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Triglycerides are associated with cardiovascular risk largely mediated by their final product of catabolism, the cholesterol-rich remnant, which may come from the liver or the intestine. There is a direct association between fasting and postprandial triglycerides and cardiovascular risk. ApoB is associated with the number of particles and the amount of RC, which explains its determining role in CVD. Non-HDL cholesterol represents atherogenic lipoproteins, with correlation and concordance with apoB; both are cardiovascular risk markers. Lipoprotein (a) is a cardiovascular risk factor not only because of the cholesterol and apoB it contributes, but also because of its proinflammatory and prothrombotic activity. Viewing these factors holistically, it is important to note that it is primarily a reduction in apoB, remnant cholesterol and non-HDL cholesterol that reduces cardiovascular events. A 10% weight loss improves TG levels without reducing apoB or cardiovascular risk. Of the classic lipid-lowering agents, high-dose statins and ethyl eicosapentanoate reduce cardiovascular risk through apoB, RC, and non-HDL reduction. To date, we do not have lipid-lowering agents aimed at reducing Lp(a), which is only slightly reduced by PCSK9 inhibitors and markedly reduced by LDL apheresis. These residual risk markers serve not only to stratify cardiovascular risk but also to establish follow-up goals. [ABSTRACT FROM AUTHOR]

Papers on the familial lipid disorder, dysbetalipoproteinemia (FD), appeared in early seventies of the last century describing the combined elevation in total cholesterol (TC) and triglycerides (TG) in the blood of affected individuals, which is associated with mutations in the apo-lipoprotein E (Apo E) gene. Different methods and measurements for diagnosis and consequent treatment of these cases had been suggested. Stress was put on the E2/E2 homozygotes, Apo B and non-high density lipoprotein cholesterol as the main obvious manifestations of the disease, with a big variation in the results among different workers. This short review will present most of these variations in nature, diagnosis and management of FD, with a reference to a recent Iraqi work on this subject. [ABSTRACT FROM AUTHOR]

Purpose of Review: Implementation of intensive LDL cholesterol (LDL-C) lowering strategies and recognition of the role of triglyceride-rich lipoproteins (TRL) in atherosclerosis has prompted re-evaluation of the suitability of current lipid profile measurements for future clinical practice. Recent Findings: At low concentrations of LDL-C (< 1.8 mmol/l/70 mg/dl), the Friedewald equation yields estimates with substantial negative bias. New equations provide a more accurate means of calculating LDL-C. Recent reports indicate that the increase in risk per unit increment in TRL/remnant cholesterol may be greater than that of LDL-C. Hence, specific measurement of TRL/remnant cholesterol may be of importance in determining risk. Non-HDL cholesterol and plasma apolipoprotein B have been shown in discordancy analyses to identify individuals at high risk even when LDL-C is low. Summary: There is a need to adopt updated methods for determining LDL-C and to develop better biomarkers that more accurately reflect the abundance of TRL remnant particles. [ABSTRACT FROM AUTHOR]

• It is acceptable to screen with nonfasting lipids. • It is recommended to follow up abnormal results with fasting levels. • Non-HDL cholesterol levels can effectively guide ASCVD prevention. • Advanced lipoprotein tests may guide therapeutic decisions in select patients. • Better harmonization of advanced lipid measurement methods is needed. • Recommendations for lipids in clinical care. Lipoprotein measurements are pivotal in the management of patients at risk for atherosclerotic coronary heart disease (CHD) with myocardial infarction and coronary death as the main outcomes, and for atherosclerotic cardiovascular disease (ASCVD), which includes CHD and stroke. Recent developments and changes in guidelines affect optimization of using lipid measures as cardiovascular biomarkers. This scientific statement reviews the pre-analytical, analytical, post-analytical, and clinical aspects of lipoprotein measurements. Highlights include the following: i) It is acceptable to screen with nonfasting lipids. ii) non-high-density lipoprotein HDL-cholesterol (non-HDL-C) is measured reliably in either the fasting or the nonfasting state and can effectively guide ASCVD prevention. iii) low density lipoprotein cholesterol (LDL-C) can be estimated from total cholesterol, high density lipoprotein cholesterol (HDL-C), and triglyceride (TG) measurements. For patients with LDL-C>100 mg/dL and TG ≤150 mg/dL it is reasonable to use the Friedewald formula. However, for those with TG 150-400 mg/dL the Friedewald formula for LDL-C estimation is less accurate. The Martin/Hopkins method is recommended for LDL-C estimation throughout the range of LDL-C levels and up to TG levels of 399 mg/dL. For TG levels ≥400 mg/dL LDL-C estimating equations are currently not recommended and newer methods are being evaluated. iv) When LDL-C or TG screening results are abnormal the clinician should consider obtaining fasting lipids. v) Advanced lipoprotein tests using apolipoprotein B (apoB), LDL Particle Number (LDL-P) or remnant cholesterol may help to guide therapeutic decisions in select patients, but data are limited for patients already on lipid lowering therapy with low LDL-C levels. Better harmonization of advanced lipid measurement methods is needed. Lipid measurements are recommended 4-12 weeks after a change in lipid treatment. Lipid laboratory reports should denote desirable values and specifically identify extremely elevated LDL-C levels (≥190 mg/dL at any age or ≥160 mg/dL in children) as severe hypercholesterolemia. Potentially actionable abnormal lipid test results, including fasting triglycerides (TG) ≥500 mg/dL, should be reported as hypertriglyceridemia. Appropriate use and reporting of lipid tests should improve their utility in the management of persons at high risk for ASCVD events. [ABSTRACT FROM AUTHOR]

