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This single-centre substudy of a double-blind, randomized, placebo-controlled trial aimed to determine the effect of 96 weeks of rosuvastatin on pulse wave velocity (PWV) in men (n = 55, 54 years) with HIV at moderate cardiovascular risk (Framingham risk score 10-15%). PWV increased in both rosuvastatin [0.54 m/s standard error of difference (SED) 0.26] and placebo [0.50 m/s (SED 0.26), P = 0.896] arms, leading to no difference in PWV at week 96 [rosuvastatin 9.40 m/s (SE 0.31); placebo 9.21 m/s (SE0.31), P = 0.676]., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The purpose of this study was to determine the causal effect of statins on osteoarthritis (OA) risk using Mendelian randomization (MR)., Methods: Single nucleotide polymorphism-based genome-wide association analyses of statins were collected from the UK Biobank and FinnGen dataset, and OA data were collected from the UK Biobank and Arthritis Research UK Osteoarthritis Genetics (arcOGEN) study. Two-sample MR analyses were performed using the inverse-variance weighted (IVW) technique. MR-Egger, weighted median, and weighted mode served as supplementary analyses. MR-Egger regression, Cochran's Q test, and Mendelian Randomization Pleiotropy Residual Sum and Outlier analysis were performed as sensitivity analyses. Hydroxymethylglutaryl-coenzyme A reductase (HMGCR) expression and OA risk were evaluated using summary data-based MR (SMR)., Results: MR analyses consistently supported a causal connection between statin use and OA risk. A causal effect was observed for atorvastatin (IVW: β = -2.989, P = 0.003) and rosuvastatin (IVW: β = -14.141, P = 0.006) treatment on hip OA. Meta-analysis showed the association between atorvastatin and knee OA was statistically significant (odds ratio 0.15; P = 0.004). Simvastatin use exhibited a protective effect against knee (IVW: β = -1.056, P = 0.004) and hip OA (IVW: β = -1.405, P = 0.001). Statin medication showed a protective effect on hip OA (IVW: β = -0.054, P = 0.013). HMGCR correlated significantly with a reduced risk of knee OA (β = -0.193, P SMR = 0.017), rather than hip OA (β = 0.067, P SMR = 0.502), which suggested that statins' protective effect on OA may not be related to its lipid-lowering effect., Conclusion: This MR study provides compelling evidence that statin treatment may be a protective factor for OA. Further research is required to clarify its underlying mechanism., (© 2024 American College of Rheumatology.)

Background: The Seattle Proportional Risk Model (SPRM) estimates the proportion of sudden cardiac death (SCD) in heart failure (HF) patients, identifying those most likely to benefit from implantable cardioverter-defibrillator (ICD) therapy (those with ≥50% estimated proportion of SCD). The GISSI-HF trial tested fish oil and rosuvastatin in HF patients. We used the SPRM to evaluate its accuracy in this cohort in predicting potential ICD benefit in patients with EF ≤50% and an SPRM-predicted proportion of SCD either ≥50% or <50%., Methods: The SPRM was estimated in patients with EF ≤50% and in a logistic regression model comparing SCD with non-SCD., Results: We evaluated 6,750 patients with EF ≤50%. There were 1,892 all-cause deaths, including 610 SCDs. Fifty percent of EF ≤35% patients and 43% with EF 36% to 50% had an SPRM of ≥50%. The SPRM (OR: 1.92, P < 0.0001) accurately predicted the risk of SCD vs non-SCD with an estimated proportion of SCD of 44% vs the observed proportion of 41% at 1 year. By traditional criteria for ICD implantation (EF ≤35%, NYHA class II or III), 64.5% of GISSI-HF patients would be eligible, with an estimated ICD benefit of 0.81. By SPRM >50%, 47.8% may be eligible, including 30.2% with EF >35%. GISSI-HF participants with EF ≤35% with SPRM ≥50% had an estimated ICD HR of 0.64, comparable to patients with EF 36% to 50% with SPRM ≥50% (HR: 0.65)., Conclusions: The SPRM discriminated SCD vs non-SCD in GISSI-HF, both in patients with EF ≤35% and with EF 36% to 50%. The comparable estimated ICD benefit in patients with EF ≤35% and EF 36% to 50% supports the use of a proportional risk model for shared decision making with patients being considered for primary prevention ICD therapy., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Statin is crucial for acute myocardial infarction (AMI) patients. However, the risk of new-onset diabetes mellitus (NODM) associated with statin is a concern. This study aimed to determine the incremental diabetogenic effects of statins according to their intensity and dose in AMI patients undergoing percutaneous coronary intervention (PCI). Among 13,104 patients enrolled in the Korea AMI Registry between 2011 and 2015, 6152 patients without diabetes mellitus (DM) who underwent PCI and received moderate-to-high-intensity atorvastatin and rosuvastatin were selected for the study. The endpoints were NODM and major adverse cardiovascular events (MACE), composite of all-cause mortality, recurrent MI, and revascularization up to 3 years. Among the participants, 3747 and 2405 received moderate- and high-intensity statins, respectively. The Kaplan-Meier curves demonstrated a higher incidence of NODM in patients with high-intensity statins than those with moderate-intensity. High-intensity statin was a significant predictor of NODM after adjusting for other co-variables (HR = 1.316, 95% CI 1.024-1.692; P < 0.032). Higher dose of rosuvastatin was associated with a higher cumulative incidence of NODM, but this dose-dependency was not apparent with atorvastatin. Cumulative incidence of MACE decreased dose-dependently only with atorvastatin. High-intensity statin was associated with a higher cumulative incidence of NODM in AMI patients, and this association was more evident in rosuvastatin. The different diabetogenic effects of the two statins provide supporting evidence for understanding the nuanced nature of statin treatment in relation to NODM., (© 2024. The Author(s).)

Background: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial., Methods: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest., Results: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007)., Conclusions: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL., Trial Registration: ClinicalTrials.gov, Identifier: NCT02579499., (© 2024. The Author(s).)

Introduction: Adherence to cardiovascular drug treatment can significantly benefit from a reduced pill burden, but data on this matter derived from real-life settings are currently scanty. This analysis assessed the possible changes in adherence in patients treated with rosuvastatin and ezetimibe (ROS/EZE) as free multi-pill combination who switched to ROS/EZE as single-pill combination in the setting of real clinical practice in Italy., Methods: A retrospective analysis was conducted on the administrative databases for a catchment area of about seven million health-assisted residents. Adults receiving ROS/EZE as a single-pill combination from January 2010 to June 2020 (followed up to 2021) were identified. The date of the first prescription of single-pill combination of ROS/EZE was considered as the index date. The analysis included the users of ROS/EZE as a free combination during the year before the index date. Baseline demographic and clinical characteristics were collected during the period of data availability prior to the index date. Adherence to therapy was evaluated as proportion of days covered (PDC), namely the percentage of days during which a patient had access to medication, in the 12-month interval preceding or following the index date (PDC < 25% non-adherence; PDC = 25-75% partial adherence; PDC > 75% adherence)., Results: A total of 1219 patients (61.1% male, aged 66.2 ± 10.4 years) were included. Cardiovascular comorbidities were found in 83.3% of them, diabetes in 26.4%, and a combination of both in 16.2%. Single-pill combination of ROS/EZE was associated with a higher proportion of adherent patients compared to free-pill combination (75.2% vs 51.8%, p < 0.001)., Conclusions: This real-world analysis suggested that switching from a regimen based on separate pills to one based on a single-pill combination resulted in improved adherence to ROS/EZE therapy., (© 2024. The Author(s).)

