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Treatment of dyslipidemia in acute coronary syndrome 急性冠状动脉综合征血脂异常的治疗。
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2024.01.011
Satyavir Yadav , Jitendra Pal Singh Sawhney

Despite numerous improvements in the management of acute coronary syndrome(ACS), it is a major cause of mortality in India. Lipids play a critical role in pathogenesis of ACS and reduction of lipid parameters plays a pivotal role in secondary prevention. High total cholesterol and high low-density lipoprotein(LDL) are the major lipid abnormalities globally as well as in Indians. Among all the lipid parameters, LDL is the primary target of lipid-lowering therapies across the globe. High-dose statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and bempedoic acid are recommended therapies for LDL reduction in ACS patients. Statins have pleiotropic effects on the modulation of thrombogenesis, endothelial dysfunction, and myocardial protection. Multiple randomised controlled trials and meta-analyses have shown that the use of high-dose statin has significant benefits in ACS. LDL reduction goal is < 55 mg/dl or at least 50 % reduction from the baseline regardless of age or gender. Non-fasting LDL should be measured soon after the ACS as it varies minimally with food intake. The first line of therapy after ACS is to advise lifestyle modifications, combination therapy including high-dose statin with ezetimibe, and evaluation after 4–6 weeks of the index event. If the goal is not achieved then PCSK 9 inhibitors or Bempedoic acid should be used in combination with statins and ezetimibe to reduce recurrent ischaemic events. Despite the proven effect of these lipid-lowering therapies, undertreatment is still a big hurdle across the globe. Prohibitive costs, adverse effects, medication non-adherence, variation in health practice in different countries, and clinical inertia to prescribe this medication by physicians are the main reasons for the undertreatment.

尽管在急性冠状动脉综合征的治疗方面取得了许多进展,但它仍然是印度人死亡的一个主要原因。血脂在 ACS 的发病机制中起着至关重要的作用,降低血脂参数在二级预防中起着关键作用。高总胆固醇和高低密度脂蛋白是全球和印度人的主要血脂异常。在所有血脂参数中,低密度脂蛋白是全球降脂疗法的主要目标。大剂量他汀类药物、依折麦布、PCSK 9 抑制剂和贝贝多克酸是降低 ACS 患者低密度脂蛋白的推荐疗法。他汀类药物在调节血栓形成、内皮功能障碍和心肌保护方面具有多效应。多项临床试验和荟萃分析表明,使用大剂量他汀类药物对 ACS 有显著疗效。降低低密度脂蛋白的目标是
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引用次数: 0
Lipid clinical trials with special reference to Indian population 特别针对印度人口的血脂临床试验。
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2024.02.003
Aseem Basha, Sivasubramanian Ramakrishnan

Indians have a pattern of atherogenic dyslipidaemia characterised by not so high LDL-C but elevated small, dense LDL-C, elevated triglyceride levels and low HDL-C levels. In addition, different lipid-lowering drugs exhibit pharmacokinetic variability in Indians, which may have implications on the optimum doses required to achieve the desired LDL-C levels. Currently the management of dyslipidaemia in Indians are based on the landmark trials, which largely included western population. This review focusses on major clinical trials of lipid lowering drugs with special reference to the Indian population.

印度人的动脉粥样硬化性血脂异常的特点是低密度脂蛋白胆固醇(LDL-C)并不高,但小而密集的低密度脂蛋白胆固醇(LDL-C)升高,甘油三酯水平升高,而高密度脂蛋白胆固醇(HDL-C)水平较低。此外,不同的降脂药物在印度人体内的药代动力学存在差异,这可能会影响到达到理想 LDL-C 水平所需的最佳剂量。目前,对印度人血脂异常的管理主要基于里程碑式的试验,这些试验主要包括西方人群。本综述重点介绍降脂药物的主要临床试验,并特别关注印度人群。
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引用次数: 0
Role of statins in the management of dyslipidaemia 他汀类药物在治疗血脂异常中的作用
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2023.11.267
Saumitra Ray

