The global population aged 80 years and older will reach approximately half a billion in the coming years, and cardiovascular prevention in this group of patients will become a global health challenge. In the era of evidence-based medicine, the use of lipid-lowering therapies (LLTs) in the elderly, particularly in primary and secondary cardiovascular prevention, remains an area of active research. Although there is broad consensus on the use of LLTs in the elderly to prevent recurrent cardiovascular events in secondary prevention, there is considerable debate about their use in primary prevention. Many efforts have been made to improve cardiovascular risk stratification in patients over 75 years of age in primary prevention. In recent years, some specific risk scores have been developed, including the Systematic Coronary Risk Evaluation 2 for Older Persons (SCORE2-OP). While there are very few specific warnings to consider for LLTs in the elderly, an important challenge in this patient population is to identify the turning point at which the disutility risk outweighs the potential benefits. However, despite the widespread recognition of the importance of this issue, there is a lack of guidance on how to identify patients who should be withdrawn from therapy. The aim of this narrative review is to examine the current state of knowledge regarding the indications for LLT in elderly patients, identify outstanding issues, and discuss future developments.

To review the latest advances in lipoprotein(a) [Lp(a)] treatment, focusing on the impact of currently available lipid-lowering therapies and highlighting the highly anticipated and most developed RNA-based therapies.

Lp(a) is a key genetically determined cardiovascular risk modifier linked to myocardial infarction and calcific aortic stenosis development and progression. Conventional lipid-lowering therapies have no substantial effect on circulating Lp(a) levels, leading current guidelines to focus on managing traditional cardiovascular risk factors. New therapies, including antisense oligonucleotides and small interfering RNAs, target Lipoprotein(A) [LPA] gene translation to reduce apo(a) synthesis and Lp(a) particles formation. The most advanced candidates, pelacarsen, olpasiran, and lepodisiran, have shown promising Lp(a) reductions, ranging from -35% to -101% in Phase 1 and 2 trials. Phase 3 studies will clarify their effects on cardiovascular outcomes and address concerns about extremely low Lp(a) levels and safety.

The RNA-based agents pelacarsen, olpasiran, and lepodisiran represent the most advanced developments in this field. Ongoing Phase 3 trials, expected to be finalized between 2025 and 2029, will be crucial in determining their efficacy in improving cardiovascular outcomes and their safety profiles.

Statins have significantly reduced mortality from cardiovascular diseases by lowering serum cholesterol levels. Beyond their lipid-lowering effects, statins improve vascular function, reduce inflammation, decrease reactive oxygen species (ROS) formation, and stabilize atherosclerotic plaques. However, the mechanisms underlying these pleiotropic effects remain unclear.

This narrative review summarizes and discusses epigenetic mechanisms that may explain part of the pleiotropic effects of statins. This approach allows for a reevaluation of statin use beyond its cholesterol-lowering benefits. A structured search was conducted in the PubMed and Scopus databases using specific search terms, including articles published up to August 2024.

The pleiotropic effects of statins, including those mediated by the isoprenoid pathway, partially explain their clinical benefits. By inhibiting histone deacetylases (HDACs, the 'erasers') and DNA methyltransferases (DNMTs, the 'writers'), statins promote increased histone acetylation and reduced DNA methylation at gene promoter regions. These epigenetic modifications enhance chromatin accessibility, facilitating gene transcription and protecting the cardiovascular system. Further investigation into these epigenetic mechanisms could support the repositioning of statins for broader therapeutic applications. Statins may have benefits extending beyond their role in managing hypercholesterolemia, as their pleiotropic effects contribute to the prevention of cardiovascular disease-related mortality through mechanisms independent of LDL cholesterol reduction.

Heart failure (HF) often coexists with cancer. Beyond the known cardiotoxicity of some cancer treatments, HF itself has been associated with increased cancer incidence. The 2 conditions share common risk factors, mechanisms, and interactions that can worsen patient outcomes. The bidirectional relationship between HF and cancer presents a complex interplay of factors that are not fully understood. Recent preclinical evidence suggests that HF may promote tumor growth via the release of protumorigenic factors from the injured heart, revealing HF as a potentially protumorigenic condition. Our review discusses the biological crosstalk between HF and cancer, emphasizing the impact of HF on tumor growth, with inflammation, and modulating the immune system as central mechanisms. We further explore the clinical implications of this connection and propose future research directions. Understanding the mechanistic overlap and interactions between HF and cancer could lead to new biomarkers and therapies, addressing the growing prevalence of both conditions and enhancing approaches to diagnosis, prevention, and treatment.

Transcatheter aortic valve replacement (TAVR) stands as a notable alternative to surgical valve replacement for severe aortic stenosis (AS). Despite the established benefits of statins in cardiovascular pathologies, their specific impact in patients with severe AS undergoing TAVR remains uncertain.

Our meta-analysis aims to assess whether periprocedural statin therapy improves survival and outcomes post-TAVR, thus addressing this gap in literature.

A comprehensive literature search using various databases with relevant keywords terms was conducted to identify studies on the impact of periprocedural statin therapy on TAVR outcomes. We assessed the primary outcome of all-cause mortality alongside various secondary outcomes including stroke/transient ischemic attack (TIA), myocardial infarction, acute kidney injury (AKI), 30-day mortality, in-hospital mortality, rehospitalization, cardiovascular complications, and pacemaker requirement. A random-effects model using Comprehensive Meta Analysis Software was employed to analyze the data for each outcome. Statistical significance was set at a p < 0.05.

Our analysis of 19 observational studies revealed that periprocedural statin therapy significantly reduces all-cause mortality following TAVR surgery (OR = 0.71, 95% CI: 0.61-0.83, p < 0.001). However, the influence of statins on other outcomes remains inconclusive. These outcomes include stroke/TIA (OR = 0.90, 95% CI: 0.68-1.19, p = 0.455), risk of MI (OR = 1.72, 95% CI: 0.73-4.04, p = 0.214), AKI (OR = 0.99, 95% CI: 0.75-1.31, p = 0.968), 30-day mortality (OR = 0.71, 95% CI: 0.46-1.10, p = 0.126), in-hospital mortality (OR = 0.42, 95% CI: 0.13-1.38, p = 0.151), rehospitalization (OR = 0.92, 95% CI: 0.66-1.29, p = 0.645), cardiovascular complications (OR = 1.12, 95% CI: 0.91-1.37, p = 0.297), and pacemaker requirement (OR = 0.83, 95% CI: 0.65-1.06, p = 0.133).

