Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study

Ria Sanghavi; Tiberiu A. Pana; Hulkar Mamayusupova; Ian Maidment; Chris Fox; S. Matthijs Boekholdt; Mamas A. Mamas; Nicholas J. Wareham; Kay-tee Khaw; Phyo K. Myint

doi:10.1111/bcp.15261

Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study

Ria Sanghavi, Tiberiu A. Pana, Hulkar Mamayusupova, Ian Maidment, Chris Fox, S. Matthijs Boekholdt, Mamas A. Mamas, Nicholas J. Wareham, Kay-tee Khaw, Phyo K. Myint^*

^*Corresponding author for this work

Aston Pharmacy School

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

Abstract

Background: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. Results: In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (−0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. Conclusion: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.

Original language	English
Pages (from-to)	3297-3306
Number of pages	10
Journal	British Journal of Clinical Pharmacology
Volume	88
Issue number	7
Early online date	3 Feb 2022
DOIs	https://doi.org/10.1111/bcp.15261
Publication status	Published - Jul 2022

Bibliographical note

© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) was funded by the Medical Research Council, Grant number (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK, Grant number (C864/A14136).

Keywords

C-reactive protein
anticholinergics
cardiovascular diseases
fibrinogen
interleukin-6
tumour necrosis factor-alpha

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10.1111/bcp.15261Licence: CC BY 4.0

Brit J Clinical Pharma - 2022 - Sanghavi
© 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 1.31 MBLicence: CC BY 4.0

http://10.22541/au.162273979.95865645/v1Licence: CC BY-NC-ND 4.0

Cite this

Sanghavi, R., Pana, T. A., Mamayusupova, H., Maidment, I., Fox, C., Boekholdt, S. M., Mamas, M. A., Wareham, N. J., Khaw, K., & Myint, P. K. (2022). Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study. British Journal of Clinical Pharmacology, 88(7), 3297-3306. https://doi.org/10.1111/bcp.15261

@article{b73ff7c379e04624b83bf50a97243891,

title = "Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study",

abstract = "Background: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. Results: In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (−0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. Conclusion: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.",

keywords = "C-reactive protein, anticholinergics, cardiovascular diseases, fibrinogen, interleukin-6, tumour necrosis factor-alpha",

author = "Ria Sanghavi and Pana, {Tiberiu A.} and Hulkar Mamayusupova and Ian Maidment and Chris Fox and Boekholdt, {S. Matthijs} and Mamas, {Mamas A.} and Wareham, {Nicholas J.} and Kay-tee Khaw and Myint, {Phyo K.}",

note = "{\textcopyright} 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) was funded by the Medical Research Council, Grant number (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK, Grant number (C864/A14136).",

year = "2022",

month = jul,

doi = "10.1111/bcp.15261",

language = "English",

volume = "88",

pages = "3297--3306",

journal = "British Journal of Clinical Pharmacology",

issn = "0306-5251",

publisher = "Wiley-Blackwell",

number = "7",

}

Sanghavi, R, Pana, TA, Mamayusupova, H, Maidment, I, Fox, C, Boekholdt, SM, Mamas, MA, Wareham, NJ, Khaw, K & Myint, PK 2022, 'Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study', British Journal of Clinical Pharmacology, vol. 88, no. 7, pp. 3297-3306. https://doi.org/10.1111/bcp.15261

Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study. / Sanghavi, Ria; Pana, Tiberiu A.; Mamayusupova, Hulkar et al.
In: British Journal of Clinical Pharmacology, Vol. 88, No. 7, 07.2022, p. 3297-3306.

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

TY - JOUR

T1 - Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study

AU - Sanghavi, Ria

AU - Pana, Tiberiu A.

AU - Mamayusupova, Hulkar

AU - Maidment, Ian

AU - Fox, Chris

AU - Boekholdt, S. Matthijs

AU - Mamas, Mamas A.

AU - Wareham, Nicholas J.

AU - Khaw, Kay-tee

AU - Myint, Phyo K.

N1 - © 2022 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. The EPIC-Norfolk study (DOI 10.22025/2019.10.105.00004) was funded by the Medical Research Council, Grant number (MR/N003284/1 and MC-UU_12015/1) and Cancer Research UK, Grant number (C864/A14136).

PY - 2022/7

Y1 - 2022/7

N2 - Background: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. Results: In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (−0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. Conclusion: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.

AB - Background: Higher medication anticholinergic burden is associated with increased risk of cardiovascular disease and cognitive decline. A mechanistic pathway has not been established. We aimed to determine whether inflammation may mediate these associations. Methods: Participants were drawn from the European Prospective Investigation into Cancer, Norfolk cohort (40-79 years at baseline). Anticholinergic burden score (ACB) was calculated at first (1HC) (1993/97) and second (2HC) (1998/2000) health checks. Fibrinogen and C-reactive protein (CRP) were measured during 1HC and tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) during 2HC. Cross-sectional associations between ACB and inflammatory markers were examined for both health checks. Prospective associations were also examined between 1HC ACB and 2HC inflammatory markers. Models were adjusted for age, sex, lifestyle factors, comorbidities and medications. Results: In total, 17 678 and 22 051 participants were included in cross-sectional analyses for CRP, and fibrinogen, respectively. Furthermore, 5101 participants with data on TNF-α and IL-6 were included in the prospective analyses. Cross-sectionally, compared to ACB = 0, ACB ≥ 4 was associated with higher fibrinogen, beta (95% confidence interval) = 0.134 g/L (0.070, 0.199), CRP 1.175 mg/L (0.715, 1.634), IL-6 0.593 pg/mL (0.254, 0.932) and TNF-α 0.137 pg/mL (0.033, 0.241). In addition, a point increase in ACB was associated with higher levels of all markers. Prospectively, compared to ACB = 0, ACB ≥ 4 was associated with higher IL-6(pg/mL) of 0.019 (−0.323, 0.361) and TNF-α (pg/mL) of 0.202% (0.81, 0.323). A unit increase in ACB was associated with a significantly higher TNF-α and IL-6. Conclusion: Higher ACB was associated with higher inflammatory markers. Inflammation may mediate the relationship between anticholinergic medications and adverse outcomes.

KW - C-reactive protein

KW - anticholinergics

KW - cardiovascular diseases

KW - fibrinogen

KW - interleukin-6

KW - tumour necrosis factor-alpha

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U2 - 10.1111/bcp.15261

DO - 10.1111/bcp.15261

M3 - Article

SN - 0306-5251

VL - 88

SP - 3297

EP - 3306

JO - British Journal of Clinical Pharmacology

JF - British Journal of Clinical Pharmacology

IS - 7

ER -

Higher anticholinergic burden from medications is associated with significant increase in markers of inflammation in the EPIC-Norfolk prospective population-based cohort study

Abstract

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Keywords

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