Search Results (49)

Serving as central signalling organelles and hubs of metabolism, mitochondria are essential for cellular homeostasis. Mitochondrial disease can arise from mutations to nuclear or mitochondrial DNA, which result in disruptions to normal mitochondrial function. This generates a suite of rare disorders which are multi-system and often fatal. Variable tissue distribution of mitochondria, alongside a high degree of heterogeneity in associated phenotype, has resulted in an inadequate understanding and characterisation of mitochondrial disease. Addressing this issue is therefore crucial for better clinical management and patient outcomes. Cholesterol dyshomeostasis is a potential pathological hallmark of numerous mitochondrial diseases. Cholesterol is an essential lipid and bioactive compound involved in numerous mitochondrial and cellular processes. A growing number of studies have reported perturbations to cholesterol biosynthesis, cholesterol import, and cholesterol ratios in cell and animal models and individuals with mitochondrial disease, suggesting it could be a unifying feature of these disparate and variable disorders. This review summarises the current experimental evidence for the role of cholesterol dyshomeostasis in mitochondrial disease. It will further discuss reports of statin intolerance, generally attributed to off-target action on mitochondrial structures, in the context of this evidence. Ultimately, the necessity of further integrative clinical and experimental studies exploring the potential of cholesterol dyshomeostasis as a pathological hallmark of mitochondrial disease will be highlighted. Full article

Despite the availability of numerous lipid-lowering agents, the treatment of lipid disorders remains a public health challenge. A substantial portion of patients, especially those with severe dyslipidemia or familial hypercholesterolemia (FH), fail to achieve the LDL-C goal. The leading causes of suboptimal LDL-C control include underprescription and poor adherence; however, in rare cases, it may result from an unusual biological response to treatment. In the presented case, a 78-year-old female with a history of transient ischemic attack and myocardial infarction was diagnosed with a heterozygous variant of FH and true statin intolerance following trials of simvastatin, rosuvastatin and pitavastatin. Initially, inclisiran was added to ezetimibe, leading to an unexpected increase in LDL-C. Due to the patient’s refusal of another statin re-challenge and the unavailability of bempedoic acid, nutraceuticals were introduced. After 6 months, inclisiran was discontinued because only a 22% reduction in LDL-C was achieved, likely attributable to the nutraceutical’s effect. Another PCSK9 inhibitor, evolocumab, was subsequently initiated. Shortly after the treatment onset, the patient complained of paraesthesia in the upper extremities and discontinued therapy. LDL-C levels increased by 7% after one month of treatment with evolocumab. The patient refused treatment with lipid apheresis. Possible causes of poor response to PCSK9 inhibitors include elevated lipoprotein(a) and FH. Full article

Background: Statins are central to primary and secondary prevention of atherosclerotic cardiovascular disease but are often underutilized due to myopathy and intolerance. While individual pharmacogenetic (PGx) variants, particularly in SLCO1B1, are linked to statin-associated muscle symptoms, the real-world impact of both clinical and cumulative PGx burden on regimen modification and adverse outcomes remains unclear. We aimed to evaluate the existing uncertainty regarding whether combined PGx scores can effectively guide statin dose titration and regimen modification, thereby filling a key clinical gap. Methods: A retrospective cohort study of 911 statin-treated patients with coronary artery disease was conducted from the Qatar Cardiovascular Biorepository with available whole-genome sequencing data. Variants in SLCO1B1, ABCG2, and CYP2C9 were combined into a functional PGx burden score, and their associations with statin regimen modification, intolerance, myopathy, liver injury, adherence, and composite adverse events were evaluated. The composite adverse events were defined as the occurrence of any statin-related adverse event, including statin-associated myopathy, liver injury, or poor medication adherence, during the follow-up period. Patients were classified as having experienced the composite outcome if at least one of these events occurred. Results: Over 12 months following statin initiation, 10.2% of patients underwent dose escalation, 11.4% de-escalation, and 78.4% remained on the same regimen. PGx burden is not statistically significantly associated with statin intolerance (OR 1.14; 95% CI: 0.73–1.76), composite adverse outcome (OR 1.08; 95% CI 0.82–1.42), or time to regimen change (HR 1.02; 95% CI 0.77–1.35). However, higher PGx burden showed a directional tendency toward dose de-escalation (RRR 1.18, 95% CI 0.76–1.84) and lower likelihood of escalation (RRR 0.93, 95% CI 0.56–1.54). Conclusions: Clinical factors, particularly statin intensity and myopathy, were the primary determinants of regimen modification. The PGx burden contributes to vulnerability to statin-related adverse effects in a context-dependent manner but does not independently drive statin regimen modification in routine clinical practice. Prospective studies are warranted to assess the clinical utility of PGx-guided workflows in statin therapy. Full article