Blood cholesterol has firmly been established as a crucial risk factor for the development of atherosclerotic cardiovascular disease (ASCVD) by elegant epidemiological studies. Naturally, means to reduce blood cholesterol level took the centerstage of research in this field. After initial lukewarm results with nicotinic acid, fibrates and some other agents, statins emerged as the most effective class of medicine to reduce blood cholesterol; in particular, the most atherogenic low density lipoprotein cholesterol (LDL-C). Also, they are very safe and well tolerated. As ASCVD comes in various stages, statins have also been tried in different settings, e.g., primary prevention, secondary prevention, as part of coronary intervention strategy, familial hypercholesterolemia, etc. Almost in all clinical scenarios, statins proved themselves to impart clinical benefit. Though side effects of statins are outweighed by their benefits, nonetheless clinicians should detect the side effects early to avoid major problems.

通过严谨的流行病学研究,血液胆固醇已被确定为动脉粥样硬化性心血管疾病(ASCVD)的重要危险因素。自然而然,降低血液胆固醇水平的方法就成了这一领域研究的重点。在最初使用烟酸、纤维酸盐和其他一些药物取得冷淡效果后,他汀类药物成为降低血液胆固醇,尤其是降低最易导致动脉粥样硬化的低密度脂蛋白胆固醇(LDL-C)的最有效药物。而且,他汀类药物非常安全,耐受性良好。由于 ASCVD 可分为不同的阶段,他汀类药物也可在不同的情况下试用,如一级预防、二级预防、作为冠状动脉干预策略的一部分、家族性高胆固醇血症等。几乎在所有临床情况下,他汀类药物都被证明能带来临床益处。虽然他汀类药物的副作用大于其益处,但临床医生应及早发现副作用,以避免出现重大问题。
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引用次数: 0
Dyslipidemia in diabetes 糖尿病患者的血脂异常
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2023.11.002
Sanjay Kalra , Nishant Raizada

Diabetes mellitus is a metabolic disorder that often predisposes to cardiovascular diseases (CVD). CVD is an important cause of morbidity and mortality in diabetes. The typical diabetic dyslipidaemia is characterized by low HDL cholesterol, high triglycerides with mildly increased or even normal LDL. This attenuated rise in LDL is due to the more atherogenic small dense LDL particles. Genetic factors, obesity, lack of physical activity, alcohol abuse, poorly controlled glucose levels are some of the common risk factors for dyslipidaemia. Non-pharmacological management of dyslipidaemia is important and includes modification in the diet, increase in physical activity and efforts to reduce weight. Statins remain the mainstay of pharmacotherapy for dyslipidaemia in diabetes. Due to the small dense LDL, even patients with diabetes who have normal LDL cholesterol, achieve reduction in cardiovascular risk with statin therapy. Those patients who do not achieve acceptable LDL reductions with statin alone can be treated with combination therapy of ezetimibe with statins. Many novel therapies have also emerged such as bempedoic acid and proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors. The targets for LDL cholesterol depend upon the patients underlying cardiovascular risk category. The use of pharmacotherapy for lowering triglycerides in patients with mild to moderate hypertriglyceridemia and diabetes is still a matter of debate. Proper management of dyslipidaemia is critical component of treatment of diabetes mellitus.

