Current Atherosclerosis Reports最新文献

Purpose of the review: This review is intended to serve as guidance for care providers working with children who have dyslipidemia and exhibit picky eating behaviors.

Recent findings: Picky eating behaviors in children can be very stressful for caregivers and children alike, even if they may not reach clinical significance. In the setting of lipid disorder treatment, picky eating can present an even greater challenge, since many of the foods considered most heart-healthy are not often considered "kid-friendly". Care providers should validate caregivers' concerns, screen for picky eating and be prepared to provide guidance to parents and a referral to a specialist, if needed. This review contains an itemized list of points to focus on with families and additional resources.

Purpose of the review: This review discusses the molecular mechanisms involved in the immuno-pathogenesis of atherosclerosis, the pleiotropic anti-inflammatory effects of approved cardiovascular therapies and the available evidence on immunomodulatory therapies for atherosclerotic cardiovascular disease (ACVD). We highlight the importance of clinical and translational research in identifying molecular mechanisms and discovering new therapeutic targets.

Recent findings: The CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) trial was the first to demonstrate a reduction in cardiovascular (CV) risk with anti-inflammatory therapy, irrespective of serum lipid levels. ACVD is the leading cause of death worldwide. Although targeting principal risk factors significantly reduces CV risk, residual risk remains unaddressed. The immunological mechanisms underlying atherosclerosis represent attractive therapeutic targets. Several commonly used and non-primarily anti-inflammatory drugs (i.e. SGLT2i, and PCSK9i) exhibit pleiotropic properties. Otherwise, recent trials have investigated the blockade of primarily inflammatory compounds, trying to lower the residual risk via low-dose IL-2, PTPN22 and CD31 pathway modulation. In the era of precision medicine, modern approaches may explore new pharmacological targets, identify new markers of vascular inflammation, and evaluate therapeutic responses.

Purpose of review: This paper reviews the existing literature on statin-related myopathy in children and adolescents, to inform development of a practical management approach.

Recent findings: Reports of statin treatment in the pediatric population revealed no evidence of muscle pathology, with asymptomatic elevation of creatine kinase(CK) levels and symptoms of muscle pain without CK elevation seen equally in subjects and controls in RCTs. By contrast, rare cases of rhabdomyolysis have now been documented in statin-treated children; this serious problem had never been previously reported. Statin-induced myopathy is rare in childhood so routine monitoring of CK levels is unnecessary in asymptomatic patients, reserved for those with muscle pain. Rare case reports of rhabdomyolysis in statin-treated children and adolescents suggest that parent and patient education on symptoms of adverse statin effects should include immediate physician contact with the appearance of dark urine, with or without muscle pain.

Purpose of the review: This review examines the pivotal role of monoclonal antibodies against PCSK9 in lipid-lowering therapy, emphasizing their biological and clinical impact.

Recent findings: Randomized controlled trials have validated that PCSK9 monoclonal antibodies (Mabs) effectively reduce LDL-c levels by approximately 50%, even when added to maximal statin therapy. They moreover produce a notable 15-20% relative decrease in major cardiovascular events, with a greater reduction among high-risk patients and no evidence for serious adverse effects, assuaging previous concerns. This review highlights the benefits of PCSK9 Mabs in high cardiovascular risk patients. Despite their efficacy and safety, these therapies are hindered by limited access, and require broader integration into clinical practice to optimize therapeutic outcomes.

Purpose of review: Pediatric healthcare providers have increasingly become aware of the need for timely and informative transition of adolescents and young adults with chronic medical conditions such as diabetes and cystic fibrosis. However, there is paucity of published data on the importance of and most effective way to transition youth with lipid disorders who are at increased risk of premature cardiovascular disease.

Recent findings: Evidence shows that atherosclerosis begins at a young age. However, there are no guidelines on the transition of adolescents and young adults with dyslipidemia. In addition, there are conflicting guidelines for lipid management in children versus adults, despite advances in medical pharmacotherapies for dyslipidemia. The lack of guidelines for transition and discordant recommendations for management of this vulnerable population places young adults at-risk for worsening of their underlying disease, and premature cardiovascular events.

Purpose of the review: The purpose of this review is to evaluate the current state of knowledge regarding the technical challenges associated with the Post-Acquisition Fat Attenuation Index (PFAI). By examining the limitations and gaps in the current methodologies, this review aims to provide a comprehensive understanding of how various factors impact the accuracy and reliability of PFAI measurements.

