Current Atherosclerosis Reports最新文献

Purpose of review: This article sumarizes pathopysiological consequencies between obesity and dyslipidemia and aims to bring some practical approach.

Recent findings: Dyslipidemia is often present in individuals with obesity and simultaneusly, many obese individuals have lipid metabolism disorders. Especially the abdominal obesity increases the cardiometabolic risk because of the presence of atherogenic dyslipidemia while the total low density lipoprotein cholesterol (LDL-C) may be normal. LDL-C is the primary goal in dyslipidemia treatment. Apoliprotein B (Apo B) and non - high density lipoprotein cholesterol (non-HDL-C) should be estimated to precise the cardiovascular risk and represents the secondary goal in treatment. Weight loss either with diet or antiobestic medication induces the decrease in triglycerides (TG) and LDL-C and the increase in HDL-C. Composition of nutrients, esp. fatty acids, influences lipid levels. Bariatric surgery is efficient in weight loss and has a significant effect on serum lipids. Dyslipidemia and obesity present common diseases that must be managed to decrease the cardiovascular risk and the risk of obesity-related complications.

Purpose of review: High-density lipoproteins (HDL) have long been regarded as an antiatherogenic lipoprotein species by virtue of their role in reverse cholesterol transport (RCT), as well as their established anti-inflammatory and antioxidant properties. For decades, HDL have been an extremely appealing therapeutic target to combat atherosclerotic cardiovascular diseases (ASCVD).

Recent findings: Unfortunately, neither increasing HDL with drugs nor direct infusions of reconstituted HDL have convincedly proven to be positive strategies for cardiovascular health, raising the question of whether we should abandon the idea of considering HDL as a treatment target. The results of two large clinical trials, one testing the latest CETP inhibitor Obicetrapib and the other testing the infusion of patients post-acute coronary events with reconstituted HDL, are still awaited. If they prove negative, these trials will seal the fate of HDL as a direct therapeutic target. However, using HDL as a therapeutic agent still holds promise if we manage to optimize their beneficial properties for not only ASCVD but also outside the cardiovascular field.

Purpose of review: The goal of this review was to summarize contemporary evidence surrounding sex differences in heart transplantation (HT).

Recent findings: Women have steadily comprised approximately 25% of waitlist candidates and HT recipients. This disparity is likely multifactorial with possible explanations including barriers in referral to advanced heart failure providers, implicit bias, and concerns surrounding sensitization. Women continue to experience higher waitlist mortality at the highest priority tiers. After HT, there are differences in post-transplant complications and outcomes. Future areas of study should include sex differences in noninvasive surveillance, renal outcomes after transplantation, and patient-reported outcomes. There are important sex-specific considerations that impact candidate selection, donor matching, waitlist and post-transplant outcomes. Concerted efforts are needed to improve referral patterns to ensure transplantation is allocated equally.

Purpose of review: Chronic kidney disease (CKD) is increasingly prevalent worldwide and is associated with increased cardiovascular risk. New therapeutic options to slow CKD progression and reduce cardiovascular morbidity and mortality have recently emerged. This review highlights recent evidence and gaps in knowledge in emerging CKD preventive strategies.

Recent findings: EMPA-Kidney trial found that empagliflozin, a sodium-glucose co-transporter 2 inhibitor (SGLT2i) led to 28% lower risk of progression of kidney disease or death from cardiovascular causes, compared to placebo. This reinforced the previous findings from DAPA-CKD and CREDENCE trials and led to inclusion of SGLT2i as the cornerstone of CKD preventive therapy in both diabetic and non-diabetic CKD. Finerenone, a selective nonsteroidal mineralocorticoid receptor antagonist, slowed diabetic kidney disease progression by 23% compared to placebo in a pool analysis of FIDELIO-DKD and FIGARO-DKD trials. Non-pharmacological interventions, including low protein diet, and early CKD detection and risk stratification strategies based on novel biomarkers have also gained momentum. Ongoing efforts to explore the wealth of molecular mechanisms in CKD, added to integrative omics modeling are well posed to lead to novel therapeutic targets in kidney care. While breakthrough pharmacological interventions continue to improve outcomes in CKD, the heterogeneity of kidney diseases warrants additional investigation. Further research into specific kidney disease mechanisms will facilitate the identification of patient populations most likely to benefit from targeted interventions.

Purpose of review: The purpose of this review is to summarize the most recent findings investigating the impact of several natural sirtuin (SIRT) activators, particularly SIRT1, on atherosclerosis.

Recent findings: Sirtuins that belong to a family of class III histone deacetylases are believed to be novel therapeutic targets to treat age-related and chronic diseases. SIRT expression is regulated by small molecules called SIRT-activating compounds that can be found in natural food products. SIRT1 may exert protective effects in atherosclerosis, which is said to be a major cause of cardiovascular diseases. Most of the evidence supporting the beneficial effects of these natural compounds comes from in vitro or animal-based studies, while there have been particularly few or inconsistent human-based studies evaluating their long-term impact in recent years. SIRT1 activation has been demonstrated to mitigate or prevent atherosclerosis through various mechanisms. However, further research is required to determine the optimal SIRT activator dosage and to establish a stronger correlation between health effects and the administration of bioactive compounds. Additionally, conducting more human clinical trials is necessary to ensure the safety of these compounds for preventing atherosclerosis development.