Background/Objectives: Botanical and nutraceutical approaches have increasingly been considered as alternatives or complements to conventional lipid-lowering therapies, particularly in individuals with mild-to-moderate dyslipidemia or statin intolerance. This study aimed to evaluate a multi-botanical formulation, combining black garlic, sesame, Gastrodia elata, and Primula veris extracts, for its effects on hepatic cholesterol regulation and the PCSK9–LDLr–SREBP-2 axis in vitro. Methods: Each extract was chemically characterised for its polysaccharide, polyphenol, flavonoid, and sesamin content. HepG2 cells were exposed to normal (5 mM) or high-glucose (30 mM) conditions to mimic metabolic stress. Dose–response studies identified optimal concentrations for cell viability. Hepatic safety was assessed via MTT and ROS assays, while cholesterol metabolism was evaluated by measuring HMG-CoA reductase levels, total cholesterol, LDL levels, bile acid production, free cholesterol levels, and the expression of PCSK9, LDLr, and SREBP-2 using ELISA and Western blot. Results: All individual extracts improved cell viability, reduced oxidative stress, and moderately modulated cholesterol metabolism. The multi-botanical combination exhibited synergistic effects, enhancing cell viability (+47.5% vs. untreated), suppressing ROS, reducing HMGR levels, and lowering total intracellular cholesterol more effectively than single extracts or the statin-like reference RYRF. Importantly, the combination strongly downregulated PCSK9 and inhibited SREBP-2 proteolytic activation while upregulating LDLr, indicating coordinated transcriptional and post-translational regulation. Bile acid production and free cholesterol excretion were also significantly increased, supporting improved cholesterol clearance. Conclusions: This four-botanical formulation effectively modulates hepatic cholesterol homeostasis via a multifactorial, synergistic mechanism distinct from statin-like agents. The results suggest its potential as a safe, non-statin strategy to support cardiometabolic health. Future studies are warranted to confirm long-term efficacy and clinical relevance. Full article

Epicardial adipose tissue (EAT), the visceral fat layer next to the myocardium, has become an important focus in heart failure with preserved ejection fraction (HFpEF). When enlarged and inflamed, EAT increases pericardial restraint, releases fibroinflammatory mediators, and disrupts myocardial energetics, thereby reproducing the high-pressure, exercise-intolerant HFpEF phenotype regardless of body mass index. Modern echocardiography, cardiac CT, and MRI, enhanced by artificial intelligence texture analytics, now enable precise depot-specific quantification, making EAT a measurable therapeutic target. Early interventional studies suggest that caloric restriction, bariatric surgery, SGLT2 inhibitors, GLP-1 receptor agonists, statins, PCSK9 antibodies, and colchicine can reduce EAT volume or alter its inflammatory profile, with concurrent improvements in haemodynamics and biomarkers. However, definitive outcome trials are still pending. Priority directions include standardising imaging cut-offs, mapping EAT immune–metabolic niches, and testing combined metabolic–inflammatory regimens to translate EAT modulation into precision therapy for HFpEF. This review aims to synthesise current mechanistic, diagnostic, and therapeutic insights on EAT in HFpEF and outline future research priorities. Full article