糖尿病是一种代谢性疾病,通常容易引发心血管疾病(CVD)。心血管疾病是糖尿病患者发病和死亡的重要原因。典型的糖尿病血脂异常以高密度脂蛋白胆固醇低、甘油三酯高和低密度脂蛋白轻度升高甚至正常为特征。低密度脂蛋白上升幅度减弱的原因是致动脉粥样硬化性更强的小密度低密度脂蛋白颗粒。遗传因素、肥胖、缺乏体育锻炼、酗酒、血糖控制不佳是导致血脂异常的一些常见风险因素。血脂异常的非药物治疗非常重要,包括调整饮食、增加体育锻炼和努力减轻体重。他汀类药物仍然是治疗糖尿病患者血脂异常的主要药物疗法。由于低密度脂蛋白密度较小,即使低密度脂蛋白胆固醇正常的糖尿病患者也能通过他汀类药物治疗降低心血管风险。对于那些单独使用他汀类药物无法达到可接受的低密度脂蛋白降低效果的患者,可以使用依折麦布和他汀类药物联合治疗。此外,还出现了许多新型疗法,如贝母多酸和丙蛋白转化酶枯草酶/kexin 9(PCSK9)抑制剂。低密度脂蛋白胆固醇的目标取决于患者潜在的心血管风险类别。对轻度至中度高甘油三酯血症和糖尿病患者使用药物疗法降低甘油三酯仍存在争议。妥善处理血脂异常是治疗糖尿病的关键组成部分。
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引用次数: 0
Comparative effectiveness and safety of prasugrel and ticagrelor in patients of acute coronary syndrome undergoing percutaneous transluminal coronary angioplasty: A propensity score-matched analysis 普拉格雷和替卡格雷在接受经皮冠状动脉腔内成形术的急性冠状动脉综合征患者中的有效性和安全性比较:倾向评分匹配分析
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2024.03.001
Avik Ray , Ahmad Najmi , Gaurav Khandelwal , Ratinder Jhaj , Balakrishnan Sadasivam

Evidence on comparative effectiveness and safety of prasugrel and ticagrelor post-percutaneous transluminal coronary angioplasty is scarce in Indian population. In a 1:1 propensity score-matched cohort with 71 individuals in each group, the incidence of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization was not significantly different in prasugrel and ticagrelor group (7.04% vs 9.86%; absolute difference, 2.8%; HR, 0.65; 95% CI, 0.21–2.1; p = 0.49). There was no significant difference in bleeding (5.63% vs 9.86%; absolute difference, −4.20%; 95% CI, −13.0%–4.5%) and dyspnea (7.04% vs 12.7%; absolute difference, −5.60%; 95% CI, −15.4%–4.1%).

在印度人群中,有关经皮冠状动脉腔内成形术后普拉格雷和替卡格雷的有效性和安全性比较的证据很少。在1:1倾向得分匹配队列(每组71人)中,普拉格雷组和替卡格雷组心血管死亡、非致死性心肌梗死、非致死性卒中或冠状动脉血运重建的复合发生率无显著差异(7.04% vs 9.86%;绝对差异,2.8%;HR,0.65;95% CI,0.21-2.1;P = 0.49)。出血(5.63% vs 9.86%;绝对差异,-4.20%;95% CI,-13.0%-4.5%)和呼吸困难(7.04% vs 12.7%;绝对差异,-5.60%;95% CI,-15.4%-4.1%)无明显差异。
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引用次数: 0
A Bayesian meta-analysis of double kissing (DK) crush or provisional stenting for coronary artery bifurcation lesions 对冠状动脉分叉病变进行双吻(DK)压碎或临时支架植入的贝叶斯荟萃分析。
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2024.03.004
Ashish Kumar , Mariam Shariff , Aayush Singal , Vivek Bhat , John Stulak , Grant Reed , Ankur Kalra

Objective

Despite the development of dedicated, two-stent strategies, including the double kissing (DK) crush technique, the ideal technique for coronary artery bifurcation stenting has not been identified. We aimed to compare and determine the absolute risk difference (ARD) of the DK crush technique alone versus provisional stenting approaches for coronary bifurcation lesions, using the Bayesian technique.

Method

We queried PubMed/MEDLINE to identify randomized controlled trials (RCTs) that compared DK crush technique with provisional stenting for bifurcation lesions, published till January 2023. We used Bayesian methods to calculate the ARD and 95% credible interval (CrI).

