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Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events

Singh, Pratibha LU ; Goncalves, Isabel LU orcid ; Tengryd, Christoffer LU ; Nitulescu, Mihaela LU ; Persson, Ana F. LU ; To, Fong LU ; Bengtsson, Eva LU orcid ; Volkov, Petr LU ; Orho-Melander, Marju LU and Nilsson, Jan LU , et al. (2020) In Cardiovascular Diabetology 19(1).
Abstract

BACKGROUND: Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target. METHODS: Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and... (More)

BACKGROUND: Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target. METHODS: Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers. RESULTS: Plaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p < 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a). CONCLUSIONS: This study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Carotid stenosis, Diabetes mellitus, Oxidized low-density lipoproteins
in
Cardiovascular Diabetology
volume
19
issue
1
article number
214
publisher
BioMed Central (BMC)
external identifiers
  • pmid:33317535
  • scopus:85098476322
ISSN
1475-2840
DOI
10.1186/s12933-020-01189-z
language
English
LU publication?
yes
id
230d7fbe-f0e6-475e-8418-8c7b450bbffd
date added to LUP
2021-01-15 08:49:47
date last changed
2024-04-03 20:50:55
@article{230d7fbe-f0e6-475e-8418-8c7b450bbffd,
  abstract     = {{<p>BACKGROUND: Type 2 diabetes (T2D) patients are at a greater risk of cardiovascular events due to aggravated atherosclerosis. Oxidized LDL (oxLDL) has been shown to be increased in T2D plaques and suggested to contribute to plaque ruptures. Despite intensified statin treatment during the last decade the higher risk for events remains. Here, we explored if intensified statin treatment was associated with reduced oxLDL in T2D plaques and if oxLDL predicts cardiovascular events, to elucidate whether further plaque oxLDL reduction would be a promising therapeutic target. METHODS: Carotid plaque OxLDL levels and plasma lipoproteins were assessed in 200 patients. Plaque oxLDL was located by immunohistochemistry. Plaque cytokines, cells and scavenger receptor gene expression were quantified by Luminex, immunohistochemistry and RNA sequencing, respectively. Clinical information and events during follow-up were obtained from national registers. RESULTS: Plaque oxLDL levels correlated with markers of inflammatory activity, endothelial activation and plasma LDL cholesterol (r = 0.22-0.32 and p ≤ 0.01 for all). T2D individuals exhibited lower plaque levels of oxLDL, sLOX-1(a marker of endothelial activation) and plasma LDL cholesterol (p = 0.001, p = 0.006 and p = 0.009). No increased gene expression of scavenger receptors was identified in T2D plaques. The lower oxLDL content in T2D plaques was associated with a greater statin usage (p = 0.026). Supporting this, a linear regression model showed that statin treatment was the factor with the strongest association to plaque oxLDL and plasma LDL cholesterol (p &lt; 0.001 for both). However, patients with T2D more frequently suffered from symptoms and yet plaque levels of oxLDL did not predict cardiovascular events in T2D (findings are summarized in Fig. 1a). CONCLUSIONS: This study points out the importance of statin treatment in affecting plaque biology in T2D. It also implies that other biological components, beyond oxLDL, need to be identified and targeted to further reduce the risk of events among T2D patients receiving statin treatment.</p>}},
  author       = {{Singh, Pratibha and Goncalves, Isabel and Tengryd, Christoffer and Nitulescu, Mihaela and Persson, Ana F. and To, Fong and Bengtsson, Eva and Volkov, Petr and Orho-Melander, Marju and Nilsson, Jan and Edsfeldt, Andreas}},
  issn         = {{1475-2840}},
  keywords     = {{Atherosclerosis; Carotid stenosis; Diabetes mellitus; Oxidized low-density lipoproteins}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Cardiovascular Diabetology}},
  title        = {{Reduced oxidized LDL in T2D plaques is associated with a greater statin usage but not with future cardiovascular events}},
  url          = {{http://dx.doi.org/10.1186/s12933-020-01189-z}},
  doi          = {{10.1186/s12933-020-01189-z}},
  volume       = {{19}},
  year         = {{2020}},
}