Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women
It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD)...
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| Published in: | Clinical chemistry (Baltimore, Md.) Vol. 63; no. 4; pp. 870 - 879 |
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| Main Authors: | , , , , , , , |
| Format: | Journal Article |
| Language: | English |
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Oxford University Press
01.04.2017
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| ISSN: | 0009-9147, 1530-8561 |
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| Abstract | It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant.
Among 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models.
Although all 3 biomarkers were correlated (
≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both
< 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk.
Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment. |
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| AbstractList | It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant.
Among 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models.
Although all 3 biomarkers were correlated (
≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both
< 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk.
Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment. BACKGROUNDIt is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant.METHODSAmong 27533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models.RESULTSAlthough all 3 biomarkers were correlated (r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to nonHDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical risk factors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk.CONCLUSIONSDiscordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement of lipoprotein particle concentration might better inform CHD risk assessment. It is uncertain whether measurement of circulating total atherogenic lipoprotein particle cholesterol mass [non-HDL cholesterol (nonHDLc)] or particle concentration [apolipoprotein B (apo B) and LDL particle concentration (LDLp)] more accurately reflects risk of incident coronary heart disease (CHD). We evaluated CHD risk among women in whom these markers where discordant. Among 27 533 initially healthy women in the Women's Health Study (NCT00000479), using residuals from linear regression models, we compared risk among women with higher or lower observed particle concentration relative to nonHDLc (highest and lowest residual quartiles, respectively) to individuals with agreement between markers (middle quartiles) using Cox proportional hazards models. Although all 3 biomarkers were correlated (r ≥ 0.77), discordance occurred in up to 20.2% of women. Women with discordant high particle concentration were more likely to have metabolic syndrome (MetS) and diabetes (both P < 0.001). Over a median follow-up of 20.4 years, 1246 CHD events occurred (514725 person-years). Women with high particle concentration relative to non-HDLc had increased CHD risk: age-adjusted hazard ratio (95% CI) = 1.77 (1.56-2.00) for apo B and 1.70 (1.50-1.92) for LDLp. After adjustment for clinical riskfactors including MetS, these risks attenuated to 1.22 (1.07-1.39) for apo B and 1.13 (0.99-1.29) for LDLp. Discordant low apo B or LDLp relative to nonHDLc was not associated with lower risk. Discordance between atherogenic particle cholesterol mass and particle concentration occurs in a sizeable proportion of apparently healthy women and should be suspected clinically among women with cardiometabolic traits. In such women, direct measurement oflipoprotein particle concentration might better inform CHD risk assessment. |
| Author | Glynn, Robert J Akinkuolie, Akintunde O Ridker, Paul M Sniderman, Allan D Lawler, Patrick R Mora, Samia Buring, Julie E Chasman, Daniel I |
| AuthorAffiliation | 4 Harvard T. H. Chan School of Public Health, Boston, MA 5 Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal, QC, Canada 1 Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 3 Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 2 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA |
| AuthorAffiliation_xml | – name: 2 Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA – name: 4 Harvard T. H. Chan School of Public Health, Boston, MA – name: 1 Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA – name: 5 Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal, QC, Canada – name: 3 Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA |
| Author_xml | – sequence: 1 givenname: Patrick R surname: Lawler fullname: Lawler, Patrick R organization: Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Harvard T.H. Chan School of Public Health, Boston, MA – sequence: 2 givenname: Akintunde O surname: Akinkuolie fullname: Akinkuolie, Akintunde O organization: Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA – sequence: 3 givenname: Paul M surname: Ridker fullname: Ridker, Paul M organization: Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA – sequence: 4 givenname: Allan D surname: Sniderman fullname: Sniderman, Allan D organization: Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre, Montreal, QC, Canada – sequence: 5 givenname: Julie E surname: Buring fullname: Buring, Julie E organization: Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Harvard T.H. Chan School of Public Health, Boston, MA – sequence: 6 givenname: Robert J surname: Glynn fullname: Glynn, Robert J organization: Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Harvard T.H. Chan School of Public Health, Boston, MA – sequence: 7 givenname: Daniel I surname: Chasman fullname: Chasman, Daniel I organization: Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA – sequence: 8 givenname: Samia surname: Mora fullname: Mora, Samia organization: Center for Lipid Metabolomics, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Cardiovascular Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, Preventive Medicine Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/28174174$$D View this record in MEDLINE/PubMed |
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| Copyright | 2016 American Association for Clinical Chemistry. Copyright American Association for Clinical Chemistry Apr 2017 |
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| SubjectTerms | Apolipoprotein B Apolipoproteins Apolipoproteins B - blood Atherosclerosis - blood Biomarkers Biomarkers - blood Cardiovascular disease Cardiovascular diseases Cholesterol Cholesterol - blood Controlled Clinical Trials as Topic Coronary artery disease Coronary Disease - blood Diabetes mellitus Discordance Female Hazards Health risk assessment Healthy Volunteers Heart Heart diseases High density lipoprotein Humans Lipids Low density lipoprotein Metabolic disorders Metabolic syndrome Middle Aged NMR Nuclear magnetic resonance Quartiles Regression analysis Risk assessment Risk Factors Women's Health Womens health |
| Title | Discordance between Circulating Atherogenic Cholesterol Mass and Lipoprotein Particle Concentration in Relation to Future Coronary Events in Women |
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