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Background: Familial hypercholesterolemia (FH) and obesity are well-established risk factors of atherosclerotic cardiovascular disease (ASCVD). Despite high prevalence, their joint association with ASCVD remains largely unknown., Objective: To investigate the association of obesity with prevalent ASCVD in individuals with heterozygous FH (HeFH) enrolled in the Hellenic Familial Hypercholesterolemia Registry (HELLAS-FH)., Methods: FH diagnosis was based on Dutch Lipid Clinic Network (DLCN) criteria. Adults with at least possible FH diagnosis (DLCN score ≥3) and available body mass index (BMI) values were included. Homozygous FH individuals were excluded., Results: 1655 HeFH adults (mean age 51.0 ± 14.4 years, 48.6% female) were included; 378 (22.8%) and 430 (26.0%) were diagnosed with probable and definite FH, respectively. Furthermore, 371 participants (22.4%) had obesity and 761 (46.0%) were overweight. Prevalence of ASCVD risk factors increased progressively with BMI. Prevalence of coronary artery disease (CAD) was 23.4% (3.2% for stroke and 2.7% for peripheral artery disease [PAD]), and increased progressively across BMI groups. After adjusting for traditional ASCVD risk factors and lipid-lowering medication, individuals with obesity had higher odds of established CAD (OR: 1.54, 95% CI: 1.04-2.27, p = 0.036) as well as premature CAD (OR: 1.74, 95% CI: 1.17-2.60, p = 0.009) compared with those with normal BMI. No association was found with stroke or PAD., Conclusions: Over half of adults with HeFH have overweight or obesity. Obesity was independently associated with increased prevalence of CAD in this population., (Copyright © 2024. Published by Elsevier Inc.)

Background: Familial hypercholesterolemia (FH) carries a high risk of atherosclerotic cardiovascular disease (ASCVD). As the population ages, the age-related influence on clinical characteristics and outcomes becomes increasingly pertinent. This cross-sectional analysis from the HELLAS-FH registry aims to explore potential differences in clinical characteristics, treatment, ASCVD, and goal achievement between those younger and older than 65 years with FH., Results: A total of 2273 adults with heterozygous FH (51.4% males) were studied. Elderly FH patients ( n = 349) had a higher prevalence of ASCVD risk factors, such as hypertension (52.1% vs. 20.9%, p < 0.05) and type 2 diabetes (16.9% vs. 6.0%, p < 0.05), compared to younger patients ( n = 1924). They also had a higher prevalence of established ASCVD (38.4% vs. 23.1%, p < 0.001), particularly CAD (33.0% vs. 20.2%, p < 0.001), even after adjusting for major ASCVD risk factors. Elderly patients were more frequently and intensively receiving lipid-lowering treatment than younger ones. Although post-treatment LDL-C levels were lower in elderly than younger patients (125 vs. 146 mg/dL, p < 0.05), both groups had similar attainment of the LDL-C target (3.7% vs. 3.0%)., Conclusions: Elderly FH patients have a higher prevalence of ASCVD, particularly CAD. Despite more aggressive treatment, the achievement of LDL-C targets remains very poor. These results emphasize the importance of early FH diagnosis and treatment in reducing ASCVD.

