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NAD+ metabolism and therapeutic strategies in cardiovascular diseases 心血管疾病中的 NAD+ 代谢和治疗策略
IF 1.6 Pub Date : 2024-06-11 DOI: 10.1016/j.athplu.2024.06.001
Chongxu Shi , Zhaozhi Wen , Yihang Yang , Linsheng Shi , Dong Liu

Nicotinamide adenine dinucleotide (NAD+) is a central and pleiotropic metabolite involved in cellular energy metabolism, cell signaling, DNA repair, and protein modifications. Cardiovascular diseases (CVDs) are the leading cause of death worldwide. Metabolic stress and aging directly affect the cardiovascular system. Compelling data suggest that NAD + levels decrease with age, obesity, and hypertension, which are all notable risk factors for CVD. In addition, the therapeutic elevation of NAD + levels reduces chronic low-grade inflammation, reactivates autophagy and mitochondrial biogenesis, and enhances oxidative metabolism in vascular cells of humans and rodents with vascular disorders. In preclinical models, NAD + boosting can also expand the health span, prevent metabolic syndrome, and decrease blood pressure. Moreover, NAD + storage by genetic, pharmacological, or natural dietary NAD + -increasing strategies has recently been shown to be effective in improving the pathophysiology of cardiac and vascular health in different animal models, and human health. Here, we review and discuss NAD + -related mechanisms pivotal for vascular health and summarize recent experimental evidence in NAD + research directly related to vascular disease, including atherosclerosis, and coronary artery disease. Finally, we comparatively assess distinct NAD + precursors for their clinical efficacy and the efficiency of NAD + elevation in the treatment of major CVD. These findings may provide ideas for new therapeutic strategies to prevent and treat CVD in the clinic.

烟酰胺腺嘌呤二核苷酸(NAD+)是一种参与细胞能量代谢、细胞信号传导、DNA 修复和蛋白质修饰的核心多效代谢物。心血管疾病(CVD)是导致全球死亡的主要原因。代谢压力和衰老直接影响心血管系统。令人信服的数据表明,NAD + 水平会随着年龄、肥胖和高血压的增加而降低,而这些都是心血管疾病的显著风险因素。此外,治疗性提高 NAD + 水平可减少慢性低度炎症,重新激活自噬和线粒体生物生成,并增强患有血管疾病的人类和啮齿动物血管细胞的氧化代谢。在临床前模型中,增加 NAD + 还能延长健康寿命、预防代谢综合征和降低血压。此外,通过遗传、药物或天然膳食增加 NAD + 的策略来储存 NAD + 最近已被证明能有效改善不同动物模型的心脏和血管健康的病理生理学以及人类健康。在此,我们回顾并讨论了对血管健康至关重要的 NAD + 相关机制,并总结了与血管疾病(包括动脉粥样硬化和冠状动脉疾病)直接相关的 NAD + 研究的最新实验证据。最后,我们比较评估了不同的 NAD + 前体在治疗主要心血管疾病方面的临床疗效和 NAD + 升高的效率。这些发现可能会为临床上预防和治疗心血管疾病的新治疗策略提供思路。
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引用次数: 0
Trends in cardiovascular disease among Inuit in Greenland from 1994 to 2021 1994 至 2021 年格陵兰因纽特人患心血管疾病的趋势
IF 1.6 Pub Date : 2024-04-25 DOI: 10.1016/j.athplu.2024.04.002
Hjalte Erichsen Larsen , Uka Wilhjelm Geisler , Finn Gustafsson , Michael Lynge Pedersen , Marit Eika Jørgensen

Background and aims

Cardiovascular disease (CVD) poses significant health challenges globally. While substantial data exists for most populations, the Arctic Inuit's CVD incidence rates remain understudied. This research aimed to change this by estimating CVD incidence and mortality rates in Greenland from 1994 to 2021.

Methods

Using nationwide registers, a retrospective observational study was conducted, focusing on individuals born in Greenland to Greenlandic-born parents. Data were sourced from the Greenlandic Hospital Discharge Register and the nationwide electronic medical record.

Results

A total of 65,824 individuals were included. the age- and sex-specific incidence rates (IR) of ischemic heart disease, stroke, and heart failure (HF) declined from 1994 to 2021, with the most substantial decline observed for HF among women. Conversely, the IR of atrial fibrillation/flutter increased in both men and women, while the IR of myocardial infarction rose among men. The IR for stroke was particularly elevated compared to other CVD subgroups. Mortality rates for those diagnosed with CVD were 2.4 times higher than those without. Men exhibited a 40 % elevated mortality risk relative to women.

