早发性冠心病患者脂蛋白(a)水平变化

观察较早发生的冠心病(CHD)患者的血清脂蛋白(a)[Lp(a)]水平变化.方法:用ELISA法测定经冠脉造影证实的185例CHD患者及31例对照(NS)Lp(a)水平.结果:(1)血清Lp(a)水平在185例CHD患者明显高于31例NS组(216.96±215.39比119.68±71.07mg/L,P<0.02).(2)CHD组中,血清Lp(a)水平,在80例<55岁比105例≥55岁者明显升高(252.86±253.77比189.61±177.24mg/P<0.05).结论:血清Lp(a)水平升高可能在较早发生的冠心病患者中更为明显.     

Lipoprotein (a) and coronary heart disease among women: beyond a cholesterol carrier?

AIMS: With its homology with plasminogen, lipoprotein(a) [Lp(a)] may be related to thrombosis and inflammation. We assessed the role of Lp(a) in coronary heart diseases (CHD) by a recently developed assay that is not affected by the plasminogen-like Kringle-type-2 repeats. METHODS AND RESULTS: Of 32 826 women from the Nurses' Health Study, who provided blood at baseline, we documented 228 CHD events during 8 years of follow-up. Each case was compared with two matched controls. In a multivariable model adjusted for body mass index, family history, hypertension, diabetes, post-menopausal hormone use, physical activity, blood drawing characteristics, and alcohol intake, the odd ratio (OR) for Lp(a) levels > or =30 mg/dL was 1.9(95% CI: 1.3-3.0) when compared with those with Lp(a)<30 mg/dL. Women with high levels of both Lp(a) (> or =30 mg/dL) and fibrinogen (> or =400 mg/dL) had an OR of 3.2(95% CI: 1.6-6.5) for CHD, when compared with the combination of low levels (P interaction=0.05). Women with high levels of both Lp(a) and C-reactive protein (> or =3 mg/L) had an OR of 3.67(95% CI: 2.03-6.64) for CHD, when compared with the combination of low levels (P interaction=0.06). CONCLUSION: Lp(a) levels >30 mg/dL are associated with twice the risk of CHD events among women and may be related to thrombosis and inflammation.     

不同类型冠心病患者血尿酸、纤维蛋白原、低密度脂蛋白和脂蛋白(a)浓度的变化

目的 研究不同类型冠心病患者血尿酸、纤维蛋白原、低密度脂蛋白和脂蛋白(a)浓度的变化及其与冠状动脉病变程度的关系.方法 185例患者包括107例急性冠状动脉综合征患者、30例冠状动脉痉挛患者及48例稳定型心绞痛患者,以31例非冠心病者为对照组.测定血清尿酸、纤维蛋白原、低密度脂蛋白和脂蛋白(a)浓度,冠状动脉病变严重程度用常规冠状动脉造影后计算Gensini积分与病变支数来估计.结果 急性冠状动脉综合征组、冠状动脉痉挛组和稳定型心绞痛组中男性患者血尿酸浓度高于对照组.急性冠状动脉综合征组和稳定型心绞痛组中女性患者血尿酸浓度高于对照组(P<0.05);急性冠状动脉综合征组血纤维蛋白原浓度高于对照组和稳定型心绞痛组(P<0.05).尿酸、纤维蛋白原和低密度脂蛋白与冠状动脉积分显著相关,尿酸、纤维蛋白原与冠状动脉病变支数显著相关.结论 各型冠心病及其严重程度与血尿酸、纤维蛋白原浓度升高有关,血低密度脂蛋白与冠状动脉积分有关.     

The Familial Hypercholesterolemia Regression Study: A Randomized Comparison of Therapeutic Reduction of Both Low-Density Lipoprotein and Lipoprotein(a) Versus Low-Density Lipoprotein Alone

Abstract: Lipoprotein (a) [Lp (a)] is a risk factor for coronary heart disease (CHD), especially in the presence of a raised low-density lipoprotein (LDL)-cholesterol (LDL-C). To ascertain whether reduction of both LDL and Lp(a) is more advantageous than reduction of LDL alone, patients with heterozygous FH and CHD were selected randomly to receive either LDL apheresis fortnightly plus simvastatin 40 mg/day or colestipol 20 g plus simvastatin 40 mg/day. Quantitative coronary angiography was undertaken before and after 2.1 years. Changes in serum lipids were similar in both groups except for the greater reduction of LDL-C and Lp(a) by apheresis. There were no significant differences in primary angiographic endpoints, and none of the angiographic changes correlated with Lp(a). Although LDL apheresis plus simvastatin was more effective than colestipol plus simvastatin in reducing LDL-C and Lp(a), it was not more beneficial in influencing coronary atherosclerosis. Decreasing Lp(a) seems unnecessary if LDL-C is reduced below 130 mg/dl.—     

