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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. 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]

Abstract: B cells play a role in atherosclerosis. B lymphocytes may reduce the progression of vascular disease. Antibody production against modified auto-antigens is an element in the atheroprotective involvement of B lymphocytes. Paradoxical evidence is emerging from animal studies that suggest a proatherogenic B-cell behaviour independently of autoantibody production. One aspect that has received limited consideration is the role of genetic susceptibility modulated by extracellular matrix proteins. Haptoglobin is a polymorphic glycoprotein that binds to CD22 on B lymphocytes. Hp phenotypes show an important molecular heterogeneity. Hp 2-2 has been linked to an increased susceptibility for atherosclerosis. Haptoglobin and its polymorphism play a role in B-cell migration and function. Hp phenotypes may influence B-T cell dialogue and T cell activation. Haptoglobin is involved in the interplay of lymphocytes, neutrophils, and monocytes. Haptoglobin binds to the CD11b/CD18 receptor and to mast cells. HDL particles can become pro-inflammatory through interactions of Hp-Hb complexes with apolipoprotein A1. Haptoglobin is a chemoattractant to pre-B lymphocytes and monocytes. Beyond the conventional view of haptoglobin as a marker of hemolysis, several findings point towards an immunomodulatory effect of haptoglobin in B-cell mediated progression of atherosclerosis. The balance between proatherogenic and protective immunological properties of the different Hp phenotypes determines if lesions progress or regress. Clinical studies indicate a strong association between the Hp 2-2 phenotype and a more frequent onset of diabetic complications and cardiovascular disease. Findings in animal models (where no haptoglobin polymorphism is present) cannot always be extrapolated to humans. [Copyright &y& Elsevier]

Abstract: Background: A new method (sLDL-EX “SEIKEN”) is commercially available for the direct quantification of small dense LDL-cholesterol (sd-LDL) on automated chemistry analyzers, without manual sample pretreatment. We evaluated the performance of this direct assay to estimate the small dense LDL subclass phenotype (“non-A”), defined by polyacrylamide gel tube electrophoresis. Methods: Fasting serum samples from 189 healthy subjects (age 18–75y, 96 females) were collected. The direct sd-LDL assay (from Randox Laboratories) was applied on a Roche Modular P analyzer. The Quantimetrix LipoprintTM LDL System was used to define LDL subclass phenotypes (A and non-A). ROC curve analysis was performed for sd-LDL and other lipids and apolipoproteins (apo) with respect to phenotype non-A. Results: sd-LDL concentrations (40.4±18.6mg/dl) in the total group correlated (P<0.0001) with apoB (r=0.831), apoB/A-I ratio (r=0.757), non-HDL-cholesterol (r=0.821), triglycerides (r=0.439), and LDL-cholesterol (r=0.641). Higher sd-LDL concentrations (P<0.0001) were measured in subjects with LDL phenotype non-A (53.6±17.0mg/dl, n=92) than in those with phenotype A (27.9±8.9mg/dl, n=97). In logistic regression analysis, sd-LDL and apoA-I were independently associated with LDL subclass phenotype non-A. Highest areas under ROC curves were obtained for sd-LDL (0.943), triglycerides (0.833), triglyceride/HDL-cholesterol (0.838) and apoB/A-I ratio (0.826) to predict phenotype non-A. The sd-LDL cut-off point for optimal sensitivity (87.9%) and specificity (92.8%) was >38.5mg/dl. Conclusions: The direct, homogeneous sd-LDL method is easily applicable on an automated chemistry analyzer and shows acceptable performance to estimate the electrophoretic LDL subclass phenotype. [Copyright &y& Elsevier]