Background/aims: Impaired high-density lipoprotein (HDL) function and composition are more strongly related to cardiovascular morbidity than HDL concentration. However, it is unclear whether HDL function and composition predict ischemic stroke severity and outcome. We aimed to evaluate these associations., Methods: We prospectively studied 199 consecutive patients who were admitted with acute ischemic stroke. The severity of stroke was evaluated at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS ≥ 5. The outcome was assessed with dependency at discharge (modified Rankin scale 2-5) and in-hospital mortality. Cholesterol efflux capacity (CEC), phospholipid levels, lecithin:cholesterol acyl transferase (LCAT)-phospholipase activity, paraoxonase-1 (PON1)-arylesterase activity and serum amyloid A1 (SAA1) content of HDL were measured., Results: CEC, phospholipid levels and LCAT-phospholipase activity of HDL were lower and SAA1 content of HDL was higher in patients with severe stroke. Patients who were dependent at discharge had lower CEC, PON1-arylesterase activity, phospholipid content and LCAT-phospholipase activity of HDL and higher HDL-SAA1 content. Independent predictors of dependency at discharge were the NIHSS at admission (RR 2.60, 95% CI 1.39-4.87), lipid-lowering treatment (RR 0.17, 95% CI 0.01-0.75), HDL-CEC (RR 0.21, 95% CI 0.05-0.87) and HDL-associated PON1-arylesterase activity (RR 0.95, 95% CI 0.91-0.99). In patients who died during hospitalization, phospholipids, LCAT-phospholipase and PON1-arylesterase activities of HDL were lower., Conclusions: Changes in CEC and composition of HDL appear to be associated with the severity and outcome of acute ischemic stroke and could represent biomarkers that may inform risk stratification and management strategies in these patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Effective treatments and vaccines against COVID-19 used in clinical practice have made a positive impact on controlling the spread of the pandemic, where they are available. Nevertheless, even if fully vaccinated, immunocompromised patients still remain at high risk of adverse outcomes. This has driven the largely expanding field of monoclonal antibodies, with variable results. Tixagevimab/Cilgavimab (AZD7442), a long-acting antibody combination that inhibits the attachment of the SARS-CoV-2 spike protein to the surface of cells, has proved promising in reducing the incidence of symptomatic COVID-19 or death in high-risk individuals without major adverse events when given as prophylaxis, as well as early treatment. Real-world data confirm the antibody combination's prophylaxis efficacy in lowering the incidence, hospitalization, and mortality associated with COVID-19 in solid organ transplant recipients, patients with immune-mediated inflammatory diseases and hematological malignancies, and patients in B-cell-depleting therapies. Data suggest a difference in neutralization efficiency between the SARS-CoV-2 subtypes in favor of the BA.2 over the BA.1. In treating COVID-19, AZD7442 showed a significant reduction in severe COVID-19 cases and mortality when given early in the course of disease, and within 5 days of symptom onset, without being associated with severe adverse events, even when it is used in addition to standard care. The possibility of the development of spike-protein mutations that resist monoclonal antibodies has been reported; therefore, increased vigilance is required in view of the evolving variants. AZD7442 may be a powerful ally in preventing COVID-19 and the mortality associated with it in high-risk individuals. Further research is required to include more high-risk groups and assess the concerns limiting its use, along the SARS-CoV-2 evolutionary trajectory., Competing Interests: K.A. has received honoraria from Angelini, Viatris, Gilead Sciences, MSD, GSK/ViiV, Pfizer Hellas, 3M; G.K. has received honoraria AbbVie, Amgen, Bristol, GENESIS Pharma,Glaxo, Demo, Janssen, Innovis, Unipharma, Novartis, Roche, Meditrina, Sanofi, Takeda; C.G. has received honoraria from Astra Zeneca, Bio-merieux, Gilead Sciences, GSK/ViiV, MSD, Pfizer Hellas, 3M. C.S. has received Menarini, Boehringer Ingelheim, Pfizer, MSD, BIANEX, Mylan, WinMedica, Bayer, Sanofi, Novo, Bausch Health, ELPEN, Lilly, Nutricia, Lavipharm. C.G. has received honoraria from Astra Zeneca, Bio-merieux, Gilead Sciences, GSK/ViiV, MSD, Pfizer Hellas, 3M. Other authors declare no conflict of interest.