Conclusion

The study provides pivotal insights into CVD trends within the Arctic Inuit population, highlighting both positive developments and areas of concern. Given the increasing elderly demographic in Greenland, proactive health strategies are crucial. Emphasizing primary prevention and addressing specific CVD risks, particularly the elevated stroke IR, is imperative for future public health efforts.

背景和目的心血管疾病(CVD)对全球健康构成重大挑战。虽然大多数人群都有大量数据,但北极因纽特人的心血管疾病发病率仍未得到充分研究。这项研究旨在通过估算 1994 年至 2021 年格陵兰岛心血管疾病的发病率和死亡率来改变这一现状。方法利用全国范围内的登记资料,开展了一项回顾性观察研究,重点关注父母均为格陵兰人、在格陵兰岛出生的人。结果共纳入 65,824 人。从 1994 年到 2021 年,缺血性心脏病、中风和心力衰竭(HF)的年龄和性别特异性发病率(IR)均有所下降,其中女性心力衰竭的发病率下降幅度最大。相反,男性和女性的心房颤动/扑动发病率均有所上升,而男性的心肌梗死发病率则有所上升。与其他心血管疾病亚组相比,中风的内因指数特别高。确诊为心血管疾病的患者死亡率是未确诊者的 2.4 倍。该研究为了解北极因纽特人的心血管疾病趋势提供了重要依据,突出了积极的发展和值得关注的领域。鉴于格陵兰岛老年人口不断增加,积极的健康战略至关重要。强调初级预防和应对特定的心血管疾病风险,尤其是中风 IR 的升高,是未来公共卫生工作的当务之急。
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引用次数: 0
Carotid intimamedia thickness in patients with severe hypertriglyceridemia 严重高甘油三酯血症患者的颈动脉内膜厚度
IF 1.6 Pub Date : 2024-04-21 DOI: 10.1016/j.athplu.2024.04.001
Maud Ahmad , Brooke A. Kennedy , Surim Son , Adam D. McIntyre , Julieta Lazarte , Jian Wang , Robert A. Hegele

Background and aims

Severe hypertriglyceridemia (HTG), defined as plasma triglyceride (TG) concentration > 10 mmol/L, is relatively uncommon, and its implications for atherosclerotic cardiovascular disease (ASCVD) risk remain somewhat unclear. We evaluated the association between severe HTG and carotid intima-media thickness (IMT), a marker for ASCVD.

Methods

We studied three clinical cohorts: 88 patients with severe HTG (mean TG level 20.6 mmol/L), 271 patients with familial hypercholesterolemia (FH) as a contrast group, and 70 normolipidemic controls. Carotid IMT was measured using standardized ultrasound imaging. Statistical analysis was conducted using one-way analysis of variance (ANOVA) to compare mean IMT values, analysis of covariance (ANCOVA) to adjust for confounding variables, specifically age and sex, as well as Spearman pairwise correlation analysis between variables.

Results

Unadjusted mean carotid IMT was greater in severe HTG and FH groups compared to controls, however, this was no longer significant for severe HTG after adjustment for age and sex. In contrast, adjusted carotid IMT remained significantly different between the FH and control groups.

Conclusions

Our findings suggest that extreme TG elevations in severe HTG patients are not significantly associated with carotid IMT, in contrast to the increased IMT seen in FH patients. These findings add perspective to the complex relationship between severe HTG and ASCVD risk.

