Acrocallosal Syndrome

点击“蓝字”关注我们尽管心血管疾病在一级和二级预防方面取得了显著进展，但证据表明，<50岁人群中早发性冠状动脉疾病（CAD）和心肌梗死（MI）的发病率呈上升趋势。这一增长与年轻人群中传统心血管危险因素的流行上升有关，如2型糖尿病、高血压、肥胖和高脂血症，这些因素均可导致动脉粥样硬化性CAD的增加。此外，最新研究还指出，非传统危险因素（包括慢性炎症、自身免疫疾病、药物使用、心理社会因素和新型生物标志物）在CAD的早期发病中可能具有一定影响。这些因素共同导致了早发性CAD的增加，凸显了针对年轻人群改进预防策略和加强公共卫生工作的必要性。近日，J Cardiovasc Dev Dis刊登了一项综述，探讨了早发性CAD的病因、新兴危险因素及新型生物标志物的作用，为这一日益严峻的公共卫生问题提供了见解。病因01.动脉粥样硬化血栓性心肌梗死动脉粥样硬化性冠心病是年轻人群急性心肌梗死的主要病因，其中60%~65%的病例由斑块破裂引起[1,2]。动脉粥样硬化的病理生理机制涉及内皮细胞活化、单核细胞浸润及巨噬细胞摄取低密度脂蛋白（LDL）的复杂相互作用，最终导致泡沫细胞形成和局部炎症。这一过程还受免疫反应（通过细胞因子和脂质介质介导）以及作用于内皮细胞的血流动力学因素影响，共同导致细胞外基质重塑和斑块形成[3]。利用血管内成像技术对动脉粥样硬化性CAD患者进行血管造影研究显示，不同年龄组罪犯斑块的形态存在差异，但各研究结果不尽一致。年轻动脉粥样硬化患者通常疾病负担较轻，表现为受累血管较少、病变较短、斑块体积较小。尽管年轻患者的动脉粥样硬化程度较轻，但其斑块不稳定风险更高。02.非阻塞性冠状动脉心肌梗死急性冠脉综合征（ACS）通常由冠状动脉阻塞引起，这种阻塞可能源于动脉粥样硬化斑块增长或斑块破裂/侵蚀后形成的血栓。然而，部分患者会出现心肌梗死的临床表现和生物标志物异常，但冠状动脉造影未显示明显阻塞性病变，这种病症被称为心肌梗死伴非阻塞性冠状动脉（MINOCA）[4]。MINOCA的患病率为5%~25%，在35岁以下患者中发病率最高（超过18%）[4]。但需注意，MINOCA仅为初步诊断，需进一步排查潜在病因。部分MINOCA病例最终可能被证实为非缺血性病因，此时需修正诊断。MINOCA患者的风险特征与阻塞性冠心病患者相似，但MINOCA患者更常表现为药物滥用、抑郁，且女性占比更高。此外，MINOCA患者的甘油三酯水平也较高，但与其他群体的差异仅处于临界显著水平[4]。03.非动脉粥样硬化性冠状动脉相关心肌梗死1.自发性冠状动脉夹层自发性冠状动脉夹层（SCAD）是一种冠状动脉壁自发分离的疾病，与创伤、医源性因素或动脉粥样硬化无关。这种分离可能因内膜撕裂或壁内血肿形成而导致冠状动脉阻塞。2.冠状动脉痉挛冠状动脉痉挛是年轻患者急性心肌梗死的一种罕见但重要的病因，可能最初被归类为MINOCA。其特征为短暂性严重冠状动脉阻塞（狭窄超过90%），导致心绞痛和缺血性心电图改变，可自发发生或由乙酰胆碱、麦角胺或过度换气等刺激诱发[5,6]。3.冠状动脉栓塞和高凝状态冠状动脉栓塞和血栓形成是导致年轻患者急性心肌梗死的重要原因，尤其是那些患有高凝疾病的患者。4.冠状动脉炎冠状动脉炎（CAV）是年轻患者不明原因急性冠脉综合征或充血性心力衰竭的重要鉴别诊断，尤其是在已知原发性或继发性血管炎的情况下。这些疾病可能在无传统心血管危险因素的年轻个体中表现为主要表现。CAV的症状可能与典型冠状动脉疾病相似，包括心绞痛、急性心肌梗死、心律失常、传导障碍或心力衰竭。年轻人群急性心肌梗死的危险因素01.传统的心血管危险因素年轻人群急性心肌梗死的主要原因是动脉粥样硬化斑块破裂，这与血脂异常、高血压、糖尿病、吸烟、肥胖和CAD家族史等传统心血管危险因素有关。然而，这些危险因素在年轻人群和老年人群中的分布不同。全球急性MI登记处一致显示，吸烟、血脂异常和早发CAD家族史在年轻患者中更为突出。相比之下，糖尿病、代谢综合征和高血压在老年人群中更常见。02.非传统风险因素①物质滥用：年轻患者发生心肌梗死的一个重要危险因素。②慢性炎症和自身免疫性疾病：动脉粥样硬化在一定程度上是一种慢性炎症过程；自身免疫性疾病也正在成为年轻急性心肌梗死患者的新危险因素；另一个值得关注的方面是口腔健康状况与心血管疾病（尤其是牙周炎）之间的复杂关系，现已知牙周炎患者患心血管疾病的风险增加。03.女性特有的危险因素女性比男性更容易发生早发性心肌梗死[7]。与男性和老年女性相比，年轻女性心肌梗死具有不同的危险因素和病理生理机制。她们更可能出现冠状动脉微血管功能障碍、SCAD和斑块侵蚀，而不是破裂。04.社会心理风险因素年轻早发性心肌梗死患者越来越多地认识到新出现的社会心理危险因素，研究强调了焦虑、抑郁和社会经济因素的重要作用。05.环境风险因素人们越来越认识到环境在心血管疾病发展中的重要性。污染、毒素暴露、建筑环境、食物供应和社会文化影响等因素都与心血管风险增加有关。新型生物标志物的作用01.脂蛋白(a)脂蛋白(a) [Lp(a)] 正逐渐成为年轻患者早发性冠状动脉疾病（CAD）和急性心肌梗死（MI）的新型生物标志物。Lp(a)水平升高与CAD及缺血性卒中的风险显著相关，尤其在45岁以下人群中风险更为突出[2]。研究表明，Lp(a)水平超过50 mg/dl的年轻个体发生急性冠脉综合征（ACS）的可能性高3倍，且这种相关性随年龄增长而减弱[8]。此外，年轻心肌梗死患者的Lp(a)水平升高还与多支冠状动脉病变相关。02.高敏C反应蛋白高敏C反应蛋白（hs-CRP）作为早发性心肌梗死生物标志物的作用仍在研究中。早期研究表明，hs-CRP可能有助于预测有急性冠脉综合征病史的年轻患者的未来冠状动脉事件，尤其是当血浆水平超过1.6 mg/L时[9]。2024年Song等人的研究进一步指出，hs-CRP与血浆致动脉粥样硬化指数（AIP）共同构成早发性CAD的独立危险因素，且hs-CRP水平升高与疾病严重程度呈正相关[10]。Liu等人则强调了CRP在评估年轻女性ACS患者风险中的价值，提示其可用于风险分层[11]。然而，hs-CRP在预测早发性心肌梗死中的确切作用及其临床实用性仍需进一步研究。03.载脂蛋白由于现有证据有限且质量较低，载脂蛋白作为年轻心肌梗死生物标志物的价值尚未明确。Zhang等人对≤40岁年轻STEMI患者的研究发现，血清载脂蛋白A可作为预后标志物，与心力衰竭和恶性心律失常风险相关[12]。Martson等人进行的一项前瞻性队列研究则表明，含载脂蛋白B的脂蛋白能更好地预测心肌梗死风险，且与血脂含量无关，提示载脂蛋白B可能是动脉粥样硬化发生的关键因素，但该结论并非专门针对年轻心肌梗死患者[13]。Aghajani等人的系统评价指出，载脂蛋白A-1水平可能与早发性CAD存在关联，但纳入的研究多为病例对照设计，结论的可靠性和强度有限[14]。因此，目前证据不足，需更多高质量前瞻性队列研究以明确载脂蛋白在年轻心肌梗死中的价值。04.同型半胱氨酸少数小型研究支持同型半胱氨酸（Hcy）作为早发性CAD和年轻心肌梗死生物标志物的作用，但证据仍有限。