Bruwer Daniel, de Lange-Loots Zelda, Koschinsky Marlys L, Boffa Michael B, Pieters Marlien
Centre of Excellence for Nutrition, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa (Drs Bruwer, de Lange-Loots and Pieters).
Centre of Excellence for Nutrition, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa (Drs Bruwer, de Lange-Loots and Pieters); SAMRC Extramural Unit for Hypertension and Cardiovascular Disease, Faculty of Health Sciences, North-West University, Potchefstroom, South Africa (Drs de Lange-Loots and Pieters). Electronic address: https://twitter.com/Zelda_dLL.
J Clin Lipidol. 2024 Nov-Dec;18(6):e1002-e1014. doi: 10.1016/j.jacl.2024.08.004. Epub 2024 Aug 12.
Case-control, intervention and laboratory studies have demonstrated a link between apolipoprotein B (ApoB)-containing lipoproteins and clot structure and thrombosis. There is, however, limited evidence on a population level.
We determined the cross-sectional relationship between lipoprotein(a) [Lp(a)], low-density lipoprotein cholesterol (LDL-C), and ApoB with fibrinogen and plasma clot properties in 1462 Black South Africans, a population with higher fibrinogen and Lp(a) levels compared with individuals of European descent.
Data were obtained from participants in the South African arm of the Prospective Urban and Rural Epidemiology study. Clot properties analyzed included lag time, slope, maximum absorbance, and clot lysis time (turbidity). Lp(a) was measured in nM using particle-enhanced immunoturbidimetry. General linear models (GLM) were used to determine the associations between ApoB and ApoB-containing lipoproteins with fibrinogen and plasma clot properties. Stepwise regression was used to determine contributors to clot properties and Lp(a) variance.
GLM and regression results combined, indicated fibrinogen concentration and rate of clot formation (slope) had the strongest association with Lp(a); clot density associated positively with both Lp(a) and LDL-C; time to clot formation associated negatively with ApoB; and clot lysis time (CLT) demonstrated strong positive associations with both ApoB and LDL-C, while its association with Lp(a) was fibrinogen concentration dependent.
These findings suggest that ApoB and the lipoproteins carrying it contribute to prothrombotic clot properties in Africans on an epidemiological level and highlight potential novel prothrombotic roles for these (apo)lipoproteins to be considered for the development of targeted therapeutic approaches to address thrombotic conditions related to clot properties.
病例对照研究、干预研究和实验室研究均已证明含载脂蛋白B(ApoB)的脂蛋白与血凝块结构及血栓形成之间存在联系。然而,在人群层面上的证据有限。
我们在1462名南非黑人中确定了脂蛋白(a)[Lp(a)]、低密度脂蛋白胆固醇(LDL-C)和ApoB与纤维蛋白原及血浆凝块特性之间的横断面关系,与欧洲血统个体相比,该人群的纤维蛋白原和Lp(a)水平更高。
数据来自城乡前瞻性流行病学研究南非分支的参与者。分析的凝块特性包括延迟时间、斜率、最大吸光度和凝块溶解时间(浊度)。使用颗粒增强免疫比浊法以纳摩尔为单位测量Lp(a)。采用一般线性模型(GLM)来确定ApoB及含ApoB的脂蛋白与纤维蛋白原和血浆凝块特性之间的关联。采用逐步回归来确定凝块特性和Lp(a)变异的影响因素。
综合GLM和回归结果表明,纤维蛋白原浓度和凝块形成速率(斜率)与Lp(a)的关联最强;凝块密度与Lp(a)和LDL-C均呈正相关;凝块形成时间与ApoB呈负相关;凝块溶解时间(CLT)与ApoB和LDL-C均呈强正相关,而其与Lp(a)的关联取决于纤维蛋白原浓度。
这些发现表明,在流行病学层面上,ApoB及其携带的脂蛋白促成了非洲人血栓前凝块特性,并突出了这些(载)脂蛋白潜在的新的促血栓形成作用,在开发针对与凝块特性相关的血栓形成疾病的靶向治疗方法时应予以考虑。