microRNAs are candidate diagnostic biomarkers for Alzheimer's disease. This study aimed to compare Silymarin with Rosuvastatin and placebo on total-Tau protein level and expression levels of microRNAs and TGF-β and COX-2 in Alzheimer's patients with secondary dyslipidemia. 36 mild AD patients with dyslipidemia were divided into three groups of 12. The first group received silymarin (140mg), the second group received placebo (140mg), and the third group recieved Rosuvastatin (10mg). Tablets were administered three times a day for Six months. The blood samples of the patients were collected before and after the intervention and the serum was separated. Using the RT-qPCR method, the expression levels of miR-124-3p and miR-125b-5p were assessed, and the serum levels of total-Tau, TGF-β, and COX-2 enzyme were measured using the ELISA method. Data were analyzed with SPSS software. In this study, the level of Δtotal-Tau was significantly lower in the Rosuvastatin group compared to the placebo (P = 0.038). Also, a significant reduction in the level of ΔTGF-β was observed in the Silymarin to Rosuvastatin group (p = 0.046) and ΔmiR-124-3p was significantly increased in the Rosuvastatin compared to the placebo group (p = 0.044). Rosuvastatin outperformed silymarin in decreasing Δtotal-Tau serum levels and enhancing expression of ΔmiR-124-3p, attributed to Rosuvastatin's capacity to lower cholesterol levels and inflammation concurrently. Conversely, silymarin was more effective than Rosuvastatin in reducing levels of ΔTGF-β. Serum miR-124-3p could serve as a promising diagnostic biomarker and a new therapeutic focus in AD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: Atherosclerotic plaque fluorine-18 sodium fluoride ( 18 F-NaF) uptake on positron emission tomography with computed tomography (PET-CT) identifies active microcalcification and has been shown to correlate with clinical instability in patients with cardiovascular (CV) disease. Statin therapy promotes coronary macrocalcification over time. Our aim was to investigate rosuvastatin effect on atheroma 18 F-NaF uptake., Methods: Subjects with high CV risk but without CV events underwent 18 F-NaF-PET-CT in a single-centre. Those with subclinical atherosclerosis and significant 18 F-NaF plaque uptake were included in a single-arm clinical trial, treated with rosuvastatin 20 mg/daily for six months, and re-evaluated by 18 F-NaF-PET-CT. Primary endpoint was reduction in maximum atheroma 18 F-NaF uptake in the coronary, aortic or carotid arteries, assessed by the tissue-to-background ratio (TBR). The secondary endpoint was corrected uptake per lesion (CUL) variation., Results: Forty individuals were enrolled and 38 included in the pharmacological trial; mean age was 64 years, two-thirds were male and most were diabetic. The 10-year expected CV risk was 9.5% (6.0-15.3) for SCORE2 and 31.7 ± 18.7% for ASCVD systems. After six months of rosuvastatin treatment (n = 34), low-density lipoprotein cholesterol lowered from 133.6 ± 33.8 to 58.8 ± 20.7 mg dL -1 (60% relative reduction, p < 0.01). There was a significant 19% reduction in maximum plaque 18 F-NaF uptake after treatment, from 1.96 (1.78-2.22) to 1.53 (1.40-2.10), p < 0.001 (primary endpoint analysis). The secondary endpoint CUL was reduced by 23% (p = 0.003)., Conclusion: In a single-centre non-randomized clinical trial of high CV risk individuals with subclinical atherosclerosis, the maximum atherosclerotic plaque 18 F-NaF uptake was significantly reduced after six months of high-intensity statin., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims/Background Rosuvastatin is a common lipid-lowering statin on the market, but its impact on the incidence of long-term cardiovascular events is not well clarified. This study aimed to explore the effects of rosuvastatin on serum asymmetric dimethylarginine (ADMA) levels and the incidence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension. Methods This retrospective study included 158 patients with hyperlipidaemia and H-type hypertension who were treated in the Hebei Cangzhou Hospital of Integrated Traditional Chinese Medicine and Western Medicine from August 2015 to August 2016. The patients were divided into an occurrence group and a non-occurrence group according to the occurrence of long-term cardiovascular events following the resuvostatin treatment. The changes in blood lipids, blood pressure, serum ADMA levels and vascular endothelial function indexes before and after treatment were compared, and the effect of ADMA on the occurrence of long-term cardiovascular events and its predictive efficacy were analysed using the Spearman correlation test and receiver operating characteristics (ROC) curve. Results After treatment, the levels of serum total cholesterol, low-density lipoprotein cholesterol, triglyceride, serum ADMA and blood pressure became significantly lower ( p < 0.001), with high-density lipoprotein cholesterol exhibiting no significant difference. Twenty-two cases developed long-term cardiovascular events after the treatment, with an incidence of 13.92%. The occurrence group had significantly higher serum ADMA levels than the non-occurrence group ( p < 0.001). The rosuvastatin treatment also lowered the levels of endothelin-1 and high-sensitivity C-reactive protein and increased the nitric oxide level ( p < 0.001). Spearman correlation analysis showed that serum ADMA levels were positively correlated with the occurrence of long-term cardiovascular events (r=0.462, p < 0.001). Meanwhile, according to the ROC curve, serum ADMA had a good predictive efficacy for long-term cardiovascular events, with an area under the curve of 0.885 (95% confidence interval 0.808-0.963; p < 0.001). Conclusion Rosuvastatin can reduce ADMA levels and exert vascular protective effects. The increase in serum ADMA levels is closely related to the occurrence of long-term cardiovascular events in patients with hyperlipidaemia and H-type hypertension, serving as a potential clinical predictor to guide disease prevention and treatment.

Background: Statins, being the primary pharmacological intervention for hypercholesterolemia, exhibit a notable degree of interpatient variability in their effectiveness, which may be associated with gut microbiota. This study sought to identify the biomarkers for evaluating differences in statin efficacy., Methods: A quasi case-control study was conducted among participants with hypercholesterolemia and coronary heart disease taking rosuvastatin essential. According to the level of low density lipoprotein cholesterol (LDL-C), participants was divided into the "Up to standard" (US) group and the "Below standard" (BS) group. 16S rDNA sequencing and untargeted metabolomics were applied to detected the information of gut microbiota and related metabolites., Results: A total of 8 US and 8 BS group matched by age and sex were included in the final analysis. 16S rDNA sequencing results indicated that the characteristic strains of the US group were f-Eubacterium&#95;coprostanoligenes and g-Papillibacter , while the characteristic flora of the BS group were o-C0119 , g-Pseudolabrys, s-Dyella-Marensis and f-Xanthobacaceae. Metabolomic results suggested that the levels of chenodeoxycholic acid-3-β-D-glucuronide, 1-methylnicotinamide and acetoacetate in stool samples of the US group were significantly higher than those of the BS group. By identifying the differentially abundant bacterial taxa, the gut microbiota could modulate the efficacy of statins through producing enzymes involved in cholesterol metabolism., Conclusions: The findings suggest that the difference in statin efficacy may be related to gut microbiota strains that can produce short-chain fatty acids and secondary bile acids and affect the efficacy of statins by regulating the activities of cholesterol metabolite-related proteins. Metabolites related to short-chain fatty acids and secondary bile acids in the gut are expected to be biomarkers indicating the efficacy of statins., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hu, Hu, zhang, Hu, Zhang, Zhang, Yu, Liu, Wang, Lin, Gong, Zhang, Li and Li.)

Cardiotoxicity is a side effect of chemotherapy in human epidermal growth factor receptor 2 (HER2) positive breast cancer patients receiving both anthracyclines and trastuzumab. We looked for a possible protective effect of rosuvastatin against chemotherapy-induced cardiotoxicity. Methods: 50 newly diagnosed HER2 positive breast cancer patients were randomly allocated into two groups: 25patients in each. Group 1(control group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy. Group 2 (treatment group) received doxorubicin for 4 cycles (3 months) followed by trastuzumab adjuvant therapy and 20 mg of oral rosuvastatin 24 h before the first cycle of chemotherapy and once daily for the rest of the follow-up period (6 months). Transthoracic echocardiography was done, and blood samples were collected for patients 24 h before the initiation of therapy, after 3 months and after 6 months to assess serum levels of high sensitivity cardiac troponin I (hs-cTnI), Myeloperoxidase (MPO), Interleukin-6 (IL-6) and Alanine aminotransferase (ALT). The study was retrospectively registered in Clinical Trials.gov in April 2022. Its ID is NCT05338723. Compared to control group, Rosuvastatin-treated group had a significantly lower decline in LVEF after 3 months and after 6 months. They had significantly lower Hs-cTnI and IL-6 after 3 months and after 6 months, and significantly lower MPO after 6 months. Four patients in control group experienced cardiotoxicity while no one in rosuvastatin-treated group. Rosuvastatin attenuated cardiotoxicity, so it is a promising protective agent against chemotherapy-induced cardiotoxicity., (© 2024. The Author(s).)

Background: Statin effects extend beyond low-density lipoprotein cholesterol reduction, potentially modulating the metabolism of bioactive lipids (BALs), crucial for biological signaling and inflammation. These bioactive metabolites may serve as metabolic footprints, helping uncover underlying processes linked to pleiotropic effects of statins and yielding a better understanding of their cardioprotective properties. This study aimed to investigate the impact of high-intensity statin therapy versus placebo on plasma BALs in the JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin; NCT00239681), a randomized primary prevention trial involving individuals with low-density lipoprotein cholesterol <130 mg/dL and high-sensitivity C-reactive protein ≥2 mg/L., Methods: Using a nontargeted mass spectrometry approach, over 11 000 lipid features were assayed from baseline and 1-year plasma samples from cardiovascular disease noncases from 2 nonoverlapping nested substudies: JUPITER discovery (n=589) and JUPITER validation (n=409). The effect of randomized allocation of rosuvastatin 20 mg versus placebo on BALs was examined by fitting a linear regression with delta values (∆=year 1-baseline) adjusted for age and baseline levels of each feature. Significant associations in discovery were analyzed in the validation cohort. Multiple comparisons were adjusted using 2-stage overall false discovery rate., Results: We identified 610 lipid features associated with statin randomization with significant replication (overall false discovery rate, <0.05), including 26 with annotations. Statin therapy significantly increased levels of 276 features, including BALs with anti-inflammatory activity and arterial vasodilation properties. Concurrently, 334 features were significantly lowered by statin therapy, including arachidonic acid and proinflammatory and proplatelet aggregation BALs. By contrast, statin therapy reduced an eicosapentaenoic acid-derived hydroxyeicosapentaenoic acid metabolite, which may be related to impaired glucose metabolism. Additionally, we observed sex-related differences in 6 lipid metabolites and 6 unknown features., Conclusions: Statin allocation was significantly associated with upregulation of BALs with anti-inflammatory, antiplatelet aggregation and antioxidant properties and downregulation of BALs with proinflammatory and proplatelet aggregation activity, supporting the pleiotropic effects of statins beyond low-density lipoprotein cholesterol reduction., Competing Interests: Disclosures The parent JUPITER trial (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) was funded by AstraZeneca (Wilmington, DE), which had no role in the current study. Quest Diagnostics and LabCorp (LipoScience) conducted assays at no additional charges. O.V. Demler received support from Kowa, not related to the current work. S. Mora has served as a consultant to Pfizer for work outside the current study. M. Jain is the founder and chief executive officer of Sapient, a private organization specialized in biotechnology research for biomarker profiling. P.M. Ridker received past investigator-initiated research grant support from AstraZeneca to conduct the JUPITER trial; has current investigator-initiated research grant support from Novartis, Novo Nordisk, Kowa, Amarin, Pfizer, Esperion, National Heart, Lung, and Blood Institute, Bristol Myers Squibb, and Operation Warp Speed; served as a consultant to Novartis, Flame, Agepha, Ardelyx, AstraZeneca, Janssen, Civi Biopharm, GlaxoSmithKline, SOCAR, Novo Nordisk, Health Outlook, Montai Health, Eli Lilly, New Amsterdam, Boehringer-Ingelheim, RTI, Cytokinetics, Horizon Therapeutics, and Cardio Therapeutics; has minority shareholder equity positions in Uppton, Bitteroot Bio, and Angiowave; received nonmonetary research support from the Pfizer Bristol Myers Squibb Alliance and from Quidel, Inc, to conduct federally funded COVID-19 research; and receives compensation for service on the Peter Munk Advisory Board (University of Toronto), the Leducq Foundation, Paris FR, and the Baim Institute (Boston, MA). None of these conflicts relate to the current article. The other authors report no conflicts.