Schaffer等人报告称，血浆Hcy水平升高与CAD独立相关[15]。Sadeghian等人的小规模病例对照研究发现，高同型半胱氨酸血症是<45岁年轻患者CAD的危险因素，尤其在男性中更为显著，且维生素B12缺乏可能参与Hcy水平升高[16]。Barghash等人则发现，Hcy水平升高与叶酸水平降低均与早发性CAD显著相关，提示Hcy、叶酸及纤溶酶原激活物抑制剂-1可能作为独立危险因素[17]。尽管这些研究指出了Hcy作为早期心血管风险标志物的潜力，但证据多基于小样本和病例对照设计，仍需更大规模、更严谨的研究以证实其在年轻CAD患者中的作用。05.肠道微生物组肠道微生物组可能在年轻人群心肌梗死的发病机制中发挥新兴作用。肠道菌群失调（dysbiosis）已被证实与心血管疾病（包括CAD）相关。研究表明，由肠道细菌（如拟杆菌）产生的代谢物三甲胺N-氧化物（TMAO）可促进动脉粥样硬化和CAD[18,19]。Liu等人的病例对照研究发现，＜44岁STEMI年轻患者与无CAD人群的肠道微生物组多样性存在显著差异，且特定细菌（如链球菌和普雷沃氏菌）的丰度发生改变[20]。值得注意的是，普雷沃氏菌丰度与肥胖呈负相关，肥胖患者中普雷沃菌减少与炎症标志物升高相关。这些发现提示，将肠道微生物组分析与临床参数相结合，可能提高早发性CAD的诊断效能，并加深对其发病机制的理解。结论年轻人群中心肌梗死发病率的不断上升已成为一项严峻的公共卫生挑战，其病因具有多因素性，既涉及动脉粥样硬化性病因，也包括非动脉粥样硬化性病因。除传统心血管危险因素的负担日益加重外，非传统危险因素、心理社会因素及新型生物标志物在早发性CAD发生发展中的作用也愈发凸显。有效的公共卫生策略必须优先预防可改变的危险因素（如吸烟、肥胖和血脂异常），同时应对新兴危险因素（如环境压力源和心理社会因素）。此外，需制定性别特异性干预措施以缩小预后差距，尤其是针对年轻女性——与年轻男性相比，年轻女性的临床结局往往更差。参考文献（上下滑动可查看）[1]Mithila Zaheen,?Patrick Pender, Quan M Dang, er al. Myocardial Infarction in the Young: Aetiology, Emerging Risk Factors, and the Role of Novel Biomarkers. J Cardiovasc Dev Dis.?2025 Apr 10;12(4):148.[2]Rallidis, L.S, Xenogiannis, I, Brilakis, E.S.; Bhatt, D.L. Causes, Angiographic Characteristics, and Management of Premature Myocardial Infarction: JACC State-of-the-Art Review.?J Am Coll Cardiol.?2022,?79, 2431–2449.[3]Libby, P; Theroux, P. Pathophysiology of coronary artery disease. Circulation?2005, 111, 3481-3488[4]Juan-Salvadores, P, et al. Clinical Features and Long-Term Outcomes in Very Young Patients with Myocardial Infarction with Non-Obstructive Coronary Arteries. J. Interv. Cardiol. 2022, 2022, 9584527[5]Slavich, M.; Patel, R.S. Coronary artery spasm: Current knowledge and residual uncertainties.?Int. J. Cardiol. Heart Vasc.?2016, 10, 47-53.[6]Matta, A.; Bouisset, F.; Lhermusier, T.; et al. Coronary Artery Spasm: New Insights.?J. Interv. Cardiol.?2020, 2020, 5894586.[7]Arora, S.; Stouffer, G.A.; Kucharska-newton, A.M.; et al. Twenty Year Trends and Sex Differences in Young Adults Hospitalized with Acute Myocardial Infarction.?Circulation?2019,?139, 1047–1056[8]Rallidis, L.S.; Pavlakis, G.; Foscolou, A.; et al. High levels of lipoprotein (a) and premature acute coronary syndrome.?Atherosclerosis?2018,?269, 29-34.[9]Speidl, W.S.; Graf, S.; Hornykewycz, S.; et al. High-sensitivity C-reactive protein in the prediction of coronary events in patients with premature coronary artery disease. Am. Heart J. 2002, 144, 449–455. [10]Song, Y.; Wang, M.; Li, Y.; Lian, Y. The evaluation value of atherogenic index of plasma and high-sensitivity C-reactive protein for the degree of coronary artery lesion in premature coronary artery disease.?BMC Cardiovasc. Disord.?2024,?24, 410. [11]Liu, R.; Xu, F.; Ma, Q.; et al. C-Reactive Protein Level Predicts Cardiovascular Risk in Chinese Young Female Population. Oxid. Med. Cell. Longev.?2021,?2021, 6538079.