Background: In cholesterol guidelines, low-density lipoprotein (LDL) cholesterol remains the primary target while apolipoprotein B (apoB) and non-high-density lipoprotein (non-HDL) cholesterol are secondary targets.Objectives: This study sought to determine if elevated apoB and/or non-HDL cholesterol are superior to elevated LDL cholesterol in identifying statin-treated patients at residual risk of all-cause mortality and myocardial infarction.Methods: In total, 13,015 statin-treated patients from the Copenhagen General Population Study were included with 8 years median follow-up. Cox regressions among apoB, non-HDL cholesterol, and LDL cholesterol, respectively, and all-cause mortality or myocardial infarction were examined on continuous scales by restricted cubic splines and by categories of concordant and discordant values defined by medians.Results: High apoB and non-HDL cholesterol were associated with increased risk of all-cause mortality and myocardial infarction, whereas no such associations were found for high LDL cholesterol. Compared with concordant values below medians, discordant apoB above the median with LDL cholesterol below yielded hazard ratios of 1.21 (95% confidence interval [CI]: 1.07 to 1.36) for all-cause mortality and 1.49 (95% CI: 1.15 to 1.92) for myocardial infarction. Corresponding values for high non-HDL cholesterol with low LDL cholesterol were 1.18 (95% CI: 1.02 to 1.36) and 1.78 (95% CI: 1.35 to 2.34). In contrast, discordant high LDL cholesterol with low apoB or non-HDL cholesterol was not associated with increased risk of all-cause mortality or myocardial infarction. Also, discordant high apoB with low non-HDL cholesterol yielded hazard ratios of 1.21 (95% CI: 1.03 to 1.41) for all-cause mortality and of 0.93 (95% CI: 0.62 to 1.40) for myocardial infarction. Furthermore, dual discordant apoB and non-HDL cholesterol above the medians with LDL cholesterol below presented hazard ratios of 1.23 (95% CI: 1.07 to 1.43) for all-cause mortality and 1.82 (95% CI: 1.37 to 2.42) for myocardial infarction.Conclusions: In statin-treated patients, elevated apoB and non-HDL cholesterol, but not LDL cholesterol, are associated with residual risk of all-cause mortality and myocardial infarction. Discordance analysis demonstrates that apoB is a more accurate marker of all-cause mortality risk in statin-treated patients than LDL cholesterol or non-HDL cholesterol, and apoB in addition is a more accurate marker of risk of myocardial infarction than LDL cholesterol. [ABSTRACT FROM AUTHOR]