Background: This study aimed to evaluate the effects of rosuvastatin and pravastatin on glucose homeostasis and other biomarkers in individuals at high risk of developing diabetes., Methods: This prospective, randomized, open-labeled, and controlled trial included prediabetic individuals with impaired fasting glucose and impaired glucose tolerance. The participants were randomized into three groups: rosuvastatin (10 mg), pravastatin (40 mg), or control. Biomarkers of diabetes and glucose and insulin responses to oral glucose tolerance tests were assessed at baseline and after 6 months of treatment. The primary outcomes were comparisons of glucose homeostasis and biomarkers of diabetes among groups at baseline and after 6 months of treatment., Results: A total of 141 subjects with impaired fasting glucose (IFG) were screened and 41 participants were recruited. Twenty-two subjects were randomized to either the rosuvastatin or pravastatin group and 19 subjects were assigned to the control group. After 6 months of treatment, all groups had similar cholesterol and triglyceride levels. Likewise, HbA1c levels, glucose, and insulin excursions during oral glucose tolerance test, were similar among the three groups. However, compared to the other groups, the rosuvastatin group had higher homeostasis model assessment for insulin resistance (HOMA-IR) (insulin resistance) and a lower Matsuda index (insulin sensitivity)., Conclusion: Among prediabetic individuals with IFG, rosuvastatin treatment was associated with increased insulin resistance and decreased insulin sensitivity compared to pravastatin and control groups. Further research is needed to elucidate the underlying mechanisms and clinical implications of these findings., Competing Interests: Conflicts of interest: Dr. Harn-Shen Chen, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: Secreted glycoproteins of the Dickkopf (DKK) family modify Wnt signaling and may influence plaque destabilization but their modulation by statins in MI patients is not known., Methods: We measured plasma DKK-1 and DKK-3 in patients with acute ST-segment elevation MI (STEMI) before percutaneous coronary intervention (PCI) and after 2 and 7 days and 2 months in patients receiving short-term high-dose (40 mg rosuvastatin, given before PCI; n = 25) and moderate dose (20 mg simvastatin, given the day after PCI; n = 34). In vitro modulation of DKK-1 in human umbilical vein endothelial cells (HUVECs) by statins were assessed., Results: (i) Patients receiving high dose rosuvastatin had a marked decline in DKK-1 at day 2 which was maintained throughout the study period. However, a more prevalent use of β-blockers in the simvastatin group, that could have contributed to higher DKK-1 levels in these patients. (ii) There was a strong correlation between baseline DKK-1 levels and change in DKK-1 from baseline to day 2 in patients receiving high dose rosuvastatin treatment. (iii) DKK-3 increased at day 2 but returned to baseline levels at 2 months in both treatment groups. (iv) Statin treatment dose-dependently decreased DKK-1 mRNA and protein levels in HUVEC., Conclusions: Our findings suggest that high dose statin treatment with 40 mg rosuvastatin could persistently down-regulate DKK-1 levels, even at 2 months after the initial event in STEMI patients., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The efficacy of rosuvastatin in reducing allergic inflammation has been established. However, its potential to reduce airway remodeling has yet to be explored. This study aimed to evaluate the efficacy of rosuvastatin in reducing airway inflammation and remodeling in a mouse model of chronic allergic asthma induced by sensitization and challenge with OVA. Histology of the lung tissue and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) showed a marked decrease in airway inflammation and remodeling in mice treated with rosuvastatin, as evidenced by a decrease in goblet cell hyperplasia, collagen deposition, and smooth muscle hypertrophy. Furthermore, levels of inflammatory cytokines, angiogenesis-related factors, and OVA-specific IgE in BALF, plasma, and serum were all reduced upon treatment with rosuvastatin. Western blotting was employed to detect AMPK expression, while immunohistochemistry staining was used to observe the expression of remodeling signaling proteins such as α-SMA, TGF-β, MMP-9, and p-AMPKα in the lungs. It was found that the activity of 5'-adenosine monophosphate-activated protein kinase alpha (AMPKα) was significantly lower in the lungs of OVA-induced asthmatic mice compared to Control mice. However, the administration of rosuvastatin increased the ratio of phosphorylated AMPK to total AMPKα, thus inhibiting the formation of new blood vessels, as indicated by CD31-positive staining mainly in the sub-epithelial region. These results indicate that rosuvastatin can effectively reduce airway inflammation and remodeling in mice with chronic allergic asthma caused by OVA, likely due to the reactivation of AMPKα and a decrease in angiogenesis., Competing Interests: The authors declare that there is no conflict of interest to declare., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Microbial infection-induced sepsis causes excessive inflammatory response and multiple organ failure. An effective strategy for the treatment of sepsis-related syndromes is still needed. Rosuvastatin, a typical β-hydroxy β-methylglutaryl-CoA reductase inhibitor licensed for reducing the levels of low-density lipoprotein cholesterol in patients with hyperlipidemia, has displayed anti-inflammatory capacity in different types of organs and tissues. However, its effects on the development of sepsis are less reported. Here, we found that the administration of Rosuvastatin reduced the mortality of sepsis mice and prevented body temperature loss. Additionally, it inhibited the production of inflammatory cytokines such as tumor necrosis factor (TNF-α), Interleukin-6 (IL-6), interleukin-1β (IL-1β), and migration inhibitory factor (MIF) in peritoneal lavage supernatants of animals. The increased number of mononuclear cells in the peritoneum of sepsis mice was reduced by Rosuvastatin. Interestingly, it ameliorated lung inflammation and improved the hepatic and renal function in the sepsis animals. Further in vitro experiments show that Rosuvastatin inhibited lipopolysaccharide (LPS)-induced production of proinflammatory cytokines in RAW 264.7 macrophages by preventing the activation of nuclear factor kappa-B (NF-κB). Our findings demonstrate that the administration of Rosuvastatin hampered organ dysfunction and mitigated inflammation in a relevant model of sepsis.

Objectives: Atherosclerotic cardiovascular disease (ASCVD) events have been shown to occur at higher frequency in patients with peripheral arterial disease (PAD). In this study, our aim is to evaluate whether statin is being used appropriately in patients with PAD and also evaluate its usage with the number of vascular beds involved., Materials and Methods: This retrospective cross-sectional study reviewed data of patients with a confirmed diagnosis of PAD based on invasive or noninvasive imaging. Demographic, clinical, laboratory, and treatment data collected were described using descriptive statistics. Multiple logistic regression analysis was conducted to determine the predictors for the prescription of statins (HIS). High-intensity statin therapy was defined as atorvastatin ≥40 mg per day, rosuvastatin ≥20 mg per day, or simvastatin ≥80 mg per day, according to American College of Cardiology (ACC)/American Heart Association (AHA) guidelines., Results: We analyzed data from 166 patients who met the inclusion criteria. The mean age was 63.34 years. The most common comorbidity was diabetes mellitus (DM) (68.86%). Statins were used in 82% of patients, among whom only 39% were on high-intensity statins. Multiple logistic regression analysis revealed that patients with cerebrovascular disease (CVD) [odds ratio (OR) = 0.19, 95% confidence interval (CI) = 0.06-0.61, p = 0.005], on oral anticoagulants (OAC) (OR = 0.16, 95% CI = 0.04-0.62, p = 0.008) and on dual antiplatelet therapy (DAPT) (OR = 0.20, 95% CI = 0.08-0.47, p < 0.000) had lower odds of receiving lower extremity revascularization (LIS) therapy., Conclusion: Despite having a high risk of future adverse cardiac events, patients with PAD are less likely to receive appropriate statin therapy. Involvement of more vascular beds was associated with higher chances of initiating high-intensity statin., (© Journal of the Association of Physicians of India 2024.)

