Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk
(2023) In Vascular Pharmacology 152.- Abstract
Background: The residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). Methods: IL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n =... (More)
Background: The residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). Methods: IL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods. Results: During 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08–3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation. Conclusions: Our findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.
(Less)
- author
- Edsfeldt, Andreas LU ; Gonçalves, Isabel LU ; Vigren, Isa ; Jovanović, Anja ; Engström, Gunnar LU ; Shore, Angela C. ; Natali, Andrea ; Khan, Faisel and Nilsson, Jan LU
- organization
- publishing date
- 2023-10
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Atherosclerosis, Atherosclerotic plaque, IL-6, Myocardial infarction, Soluble IL-6 receptor
- in
- Vascular Pharmacology
- volume
- 152
- article number
- 107214
- publisher
- Elsevier
- external identifiers
-
- scopus:85169804872
- pmid:37634789
- ISSN
- 1537-1891
- DOI
- 10.1016/j.vph.2023.107214
- language
- English
- LU publication?
- yes
- id
- de4b0246-4c3e-4e8c-8f78-d4aa17ad14f4
- date added to LUP
- 2023-10-25 15:50:41
- date last changed
- 2024-06-28 09:19:15
@article{de4b0246-4c3e-4e8c-8f78-d4aa17ad14f4, abstract = {{<p>Background: The residual cardiovascular risk in subjects receiving guideline-recommended therapy is related to persistent vascular inflammation and IL-6 represents a target for its treatment. IL-6 binds to receptors on leukocytes and hepatocytes and/or by forming complexes with soluble IL-6 receptors (sIL-6R) binding to gp130 which is present on all cells. Here we aimed to estimate the associations of these two pathways with risk of cardiovascular disease (CVD). Methods: IL-6 and sIL-6R were analyzed using the proximity extension assay. Baseline plasma samples were obtained from participants in the prospective Malmö Diet and Cancer (MDC) study (n = 4661), the SUMMIT VIP study (n = 1438) and the Carotid Plaque Imaging Project (CPIP, n = 285). Incident clinical events were obtained through national registers. Plaques removed at surgery were analyzed by immunohistochemistry and biochemical methods. Results: During 23.1 ± 7.0 years follow-up, 575 subjects in the MDC cohort suffered a first myocardial infarction. Subjects in the highest tertile of IL-6 had an increased risk compared to the lowest tertile (HR and 95% CI 2.60 [2.08–3.25]). High plasma IL-6 was also associated with more atherosclerosis, increased arterial stiffness, and impaired endothelial function in SUMMIT VIP, but IL-6 was only weakly associated with plaque inflammation in CPIP. sIL-6R showed no independent association with risk of myocardial infarction, atherosclerosis severity or vascular function, but was associated with plaque inflammation. Conclusions: Our findings show that sIL-6R is a poor marker of CVD risk and associated vascular changes. However, the observation that sIL-6R reflects plaque inflammation highlights the complexity of the role of IL-6 in CVD.</p>}}, author = {{Edsfeldt, Andreas and Gonçalves, Isabel and Vigren, Isa and Jovanović, Anja and Engström, Gunnar and Shore, Angela C. and Natali, Andrea and Khan, Faisel and Nilsson, Jan}}, issn = {{1537-1891}}, keywords = {{Atherosclerosis; Atherosclerotic plaque; IL-6; Myocardial infarction; Soluble IL-6 receptor}}, language = {{eng}}, publisher = {{Elsevier}}, series = {{Vascular Pharmacology}}, title = {{Circulating soluble IL-6 receptor associates with plaque inflammation but not with atherosclerosis severity and cardiovascular risk}}, url = {{http://dx.doi.org/10.1016/j.vph.2023.107214}}, doi = {{10.1016/j.vph.2023.107214}}, volume = {{152}}, year = {{2023}}, }