Background
The cholesterol content of low-density lipoprotein (LDL) particles is variable, causing
frequent discrepancies between concentrations of LDL cholesterol (LDL-C) and LDL particle
number (LDL-P). In managing patients at risk for cardiovascular disease (CVD) to LDL
target levels, it is unclear whether LDL-C provides the optimum measure of residual
risk and adequacy of LDL-lowering treatment.
Objective
To compare the ability of alternative measures of LDL to provide CVD risk discrimination
at relatively low levels consistent with current therapeutic targets.
Methods
Concentrations of LDL-C and non–HDL-C were measured chemically and LDL-P and VLDL-P
were measured by nuclear magnetic resonance in 3066 middle-aged white participants
(53% women) without CVD in the Framingham Offspring cohort. The main outcome measure
was incidence of first CVD event.
Results
At baseline, the cholesterol content per LDL particle was negatively associated with
triglycerides and positively associated with LDL-C. On follow-up (median 14.8 years),
265 men and 266 women experienced a CVD event. In multivariable models adjusting for
nonlipid CVD risk factors, LDL-P was related more strongly to future CVD in both genders
than LDL-C or non–HDL-C. Subjects with a low level of LDL-P (<25th percentile) had
a lower CVD event rate (59 events per 1000 person-years) than those with an equivalently
low level of LDL-C or non–HDL-C (81 and 74 events per 1000 person-years, respectively).
Conclusions
In a large community-based sample, LDL-P was a more sensitive indicator of low CVD
risk than either LDL-C or non–HDL-C, suggesting a potential clinical role for LDL-P
as a goal of LDL management.
Keywords
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References
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin Chem. 1972; 18: 499-502
- Effect of moderate hypertriglyceridemia on the relation of plasma total and LDL apoB levels.Atherosclerosis. 1991; 89: 109-116
- Lipoprotein particle analysis by nuclear magnetic resonance spectroscopy.Clin Lab Med. 2006; 26: 847-870
- Executive Summary of The Third Report of The National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).JAMA. 2001; 285: 2486-2497
- Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines.Circulation. 2004; 110: 227-239
- Measurement issues related to lipoprotein heterogeneity.Am J Cardiol. 2002; 90: 22i-29i
- Low-density lipoprotein particle number and risk for cardiovascular disease.Curr Atheroscler Rep. 2004; 6: 381-387
- Apolipoproteins versus lipids as indices of coronary risk and as targets for statin therapy treatment.Lancet. 2003; 361: 777-780
- Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk.Am J Cardiol. 2003; 91: 1173-1177
- Comparison of the relationships between serum apolipoprotein B and serum lipid distributions.Clin Chem. 2005; 51: 2257-2263
- Assessment of reaching goal in patients with combined hyperlipidemia: low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, or apolipoprotein B.Am J Cardiol. 2005; 96: 36K-43K
- Increased small low-density lipoprotein particle number: a prominent feature of the metabolic syndrome in the Framingham Heart Study.Circulation. 2006; 113: 20-29
- Heterogeneity of low density lipoprotein particle number in patients with type 2 diabetes mellitus and low density lipoprotein cholesterol <100 mg/dl.Am J Cardiol. 2006; 98: 1599-1602
- Clinical utility of different lipid measures for prediction of coronary heart disease in men and women.JAMA. 2007; 298: 776-785
- Low-density lipoprotein, non-high-density lipoprotein, and apolipoprotein B as targets of lipid-lowering therapy.Circulation. 2002; 106: 2526-2529
- Non–high-density lipoprotein and very-low-density lipoprotein cholesterol and their risk predictive values in coronary heart disease.Am J Cardiol. 2006; 98: 1363-1368
- An investigation of coronary heart disease in families.Am J Epidemiol. 1979; 110: 281-290
- Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions.Clin Chim Acta. 1987; 166: 1-8
- Sex and age differences in lipoprotein subclasses measured by nuclear magnetic resonance spectroscopy: The Framingham Study.Clin Chem. 2004; 50: 1189-1200
- Differences in LDL subspecies involve alterations in lipid composition and conformational changes in apolipoprotein B.J Lipid Res. 1996; 37: 1924-1935
- Some risk factors related to the annual incidence of cardiovascular disease and death in pooled repeated biennial measurements.Framingham Heart Study: 30 Year Follow-Up. US Department of Health and Human Services, Bethesda, MD1987
- Short-term effects of beta blockers atenolol, nadolol, pindolol, and propranolol on lipoprotein metabolism in normolipemic subjects.J Clin Pharmacol. 1987; 27: 475-480
- Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the Insulin Resistance Atherosclerosis Study (IRAS).Circulation. 2005; 111: 3465-3472
- Nuclear magnetic resonance spectroscopy of lipoproteins and risk of coronary heart disease in the Cardiovascular Health Study.Arterioscler Thromb Vasc Biol. 2002; 22: 1175-1180
- Relations of lipoprotein subclass levels and low-density lipoprotein size to progression of coronary artery disease in the Pravastatin Limitation of Atherosclerosis in the Coronary Arteries (PLAC-I) Trial.Am J Cardiol. 2002; 90: 89-94
- Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women.Circulation. 2002; 106: 1930-1937
- LDL and HDL particle subclasses predict coronary events and are changed favorably by gemfibrozil therapy in the Veterans Affairs HDL Intervention Trial (VA-HIT).Circulation. 2006; 113: 1556-1563
- Lack of evidence for recommended low-density lipoprotein treatment targets: a solvable problem.Ann Intern Med. 2006; 145: 520-530
- Reducing residual risk for patients on statin therapy: the potential role of combination therapy.Am J Cardiol. 2005; 96: 3K-13K
- MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial.Lancet. 2002; 360: 7-22
- Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study.Lancet. 2006; 368: 919-928
- Metabolic origins and clinical significance of LDL heterogeneity.J Lipid Res. 2002; 43: 1363-1379
- Cholesteryl ester transfer protein: a novel target for raising HDL and inhibiting atherosclerosis.Arterioscler Thromb Vasc Biol. 2003; 23: 160-167
- Action of atorvastatin in combined hyperlipidemia: preferential reduction of cholesterol ester transfer from HDL to VLDL1 particles.Arterioscler Thromb Vasc Biol. 2000; 20: 189-197
- Effectiveness of high doses of simvastatin as monotherapy in mixed hyperlipidemia.Am J Cardiol. 2001; 87: 232-234
- Effects of pravastatin treatment on lipoprotein subclass profiles and particle size in the PLAC-I Trial.Atherosclerosis. 2002; 160: 41-48
- Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial.Eur Heart J. 2003; 24: 1843-1847
- The effect of atorvastatin on serum lipids, lipoproteins and NMR spectroscopy defined lipoprotein subclasses in type 2 diabetic patients with ischemic heart disease.Atherosclerosis. 2003; 167: 243-255
- Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.J Intern Med. 2006; 259: 247-258
Article info
Publication history
Published online: October 22, 2007
Accepted:
October 11,
2007
Received:
June 19,
2007
Identification
Copyright
© 2007 National Lipid Association. Published by Elsevier Inc. All rights reserved.
