Discordance between lipoprotein particle number and cholesterol content: an update

Cantey, Eric; Wilkins, John T.

doi:10.1097/med.0000000000000389

Cited by 36 publications

(27 citation statements)

References 36 publications

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“…Indeed, despite the Emerging Risk Factor Collaboration results, many investigators and guidelines have continued to recommend measurement of apolipoproteins in risk factor assessment. 9,14,28,29 Our results broadly fit and extend data from Emerging Risk Factor Collaboration and are in line with recommendations made by other investigators, 30 as well as recent clinical guidelines; indeed, in these guidelines, it was noted the apolipoproteins were not available to all clinicians and were more expensive than usual lipid measures. 4 Furthermore, a recent study showed that ApoB may be more informative than LDL-C in estimating the impact of genetic variation in lipid processing pathways.…”

Section: Discussionsupporting

confidence: 88%

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease

et al. 2019

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Section: Discussionsupporting

confidence: 88%

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease

et al. 2019

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“…Chylomicron particles each contain one molecule of apoB48 and are present in plasma either as intact or remnant particles (5). Within minutes of entering the systemic circulation, a chylomicron particle binds to multiple molecules of LPL on the capillary endothelium of adipose tissue, skeletal muscle, and the heart.…”

Section: Chylomicron Particlesmentioning

confidence: 99%

“…This discordance between lipid composition and particle number is important because there is considerable evidence that the atherogenic risk associated with the apoB lipoproteins relates more closely to the number of apoB particles compared with the mass of cholesterol within them (5). Moreover, with the exception of type III hyperlipoproteinemia, while the proportion of VLDL apoB versus LDL apoB particles is greater in patients with hypertriglyceridemia than in others, LDL particles continue to account for the majority of apoB particles (6).…”

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confidence: 99%

Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding

Sniderman

Couture

Martin

et al. 2018

Journal of Lipid Research

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Triglycerides are the conventional tool to measure VLDLs, whereas LDL cholesterol (LDL-C) is the conventional tool to measure LDLs. Multiple epidemiological studies, including a series of genetically based analyses, have demonstrated that cardiovascular risk is related to triglycerides independently of LDL-C, and this has led to a series of new therapeutic agents designed specifically to reduce plasma triglycerides. The triglyceride hypothesis posits that increased levels of triglycerides increase cardiovascular risk and decreasing plasma triglycerides decreases cardiovascular risk. In this work, we will examine the validity of the triglyceride hypothesis by detailing the biological complexities associated with hypertriglyceridemia, the genetic epidemiological evidence in favor of hypertriglyceridemia, the evidence from the fibrate randomized clinical trials relating triglycerides and clinical outcomes, and the completeness of the evidence from the initial studies of novel mutations and the therapeutic agents based on these mutations that lower triglycerides. Because of the multiple metabolic links between VLDL and LDL, we will try to demonstrate that measuring triglycerides and LDL-C alone are inadequate to document the lipoprotein profile. We will try to demonstrate that apoB must be measured, as well as triglycerides and cholesterol, to have an accurate estimate of lipoprotein status.

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“…They are most commonly quantified by their cholesterol content (LDL cholesterol [LDL‐C]) using indirect (Friedewald) calculation . On the other hand, cholesterol content of LDL particles (LDL‐P) can vary in the same person as well as between individuals . This variation sometimes results in a discordance between measures of LDL‐C and the actual number of LDL‐P.…”

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confidence: 99%

NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

Schettler¹,

Muellendorff²,

Schettler³

et al. 2019

Ther Apher Dial

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Taking into account the discordance between low‐density lipoprotein cholesterol (LDL‐C) and LDL particle (LDL‐P) number, cardiovascular risk more closely correlates with LDL‐P in patients. The aim of our study was to evaluate the number of lipid particles in patients with severe hypercholesterolemia treated with different lipid‐lowering regimens. Four groups of patients differing with respect to lipid‐lowering therapy were recruited from hypercholesterolemic outpatients and lipoprotein apheresis (LA) facilities, and were treated with statins alone (group A), with statins and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (PCSK9i) (group B), with statins and LA (group C), or with statins, PCSK9i, and LA (group D). Cholesterol, triglycerides, LDL‐C, high‐density lipoprotein cholesterol (HDL‐C), LDL‐P number and size, HDL‐P number and size were determined using nuclear magnetic resonance spectroscopy. The lowest LDL‐P number was achieved at the end of LA sessions in combination with statins or in combination with statins and a monoclonal PCSK9i (median; 25th and 75th percentile) (group C: 244 nmoL/L: 237, 244, P < 0.05; group D: 244 nmoL/L: 99, 307, P < 0.05). Comparing LDL‐P number at the start of LA (group C: 978 nmoL/L: 728, 1404; group D: 954 nmoL/L: 677, 1521) to the other patient groups (groups A and B), the lowest LDL‐P number was measured in patients treated with PCSK9i and a statin (group B): LDL‐P (762 nmoL/L: 604, 1043, P < 0.05), large LDL‐P (472 nmoL/L: 296, 574, P < 0.05), and small LDL‐P (342 nmoL/L: 152, 494, P < 0.05). Very low‐density lipoprotein and HDL particle sizes remained approximately the same in all groups. LA in combination with statins or in combination with statins and PCSK9i most reduced LDL‐P numbers in hypercholesterolemic patients.

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Discordance between lipoprotein particle number and cholesterol content: an update

Abstract: In addition to traditional lipid fractions, assessments of atherogenic particle number should be strongly considered whenever assessing CVD risk in nontreated and treated individuals. There is a need for clinical trials that focus not only on the reduction in LDL-C but apoB, as well.

Cited by 36 publications

References 36 publications

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease

Comparison of Conventional Lipoprotein Tests and Apolipoproteins in the Prediction of Cardiovascular Disease

Hypertriglyceridemia and cardiovascular risk: a cautionary note about metabolic confounding

NMR‐based lipoprotein analysis for patients with severe hypercholesterolemia undergoing lipoprotein apheresis or PCSK9‐inhibitor therapy (NAPALI‐Study)

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