to HDL-C, LDL-C to HDL-C, apolipoprotein B(100) to apolipoprotein A-I, and apolipoprotein B(100) to HDL-C as predictors of future cardiovascular events in women., Design, Setting, and Participants: Prospective cohort study of 15,632 initially healthy US women aged 45 years or older (interquartile range, 48-59 years) who were enrolled between November 1992 and July 1995. All participants were followed up over a 10-year period for the occurrence of future cardiovascular events., Main Outcome Measure: Hazard ratios (HRs) and 95% confidence intervals (CIs) for first-ever major cardiovascular events (N = 464) according to baseline levels of each biomarker., Results: After adjustment for age, smoking status, blood pressure, diabetes, and body mass index, the HRs for future cardiovascular events for those in the extreme quintiles were 1.62 (95% CI, 1.17-2.25) for LDL-C, 1.75 (95% CI, 1.30-2.38) for apolipoprotein A-I, 2.08 (95% CI, 1.45-2.97) for total cholesterol, 2.32 (95% CI, 1.64-3.33) for HDL-C, 2.50 (95% CI, 1.68-3.72) for apolipoprotein B(100), 2.51 (95% CI, 1.69-3.72) for non-HDL-C, and 2.98 (95% CI, 1.90-4.67) for high-sensitivity CRP (P<.001 for trend across all quintiles). The HRs for the lipid ratios were 3.01 (95% CI, 2.01-4.50) for apolipoprotein B(100) to apolipoprotein A-I, 3.18 (95% CI, 2.12-4.75) for LDL-C to HDL-C, 3.56 (95% CI, 2.31-5.47) for apolipoprotein B(100) to HDL-C, and 3.81 (95% CI, 2.47-5.86) for the total cholesterol to HDL-C (P<.001 for trend across all quintiles). The correlation coefficients between high-sensitivity CRP and the lipid parameters ranged from -0.33 to 0.15, and the clinical cut points for CRP of less than 1, 1 to 3, and higher than 3 mg/L provided prognostic information on risk across increasing levels of each lipid measure and lipid ratio., Conclusions: Non-HDL-C and the ratio of total cholesterol to HDL-C were as good as or better than apolipoprotein fractions in the prediction of future cardiovascular events. After adjustment for age, blood pressure, smoking, diabetes, and obesity, high-sensitivity CRP added prognostic information beyond that conveyed by all lipid measures.

We wanted to ascertain whether the current format of lipid laboratory reports seemed adequate to promote identification and treatment of patients with dyslipidemia. In a random survey of lipid laboratory reports from 25 laboratories, we found great inconsistencies among reporting formats and contents. Fewer than half the laboratories correctly reported the ranges for cholesterol, only 4 correctly reported ranges for high-density lipoprotein cholesterol, only 2 correctly reported ranges for triglycerides, and none presented low-density lipoprotein cholesterol ranges in terms of risk factors for coronary heart disease. Reports typically were disjointed and difficult to read. The current practice of reporting results for lipid panels is confusing and does not follow the National Cholesterol Education Program (NCEP) guidelines. We recommend that reporting of results be standardized, and a "model" standardized report is presented herein, based on consensus from a team of experts. The standardized report uses current recommendations for ranges, follows the flowcharts of the NCEP guidelines, and takes the patient's clinical condition (the number of risk factors and the presence of coronary heart disease) into consideration. Standardizing lipid reports should decrease confusion and perhaps increase application of the guidelines and patient compliance with treatment.

Race and gender differences in lipoproteins and apolipoproteins have repeatedly been demonstrated in adults. The same disparities have been observed in children of different race and gender, implying that these differences may be influenced by genetic factors. To further explore this hypothesis, cord blood concentrations of both lipoproteins and apolipoproteins were examined in black and white neonates of both sexes. Results were controlled for the observed effects of gestational age and growth parameters. Similar patterns of lipoprotein differences to those observed in adults and children were also detected between black and white, and between male and female neonates. These findings support the concept that the aetiology of the difference in lipoprotein concentration observed between race and gender groups includes a significant genetic component.

Exercise is associated with changes in lipids that may protect against coronary heart disease (CHD). In this study of 28 triathletes, we analyzed acute changes in serum lipid and lipoprotein concentrations after completion of the 1995 World Championship Hawaii Ironman Triathlon. With standard laboratory assays, we demonstrate significant decreases in total cholesterol, VLDL cholesterol, ApoB100, and Lp(a). Total HDL cholesterol increased significantly immediately after the race. With a novel proton NMR spectroscopy assay, we demonstrate that smaller diameter LDL particles, corresponding to small, dense LDL, declined by 62%. Moreover, larger HDL subclasses, whose levels are inversely associated with CHD, increased significantly by 11%. Smaller HDL subclasses, which have been directly associated with CHD in some studies, acutely decreased by 16%. Therefore, exercise not only acutely induces changes in lipoprotein concentrations among the standard species in a manner that favorably affects CHD risk, but also induces favorable changes in specific lipoprotein subclass size distribution that also may alter CHD risk independently of the total lipoprotein serum concentration.