Background: The triglyceride/glucose index (TyG) reflects insulin resistance and predicts the risk of acute ischemic stroke (aIS). However, it is uncertain if this index predicts the severity and outcome of aIS because studies that addressed this question are few and all were performed in Asian subjects. Moreover, there are no studies that focused on patients with hypercholesterolemia., Methods: We studied 997 Caucasian patients who were hospitalized for aIS and had hypercholesterolemia. aIS severity was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS) and severe aIS was defined as NIHSS ≥ 21. The outcome was assessed with the functional outcome at discharge and with in-hospital mortality. An unfavorable functional outcome was defined as modified Rank in scale (mRs) at discharge between 3 and 6., Results: The TyG index did not correlate with the NIHSS at admission (r = 0.032, p = NS) and was similar in patients with severe and non-severe aIS (8.7 ± 0.6 and 8.6 ± 0.6, respectively; p = NS). Risk factors for severe aIS were age, female gender, atrial fibrillation (AF) and diastolic blood pressure (DBP) at admission. The TyG index also did not correlate with the mRs(r = 0.037, p = NS) and was similar in patients who had unfavorable and favorable functional outcome (8.7 ± 0.6 and 8.6 ± 0.5, respectively; p = NS). Risk factors for unfavorable functional outcome were age, previous ischemic stroke, body mass index and the NIHSS at admission. The TyG index was similar in patients who died during hospitalization and patients who were discharged (8.7 ± 0.6 and 8.7 ± 0.6, respectively; p = NS). Risk factors for in-hospital mortality were AF and DBP and NIHSS at admission., Conclusions: The TyG index does not appear to be associated with the severity or the outcome of aIS. Nevertheless, since there are few relevant data in Caucasians and the TyG index is an inexpensive and widely available biomarker, more studies in this ethnic group are required to determine the predictive role of this index in patients with aIS., Competing Interests: The authors declare no conflict of interest. Konstantinos Tziomalos is serving as Guest Editor of this journal. We declare that Konstantinos Tziomalos had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Brian Tomlinson., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Neuropathy is a frequent complication of diabetes mellitus (DM) and is associated with the increased risk ofamputation and vascular events. Tight glycemic control is an important component inthe prevention of diabetic neuropathy. However, accumulating data suggest that angiotensin receptor blockers (ARBs) might also be useful in this setting. We discuss the findings of both experimental and clinical studies that evaluated the effects of ARBs on indices of diabetic neuropathy. We also review the implicated mechanisms of the neuroprotective actions of these agents. Overall, it appears that ARBs might be a helpful tool for preventing and delaying the progression of diabetic neuropathy, but more data are needed to clarify their role in the management of this overlooked complication of DM.

Introduction : Heterozygous familial hypercholesterolemia (heFH) is associated with a very high risk for cardiovascular events. Treatment with potent statins substantially reduces cardiovascular morbidity in these patients. Moreover, combination therapy with statins plus ezetimibe and/or proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors facilitates achievement of low-density lipoprotein cholesterol (LDL-C) targets in patients with heFH. However, heFH remains underdiagnosed and undertreated worldwide. Areas covered : In this review, we summarize current evidence on the prevalence and control rates of heFH. Accumulating data suggest that heFH is one of the most common hereditary metabolic disorders, affecting approximately 1 in every 300 individuals. However, only a small minority of patients with heFH achieve LDL-C targets, even in high-income countries and in subjects followed-up in specialized lipid clinics. Expert opinion : Given the underdiagnosis of heFH using cascade and opportunistic screening, wider, population-based screening strategies should be evaluated for their feasibility and cost-effectiveness if we aspire to timely diagnosis and therefore prevention of cardiovascular morbidity and mortality in this very high risk population. Overcoming inertia in uptitrating statin dose, adding ezetimibe and/or PCSK9 inhibitors along with more generous reimbursement for lipid-lowering agents in patients with heFH are essential for improving goal attainment rates.

HbA1c is a biomarker with a central role in the diagnosis and follow-up of patients with diabetes, although not a perfect one. Common comorbidities encountered in patients with diabetes mellitus, such as renal insufficiency, high output states (iron deficiency anaemia, haemolytic anaemia, haemoglobinopathies and pregnancy) and intake of specific drugs could compromise the sensitivity and specificity of the biomarker. COVID-19 pandemic poses a pressing challenge for the diabetic population, since maintaining optimal blood glucose control is key to reduce morbidity and mortality rates. Alternative methods for diabetes management, such as fructosamine, glycosylated albumin and device-based continuous glucose monitoring, are discussed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Dasatinib associated lymphadenopathy (DAL) is a rare adverse event in chronic myeloid leukemia patients (CML). A case of voluminous lymphadenopathy in the context of DAL is presented., Patient Concerns: A 40-year-old male patient was diagnosed with BCR-ABL1 positive chronic stage CML 2 years ago and achieved complete molecular response on nilotinib, which was switched to dasatinib due to nilotinib intolerance. After 5 months on dasatinib, the patient presented with a large mass in the axillary region., Diagnosis: Common infectious and autoimmune etiologies of lymphadenopathy were ruled out. The positron emission tomography/computed tomography (PET/CT) demonstrated a hypermetabolic lymphadenopathy highly suspicious of lymphoma. The subsequent biopsy excluded lymphoma or extramedullary blastic transformation of CML and revealed reactive lymphadenopathy with mixed (cortical and paracortical) pattern. Clinical history and clinicopathological correlation suggested the diagnosis of DAL., Intervention: Dasatinib was discontinued and the patient remained in close follow-up. TKI treatment with nilotinib was reinitiated., Outcomes: Lymphadenopathy resolved clinically at 4 weeks and normalization of PET/CT findings was documented at 9 weeks after cessation of the drug. TKI treatment with nilotinib was reinitiated with good tolerance., Lessons: DAL may present with voluminous lymphadenopathy consistent with malignancy in clinical and imaging workup. We describe the spectrum of lesions associated with DAL and identify common features with drug-induced lymphadenopathy.