背景和目的严重的高甘油三酯血症(HTG)定义为血浆甘油三酯(TG)浓度大于或等于 10 mmol/L,这种情况相对少见,其对动脉粥样硬化性心血管疾病(ASCVD)风险的影响仍不明确。我们评估了重度高血脂症与 ASCVD 标志物--颈动脉内膜中层厚度(IMT)之间的关系:我们研究了三个临床队列:88 名重度高胆固醇血症患者(平均 TG 水平为 20.6 mmol/L)、271 名作为对比组的家族性高胆固醇血症(FH)患者和 70 名血脂正常的对照组。采用标准化超声成像测量颈动脉内中膜厚度。统计分析采用单因素方差分析(ANOVA)比较平均IMT值,协方差分析(ANCOVA)调整混杂变量,特别是年龄和性别,以及变量之间的斯皮尔曼配对相关分析。结论我们的研究结果表明,重度高血压患者的总胆固醇极度升高与颈动脉内径无明显关系,这与高脂血症患者的颈动脉内径增大形成鲜明对比。这些发现为重度高血压与 ASCVD 风险之间的复杂关系增添了新的视角。
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引用次数: 0
Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial 胰高血糖素样肽-1 类似物与他汀类药物治疗的 2 型糖尿病冠心病患者冠状动脉粥样斑块的脱脂作用:OPTIMAL 随机临床试验的预设子分析
IF 1.6 Pub Date : 2024-04-04 DOI: 10.1016/j.athplu.2024.03.001
Yu Kataoka , Satoshi Kitahara , Sayaka Funabashi , Hisashi Makino , Masaki Matsubara , Miki Matsuo , Yoko Omura-Ohata , Ryo Koezuka , Mayu Tochiya , Tamiko Tamanaha , Tsutomu Tomita , Kyoko Honda-Kohmo , Michio Noguchi , Kota Murai , Kenichiro Sawada , Takamasa Iwai , Hideo Matama , Satoshi Honda , Masashi Fujino , Kazuhiro Nakao , Teruo Noguchi

Background and aims

Randomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet.

Methods

The OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72).

Results

All patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02).

Conclusions

In statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

背景和目的随机临床试验证明,胰高血糖素样肽-1类似物(GLP-1RA)能够减少2型糖尿病(T2D)患者的动脉粥样硬化性心血管疾病事件。方法OPTIMAL研究是一项前瞻性随机对照研究,目的是在94名经他汀治疗的T2D患者中比较48周连续血糖监测和HbA1c指导的血糖控制对近红外光谱(NIRS)/血管内超声(IVUS)得出的斑块测量结果的疗效(jRCT1052180152,UMIN000036721)。结果所有患者都接受了他汀类药物治疗,两组患者治疗时的 LDL-C 水平相似(66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL,p = 0.84)。接受 GLP-1RAs 治疗的患者 HbA1c 下降幅度更大 [-1.0 (-1.4 to -0.5) vs. -0.4 (-0.6 to -0.2)%,p = 0.02],出现血糖水平 >180 mg/dL [-7.5 (-14.9 to -0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04],同时残余胆固醇水平显著下降[-3.8 (-6.3 to -1.3) vs. -0.1 (-0.8 - 1.1)mg/dL, p = 0.008]。在 NIRS/IVUS 成像分析中,两组之间动脉粥样斑块体积百分比的变化没有差异(-0.9 ± 0.25 vs. -0.2 ± 0.2%,p = 0.23)。然而,GLP-1RA 治疗患者的 maxLCBI4mm 回归率更高(85.6 ± 0.1 vs. 42.0 ± 0.6%,p = 0.01)。多变量分析表明,GLP-1RA 的使用与 maxLCBI4mm 的消退独立相关(几率比 = 4.41,95%CI = 1.19-16.30,p = 0.02)。
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引用次数: 0
The effect of hydroxychloroquine on cholesterol synthesis depends on the profile of cholesterol metabolism. A controlled clinical study 羟氯喹对胆固醇合成的影响取决于胆固醇代谢情况。临床对照研究
IF 1.6 Pub Date : 2024-03-01 DOI: 10.1016/j.athplu.2024.02.002
Piia Simonen , Lotta Ulander , Kari K. Eklund , Mikko Niemi , Janne T. Backman , Helena Gylling , Juha Sinisalo , OXI pilot trial

Background and aims

Hydroxychloroquine (HCQ) has a variable effect on cholesterol synthesis. To clarify this, we assessed the effect of HCQ on the cholesterol-synthesis pathway in individuals with low and high cholesterol absorption efficiency.

Method

A total of 53 acute myocardial infarction patients with a constant statin dose randomized to receive HCQ or placebo for six months in a double-blind manner, were classified further into low (n = 26) and high (n = 27) cholesterol absorbers based on the median baseline serum cholestanol level. Serum lipids and biomarkers of cholesterol synthesis (squalene, lanosterol, zymostenol, desmosterol, and lathosterol) and absorption efficiency (sitosterol and cholestanol), were measured at baseline and one-, six-, and 12-month follow-up visits.