Non-high density lipoprotein cholesterol (non-HDLC) represents the cholesterol in triglyceride-rich lipoproteins (TRL) and low-density lipoproteins (LDL). Apolipoprotein B (apoB) reflects the number of TRL and LDL particles. In hypertriglyceridemia (HTG), there is triglyceride (TG) enrichment of TRLs, and also a substantial increase of cholesterol in larger TRLs that considerably augments the non-HDLC value. Therefore, in HTG, non-HDLC could increase disproportionately with respect to apoB. We aimed to compare the relative effect of the full range of mild, moderate, and severe HTG on the status of non-HDLC and apoB as cardiovascular disease (CVD) risk markers. Analysis of lipid profile data from 4347 patients in a Lipid Clinic cohort with baseline fasting lipid profiles documented prior to starting lipid-lowering medications. The correlation between non-HDLC and apoB was assessed in intervals of increasing TG. Non-HDLC and apoB were analyzed at each TG level using comparative CVD risk equivalent categories and assessed for divergence and discordance. With increasing TG levels: (1) the correlation between non-HDLC and apoB diminished progressively, (2) non-HDLC levels increased continuously, whereas apoB levels plateaued after an initial increase up to TG of ~ 4.0-5.0 mmol/L (~354-443 mg/dL), (3) there was divergence in the stratification of non-HDLC and apoB into CVD risk equivalent categories. Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in the presence of severe HTG. This has never been tested. With increasing HTG severity, discordance between non-HDLC and apoB can cause clinically important divergence in CVD risk categorization. • As TG increases, the correlation between non-HDLC and apoB decreases progressively. • In HTG, discordant non-HDLC and apoB causes divergence in CVD risk categorization. • Non-HDLC and apoB should not be viewed as interchangeable CVD risk markers in HTG. [ABSTRACT FROM AUTHOR]

Purpose of Review: Guidelines propose using non-HDL cholesterol or apolipoprotein (apo) B as a secondary treatment target to reduce residual cardiovascular risk of LDL-targeted therapies. This review summarizes the strengths, weaknesses, opportunities, and threats (SWOT) of using apoB compared with non-HDL cholesterol. Recent Findings: Non-HDL cholesterol, calculated as total-HDL cholesterol, includes the assessment of remnant lipoprotein cholesterol, an additional risk factor independent of LDL cholesterol. ApoB is a direct measure of circulating numbers of atherogenic lipoproteins, and its measurement can be standardized across laboratories worldwide. Discordance analysis of non-HDL cholesterol versus apoB demonstrates that apoB is the more accurate marker of cardiovascular risk. Baseline and on-treatment apoB can identify elevated numbers of small cholesterol-depleted LDL particles that are not reflected by LDL and non-HDL cholesterol. Summary: ApoB is superior to non-HDL cholesterol as a secondary target in patients with mild-to-moderate hypertriglyceridemia (175–880 mg/dL), diabetes, obesity or metabolic syndrome, or very low LDL cholesterol < 70 mg/dL. When apoB is not available, non-HDL cholesterol should be used to supplement LDLC. [ABSTRACT FROM AUTHOR]

Background: Lipid-lowering therapy is guided by Low-density-lipoprotein cholesterol (LDL-c) levels, although the cardiovascular disease (CVD) risk could be better reflected by other lipid parameters. This study aimed at comparing a comprehensive lipid profile between patients with type 2 diabetes mellitus (T2DM) with LDL-c concentration within and above target. Methods: A comprehensive lipid profile was characterized in 96 T2DM patients. The European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2016 and 2019 Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. Results: In this population, only 28.1 and 16.7% of patients had mean LDL-c levels within target, as defined by the 2016 and 2019 guidelines, respectively. Applying the 2016 guidelines criteria, in patients with LDL-c within target, 22, 25 and 44% presented non-high-density lipoprotein cholesterol (non-HDL-c), Apolipoprotein B (ApoB) and oxidized LDL-c levels above the recommended range, respectively, whereas according to the 2019 guidelines criteria, 50, 39 and 44% of the patients with LDL-c within target had elevated high-density lipoprotein cholesterol (HDL-c), ApoB and oxidized LDL-c levels, respectively. LDL-c was strongly correlated with non-HDL-c (r = 0.850), ApoB (r = 0.656) and oxidized LDL-c (r = 0.508). Similarly, there was a strong correlation between non-HDL-c with both ApoB (r = 0.808) and oxidized LDL-c (r = 0.588). Conclusions: These findings emphasize the limitations of only considering LDL-c concentration for cardiovascular (CV) risk assessment. Targeting only LDL-c could result in missed opportunities for CV risk reduction in T2DM patients. These data suggest that non-HDL-c, ApoB and oxidized LDL-c levels could be considered as an important part of these patients' evaluation allowing for a more accurate estimation of CV risk and hopefully better management of these high-risk patients. [ABSTRACT FROM AUTHOR]

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 (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total – HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipid-lowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]-cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2–10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC 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. [ABSTRACT FROM AUTHOR]

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. Image 1 • 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. • Lipoprotein(a)-cholesterol is part of measured or calculated LDL cholesterol and lipoprotein(a) should be measured at least once in all patients. • 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. • Laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds. [ABSTRACT FROM AUTHOR]