[12]Zhang, Z.; Qin, S.; Wang, R.; et al. Prognostic factors in young patients with ST-segment elevation myocardial infarction. Coron. Artery Dis. 2023, 34, 298–305. [13]Marston, N.A.; Giugliano, R.P.; Melloni, G.E.M.; et al. Association of Apolipoprotein B-Containing Lipoproteins and Risk of Myocardial Infarction in Individuals with and Without Atherosclerosis: Distinguishing Between Particle Concentration, Type, and Content. JAMA Cardiol. 2022, 7, 250–256. [14]Aghajani, M.H.; Neishaboori, A.M.; Ahmadzadeh, K.; et al. The association between apolipoprotein A-1 plasma level and premature coronary artery disease: A systematic review and meta-analysis. Int. J. Clin. Pract. 2021, 75, e14578.[15]Schaffer, A.; Verdoia, M.; Cassetti, E.; et al.Novara Atherosclerosis Study Group (NAS). Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study. Thromb. Res.2014,?134, 288–293.[16]Center, T.H.; Sadeghian, S.; Fallahi, F.; et al. Homocysteine, vitamin B12 and folate levels in premature coronary artery disease.?BMC Cardiovasc. Disord. 2006, 6, 38. [17]Barghash, N.; Elewa, S.; Hamdi, E.; et al. Role of plasma homocysteine and lipoprotein (a) in coronary artery disease.?Br. J. Biomed. Sci.?2004, 61, 78–83.[18]Koeth, R.A.; Wang, Z.; Levison, B.S.; et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013, 19, 576–585. [19]Yoshida, N.; Emoto, T.; Yamashita, T.; et al. Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis.?Circulation?2018,?138, 2486–2498. [20]Liu, M.; Wang, M.; Peng, T.; et al. Gut-microbiome-based predictive model for ST-elevation myocardial infarction in young male patients. Front. Microbiol. 2022, 13, 1031878.声明：本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。最新《国际糖尿病》读者专属微信交流群建好了，快快加入吧！扫描左边《国际糖尿病》小助手二维码（微信号：guojitnb），回复“国际糖尿病读者”，ta会尽快拉您入群滴！（来源：《心肾代谢时讯》编辑部）

Injuries of the anterior cruciate ligament (ACL), located in the knee, are typically thought to be caused by acute traumatic events, such as sudden twists. New work analyzing an animal model of ACLs suggests that such injuries can also occur as a result of chronic overuse, specifically due to a reduced ability to repair microtraumas associated with overuse. Importantly, the team said, females also are less able to heal from these microtraumas than males, which may explain why females are two to eight times more likely to tear their ACL ligaments than males. Injuries of the anterior cruciate ligament (ACL), located in the knee, are typically thought to be caused by acute traumatic events, such as sudden twists. Led by Penn State researchers, new work analyzing an animal model of ACLs suggests that such injuries can also occur as a result of chronic overuse, specifically due to a reduced ability to repair microtraumas associated with overuse. Importantly, the team said, females also are less able to heal from these microtraumas than males, which may explain why females are two to eight times more likely to tear their ACL ligaments than males. "ACL tears are one of the most common injuries, affecting more than 200,000 people in the U.S. each year, and women are known to be particularly susceptible," said