Results

In low cholesterol absorbers, serum cholesterol concentration and cholesterol synthesis and absorption biomarkers did not differ between the HCQ and placebo groups. At one month, high cholesterol absorbers with HCQ had lower serum cholesterol concentration and serum lanosterol to cholesterol ratio in comparison to the placebo group (HCQ 3.18 ± 0.62 vs. placebo 3.71 ± 0.65, p = 0.042, and HCQ 10.4 ± 2.55 vs. placebo 13.1 ± 2.36, p = 0.008, respectively). At 12 months, serum desmosterol to cholesterol ratio was lower in HCQ users (HCQ 47.1 ± 7.08 vs. placebo 59.0 ± 13.1, p = 0.011).

Conclusions

HCQ affects the cholesterol-synthesis pathway in high cholesterol absorbers. It reduces serum lanosterol and desmosterol ratios and consequently serum cholesterol concentration possibly by inhibiting the activity of lanosterol synthase as described earlier in vitro studies.

Trial registration

ClinicalTrials.gov Identifier: NCT02648464.

背景和目的羟基氯喹(HCQ)对胆固醇合成的影响各不相同。为了澄清这一点,我们评估了HCQ对胆固醇吸收效率低和高的人的胆固醇合成途径的影响。方法 共有53名急性心肌梗死患者,他们在双盲的情况下随机接受HCQ或安慰剂治疗6个月,并根据血清胆固醇吸收效率的中位数水平进一步分为胆固醇吸收效率低的人(26人)和胆固醇吸收效率高的人(27人)。结果 在低胆固醇吸收者中,血清胆固醇浓度、胆固醇合成和吸收生物标志物(角鲨烯、羊毛甾醇、颧烯醇、去甲斑蝥素和板蓝根醇)在 HCQ 组和安慰剂组之间没有差异。一个月后,与安慰剂组相比,使用 HCQ 的高胆固醇吸收者的血清胆固醇浓度和血清羊毛甾醇与胆固醇的比率较低(HCQ 3.18 ± 0.62 vs. 安慰剂 3.71 ± 0.65,p = 0.042;HCQ 10.4 ± 2.55 vs. 安慰剂 13.1 ± 2.36,p = 0.008)。12 个月后,HCQ 使用者的血清去脂醇和胆固醇比率降低(HCQ 47.1 ± 7.08 vs. 安慰剂 59.0 ± 13.1,p = 0.011)。它降低了血清中的羊毛甾醇和脱毛甾醇比率,从而降低了血清中的胆固醇浓度,这可能是通过抑制羊毛甾醇合成酶的活性实现的,正如之前的体外研究中所描述的那样:NCT02648464。
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引用次数: 0
Treatment intensification with bempedoic acid to achieve LDL-C goal in patients with ASCVD: A simulation model using a real-world patient cohort in the US 使用贝母倍多酸加强治疗以实现 ASCVD 患者的低密度脂蛋白胆固醇目标:使用美国真实世界患者队列的模拟模型
IF 1.6 Pub Date : 2024-03-01 DOI: 10.1016/j.athplu.2024.01.006
Kristen Migliaccio-Walle , David Elsea , Anand Gupta , Evelyn Sarnes , Kristel Griffith , Rajshree Pandey , Kristin Gillard

Background and aims

Guidelines recommend that high-risk patients with atherosclerotic cardiovascular disease (ASCVD) be treated with maximally tolerated statins to lower low-density lipoprotein cholesterol (LDL-C) levels and reduce the risk of major adverse cardiovascular events. In patients whose LDL-C remains elevated, non-statin adjunct therapies, including ezetimibe (EZE), bempedoic acid (BA), and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are recommended.

Methods

The impact of BA and EZE in a fixed-dose combination (FDC) on LDL-C goal attainment was evaluated using a simulation model developed for a United States cohort of high-risk adults with ASCVD. Treatment was simulated for 73,056 patients not at goal (LDL-C >70 mg/dL), comparing BA + EZE (FDC), EZE only, and no oral adjunct therapy (NOAT). The addition of PCSK9 inibitors was assumed after 1 year in patients not at LDL-C goal. Treatment efficacy was estimated from clinical trials. Patient-level outcomes were predicted over a 10-year horizon accounting for treatment discontinuation and general mortality.