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Background: Apolipoprotein B (apoB) is known to be a more powerful predictor of cardiovascular disease than conventional lipids. We aimed to determine the clinical relevance of a newly developed equation to estimate serum apoB levels based on total cholesterol, HDL cholesterol and triglycerides in patients with high cardiovascular risk. Methods: The occurrence of a major cardiovascular event (MCVE) was assessed using the data from the Treating to New Targets (TNT) and Incremental Decrease in End points through Aggressive Lipid lowering (IDEAL) trials. Results: Pooled analysis of these two data sets showed that both directly-measured apoB (HR per 1-SD (95% CI): 1.16 (1.11--1.21), P < 0.001) and apoB estimated from the eq. (HR per 1-SD (95% CI): 1.14 (1.09--1.19), P < 0.001) were significantly associated with the development of a future MCVE. Prediction of MCVEs by the apoB eq. (C statistic 0.650) was nearly identical to that of directly-measured apoB (0.651). In addition, the net reclassification indices indicated no difference in the prediction of MCVEs between models including the apoB equation and directlymeasured apoB (1% (--1.3--4.0), P = 0.31). Conclusions: Our equation to predict apoB levels showed MCVE risk prediction comparable to directly-measured apoB in high risk patients with previous coronary heart disease. [ABSTRACT FROM AUTHOR]

Purpose of Review: The objective of this review was to summarize evidence gathered for the prognostic value of routine and novel blood lipids and lipoproteins measured in patients with acute coronary syndromes (ACS). Recent Findings: Data supports clear association with risk and actionable value for non-high-density lipoprotein (Non-HDL) cholesterol and plasma ceramides in a setting of ACS. The prognostic value and clinical actionability of apolipoprotein B (apoB) and lipoprotein(a) [Lp(a)] in ACS have not been thoroughly tested, while the data for omega-3 fatty acids and oxidized low-density lipoprotein (Ox-LDL) are either untested or more varied. Summary: Measuring basic lipids, which should include Non-HDL cholesterol, at the time of presentation for ACS is guideline mandated. Plasma ceramides also provide useful information to guide both treatment decisions and follow-up. Additional studies targeting ACS patients are necessary for apoB, Lp(a), omega-3 fatty acids, and Ox-LDL. [ABSTRACT FROM AUTHOR]

Background Atherogenic dyslipidemia is highly prevalent in the Arabian Gulf. Non–high-density lipoprotein cholesterol (non-HDL-C) reduction has been proposed as an additional goal to low-density lipoprotein cholesterol (LDL-C) lowering to prevent atherosclerotic cardiovascular disease (ASCVD). Data on non–HDL-C goal attainment in patients with high triglycerides (TGs) on lipid-lowering drugs (LLDs) in the region is scarce. Objective Evaluate non–HDL-C target attainment according to the National Lipid Association in patients on LLDs stratified by TG (<150 [1.69], 150–200 [1.69–2.26], >200 [2.26] mg/dL [mmol/L]) levels in the Arabian Gulf. Methods Overall, 4383 patients on LLD treatment from 6 Middle Eastern countries participating in the Centralized Pan-Middle East Survey on the Undertreatment of Hypercholesterolemia study were evaluated. Patients were classified according to TG levels and ASCVD risk. Results The overall non–HDL-C goal attainment was 41% of the subjects. Non–HDL-C goal was less likely attained in patients with high TGs (12% vs 27% vs 55%; P < .001). Very high ASCVD risk patients with high TGs attained less their non–HDL-C targets compared with those with lower TG levels (8% vs 23% vs 51%; P < .001). Similarly, high ASCVD risk patients with high TGs also failed more in attaining non–HDL-C targets compared with those with lower TGs (26% vs 42% vs 69%; P < .001). In addition, those with high TG also succeeded less in attaining LDL-C and apolipoprotein B goals ( P < .001). Conclusions A large proportion of very high and high ASCVD patients on LLDs in the Arabian Gulf are not at recommended non–HDL-C targets and hence remain at a substantial residual risk. [ABSTRACT FROM AUTHOR]