国人健康男女及冠心病患者血浆脂蛋白(a)水平

为了了解国人人群脂蛋白(a)的分布及水平,探讨脂蛋白(a)与冠心病及其它血脂与载脂蛋白的关系,本文应用单价抗载脂蛋白(a)及抗载脂蛋白B抗体夹心酶联法测定668名健康人血浆脂蛋白(a),测得(?);122.34±141.97mg/L,M为81.07mg/L(0～1 250mg/L),呈典型的正偏态分布,无性别年龄差异,与其它脂类及载脂蛋白不相关。48例冠心病患者血浆脂蛋白(a)水平及>200mg/L的频率分布均明显高于同年龄对照组,提示高脂蛋白(a)水平是致动脉粥样硬化的一个独立危险因素。     

冠脉病变与血清同型半胱氨酸及脂蛋白（a）的相关性研究

目的:观察冠心病(CHD)患者冠状动脉病变程度与血清同型半胱氨酸(Hcy)和血清脂蛋白(a)[Lp(a)]水平间的相关性。方法:选择经冠状动脉造影确诊的CHD患者108例为CHD组,其中亚组:稳定型心绞痛(SAP)37例,不稳定型心绞痛(UAP)36例,急性心肌梗死(AMI)35例,另选择82例健康体检者为健康对照组,比较两组及CHD组内各亚组血清Hcy和Lp(a)水平,分析冠状动脉病变程度与血清Hcy、Lp (a)水平的相关性。结果:与健康对照组比较,CHD组血清Hcy[(7.1±2.1)μmol/L比(15.6±5.0)μmol/L]和Lp(a)[(122.6±20.4)mg/L比(220.2±42.6)mg/L]水平均显著升高(P均=0.001);且与SAP组比较,UAP组和AMI组血清Hcy[(12.5±4.0)μmol/L比(18.1±5.9)μmol/L、(20.1±6.0)μmol/L]和Lp(a)[(150.8±30.8)mg/L比(272.8±50.3)mg/L、(280.6±52.9)mg/L]水平及Gensini评分[(15.5±8.5)分比(50.6±11.2)分、(54.3±12.8)分]均显著升高(P均=0.001);Pearson相关分析显示,CHD患者冠状动脉病变程度与血清Hcy及Lp(a)水平呈显著正相关(r=0.582、0.663,P均=0.001)。结论:血清Hcy和Lp(a)水平与CHD冠状动脉病变程度呈正相关,联合检测之有助于了解病情,并指导治疗。     

冠心病患者脂蛋白(a)及三酰甘油/高密度脂蛋白胆固醇比值变化的研究

目的　探讨冠心病 (CHD)病情程度与脂蛋白 (a) [L p(a) ]及三酰甘油 /高密度脂蛋白胆固醇 (TG/ HDL- C)比值的关系。方法　测定 138例 CHD患者血清 L p(a)及 TG/ HDL- C比值 ,并与对照组健康人 82例相比较 ,分析 L p(a)及 TG/ HDL - C比值的临床意义。结果　 L p(a)浓度及 TG/ HDL - C比值在稳定型心绞痛组及不稳定型心绞痛组明显高于对照组 (分别 P<0 .0 5 ,P<0 .0 1) ,CHD组中两指标在慢性充血性心力衰竭 I°组、 °组、 °组呈上升的趋势 ,同时 L p(a)与 TG呈正相关 (r=0 .30 8,P<0 .0 1)。结论　 L p(a)及 TG/ HDL - C比值联合监测有助于 CHD的早期发现 ,了解病情程度     