Background/Objectives: High concentration of plasma low-density lipoprotein cholesterol (LDL-C) is the predominant cause of atherosclerotic cardiovascular disease progression and coronary heart disease. Nutraceutical combination together with a cholesterol-lowering action provides an alternative to pharmacotherapy in patients reporting intolerance to statins and in subjects with low cardiovascular risk. The effects on lipid parameters were evaluated over 6 months for a food supplement containing aqueous extract of Berberis aristata and Olea europea, fenugreek seed extract, water/ethanol extract of artichoke leaf and phytosterols from sunflower seeds (Ritmon Colesystem^®). Methods: Laboratory data were obtained at baseline from 44 otherwise healthy subjects (33 males, mean 50 ± 11 years) without cardiovascular disease having LDL-C in the range 115 to 190 mg/dL pharmacologically untreated for hypercholesterolemia. Subjects were re-evaluated at 1, 3 and 6 months during which they took one tablet of Ritmon Colesystem^® after dinner. Results: At baseline, the mean values were 151 ± 21 mg/dL for LDL-C, 223 ± 24 mg/dL for total cholesterol (T-C), 52 ± 14 mg/dL for high-density lipoprotein cholesterol (HDL-C), and 124 ± 58 mg/dL for triglycerides. A significant reduction in LDL-C was observed; 9 mg/dL (95% confidence interval 3–14), 10 (4–17) and 7 (1–14) at 1, 3 and 6 months. A similar significant trend was detected for T-C while triglycerides did not show significant changes and HDL-C had lower values only at 3 months. Conclusions: These nutraceuticals in individuals with sub-optimal blood cholesterol levels at intermediate–low cardiovascular risk reduced LDL-C and T-C over 6 months contributing to the improvement of cholesterol control by dietary supplements. Full article

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, with hypercholesterolemia identified as a major, but modifiable risk factor. This review serves as the second part of a comprehensive analysis of dyslipidemia management. The first installment laid the groundwork by detailing the key pathophysiological mechanisms of lipid metabolism, the development of atherosclerosis, major complications of hyperlipidemia, and the importance of cardiovascular risk assessment in therapeutic decision-making. It also examined non-pharmacological interventions and conventional therapies, with a detailed focus on statins and ezetimibe. Building upon that foundation, the present article focuses exclusively on emerging pharmacological therapies designed to overcome limitations of standard treatment. It explores the mechanisms, clinical applications, safety profiles, and pharmacogenetic aspects of novel agents such as proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (alirocumab, evolocumab), small interfering RNA (siRNA) therapy (inclisiran), adenosine triphosphate–citrate lyase (ACL) inhibitor (bempedoic acid), microsomal triglyceride transfer protein (MTP) inhibitor (lomitapide), and angiopoietin-like protein 3 (ANGPTL3) inhibitor (evinacumab). These agents offer targeted strategies for patients with high residual cardiovascular risk, familial hypercholesterolemia (FH), or statin intolerance. By integrating the latest advances in precision medicine, this review underscores the expanding therapeutic landscape in dyslipidemia management and the evolving potential for individualized care. Full article

Background/Objectives: Immune-mediated necrotizing myopathy (IMNM) is a severe inflammatory myopathy marked by proximal muscle weakness, elevated creatine kinase (CK), and the presence of anti-HMGCR antibodies. Statin exposure is a recognized trigger for anti-HMGCR-positive IMNM, which may persist despite statin withdrawal. This pilot case series explores, for the first time, the use of bempedoic acid—a liver-specific lipid-lowering agent with minimal muscle toxicity—as an alternative to statins in these patients. Methods: We report 10 anti-HMGCR-antibody-positive IMNM patients (6 females, 4 males) previously on statins for primary prevention (8 on atorvastatin, 2 on simvastatin) without prior cardiovascular events. Statins were discontinued at myositis onset. All patients received prednisone and immunosuppressants (methotrexate in 7, mycophenolate in 3), plus bempedoic acid. Anti-HMGCR antibodies were measured using a chemiluminescence method. Results: Their mean anti-HMGCR antibody levels decreased significantly from 390.93 ± 275.22 to 220.89 ± 113.37 CU/L (p = 0.027) after 6 months of treatment. Their CK levels dropped from 1278.9 ± 769.39 to 315.1 ± 157.72 IU/L (p = 0.001), and aldolase dropped from 11.63 ± 2.18 to 6.61 ± 1.22 U/L (p = 0.0001). The mean LDL-C value was 96.1 ± 8.16 mg/dL. No disease recurrence was observed. Autoimmune panels were negative for other myositis-associated and/or -specific antibodies. Conclusions: Bempedoic acid appears to be a safe, effective, and cost-efficient lipid-lowering alternative in statin-intolerant IMNM patients. Larger studies are warranted to confirm its efficacy across different subgroups and to optimize dyslipidemia management in this setting. Full article