Purpose of review: Characterize the risk of cardiovascular disease (CVD) in individuals with polycystic ovarian syndrome (PCOS). Review the pathophysiological pathways that confers CVD risk in individuals with PCOS and interventions to reduce CVD risk.

Recent findings: PCOS is a complex syndrome characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries that has metabolic and cardiovascular implications. Intrinsic hormonal dysregulation and chronic low-grade inflammation play an important role in the progression of atherosclerosis in young premenopausal individuals and development of CVD independently of associated traditional risk factors. Management with metformin reduces CVD risk by reducing atherosclerosis progression. PCOS is an important CVD risk factor among individuals of reproductive age. Early detection and interventions are needed to mitigate development of CVD.

Purpose of review: This review aims to summarize the existing research on sex differences in familial hypercholesterolemia (FH) across the lifespan.

Recent findings: From childhood onward, total- and low-density lipoprotein cholesterol (LDL-C) levels in girls are higher than those in boys with FH. By the age of 30 years, women with FH have a higher LDL-C burden than men. In adulthood, women are diagnosed later than men, receive less lipid-lowering treatment, and consequently have higher LDL-C levels. An excessive atherosclerotic cardiovascular disease risk is reported in young female compared to male FH patients. The periods of pregnancy and breastfeeding contribute to treatment loss and increased cholesterol burden. Earlier initiation of treatment, especially in girls with FH, and lifelong treatment during all life stages are important. Future research should aim to recruit both women and men, report sex-specific data, and investigate the impact of the female life course on cardiovascular outcomes. Future guidelines should include sex-specific aspects.

Purpose of review: This review aimed to determine the association between statin use and coronary artery calcification (CAC), as detected by computed tomography in the general population, in previously published observational studies (OSs) and randomized controlled trials (RCTs).

Recent findings: A systematic search until February 2022 identified 41 relevant studies, comprising 29 OSs and 12 RCTs. We employed six meta-analysis models, stratifying studies based on design and effect metrics. For cohort studies, the pooled β of the association with CAC quantified by the Agatston score was 0.11 (95% CI = 0.05; 0.16), with an average follow-up time per person (AFTP) of 3.68 years. Cross-sectional studies indicated a pooled odds ratio of 2.11 (95% CI = 1.61; 2.78) for the presence of CAC. In RCTs, the pooled standardized mean differences (SMDs) for CAC, quantified by Agatston score or volume, over and AFTP of 1.25 years were not statistically significant (SMD =  - 0.06, 95% CI =  - 0.19; 0.06 and SMD = 0.26, 95% CI =  - 0.66; 1.19), but significantly different (p-value = 0.04). Meta-regression and subgroup analyses did not show any significant differences in pooled estimates across covariates. The effect of statins on CAC differs across study designs. OSs demonstrate associations between statin use and higher CAC scores and presence while being prone to confounding by indication. Effects from RCTs do not reach statistical significance and vary depending on the quantification method, hampering drawing conclusions. Further investigations are required to address the limitations inherent in each approach.

Purpose of review: Atherosclerotic cardiovascular disease (ASCVD) is still the leading cause of death worldwide. Despite excellent pharmacological approaches, clinical registries consistently show that many people with dyslipidemia do not achieve optimal management, and many of them are treated with low-intensity lipid-lowering therapies. Beyond the well-known association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular prevention, the atherogenicity of lipoprotein(a) and the impact of triglyceride (TG)-rich lipoproteins cannot be overlooked. Within this landscape, the use of RNA-based therapies can help the treatment of difficult to target lipid disorders.

Recent findings: The safety and efficacy of LDL-C lowering with the siRNA inclisiran has been documented in the open-label ORION-3 trial, with a follow-up of 4 years. While the outcome trial is pending, a pooled analysis of ORION-9, ORION-10, and ORION-11 has shown the potential of inclisiran to reduce composite major adverse cardiovascular events. Concerning lipoprotein(a), data of OCEAN(a)-DOSE trial with olpasiran show a dose-dependent drop in lipoprotein(a) levels with an optimal pharmacodynamic profile when administered every 12 weeks. Concerning TG lowering, although ARO-APOC3 and ARO-ANG3 are effective to lower apolipoprotein(apo)C-III and angiopoietin-like 3 (ANGPTL3) levels, these drugs are still in their infancy. In the era moving toward a personalized risk management, the use of siRNA represents a blossoming armamentarium to tackle dyslipidaemias for ASCVD risk reduction.

Purpose of review: Stroke is the second leading cause of death and disability-adjusted life years worldwide, and the global lifetime risk of stroke is rising. Moreover, patients with a prior stroke are at high risk of recurrent events. We aimed at reviewing the evidence supporting aggressive secondary prevention strategies for lipid-lowering treatment in this population.

Recent findings: Statins are the key players in such aggressive management; however, stroke survivors remain at significant residual risk suggesting the need for both better implementation of statin use as well as additional lipid lowering therapies. Newer drugs have become available and represent important tools in the management of patients with prior ischemic stroke. The role of lipid lowering treatment in hemorrhagic stroke is more controversial, given epidemiological data linking low lipid levels with increased risk of first and recurrent events. Aggressive secondary prevention strategies, including lipid lowering treatments, have proven to mitigate the risk of recurrent events in post-stroke patients. The tools available for treating such high-risk population have expanded beyond statins, and clinicians should familiarize themselves with them.