Our meta-analysis indicates a potentially promising role for periprocedural statin therapy in enhancing patient outcomes post-TAVR surgery. We found a notable association between statin therapy and a reduction in all-cause mortality. However, the effects on secondary outcomes did not reach statistical significance, which warrants further investigation through larger, well-designed, randomized controlled trials.

Patients with an autoimmune or inflammatory disease (AIID) are at increased cardiovascular risk and may benefit more from statin therapy. In the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab lowered low-density lipoprotein cholesterol levels, but not hsCRP (high-sensitivity C-reactive protein) levels, and reduced the risk of cardiovascular events.

FOURIER was a randomized trial of evolocumab versus placebo in 27 564 patients with stable atherosclerosis who were taking statins. This analysis focused on the effect of evolocumab in patients with or without an AIID, defined as any autoimmune or chronic inflammatory condition. The primary end point was a composite of cardiovascular death, myocardial infarction, stroke, unstable angina, or coronary revascularization.

At baseline, 889 patients (3.2%) had an AIID, most commonly rheumatoid arthritis (33.7%) or psoriasis (15.6%). Median (interquartile range) low-density lipoprotein cholesterol levels were 90.0 mg/dL (79.5-105.5) and 91.5 mg/dL (79.5-108.5) in patients with or without an AIID, respectively (P=0.025), and the placebo-adjusted percent reduction with evolocumab was consistent (60.2% versus 59.0%; P=0.57). Baseline hsCRP was higher in patients with an AIID (median 2.1 versus 1.7 mg/L; P<0.001) and did not significantly change with evolocumab in either group. Compared with placebo, evolocumab reduced the rate of the primary end point by 14% in patients without an AIID (hazard ratio, 0.86 [95% CI, 0.80-0.93]) and by 42% in patients with an AIID (hazard ratio, 0.58 [95% CI, 0.38-0.89]; Pinteraction=0.066). Likewise, evolocumab reduced the key secondary end point of cardiovascular death, myocardial infarction, or stroke by 19% in patients without an AIID (hazard ratio, 0.81 [95% CI, 0.74-0.89]) and 58% in those with an AIID (hazard ratio, 0.42 [95% CI, 0.24-0.74]; Pinteraction=0.022).

Intensive lowering of low-density lipoprotein cholesterol levels with evolocumab may lead to greater relative reduction in cardiovascular events in patients with an AIID.

URL: https://www.clinicaltrials.gov; Unique identifier: NCT01764633.

The LoDoCo2 (Low-Dose Colchicine 2) trial showed that colchicine reduced the risk for cardiovascular events in patients with chronic coronary syndrome. Current guidelines recommend colchicine use in selected high-risk patients. The aim of this secondary analysis was to explore the relative and absolute benefits of colchicine according to baseline risk.

The LoDoCo2 trial randomized 5522 patients to colchicine 0.5 mg or placebo. The primary end point was a composite of cardiovascular death, spontaneous myocardial infarction, ischemic stroke, or ischemia-driven coronary revascularization. First, a LoDoCo2 risk score was developed by Cox regression to identify high-risk features for the primary end point. Second, the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention was applied to explore robustness of findings.

In the LoDoCo2 risk score, high-risk features were age ≥75, diabetes, and current smoker. In high-risk (≥1 high-risk feature), compared with low-risk (0 high-risk features) patients, colchicine was associated with consistent relative (high risk: hazard ratio [HR], 0.72 [95% CI, 0.56-0.94] versus low risk: HR, 0.67 [95% CI, 0.52-0.88]; P for interaction=0.73) and absolute benefits (high risk: HR, -1.33 [95% CI, -2.38 to -0.27] versus low risk: HR, -0.93 [95% CI -1.57 to -0.30] events per 100 person-years). Using the Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention, consistent relative and absolute benefits were found in high-, intermediate-, and low-risk patients.

In patients with chronic coronary syndrome, the relative and absolute benefits of colchicine were consistent in those at high, intermediate, and low risk for cardiovascular events. These findings support the use of colchicine across the spectrum of baseline risk.

URL: https://www.anzctr.org.au; Unique identifier: 12614000093684.

Chemotherapy-induced cardiomyopathy (CICM) is a critical adverse consequence associated with chemotherapeutic treatments such as anthracyclines, taxanes, and alkylating agents. Cardiac dysfunction, characterized by left ventricular systolic dysfunction, is the primary effect found in these patients. This may result in heart failure, with heart failure related to chemotherapy resulting in a 3.5-fold increased risk of mortality compared with idiopathic cardiomyopathy alone. Multiple factors, including oxidative stress, inflammation, and disruption of key cellular pathways, are involved in cardiomyocyte damage and influence CICM pathophysiology. So far, dexrazoxane is the sole FDA-approved preventive therapy, but alternative interventions, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins, have been studied for their cardioprotective potential. Statins, beyond their cholesterol-lowering capabilities, stand out for their pleiotropic effects, including antioxidant, anti-inflammatory, and endothelial-protective actions, which counteract inflammatory effects. Multiple studies and meta-analyses suggest that statin therapy may decrease both the incidence and severity of chemotherapy-related cardiotoxicity (CTX), as evidenced by smaller declines in left ventricular ejection fraction and lower rates of heart failure in statin-treated patients. However, not all investigations confirm these protective benefits; for instance, some trials, including SPARE-HF, reported no significant differences in cardiac outcomes. While these conflicting findings underscore the need for larger randomized trials, they also reflect the heterogeneity of cancer types, chemotherapy regimens, and patient profiles. Statins show promise as a cardioprotective strategy for individuals at risk of CICM. Enhancing patient selection and specifying the timing and duration of statin therapy are essential steps for incorporating these agents into standard care. Optimizing these parameters may reduce chemotherapy-related cardiac damage, improve long-term cardiac function, and enhance overall survival in cancer survivors.

Type 2 diabetes mellitus (T2DM) is a global health crisis, with cardiovascular disease (CVD) accounting for 75% of mortality in this population. Despite advances in managing traditional risk factors, such as low-density lipoprotein cholesterol (LDL) cholesterol reduction (IMPROVE-IT, FOURIER), antithrombotic therapies (PEGASUS, COMPASS), and triglyceride-lowering agents (REDUCE-IT), a substantial residual cardiovascular risk persists, driven in part by chronic low-grade systemic inflammation. Chronic low-grade inflammation is a central driver of cardiovascular-kidney-metabolic (CKM) syndrome in T2DM, perpetuating residual cardiovascular risk despite optimal management of traditional risk factors. This narrative review synthesizes evidence on how inflammation accelerates coronary heart disease (CHD), heart failure (HF), stroke, diabetic kidney disease (DKD), and peripheral artery disease (PAD). We evaluate the anti-inflammatory mechanisms of current therapies such as statins, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists, as well as emerging agents like colchicine and interleukin (IL)-1β/IL-6 inhibitors, emphasizing their differential efficacy across CKM traits. By integrating pathophysiological insights with clinical trial data, we propose biomarker-guided strategies to target inflammation as a modifiable risk factor, offering a roadmap to bridge the gap in diabetes-related cardiovascular care.