Introduction: Heterozygous familial hypercholesterolemia (heFH) is a common metabolic disease associated with increased cardiovascular risk. Despite treatment with the currently available lipid-lowering agents (statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors), a substantial proportion of patients with heFH does not achieve low-density lipoprotein cholesterol (LDL-C) targets., Areas Covered: The PubMed database was reviewed for relevant papers published up to August 2020. The safety and efficacy of novel agents, namely inclisiran and bempedoic acid, that lower LDL-C levels and might be useful in the management of patients with heFH are discussed., Expert Opinion: The prolonged lipid-lowering effect of inclisiran might improve adherence to treatment in patients with heFH. Bempedoic acid provides additional reductions in LDL-C levels in patients on high-intensity statin treatment; oral administration of this agent might be attractive to some patients. However, it is important to evaluate the effects of these agents on cardiovascular morbidity before they are incorporated in the management of heFH. The cost/benefit of treatment should also be considered, given the increasing complexity of lipid-lowering treatment.

Patients with type 2 diabetes mellitus (T2DM) appear to have increased risk for fractures. In this context, the finding that canagliflozin, a sodium-glucose co-transporter-2 (SGLT) inhibitor, increased the risk for fracture compared with placebo in the Canagliflozin Cardiovascular Assessment Study (CANVAS), a large randomized controlled trial (RCT) in patients with established cardiovascular disease or multiple cardiovascular risk factors, created concern. In the present review, we summarize the data regarding the association between SGLT2 inhibitors and fracture risk in patients with T2DM. In contrast to the findings reported in CANVAS, canagliflozin did not affect the risk of fracture in a more recent, large RCT in patients with diabetic nephropathy. In addition, empagliflozin and dapagliflozin, other members of this class, also do not appear to affect the incidence of fracture. Moreover, there is no clear pathogenetic mechanism through which SGLT2 inhibitors increase the risk for fractures. Therefore, available data are inconclusive to attribute to these drugs a direct responsibility for bone fractures.

Introduction: Even though statins represent the mainstay of treatment of heterozygous familial hypercholesterolemia (FH), their low-density lipoprotein cholesterol (LDL-C) lowering efficacy is finite and most patients with FH will not achieve LDL-C targets with statin monotherapy. Addition of ezetimibe with or without bile acid sequestrants will also not lead to treatment goals in many of these patients, particularly in those with established cardiovascular disease. In this selected subgroup of the FH population, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors provide substantial reductions in LDL-C levels, reduce cardiovascular morbidity and appear to be safe. Mipomersen, an antisense single-strand oligonucleotide that inhibits the production of apoB by binding to the mRNA that encodes the synthesis of apoB, and lomitapide, an inhibitor of microsomal triglyceride transfer protein, also reduce LDL-C levels but are currently indicated only for the management of homozygous FH. Areas covered: In the present review, the role of PCSK9 inhibitors, mipomersen and lomitapide in the management of FH is briefly discussed. Other LDL-C-lowering agents under evaluation include inclisiran, a small interference RNA molecule that induces long-term inhibition of PSCK9 synthesis, anacetrapib, a cholesterol ester-transfer protein inhibitor, ETC-1002 (bempedoic acid), an inhibitor of adenosine triphosphate citrate lyase, and gemcabene, which reduces hepatic apolipoprotein C-III mRNA. The safety and efficacy of these agents are also reviewed. Expert Commentary: Even though several novel treatment options for heterozygous FH are under development, it remains to be shown whether these treatments will also reduce cardiovascular morbidity in these high-risk patients.