Objectives: We wish to examine the role of lipoproteins in the transport and cellular uptake of cyclosporine (CsA) and tacrolimus., Design and Methods: The distribution of tritiated CsA and tacrolimus among lipoproteins was determined in normo- and hypertriglyceridemic sera. The uptake of these two drugs into HepG2 and JURKAT cell lines was assessed in the presence of various concentrations of low density lipoproteins. (LDL)., Results: Our data showed that about 60% of these drugs were transported by high density lipoprotein in normolipidemic sera, while about 50-60% were carried by very low density lipoprotein in hypertriglyceridemic sera. Almost 80% of CsA and 70% of tacrolimus entered HepG2 and JURKAT cells within the first hour of incubation in lipoprotein free media. However, the uptake was decreased (CsA by 60% and tacrolimus by 40%) in the presence of LDL., Conclusions: Lipoproteins play a major role in the transport of CsA and tacrolimus, but not in their cellular uptake.

It has been shown that blacks have considerably higher concentrations than whites of lipoprotein(a) (Lp(a)), which has been identified as an independent risk factor for coronary heart disease, vein graft restenosis, and cerebrovascular disease. Smaller differences in Lp(a) concentrations have been noted between males and females. To examine whether gender and race differences are already detectable at birth, we examined Lp(a) concentrations in cord blood samples of 109 black (49 male and 60 female) and 123 white (67 male and 56 female) newborns. Maternal age, gestational age, fetal maturity indicators, weight, height and head circumference were analyzed as covariates. For race and sex combined, the mean Lp(a) concentration was 4.0 mg/dl (S.D. of 3.94 mg/dl), approximately 5-fold lower than that observed in adults. No statistically significant differences were found between race or gender groups. The cross-sectional examination of serum Lp(a) concentrations of 221 infants, children and adults showed a gradual increase in Lp(a) concentrations from birth to adult values by the second year of life. We conclude that the system responsible for the production and control of Lp(a) concentration is not yet mature--or has not yet been challenged--at birth.

This study examined the effects of aerobic exercise on lipid levels in premenopausal and postmenopausal women. Fifty healthy middle-aged women (mean age, 50 years) were randomly assigned to 12 weeks of either aerobic exercise (walking and jogging) or nonaerobic strength exercise (circuit Nautilus training). Concentrations of total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and very low density lipoprotein cholesterol were assessed, along with apolipoprotein (apo) A-I, apo A-II, apo B, and triglycerides. To document changes in aerobic capacity, maximum treadmill testing was performed with expired-gas analysis before and after the exercise program. Aerobic exercise was associated with an 18% improvement in peak VO2. Women in the aerobic group had an increased VO2, from 26.7 to 31.4 ml/kg/min (p less than 0.0001), while the VO2 of the women in the strength training group did not change (25.8 ml/kg/min before and after). There were no differential changes in lipid levels because all subjects experienced slight reductions in high density lipoprotein cholesterol and total cholesterol and increases in apo A-I and the apo A-I to apo B ratio. There was a tendency for the aerobic group to exhibit lower levels of apo A-II and a greater apo A-I to apo A-II ratio, however. We conclude that premenopausal and postmenopausal women experience similar changes in aerobic capacity and lipid levels with exercise and that the short-term effects of aerobic and nonaerobic exercise on lipid profiles are generally comparable.

We investigated the effect of a fatty meal on plasma concentrations of lipids, apolipoproteins, and the cholesterol component of lipoproteins. Sixteen nonobese, healthy, asymptomatic males, 22-34 years of age, served as subjects for this study. None smoked, consumed more than two alcoholic drinks per day, or took any medication known to alter plasma lipids. After a 12 h fast, baseline plasma samples were obtained just before subjects consumed a high fat meal. The meal, standardized to a 70 kg individual, contained approximately 70 g fat, 580 mg cholesterol, and 1,100 cal, with 56% of the calories coming from fat. During the 8 h following consumption of the meal, subjects rested quietly and consumed no food or beverages except water. Blood specimens were obtained hourly. There was a significant increase in plasma triglyceride (150% from baseline at 3 h, P less than 0.0005). Very low density lipoprotein cholesterol (VLDL-C) concentrations increased 150% at 3 h (P less than 0.0005) while low density lipoprotein cholesterol (LDL-C) concentration decreased 37% at 3 h (P less than 0.005) when estimated by Friedewald's formula. No statistically significant differences were observed between fasting total cholesterol, high density lipoprotein cholesterol (HDL-C). HDL2-C, and HDL3-C, apolipoprotein AI (apo AI, AII), and B-100 concentrations and non-fasting samples. We conclude that plasma triglyceride concentration is significantly affected in the post-prandial state. As a result, VLDL-C and LDL-C when assessed by the Friedewald formula are also altered. A minimum of 8 h fasting is required to assess these concentrations accurately in this population.(ABSTRACT TRUNCATED AT 250 WORDS)