Background: Statins are lipid-lowering drugs with favorable anti-inflammatory effects. This study aimed to explore different statin-based lipid-lowering strategies to reduce high-sensitivity C-reactive protein (hs-CRP)., Hypothesis: The hypothesis is that different statin-based lipid-lowering strategies might reduce hs-CRP., Methods: This retrospective study included 3653 patients who underwent percutaneous coronary intervention (PCI). Three statin-based lipid-lowering strategies were investigated, including different types of statins (atorvastatin vs. rosuvastatin), statin combined with ezetimibe therapy (vs. without), and intensive statin therapy (vs. regular). The hs-CRP levels and blood lipid indicators were measured at baseline and after 1-month lipid-lowering therapy. Multivariable linear regression analysis and structural equation mode analysis were conducted to verify the association between different lipid-lowering strategies, Δhs-CRP (%) and ΔLDL-C (%)., Results: Totally, 3653 patients were enrolled with an average age of 63.81 years. Multivariable linear regression demonstrated that statin combined with ezetimibe therapy was significantly associated with decreased Δhs-CRP (%) (β = -0.253, 95% CI: [-0.501 to -0.005], p = 0.045). The increased ΔLDL-C (%) was an independent predictor of elevated levels of Δhs-CRP (%) (β = 0.487, 95% CI: [0.15-0.824], p = 0.005). Furthermore, structural equation model analysis proved that statin combined with ezetimibe therapy (β = -0.300, p < 0.001) and intensive statin therapy (β = -0.032, p = 0.043) had an indirect negative effect on Δhs-CRP via ΔLDL-C., Conclusions: Compared with routine statin use, statin combined with ezetimibe therapy and intensive statin therapy could further reduce hs-CRP levels., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background and Aims: Proper prescription and high adherence to intensive lipid lowering drugs (LLD) in patients with coronary heart disease (CHD) are crucial and strongly recommended. The aim of this study is to investigate long-term treatment patterns and adherence to LLD following hospitalization for a CHD event., Methods: Patients admitted to two Norwegian hospitals with a CHD event from 2011 to 2014 (N = 1094) attended clinical examination and completed a questionnaire, median 16 months later. Clinical data were linked to pharmacy dispensing data from 2010 to 2020. The proportions using high-intensity statin therapy (atorvastatin 40/80 mg or rosuvastatin 20/40 mg) and non-statin LLD after the CHD event were assessed. Adherence was evaluated by proportion of days covered (PDC) and gaps in treatment., Results: Median age at hospitalization was 63 (IQR 12) years, 21 % were female. Altogether, 1054 patients (96 %) were discharged with a statin prescription, while treatment was dispensed in 85 % within the following 90 days. During median 8 (SD 2.5) years follow-up, the proportion using high-intensity statin therapy ranged 62-68 %, whereas the use of ezetimibe increased from 4 to 26 %. PDC <0.8 was found in 22 % of statin users and 26 % of ezetimibe users. The proportions with a treatment gap exceeding 180 days were 22 % for statins and 28 % for ezetimibe. Smoking at hospitalization and negative affectivity were significantly associated with reduced statin adherence, regardless of adherence measure., Conclusions: In this long-term follow-up of patients with CHD, less than 70 % used high-intensity statin therapy with only small changes over time, and only 25 % used additional treatment with ezetimibe. We identified factors associated with reduced statin adherence that may be target for interventions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:IE and CB are affiliated with Oslo Economics and have completed consultancy assignments outside the submitted work for several public and private institutions in recent years. HS is affiliated with Steno Diabetes Center Aarhus and has received consultancy fees from Novartis, Arla Foods AMBA, Bristol-Myers Squibb, Pfizer and Neumirna outside the submitted work. EH, ES and TD reports no conflicts of interest. SH has received lecture fees from Sanofi, Novartis, and Pfizer outside the submitted work. JM received lecture fees from Sanofi, Novartis, Boehringer Ingelheim, and Bayer outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Based on a clinical case report, the article shows the individual selection of effective therapy for a patient with arterial hypertension and dyslipidemia. Taking into account the risk factors for cardiovascular diseases, Equamer® was selected as a fixed combination of amlodipine + lisinopril + rosuvastatin capsules 10 mg+20 mg+10 mg (Gedeon Richter Plc, Budapest, Hungary). In the patient with hypertension, ischemic heart disease was verified, and stenting of the anterior descending artery was performed. According to the clinical guidelines, when arterial hypertension is associated with ischemic heart disease, the drug therapy of choice should be a combination of dihydropyridine slow calcium channel blockers with an angiotensin-converting enzyme inhibitor. The fixed triple combination of amlodipine, lisinopril, and rosuvastatin is one of the most appropriate in this clinical situation; this combination targets the two major risk factors for cardiovascular diseases, arterial hypertension and dyslipidemia.

Background: Statins are the first-line treatment for dyslipidemia, which is a major modifiable risk factor for atherosclerotic cardiovascular disease. Studies have shown that in addition to the beneficial lipid-lowering effect, statins also exhibit a number of pleiotropic effects that may find application in other diseases, including osteoporosis. This study aimed to assess the effect of statins on bone turnover, as measured by the concentration of bone turnover markers, and to compare the effect of atorvastatin as a lipophilic statin and rosuvastatin as a hydrophilic statin., Methods: This study included 34 postmenopausal women aged < 65 years with newly diagnosed dyslipidemia requiring statin therapy. Patients were randomly assigned to receive a statin drug. Statins were initiated at standard doses of 5 to 10 mg of rosuvastatin and 20 mg of atorvastatin. The levels of C-terminal telopeptide of type I collagen as a bone resorption marker and N-terminal propeptide of procollagen type I as a marker of bone formation, lipid concentrations and other biochemical parameters were assessed at baseline and after 6 and twelve months of treatment., Results: There were no statistically significant differences between the levels of bone turnover markers before and 6 months after statin implementation (P > .05) - for all patients or subgroups according to statin use. Analysis of the results showed that after 12 months, there was a statistically significant decrease in N-terminal propeptide of procollagen type I concentration in all subjects (P = .004). By statin subgroup, a statistically significant decrease in N-terminal propeptide of procollagen type I was observed only in patients receiving rosuvastatin (P = .012) and not in those receiving atorvastatin (P = .25). Moreover, changes in bone turnover markers did not correlate with changes in lipid concentrations., Conclusions: These results may indicate the superiority of atorvastatin over rosuvastatin in inhibiting adverse changes in bone turnover in postmenopausal women. Confirmed by studies involving a larger population, the observed differences might find particular applications in clinical practice, and the choice of atorvastatin over rosuvastatin for women could be considered in the early postmenopausal period to reduce the risk of osteoporosis and subsequent osteoporotic fractures., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Cholesterol-lowering statins are frequently prescribed for primary and secondary prevention of ischaemic vascular events. Whereas most patients tolerate statins without problems, statin-associated myopathy is well documented, as are several risk factors. We present a case report of an 80-90-year-old man with coronary artery disease who rapidly developed severe rhabdomyolysis during treatment with rosuvastatin while in intensive care. He had several concomitant risk factors for statin-induced myopathy including high dosage, old age, renal and hepatic impairment, and a pharmacogenetic SLCO1B1*1 a/*5 variant. Single known risk factors have a low predictive value for statin-induced myopathy and may therefore be underestimated in clinical practice. However, adverse drug reactions frequently involve the joint action of a multitude of environmental and genetic component causes, and statin-induced myopathy should be regarded as a multicausal event. We therefore advocate a proactive multifactorial risk assessment to guide and individualise statin therapy in high-risk patients., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: The latest evidence indicates that ATP-binding cassette superfamily G member 2 (ABCG2) is critical in regulating lipid metabolism and mediating statin or cholesterol efflux. This study investigates whether the function variant loss within ABCG2 (rs2231142) impacts lipid levels and statin efficiency., Methods: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until November 18, 2023., Results: Fifteen studies (34,150 individuals) were included in the analysis. The A allele [Glu141Lys amino acid substitution was formed by a transversion from cytosine (C) to adenine (A)] of rs2231142 was linked to lower levels of high-density lipoprotein cholesterol (HDL-C), and higher levels of low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). In addition, the A allele of rs2231142 substantially increased the lipid-lowering efficiency of rosuvastatin in Asian individuals with dyslipidemia. Subgroup analysis indicated that the impacts of rs2231142 on lipid levels and statin response were primarily in Asian individuals., Conclusions: The ABCG2 rs2231142 loss of function variant significantly impacts lipid levels and statin efficiency. Preventive use of rosuvastatin may prevent the onset of coronary artery disease (CAD) in Asian individuals with dyslipidemia., (© 2024. The Author(s).)

Purpose: Hypertensive emergency, a sudden and severe increase in blood pressure, necessitates immediate intervention to avoid end-organ damage. Cilostazol, a selective phosphodiesterase-III inhibitor, has vasodilator effect. Here, we investigated the effect of two commonly used statins, atorvastatin or rosuvastatin, on cilostazol antihypertensive activity in acute model of hypertension., Methods: Hypertensive emergency was induced via angiotensin II intravenous infusion (120 ng.kg -1 .min -1 ). Rats were subjected to real-time arterial hemodynamics and electrocardiogram recording while investigated drugs were injected slowly at cumulative doses 0.5, 1, and 2 mg.kg -1 , individually or in combination, followed by baroreflex sensitivity (BRS) analysis and serum electrolytes (Na + and K + ) and vasomodulators (norepinephrine (NE), and nitric oxide (NO)) assessment., Results: Cilostazol reduced systolic blood pressure (SBP), while co-injection with rosuvastatin augmented cilostazol SBP-reduction up to 30 mmHg. Compared to atorvastatin, rosuvastatin boosted the cilostazol-associated reduction in peripheral resistance, as evidenced by further decrease in diastolic, pulse, and dicrotic-notch pressures. Rosuvastatin co-injection prevented cilostazol-induced changes of ejection and non-ejection durations. Additionally, rosuvastatin coadministration produced better restoration of BRS, with an observed augmented increase in BRS indexes from spectral analysis. Greater reduction in sympathetic/parasympathetic ratio and serum NE upon rosuvastatin coadministration indicates further shift in sympathovagal balance towards parasympathetic dominance. Additionally, rosuvastatin coinjection caused a greater decrease in serum sodium, while more increase in NO indicating augmented reduction of extracellular volume and endothelial dysfunction., Conclusion: Rosuvastatin boosted cilostazol's antihypertensive actions through effects on peripheral resistance, BRS, sympathovagal balance, endothelial dysfunction, and electrolytes balance, while atorvastatin did not demonstrate a comparable impact., (© 2023. The Author(s).)

