Purpose of reviewSubfractions of LDL and HDL defined by differences in particle size and density have been associated to varying degrees with risk of cardiovascular disease (CVD). Assessment of these relationships has been clouded by lack of standardization among the various analytic methodologies a

Lipoprotein subfractions and cardiovascular disease risk.

Although the inverse relationship between plasma levels of high-density lipoprotein (HDL) and cardiovascular disease has been largely demonstrated, many observations have suggested that the assessment of HDL functionality might be more informative than a simple measurement of HDL-cholesterol plasma levels. HDLs are a class of structurally and functionally heterogeneous particles; in atherosclerosis-related diseases, changes in HDL subfraction levels and functions are frequently observed. Circulating levels of large HDL particles are decreased in dyslipidaemic conditions, while levels of small dense HDL particles are increased in patients with coronary heart disease. Furthermore, specific genetic defects in proteins involved in HDL metabolism significantly impact the distribution of HDL subpopulations. Finally, many drugs used for dyslipidaemia induce changes in HDL subfractions strictly related to cardiovascular disease. Although several methods exist to evaluate HDL subclass levels, most of them are not easily applicable in clinical practice, due to the costs and high variability. However, the possibility to measure the levels of specific HDL subfractions in patients with atherosclerosis-related diseases might help to better define their cardiovascular risk.

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High-Density Lipoprotein Subfractions - What the Clinicians Need to Know

Review Form First Author, Year: ___________________ Ref ID #__________ Abstractor Initials: ___ ___ ___ Primary Inclusion/Exclusion Criteria 1. Relevant to SER topic Yes No Cannot Determine 2. Attempts internal or external validation Yes No Cannot Determine 3. Published in English Yes No Cannot Determine 4. Original research (exclude reviews, editorials, commentaries, letters to editor, etc.) Yes No Cannot Determine 5. Eligible Study types a. Randomized controlled trials b. Controlled clinical trials

Systematic Review of Cardiovascular Disease Risk Assessment Tools

High-density lipoprotein subclasses and their relationship to cardiovascular disease

The role of low-density lipoprotein cholesterol (LDL-C) in the pathogenesis of cardiovascular disease (CVD) and the clinical benefit of lowering LDL-C in high-risk patients is well established. What remains controversial is whether we are using the best measure(s) of LDL characteristics to identify all individuals who are at CVD risk or if they would benefit from specific therapies. Despite the successful LDL-C reduction trials, substantial numbers of patients continue to have clinical events in the treatment groups. The size of LDL particles and assessment of the number of LDL particles (LDL-Num) have been suggested as a more reliable method of atherogenicity. Each LDL particle has one apoprotein B-100 measure attached; therefore, determination of whole plasma apoprotein B can be considered the best measure of LDL-Num. Because the cholesterol content per LDL particle exhibits large interindividual variation, the information provided by LDL-C and LDL-Num is not equivalent. Individuals with the same level of LDL-C may have higher or lower numbers of LDL particles and, as a result, may differ in terms of absolute CVD risk. LDL particle size and number provide independent measures of atherogenicity and are strong predictors of CVD.

Is it LDL particle size or number that correlates with risk for cardiovascular disease

Background: High-density lipoprotein (HDL) subtractions are among the new emerging risk factors for atherosclerosis. In particular, HDL 2b has been shown to be linked to cardiovascular risk. This study uses a novel microfluidics-based method to establish HDL 2b clinical utility using samples from the Prospective Cardiovascular Muenster (PROCAM) Study. Methods: Method performance was established by measuring accuracy, precision, linearity and inter-site precision. Serum samples from 503 individuals collected in the context of the PROCAM study were analyzed by electrophoresis on a microfluidics system. Of these, 251 were male survivors of myocardial infarction (cases), while 252 individuals were matched healthy controls. HDL cholesterol, HDL 2b concentration and HDL 2b percentage were analyzed. Results: This novel method showed satisfactory assay performance with an inter-site coefficient of variance of <10% for HDL 2b percentage. Parallel patient testing on 52 samples between two sites resulted in a correlation coefficient of r=0.95. Significant differences were observed in the HDL 2b subfraction between cases and controls independent of other risk factors. Including HDL 2b percentage in logistic regression reduced the number of false positives from 64 to 39 and the number of false negative cases from 48 to 45, in the context of this study. Conclusions: The novel method showed satisfactory assay performance in addition to drastically reduced analysis times and improved ease of use as compared to other methods. Clinical utility of HDL 2b was demonstrated supporting the findings of previous studies.

PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol.

Mark Van Cleve

Papers

PROCAM Study: risk prediction for myocardial infarction using microfluidic high-density lipoprotein (HDL) subfractionation is independent of HDL cholesterol.