Results

We included three RCTs, with 916 patients, in the final analysis. The ARD of cardiac death was centered at −0.01 (95% CrI: −0.04 to 0.02; Tau: 0.02, 85% probability of ARD of DK crush vs. provisional stenting <0). ARD for myocardial infarction was centered at −0.03 (95%CrI: −0.9 to 0.03; Tau: 0.05, 87% probability of ARD of DK crush vs. provisional stenting <0). ARD for stent thrombosis was centered at 0.00 (95% CrI: −0.04 to 0.03, Tau: 0.03, 51% probability of ARD for DK crush vs. provisional stenting <0). Finally, ARD for target lesion revascularization was centered at −0.05 (95% CrI: −0.08 to −0.03, Tau: 0.02, 99.97% probability of ARD for DK crush vs. provisional stenting <0).

Conclusions

Bayesian analysis demonstrated a lower probability of cardiac death, myocardial infarction and target lesion revascularization, with DK crush compared with provisional stenting techniques, and a minimal probability of difference in stent thrombosis.

目的:尽管开发了包括双吻合(DK)压碎技术在内的专用双支架策略,但冠状动脉分叉支架置入的理想技术仍未确定。我们的目的是利用贝叶斯技术,比较并确定冠状动脉分叉病变中单独使用 DK 压碎技术与使用临时支架方法的绝对风险差异(ARD):我们查询了PubMed/MEDLINE,以确定截至2023年1月发表的比较DK粉碎技术与临时支架术治疗分叉病变的随机对照试验(RCT)。我们采用贝叶斯方法计算了ARD和95%可信区间(CrI):我们在最终分析中纳入了三项研究,共916名患者。心脏死亡的ARD以-0.01为中心(95% CrI:-0.04至0.02;Tau:0.02,DK挤压与临时支架置入的ARD概率为85%):贝叶斯分析表明,与临时支架技术相比,DK压碎技术发生心源性死亡、心肌梗死和靶病变血管再通的概率更低,而支架血栓形成的概率差异极小。
{"title":"A Bayesian meta-analysis of double kissing (DK) crush or provisional stenting for coronary artery bifurcation lesions","authors":"Ashish Kumar ,&nbsp;Mariam Shariff ,&nbsp;Aayush Singal ,&nbsp;Vivek Bhat ,&nbsp;John Stulak ,&nbsp;Grant Reed ,&nbsp;Ankur Kalra","doi":"10.1016/j.ihj.2024.03.004","DOIUrl":"10.1016/j.ihj.2024.03.004","url":null,"abstract":"<div><h3>Objective</h3><p>Despite the development of dedicated, two-stent strategies, including the double kissing (DK) crush technique, the ideal technique for coronary artery bifurcation stenting has not been identified. We aimed to compare and determine the absolute risk difference (ARD) of the DK crush technique alone versus provisional stenting approaches for coronary bifurcation lesions, using the Bayesian technique.</p></div><div><h3>Method</h3><p>We queried PubMed/MEDLINE to identify randomized controlled trials (RCTs) that compared DK crush technique with provisional stenting for bifurcation lesions, published till January 2023. We used Bayesian methods to calculate the ARD and 95% credible interval (CrI).</p></div><div><h3>Results</h3><p>We included three RCTs, with 916 patients, in the final analysis. The ARD of cardiac death was centered at −0.01 (95% CrI: −0.04 to 0.02; Tau: 0.02, 85% probability of ARD of DK crush vs. provisional stenting &lt;0). ARD for myocardial infarction was centered at −0.03 (95%CrI: −0.9 to 0.03; Tau: 0.05, 87% probability of ARD of DK crush vs. provisional stenting &lt;0). ARD for stent thrombosis was centered at 0.00 (95% CrI: −0.04 to 0.03, Tau: 0.03, 51% probability of ARD for DK crush vs. provisional stenting &lt;0). Finally, ARD for target lesion revascularization was centered at −0.05 (95% CrI: −0.08 to −0.03, Tau: 0.02, 99.97% probability of ARD for DK crush vs. provisional stenting &lt;0).</p></div><div><h3>Conclusions</h3><p>Bayesian analysis demonstrated a lower probability of cardiac death, myocardial infarction and target lesion revascularization, with DK crush compared with provisional stenting techniques, and a minimal probability of difference in stent thrombosis.</p></div>","PeriodicalId":13384,"journal":{"name":"Indian heart journal","volume":null,"pages":null},"PeriodicalIF":1.5,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11143502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140305501","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
Non adherence to lipid-lowering therapy and strategies to improve adherence 不坚持降脂治疗和改善坚持治疗的策略。
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2024.01.006
Ashwani Mehta