Recent findings: PFAI correlates with plaque instability, as inflammation in coronary plaque alters surrounding adipose tissue composition, increasing its water content and reducing lipid content, which is detectable via cardiac CT as increased attenuation. Recent studies have demonstrated PFA's prognostic value, with elevated levels linked to higher risks of cardiac events and plaque instability. A 2022 meta-analysis confirmed its association with major adverse cardiac events. Machine learning algorithms incorporating PFA and additional imaging features have further enhanced risk prediction beyond traditional metrics. Pericoronary fat attenuation is a promising marker for assessing coronary inflammation and could be useful in predicting plaque development, rupture, and monitoring treatment response, though further prospective studies and technical standardization are needed to fully establish its clinical benefits.

Purpose of review: Dyslipidemia is a casual risk factor for atherosclerotic cardiovascular disease (ASCVD). There is an unmet need for more effective treatments for patients with dyslipidemias. Angiopoietin-like protein 3 (ANGPTL3) and ANGPTL8 play key roles in triglyceride trafficking and energy balance in humans. We review the functional role of these ANGPTL proteins in the regulation of lipoprotein metabolism, and recent clinical trials targeting ANGPTL3 and ANGPTL3/8 with monoclonal antibody and/or nucleic acid therapies, including antisense oligonucleotides and small interfering RNA.

Recent findings: Cumulative evidence supports the roles of ANGPTL3 and ANGPTL8 in lipid metabolism through inhibition of lipoprotein lipase and endothelial lipase activity. ANGPTL3 and ANGPTL3/8 inhibitors are effective in lowering plasma triglycerides and low-density lipoprotein (LDL)-cholesterol, with the possible advantage of raising high-density lipoprotein (HDL)-cholesterol with the inhibition of ANGPTL3/8. Therapeutic inhibition of ANGPTL3 and ANGPTL3/8 can lower plasma triglyceride and LDL-cholesterol levels possibly by lowering production and upregulating catabolism of triglyceride-rich lipoprotein and LDL particles. However, the effect of these novel agents on HDL metabolism remains unclear. The cardiovascular benefits of ANGPTL3 and ABGPTL3/8 inhibitors may also include improvement in vascular inflammation, but this requires further investigation.

Purpose of review: Statins are first-line pharmacotherapy for the treatment of elevated low-density lipoprotein cholesterol and are generally well-tolerated. However, some patients may experience statin-associated muscle symptoms (SAMS). This paper reviews recommendations for identification and management of patients with SAMS.

Recent findings: The National Lipid Association and other professional societies have issued guidance to assist clinicians in identifying and managing patients with partial or complete statin intolerance. The most common reason for intolerance is SAMS. This review discusses strategies to achieve therapeutic objectives for atherogenic lipoprotein management in patients with SAMS. Many patients who experience SAMS can tolerate some degree of statin therapy and non-statin medications are available as adjunctive or alternative treatments. With a thorough clinician-patient discussion and shared decision-making, a treatment plan can be identified to achieve therapeutic objectives and reduce the risk of atherosclerotic cardiovascular disease.

Purpose of review: There is a growing recognition of plaque erosion as a cause of acute coronary syndrome. This review aims to examine the potential involvement of T cells in this process.

Recent findings: Immune-vascular interactions have been identified in the development of plaque erosions. Up to one-third of eroded plaques show evidence of active immune infiltration, with the presence of T cells. We propose that microerosions may frequently occur in association with the infiltration of T cells and macrophages in early atherosclerotic lesions. Healing of erosions could trigger the deposition of excessive extracellular matrix. The pro-inflammatory and cytotoxic actions of T cells, along with reduced endothelial integrity and other mechanisms, may subsequently give rise to clinical symptoms. To gain a better understanding of the role of T cells in plaque erosion, it is crucial to develop improved models for conducting controlled experiments and to study atherosclerosis in younger individuals.

Purpose of review: Multiple agents are being developed that inhibit apolipoprotein (apo) C-III. This state-of-the-art review examines their potential for atherosclerotic cardiovascular disease (ASCVD) risk reduction.

Recent findings: Apo C-III, an apolipoprotein on the surface of triglyceride-rich lipoproteins (TRLs), impairs clearance of TRLs through both lipoprotein lipase dependent and independent pathways, thereby resulting in increased concentrations of triglycerides. Apo C-III has also been shown to have pro-atherogenic effects when bound to high-density lipoprotein (HDL) particles. Classical and genetic epidemiology studies provide support for the concept that apo C-III is associated with an increased risk of ASCVD events. Drug efficacy of agents that silence APOC3 mRNA has been studied in populations with varying hypertriglyceridemia severity, including those with familial chylomicronemia syndrome, multifactorial chylomicronemia syndrome/severe hypertriglyceridemia, and mixed hyperlipidemia. Randomized controlled trials have reported significant reductions in TG and non-HDL cholesterol levels among these patients treated with APOC3 inhibitors. Upcoming clinical outcomes trials seek to establish a role for APOC3 inhibitors to reduce risk of ASCVD.