血浆脂蛋白(a)与冠心病的相关性研究

目的 探讨血浆脂蛋白(a)[Iipeprotein(a),Lp(a)]水平升高与冠心病的相关性.方法 入选2007年10月至2009年3月因胸痛人院的患者1011例,其中经冠状动脉造影确诊为冠心病的患者613例(占60.6%),设为冠心病组,非冠心病患者398例(占39.4%),设为对照组.以免疫透射比浊法测定Lp(a)、载脂蛋白A1(apoAl)、载脂蛋白B(apoB).以酶法测甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C),计算LDL-C/HDL-C比值,进行多因素logistic回归分析.结果 (1)冠心病组的Lp(a)、TC、TC、LDL-C、apoB水平及LDL-C/HDL-C比值分别为(170.00±160.00)ms/L、(1.84±0.90)naml/L、(4.86±0. 88)mmol/L、(3.31±0.72)mmol/L、(0.97±0.17)mmol/L及3.39±0.93,而对照组相应值分别为(120.00±100.00)mg/L、(1.67±0.72)mmol/L、(4.61±0.95)mmol/L、(2.96±0.80)mmol/L、(0.90±0.18)mmol/L及2.89±0.92,冠心病组均显著高于对照组(P均<0.05).(2)多因素logistic回归分析(前进法)显示Lp(a)是诊断冠心病最显著的独立危险因素(DR=16.201,95%可信区间3.477,75.489,P=0.0001).结论 Lp(a)为冠心病最显著的独立危险因素.     

天然及氧化型脂蛋白(a)与巨噬细胞表面结合

为探讨脂蛋白 (a)及氧化型脂蛋白 (a)在巨噬细胞上的结合和降解途径 ,将生物素标记的脂蛋白与小鼠腹腔巨噬细胞进行结合和竞争性结合试验。结果发现 ,脂蛋白 (a)能以一定的亲和力、可饱和性地与巨噬细胞表面结合 ;低密度脂蛋白对其结合无明显抑制作用 ,而氧化型低密度脂蛋白、氧化型脂蛋白 (a)均能不同程度地抑制这种结合。脂蛋白 (a)经氧化修饰后 ,与巨噬细胞的结合量显著增加。脂蛋白 (a)、低密度脂蛋白不能有效竞争氧化型脂蛋白 (a)的结合 ,而氧化型脂蛋白 (a)和氧化型低密度脂蛋白为有效的竞争性抑制剂。提示脂蛋白 (a)主要经清道夫受体与巨噬细胞表面结合 ;氧化型脂蛋白 (a)除经清道夫受体介导外 ,可能还通过其它特异性受体与巨噬细胞表面结合。     

脂蛋白α水平与冠心病发生及严重程度的相关性探究

目的 探究未经治疗的冠心病(CAD)患者中,脂蛋白α[Lp(α)]在预测CAD发病和严重程度方面的作用.方法 连续入选2012年10月至2017年4月于阜外医院血脂异常与心血管疾病诊治中心的1980例接受冠状动脉造影的患者,其中1162例确诊患有CAD,用Gensini评分(GS)来评估CAD严重程度,免疫比浊法测定Lp(α).结果 与无CAD患者相比,CAD患者LDL-C水平更高(P<0.05).多变量Logistic回归分析表明,Lp(α)>205 mg/L(第三分位)时患CAD的风险是Lp(α)处于第一分位者的1.437倍(95%CI 1.108~1.865,P=0.006),高GS的风险是Lp(α)处于第一分位者的1.480倍(95%CI 1.090~2.009,P=0.012).而且,高水平的Lp(α)和LDL-C并存时预示着CAD发病风险(OR=1.845,95%CI 1.339~2.541,P<0.001)和冠状动脉严重程度(OR=1.736,95%CI 1.188~2.538,P=0.004)最高.结论 脂蛋白α可作为预测冠状动脉疾病存在和程度的标志物,尤其是与LDL-C联合使用时.     

绝经后女性冠心病患者血清脂蛋白(a)的研究

目的 :研究脂蛋白 (a) [L p(a) ]与绝经后女性冠心病 (CH D)的关系 ,并初步探讨内源性雌激素对血清 L p(a)水平的影响。方法 :采用 EL ISA法测定 5 2例绝经后女性 CHD患者及 48例健康者的血清 L p(a)浓度 ,并测定了其中 40例 CHD患者和 30例健康者的雌激素水平。结果 :CHD组平均 L p(a)浓度显著高于对照组 [(2 5 2 .9± 31.5 )∶ (12 9.2± 2 0 .0 ) mg/L ,P <0 .0 1],且与冠状动脉病变支数相关 ,r =0 .398,P <0 .0 0 1;而血清 L p(a)浓度与雌二醇水平未见显著关联。结论 :血清 L p(a)水平的增加是 CHD的独立危险因子 ,也是冠状动脉病变严重程度的一个预测因素 ,其浓度与内源性雌激素水平无关。     