Lipid lowering therapies is well-established to prevent cardiovascular events in adults with dyslipidemia and multiple risk factors. However, global clinical usage of LLT,particularly statins remains suboptimal, with adherence low rates for primary prevention and secondary prevention. Low adherence is influenced by concerns about side effects, misconceptions about benefits. Patients often discontinue statins due to perceived side effects, despite clinical trials showing no increase in symptoms compared to placebo. Poor understanding of statin benefits, doubts about their necessity, and suspicions of over prescription contribute to nonadherence, which is often amplified by negative portrayal of LLT specialy statins on social media. Strategies to improve adherence include addressing patient concerns, enhancing physician-patient communication, and increasing patient education. Optimizing statin usage and reducing the burden of cardiovascular disease necessitates addressing patient perceptions and improving communication between healthcare providers and patients.

对于血脂异常并存在多种危险因素的成年人来说,降脂疗法在预防心血管事件方面已得到广泛认可。然而,在全球范围内,降脂药物(尤其是他汀类药物)的临床使用情况仍不理想,一级预防和二级预防的依从性较低。患者对他汀类药物副作用的担忧和对其益处的误解影响了患者对他汀类药物的依从性。尽管临床试验表明,与安慰剂相比,他汀类药物的症状并没有增加,但患者往往会因为感觉到的副作用而停用他汀类药物。对他汀类药物的益处缺乏了解、对其必要性存在疑虑以及怀疑处方过量也是导致患者不坚持用药的原因之一,而社交媒体上对低剂量他汀类药物的负面描述往往会加剧这种情况。提高依从性的策略包括解决患者的顾虑、加强医患沟通和加强患者教育。要优化他汀类药物的使用并减轻心血管疾病的负担,就必须解决患者的看法问题,并改善医疗服务提供者与患者之间的沟通。
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引用次数: 0
Overview of a collaborative global effort to address the burden of familial hypercholesterolaemia 解决家族性高胆固醇血症负担的全球合作努力概述
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2023.11.005
Alexander R.M. Lyons , Christophe A.T. Stevens , Kanika I. Dharmayat , Dr Antonio J. Vallejo-Vaz , Kausik K. Ray

This is an overview of the EAS Familial Hypercholesterolaemia (FH) Studies Collaboration (FHSC) global consortium and registry (established 2015), which broadly addresses the global burden of FH. Eighty-seven National Lead Investigators from 74 countries form this expanding global consortium, and this global registry currently includes pooled data on 70,000 participants from participating countries to facilitate FH surveillance. Published first results from this global registry concluded that FH is diagnosed late, and management of LDL-cholesterol falls below guideline recommendations, and therefore earlier detection of FH and wider use of combination therapy is required. Further FHSC studies will follow on updated data including new countries, participants and variables, and non-DNA genetic information, and on the remaining cohorts in the registry. FHSC cross-sectional collaborative global studies are expected to promote FH detection earlier in life to subsequently initiate early lipid lowering therapy to reduce lifelong exposure to cumulative LDL-cholesterol thus reducing cardiovascular disease risk.

