Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population

Observations from the Dallas Heart Study

Htet W. Khine, John F. Teiber, Robert W. Haley, Amit Khera, Colby R. Ayers, Anand Rohatgi

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Background and aims Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. Methods Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). Conclusions Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

Original languageEnglish (US)
Pages (from-to)156-162
Number of pages7
JournalAtherosclerosis
Volume263
DOIs
StatePublished - Aug 1 2017

Fingerprint

HDL Lipoproteins
Peroxidase
Cardiovascular Diseases
Serum
Population
Aryldialkylphosphatase
Interleukin-18
Proportional Hazards Models
C-Reactive Protein
Lipoproteins
Coronary Disease
Body Mass Index
Smoking
Stroke
Myocardial Infarction
Cholesterol
Inflammation

Keywords

  • HDL particle concentration
  • Incident cardiovascular disease
  • Myeloperoxidase
  • Paroxonase-1

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

@article{19748ec9060b482eb57b572badff3d5a,
title = "Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population: Observations from the Dallas Heart Study",
abstract = "Background and aims Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. Methods Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74{\%} increase in incident ASCVD (aHR, 1.74, 95{\%} CI 1.12–2.70) and a 91{\%} increase in total incident CVD (aHR, 1.91, 95{\%} CI 1.27–2.85). Conclusions Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.",
keywords = "HDL particle concentration, Incident cardiovascular disease, Myeloperoxidase, Paroxonase-1",
author = "Khine, {Htet W.} and Teiber, {John F.} and Haley, {Robert W.} and Amit Khera and Ayers, {Colby R.} and Anand Rohatgi",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.atherosclerosis.2017.06.007",
language = "English (US)",
volume = "263",
pages = "156--162",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",

}

TY - JOUR

T1 - Association of the serum myeloperoxidase/high-density lipoprotein particle ratio and incident cardiovascular events in a multi-ethnic population

T2 - Observations from the Dallas Heart Study

AU - Khine, Htet W.

AU - Teiber, John F.

AU - Haley, Robert W.

AU - Khera, Amit

AU - Ayers, Colby R.

AU - Rohatgi, Anand

PY - 2017/8/1

Y1 - 2017/8/1

N2 - Background and aims Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. Methods Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). Conclusions Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

AB - Background and aims Myeloperoxidase (MPO), a product of systemic inflammation, promotes oxidation of lipoproteins; whereas, high-density lipoprotein (HDL) exerts anti-oxidative effects in part via paraoxonase-1 (PON1). MPO induces dysfunctional HDL particles; however, the interaction of circulating levels of these measures in cardiovascular disease (CVD) has not been studied in humans. We tested whether serum levels of MPO indexed to HDL particle concentration (MPO/HDLp) are associated with increased CVD risk in a large multiethnic population sample, free of CVD at baseline. Methods Levels of MPO, HDL-C, and HDL particle concentration (HDLp) by NMR were measured at baseline in 2924 adults free of CVD. The associations of MPO/HDLp with incident ASCVD (first non-fatal myocardial infarction, non-fatal stroke, coronary revascularization, or CVD death) and total CVD were assessed in Cox proportional-hazards models adjusted for traditional risk factors. The median follow-up period was 9.4 years. Results Adjusted for sex and race/ethnicity, MPO/HDLp was associated directly with body mass index, smoking status, high-sensitivity C-reactive protein, and interleukin 18, and inversely with age, HDL-C levels, HDL size, and PON1 arylesterase activity, but not with cholesterol efflux. In fully adjusted models, the highest versus lowest quartile of MPO/HDLp was associated with a 74% increase in incident ASCVD (aHR, 1.74, 95% CI 1.12–2.70) and a 91% increase in total incident CVD (aHR, 1.91, 95% CI 1.27–2.85). Conclusions Increased MPO indexed to HDL particle concentration (MPO/HDLp) at baseline is associated with increased risk of incident CVD events in a population initially free of CVD over the 9.4 year period.

KW - HDL particle concentration

KW - Incident cardiovascular disease

KW - Myeloperoxidase

KW - Paroxonase-1

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U2 - 10.1016/j.atherosclerosis.2017.06.007

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EP - 162

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

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