Clinical implications of discordance between low-density lipoprotein cholesterol and particle number

Otvos, James D.; Mora, Samia; Shalaurova, Irina; Greenland, Philip; Mackey, Rachel H.; Goff, David C.

doi:10.1016/j.jacl.2011.02.001

Cited by 311 publications

(258 citation statements)

References 31 publications

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“…In addition, our study measured LDL particle number as opposed to LDL cholesterol obtained by the Friedewald calculation. While both measures predict cardiovascular risk, they do not always correlate (1,54). In support of our findings are the reports of higher cholesterol levels in partially (55) or completely CD36-deficient individuals (9) and the higher LDL levels and abnormal cholesterol absorption of CD36-null mice (24,56).…”

Section: 11supporting

confidence: 83%

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Love‐Gregory

Kraja

Allum

et al. 2016

Journal of Lipid Research

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Elevated fasting lipid levels have traditionally been associated with increased risk of heart disease, diabetes, and stroke. More recently, similar and independent associations were found with levels of nonfasting or postprandial lipids (1, 2). Nonfasting measurements incorporate those of chylomicrons (CMs) produced in response to dietary fat Abstract Cluster of differentiation 36 (CD36) variants influence fasting lipids and risk of metabolic syndrome, but their impact on postprandial lipids, an independent risk factor for cardiovascular disease, is unclear. We determined the effects of SNPs within a 410 kb region encompassing CD36 and its proximal and distal promoters on chylomicron (CM) remnants and LDL particles at fasting and at 3.5 and 6 h following a high-fat meal (Genetics of Lipid Lowering Drugs and Diet Network study, n = 1,117). Five promoter variants associated with CMs, four with delayed TG clearance and five with LDL particle number. To assess mechanisms underlying the associations, we queried expression quantitative trait loci, DNA methylation, and ChIP-seq datasets for adipose and heart tissues that function in postprandial lipid clearance. Several SNPs that associated with higher serum lipids correlated with lower adipose and heart CD36 mRNA and aligned to active motifs for PPAR, a major CD36 regulator. The SNPs also associated with DNA methylation sites that related to reduced CD36 mRNA and higher serum lipids, but mixed-model analyses indicated that the SNPs and methylation independently influence CD36 mRNA. The findings support contributions of CD36 SNPs that reduce

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Section: 11supporting

confidence: 83%

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Love‐Gregory

Kraja

Allum

et al. 2016

Journal of Lipid Research

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“…Coronary atherosclerosis severity as evaluated logical and/or case-control studies and randomized controlled statin trials that compared LDL-C, non-HDL-C, and apolipoprotein B for the risk of cardiovascular events demonstrated that non-HDL-C and apolipoprotein B were somewhat superior to LDL-C [42][43][44] . Large prospective cohort studies using nuclear magnetic resonance spectroscopy to compare LDL particle number to LDL-C reported that LDL particle number was more strongly associated with the risk of cardiovascular events than LDL-C [45][46][47] . These results support the hypothesis that the total number of atherogenic lipoproteins is more important than LDL-C for CVD risk.…”

Section: Discussionmentioning

confidence: 99%

Elevated Small Dense Low-Density Lipoprotein Cholesterol as a Predictor for Future Cardiovascular Events in Patients with Stable Coronary Artery Disease

Nishikura

Koba

Yokota

et al. 2014

JAT

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Aim:The aim of the present study was to investigate how small dense low-density lipoprotein cholesterol (sdLDL-C) compared with LDL-C affect the long-term prognosis in patients with stable coronary artery disease (CAD). Methods: sdLDL-C measured by heparin magnesium precipitation and LDL particle size measured by non-denatured gradient-gel electrophoresis were compared in 190 consecutive CAD patients who underwent coronary arteriography between 2003 and 2004 who did or did not develop cardiovascular events during a seven-year follow-up period. Cardiovascular events were death caused by cardiovascular diseases (CVDs), onset of acute coronary syndrome, need for coronary and peripheral arterial revascularization, hospitalization for heart failure, surgical procedure for any CVDs, and/or hospitalization for stroke. Results: First-time cardiovascular events were observed in 72 patients. Those who experienced cardiovascular events were older and had higher prevalence rates of hypertension and diabetes; significantly higher Gensini coronary atherosclerotic scores; significantly higher levels of sdLDL-C, sdLDL-C/LDL-C, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratios; and greater glycated hemoglobin (Hb)A1c and brain natriuretic peptide (BNP) levels. They also had significantly smaller LDL particle sizes, HDL-C, apolipoprotein A-1, and estimated glomerular filtration rate (GFR) compared with patients without cardiovascular events. Conversely, LDL-C, non-HDL-C, apolipoprotein B, remnantlike particle cholesterol, and high-sensitivity C-reactive protein (hs-CRP) levels were similar between the two groups. A Kaplan-Meyer event-free survival curve demonstrated that patients with sdLDL-C ≥ 35 mg/dL (median level) had significantly poorer prognosis compared with those with lower sdLDL-C levels, while patients with LDL-C ≥ 100 mg/dL had a non-significantly lower survival rate. Conclusion: These results confirm that sdLDL-C is a very promising biomarker to predict future cardiovascular events in the secondary prevention of stable CAD. J Atheroscler Thromb, 2014; 21:755-767.