Objectives: Chronic low-grade inflammation is widely recognized as a pathophysiological defect contributing to β-cell failure in type 2 diabetes mellitus (T2DM). Statin therapy is known to ameliorate CD8+ T cell senescence, a mediator of chronic inflammation. However, the additional immunomodulatory roles of ezetimibe are not fully understood. Therefore, we investigated the effect of statin or statin/ezetimibe combination treatment on T cell senescence markers., Methods: In this two-group parallel and randomized controlled trial, we enrolled 149 patients with T2DM whose low-density lipoprotein cholesterol (LDL-C) was 100 mg/dL or higher. Patients were randomly assigned to either the rosuvastatin group (N=74) or the rosuvastatin/ezetimibe group (N=75). The immunophenotype of peripheral blood mononuclear cells and metabolic profiles were analyzed using samples from baseline and post-12 weeks of medication., Results: The fractions of CD8+CD57+ (senescent CD8+ T cells) and CD4+FoxP3+ (T reg ) significantly decreased after intervention in the rosuvastatin/ezetimibe group (-4.5 ± 14.1% and -1.2 ± 2.3%, respectively), while these fractions showed minimal change in the rosuvastatin group (2.8 ± 9.4% and 1.4 ± 1.5%, respectively). The degree of LDL-C reduction was correlated with an improvement in HbA1c (R=0.193, p =0.021). Changes in the CD8+CD57+ fraction positively correlated with patient age (R=0.538, p =0.026). Notably, the fraction change in senescent CD8+ T cells showed no significant relationship with changes in either HbA1c ( p =0.314) or LDL-C ( p =0.592). Finally, the ratio of naïve to memory CD8+ T cells increased in the rosuvastatin/ezetimibe group ( p =0.011), but not in the rosuvastatin group ( p =0.339)., Conclusions: We observed a reduction in senescent CD8+ T cells and an increase in the ratio of naive to memory CD8+ T cells with rosuvastatin/ezetimibe treatment. Our results demonstrate the immunomodulatory roles of ezetimibe in combination with statins, independent of improvements in lipid or HbA1c levels., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ju, Lim, Song, Kim, Kang, Yi, Joung, Lee, Kim and Ku.)

Objectives: The high cardiovascular disease burden globally and in Australia necessitates attention on statin expenditure, the primary pharmacological intervention for cardiovascular disease risk factors. The Pharmaceutical Benefits Scheme (PBS) subsidies approved statins for Australians. Managing PBS government expenditure occurs through price control strategies of statutory price decreases upon first generic entry and price disclosure. This study investigates the impact price control measures had on statin price evolution and government expenditure between 2010 and 2022., Methods: Prescription and pricing data were obtained from Services Australia Medicare Statistics, and price reduction strategies from the PBS. Summary statistics compared and described statin price, prescription, number of brands, market share, and government expenditure to atorvastatin, fluvastatin, pravastatin, rosuvastatin, and simvastatin price control timelines., Results: Statin prices exposed to price control measures decreased irrespective of dosage and correlated with reductions in government expenditure, with a comparison of 2010 and 2022 showing annual statin expenditure declined by AU$833.5 million (83.25%) whereas prescriptions reduced by 3.0 million (15.7%). Effects of price disclosure on atorvastatin and rosuvastatin market share suggest industry-prompted price reductions may arise from market share loss, whereas reasons external to pricing prompted rosuvastatin to gain market share., Conclusions: Limited publications on contemporary effects of statin price control measures exist. This investigation found these measures reduced government expenditure for statins by AU$949.1 million, with the price reduction correlating with price control measures. In addition to affirming price control mechanisms remain effective in contemporary times, this investigation provides data for key insights into the Australian statin industry., (Copyright © 2023 International Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

This study aimed to compare and evaluate the efficacy of the blood pressure (BP) control and cholesterol-lowering effects and safety of combination therapy with telmisartan, rosuvastatin, and ezetimibe versus rosuvastatin and ezetimibe double therapy or telmisartan single therapy in dyslipidemia patients with hypertension. After a wash-out/therapeutic lifestyle change period of ≥4 weeks, a total of 100 eligible patients were randomized and received one of three treatments for 8 weeks: (1) telmisartan 80 mg/rosuvastatin 20 mg/ezetimibe 10 mg (TRE), (2) rosuvastatin 20 mg/ezetimibe 10 mg (RE), or (3) telmisartan 80 mg (T). The primary endpoint was the efficacy evaluation of TRE by comparing changes in mean sitting systolic blood pressure (msSBP) and mean percentage change in low-density lipoprotein-C (LDL-C) from baseline after 8 weeks of treatment. The least square (LS) mean (SE) changes in msSBP at 8 weeks compared with baseline were -23.02 (3.04) versus -7.18 (3.09) mmHg in the TRE and RE groups, respectively (p < .0001), and -25.80 (2.74) versus -14.92 (2.65) mmHg in the TRE and T groups, respectively (p = .0005). The percentage changes in the mean (SD) LDL-C at 8 weeks compared with baseline were -54.97% (3.49%) versus -0.17% (3.23%) in the TRE and T groups, respectively (p < .0001). No serious adverse events occurred, and no statistically significant differences in the incidence of overall AEs and adverse drug reactions occurred among the three groups. TRE therapy significantly decreased msSBP and LDL-C compared to RE or T therapy with comparable safety and tolerability profiles., (© 2024 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Nephropathis epidemica (NE), a mild form of hemorrhagic fever with renal syndrome (HFRS), is an acute zoonotic disease endemic in the Republic of Tatarstan. This study aimed to assess the impact of rosuvastatin on the clinical and laboratory results of NE. A total of 61 NE patients and 30 controls were included in this study; 22 NE patients and 7 controls received a daily dose of rosuvastatin (10 mg) for ten consecutive days. Serum samples were collected on days 1, 5, and 10 after admission to the hospital. These samples were analyzed to determine the levels of lipids, cytokines, and kidney toxicity markers. Our findings indicate that rosuvastatin reduced the duration of the second wave of fever and alleviated back pain and headache symptoms. Additionally, low-density lipoprotein cholesterol (LDL-C) serum levels were significantly decreased on days 5 and 10 upon rosuvastatin treatment. Furthermore, rosuvastatin decreased the levels of cytokines in the serum, particularly proinflammatory cytokines IL-1β and IL-8. NE patients had significantly altered levels of the kidney toxicity markers albumin and osteopontin. The data from our study provide evidence supporting the therapeutic potential of rosuvastatin in NE cases.

Background: Coronary artery bypass graft (CABG) is generally used to treat complex coronary artery disease. Treatment success is affected by neointimal hyperplasia (NIH) of graft and anastomotic sites. Although sirolimus and rosuvastatin individually inhibit NIH progression, the efficacy of combination treatment remains unknown., Methods: We identified cross-targets associated with CABG, sirolimus, and rosuvastatin by using databases including DisGeNET and GeneCards. GO and KEGG pathway enrichment analyses were conducted using R studio, and target proteins were mapped in PPI networks using Metascape and Cytoscape. For in vivo validation, we established a balloon-injured rabbit model by inducing NIH and applied a localized perivascular drug delivery device containing sirolimus and rosuvastatin. The outcomes were evaluated at 1, 2, and 4 weeks post-surgery., Results: We identified 115 shared targets between sirolimus and CABG among databases, 23 between rosuvastatin and CABG, and 96 among all three. TNF, AKT1, and MMP9 were identified as shared targets. Network pharmacology predicted the stages of NIH progression and the corresponding signaling pathways linked to sirolimus (acute stage, IL6/STAT3 signaling) and rosuvastatin (chronic stage, Akt/MMP9 signaling). In vivo experiments demonstrated that the combination of sirolimus and rosuvastatin significantly suppressed NIH progression. This combination treatment also markedly decreased the expression of inflammation and Akt signaling pathway-related proteins, which was consistent with the predictions from network pharmacology analysis., Conclusions: Sirolimus and rosuvastatin inhibited pro-inflammatory cytokine production during the acute stage and regulated Akt/mTOR/NF-κB/STAT3 signaling in the chronic stage of NIH progression. These potential synergistic mechanisms may optimize treatment strategies to improve long-term patency after CABG., (© 2024. The Author(s).)