Results

Baseline mean age of the cohort was 67 years, most were White (79%) and male (56%). A majority had established coronary artery disease (75%), 48% had diabetes, and mean LDL-C was 103.0 mg/dL. After 1 year, 79% of patients achieved LDL-C goal (mean, 61.1 mg/dL) with BA + EZE (FDC) compared to 58% and 42% with EZE (71.7 mg/dL) and NOAT (78.4 mg/dL), respectively.

Conclusions

This simulation shows that adding BA + EZE (FDC) to maximally tolerated statins would result in more patients achieving LDL-C goal than adding EZE alone or NOAT.

背景和目的指南建议动脉粥样硬化性心血管疾病(ASCVD)高危患者接受最大耐受量他汀类药物治疗,以降低低密度脂蛋白胆固醇(LDL-C)水平,减少主要不良心血管事件的风险。对于低密度脂蛋白胆固醇(LDL-C)仍然升高的患者,建议使用非他汀类辅助疗法,包括依折麦布(EZE)、贝美多酸(BA)和9型丙蛋白转换酶亚基酶/kexin(PCSK9)抑制剂。方法使用针对美国高风险成人 ASCVD 患者队列开发的模拟模型,评估了固定剂量复方制剂(FDC)中的 BA 和 EZE 对实现 LDL-C 目标的影响。对 73,056 名未达目标(LDL-C 70 mg/dL)的患者进行了模拟治疗,比较了 BA + EZE(FDC)、仅 EZE 和无口服辅助疗法(NOAT)。假定未达到 LDL-C 目标的患者在 1 年后添加 PCSK9 抑制剂。疗效根据临床试验估算。在考虑治疗中断和一般死亡率的情况下,对 10 年内的患者水平结果进行了预测。大多数患者已患有冠状动脉疾病(75%),48%患有糖尿病,平均低密度脂蛋白胆固醇为 103.0 mg/dL。1 年后,79% 的患者使用 BA + EZE (FDC) 达到了 LDL-C 目标(平均值为 61.1 mg/dL),而使用 EZE(71.7 mg/dL)和 NOAT(78.4 mg/dL)的患者分别为 58% 和 42%。
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引用次数: 0
Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023 希腊动脉粥样硬化学会血脂异常诊断和治疗指南执行摘要 - 2023 年
IF 1.6 Pub Date : 2024-02-17 DOI: 10.1016/j.athplu.2024.01.004
Katsiki N , Filippatos Td , Vlachopoulos C , Panagiotakos D , Milionis H , Tselepis A , Garoufi A , Rallidis L , Richter D , Nomikos T , Kolovou G , Kypreos K , Chrysohoou C , Tziomalos K , Skoumas I , Koutagiar I , Attilakos A , Papagianni M , Boutari C , Kotsis V , Liberopoulos E

Atherosclerotic cardiovascular disease (ASCVD) remains the main cause of death worldwide, and thus its prevention, early diagnosis and treatment is of paramount importance. Dyslipidemia represents a major ASCVD risk factor that should be adequately managed at different clinical settings. 2023 guidelines of the Hellenic Atherosclerosis Society focus on the assessment of ASCVD risk, laboratory evaluation of dyslipidemias, new and emerging lipid-lowering drugs, as well as diagnosis and treatment of lipid disorders in women, the elderly and in patients with familial hypercholesterolemia, acute coronary syndromes, heart failure, stroke, chronic kidney disease, diabetes, autoimmune diseases, and non-alcoholic fatty liver disease. Statin intolerance is also discussed.

动脉粥样硬化性心血管疾病(ASCVD)仍然是全球的主要死因,因此其预防、早期诊断和治疗至关重要。血脂异常是动脉粥样硬化性心血管疾病的一个主要风险因素,应在不同的临床环境中加以适当管理。希腊动脉粥样硬化学会 2023 年指南重点关注 ASCVD 风险评估、血脂异常的实验室评估、新出现的降脂药物,以及女性、老年人和家族性高胆固醇血症、急性冠状动脉综合征、心力衰竭、中风、慢性肾病、糖尿病、自身免疫性疾病和非酒精性脂肪肝患者的血脂紊乱诊断和治疗。此外,还讨论了他汀类药物不耐受的问题。
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引用次数: 0
Refined metabolite profiling in the collateral circulation of chronic total occlusion of coronary arteries: Insights from a metabolomics investigation 慢性冠状动脉完全闭塞侧支循环的精细代谢物分析:代谢组学调查的启示
IF 1.6 Pub Date : 2024-02-12 DOI: 10.1016/j.athplu.2024.02.001
Hu Sigan, Li Min, Cheng Zengwei, Gao Shiyi, Kang Pinfang, Gao Dasheng

Background and aims

To investigate the disparities in coronary collateral circulation (CCC) and peripheral serum metabolites among patients presenting with chronic total occlusion (CTO) of the coronary arteries, a non-targeted metabolic approach was employed.