甘露聚糖、壳聚糖、α-酸性糖蛋白和姜黄素对脂蛋白(a)和去唾液酸脂蛋白(a)代谢影响的对比分析

分析多糖和姜黄素对脂蛋白 (a)和去唾液酸脂蛋白 (a)代谢的影响 ,从刺猬腋下静脉注入甘露聚糖、壳聚糖、α -酸性糖蛋白和姜黄素 ,2min后注射12 5I-脂蛋白 (a)或12 5I-去唾液酸脂蛋白 (a) ,1h后处死动物 ,测定血、肝、肾、脾、胆汁和肾上腺的同位素含量。结果发现 ,脂蛋白 (a)去唾液酸后能大量进入肝脏 ,加速在体内的分解代谢 ,使血中浓度迅速降低。α -酸性糖蛋白抑制组织对脂蛋白 (a)和去唾液酸脂蛋白 (a)的摄入 ,使血中脂蛋白 (a)和去唾液酸脂蛋白 (a)含量显著增高。壳聚糖和姜黄素增加肝脏和肾上腺对脂蛋白 (a)的摄取 ,使血中脂蛋白 (a)含量略降低 ,但对去唾液酸脂蛋白 (a)代谢无明显影响。甘露聚糖增加脾脏对脂蛋白 (a)的摄取 ,减少胆囊中脂蛋白 (a)含量 ,但增加肾脏和胆囊对去唾液酸脂蛋白 (a)的摄取 ,降低肾上腺对去唾液酸脂蛋白 (a)的摄取。结果提示 ,脂蛋白 (a)去唾液酸后能使脂蛋白 (a)分解代谢加快 ,脂蛋白 (a)分子中的唾液酸在结构稳定中起重要的作用。α -酸性糖蛋白抑制脂蛋白 (a)和去唾液酸脂蛋白 (a)代谢 ,而壳聚糖和姜黄素则促进脂蛋白 (a)代谢     

甘露聚糖、壳聚糖、α-酸性糖蛋白和姜黄素对脂蛋白(a)和去唾液酸脂蛋白(a)代谢影响的对比分析

分析多糖和姜黄素对脂蛋白（ａ）和去唾液酸脂蛋白（ａ）和去唾液酸脂蛋白（ａ）代谢的影响,从刺猥腋下静脉注入甘露聚糖、壳聚糖、α－酸性糖蛋白和姜黄素,２ｍｉｎ后注射＾１２５Ｉ－脂蛋白（ａ）或＾１２５Ｉ－去唾液酸脂蛋白（ａ）,１ｈ后处死动物,测定血、肝、肾、脾、胆汁和肾上腺的同位素含量。结果发现,脂蛋白（ａ）去唾液酸后能大量进入肝脏,加速在体内的分解代谢,使血中浓度迅速降低。α－酸性糖蛋白抑制组织对脂蛋白（ａ）和去唾液酸脂蛋白（ａ）的摄入,使血中脂蛋白（ａ）和去唾液酸脂蛋白（ａ）含量显著增高。壳聚糖和姜黄素增加肝脏和肾上腺对脂蛋白（ａ）的摄取,使血中脂蛋白（ａ）含量略降低,但对去唾液酸脂蛋白（ａ）代谢无明显影响。甘露聚糖增加脾脏对脂蛋白（ａ）的摄取,减少胆囊中脂蛋白（ａ）含量,但增加肾脏和胆囊对去唾液酸脂蛋白（ａ）的     

Lipoprotein(a) in Type 1 Diabetic Patients with Renal Disease

Lp(a) was measured in 64 normoalbuminuric, 52 microalbuminuric, and 37 proteinuric Type 1 diabetic patients and 54 healthy subjects. Microalbuminuric and proteinuric Type 1 diabetic patients had higher median Lp(a) values (133 (16–1932) and 169 (17–1149) mg I^?1) than patients with normal AER (73 (15–1078) mg I^?1; p=0.048 and p=0.027). Lp(a) in healthy subjects (110 (15–1630)mg I^?1) did not differ from the diabetic subgroups. The frequency of Lp(a) values in the upper quarter of the normal distribution was similar in the diabetic groups and did not differ between diabetic and control subjects. The cumulative distribution of Lp(a) was similar in all groups. Lp(a) concentrations were not related to AER, age, gender, duration of diabetes, body mass index, glycaemic control, serum creatinine, free insulin or systolic blood pressure. Cholesterol, LDL-cholesterol, triglycerides, and apo B were higher in microalbuminuric and proteinuric than in normoalbuminuric Type 1 diabetic patients. Lp(a) was independently related to diastolic blood pressure, fibrinogen, and macroangiopathy. In conclusion, median Lp(a) concentrations tend to be higher in Type 1 diabetic patients with early and established renal disease, although the differences are small and the overlap between groups large. Lp(a) is related to diastolic blood pressure and fibrinogen, and this association of powerful risk factors suggests that Lp(a) may play a role in the pathogenesis of cardiovascular disease in Type 1 diabetic patients with proteinuria. Whether Lp(a) is an independent determinant of increased cardiovascular risk in these patients needs to be elucidated by prospective studies.     