Statins are frequently prescribed to older adults, yet their effects on ageing phenotypes such as frailty or physiological reserves remain poorly understood. Gait Speed Reserve (GSR), defined as the difference between maximal and usual gait speeds, serves as an indicator of physiological reserve, reflecting the body's ability to perform beyond baseline functional levels. Polypharmacy, prevalent in this population, may contribute to inconsistent findings through interactions between statins and concomitant medications. We aimed to investigate how concomitant medications moderate the association between statin use and GSR in older adults. To this end, we conducted a cross-sectional observational cohort study using data from the Mobility Center at the University Department of Geriatric Medicine FELIX PLATTER, Basel, Switzerland (n = 5519 adults aged ≥ 60 years). Moderation regression analyses with propensity score weighting were used to evaluate the effect of concomitant medications on the association between statin use and GSR. Results showed statin use was associated with a lower GSR compared to non-use (- 1.9 cm/s [95% CI, - 3.1 to - 0.72]). However, ACE inhibitors and aspirin significantly influenced this association. The GSR difference for statin users compared to non-users increased by 3.7 cm/s (from - 2.2 to 1.5 cm/s; 95% CI, 0.0 to 7.4) with concomitant ACE inhibitor use and by 5.8 cm/s (from - 3.4 to 2.3 cm/s; 95% CI, 2.5 to 9.1) with aspirin use. We found no statistically significant association between statin use and usual gait speed, the secondary outcome. In conclusion, ACE inhibitors and aspirin interacted with statins, reversing the negative association with GSR into a positive one when co-used. Future clinical trials are needed to determine causality and further investigate the impact of concomitant medication use on statin effects in aging populations. Meanwhile, our findings underscore the importance of considering concomitant medication use when assessing the effects of statins in older adults.

Obesity rates have surged since 1990 worldwide. This rise is paralleled by increases in pathological processes affecting organs such as the heart, liver, and kidneys, here termed systemic metabolic disorders (SMDs). For clinical management of SMD, the European Atherosclerosis Society proposes a pathophysiology-based system comprising three stages: Stage 1, where metabolic abnormalities such as dysfunctional adiposity and dyslipidaemia occur without detectable organ damage; Stage 2, which involves early organ damage manifested as Type 2 diabetes, asymptomatic diastolic dysfunction, metabolic-associated steatohepatitis (MASH), and chronic kidney disease (CKD); and Stage 3, characterized by more advanced organ damage affecting multiple organs. Various forms of high-risk obesity, driven by maintained positive energy balance, are the most common cause of SMD, leading to ectopic lipid accumulation and insulin resistance. This progression affects various organs, promoting comorbidities such as hypertension and atherogenic dyslipidaemia. Genetic factors influence SMD susceptibility, and ethnic disparities in SMD are attributable to genetic and socioeconomic factors. Key SMD features include insulin resistance, inflammation, pre-diabetes, Type 2 diabetes, MASH, hypertension, CKD, atherogenic dyslipidaemia, and heart failure. Management strategies involve lifestyle changes, pharmacotherapy, and metabolic surgery in severe cases, with emerging treatments focusing on genetic approaches. The staging system provides a structured approach to understanding and addressing the multi-faceted nature of SMD, which is crucial for improving health outcomes. Categorization of SMD abnormalities by presence and progression is aimed to improve awareness of a multi-system trait and encourage a tailored and global approach to treatment, ultimately aiming to reduce the burden of obesity-related comorbidities.

Anthocyanins are dietary flavonoids shown to have a therapeutic capacity to mitigate inflammation and oxidative stress. The present secondary analyses from the "Anthocyanins in People at Risk for Dementia Study" were aimed at (I) determining the intervention's effect on blood-based markers of cardiovascular disease and inflammation and (II) evaluating whether baseline factors such as age, sex, inflammation, or cardiometabolic score may moderate the intervention's effect on inflammatory status. This study was an ancillary, 24-week randomized, double-blind, placebo-controlled Phase II trial. Sub-sample participants (n = 99), aged 60-80 years with mild cognitive impairment or cardiometabolic disorders, were randomized to receive either 320 mg/day of anthocyanins or placebo. The biomarkers analyzed included inflammatory biomarker assessment (IL - 6, IL - 8, IL - 10, IL - 1b, TNF - α, IFN - γ), and C-reactive protein (CRP), as well as albumin, thrombocytes, cholesterol, LDL, HDL, and triglycerides, which were longitudinally compared between both groups. Baseline characteristics were balanced between the groups. ANCOVA analyses reveal 24-week differences favoring the anthocyanin treatment in LDL cholesterol levels (ƞp2 = 0.078; p = 0.015), cardiometabolic score (ƞp2 = 0.073; p = 0.021), CRP levels (ƞp2 = 0.417; p = 0.0001), IL - 6 (ƞp2 = 0.085; p = 0.015), IL - 1b (ƞp2 = 0.058; p = 0.037), and Inflam z-score 5 (ƞp2 = 0.059, p = 0.004). Moderation analysis demonstrated that the inflammatory score at baseline was a significant predictor of the effect of the intervention on the CRP levels. Anthocyanin supplementation reduces CRP and cardiovascular disease biomarkers in individuals at risk of dementia, especially when there is increased inflammation at baseline. ClinicalTrials.gov study identifier: NCT03419039.

Findings from RCTs and observational studies indicate a positive association between statin use and risk of type 2 diabetes. Mendelian randomisation studies provide evidence to support that the effect is causal. However, little is known about the long-term effects, and data on different types of statins remain limited.

We analysed participants with hypercholesterolaemia from the Nurses' Health Study (NHS; 30,510 participants), the Nurses' Health Study II (NHSII; 21,547 participants) and the Health Professionals Follow-Up Study (HPFS; 9934 participants) who were free of diabetes, CVD and cancer at baseline. Statin use was assessed every 2 years starting in 2000 in the NHS and the HPFS and in 1999 in the NHSII. Incident cases of type 2 diabetes were confirmed by a validated supplementary questionnaire until the end of follow-up (31 January 2023).

