Non-steroidal anti-inflammatory drugs (NSAIDs) require particular attention, as these pharmaceutical compounds have been associated with a range of adverse effects, such as renal and gastrointestinal toxicity. In addition, data suggest an increased cardiovascular (CV) risk in the general population, which indicates a need for caution regarding its application in patients with elevated CV risk. Patients with inflammatory arthritis demonstrate an inherent predisposition to an elevated risk of CV morbidity and mortality. In this publication, we examine the available data indicating that the utilization of NSAIDs among patients diagnosed with inflammatory joint disease is not associated with an elevated risk of developing CV disease. The analgesic and anti-inflammatory properties of NSAIDs are discussed as a potential underlying mechanism contributing to a cardioprotective effect. In this context, patients diagnosed with rheumatoid arthritis (RA) or ankylosing spondylitis (AS), who also exhibit systemic inflammation, have been observed to benefit in respect to CV events in response to utilization of NSAIDs.

Atherosclerosis remains the principal cause of cardiovascular morbidity and mortality worldwide, with vascular smooth muscle cells (VSMC) serving as central effectors in plaque initiation, progression, and destabilization. Although originally characterized as a hepatic regulator of LDL receptor degradation and systemic cholesterol homeostasis, PCSK9 is increasingly recognized as a pivotal mediator of vascular pathology. Within the arterial wall, VSMC constitute the predominant extrahepatic source of PCSK9, through which it exerts autocrine and paracrine effects on proliferation, migration, phenotypic plasticity, foam cell formation, oxidative stress, inflammation, and calcification. Collectively, these processes destabilize vascular homeostasis and amplify maladaptive crosstalk with endothelial and immune cells, thereby accelerating atherogenesis. Therapeutic inhibition of PCSK9 provides benefits beyond lipid lowering, reinforcing fibrous cap stability, and dampening inflammatory activity within plaques. While monoclonal antibodies and RNA-based silencing therapies are supported of a growing body of clinical data, recent advances include the development of novel oral PCSK9 inhibitors, among which MK-0616 (Enlicitide) has progressed to phase 3 evaluation. Conversely, genome editing, peptide vaccination, and CAP1-targeted biologics remain at a conceptual or early investigational stage and are still distant from regulatory approval. Yet PCSK9 lives a double life: circulating as a systemic regulator of lipids while acting locally as a driver of vascular pathology. Unraveling this duality through focused research is essential to unlock its full potential in cardiovascular medicine.

The imbalance of carotid plaque stability is a key cause of acute cardiovascular and cerebrovascular events. Lipid metabolism disorder and endoplasmic reticulum stress (ERS) are both involved in the progression of atherosclerotic plaque. This study aims to reveal the role and molecular mechanism of abnormal phosphatidylcholine metabolism in ERS-induced carotid plaque instability, and to provide theoretical basis for plaque stabilization intervention. With carotid plaques intima-media specimens as the research object, by HE staining is divided into a stable plaque group (group S) and unstable plaque group (U); The differences of metabolic profiles between the two groups were analyzed by principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA). The differential metabolites were screened by cluster heat map and volcano map. Metabolic pathway enrichment analysis and IPA pathway analysis were used to identify key pathways. Finally, Western blot and RT-qPCR were used to verify the protein and mRNA expression levels of key molecules in ERS pathway. Two groups of baseline characteristics have no statistical difference (P>0.05); PCA and OPLS-DA showed that the metabolic profiles of group S and group U were significantly separated. A total of 198 potential biomarkers were identified. Among them, changes in phospholipid metabolites (including phosphatidylcholine) were significant, and these are the core markers for differentiating plaque stability. Metabolic pathway enrichment analysis showed that glycerophospholipid metabolic pathway was the key core pathway regulating plaque stability. The protein and mRNA expressions of key molecules of ERS pathway (GRP78, ATF6, PERK, CHOP and IRE1) in group U were significantly higher than those in group S. Abnormal metabolism of phosphatidylcholine can drive the transformation of carotid plaques to an unstable phenotype by activating the ER stress (ERS) pathway (especially the PERK/CHOP branch pathway); this study verified the association mechanism between abnormal phosphatidylcholine metabolism and the activation of the ER stress pathway and the occurrence of unstable carotid plaques, providing experimental evidence for the study of the mechanism of unstable carotid plaques and the formulation of targeted clinical intervention strategies.

Statins remain to date the primary therapeutic option for dyslipidemia. However, a significant portion of patients with dyslipidemia fail to achieve optimal low-density lipoprotein targets for reasons often related to treating physicians. The aim of STAtin Treatment in Routine clinical Practice (STATRIP) survey was to report and quantify perceptions and common beliefs regarding treatment with statins, among physicians implicated in the primary and secondary care of patients with dyslipidemia. This observational cross-sectional study was conducted using an online-distributed questionnaire, which was designed to cover a wide range of physicians' knowledge and perceptions on treatment with statins. A total of 261 health care providers filled out the survey, mostly general practitioners and internists (93.5%). Study participants clearly expressed their concerns regarding statin-related side effects, including fears on interactions with other medication, muscle aches and pain, increase in liver enzymes, and gastrointestinal disorders. Myalgias were observed by physicians in as many as 29.2% of patients receiving rosuvastatin, and in as many as 26.5% receiving atorvastatin. Combination lipid-lowering therapy with ezetimibe was reported by only 53.6% of participants as a prevalent strategy for uncontrolled individuals. Only 58.6% apply non-HDL cholesterol measurements in their clinical practice. Our study provides a clear perspective of treating physicians regarding statin prescription patterns. Several misconceptions, especially regarding statin-related adverse effects, hold well among treating physicians. Insufficient implementation of dyslipidemia guidelines calls for more targeted educational interventions to achieve optimal management of patients with dyslipidemia.