Numerous efforts to manage acute kidney injury (AKI) were unsuccessful because its pathophysiology is still poorly understood. Thus, our research hotspot was to explore the possible renoprotective effects of rosuvastatin (Ros) and diosmetin (D) on macrophage polarization and the role of HSP70/TLR4/MyD88/NF-κB p65/NLRP3/STAT3 signaling in cis-induced AKI and study the activity of D against uropathogenic bacteria. Fifty-four albino male rats were randomized into 9 groups equally: Control, Ros, D20, D40, untreated Cis, and Cis groups cotreated with Ros, D20, D40 and Ros+D40 for 10 days. Our results indicated that Ros and D, in a dose-dependent manner, markedly restored body weight, systolic blood pressure, and renal histological architecture besides significantly upregulated SOD levels, expression of anti-inflammatory CD163 macrophages, arginase1levels, IL-10 levels,STAT3 and PCNA immunoreactivity. Also, they significantly downregulated renal index, serum urea, serum creatinine, serum cystatin c, inflammatory biomarkers (C reactive protein, IL1β & TNF-α), MDA levels, HSP70/TLR4/MyD88/NF-κB p65/NLRP3 expressions, proinflammatory CD68 macrophages and caspase-3 immunoreactivity, resulting in a reversal of cis-induced renal damage. These findings were further confirmed by molecular docking that showed the binding affinity of Ros and D towards TLR4 and NLRP3. Furthermore, D had antibacterial action with a minimum inhibitory concentration ranging from 128 to 256 µg/mL and caused a delay in the growth of the tested isolates, and negatively affected the membrane integrity. In conclusion, Ros and D had antioxidant, anti-inflammatory and antiapoptotic properties and switched macrophage from proinflammatory CD68 to anti-inflammatory CD163. Additionally, the targeting of HSP70/TLR4/MyD88/NF-κB p65/NLRP3/STAT3 signals are effective therapeutic strategy in AKI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Recent lipid lowering therapy trials have provided important insights on certain agents while also continuing to expand our understanding of atherosclerotic cardiovascular disease (ASCVD) risk. Findings from current trials include the impact of statin therapy on ASCVD among populations with HIV, the benefit of lowering low-density lipoprotein cholesterol with bempedoic acid among patients considered statin intolerant, the safety and efficacy of inclisiran over a 4-year period, another failed attempt for fibrates to reduce ASCVD risk, which omega-3 fatty to utilize for lowering cardiovascular events, 'n-of-1' trials evaluating statin intolerance, and how low-dose rosuvastatin compared with commonly utilized supplements for lowering lipid parameters. Such data help inform so clinicians can optimize lipid lowering therapy and improve ASCVD outcomes.

Coronary artery disease is defined by the existence of atherosclerotic plaque on the arterial wall, which can cause blood flow impairment, or plaque rupture, and ultimately lead to myocardial ischemia. Intravascular ultrasound (IVUS) imaging can provide a detailed characterization of lumen and vessel features, and so plaque burden, in coronary vessels. Prediction of the regions in a vascular segment where plaque burden can either increase (progression) or decrease (regression) following a certain therapy, has remained an elusive major milestone in cardiology. Studies like IBIS-4 showed an association between plaque burden regression and high-intensity rosuvastatin therapy over 13 months. Nevertheless, it has not been possible to predict if a patient would respond in a favorable/adverse fashion to such a treatment. This work aims to (i) Develop a framework that processes lumen and vessel cross-sectional contours and extracts geometric descriptors from baseline and follow-up IVUS pullbacks; and to (ii) Develop, train, and validate a machine learning model based on baseline/follow-up IVUS datasets that predicts future percent of atheroma volume changes in coronary vascular segments using only baseline information, i.e. geometric features and clinical data. This is a post hoc analysis, revisiting the IBIS-4 study. We employed 140 arteries, from 81 patients, for which expert delineation of lumen and vessel contours were available at baseline and 13-month follow-up. Contour data from baseline and follow-up pullbacks were co-registered and then processed to extract several frame-wise features, e.g. areas, plaque burden, eccentricity, etc. Each pullback was divided into regions of interest (ROIs), following different criteria. Frame-wise features were condensed into region-wise markers using tools from statistics, signal processing, and information theory. Finally, a stratified 5-fold cross-validation strategy (20 repetitions) was used to train/validate an XGBoost regression models. A feature selection method before the model training was also applied. When the models were trained/validated on ROI defined by the difference between follow-up and baseline plaque burden, the average accuracy and Mathews correlation coefficient were 0.70 and 0.41 respectively. Using a ROI partition criterion based only on the baseline's plaque burden resulted in averages of 0.60 accuracy and 0.23 Mathews correlation coefficient. An XGBoost model was capable of predicting plaque progression/regression changes in coronary vascular segments of patients treated with rosuvastatin therapy in 13 months. The proposed method, first of its kind, successfully managed to address the problem of stratification of patients at risk of coronary plaque progression, using IVUS images and standard patient clinical data., (© 2024. The Author(s).)

The patient was a 54-year-old woman with familial hypercholesterolemia and remarkable Achilles tendon thickening. At 20 years old, the patient had a total cholesterol level of approximately 300 mg/dL. She started receiving rosuvastatin (5 mg/day) for low-density lipoprotein cholesterol (LDL-C) 235 mg/dL at 42 years old, which was increased to 10 mg/day at 54 years old, decreasing her serum LDL-C level to approximately 90 mg/dL. The serum Lp (a) level was 9 mg/dL. A computed tomography coronary angiogram showed no significant stenosis. Next-generation sequencing revealed a frameshift variant in LDL receptor (LDLR) (heterozygous) and a missense variant in proprotein convertase subtilisin/kaxin type 9 (PCSK9) (heterozygous). Continued statin therapy, in addition to low Lp (a) and female sex, can help prevent cardiovascular disease.

There is limited and inconsistent evidence for the association of statin therapy and statin treatment patterns with the risk of recurrent intracerebral hemorrhage (ICH) in patients with prior ICH. To assess the association of statin therapy and its intensity, type, initiation time, and discontinuation with the risk of recurrent ICH and mortality in Chinese patients with ICH. Patients with newly diagnosed ICH in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. Post-ICH statin users (post-diagnosis only) and nonusers (never), statin discontinuers (pre-diagnosis only) and continuers (pre- and post-diagnosis) were matched on a 1:1 propensity score, respectively. Adjusted Cox proportional risk models were used to estimate the risk ratios for ICH readmission and mortality under various statin patterns. A total of 2668 post-ICH statin users and 2668 nonusers without a history of statin use were enrolled. Post-ICH statin users had a lower risk of ICH readmission (HR, 0.57; 95% CI 0.48, 0.69) and all-cause death (0.56: 0.49, 0.63) than nonusers. Low/moderate-intensity treatment was associated with a 63% lower risk of recurrent ICH compared with nonusers (0.37: 0.29, 0.46), whereas high-intensity treatment did not reduce the risk (0.93: 0.74, 1.16). Both low/moderate-intensity (0.42: 0.36, 0.48) and high-intensity statins (0.57: 0.48, 0.69) were associated with a lower risk of all-cause mortality. The risk of ICH readmission was 53% (0.47: 0.30, 0.74) lower with adherence to rosuvastatin than with atorvastatin. Only starting medication within 30 days of the first diagnosis of ICH reduced the risk of ICH readmission (0.49: 0.40, 0.60). Among patients with a history of statin use, 1807 discontinuing and 1,807 continuing users of statins were included. The risk of ICH readmission (4.00: 3.32, 4.80) and the risk of all-cause death (4.01: 3.57, 4.50) were substantially increased in statin discontinuation compared with continued statin use. Statin therapy after ICH was associated with lower risks for ICH readmission and all-cause mortality compared with non-statin therapy, especially at low/moderate intensity and early initiation of statins after ICH. Adherence to rosuvastatin was associated with a lower risk of recurrence of ICH than atorvastatin. Among patients with a statin history prior to ICH, discontinuation of statins after ICH was associated with increased risk of ICH recurrence and death., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The article analyzes the results of a set of biochemical indicators in the course of treatment with the combined use of rosuvastatin with quercetin in patients with metabolic syndrome (MS) combined with non-alcoholic fatty liver disease. Changes in blood biochemical parameters have been identified and presented with MS, essential for revealing generalbiological mechanisms development and interrelationship between the components of MS and non-alcoholic fatty liver. The effect of an increase in free cholesterol and triglycerides and activation of freeradical oxidation of lipids followed by theaccumulation of oxidative stress products was noted. In the course of long-term hypolipidemic therapy (90 days), 86 patients with non-alcoholic fatty liver disease on the background of metabolic syndrome were previously divided into 2 groups: a comparison group (45 patients), who weretreated with basic therapy - only rosuvastatin, the main group (41 patients) received quercetin together with rosuvastatin -40 mg 3 times a day, clinical and laboratory-instrumental examinations were carried out. On the 90th day of treatment, positive results in the functional state of the liver and lipid spectrum of the blood wereregistered in all patients. A more significant advantage of the therapeutic combination of rosuvastatin with quercetin was proved. The inclusion of quercetin contributed to reducing the intensity of oxidative stress and enhancing antioxidant protection activity, resultingin a decrease in apoptosis of hepatocytes (cytokeratin-18 level was 1.27 times decreased). The studies have shown the feasibility of combined use of quercetin with rosuvastatin for the prevention of the development and progression of metabolic disorders associated with non-alcoholic fatty liver disease.

Backgruound: Type 2 diabetes mellitus (T2DM) induces endothelial dysfunction and inflammation, which are the main factors for atherosclerosis and cardiovascular disease. The present study aimed to compare the effects of rosuvastatin monotherapy and rosuvastatin/ezetimibe combination therapy on lipid profile, insulin sensitivity, and vascular inflammatory response in patients with T2DM., Methods: A total of 101 patients with T2DM and dyslipidemia were randomized to either rosuvastatin monotherapy (5 mg/day, n=47) or rosuvastatin/ezetimibe combination therapy (5 mg/10 mg/day, n=45) and treated for 12 weeks. Serum lipids, glucose, insulin, soluble intercellular adhesion molecule-1 (sICAM-1), and peroxiredoxin 4 (PRDX4) levels were determined before and after 12 weeks of treatment., Results: The reduction in low density lipoprotein cholesterol (LDL-C) by more than 50% from baseline after treatment was more in the combination therapy group. The serum sICAM-1 levels increased significantly in both groups, but there was no difference between the two groups. The significant changes in homeostasis model assessment of insulin resistance (HOMA-IR) and PRDX4 were confirmed only in the subgroup in which LDL-C was reduced by 50% or more in the combination therapy group. However, after adjusting for diabetes mellitus duration and hypertension, the changes in HOMA-IR and PRDX4 were not significant between the two groups., Conclusion: Although rosuvastatin/ezetimibe combination therapy had a greater LDL-C reduction effect than rosuvastatin monotherapy, it had no additional effects on insulin sensitivity and vascular inflammatory response. Further studies are needed on the effect of long-term treatment with ezetimibe on insulin sensitivity and vascular inflammatory response.