We documented 6762 incident type 2 diabetes cases during up to 23 years of follow-up. Compared with non-users, statin users had a significantly higher risk of type 2 diabetes after adjustment for BMI and other potential confounding variables (pooled HR 1.40; 95% CI 1.33, 1.48). Compared with non-use, durations of statin use of 1-5, 6-10, 11-15 and >15 years were associated with HRs of 1.36 (95% CI 1.27, 1.44), 1.41 (95% CI 1.31, 1.52), 1.60 (95% CI 1.44, 1.78) and 1.76 (95% CI 1.50, 2.06), respectively; significant linear trends were observed when the comparison included non-users and within statin users only (both ptrend<0.001). Compared with non-users, the HRs for type 2 diabetes associated with 10 year use of specific types of statins were 1.99 (95% CI 1.45, 2.73) for rosuvastatin, 1.66 (95% CI 1.12, 2.47) for lovastatin, 1.62 (95% CI 1.39, 1.89) for atorvastatin, 1.44 (95% CI 1.06, 1.97) for pravastatin and 1.37 (95% CI 1.13, 1.66) for simvastatin. Use of a low-potency statin for 10 years was associated with a 34% higher risk of type 2 diabetes (HR 1.34; 95% CI 1.15, 1.56), while use of a high-potency statin for 10 years was associated with a 72% higher risk (HR 1.72; 95% CI 1.46, 2.04). The difference in the 10 year cumulative risk of type 2 diabetes comparing statin users vs non-users was most pronounced in participants with the least healthy lifestyles (4.5% vs 3.1%), while the smallest risk differential was observed among participants who adhered to the healthiest lifestyles (1.0% vs 0.4%).

The positive association between statin use and type 2 diabetes was more pronounced with a longer duration of use, and the association varied across different types of statins. Adopting and maintaining a healthy lifestyle can serve as a viable approach to diabetes prevention during statin treatment.

This study aimed to compare the lipid-lowering effect and safety of low-intensity atorvastatin (5 mg) plus ezetimibe (10 mg) combination therapy (A5E10) with monotherapy regimens-atorvastatin 5 mg [A5], ezetimibe 10 mg [E10], and atorvastatin 10 mg [A10])-in dyslipidemia patients.

A randomized, double-blind, placebo-controlled trial involving 252 dyslipidemia patients was conducted at 25 centers in South Korea (NCT05970679). Participants aged ≥ 19 years were randomized into four groups: A5E10, A5, E10, and A10. The primary endpoint was the percentage change in low-density lipoprotein cholesterol (LDL-C) levels from baseline to 8 weeks. Secondary endpoints included changes in other lipid parameters, lipid ratios, LDL-C goal achievement rates and safety assessments.

The mean age of the patients was 63 years, and 51.2% were male. The A5E10 group showed significantly greater LDL-C reduction (47.6%) compared with A5 (33.4%), E10 (19.4%), and A10 (40.1%) at 8 weeks (p < 0.0001). A5E10 also significantly reduced triglyceride, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. In addition, a significant reduction in LDL-C levels was observed over the 4 weeks, with a 46.7% reduction in LDL-C levels after 4 weeks of A5E10 administration. No severe adverse events were observed in the A5E10 group.

The combination of low-intensity atorvastatin and ezetimibe was more effective than moderate-intensity atorvastatin monotherapy in lowering LDL-C levels and improving other lipid parameters. It was well-tolerated and demonstrated rapid benefits within a month, offering a promising alternative for patients with low to moderate cardiovascular risk who do not achieve adequate control with statin monotherapy.

Inflammatory bowel disease (IBD) is a complex condition characterized by inflammation of the gastrointestinal system, encompassing Crohn's disease and ulcerative colitis. Patients diagnosed with IBD have an increased risk of atherosclerotic cardiovascular disease. This heightened risk can be attributed to a combination of mechanisms, including traditional risk factors, chronic inflammation, intestinal dysbiosis, increased risk of thrombosis, and the use of certain medications such as corticosteroids. There are significant gaps in current knowledge, particularly regarding the management of risk factors and the use of medications for cardiovascular disease prevention. Similarly, the cardiovascular effects of specific IBD therapies, particularly the newer ones, are not yet fully understood. This review focuses on the epidemiological evidence linking IBD with cardiovascular risk factors and cardiovascular disease. It describes the potential pathophysiological mechanisms underlying this association and examines the challenges involved in accurately assessing cardiovascular risk in these patients, including the utility of complementary tools such as subclinical atherosclerosis detection. Additionally, we consider the potential therapeutic implications for managing these patients. Finally, this review also underscores the importance of multidisciplinary collaboration. Effective teamwork among gastroenterologists, cardiologists, and general practitioners is essential for providing comprehensive care to patients with IBD.

C-reactive protein (CRP) is an inflammatory biomarker, implicated in the pathogenesis of atherosclerotic lesion formation, plaque rupture, and coronary thrombosis. The relationship between preprocedural CRP levels and subsequent development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) however remains uncertain. Against this background, we performed a systematic review and meta-analysis, investigating the association between baseline CRP levels and the incidence of ISR after PCI.

Relevant published studies were identified following a PubMed, EMBASE, MEDLINE, Scopus and Web of Knowledge databases search until April 30, 2024. To be included, studies had to be original research with: (i) angiographically determined ISR group, (ii) angiographically or clinically determined no-ISR group, and (iii) CRP levels measured before the index PCI procedure for both groups. The mean difference in baseline CRP levels and associated 95% confidence interval (CI) between the ISR and no-ISR groups was ascertained for each included study. The pooled standard mean difference (SMD) and its 95% CI was derived after pooling study-level results using a random effects model, employing a Z-test. Begg's funnel plots and Egger's test were used for publication bias assessment.

Out of a total of 1018 unique results, 19 studies, with a total sample size of 4744 patients (1154 restenosis cases/3590 controls), were included for quantitative synthesis. ISR group had higher baseline CRP levels (SMD = 0.41, 95% CI = 0.16, 0.66 mg/L, p = 0.001) in comparison to the no-ISR group. No evidence of publication bias was detected either visually by Begg's funnel plots or by Egger's test (p = 0.08). Our leave-one-out sensitivity analysis further attested our obtained associations.

The present systematic review and meta-analysis suggests a significant association of elevated pre-PCI CRP with subsequent angiographically confirmed ISR. These results warrant further validation in dedicated large cohorts, ideally in a prospective setting.