Recent clinical trials in hypertension suggest that thiazide diuretics may increase coronary heart deaths in selected patients, possibly through adverse effects on serum potassium, lipids, lipoproteins, and/or apolipoproteins. Administration of smaller doses of diuretics has been recommended to decrease this risk. We evaluated 12.5-mg and 112.5-mg daily doses of hydrochlorothiazide (HCTZ) administered for 1 month to nine postmenopausal black female hypertensives using a double-blind, randomized, crossover design. Both regimens produced significant reductions in sitting diastolic blood pressure, a mean of 11 mm Hg with the high dose and 8 mm Hg with the low dose. The high dose produced a mean 0.7 mEq/L reduction in serum potassium while the low dose caused no change. Both doses produced similar changes in serum lipoproteins. Statistically significant elevations were seen in total cholesterol (approximately 12%), LDL cholesterol (approximately 20%), cholesterol: HDL ratio (approximately 15%), and apolipoprotein B (approximately 20%). Apolipoprotein A1 was significantly reduced (approximately 6%). These results support the use of low doses of HCTZ in mild hypertension to avoid hypokalemia, but suggest that adverse changes in serum lipids will occur.

Premature coronary artery disease is believed to be a major cause of death in patients undergoing long-term haemodialysis. We investigated the effects of chronic maintenance haemodialysis on lipid, lipoprotein and apolipoprotein levels of 42 black patients with chronic renal failure and compared them with those of 40 age- and sex-matched black controls to determine the changes in the lipoprotein profile and their possible contributions to increased risk of coronary heart disease in these patients. There were increases in triglyceride levels and in total/high density lipoprotein cholesterol ratios and decreases in high density lipoprotein cholesterol, in LDL cholesterol, in apolipoprotein AI and in apolipoprotein AII in haemodialysis patients in comparison to controls. No significant differences were observed in any of the lipid, lipoprotein and apolipoprotein levels between male and female patients and between patients receiving anti-hypertensive therapy and those who were not. Our findings suggest that haemodialysis and/or events associated with maintenance dialysis may contribute to unfavourable variations in lipoprotein metabolism and, in turn, the increased mortality from coronary artery disease in this patient population.

Apolipoproteins play major roles in regulating lipoprotein synthesis and catabolism. Apolipoprotein AI activates the lecithin cholesterol acyltransferase, apolipoprotein CII and CIII regulate the lipoprotein lipase, and apolipoprotein B-100, B-48, and E control the cholesterol uptake into hepatic and extrahepatic cells. Therefore, investigating the alterations of lipoprotein metabolism in disease states at the apolipoprotein level may give increased insight into the underlying mechanisms of lipoprotein changes and provide better understanding about the premature development of the atherogenic process.

Aims: We examined the association between lipoprotein (Lp)(a) and CHD among women with type 2 diabetes. Methods: Of 32,826 women from the Nurses' Health Study who provided blood at baseline, we followed 921 who had a confirmed diagnosis of type 2 diabetes. Results: During 10 years of follow-up (6,835 person-years), we documented 122 incident cases of CHD. After adjustment for age, smoking, BMI, glycosylated HbA1c, triglycerides (TGs), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and other cardiovascular risk factors, the relative risk (RR) comparing extreme quintiles of Lp(a) was 1.95 (95% CI 1.07–3.56). The association was not appreciably altered after further adjustment for apolipoprotein B100 or several inflammatory biomarkers. Increasing levels of Lp(a) were associated with lower levels of TGs. The probability of developing CHD over 10 years was higher among diabetic women with substantially higher levels of both Lp(a) (>1.07 μmol/l) and TGs (>2.26 mmol/l) than among diabetic women with lower levels (22 vs 10%, p log-rank test= 0.049). Diabetic women with a higher level of only Lp(a) or TGs had a similar (14%) risk. In a multivariate model, diabetic women with higher levels of Lp(a) and TGs had an RR of 2.46 (95% CI 1.21–5.01) for developing CHD, as compared with those with lower levels of both biomarkers (p for interaction=0.413). The RRs for women with a higher level of either Lp(a) (RR=1.22, 95% CI 0.77–1.92) or TGs (RR=1.39, 95% CI 0.78–2.42) were comparable. Conclusions/interpretation: Increased levels of Lp(a) were independently associated with risk of CHD among diabetic women. [ABSTRACT FROM AUTHOR]

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 beta 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 > or = 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. [ABSTRACT FROM AUTHOR]