Purpose: There are few studies in the literature on the dosage of statin that equivalently reduces low-density lipoprotein cholesterol (LDL-C) compared to an ezetimibe combination and whether such regimens have differences in safety. We compared the lipid-modifying efficacy and safety of 5 mg rosuvastatin/10 mg ezetimibe to those of 20 mg rosuvastatin., Materials and Methods: A literature search was conducted using the PubMed, EMBASE, Cochrane, Web of Sciences, and SCOPUS databases up to December 2021. Human studies investigating the two aforementioned regimens with a randomized controlled design were selected. Outcome variables included the percentage reduction in LDL-C and other lipid parameters and rates of composite adverse events (AEs), including muscle-related symptoms. A random-effects meta-analysis was performed after heterogeneity testing between studies., Results: Seven studies were included in this meta-analysis. The percentage LDL-C reduction did not differ between the combination and monotherapy groups [standardized mean difference (SMD) 0.08; 95% confidence interval (CI) -0.09 to 0.26; p =0.35]. The risk of composite AEs (odds ratio 0.50; 95% CI 0.15 to 1.72; p =0.27) of the combination was not different compared to the monotherapy group. The percentage of total cholesterol reduction was greater in the combination group (SMD 0.22; p =0.02), whereas that of triglyceride reduction and high-density lipoprotein cholesterol elevation did not differ between the two groups., Conclusion: This meta-analysis showed that 5 mg rosuvastatin/10 mg ezetimibe had largely comparable lipid-modifying efficacy and tolerability as 20 mg rosuvastatin., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

This study aimed to investigate the effect of rosuvastatin treatment on anxiety-related behavior and short- and long-term memory impairment in mice infected with acute RH and BRI strains of Toxoplasma gondii. Balb/C mice were infected intraperitoneally and after 2 h, oral treatment with rosuvastatin (40 mg/kg/day) was initiated for 4 days. Behaviors related to anxiety and locomotion were evaluated in the open field (OF), and short- and long-term memory through the novel object recognition test (NOR). At the end of the experiments, peritoneal fluid, brain, liver, and lung were collected for T. gondii DNA quantification and histopathological analysis. Infection with BRI strain reduced the dwell time and central locomotion in the OF (p < 0.05), indicating anxiogenic type behavior, while treatment with rosuvastatin reversed this response (p < 0.05). RH strain infection did not alter any behavior in the OF (p > 0.05) and both strains impaired short- and long-term memory (NOR test), but with no significant treatment effect (p > 0.05). The BRI strain was shown to be more damaging in relation to anxiogenic type behavior when compared to the RH strain (p < 0.05), whereas rosuvastatin reduced this damaging effect in BRI. The treatment reduced the parasite load in the peritoneal lavage, liver, and lung of animals infected with both acute strains; however, it significantly (p < 0.05) attenuated the inflammatory process only in BRI-infected and treated animals, showing that non-archetypal genotypes are more damaging in rodents. This suggests that rosuvastatin may be a drug with great therapeutic potential against T. gondii mainly to reduce damage from virulent strains., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Venous thromboembolism (VTE) remains a significant source of postinjury morbidity and mortality. Beta-hydroxy beta-methylglutaryl-CoA (HMG-CoA) reductase inhibitors (rosuvastatin) significantly reduced pathologic clotting events in healthy populations in a prior trial. Furthermore, acetylsalicylic acid (ASA) has been shown to be noninferior to prophylactic heparinoids for VTE prevention following orthopedic surgery. We hypothesized that a combination of rosuvastatin/ASA, in addition to standard VTE chemoprophylaxis, would reduce VTE in critically ill trauma patients., Methods: This was a double-blind, placebo-controlled, randomized trial, evaluating VTE rates in two groups: ASA + statin (Experimental) and identical placebos (Control). Injured adults, 18-65 years old, admitted to the surgical intensive care unit without contraindications for VTE prophylaxis were eligible. Upon initiation of routine VTE chemoprophylaxis (i.e. heparin/heparin-derivatives), they were randomized to the Experimental or Control group. VTE was the primary outcome., Results: Of 112 potentially eligible patients, 33% (n = 37, median new injury severity scale = 27) were successfully randomized, of whom 11% had VTEs. The Experimental group had no VTEs, while the Control group had 6 VTEs (4 PEs and 2 DVTs) in 4 (22%) patients (P = 0.046). The Experimental treatment was not associated with any serious adverse events. Due to the COVID-19 pandemic, the study was interrupted at the second interim analysis at <10% of the planned enrollment, with significance declared at P < 0.012 at that stage., Discussion: The combination of ASA and rosuvastatin with standard VTE prophylaxis showed a favorable trend toward reducing VTEs with no serious adverse events. An appropriately powered phase III multicenter trial is needed to further investigate this therapeutic approach., Level of Evidence: Level II, Therapeutic., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Many patients with primary hypercholesterolemia do not achieve their plasma low-density lipoprotein cholesterol (LDL-C) goals with statin alone under a recommended dose of statin (e.g., 10 mg rosuvastatin) in China. The objective of this phase III study was to evaluate the efficacy and safety of a new single-pill combination (SPC) of rosuvastatin 10 mg/ezetimibe 10 mg (R10/E10) in this population., Methods: This was a randomized, double-blind, double-dummy, active-controlled study in patients with primary hypercholesterolemia inadequately controlled with statin alone. The participants were randomized 1:1 to receive SPC R10/E10 or R10. The primary objective was to demonstrate the superiority of SPC R10/E10 vs. R10 in reducing the LDL-C levels after 8 weeks., Results: This trial randomized 305 participants to SPC R10/E10 (n = 153) and R10 (n = 152). The superiority of SPC R10/E10 over R10 was demonstrated with the least square (LS) mean difference of percent change in LDL-C from baseline to week 8: - 13.85% (95% confidence interval [CI] - 20.15% to - 7.56%, P < 0.0001). The proportion of participants who achieved the LDL-C target (< 2.6 mmol/l) at week 8 was larger with SPC R10/E10 (n = 80, 54.1%) than with R10 (n = 42, 29.2%) (Odds ratio = 2.80, 95% CI 1.70 to 4.61, P < 0.0001). No unexpected safety findings were reported., Conclusion: The results suggest that SPC R10/E10 improve LDL-C reduction and goal achievement in Chinese patients with primary hypercholesterolemia not adequately controlled on statin therapy, without new safety findings., Trial Registration: ClinicalTrials.gov (NCT04669041)., (© 2023. The Author(s).)

Purpose: To investigate the impact of statin use on primary prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) in a dose-, class-, and use intensity-dependent manner., Methods: We used an inverse probability treatment-weighted Cox hazards model, with statin use status as a time-dependent variable., Results: Our results showed that statin use was associated with a significant reduction in CVD risk with an adjusted hazard ratio of 0.39. Pitavastatin was found to have the lowest CVD risk among the different classes of statins, followed by rosuvastatin, pravastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin. Our analysis also revealed that a higher cumulative defined daily dose per year of statin was associated with a lower CVD risk. Additionally, a higher intensity of daily statin dose was associated with a lower CVD risk in patients with T2DM., Conclusion: This study highlights the importance of statin use in reducing the risk of CVD in patients with T2DM, and the significance of dose, class, and intensity of statin use, in particular, pitavastatin class of statins was found to be the most effective in primary prevention of CVD in T2DM., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Memory impairment is a result of multiple factors including amyloid-beta (Aβ) accumulation. Several receptors are mediated for Aβ transport and signaling. Moreover, blood lipids are involved in Aβ signaling pathway through these receptors. Mediated blood lipid level by statins aims to regulate Aβ signaling cascade. First, the structure of receptors was taken from the RCSB PDB database and prepared with MGLTools and AutoDock tool 4. Second, the ligand was prepared for docking through AutoDock Vina. The binding affinity was calculated, and the binding sites were determined through LigPlot+ software. Besides, pharmacokinetic properties were calculated through multiple software. Finally, a molecular dynamics (MD) simulation was conducted to evaluate ligands stability along with clustering analysis to evaluate proteins connection. Our molecular docking and dynamic analyses revealed silymarin as a potential inhibitor of acetylcholinesterase (AChE), P-glycoprotein, and angiotensin-converting enzyme 2 (ACE2) with 0.704, 0.85, and 0.83 Å for RMSD along with -114.27, -107.44, and -122.51 kcal/mol for free binding energy, respectively. Moreover, rosuvastatin and quercetin have more stability compared to silymarin and donepezil in complex with P-glycoprotein and ACE2, respectively. Eventually, based on clustering and pharmacokinetics analysis, silymarin, rosuvastatin, and quercetin are suggested to be involved in peripheral clearance of Aβ. The bioactivity effects of mentioned statins and antioxidants are predicted to be helpful in treating memory impairment in Alzheimer's disease (AD). Nevertheless, mentioned drug effect could be improved by nanoparticles to facilitate penetration of the blood-brain barrier (BBB)., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: There has been concern that statin therapy may be associated with an increased risk of intracerebral hemorrhage (ICH). We investigated whether the intensity and type of statin therapy instituted after ischemic stroke (IS) were associated with risk of future ICH in a region of northern China with a high incidence of stroke., Methods: Newly diagnosed IS patients who were not treated with lipid-lowering drugs in the Beijing Employee Medical Claims Data database from 2010 to 2017 were included. The primary exposure variable was any statin prescription within 1 month of the first documented stroke diagnosis. High-intensity statin therapy was defined as atorvastatin ⩾ 80 mg, simvastatin ⩾ 80 mg, pravastatin ⩾ 40 mg, and rosuvastatin ⩾ 20 mg per day or equivalent combination. An adjusted Cox proportional hazards model was used to estimate the hazard ratio (HR) for ICH during follow-up in groups exposed and not exposed to statins., Results: Of 62,252 participants with IS and 628 ICH readmissions were recorded during a median follow-up of 3.17 years. The risk of ICH among statin users (N = 43,434) was similar to that among nonusers (N = 18,818) with an adjusted HR and 95% confidence interval (CI) of 0.86 (0.73, 1.02). Compared with non-statin therapy, patients with low/moderate-intensity therapy had a lower risk of ICH (0.62: 0.52, 0.75), while patients with high-intensity therapy had a substantially higher risk (2.12: 1.72, 2.62). For patients with different types of statin therapy, adherence to rosuvastatin had the lowest risk of ICH compared to adherence to atorvastatin (0.46: 0.34, 0.63), followed by simvastatin (0.60: 0.45, 0.81)., Conclusion: In patients with IS, any statin therapy was not associated with an increased risk of ICH. However there appeared to be differential risk according to the dose of statin with high-intensity statin therapy being associated with an increased risk of ICH, while low/moderate-intensity therapy was associated with a lower risk.