Cardiovascular diseases (CVD) are the leading cause of death worldwide. Therefore, it is essential to understand their relationship and prevalence in different diseases that may present specific risk factors for them. The objective of this document is to analyze the specific prevalence of CVD in patients with inflammatory bowel disease (IBD), describing the presence of classical and non-classical cardiovascular risk factors in these patients. Additionally, we will detail the pathophysiology of atherosclerosis in this patient group and the different methods used to assess cardiovascular risk, including the use of risk calculators in clinical practice and different ways to assess subclinical atherosclerosis and endothelial dysfunction. Furthermore, we will describe the potential influence of medication used for managing patients with IBD on cardiovascular risk, as well as the potential influence of commonly used drugs for managing CVD on the course of IBD. The document provides comments and evidence-based recommendations based on available evidence and expert opinion. An interdisciplinary group of gastroenterologists specialized in IBD management, along with a consulting cardiologist for this type of patients, participated in the development of these recommendations by the Spanish Group of Work on Crohn's Disease and Ulcerative Colitis (GETECCU).

Patients with atherosclerotic cardiovascular disease (ASCVD), such as those with a history of MI or stroke, are at high risk for morbidity and mortality associated with future cardiovascular events. Ideal management of these patients requires a multifactorial strategy for risk factor mitigation and prevention of additional cardiovascular events. Traditional management of secondary prevention patients involves lipid-lowering with statins, blood pressure control, and anti-platelet treatment. Several additional targets have been identified to optimize the secondary prevention of ASCVD, such as further lipid control, inflammation management, lifestyle and weight optimization, strict diabetes control, use of β-blockers, use of renin-angiotensin-aldosterone system inhibitors, vaccinations, and additional considerations of anti-thrombotic therapies. This review will describe the interventions associated with these targets, as well as the relevant research and indications for these therapies.

Atherosclerosis (AS) is a major pathological factor contributing to the mortality associated with ischemic heart disease and is driven primarily by macrophage-mediated lipid accumulation and inflammatory processes. Conventional cardiovascular pharmacotherapies address these pathological mechanisms but often show limited efficacy, highlighting the need for innovative agents capable of effectively reducing lipid accumulation and inflammation with minimal toxicity. In this study, decursin, a monomer derived from traditional Chinese medicine, is shown to inhibit both lipid accumulation and inflammatory responses in macrophages through direct interaction with protein kinase Cδ (PKCδ), resulting in low cytotoxicity in vitro and negligible toxicity in vivo. To address the short half-life of decursin, a targeted cascade drug delivery system (ALD@EM), which is specifically designed to target AS pathophysiology, is developed. This system employs ICAM-1 and VCAM-1 antibodies for plaque localization and incorporates low-density lipoproteins (LDLs) to facilitate chemotaxis to lesion sites, with an inner layer of apoptotic endothelial cell membranes to increase macrophage internalization and drug release. As a result, ALD@EM nanovesicles significantly increased the accumulation and therapeutic efficacy of decursin within plaques, substantially reducing lipid deposition and plaque inflammation, thereby offering a novel strategy for targeted AS treatment.

The risk of atherosclerotic cardiovascular disease increases with advancing age. Elevated LDL-cholesterol and non-HDL-cholesterol levels remain predictive of incident atherosclerotic cardiovascular events among individuals older than 75 years. Risk prediction among older individuals is less certain because most current risk calculators lack specificity in those older than 75 years and do not adjust for co-morbidities, functional status, frailty, and cognition which significantly impact prognosis in this age group. Data on the benefits and risks of lowering LDL-cholesterol with statins in older patients without atherosclerotic cardiovascular disease are also limited since most primary prevention trials have included mostly younger patients. Available data suggest that statin therapy in older primary prevention patients may reduce atherosclerotic cardiovascular events and that benefits from lipid-lowering with statins outweigh potential risks such as statin-associated muscle symptoms and incident Type 2 diabetes mellitus. While some evidence suggests the possibility that statins may be associated with incident cognitive impairment in older adults, a preponderance of literature indicates neutral or even protective statin-related cognitive effects. Shared decision-making which is recommended for all patients when considering statin therapy is particularly important in older patients. Randomized clinical trial data evaluating the use of non-statin lipid-lowering therapy in older patients are sparse. Deprescribing of lipid-lowering agents may be appropriate for select patients older than 75 years with life-limiting diseases. Finally, a patient-centered approach should be taken when considering primary prevention strategies for older adults.

Cardiometabolic risk increases cardiovascular (CVD), chronic kidney (CKD) and non-alcoholic fatty liver (NAFLD) disease risk. High myeloperoxidase (MPO) levels identify individuals at risk for CVD. We whether elevation of MPO associated with kidney and liver disease risk in subgroups stratified by ASCVD risk and intensity of therapy. Adjusted logistic models assessed the associations of MPO with markers of kidney disease (estimated glomerular filtration rate) and liver fibrosis (NAFLD score > 0.676 or Fibrosis-4 [FIB-4] score > 2.67) across ASCVD risk (low < 7.5%; intermediate 7.5% to < 20%; high ≥ 20%). This retrospective study comprised 20,772 participants in an employer-sponsored health assessment. High MPO associated with impaired kidney function with low (OR 2.2, 95% CI 1.6-3.7) and intermediate (OR 2.0, 95% CI 1.3-3.5) ASCVD risk, and with high FIB-4 or NAFLD scores in low (OR 2.4, 95% CI 1.2-4.7), intermediate (OR 3.1, 95% CI 2.0-6.0), and high (OR 3.8, 95% CI 2.9-7.4) ASCVD risk groups. High MPO was associated with markers of CKD and liver fibrosis in low to intermediate ASCVD risk and treated groups. These findings demonstrate the commonality of cardiometabolic biomarkers across multiple organs.   Prospective studies are warranted to assess whether high MPO levels identify persons at risk for CKD and liver fibrosis who may benefit from preventive strategies.

Elevated LDL-cholesterol levels and inflammation, as assessed by high-sensitivity C-reactive protein, correlate with cardiovascular risk. However, data on the relative impact of residual LDL-cholesterol and inflammatory risk among statin-treated patients undergoing percutaneous coronary intervention (PCI) is lacking. Hence, this study aimed to investigate the impact of residual cholesterol/inflammatory risk in patients on statin therapy undergoing PCI.

From 2012 to 2022, patients at a tertiary centre undergoing PCI were analysed. Patients were stratified according to LDL-cholesterol (≥70 vs <70 mg/dL) and high-sensitivity C-reactive protein (≥2 vs <2 mg/L) levels: no residual cholesterol or inflammatory risk, residual cholesterol risk, residual inflammatory risk, and combined residual cholesterol and inflammatory risk. Patients presenting with acute myocardial infarction, cancer, no statin treatment at admission, or high-sensitivity C-reactive protein levels >10 mg/L were excluded. The primary endpoint was major adverse cardiovascular events (MACEs), defined as the composite of all-cause mortality, spontaneous myocardial infarction, and stroke 1 year after the index PCI.