Background Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy in people at risk for cardiovascular diseases. Mipomersen inhibits apolipoprotein B-100 (apoB) synthesis and causes reduction in LDL-C by reducing apoB. Objective We aimed to perform a meta-analysis of all published randomized controlled trials comparing safety and efficacy of mipomersen with placebo in adults with dyslipidemia. Methods We searched PUBMED, CENTRAL, and EMBASE from inception through March 2014 and used random-effects model to compute the effect size. Results We identified 8 randomized controlled trials (n = 462). Mipomersen compared with placebo significantly reduced LDL-C by 32.37% (95% confidence interval, 25.55–39.18; P < .00001), total cholesterol by 24.18% (18.54–29.83; P < .00001), very low–density lipoprotein cholesterol by 21.59% (9.16–34.02; P = .0007), non–high-density lipoprotein cholesterol (HDL-C) by 30.83% (23.92–37.74; P < .00001), and triglycerides by 36.26% (22–50.54; P < .00001). It also significantly reduced apoB, lipoprotein(a), and apolipoprotein A1. However, mipomersen did not significantly change HDL-C levels. In safety analysis, mipomersen compared with placebo increased the risks of injection-site reaction (risk ratio, 2.05; 95% confidence interval, 1.39–3.04; P = .0003), flu-like symptoms (1.63; 1.22–2.17; P = .0008), alanine aminotransferase ≥3X upper limit of normal (4.44; 1.67–11.86; P = .003), and hepatic steatosis (3.85, 1.39–10.67; P = .01). The risks of alanine aminotransferase ≥10X upper limit of normal did not reach statistical significance (1.57; 0.32–7.6, P = .58). Conclusion Mipomersen resulted in a significant improvement in lipid parameters except for HDL-C and increased the risks of injection-site reactions, flu-like symptoms, and hepatic steatosis compared with placebo. [ABSTRACT FROM AUTHOR]

The association between atherogenic dyslipidemia (AD) and incident type 2 diabetes (T2D) in the low-risk group for T2D has not yet been determined. The aims of this study were to investigate whether AD, characterized by increased serum apoB and non-HDL cholesterol, could predict the development of T2D in subjects with normal glucose tolerance (NGT). A total of 84,394 subjects with NGT (48,906 men and 35,488 women), aged 20-89 years (mean age 38.4 years), were enrolled in this study and were followed for a mean duration of 3.3 years. ApoB and non-HDL cholesterol levels showed stronger associations with the development of T2D compared with conventional lipid measurements and their ratios (HR per 1-SD (95 % CI) 1.27 (1.23-1.30) and 1.27 (1.24-1.29), respectively, both P < 0.001). In multivariate Cox regression models, both apoB and non-HDL cholesterol were associated with the development of T2D, independent of other risk factors for T2D, fasting serum glucose, HbA1c, and conventional lipid measurements such as triglycerides and HDL cholesterol (HR per 1-SD (95 % CI) 1.16 (1.11-1.21) and 1.15 (1.11-1.19), respectively, both P < 0.001). However, fasting serum glucose was not associated with the development of T2D in these models. In conclusion, AD was more closely associated with the development of T2D than fasting glucose or glycated hemoglobin in subjects with NGT. [ABSTRACT FROM AUTHOR]

Abstract: Background: The ratio of apolipoprotein B (apoB) to apolipoprotein A1 (apoA1) has been reported to be associated with metabolic syndrome (MetS) and insulin resistance (IR). Non-HDL-C is regarded as a surrogate marker for apoB in routine clinical practice. However, it is unclear whether the ratio of non-HDL-C to HDL-C is an equal or a better predictor than the apoB/apoA1 ratio for the identification of MetS and IR. Methods: We performed a retrospective study of 41,821 Korean adults who participated in a routine health screening examination. Anthropometry, fasting glucose, fasting insulin, HOMA-IR, CRP, lipid profiles, apoB, and apoA1 were measured. Results: To compare the predictive value for MetS between different lipid ratios, we analyzed the ROC curves of apoB/apoA1 and non-HDL-C/HDL-C ratios. ROC analysis showed that the AUCs of non-HDL-C/HDL-C (0.75 [95% CI=0.74–0.76] in men and 0.84 [95% CI=0.83–0.85] in women) were significantly higher than those of apoB/apoA1 (0.66 [95% CI=0.65–0.67] in men and 0.77 [95% CI=0.76–0.78] in women). The non-HDL-C/HDL-C ratio also showed a significantly stronger association with HOMA-IR than the apoB/apoA1 ratio. The optimal cutoff value of the non-HDL-C/HDL-C ratio for detection of MetS in men was 3.39, with a sensitivity of 66.7% and a specificity of 71.8%, whereas the optimal ratio cutoff value in women was 2.89, with a sensitivity of 75.7% and a specificity of 78.1%. Conclusions: Our findings indicate that the non-HDL-C/HDL-C ratio is a better marker than the apoB/apoA1 ratio for identifying IR and MetS in Koreans. [Copyright &y& Elsevier]

