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

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 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.

The Effects of Statin Therapy on Oxidized LDL and Its Antibodies: A Systematic Review and Meta-Analysis

“…Irrespective of cholesterol-dependent or cholesterol-independent (pleiotropic) effects of statins [ 69 – 72 ], plaque oxLDL levels might be associated with plaque inflammation. However, a recent study showed that plaque oxLDL levels were not associated with future ASCVD events [ 73 ]. It is important to stress that plaque levels of oxLDL were lower in patients who were treated with statins.…”

A new approach of statin therapy in carotid atherosclerosis: Targeting indices of plaque vulnerability on the top of lipid-lowering. A narrative review

“…p l / k a r d i o l o g i a _ p o l s k a between carotid plaque stabilization and suppressed inflammation after statins was observed across heterogeneous studies using a wide spectrum of statins, doses, and therapy duration. Nevertheless, the inhibition of inflammatory pathways remains among the predominant pleiotropic mechanisms of intensive statin therapy, leading to histopathologically stable carotid plaques and fewer cardiovascular events [60][61][62]. Provisionally, close monitoring of those biomarkers in statin-treated patients could predict atherosclerotic plaque destabilization and cardiovascular disease progression (Figure 2).…”

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

“…Following publication of the original article [ 1 ], the authors provided the additional corrections which were not included by the typesetter before publication. The following corrections are presented with this erratum.…”