A total of 15 494 patients were included. After 1-year follow-up, individuals with isolated residual inflammatory risk had the highest MACE rate (5.1%), followed by patients with combined cholesterol and inflammatory risk, no residual risk, and isolated residual cholesterol risk. After multivariable Cox regression analysis, patients with residual inflammatory risk had a 1.8-fold higher risk for MACE (adjusted hazard ratio: 1.78, 95% confidence interval 1.36-2.33, P < .001) compared with those with no residual cholesterol or inflammatory risk. This was similar in patients with combined residual cholesterol and inflammatory risk (adjusted hazard ratio: 1.56, 95% confidence interval 1.19-2.04, P = 0.001). Of note, no independent association of isolated residual cholesterol risk (adjusted hazard ratio: 1.01, 95% confidence interval .76-1.35, P-value = .920) with MACE was noted (P-trend across all groups <.001).

Among statin-treated patients undergoing PCI, residual inflammation but not cholesterol risk was associated with an increased risk of MACE during follow-up.

Metabolic syndrome (MetS) is a complex cluster of interrelated metabolic disorders that significantly elevate the risk of cardiovascular disease, making it a pressing public health concern worldwide. Among the key features of MetS, dyslipidemia-characterized by altered levels of high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG)-plays a crucial role in the disorder's progression. This review aims to elucidate the intricate interplay between HDL-C and TG within the context of lipid metabolism and cardiovascular health, while also addressing the detrimental impact of various cardiovascular risk factors and associated comorbidities. The dynamics of HDL-C and TG are explored, highlighting their reciprocal relationship and respective contributions to the pathophysiology of MetS. Elevated levels of TGs are consistently associated with reduced concentrations of HDL-C, resulting in a lipid profile that promotes the development of vascular disease. Specifically, as TG levels rise, the protective cardiovascular effects of HDL-C are diminished, leading to the increased accumulation of pro-atherogenic TG-rich lipoproteins and low-density lipoprotein particles within the vascular wall, contributing to the progression of atheromas, which can ultimately result in significant ischemic cardiovascular events. Ultimately, this paper underscores the significance of HDL and TG as essential targets for therapeutic intervention, emphasizing their potential in effectively managing MetS and reducing cardiovascular risk.

Observational studies have linked LDL-C (low-density lipoprotein-cholesterol)-lowering drugs with lower blood pressure (BP) and higher fasting glucose, but the causality remains unclear. We conducted a drug target Mendelian randomization study to assess the causal associations of genetically proxied inhibition of HMGCR (3-hydroxy-3-methylglutaryl coenzyme A reductase), PCSK9 (proprotein convertase subtilisin/kexin type 9), and NPC1L1 (Niemann-Pick C1-Like 1) with BP and fasting glucose.

Single-nucleotide polymorphisms in HMGCR, NPC1L1, and PCSK9 associated with LDL-C in a genome-wide association study meta-analysis from the Global Lipid Genetics Consortium (173 082 European individuals) were used to proxy LDL-C-lowering drug targets. BP and fasting glucose data were obtained from genome-wide association studies conducted by the International Consortium of Blood Pressure (757 601 European participants) and the Glucose and Insulin-related Traits Consortium (58 074 European participants). We used the inverse-variance weighted method and a series of sensitivity analyses for assessment.

Genetically proxied inhibition of HMGCR was negatively associated with systolic BP (β, -0.81 [95% CI, -1.26 to -0.37 mm Hg]; P=3.72×10-4) and diastolic BP (β, -1.58 [95% CI, -2.24 to -0.91 mm Hg]; P=3.23×10-6). Conversely, we observed a positive association between genetically proxied inhibition of HMGCR and high fasting glucose (β, 0.13 [95% CI, 0.08-0.17 mmol/L]; P=4.25×10-8). However, there was no association of PCSK9 and NPC1L1 inhibition with BP or fasting glucose.

Genetically proxied inhibition of HMGCR was significantly associated with low BP and high fasting glucose, while there was no effect of PCSK9 and NPC1L1 inhibition on BP or fasting glucose.

Previous research on how changes in CRP (C-reactive protein) levels predict stroke risk is limited. This study aimed to examine the association between CRP change and the risk of stroke and its subtypes.

Based on the UK Biobank data, we investigated the association between CRP change and the risk of stroke and its subtypes with Cox proportional hazards regression analysis. We further performed genetic analyses including genetic correlation, pairwise genome-wide association study, and polygenic risk score. Our study involved 14 754 participants with a median follow-up time of 10.4 years. After categorizing participants by CRP percentage change and making adjustments for potential confounders, it was observed that those with an elevated percentage of CRP change had a higher risk of any stroke (hazard ratio [HR], 1.44 [95% CI, 1.12-1.85]) and ischemic stroke (HR, 1.65 [95% CI, 1.24-2.18]). After categorization by CRP change types and adjustment for confounders, the group that became high level had a higher any-stroke risk (HR, 1.45 [95% CI, 1.04-2.02]), with the group that remained at a high level facing the greatest risk (HR, 1.74 [95% CI, 1.30-2.33]). Similar trends were observed for ischemic stroke. The group that remained at a high level also had a heightened hemorrhagic stroke risk (HR, 1.91 [95% CI, 1.07-3.44]). Genetic analysis showed a significant genetic correlation between CRP and stroke (rg, 0.257; rg_P=2.39E-07). Pairwise genome-wide association study analysis identified 5 shared genomic regions between CRP and stroke. Polygenic risk score analysis showed that participants with high stroke polygenic risk score and elevated or remaining high CRP levels have the highest risk of stroke.

Both any stroke and ischemic stroke are related to elevated and remaining high CRP levels, while hemorrhagic stroke is only related to remaining high CRP levels.

Treatment to lower high levels of low-density lipoprotein cholesterol (LDL-C) reduces incident coronary artery disease (CAD) risk but modestly increases the risk for incident type 2 diabetes (T2D). The extent to which genetic factors across the cholesterol spectrum are associated with incident T2D is not well understood.

To investigate the association of genetic predisposition to increased LDL-C levels with incident T2D risk.

In this large prospective, population-based cohort study, UK Biobank participants who underwent whole-exome sequencing and genome-wide genotyping were included. Participants were separated into 7 groups with familial hypercholesterolemia (FH), predicted loss of function (pLOF) in APOB or PCSK9 variants, and LDL-C polygenic risk score (PRS) quintiles. Data were collected between 2006 and 2010, with a median follow-up of 13.7 (IQR, 12.9-14.5) years. Data were analyzed from March 1 to November 1, 2024.