Background: The preference of the apolipoprotein (apo) B/apoA-I ratio over the total cholesterol/HDL cholesterol (TC/HDL-C) ratio in cardiovascular risk prediction is disputed. Cholesteryl ester transfer protein (CETP) is instrumental in lipoprotein remodelling and affects the cholesterol content in pro- and antiatherogenic lipoproteins relative to their major apolipoproteins. We tested the influence of common CETP variations on the strength of associations of a first major adverse cardiovascular event (MACE) with the apoB/apoA-I ratio compared with the TC/HDL-C ratio. Methods: A prospective case-cohort study was performed (PREVEND cohort; no previous cardiovascular disease and no use of lipid-lowering drugs initially). Fasting serum TC/HDL-C, apoB/apoA-I, triglycerides, and common CETP variations (TaqIB [rs708272] and -629C>A [rs1800775] polymorphisms) were measured at baseline. The composite end point was incident MACE. Results: A total of 532 of 6780 subjects experienced a first MACE during 10.8 years follow-up. The age- and sex-adjusted hazard ratio was 1.31 (95 % confidence interval 1.23–1.41) for the apoB/apoA-I ratio and 1.22 (95% confidence interval 1.26–1.39) for the TC/HDL-C ratio (both P < .001). These relationships were essentially similar within each TaqIB and -629C>A CETP genotype group. No interactions of the apoB/apoA-I ratio and the TC/HDL-C ratio with the TaqIB and the -629C>A CETP variations on incident MACE were observed (P > .20 for all). Conclusion: The relationship of first MACE with the TC/HDL-C and the apoB/apoA-I ratio is not to an important extent dependent on common CETP variations. CETP variations are unlikely to affect the strength of the relationship of first MACE with the apoB/apoA-I ratio compared with the TC/HDL-C ratio. [ABSTRACT FROM AUTHOR]

Despite aggressive lipid-lowering therapy, patients continue to be at significant risk of coronary heart disease (CHD). Assessment of non-high-density lipoprotein cholesterol (non-HDL-C) provides a measure of cholesterol contained in all atherogenic particles. In the third Adult Treatment Panel (ATP III) guidelines of the US National Cholesterol Education Program, non-HDL-C was introduced as a secondary target of therapy in persons with triglycerides ≥200 mg/dL. A recent meta-analysis of the relationship between non-HDL-C reduction and CHD risk showed non-HDL-C as an important target of therapy for CHD prevention. Most lipid-modifying drugs used as monotherapy have a 1:1 relationship between percent non-HDL-C lowering and percent CHD reduction. In the EPIC-Norfolk prospective population study, 21,448 participants without diabetes or CHD between 45 and 79 years of age were followed for 11.0 years. Participants with high non-HDL-C levels were at increased CHD risk independently of their LDL-C levels. Also, compared to apolipoprotein B, non-HDL-C appears to be a better choice given the fact that no additional tests or costs are needed and established cut points are already available. Future guidelines should emphasize the importance of non-HDL-C for guiding cardiovascular prevention strategies with an increased need to have non-HDL-C reported on routine lipid panels. [ABSTRACT FROM AUTHOR]

Abstract: There is little understanding of the reliability of laboratory measurements among clinicians. Low-density lipoprotein cholesterol (LDL-C) measurement is the cornerstone of cardiovascular risk assessment and prevention, but it is fraught with error. Therefore, we have reviewed issues related to accuracy and precision for the measurement of LDL-C and the related markers non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B. Despite the widespread belief that LDL-C is standardized and reproducible, available data suggest that results can vary significantly as the result of methods from different manufacturers. Similar problems with direct HDL-C assays raise concerns about the reliability of non-HDL-C measurement. The root cause of method-specific bias relates to the ambiguity in the definition of both LDL and HDL, and the heterogeneity of LDL and HDL particle size and composition. Apolipoprotein B appears to provide a more reliable alternative, but assays for it have not been as rigorously tested as direct LDL-C and HDL-C assays. [Copyright &y& Elsevier]