Methods

A cohort of 22 patients diagnosed with CTO of coronary arteries in the context of coronary heart disease (CHD) was selected for blood sample collection from CCC and peripheral arteries. The patients were categorized into two groups, namely CTO-C and CTO-P. The Waters UPLC I-Class Plus is combined with the Q Exactive high-resolution mass spectrometer for metabolite separation and detection. The acquired raw data from mass spectrometry is subsequently imported into Compound Discoverer 3.2 software for comprehensive analysis, which seamlessly integrates the BGI Metabolome Database (BMDB), mzCloud database, and ChemSpider online database. Subsequently, the identified differential metabolites were subjected to a metabolic pathway enrichment analysis, as documented in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database.

Results

A total of 403 differential metabolites were identified in CCC and peripheral serum samples from patients with CTO of coronary arteries in CHD. Compared to the CTO-P group, the CTO-C group exhibited decreased levels of metabolites such as Testosterone, dehydroepiandrosterone (DHA), deoxyacetone, while demonstrating increased levels of metabolites including Progesterone, androstanone, l-threonine. The biosynthesis pathway of steroid hormones emerges as the key metabolic pathway significantly associated with differential metabolites.

Conclusions

Through metabolomics analysis, distinct differences in the CCC and peripheral serum metabolites have been identified among patients with CTO of coronary artery. Notably, a significant association between the steroid hormone biosynthesis pathway and CCC has been observed.

背景和目的为了研究冠状动脉慢性全闭塞(CTO)患者冠状动脉侧支循环(CCC)和外周血清代谢物的差异,我们采用了一种非靶向代谢方法。方法我们选取了22例被诊断为冠状动脉CTO的冠心病(CHD)患者,采集他们的CCC和外周动脉血样本。患者被分为两组,即 CTO-C 组和 CTO-P 组。沃特世 UPLC I-Class Plus 与 Q Exactive 高分辨率质谱仪相结合,用于代谢物的分离和检测。质谱获得的原始数据随后被导入 Compound Discoverer 3.2 软件进行综合分析,该软件无缝集成了 BGI 代谢组数据库(BMDB)、mzCloud 数据库和 ChemSpider 在线数据库。结果 在冠状动脉CTO患者的CCC和外周血清样本中,共鉴定出403种差异代谢物。与CTO-P组相比,CTO-C组睾酮、脱氢表雄酮(DHA)、脱氧丙酮等代谢物水平降低,而黄体酮、雄甾酮、l-苏氨酸等代谢物水平升高。结论通过代谢组学分析,发现冠状动脉 CTO 患者的 CCC 和外周血清代谢物存在明显差异。值得注意的是,类固醇激素生物合成途径与 CCC 之间存在明显关联。
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引用次数: 0
Changing from lipoprotein apheresis to evolocumab treatment lowers circulating levels of arachidonic acid and oxylipins 从脂蛋白清除疗法转为 evolocumab 治疗可降低花生四烯酸和氧脂素的循环水平
IF 1.6 Pub Date : 2024-02-12 DOI: 10.1016/j.athplu.2024.01.005
Chaoxuan Wang , Anne Kaufmann , Nadja Kampschulte , Ulf Elbelt , Ursula Kassner , Elisabeth Steinhagen-Thiessen , Anne Pietzner , Christoph Schmöcker , Dev Datta , Tiziana Sanpietro , Nils Helge Schebb , Karsten-H. Weylandt , Nadine Rohwer

Background and aims

Previous studies have shown that lipoprotein apheresis can modify the plasma lipidome and pro-inflammatory and pro-thrombotic lipid mediators. This has not been examined for treatment with protein convertase subtilisin/kexin type 9 inhibitors such as evolocumab, which are increasingly used instead of lipoprotein apheresis in treatment-resistant familial hypercholesterolemia. The aim of this study was to compare the effects of evolocumab treatment and lipoprotein apheresis on the fatty acid profile and on formation of lipid mediators in blood samples.