这是EAS家族性高胆固醇血症(FH)研究合作(FHSC)全球联盟和注册(成立于2015年)的概述,该联盟和注册广泛解决了FH的全球负担。来自74个国家的87名国家首席调查员组成了这个不断扩大的全球联盟,这个全球登记目前包括来自参与国的近7万名参与者的汇总数据,以促进FH监测。从这一全球登记中发表的第一批结果得出结论,FH诊断较晚,低密度脂蛋白胆固醇的管理低于指南建议,因此需要更早发现FH并更广泛地使用联合治疗。进一步的FHSC研究将遵循更新的数据,包括新的国家、参与者和变量、非dna遗传信息,以及注册表中剩余的队列。FHSC横断面全球合作研究有望促进FH在生命早期的检测,随后启动早期降脂治疗,以减少累积ldl -胆固醇的终生暴露,从而降低心血管疾病的风险。
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引用次数: 0
Familial hypercholesterolemia 家族性高胆固醇血症
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2023.12.002
J.P.S. Sawhney, Kushal Madan

Familial hypercholesterolemia is a common genetic disorder of autosomal inheritance associated with elevated LDL-cholesterol. It is estimated to affect 1:250 individuals in general population roughly estimated to be 5 million in India. The prevalence of FH is higher in young CAD patients (<55 years in men; <60 years in women). FH is underdiagnosed and undertreated. Screening during childhood and Cascade screening of family members of known FH patients is of utmost importance in order to prevent the burden of CAD. Early identification of FH patients and early initiation of the lifelong lipid lowering therapy is the most effective strategy for managing FH. FH management includes pharmaceutical agents (statins and non statin drugs) and lifestyle modification. Inspite of maximum dose of statin with or without Ezetimibe, if target levels of LDL-C are not achieved, Bempedoic acid, proprotein convertase subtilisin/kexin type 9 (PCSK9) Inhibitors/Inclisiran can be added.

家族性高胆固醇血症是一种常见的常染色体遗传疾病,与低密度脂蛋白胆固醇升高有关。据估计,在印度,该病的发病率约为总人口的 1:250,约 500 万人。FH在年轻的CAD患者(男性55岁;女性60岁)中发病率较高。FH诊断不足,治疗不力。在儿童时期进行筛查,并对已知 FH 患者的家庭成员进行级联筛查,对于防止加重 CAD 负担至关重要。早期发现 FH 患者并尽早开始终身降脂治疗是控制 FH 的最有效策略。FH 的治疗包括药物(他汀类和非他汀类药物)和生活方式的改变。尽管服用了最大剂量的他汀类药物(无论是否服用依折麦布),如果低密度脂蛋白胆固醇(LDL-C)仍未达到目标水平,可加用本贝多酸、9 型丙蛋白转换酶枯草酶/kexin(PCSK9)抑制剂/英克利西兰(Inclisiran)。
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引用次数: 0
Pediatric hyperlipidemia 小儿高脂血症
IF 1.5 Q3 Medicine Pub Date : 2024-03-01 DOI: 10.1016/j.ihj.2023.11.269
Ankit Garg, S. Radhakrishnan

The leading cause of mortality worldwide is atherosclerotic cardiovascular disease. Atherosclerotic plaques are well known to originate early in the childhood. Identifying hyperlipidemia in early childhood creates an opportunity to prevent major cardiovascular events in adults. Children with identified risk factors are at an increased risk of developing cardiovascular incidents in later life. This article emphasizes the diagnosis and management of pediatric hyperlipidemia with reference to the recent guidelines. In terms of etiology pediatric hyperlipidemia are divided into primary and secondary causes. The mainstay of management includes high-risk target screening, early risk factor identification and lifestyle modifications in vulnerable population. Drug therapy is recommended in primary hyperlipidemia and in children with no response to lifestyle changes.

动脉粥样硬化性心血管疾病是导致全球死亡的主要原因。众所周知,动脉粥样硬化斑块起源于儿童早期。在儿童早期发现高脂血症为预防成年后发生重大心血管事件创造了机会。具有已识别风险因素的儿童日后发生心血管事件的风险会增加。本文将参照最新指南,重点介绍小儿高脂血症的诊断和管理。就病因而言,小儿高脂血症分为原发性和继发性两种。治疗的主要方法包括高危目标筛查、早期危险因素识别以及对易感人群进行生活方式调整。对于原发性高脂血症和对改变生活方式无反应的儿童,建议采用药物治疗。
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引用次数: 0
期刊
Indian heart journal
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