Cardiovascular disease remains a significant global health burden. Bempedoic acid is a novel, oral adenosine triphosphate-citrate lyase inhibitor that lowers low-density lipoprotein cholesterol (LDL-C). While randomized controlled trials (RCTs) have established its efficacy and safety, evidence from real-world clinical practice is needed. A systematic literature review (SLR) was conducted to identify studies reporting real-world use of bempedoic acid as monotherapy, in fixed dose combination with ezetimibe, or in combination with any other lipid lowering therapy (LLT). MEDLINE, EMBASE, and Cochrane Library were searched from inception to February 19, 2025. Two reviewers independently screened studies, with discrepancies resolved by a third. Data extraction and validation were conducted, and the risk of bias assessed using the Newcastle-Ottawa Scale. Of 269 records, 28 reports on 22 unique studies met the eligibility criteria. Most studies evaluated LDL-C changes from baseline after initiation of bempedoic acid; one pragmatic randomized trial was identified. Bempedoic acid achieved LDL-C reductions of 15% to 39% when added to maximally tolerated statins, 22% to 38% in statin intolerant cohorts, and 18% to 42% in mixed statin intolerant cohorts. Safety data was limited; treatment discontinuation ranged from 9% to 36%, with higher rates in cohorts with greater statin-intolerance. This SLR shows bempedoic acid, with or without other LLTs, achieves a minimum of approximately 20% LDL-C reductions, consistent with RCTs. Data suggests it may be effective as an adjunct to statins and as an oral alternative for statin-intolerant patients.

BackgroundG9A, a histone methyltransferase that facilitates H3K9 dimethylation, has been implicated in the epigenetic regulation of vascular processes. This study encapsulates its involvement in the calcification and stability of atherosclerotic plaques, further investigating its interaction with bone morphogenetic protein 2 (BMP2), a pivotal factor in vascular calcification, unveiling that G9A fosters plaque calcification and instability via the BMP2 signaling pathway.MethodsThe progression of unstable plaques, histone methylation status, and vascular calcification incidence were monitored in the carotid plaques of ApoE−/− mice subjected to a high-fat diet over 30 weeks. Additionally, these parameters were scrutinized in pathological specimens from patients who underwent carotid plaque excision. In vitro, rat thoracic aortic smooth muscle A7R5 cells were cultured, with the G9A gene being manipulated through techniques of gene knockdown and overexpression.ResultsIn ApoE−/−mice and human carotid arteries, calcification exacerbated plaque instability in the context of a high-fat diet. This phenomenon was accompanied by elevated levels of G9A and dimethylation of histone H3 at lysine 9, alongside G9A expression in vitro. The absence of G9A in vitro impeded the calcification process of vascular smooth muscle cells (VSMCs), whereas G9A overexpression prompted a shift in the phenotypic attributes of smooth muscle cells.ConclusionsOur findings indicate that G9A amplifies vascular calcification through the activation of Bmp2 signaling, a fundamental mediator of vascular calcification. The relationship between vascular calcification and the emergence of unstable plaques may be intricately associated with histone methylation.

IntroductionRestenosis of the carotid or intracranial (IC) arteries, shown to be associated with increased risk of ischemic stroke, represents an unresolved clinical issue. Residual local and systemic inflammation at the time of the index revascularization, of which C-reactive protein (CRP) is a marker of, has been associated with coronary restenosis. Its association with carotid or IC restenosis post revascularization, however, remains uncertain. We therefore conducted a systematic review and a study-level meta-analysis investigating the association of pre-procedural CRP levels and the subsequent incidence of carotid and IC restenosis.MethodsOnline databases of PubMed, EMBASE, MEDLINE, Scopus, and Web of Science were systematically searched for articles published until August 31st, 2025. Pooled effect sizes were obtained from study-level standard mean differences (SMD) and their 95% confidence intervals (CI), employing a Z-test, with random effects for analysis.ResultsOut of 175 unique articles screened, 12 case-control studies, with a total sample of 2040 (325 restenosis cases/1715 no-restenosis controls), were included for quantitative synthesis. The pooled results demonstrated that pre-procedural CRP levels were associated with carotid or IC restenosis, with significantly higher pre-procedural CRP levels amongst the restenosis group in comparison to the no-restenosis group (SMD = 0.50, 95% CI = 0.11–0.89, p = 0.01). No apparent publication bias was detected either visually by Begg's funnel plot or Egger's test (p = 0.51). Leave-one-out sensitivity analysis supported the robustness of the results.ConclusionsThis meta-analysis suggests a significant association between pre-procedural CRP levels and the subsequent incidence of carotid and intracranial artery restenosis.