Background: Dysbetalipoproteinemia, also known as type III hyperlipoproteinemia (type III HL), is characterized by the accumulation of β-very low density lipoprotein (β-VLDL). However, demonstration of the presence of β-VLDL is not easy because it requires preparative ultracentrifugation of lipoproteins. The primary genetic defect in type III HL is the presence of apolipoprotein (apo) E2, a mutant form of apoE. However, another metabolic defect, such as overproduction of VLDL, is also required for the full phenotype. Patients with only E2 homozygosity usually do not have HL. Because apoE genotyping is expensive, the selection of patients for this analysis by effective use of common clinical measures would be very helpful. Objective: We examined the non-HDL-C/apoB ratio as an index for type III HL screening. Methods: We studied nine patients with type III HL. Most patients with type III HL show mixed hyperlipidemia. We compared the plasma of patients with combined hyperlipidemia and the dyslipidemia of hypothyroidism with those with type III HL. The serum levels of total cholesterol, triglyceride, and high-density lipoprotein cholesterol (HDL-C), as well as the serum apoB and apoE levels, were measured by routine laboratory methods. Results: Individual values of serum lipids and apolipoproteins did not distinguish type III HL from the two other types of HL. The non-HDL-C/apoB ratio in type III HL was significantly greater than that in the two comparison groups, with no overlap. Conclusion: The non-HDL-C/apoB ratio is a novel index that appears to be reliable for screening of patients for type III HL, and the index can be determined at regular clinical laboratories without the need for any complicated lipoprotein analysis. Thus, we propose the clinical usefulness of this index. [Copyright &y& Elsevier]

Abstract: Epidemiological evidence supports the use of non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B-100 (apoB), and low-density lipoprotein particles as markers of atherogenic risk. Treatment guidelines also identify these as additional targets of lipid-modifying intervention in patients with elevated triglycerides (TG). Even when TG are only moderately elevated, many patients on statin monotherapy who have achieved targets for low-density lipoprotein cholesterol (LDL-C) fail to reach non-HDL-C treatment goals, and even fewer reach apoB goals. Combination lipid-modifying therapy is therefore indicated for comprehensive lipid management, particularly in patients with type 2 diabetes and metabolic syndrome in whom LDL-C levels are often considered ‘optimal’. Of the available options, adding either a niacin, fibrate or omega-3 fatty acids provides greater opportunity to achieve non-HDL-C and apoB targets, given complementary profiles of lipid-modifying activity and supported by evidence from clinical studies. Improvement in lipid control and reduction in atherogenic risk could be anticipated to translate to benefits in clinical outcomes. [Copyright &y& Elsevier]

Summary: Objectives: To assess the relationship between non-classical cardiovascular (CV) risk factors including non-HDL cholesterol (non-HDL-C), apolipoprotein B, triglycerides to HDL ratio, LDL size, inflammation or oxidative stress parameters and carotid intima-media thickness (CIMT), in order to better identify prevention or therapeutic targets. In addition, we studied the relationship between metabolic syndrome (MS) and CIMT. Methods: Cross-sectional study including 232 HIV-positive (HIV+) adults (80% treated by combined antiretroviral therapy) extracted from the ANRS CO3 Aquitaine Cohort. Results: There was a significant association of higher non-HDL-C (p <0.01), apolipoprotein B (p <0.01) levels or TG/HDL ratio (p <0.05) with higher CIMT when compared the first vs fourth quartile, while there is no association between CIMT and LDL-C (p =0.09) or LDL size (p =0.55). In multivariate analysis, only the TG/HDL molar ratio > 1.5 tend toward significance (p =0.08). MS was observed in only 7.3% of patients with the NCEP-ATP III definition and 11.2% with the IDF criteria. Whatever the used definition, there was a significant association between MS presence and increased CIMT (p <0.05) in univariate and multivariate model. Conclusions: Non-HDL-C, TG/HDL ratio and apolipoprotein B levels, which are closely linked to lipid disorders associated to the MS, appear as stronger predictive markers than LDL-C for screening subclinical atherosclerosis in HIV+ populations. Achieving non-HDL-C target defined by the NCEP-ATP III guidelines appears of great importance to reduce CV complications in HIV+ patients. [Copyright &y& Elsevier]