Methods

We analyzed blood samples from 37 patients receiving either lipoprotein apheresis or evolocumab treatment as part of a previous study. Patients were stratified according to receiving lipoprotein apheresis (n = 19) and evolocumab treatment (n = 18). Serum fatty acid analysis was performed using gas chromatography flame ionization detection and plasma oxylipin analysis was done using liquid chromatography tandem mass spectrometry.

Results

Changing from lipoprotein apheresis to evolocumab treatment led to lower levels of omega-6 polyunsaturated fatty acid (n-6 PUFA) including arachidonic acid, dihomo-γ-linolenic acid and linoleic acid. Moreover, several n-6 PUFA-derived oxylipins were reduced after evolocumab treatment.

Conclusions

Given that arachidonic acid, either directly or as a precursor, is associated with the development of inflammation and atherosclerosis, evolocumab-mediated reductions of arachidonic acid and its metabolites might have an additional beneficial effect to lower cardiovascular risk.

背景和目的以前的研究表明,脂蛋白清除术可以改变血浆脂质体以及促炎症和促血栓形成的脂质介质。目前还没有对使用蛋白转化酶枯草酶/kexin 9 型抑制剂(如 evolocumab)进行治疗的情况进行研究,在治疗耐药家族性高胆固醇血症时,越来越多地使用 evolocumab 代替脂蛋白清除疗法。本研究旨在比较 evolocumab 治疗和脂蛋白清除术对血液样本中脂肪酸谱和脂质介质形成的影响。患者按接受脂蛋白清除术(19 人)和依维莫单抗治疗(18 人)进行了分层。结果从脂蛋白清除疗法转为依维莫单抗疗法后,包括花生四烯酸、二氢-γ-亚麻酸和亚油酸在内的ω-6多不饱和脂肪酸(n-6 PUFA)水平降低。结论鉴于花生四烯酸直接或作为前体与炎症和动脉粥样硬化的发生有关,evolocumab介导的花生四烯酸及其代谢物的减少可能对降低心血管风险有额外的益处。
{"title":"Changing from lipoprotein apheresis to evolocumab treatment lowers circulating levels of arachidonic acid and oxylipins","authors":"Chaoxuan Wang ,&nbsp;Anne Kaufmann ,&nbsp;Nadja Kampschulte ,&nbsp;Ulf Elbelt ,&nbsp;Ursula Kassner ,&nbsp;Elisabeth Steinhagen-Thiessen ,&nbsp;Anne Pietzner ,&nbsp;Christoph Schmöcker ,&nbsp;Dev Datta ,&nbsp;Tiziana Sanpietro ,&nbsp;Nils Helge Schebb ,&nbsp;Karsten-H. Weylandt ,&nbsp;Nadine Rohwer","doi":"10.1016/j.athplu.2024.01.005","DOIUrl":"https://doi.org/10.1016/j.athplu.2024.01.005","url":null,"abstract":"<div><h3>Background and aims</h3><p>Previous studies have shown that lipoprotein apheresis can modify the plasma lipidome and pro-inflammatory and pro-thrombotic lipid mediators. This has not been examined for treatment with protein convertase subtilisin/kexin type 9 inhibitors such as evolocumab, which are increasingly used instead of lipoprotein apheresis in treatment-resistant familial hypercholesterolemia. The aim of this study was to compare the effects of evolocumab treatment and lipoprotein apheresis on the fatty acid profile and on formation of lipid mediators in blood samples.</p></div><div><h3>Methods</h3><p>We analyzed blood samples from 37 patients receiving either lipoprotein apheresis or evolocumab treatment as part of a previous study. Patients were stratified according to receiving lipoprotein apheresis (n = 19) and evolocumab treatment (n = 18). Serum fatty acid analysis was performed using gas chromatography flame ionization detection and plasma oxylipin analysis was done using liquid chromatography tandem mass spectrometry.</p></div><div><h3>Results</h3><p>Changing from lipoprotein apheresis to evolocumab treatment led to lower levels of omega-6 polyunsaturated fatty acid (n-6 PUFA) including arachidonic acid, dihomo-γ-linolenic acid and linoleic acid. Moreover, several n-6 PUFA-derived oxylipins were reduced after evolocumab treatment.</p></div><div><h3>Conclusions</h3><p>Given that arachidonic acid, either directly or as a precursor, is associated with the development of inflammation and atherosclerosis, evolocumab-mediated reductions of arachidonic acid and its metabolites might have an additional beneficial effect to lower cardiovascular risk.</p></div>","PeriodicalId":72324,"journal":{"name":"Atherosclerosis plus","volume":null,"pages":null},"PeriodicalIF":1.6,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2667089524000051/pdfft?md5=23f877b024fd65e2df6b11040ee4351a&pid=1-s2.0-S2667089524000051-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139748466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Endothelial dysfunction and cardiovascular diseases in people living with HIV on specific highly active antiretroviral therapy regimen: A systematic review of clinical studies 采用特定高活性抗逆转录病毒疗法的艾滋病病毒感染者的内皮功能障碍和心血管疾病:临床研究的系统回顾
IF 1.6 Pub Date : 2024-02-05 DOI: 10.1016/j.athplu.2024.01.003
Haskly Mokoena , Sihle E. Mabhida , Joel Choshi , Phiwayinkosi V. Dludla , Bongani B. Nkambule , Zandile J. Mchiza , Duduzile E. Ndwandwe , André P. Kengne , Sidney Hanser

