Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study

Sharon Remmelzwaal; Joline W. J. Beulens; Petra J. M. Elders; Coen D. A. Stehouwer; Zhenyu Zhang; M. Louis Handoko; Yolande Appelman; Vanessa van Empel; Stephane R. B. Heymans; Lutgarde Thijs; Jan A. Staessen; A. Johanne van Ballegooijen

doi:10.1371/journal.pone.0251148

Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study

Sharon Remmelzwaal^*, Joline W. J. Beulens, Petra J. M. Elders, Coen D. A. Stehouwer, Zhenyu Zhang, M. Louis Handoko, Yolande Appelman, Vanessa van Empel, Stephane R. B. Heymans, Lutgarde Thijs, Jan A. Staessen, A. Johanne van Ballegooijen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Background This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. Methods Biomarkers and echocardiographic measures were measured at both baseline and followup in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. Results Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. Conclusion Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.

Original language	English
Article number	e0251148
Number of pages	14
Journal	PLOS ONE
Volume	16
Issue number	5
DOIs	https://doi.org/10.1371/journal.pone.0251148
Publication status	Published - 4 May 2021

Keywords

VENTRICULAR EJECTION FRACTION
CHRONIC HEART-FAILURE
DIASTOLIC DYSFUNCTION
REACTIVE PROTEIN
EUROPEAN-SOCIETY
TASK-FORCE
PREVALENCE
DIAGNOSIS
ASSOCIATION
ADULTS

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Remmelzwaal, S., Beulens, J. W. J., Elders, P. J. M., Stehouwer, C. D. A., Zhang, Z., Handoko, M. L., Appelman, Y., van Empel, V., Heymans, S. R. B., Thijs, L., Staessen, J. A., & van Ballegooijen, A. J. (2021). Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study. PLOS ONE, 16(5), Article e0251148. https://doi.org/10.1371/journal.pone.0251148

@article{4f285cef4cdb45498e5c2d743502d0aa,

title = "Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study",

abstract = "Background This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. Methods Biomarkers and echocardiographic measures were measured at both baseline and followup in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. Results Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. Conclusion Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.",

keywords = "VENTRICULAR EJECTION FRACTION, CHRONIC HEART-FAILURE, DIASTOLIC DYSFUNCTION, REACTIVE PROTEIN, EUROPEAN-SOCIETY, TASK-FORCE, PREVALENCE, DIAGNOSIS, ASSOCIATION, ADULTS",

author = "Sharon Remmelzwaal and Beulens, {Joline W. J.} and Elders, {Petra J. M.} and Stehouwer, {Coen D. A.} and Zhenyu Zhang and Handoko, {M. Louis} and Yolande Appelman and {van Empel}, Vanessa and Heymans, {Stephane R. B.} and Lutgarde Thijs and Staessen, {Jan A.} and {van Ballegooijen}, {A. Johanne}",

note = "Publisher Copyright: {\textcopyright} 2021 Remmelzwaal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",

year = "2021",

month = may,

day = "4",

doi = "10.1371/journal.pone.0251148",

language = "English",

volume = "16",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

number = "5",

}

Remmelzwaal, S, Beulens, JWJ, Elders, PJM, Stehouwer, CDA, Zhang, Z, Handoko, ML, Appelman, Y, van Empel, V , Heymans, SRB, Thijs, L, Staessen, JA & van Ballegooijen, AJ 2021, 'Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study', PLOS ONE, vol. 16, no. 5, e0251148. https://doi.org/10.1371/journal.pone.0251148

TY - JOUR

T1 - Sex differences in the longitudinal relationship of low-grade inflammation and echocardiographic measures in the Hoorn and FLEMENGHO Study

AU - Remmelzwaal, Sharon

AU - Beulens, Joline W. J.

AU - Elders, Petra J. M.

AU - Stehouwer, Coen D. A.

AU - Zhang, Zhenyu

AU - Handoko, M. Louis

AU - Appelman, Yolande

AU - van Empel, Vanessa

AU - Heymans, Stephane R. B.

AU - Thijs, Lutgarde

AU - Staessen, Jan A.

AU - van Ballegooijen, A. Johanne

N1 - Publisher Copyright: © 2021 Remmelzwaal et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2021/5/4

Y1 - 2021/5/4

N2 - Background This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. Methods Biomarkers and echocardiographic measures were measured at both baseline and followup in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. Results Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. Conclusion Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.

AB - Background This study aimed to determine the within-person and between-persons associations of low-grade inflammation (LGI) and endothelial dysfunction (ED) with echocardiographic measures related to diastolic dysfunction (DD) in two general populations and whether these associations differed by sex. Methods Biomarkers and echocardiographic measures were measured at both baseline and followup in the Hoorn Study (n = 383) and FLEMENGHO (n = 491). Individual biomarker levels were combined into either a Z-score of LGI (CRP, SAA, IL-6, IL-8, TNF-α and sICAM-1) or ED (sICAM-1, sVCAM-1, sE-selectin and sTM). Mixed models were used to determine within-person and between-persons associations of biomarker Z-scores with left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI) and left atrial volume index (LAVI). These associations were adjusted for a-priori selected confounders. Results Overall Z-scores for LGI or ED were not associated with echocardiographic measures. Effect modification by sex was apparent for ED with LVEF in both cohorts (P-for interaction = 0.08 and 0.06), but stratified results were not consistent. Effect modification by sex was apparent for TNF-α in the Hoorn Study and E-selectin in FLEMENGHO with LVEF (P-for interaction≤0.05). In the Hoorn Study, women whose TNF-α levels increased with 1-SD over time had a decrease in LVEF of 2.2 (-4.5;0.01) %. In FLEMENGHO, men whose E-selectin levels increased with 1-SD over time had a decrease in LVEF of 1.6 (-2.7;-0.5) %. Conclusion Our study did not show consistent associations of LGI and ED with echocardiographic measures. Some evidence of effect modification by sex was present for ED and specific biomarkers.

KW - VENTRICULAR EJECTION FRACTION

KW - CHRONIC HEART-FAILURE

KW - DIASTOLIC DYSFUNCTION

KW - REACTIVE PROTEIN

KW - EUROPEAN-SOCIETY

KW - TASK-FORCE

KW - PREVALENCE

KW - DIAGNOSIS

KW - ASSOCIATION

KW - ADULTS

U2 - 10.1371/journal.pone.0251148

DO - 10.1371/journal.pone.0251148

M3 - Article

C2 - 33945586

SN - 1932-6203

VL - 16

JO - PLOS ONE

JF - PLOS ONE

IS - 5

M1 - e0251148

ER -