脂蛋白(a)水平与心血管疾病相关性研究进展

脂蛋白(a)是一种与低密度脂蛋白类似的脂蛋白,可以促进动脉粥样硬化及血栓形成,与冠状动脉粥样硬化性心脏病、脑血管病、糖尿病等多种疾病密切相关。流行病学资料及多个临床试验均显示脂蛋白(a)可以预测动脉硬化的风险,是冠状动脉粥样硬化性心脏病的独立危险因素之一;高浓度脂蛋白(a)还将加速动脉硬化的发展。随着对脂蛋白(a)的病理生理,致病机制等方面研究的进展,高脂蛋白(a)浓度的治疗方法也有了令人鼓舞的成果。现就脂蛋白(a)与心血管疾病的相关性作如下综述。     

Single Lipoprotein Apheresis Session Improves Cardiac Microvascular Function in Patients With Elevated Lipoprotein(a): Detection by Stress/Rest Perfusion Magnetic Resonance Imaging

The aim of this study was to explore the effects of a single lipoprotein apheresis session on myocardial stress/rest (S/R) perfusion in patients with elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac magnetic resonance imaging. Twenty patients with Lp(a) > 60 mg/dL and coronary artery disease were randomized into a control or a treatment group. Both groups underwent cardiac magnetic resonance imaging with assessment of left ventricular function, perfusion and viability, and the treatment group underwent lipoprotein apheresis immediately afterwards. Repeat magnetic resonance imaging was performed at 24 h for both groups and at 96 h for just the treatment group. The transmyocardial perfusion gradient (i.e. endo-epi ratio [EER]) was determined and a comprehensive parameter of resting and adenosine-induced stress perfusion was derived (EER-S/R). While the hematocrit remained unchanged, apheresis reduced lipoproteins and rheological parameters: Lp(a) − 55.1%, total cholesterol − 34.5%, low density lipoprotein (LDL) − 54.6%, Lp(a)-corrected LDL − 54.3%, high density lipoprotein − 17.4%, apolipoprotein B − 39.2%, plasma viscosity − 10.7%, and fibrinogen − 30.6% at 24 h (P < 0.05 for all). At 96 h these parameters, except for plasma viscosity, apolipoprotein B and Lp(a)-corrected LDL, recovered but did not reach baseline values (P < 0.05 for all). The EER-S/R at 24 h was lowered by therapy (ΔEER-S/R 5%; P < 0.03), whereas this effect disappeared at 96 h. The ejection fraction (EF) was slightly improved at 24 h (67.07 ± 6.28% vs. 64.89 ± 6.39%; ΔEF 2.2%, P < 0.05) and returned to baseline at 96 h. In the control group no corresponding changes were detected. In conclusion, cardiac magnetic resonance imaging detects subtle treatment-related changes in regional myocardial perfusion in patients with elevated Lp(a) and coronary artery disease undergoing lipoprotein apheresis.     