Despite the improved efficacy of highly active antiretroviral therapy (HAART) in viral suppression, emerging evidence indicates an increased burden of noncommunicable diseases in people living with HIV (PLWH). Immune activation and persistently elevated levels of inflammation have been associated with endothelial dysfunction in PLWH, likely contributing to the development of cardiovascular diseases (CVDs). Here, electronic search databases including PubMed, Google Scholar, Cochrane Library, and Science Direct were used to retrieve scientific evidence reporting on any association between markers of endothelial function and CVD-related outcomes in PLWH on HAART. Extracted data was subjected to quality assessment using the Downs and Black checklist. Most (60 %) of the results indicated the presence of endothelial dysfunction in PLWH on HAART, and this was mainly through reduced flow mediated dilation and elevated serum makers of adhesion molecules like ICAM-1, VCAM-1, and P-selectin. The summarized evidence indicates an association between persistently elevated markers of endothelial dysfunction and a pro-inflammatory state in PLWH on HAART. Only a few studies reported on improved endothelial function markers in PLWH on HAART, while limited evidence is available to prove that endothelial dysfunction is associated with CVD-risk, which could be attributed to therapeutic effects of HAART. Limited studies with relatively high quality of evidence were included in this systematic review. In conclusion, results from this review lay an important foundation for future research, even a meta-analysis, that will improve the understanding of the contributing factors to the burden of CVDs in PLWH on HAART.

尽管高效抗逆转录病毒疗法(HAART)在抑制病毒方面的疗效有所提高,但新出现的证据表明,艾滋病病毒感染者(PLWH)的非传染性疾病负担加重。免疫激活和持续升高的炎症水平与艾滋病病毒感染者的内皮功能障碍有关,可能会导致心血管疾病(CVDs)的发生。在此,我们使用电子检索数据库(包括PubMed、Google Scholar、Cochrane Library和Science Direct)检索了有关接受HAART治疗的PLWH患者内皮功能标志物与心血管疾病相关结果之间关系的科学证据。提取的数据采用唐斯和布莱克核对表进行质量评估。大多数(60%)研究结果表明,接受 HAART 治疗的 PLWH 存在内皮功能障碍,主要表现为血流介导的扩张减少以及血清中 ICAM-1、VCAM-1 和 P-selectin 等粘附分子的含量升高。总结的证据表明,在接受 HAART 治疗的 PLWH 患者中,内皮功能障碍标志物的持续升高与促炎状态之间存在关联。只有少数研究报告了接受 HAART 治疗的 PLWH 患者的内皮功能指标有所改善,而证明内皮功能障碍与心血管疾病风险相关的证据有限,这可能是由于 HAART 的治疗效果所致。本系统综述纳入了证据质量相对较高的有限研究。总之,本综述的结果为今后的研究(甚至是荟萃分析)奠定了重要基础,有助于更好地了解导致接受 HAART 治疗的 PLWH 患者心血管疾病负担的因素。
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引用次数: 0
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Atherosclerosis plus
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