Dyslipidaemia is one of the main causes of atherosclerotic cardiovascular disease (ASCVD) worldwide. Although statins remain the cornerstone of lipid-lowering therapy, many patients do not achieve optimal target levels of low-density lipoprotein cholesterol (LDL-C) due to intolerance or inadequate response. Bempedoic acid, an oral ATP citrate lyase inhibitor, provides a liver-specific mechanism that lowers LDL-C levels while minimising muscle-related side effects. Recent clinical trials, including the CLEAR Outcomes Study, have shown that bempedoic acid was able to reduce LDL-C by approximately 29 mg/dL and major adverse cardiovascular events (MACEs) by 13% in patients intolerant to statins. Combination therapy with ezetimibe further enhances this effect. However, adverse effects such as increased uric acid and gout have been reported, requiring careful patient selection and continuous monitoring. This review provides a comparative synthesis of the latest evidence on bempedoic acid, including its pharmacological profile, its efficacy in different patient groups, and its place within current treatment strategies for dyslipidaemia. It also identifies research gaps and directions for future studies. Full article

Background: Statin intolerance is a serious therapeutic dilemma in secondary cardiovascular prevention (e.g., ESC/EAS Guidelines 2023). This is especially true when confirmed by genetic predisposition and complicated by rhabdomyolysis. Although several non-statin agents have become available in recent years, evidence regarding their combined use in high-risk statin-intolerant patients remains limited. Furthermore, the pharmacokinetics of statins in toxic concentrations are poorly characterized in clinical settings. Case Presentation: We present two cases of genetically confirmed statin-induced rhabdomyolysis, both accompanied by severe acute kidney injury requiring renal replacement therapy. In both patients, serial measurements of rosuvastatin plasma concentrations revealed markedly delayed elimination, with detectable levels persisting for several weeks despite ongoing dialysis. Estimated half-lives exceeded 7 days in both cases, far beyond the known therapeutic range. Genetic testing identified SLCO1B1, ABCB1, and CYP2C9 polymorphisms linked to reduced hepatic uptake and impaired drug clearance. Following biochemical recovery, both patients were initiated on a triple non-statin lipid-lowering regimen consisting of ezetimibe, bempedoic acid, and inclisiran. The combination was well tolerated, with no recurrence of muscle-related symptoms or biochemical toxicity. LDL-C levels were reduced from 3.05 to 1.59 mmol/L and from 4.99 to 1.52 mmol/L, respectively, with sustained response over 12 and 40 weeks. Full lipid profiles demonstrated favorable changes across all parameters. Conclusions: These two cases suggest that the combination of ezetimibe, inclisiran, and bempedoic acid may serve as a safe and effective therapeutic option in patients with severe statin intolerance. Pharmacogenetic testing and serial pharmacokinetic assessment may guide personalized lipid-lowering strategies and improve outcomes in this challenging patient population. Full article

The purpose of this paper is to comprehensively review the research progress of nattokinase in lowering blood lipid, including its source, structure and physicochemical properties, mechanisms of functions, clinical research status, and safety considerations, so as to provide reference for further research on the application of nattokinase in the treatment of dyslipidemia. Natto is a traditional Japanese fermented food, which is made from soybeans fermented by Bacillus natto. During the fermentation process, natto will produce a variety of biologically active substances, including nattokinase. Nattokinase (NK) is a serine protease with stable enzyme activity and good freeze–thaw tolerance, which exerts lipid-lowering and anti-atherosclerotic effects by activating hormone-sensitive lipase (HSL), inhibiting hydroxymethylglutaryl monoacyl coenzyme A reductase (HMG-CoA reductase), and enhancing lipoprotein lipase (LPL) activity. Large-scale clinical trials have confirmed that nattokinase significantly improves the lipid profile and reduces the atherosclerotic plaque area and intima-media thickness with a favorable safety profile. Compared with traditional lipid-lowering drugs (e.g., statins and fibrates), nattokinase has a multifaceted lipid-lowering mechanism and lower risk of side effects, which makes it suitable for patients intolerant of traditional drugs; when combined with natural products such as statins, fibrates, red yeast, and lifestyle interventions, it can play a synergistic role and further reduce the risk of cardiovascular disease. There are various types of nattokinase preparations on the market, and consumers should choose regular products with high activity and purity, and pay attention to their safety and applicable population. Full article

