Khan Tina Z, Hartley Adam, Haskard Dorian, Caga-Anan Mikhail, Pennell Dudley J, Collins Peter, Barbir Mahmoud, Khamis Ramzi
National Heart and Lung Institute, Imperial College London, Guy Scadding Building, Cale Street, London SW3 6LY, UK.
Royal Brompton and & Harefield NHS Foundation Trust, Sydney Street, London SW3 6NP, UK.
Antioxidants (Basel). 2021 Jan 18;10(1):132. doi: 10.3390/antiox10010132.
An abundance of epidemiological evidence demonstrates that elevated lipoprotein(a) (Lp(a)) represents a significant contributing risk factor towards the development of cardiovascular disease. In particular, raised Lp(a) may play a mechanistic role in patients with refractory angina. Studies have also shown a correlation between oxidised LDL (oxLDL) levels and atherosclerotic burden as well as rates of cardiovascular events. Antibodies against oxLDL (anti-oxLDL) are involved in the removal of oxLDL. Lipoprotein apheresis (LA), which removes lipoproteins using extra-corporeal processes, is an established means of reducing Lp(a), and thereby reduces cardiovascular events. The aim of this study was to investigate the effect of LA on oxLDL and anti-oxLDL levels amongst those with refractory angina in the context of raised Lp(a). We performed a sub-study within a randomised controlled crossover trial involving 20 patients with refractory angina and raised Lp(a) > 500 mg/L, comparing the effect of three months of blinded weekly LA or sham, followed by crossover to the opposite study arm. We utilized enzyme-linked immunosorbent assays (ELISA) to quantify oxLDL and IgG/ IgM anti-oxLDL antibody levels at baseline and following three months of active LA or sham sessions. Following three months of LA, there was a 30% reduction in oxLDL from 0.37 ± 0.06 to 0.26 ± 0.04 with a mean drop of -0.11 units (U) (95% CI -0.13, -0.09) compared to no significant change with sham therapy ( < 0.0001 between treatment arms). LA also led to a 22% reduction in levels of IgG and IgM anti-oxLDL, again with no significant change demonstrated during sham ( = 0.0036 and = 0.012, respectively, between treatment arms). Amongst patients with refractory angina in the context of elevated Lp(a), LA significantly lowers levels of oxLDL and anti-oxLDL antibodies, representing potential mechanisms by which LA yields symptomatic and prognostic benefits in this patient cohort.
大量流行病学证据表明，脂蛋白(a)[Lp(a)]水平升高是心血管疾病发生的一个重要风险因素。特别是，Lp(a)升高可能在难治性心绞痛患者中起作用机制。研究还表明，氧化型低密度脂蛋白(oxLDL)水平与动脉粥样硬化负担以及心血管事件发生率之间存在相关性。抗oxLDL抗体(抗oxLDL)参与oxLDL的清除。脂蛋白分离术(LA)通过体外过程去除脂蛋白，是降低Lp(a)从而减少心血管事件的一种既定方法。本研究的目的是在Lp(a)升高的情况下，研究LA对难治性心绞痛患者oxLDL和抗oxLDL水平的影响。我们在一项随机对照交叉试验中进行了一项子研究，该试验涉及20名难治性心绞痛且Lp(a)>500mg/L的患者，比较了三个月每周一次的盲法LA或假治疗的效果，然后交叉到相反的研究组。我们利用酶联免疫吸附测定(ELISA)在基线时以及在进行三个月的活性LA或假治疗后对oxLDL和IgG/IgM抗oxLDL抗体水平进行定量。在进行三个月的LA治疗后，oxLDL从0.37±0.06降至0.26±0.04，平均下降-0.11单位(U)(95%CI-0.13，-0.09)，而假治疗无显著变化(治疗组之间<0.0001)。LA还使IgG和IgM抗oxLDL水平降低了22%，同样，假治疗期间无显著变化(治疗组之间分别为=0.0036和=0.012)。在Lp(a)升高的难治性心绞痛患者中，LA显著降低oxLDL和抗oxLDL抗体水平，这代表了LA在该患者队列中产生症状改善和预后益处的潜在机制。
