Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease

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Abstract

Background

Lipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD).

Methods

Three hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels.

Results

After dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 μg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 μg/L and in the 1st tertile (Lp-PLA2 values < 101 μg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 μg/L. A linear regression analysis showed that Lp-PLA2 values > 138 μg/L negatively correlated to FMD [b = − 0.45 (95% CI: − 0.79 – -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57–3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with β-blockers.

Conclusions

Elevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12944-021-01438-4.

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Most cited references 29

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The influence of heart rate on augmentation index and central arterial pressure in humans.

I Wilkinson, H MacCallum, L. Flint … (2000)

Arterial stiffness is an important determinant of cardiovascular risk. Augmentation index (AIx) is a measure of systemic arterial stiffness derived from the ascending aortic pressure waveform. The aim of the present study was to assess the effect of heart rate on AIx. We elected to use cardiac pacing rather than chronotropic drugs to minimize confounding effects on the systemic circulation and myocardial contractility. Twenty-two subjects (13 male) with a mean age of 63 years and permanent cardiac pacemakers in situ were studied. Pulse wave analysis was used to determine central arterial pressure waveforms, non-invasively, during incremental pacing (from 60 to 110 beats min-1), from which AIx and central blood pressure were calculated. Peripheral blood pressure was recorded non-invasively from the brachial artery. There was a significant, inverse, linear relationship between AIx and heart rate (r = -0.76; P < 0.001). For a 10 beats min-1 increment, AIx fell by around 4 %. Ejection duration and heart rate were also inversely related (r = -0. 51; P < 0.001). Peripheral systolic, diastolic and mean arterial pressure increased significantly during incremental pacing. Although central diastolic pressure increased significantly with pacing, central systolic pressure did not. There was a significant increase in the ratio of peripheral to central pulse pressure (P < 0.001), which was accounted for by the observed change in central pressure augmentation. These results demonstrate an inverse, linear relationship between AIx and heart rate. This is likely to be due to alterations in the timing of the reflected pressure wave, produced by changes in the absolute duration of systole. Consideration of wave reflection and aortic pressure augmentation may explain the lack of rise in central systolic pressure during incremental pacing despite an increase in peripheral pressure.

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AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE

Alan J. Garber, Paul S. Jellinger, Yehuda Handelsman … (2017)

The development of these guidelines is mandated by the American Association of Clinical Endocrinologists (AACE) Board of Directors and American College of Endocrinology (ACE) Board of Trustees and adheres with published AACE protocols for the standardized production of clinical practice guidelines (CPGs).

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Is Open Access

Inflammatory Biomarkers Interleukin‐6 and C‐Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial

Claes Held, Harvey White, Ralph Stewart … (2017)

Background Evaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population. Methods and Results Overall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin‐6 (IL‐6) and high‐sensitivity C‐reactive protein were measured in plasma samples: median levels were 2.1 (interquartile range, 1.4–3.2) ng/L and 1.3 (interquartile range, 0.6–3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL‐6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.30–1.97; P<0.0001); cardiovascular death (HR, 2.15; 95% CI, 1.53–3.04; P<0.0001); myocardial infarction (HR, 1.53; 95% CI, 1.14–2.04; P<0.05); all‐cause mortality (HR, 2.11; 95% CI, 1.62–2.76; P<0.0001); and risk of hospitalization for heart failure (HR, 2.28; 95% CI, 1.34–3.89; P<0.001). Cancer death was doubled in the highest IL‐6 quartile group (HR, 2.34; 95% CI, 1.20–4.53; P<0.05). High‐sensitivity C‐reactive protein was associated with both cardiovascular and non‐cardiovascular events in the unadjusted model, but these did not remain after multivariable adjustments. Conclusions IL‐6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all‐cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL‐6 might reflect a pathophysiological process involved in the development of these events. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00799903.

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Author and article information

Contributors

Gerasimos Siasos: gsiasos@med.uoa.gr , gsiasos@bwh.harvard.edu

Journal

Journal ID (nlm-ta): Lipids Health Dis

Journal ID (iso-abbrev): Lipids Health Dis

Title: Lipids in Health and Disease

Publisher: BioMed Central (London )

ISSN (Electronic): 1476-511X

Publication date (Electronic): 14 February 2021

Publication date PMC-release: 14 February 2021

Publication date Collection: 2021

Volume: 20

Electronic Location Identifier: 12

Affiliations

[1 ]GRID grid.5216.0, ISNI 0000 0001 2155 0800, 1st Cardiology Department, Hippokration Hospital, , Athens Medical School, National and Kapodistrian University of Athens, ; Athens, Greece

[2 ]GRID grid.411095.8, ISNI 0000 0004 0477 2585, Medizinische Klinik und Poliklinik I, Klinikum der Universität München, ; Munich, Germany

[3 ]Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA USA

[4 ]GRID grid.5216.0, ISNI 0000 0001 2155 0800, Department of Anatomy, Laiko General Hospital, , National and Kapodistrian University of Athens, School of Medicine, ; Athens, Greece

Author information

Konstantinos Mourouzis http://orcid.org/0000-0001-8702-7369

Article

Publisher ID: 1438

DOI: 10.1186/s12944-021-01438-4

PMC ID: 7883455

PubMed ID: 33583415

SO-VID: 1bbc03b2-c3c5-49ae-b4b4-5e8a487a29d9

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 13 October 2020

Date accepted : 27 January 2021

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ScienceOpen disciplines: Biochemistry

Keywords: lipoprotein-associated phospholipase a2,endothelial dysfunction,wave reflections,coronary artery disease,arterial stiffness

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ScienceOpen disciplines: Biochemistry

Keywords: lipoprotein-associated phospholipase a2, endothelial dysfunction, wave reflections, coronary artery disease, arterial stiffness

Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease

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Most cited references 29

The influence of heart rate on augmentation index and central arterial pressure in humans.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY GUIDELINES FOR MANAGEMENT OF DYSLIPIDEMIA AND PREVENTION OF CARDIOVASCULAR DISEASE

Inflammatory Biomarkers Interleukin‐6 and C‐Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial

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