Due to the routine use of endovascular revascularization and improved medical therapy, the majority of acute coronary syndrome (ACS) cases now have an uncomplicated course. However, in spite of the currently accepted secondary prevention standards, the residual risk of remote major adverse cardiovascular events (MACEs) after ACS remains high. Ultrasound carotid/subclavian atherosclerotic plaque assessment may represent an alternative approach to estimate the MACE risk after ACS and to control the quality of secondary prevention. Aim: To find the most important clinical predictors of MACEs in contemporary patients with predominantly uncomplicated ACS treated according to the Guidelines, and to study the potential of the longitudinal assessment of quantitative and qualitative ultrasound carotid/subclavian atherosclerotic plaque characteristics for MACE prediction after ACS. Methods: Patients with ACS, obstructive coronary artery disease (CAD) confirmed by coronary angiography, and carotid/subclavian atherosclerotic plaque (AP) who underwent interventional treatment were prospectively enrolled. The exclusion criteria were as follows: death or significant bleeding at the time of index hospitalization; left ventricular ejection fraction (EF) <30%; and statin intolerance. The clinical variables potentially affecting cardiovascular prognosis after ACS as well as the quantitative and qualitative AP characteristics at baseline and 6 months after the index hospitalization were studied as potential MACE predictors. Results: A total of 411 primary patients with predominantly uncomplicated ACS were included; AP was detected in 343 of them (83%). The follow-up period duration was 450 [269; 634] days. MACEs occurred in 38 patients (11.8%): seven—cardiac death, twenty-five—unstable angina/acute myocardial infarction, and six—acute ischemic stroke. In multivariate regression analyses, the most important baseline predictors of MACEs were diabetes (HR 2.22, 95% CI 1.08–4.57); the decrease in EF by every 5% from 60% (HR 1.22, 95% CI 1.03–1.46); the Charlson comorbidity index (HR 1.24, 95% CI 1.05–1.48); the non-prescription of beta-blockers at discharge (HR 3.24, 95% CI 1.32–7.97); and a baseline standardized AP gray scale median (GSM) < 81 (HR 2.06, 95% CI 1.02–4.19). Among the predictors assessed at 6 months, after adjustment for other variables, only ≥ 3 uncorrected risk factors and standardized AP GSM < 81 (cut-off value) at 6 months were significant (HR 3.11, 95% CI 1.17–8.25 and HR 3.77, 95% CI 1.43–9.92, respectively) (for all HRs above, all p-values < 0.05; HR and 95% CI values varied minimally across regression models). The baseline quantitative carotid/subclavian AP characteristics and their 6-month longitudinal changes were not associated with MACEs. All predictors retained significance after the internal validation of the models, and models based on the baseline predictors also demonstrated good calibration; the latter were used to create MACE risk calculators. Conclusions: In typical contemporary patients with uncomplicated interventionally treated ACS, diabetes, decreased EF, Charlson comorbidity index, non-prescription of beta-blockers at discharge, and three or more uncontrolled risk factors after 6 months were the most important clinical predictors of MACEs. We also demonstrated that a lower value of AP GSM reflecting the plaque vulnerability, measured at baseline and after 6 months, was associated with an increased MACE risk; this effect was independent of clinical predictors and risk factor control. According to our knowledge, this is the first demonstration of the independent role of longitudinal carotid/subclavian AP GSM assessment in MACE prediction after ACS. Full article

Background/Objectives: Bempedoic acid (BA) is a novel lipid-lowering agent that reduces low-density lipoprotein cholesterol (LDL-c) and cardiovascular events. Limited real-world data on its effectiveness and safety are available. This study aimed to evaluate the utilization and clinical performance of BA in routine clinical practice. Moreover, an explorative pharmacoeconomic analysis was performed. Methods: We prospectively enrolled consecutive patients with dyslipidemia who started 180 mg BA, alone or with 10 mg ezetimibe, across five outpatient clinics in Campania Region, Italy from September to December 2023. Clinical and laboratory assessments, including lipid profile, hepatic function, and creatine phosphokinase levels, were performed at baseline and at least after one month follow-up. Side effects were recorded. Results: 111 patients (age 65 ± 9 years, 61% male) were included. At BA initiation, 70.3% were on maximally tolerated statin dosage and ezetimibe, 16.2% on ezetimibe alone, and 13.5% on PCSK9 inhibitors due to statin intolerance. BA significantly reduced LDL-c serum levels (89.9 ± 33.0 vs. 56 ± 27.6 mg/dL; p < 0.0001), with 46% achieving therapeutic targets. LDL-c decreased by 28% in patients on intensive statins/ezetimibe and by 45% in statin-intolerant patients, with reduced healthcare costs. Side effects were infrequent (10%) and reversible. Adherence was 99%, and persistence 90%. Conclusions: In our clinical pratice, BA was primarily used in high-risk patients with dyslipidemia who failed to reach LDL-c therapeutic target with statins/ezetimibe, and to a lesser extent, in statin-intolerant individuals. BA treatment enabled 54% to reach LDL-c therapeutic target. BA was well tolerated, and showed high adherence and persistence, contributing to cost savings. Full article