Summary: Objective: Few studies have compared non-HDL cholesterol (non-HDLc) and Apolipoprotein B (apoB) as markers of atherosclerotic risk. No such study has yet been undertaken in Asian-Indians who have a different lipid–lipoprotein profile than their Western counterparts. Our aim, therefore, was to evaluate the role of non-HDLc and apoB, as markers of all potentially atherogenic species, and to further assess as to which is the better index of the risk of cardiovascular disease (CVD) in type 2 diabetic subjects. Research design and methods: Lipidic parameters, apoB and carotid mean intima–media thickness (IMT) were determined in the 95 diabetic subjects included in the study. Subjects were classified on the basis of apoB and triglyceride as well as non-HDLc and triglyceride levels. Agreement of the resultant phenotypes with IMT was assessed (correlation and concordance (κ) analysis), and the major contributor to the variance of IMT was determined using multistep linear regression. Results: HyperapoB was the most prevalent lipoproteic abnormality. The correlation between apoB and non-HDLc was strong in the whole cohort (r =0.60, p <0.01) and better in the hypertriglyceridemic subgroup (r =0.67, p <0.01). There was significant concordance between IMT and apoB and non-HDLc in the whole cohort (κ =0.490, p <0.0001; κ =0.403, p <0.000); while the concordance between the apoB and non-HDLc dependent phenotypes and IMT was better in the hypertriglyceridemic subgroup (HtgHapob-κ =0.598, p <0.0001; HtgHnonhdl-κ =0.481, p <0.0001) as opposed to the normotriglyceridemic subgroup (NtgHapob-κ =0.387, p <0.0001; NtgHnonhdl-κ =0.043, p =NS). Further apoB was a better predictor of IMT in all the subgroups as well as the whole cohort (R 2 =0.378, β-coefficient=0.002) as compared to non-HDLc (R 2 change=0.030, β-coefficient=0.0017). Conclusions: Non-HDLc and apoB are equivalent atherogenic markers of cardiovascular risk in hypertriglyceridemic diabetic subjects, but apoB is a better index of the risk of cardiovascular disease in normotriglyceridemic subjects. Thus, measurement of apoB might be helpful in identification of a subgroup of apparently normolipidemic subjects who have hyperapoB and thus stand increased cardiovascular risk. [Copyright &y& Elsevier]

Lipid abnormalities associated with urinary albumin excretion rate in Taiwanese type 2 diabetic patients.Background.The purpose of this study was to examine the lipid abnormalities associated with urinary albumin excretion rate (UAER) in type 2 diabetic patients.Methods.A total of 275 (122 men and 153 women; aged 60.6± 11.1 years) patients were selected with stringent criteria to prevent confounders. Normoalbuminuria (N= 152) and albuminuria (N= 123) were defined as urinary albumin-to-creatinine ratio (ACR) of<30 and≥30μg/mg, respectively. Total cholesterol, triglycerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, and apolipoproteins A1 (ApoA1) and B (ApoB) were measured and non-HDL cholesterol calculated. The subjects were divided into four phenotypes based on triglycerides (<1.5 or≥1.5 mmol/L) and ApoB (<1.2 or≥1.2 g/L).Results.Total cholesterol, ApoB, and non-HDL cholesterol were significantly (P<0.05) higher in patients with albuminuria. For quartiles of the lipid parameters, prevalences of albuminuria showed significant association with ApoB and non-HDL cholesterol (Ptrend<0.05). After adjusting for age, systolic blood pressure and hemoglobin A1c (HbA1c) correlation coefficients between the natural logarithm (ln) ACR and lipid parameters, odds ratios for albuminuria, and standardized regression coefficients for ln ACR, were significant for total cholesterol, ApoB and non-HDL cholesterol in all subjects and in men, but only ApoB was significant in women. For patients with normoalbuminuria, frequencies of normotriglycerides/normo-ApoB, hypertriglycerides/normo-ApoB, normotriglycerides/hyper-ApoB, and hypertriglycerides/hyper-ApoB were 44.7%, 28.9%, 10.5%, and 15.8%, respectively; and were 30.1%, 19.5%, 15.4%, and 35.0% for patients with albuminuria (P<0.001). The respective adjusted odds ratio for albuminuria for the four phenotypes was 1.00, 1.04 (0.54 to 2.00), 2.25 (1.02 to 5.00), and 3.38 (1.75 to 6.53).Conclusion.Increased UAER is associated with ApoB-containing lipoproteins and the phenotype of hypertriglycerides/hyper-ApoB is associated with the highest risk of albuminuria. The surrogate marker of non-HDL cholesterol for ApoB is more applicable to the diabetic men. [ABSTRACT FROM AUTHOR]