Atorvastatin Reduces Circulating S100A12 Levels in Patients with Carotid Atherosclerotic Plaques - A Link with Plaque Inflammation

Abstract

Inflammation is involved in various processes of atherosclerosis development. Serum C-reactive protein (CRP) levels, a predictor for cardiovascular risk, are reportedly reduced by statins. However, several studies have demonstrated that CRP is a bystander during atherogenesis. While S100A12 has been focused on as an inflammatory molecule, it remains unclear whether statins affect circulating S100A12 levels. Here, we investigated whether atorvastatin treatment affected S100A12 and which biomarkers were correlated with changes in arterial inflammation. Methods:We performed a prospective, randomized open-labeled trial on whether atorvastatin affected arterial (carotid and thoracic aorta) inflammation using 18 fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) and inflammatory markers. Thirty-one statin-naïve patients with carotid atherosclerotic plaques were randomized to either a group receiving dietary management (n 15) or one receiving atorvastatin (10mg/day, n 16) for 12weeks. 18 F-FDG-PET/CT and flow-mediated vasodilation (FMD) were performed, the latter to evaluate endothelial function.Results: Atorvastatin, but not the diet-only treatment, significantly reduced LDL-cholesterol (LDL-C, -43%), serum CRP (-37%) and S100A12 levels (-28%) and improved FMD (+38%). 18 F-FDG-PET/CT demonstrated that atorvastatin, but not the diet-only treatment, significantly reduced accumulation of 18 F-FDG in the carotid artery and thoracic aorta. A multivariate analysis revealed that reduction in CRP, S100A12, LDL-C, oxidized-LDL, and increase in FMD were significantly associated with reduced arterial inflammation in the thoracic aorta, but not in the carotid artery.Conclusions: Atorvastatin treatment reduced S100A12/CRP levels, and the changes in these circulating markers mirrored the improvement in arterial inflammation. Our observations suggest that S100A12 may be an emerging therapeutic target for atherosclerosis.C-reactive protein (CRP) levels are a good predictor for incidence of cardiovascular diseases (CVD) 2) . A number of clinical trials have shown that CVD events are reduced by treatment with statins (HMG-CoA

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

“…In other words, PET/CT can detect even small changes in arterial wall inflammation, which is a unique property among other imaging techniques or biomarkers. So far, seven prospective studies have used scintigraphy to evaluate the impact of statins on carotid plaque inflammation by measuring target-to-background ratio (TBR) (n = 5 studies) [45][46][47][48] and/or standardized uptake value (SUV) (n = 3 studies) [39,49,50]. Most of them supported a significant reduction of arterial wall inflammation after either 3-month atorvastatin (10-80 mg/d) [46,[48][49][50] therapy, or 1-month atorvastatin (20 mg/d) [45] administration, or 6-month therapy with either simvastatin (10 mg/d), rosuvastatin (10 mg/d) [39], pitavastatin (2 mg/d), or pravastatin (10 mg/d) [39].…”

“…Twenty-four prospective clinical trials have assessed the influence of statins on carotid plaque vulnerability concomitantly with the modulation of circulating inflammatory biomarkers. Based on imaging indices of plaque vulnerability, such as PET scans [47,[48][49][50]52] and carotid plaque echogenicity [53,54], most of those studies suggested an improvement in plaque stability after statin administration, accompanied by a significant reduction in inflammatory biomarkers. Those studies used the most known inflammatory biomarkers, like CRP [47][48][49][53][54][55][56][57][58][59], interleukin (IL)-6 [53,[55][56][57]59], tumor necrosis factor (TNF)-a [49,54,56,59], and monocyte chemoattractant protein-1 [49].…”

“…Based on imaging indices of plaque vulnerability, such as PET scans [47,[48][49][50]52] and carotid plaque echogenicity [53,54], most of those studies suggested an improvement in plaque stability after statin administration, accompanied by a significant reduction in inflammatory biomarkers. Those studies used the most known inflammatory biomarkers, like CRP [47][48][49][53][54][55][56][57][58][59], interleukin (IL)-6 [53,[55][56][57]59], tumor necrosis factor (TNF)-a [49,54,56,59], and monocyte chemoattractant protein-1 [49]. Nevertheless, two studies [52,58] failed to demonstrate the stabilizing effects of statins despite their anti-inflammatory action while other studies failed to find any effect of statins on the aforementioned anti-inflammatory biomarkers at all.…”

“…Nevertheless, two studies [52,58] failed to demonstrate the stabilizing effects of statins despite their anti-inflammatory action while other studies failed to find any effect of statins on the aforementioned anti-inflammatory biomarkers at all. Using less-known inflammatory biomarkers such as tumor necrosis factor receptor (TNFR)-I and II [58], IL-2, -8, -10, -18, -23, interferon-γ, transforming growth factor (TGF)-β [59], pentraxin-3 [49], and others, statins have shown anti-inflammatory impact as well. The association w w w .…”

The Chinese-Han Population Carrying Wild-type Genotypes of SLCO1B1 388A>G, SLCO1B1 521T>C, CYP3A4 1B, CYP3A4 1G, and CYP3A5*3 Exhibits a Significant Alteration in the Pharmacokinetics of Atorvastatin Calcium

“…By lowering levels of low-density lipoprotein-bound cholesterol, AC can reduce the risk of atherosclerosis. The efficacy and safety of AC in facilitating the primary and secondary prevention of cardiovascular events have been demonstrated in various clinical trials [1][2][3]. However, due to the diverse genetic characteristics of metabolism and high drug plasma exposure, individual differences exist in clinical efficacy and adverse events, especially statin-induced myopathy [4,5].…”