principal investigator Spencer Szczesny, associate professor of biomedical engineering and of orthopaedics and rehabilitation at Penn State. "While recent research suggests that chronic overuse can lead to ACL injuries, until now, no one had investigated the differential biological response of female and male ACLs to applied force." In the study, which was published in the Journal of Orthopaedic Research, researchers placed ACLs from deceased male and female rabbits in a custom-made bioreactor that simulated the conditions of a living animal but allowed direct observation and measurement of the tissue. Next, they applied repetitive forces to the ACLs that mimicked those that would naturally occur during activities such as standing, walking and trotting and measured the expression of genes related to healing. In male samples, the team found that low and moderate applied forces, such as those that would occur during standing or walking, resulted in increased expression of anabolic genes, which are related to building molecules needed for healing. By contrast, larger applied forces, such as those that would occur with repetitive trotting, decreased expression of these anabolic genes. For female samples, however, the amount of force applied did not influence the level of anabolic gene expression. "It didn't matter whether there was low, medium or high activity for females," said Lauren Paschall, graduate student in biomedical engineering at Penn State and first author on the paper. "Female ACLs exposed to chronic use just didn't heal as well as male ACLs, which may explain why women are predisposed to injuries. This supports the hypothesis that noncontact ACL injuries are attributed to microtraumas associated with chronic overuse that predispose the ACL to injury." According to the researchers, one explanation for the sex differences the team observed could be due to the higher amounts of estrogen in females. "Some studies have found that the overall effect of estrogen on ACL injury is negative," Paschall said. "Specifically, studies have shown that human women are more likely to tear their ACLs during the preovulatory phase, when estrogen levels are high, than during the postovulatory phase, when estrogen levels are low." She said the team plans to further investigate the role of estrogen on ACL injury. Szczesny noted that although the team's study was not in humans, the findings may suggest that providing additional recovery time for women following injuries could be advantageous. "Ultimately, this work could also help to identify targets for therapeutics to prevent ACL injuries in women," he said. Other Penn State authors on the paper include Sabrina Carrozzi, graduate student; Erdem Tabdanov, assistant professor of pharmacology; and Aman Dhawan, professor of orthopaedics and rehabilitation. The Orthopaedic Research and Education Foundation and the Congressionally Directed Medical Research Program supported this research.