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“…In patients with discordant LDL‐C and LDL‐P levels, LDL‐attributable atherogenic risk was shown to be more strongly correlated with LDL‐P than LDL‐C levels 27, 28. Similarly, HDL‐P is proposed to be better correlated with CVD risk than HDL‐C 29, 30, 31, 32.…”

Section: Introductionmentioning

confidence: 99%

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

Tomassini

Tershakovec

et al. 2015

JAHA

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BackgroundPatients with diabetes mellitus and cardiovascular disease may not achieve adequate low‐density lipoprotein cholesterol (LDL‐C) lowering on statin monotherapy, attributed partly to atherogenic dyslipidemia. More intensive LDL‐C–lowering therapy can be considered for these patients. A previous randomized, controlled study demonstrated greater LDL‐C lowering in diabetic patients with symptomatic cardiovascular disease who switched from simvastatin 20 mg (S20) or atorvastatin 10 mg (A10) to combination ezetimibe/simvastatin 10/20 mg (ES10/20) therapy, compared with statin dose‐doubling (to S40 or A20) or switching to rosuvastatin 10 mg (R10). The effect of these regimens on novel biomarkers of atherogenic dyslipidemia (low‐ and high‐density lipoprotein particle number and lipoprotein‐associated phospholipase A2 [Lp‐PLA2]) was assessed.Methods and ResultsTreatment effects on low‐ and high‐density lipoprotein particle number (by NMR) and Lp‐PLA2 (by ELISA) were evaluated using plasma samples available from 358 subjects in the study. Switching to ES10/20 reduced low‐density lipoprotein‐particle number numerically more than did statin dose‐doubling and was comparable with R10 (−133.3, −94.4, and −56.3 nmol/L, respectively; P>0.05). Increases in high‐density lipoprotein particle number were significantly greater with switches to ES10/20 versus statin dose‐doubling (1.5 and −0.5 μmol/L; P<0.05) and comparable with R10 (0.7 μmol/L; P>0.05). Percentages of patients attaining low‐density lipoprotein particle number levels <990 nmol/L were 62.4% for ES10/20, 54.1% for statin dose‐doubling, and 57.0% for R10. Switching to ES10/20 reduced Lp‐PLA2 activity significantly more than did statin dose‐doubling (−28.0 versus −3.8 nmol/min per mL, P<0.05) and was comparable with R10 (−28.0 versus −18.6 nmol/min per mL; P>0.05); effects on Lp‐PLA2 concentration were modest.ConclusionsIn diabetic patients with dyslipidemia, switching from statins to combination ES10/20 therapy generally improved lipoprotein subclass profile and Lp‐PLA2 activity more than did statin dose‐doubling and was comparable with R10, consistent with its lipid effects.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00862251.

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Clinical implications of discordance between low-density lipoprotein cholesterol and particle number

Abstract: Background-The amount of cholesterol per LDL particle is variable and related in part to particle size, with smaller particles carrying less cholesterol. This variability causes concentrations of LDL cholesterol (LDL-C) and LDL particles (LDL-P) to be discordant in many individuals.

Cited by 311 publications

References 31 publications

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Higher chylomicron remnants and LDL particle numbers associate with CD36 SNPs and DNA methylation sites that reduce CD36

Elevated Small Dense Low-Density Lipoprotein Cholesterol as a Predictor for Future Cardiovascular Events in Patients with Stable Coronary Artery Disease

Effect of Switching From Statin Monotherapy to Ezetimibe/Simvastatin Combination Therapy Compared With Other Intensified Lipid‐Lowering Strategies on Lipoprotein Subclasses in Diabetic Patients With Symptomatic Cardiovascular Disease

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