Infection by Toxoplasma gondii may compromise the intestinal histoarchitecture through the tissue reaction triggered by the parasite. Thus, this study evaluated whether treatment with rosuvastatin modifies duodenal changes caused by the chronic infection induced by cysts of T. gondii. For this, female Swiss mice were distributed into infected and treated group (ITG), infected group (IG), group treated with 40 mg/kg rosuvastatin (TG) and control group (CG). After 72 days of infection, the animals were euthanized, the duodenum was collected and processed for histopathological analysis. We observed an increase in immune cell infiltration in the IG, TG and ITG groups, with injury to the Brunner glands. The infection led to a reduction in collagen fibers and mast cells. Infected and treated animals showed an increase in collagen fibers, acidic mucin-producing goblet cells, intraepithelial lymphocytes and mast cells, in addition to the reduction of muscle, neutral mucin-producing and Paneth cells. While treatment with rosuvastatin alone led to increased muscle layer, proportion of neutral mucin-producing goblet cells, Paneth cells, and reduction of collagen fibers. These findings indicate that the infection and treatment caused changes in the homeostasis of the intestinal wall and treatment with rosuvastatin potentiated most parameters indicative of inflammation., Competing Interests: Declaration of Competing Interest The authors declare that there are not conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background We aimed to compare statin monotherapy and upfront combination therapy of statin and ezetimibe in patients with acute coronary syndromes (ACSs). Methods and Results The study included consecutive patients with ACS included in the PL-ACS (Polish Registry of Acute Coronary Syndromes), which is a national, multicenter, ongoing, prospective observational registry that is mandatory for patients with ACS hospitalized in Poland. Data were matched using the Mahalanobis distance within propensity score matching calipers. Multivariable stepwise logistic regression analysis, including all variables, was next used in propensity score matching analysis. Finally, 38 023 consecutive patients with ACS who were discharged alive were included in the analysis. After propensity score matching, 2 groups were analyzed: statin monotherapy (atorvastatin or rosuvastatin; n=768) and upfront combination therapy of statin and ezetimibe (n=768 patients). The difference in mortality between groups was significant during the follow-up and was present at 1 (5.9% versus 3.5%; P =0.041), 2 (7.8% versus 4.3%; P =0.019), and 3 (10.2% versus 5.5%; P =0.024) years of follow-up in favor of the upfront combination therapy, as well as for the overall period. For the treatment, rosuvastatin significantly improved prognosis compared with atorvastatin (odds ratio [OR], 0.790 [95% CI, 0.732-0.853]). Upfront combination therapy was associated with a significant reduction of all-cause mortality in comparison with statin monotherapy (OR, 0.526 [95% CI, 0.378-0.733]), with absolute risk reduction of 4.7% after 3 years (number needed to treat=21). Conclusions The upfront combination lipid-lowering therapy is superior to statin monotherapy for all-cause mortality in patients with ACS. These results suggest that in high-risk patients, such an approach, rather than a stepwise therapy approach, should be recommended.

The advancements in proteomics have provided a better understanding of the functionality of apolipoproteins and lipoprotein-associated proteins, with the HDL lipoprotein fraction being the most studied. The focus of this study was to evaluate the HDL proteome in dyslipidemic subjects without an established cardiovascular disease, as well as to test whether rosuvastatin treatment alters the HDL proteome. Patients with primary hypercholesterolemia or mixed dyslipidemia were assigned to 20 mg/day rosuvastatin and blood samples were drawn at study entry and after 12 weeks of treatment. A label-free LC-MS/MS protein profiling was conducted, coupled with bioinformatics analysis. Sixty-nine HDL proteins were identified, belonging to four main biological function clusters: lipid transport and metabolism; platelet activation, degranulation, and aggregation, wound response and wound healing; immune response; inflammatory and acute phase response. Five HDL proteins showed statistically significant differences in the abundance (Anova ≤ 0.05), before and after rosuvastatin treatment. Platelet factor 4 variant (PF4V1), Pregnancy-specific beta-1-glycoprotein 2 (PSG2), Profilin-1 (PFN1) and Keratin type II cytoskeletal 2 epidermal (KRT2) showed decreased expressions, while Integrin alpha-IIb (ITGA2B) showed an increased expression after treatment with rosuvastatin. The ELISA validation of PFN1 segregated the subjects into responders and non-responders, as PFN1 levels after rosuvastatin were shown to mostly depend on the subjects' inflammatory phenotype. Findings from this study introduce novel insights into the HDL proteome and statin pleiotropism., (© 2023 Ana Vavlukis et al., published by Sciendo.)

Importance: High-intensity statin is strongly recommended in patients at very high risk (VHR) of atherosclerotic cardiovascular disease (ASCVD). However, concerns about statin-associated adverse effects result in underuse of this strategy in practice., Objective: To evaluate the outcomes of a moderate-intensity statin with ezetimibe combination in VHR and non-VHR patients with ASCVD., Design, Setting, and Participants: This was a post hoc analysis of the Randomized Comparison of Efficacy and Safety of Lipid Lowering With Statin Monotherapy vs Statin/Ezetimibe Combination for High-Risk Cardiovascular Disease (RACING) open-label, multicenter, randomized clinical trial. The study was conducted from February 2017 to December 2018 at 26 centers in Korea. Study participants included patients with documented ASCVD. Data were analyzed from April to June 2022., Interventions: Patients were randomly assigned to moderate-intensity statin with ezetimibe (rosuvastatin, 10 mg, with ezetimibe, 10 mg) or high-intensity statin monotherapy (rosuvastatin, 20 mg). Patients at VHR for ASCVD were defined according to the 2018 American Heart Association/American College of Cardiology guidelines., Main Outcomes and Measures: The primary end point was the 3-year outcome of cardiovascular death, coronary or peripheral revascularization, hospitalization of cardiovascular events, or nonfatal stroke., Results: A total of 3780 patients (mean [SD] age, 64 [10] years; 2826 male [75%]) in the RACING trial, 1511 (40.0%) were categorized as VHR, which was associated with a greater occurrence of the primary end point (hazard ratio [HR], 1.42; 95% CI, 1.15-1.75). There was no significant difference in the primary end point between those who received combination therapy and high-intensity statin monotherapy among patients with VHR disease (11.2% vs 11.7%; HR, 0.96; 95% CI, 0.71-1.30) and non-VHR disease (7.7% vs 8.7%; HR, 0.88; 95% CI, 0.66-1.18). The median low-density lipoprotein cholesterol (LDL-C) level was significantly lower in the combination therapy group than in the high-intensity statin group (VHR, 1 year: 57 [47-71] mg/dL vs 65 [53-78] mg/dL; non-VHR, 1 year: 58 mg/dL vs 68 mg/dL; P < .001). Furthermore, in both the VHR and non-VHR groups, combination therapy was associated with a significantly greater mean change in LDL-C level (VHR, 1 year: -19.1 mg/dL vs -10.1 mg/dL; 2 years: -22.3 mg/dL vs -13.0 mg/dL; 3 years: -18.8 mg/dL vs -9.7 mg/dL; non-VHR, 1 year: -23.7 mg/dL vs -12.5 mg/dL; 2 years: -25.2 mg/dL vs -15.1 mg/dL; 3 years: -23.5 mg/dL vs -12.6 mg/dL; all P < .001) and proportion of patients with LDL-C level less than 70 mg/dL (VHR, 1 year: 73% vs 58%; non-VHR, 1 year: 72% vs 53%; P < .001). Discontinuation or dose reduction of the lipid-lowering drug due to intolerance occurred less frequently in the combination therapy group (VHR, 4.6% vs 7.7%; P = .02; non-VHR, 5.0% vs 8.7%; P = .001)., Conclusions and Relevance: Results suggest that the outcomes of ezetimibe combination observed in the RACING trial were consistent among patients at VHR of ASCVD., Trial Registration: ClinicalTrials.gov Identifier: NCT03044665.