LDL-C level, LDL-C PRS, FH, or pLOF variant status.

Cox proportional hazards regression models adjusted for age, sex, genotyping array, lipid-lowering medication use, and the first 10 genetic principal components were fitted to assess the association between LDL-C genetic factors and incident T2D and CAD risks.

Among the 361 082 participants, mean (SD) age was 56.8 (8.0) years, 194 751 (53.9%) were female, and mean (SD) baseline LDL-C level was 138.0 (33.6) mg/dL. During the follow-up period, 22 619 (6.3%) participants developed incident T2D and 17 966 (5.0%) developed incident CAD. The hazard ratio for incident T2D was lowest in the FH group (0.65; 95% CI, 0.54-0.77), while the highest risk was in the pLOF group (1.48; 95% CI, 1.18-1.86). The association between LDL-C PRS and incident T2D was 0.72 (95% CI, 0.66-0.79) for very high LDL-C PRS, 0.87 (95% CI, 0.84-0.90) for high LDL-C PRS, 1.13 (95% CI, 1.09-1.17) for low LDL-C PRS, and 1.26 (95% CI, 1.15-1.38) for very low LDL-C PRS. CAD risk increased directly with the LDL-C PRS.

In this cohort study, LDL-C and T2D risks were inversely associated across genetic mechanisms for LDL-C variation. Further elucidation of the mechanisms associating low LDL-C risk with increased risk of T2D is warranted.

Views on the etiopathogenesis of atherosclerosis are subject to evolution. In addition to the classic well-known risk factors, new ones related to mental state, social life and environment are being discovered. Both acute and chronic stress stimulate inflammatory processes. Due to the change in lifestyle and eating habits, the accumulation of risk factors in childhood is an increasing problem. Knowledge of risk factors allows for effective primary prevention of cardiovascular diseases. The effectiveness of prevention increases when the activities cover the largest possible part of the society, and access to a doctor is easy. Therefore, government programs are being implemented offering patients easier access to diagnostics of cardiovascular diseases at the level of primary health care, which enables faster identification of people at the greatest cardiovascular risk. Easier access to primary care and a good doctor-patient relationship improve patient compliance. In this situation, the importance of the family doctor as a key link in the diagnosis, prevention and treatment of cardiovascular diseases is increasing.

Inflammation plays a role in cardiovascular disease (CVD). We defined various noncardiovascular and noncancer conditions, both infectious and noninfectious, with a common basis of inflammation, collectively termed chronic inflammatory-related disease (ChrIRD). We describe ChrIRD and its interplay with CVD during follow-up in the Multi-Ethnic Study of Atherosclerosis.

The aim of the study was to describe ChrIRD, its associations with CVD, and its association with mortality.

Participants were free of overt CVD at baseline with median 17.9 (Q1-Q3: 14.9-18.6) years of follow-up. ChrIRD was determined by review of hospitalization and death records of International Classification of Diseases codes. CVD diagnosis was adjudicated based on medical records. We performed time-dependent proportional hazard regressions to identify risks related to ChrIRD or CVD events.

MESA (Multi-Ethnic Study of Atherosclerosis) participants (n = 6,791) had a mean age of 62 ± 10 years, with 47% (3,201/6,791) men, 39% (2,617/6,791) White, 28% (1,882/6,791) Black, 22% (1,489/6,791) Hispanic, and 12% (803/6,791) Chinese race/ethnicity. ChrIRD was observed in 29% (1,965/6,791) and CVD in 21% (1,420/6,791); including 11% (761/6,791) with both conditions. Mortality after ChrIRD only was 47% (567/1,204; 95% CI: 44%-49%); after CVD only was 45% (300/659; 95% CI: 41%-49%); and after both conditions was 67% (510/761; 95% CI: 63%-70%). CVD was associated with increased risk of ChrIRD (HR: 1.48; 95% CI: 1.23-1.77) and ChrIRD was associated with increased risk of CVD (HR: 2.23; 95% CI: 1.97-2.52). Baseline inflammatory markers predicted both conditions.

ChrIRD is common, present in all organ systems, and is associated with significant mortality, particularly in combination with CVD. The association between CVD and ChrIRD is bidirectional, and baseline inflammatory markers are associated with ChrIRD and CVD.

High-intensity statin therapy significantly reduces mortality and cardiovascular events in patients with atherosclerotic cardiovascular disease (ASCVD). However, moderate-intensity statins are often preferred for elderly patients due to their higher risk of intolerance to high-intensity statins.

To compare the incidence of statin-associated muscle symptoms (SAMS) and the effect on low-density lipoprotein cholesterol (LDL-C) levels between elderly ASCVD patients receiving high-intensity statin monotherapy and those receiving moderate-intensity statin with ezetimibe in a combination therapy.

In a prospective, multicenter, open-label trial conducted in South Korea, 561 patients aged 70 years or above with ASCVD were randomly assigned to receive either moderate-intensity statin with ezetimibe combination therapy (rosuvastatin 5 mg with ezetimibe 10 mg) or high-intensity statin monotherapy (rosuvastatin 20 mg) over 6 months. The primary endpoint was the incidence of SAMS, and the key secondary endpoint was the achievement of target LDL-C levels (<70 mg/dL) within 6 months.

The primary endpoint showed a lower incidence of SAMS in the combination therapy group (0.7%) compared to the high-intensity statin monotherapy group (5.7%, p = 0.005). Both groups achieved similar LDL-C levels, with 75.4% in the combination therapy group and 68.7% in the monotherapy group reaching target levels.

Moderate-intensity statin with ezetimibe combination therapy offers a lower risk of SAMS and similar LDL-C reduction in elderly patients with ASCVD, compared to high-intensity statin monotherapy.