脂蛋白(a)、纤维蛋白原和高敏C反应蛋白联合检测在冠心病诊断中的应用价值

目的探讨脂蛋白(a)、纤维蛋白原和高敏C反应蛋白联合检测对冠心病的诊断价值。方法对166例疑诊冠心病的患者进行冠状动脉造影检查,根据造影结果分为冠心病组和非冠心病组,收集2 mL抗凝全血标本,分离血浆,采用免疫比浊法,将同一标本同时在日立7170全自动生物化学分析仪测定脂蛋白(a)、纤维蛋白原和高敏C反应蛋白三个指标。结果冠心病组脂蛋白(a)、纤维蛋白原和高敏C反应蛋白测定值均显著高于非冠心病组(P<0.01);单个指标脂蛋白(a)、纤维蛋白原和高敏C反应蛋白诊断冠心病的灵敏度依次为脂蛋白(a)(73.9%)>高敏C反应蛋白(63%)>纤维蛋白原(56.5%),特异性为高敏C反应蛋白(86.5%)>纤维蛋白原(75.7%)>脂蛋白(a)(70.3%)。三项指标联合检测对冠心病患者诊断的特异度(91.9%)高于分别应用脂蛋白(a)(70.3%)、纤维蛋白原(75.7%)和高敏C反应蛋白(86.5%)单一指标。结论联合应用脂蛋白(a)、纤维蛋白原和高敏C反应蛋白进行检测,能更准确诊断冠心病的发生,这为建立一种集成检测来提高对心脑血管疾病诊断的新方法提供了理论依据。     

脂蛋白(a)与心血管疾病的关系

脂蛋白(a)[Lp(a)]结构类似于低密度脂蛋白(LDL),高水平Lp(a)是一种公认的心血管疾病危险因子。体内存在氧化型Lp(a)更易于促进动脉粥样硬化的发生发展。Lp(a)中的载脂蛋白(a)[apo(a)]存在异质性,研究显示其危险性可能是由于apo(a)等位基因水平差异引起的,而且apo(a)的多态性影响到Lp(a)水平的临床测定,如何降低apo(a)对结果的影响还需要更多深入研究。目前针对高Lp(a)水平的人群尚无统一的治疗标准,但降脂治疗有益于预防心脑血管疾病的发生。     

脂蛋白(a)及高敏C-反应蛋白与冠状动脉狭窄病变的相关研究

目的探讨脂蛋白（a）[Lp（a）]、高敏C-反应蛋白（hs—CRP）与冠状动脉（冠脉）狭窄的相关性。方法480例怀疑患有冠心病的患者在冠状动脉造影术前测定血清LD（a）和hs—CRP，冠脉病变的范围用冠脉病变的血管支数表示。结果①冠脉狭窄病变组351例，对照组129例。冠脉狭窄病变组患者的血清Lp（a）和hs—CRP水平分别为（129．18±2．21）mg／L和（1．68±3．40）mg／L，对照组分别为（50．18±1．84）mg／L和（0．81±2．86）mg／L，冠脉狭窄病变组患者的血清Lp（a）和hs—CRP水平均显著高于对照组（P〈0．01）。②单支病变组133例，双支病变组118例，三支病变组100例。单支病变组Lp（a）和hs—CRP水平分别为（116．90±2．15）mg／L和（1．54±3．24）mg／L，双支病变组分别为（128．77±2．16）mg／L和（1．89±3．14）mg／L，三支病变组分别为（148．15±2．31）mg／L和（1．99±3．95）mg／L。单支、双支及三支病变组LD（a）及hs—CRP均显著高于对照组（P〈0．01）。③Logistic回归分析结果显示，Lp（a）〉300mg／L者，发生冠心病的危险性增加（OR为1．025，95％CI：1．018～1．032，P〈0．001）；hs—CRP〉3．00mg／L者，发生冠心病的危险性增加（OR为1．281，95％CI：1．120～1．465，P〈0．001）。④Lp（a）与hs—CRP之间呈正相关（r=0．172，P〈0．01）。结论血清Lp（a）和hs—CRP水平与冠脉狭窄病变密切相关，均是冠心病的独立危险因素。     

The role of Lipoprotein(a) in cardiovascular disease: Current concepts and future perspectives

High lipoprotein(a) [Lp(a)] levels are associated with the development of atherosclerotic cardiovascular disease (ASCVD) and with calcific aortic valve stenosis (CAVS) both observationally and causally from human genetic studies. The mechanisms are not well characterized but likely involve its role as a carrier of oxidized phospholipids (OxPLs), which are known to be increased in pro-inflammatory states, to induce pro-inflammatory changes in monocytes leading to plaque instability, and to impair vascular endothelial cell function, a driver of acute and recurrent ischemic events. In addition, Lp(a) itself has prothrombotic activity. Current lipid-lowering strategies do not sufficiently lower Lp(a) serum levels. Lp(a)-specific-lowering drugs, targeting apolipoprotein(a) synthesis, lower Lp(a) by up to 90% and are being evaluated in ongoing clinical outcome trials. This review summarizes the current knowledge on the associations of Lp(a) with ASCVD and CAVS, the current role of Lp(a) assessment in the clinical setting, and emerging Lp(a)-specific-lowering therapies.