Background and Aims: Statin-associated muscle symptoms (SAMS) is a frequent side effect of statin therapy, limiting its clinical use and increasing cardiovascular risk. Its relationship with muscle performance and quality is not completely understood. The aim of our study was to retrospectively assess the differences between body composition and muscle strength in patients with SAMS, compared with matched controls. Material and Methods: cardiovascular risk factors, lipid profile, and body mass index (BMI), were analyzed in 148 statin-intolerant (SI) and in 145 sex- and age-matched statin-tolerant (ST) patients attending a secondary-level outpatient lipid clinic. At the end of follow-up (mean 45 months), the evaluations were reassessed and bioelectrical impedance analysis (BIA)-assessed body composition, and muscle quality (handgrip/skeletal muscle mass) were further determined. Results: At baseline, BMI, cholesterol, and triglycerides in SI were higher than in ST patients. During follow-up, SI patients underwent a further increase in BMI and low-density lipoproteins (LDL)-cholesterol remained significantly higher than in ST patients. At the end of the follow-up, BIA-assessed fat mass percentage was higher in SI than in ST. Handgrip absolute values or standardized for skeletal muscle mass (muscle quality) were significantly lower in SI patients (p < 0.001), but this was confirmed only in their non-dominant arm (p < 0.01 for all arms). Circulating creatine kinase levels, which was higher in SI patients at baseline (p < 0.001), remained higher in those who never restarted statins after re-challenge (p = 0.029). Conclusions: Statin intolerance is clinically associated with lower muscle quality, particularly in less exercised arms. Full article

In recent years, many atherogenesis researchers have focused on the role of inflammatory cytokines in the development of cardiovascular disease (CVD). Interleukin-6 (IL-6) cytokine is independently associated with higher CVD risk in patients with rheumatoid arthritis (RA). The effect of IL-6 inhibitors on the cardiovascular system in RA patients remains poorly understood, especially with its long-term use. This study investigates the effect of therapy with IL-6 receptor blocker tocilizumab (TCZ) on the dynamics of cardiovascular risk (CVR), modifiable risk factors (RFs), carotid artery (CA) structural changes, and the incidence of cardiovascular complications (CVCs) in RA patients during a 265-week follow-up period. Forty-five patients with active RA (DAS28-ESR 6.2 (5.5;6.8) with ineffectiveness and/or intolerance to disease-modifying antirheumatic drugs (DMARDs) were included in this study. During long-term therapy with TCZ in RA patients, no increase in CVR and no significant structural changes in CA were observed. No significant changes in the blood lipid spectrum were observed in patients without statin therapy. In the group of patients receiving statins, there was a 43% increase in high-density lipoprotein cholesterol (HDL-C), a 15% reduction in total cholesterol levels, and a 56% decrease in the atherogenicity index (p < 0.01 in all cases). Associations were found between ∆ total cholesterol and ∆ C-reactive protein (CRP) (R = 0.36, p = 0.04), ∆ low-density lipoprotein cholesterol (LDL-C), and ∆-CRP (R = 0.42, p = 0.03) in RA patients receiving statins. Initially, the thickness of the intima–media complex of carotid arteries (cIMT) positively moderately correlated with age (R = 0.7; p < 0.01), BMI (R = 0.37; p < 0.01), and systolic blood pressure (R = 0.64; p < 0.01); however, it weakly correlated with the lipid spectrum parameters: total cholesterol (R = 0.29; p < 0.01) and LDL-C (R = 0.33; p < 0.01). No new associations of cIMT by the end of the follow-up period, as well as the relationship of cIMT value with RA activity and therapy, were revealed. Patients with carotid ASPs showed an oppositely directed relationship between total cholesterol and sVCAM-1 at baseline (R = −0.25, p = 0.01) and at the end of this study (R = 0.29, p < 0.01). The incidence of cardiovascular events was 0.53 per 100 patient-years during the 265-week period of TCZ therapy. Full article