Background Thyroid eye disease is a sight-threatening disorder associated with Graves's disease. While treatment is aimed at stabilizing established thyroid eye disease, there are limited investigations regarding prevention. Statins, known for their anti-inflammatory properties, are one such treatment that has been investigated for thyroid eye disease. This study retrospectively analyzes the impact of statin medications on thyroid eye disease and related outcomes from real-world data using TriNetX Global Collaborative Network (TriNetX, Cambridge, MA, USA). Objective The primary objective of this study is to analyze the risk of developing thyroid eye disease in patients with Graves' disease treated with statin medications relative to those without exposure up to five years. Secondary objectives of this study include analyzing thyroid eye disease-related outcomes, including diplopia, optic nerve surgery, optic nerve injury, strabismus, blindness, requirement for teprotumumab, color vision deficiencies, and referral to ophthalmology. Methods Data were collated utilizing TriNetX Global Collaborative Network, a platform of globally de-identified patient information from over 140 healthcare organizations. Patients more than 18 years of age with a diagnosis of Graves' disease (ICD-10: E05.0 Thyrotoxicosis with Diffuse Goiter) were divided into Cohorts A (administration of statin medication following diagnosis of Graves' disease, n = 66,444) and B (no statin medication administration, n = 225,905). Via implementation of propensity score matching to control for confounding factors, a total of n = 43,025 matched patients per cohort was obtained. Hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the primary and secondary objectives over a five-year follow-up period. The t-test was used for the calculation of mean averages of ophthalmology referrals and to determine statistical significance. Results Patients treated with statin medications (Cohort A) demonstrated a significantly lower HR for the development of exophthalmos (HR = 0.559, 95% CI 0.521-0.601, p < 0.001). Statin medications were furthermore associated with a reduced HR for diplopia (p < 0.001), optic nerve surgery (p = 0.018), and requirement for teprotumumab (p = 0.047). No significant reduction in hazards for color vision deficits, strabismus, optic nerve injury, or blindness was noted. Additionally, there was no significant difference in referrals to ophthalmology. Conclusion The findings from this study suggest that statin therapy may be protective against the development of thyroid eye disease and associated complications. Further randomized controlled trials are required to validate these findings and establish a therapeutic role for statins in thyroid eye disease.

A major public health concern gripping the nation is chronic kidney disease (CKD), and for individuals concomitantly diagnosed with type 2 diabetes mellitus (T2DM), the coexistence significantly increases the cardiovascular morbidity and mortality by two to three times higher than patients diagnosed without CKD. CKD management encompasses both non-pharmacological approaches, such as dietary sodium restriction and lifestyle modification for blood pressure control, and pharmacological approaches. Current pharmacological management focuses on four key pillars: renin-angiotensin system inhibitors (RASi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and mineralocorticoid receptor antagonists (MRAs), all of which have shown renoprotective and cardiovascular benefits. An incomplete block of aldosterone activity remains a challenge and is one of the factors contributing to the progression of kidney damage. Aldosterone synthase inhibitors (ASIs), such as vicadrostat, may represent a new horizon in selectively inhibiting aldosterone synthesis while preserving cortisol production. Early-phase trials have shown reductions in albuminuria and a potential for renal protection. The question is, could ASIs emerge as a fifth pillar in CKD management and help curb the progression?

Virus-specific CD8+ T cells play a major role in the natural control of HIV infection, linked to memory-like features such as high survival capacity and polyfunctionality. However, virus-specific CD8+ T cells from HIV non-controllers exhibit an effector-like and exhausted profile, with limited antiviral potential. Metabolic reprogramming of cells from non-controllers could reinvigorate their functional capacities. Considering the implication of the cholesterol pathway in the induction of T cell exhaustion, here we evaluated the impact of rosuvastatin, an inhibitor of cholesterol synthesis, on the functionality and memory profile of HIV-specific CD8+ T cells from people on antiretroviral treatment.

We analysed samples from 10 individuals with HIV-1 on ART who participated in the IMEA 043-CESAR trial and received rosuvastatin for 12 weeks. We explored whether rosuvastatin treatment was accompanied by changes in the memory potential of CD8+ T cells. We evaluated the phenotype and functionality of total and HIV-specific CD8+ T cells before, during, and after treatment with rosuvastatin. A mixed effects model was used for repeated measures and corrected for multiple comparisons.

Total and HIV-specific CD8+ T cell survival and functionality were enhanced in individuals who received a 12-week course of rosuvastatin, with a consistent increase in polyfunctional IFN-γ+ TNF-α+ cells. The superior CD8+ T cell functionality after rosuvastatin treatment was associated with intrinsic metabolic changes, including the decrease of fatty acid uptake, as well as a reduction in effector/exhaustion markers. Changes in the characteristics of CD8+ T cells coincided with the duration of rosuvastatin administration, and most effects waned after the cessation of the treatment.

CD8+ T cell metabolic reprogramming by targeting the cholesterol pathway, combined with other available immunotherapies, might represent a promising strategy in the search for the cure of HIV or other chronic viral infections.

The CESAR trial was sponsored by IMEA. This work was supported by the NIH (grants UM1AI164562 and R01DK131476).

Loss of skeletal muscle mass and systemic inflammation may offer prognostic value in patients with abdominal aortic aneurysm (AAA). The longitudinal progression of abnormal body composition parameters and their determinants is poorly reported. Statins are widely used medications that improve the prognosis of cardiovascular disease and interact with both muscle tissue and systemic inflammation. The present study aimed to describe the association between statin therapy and both pre-operative and longitudinal CT-derived body composition in patients undergoing elective intervention for AAA.

A total of 756 consecutive patients undergoing elective intervention for AAA at three centres were retrospectively recruited. Body composition analysis was performed on pre-operative and follow-up CTs at L3 to generate subcutaneous adipose tissue index, visceral adipose tissue index and skeletal muscle index and density (SMI and SMD). Systemic inflammation was assessed using the systemic inflammatory grade.

A total of 756 patients (702 [93%] males, median [interquartile range, IQR] age 73.0 [11.0] years) were included, with a median (IQR) follow-up of 67.0 (32) months and 235 deaths during the follow-up period. There were 582 patients (77%) receiving statin therapy and 174 patients (23%) not receiving statin therapy. Follow-up CTs were available for 273 patients. From pre-operative to follow-up CTs, there was a decrease in median SMI (P < 0.001) and SMD (P < 0.001) and an increase in the comparative prevalences of low SMI (43% vs. 50%, P < 0.01) and low SMD (64% vs. 88%, P < 0.001). There were no differences in baseline clinicopathological characteristics, systemic inflammation or pre-operative CT-derived body composition parameters between patients with and without >10% loss of skeletal muscle mass. In patients with ≤10% loss of SMI, mean (95% confidence interval) survival was 91.6 (87.2-95.9) months versus 89.3 (80.4-98.2) months in patients with >10% loss of SMI (P = 0.58). Patients receiving statin therapy had a higher American Society of Anesthesiologists grade (P < 0.001), a higher body mass index (BMI) (P < 0.05) and a greater prevalence of normal pre-operative SMI (P < 0.001).

In patients with AAA, skeletal muscle mass and density appear to progressively decline despite treatment of AAA, though specific determinants of this are uncertain, and statin use does not appear to predispose to either muscle loss or preservation. Statin therapy appears to be associated with a lower rate of pre-operative low skeletal muscle mass, despite greater comorbidity and BMI. Further investigation of the progressive changes in muscle mass and quality, statin therapy and systemic inflammation is warranted.