心房颤动患者体内溶血磷脂类分子含量与无症状性脑梗死的相关性

Elevated plasma lysophosphatidic acid levels and risk of silent brain infarction in patients with atrial fibrillation

目的观察非瓣膜性心房颤动（NVAF）患者中无症状性脑梗死（SBI）的发病率及其血浆溶血磷脂类分子（LPA／AP）含量的变化，探索房颤相关性脑卒中的病理生理学机制，为临床进行抗栓治疗提供依据。方法选取经临床和辅助检查确诊的235例未接受抗栓治疗的NVAF患者、116例无NVAF的SBI患者及120名年龄大于60岁的健康体检者纳入本研究。测定其血浆溶血磷脂酸（LPA）及其极性相似总磷脂（AP）的含量变化。同时观察NVAF合并SBI时体内血小板的活化状态。结果235例NVAF患者中，SBI的发生率为31．5％，其中年龄大于60岁的157例NVAF患者中，SBI的发生率为37．6％。NVAF合并SBI患者血浆LPA含量[（3．78±0．61）μmol／L]显著高于对照组[（2．66±0．49）μmo]／L，95％CI 3．47—4．21，P=0．000]、NVAF无SBI组[（3．29±0．57）wmo]／L，95％CI 3．01—3．76，P=0．008]及无NVAF的SBI组[（3．17±0．54）wmo]／L，95％CI 2．86—3．54，P=0．004]。NVAF无SBI组及无NVAF的SBI组血浆LPA含量也显著高于对照组。NVAF合并SBI患者血浆AP含量显著高于对照组、NVAF无SBI组及无NVAF的SBI组。NVAF无SBI组及无NVAF的SBI组血浆AP含量也显著高于对照组。与对照组相比，年龄大于60岁的NVAF患者合并存在SBI的比率显著升高。NVAF患者合并存在SBI时体内血小板的活化程度显著升高。结论NVAF是SBI的重要危险因素。NVAF患者合并存在SBI时体内血小板的活化程度升高。NVAF或NVAF合并SBI患者均存在缺血性膜损伤。对于NVAF或合并SBI患者在进行抗栓治疗时应充分考虑抗血小板治疗的重要性。LPA可作为一种理想的分子标记物用于判断NVAF或NVAF合一并SBI患者体内血小板的活化状态。

Objective To investigate the changes of plasma lysophosphatidic acid （LPA） or acidic phospholipids （AP） levels in patients with nonvalvular atrial fibrillation （NVAF）or NVAF associated with silent brain infarction （SBI） and to provide biochemistry evidence to antithrombotic therapy. Methods Plasma LPA/AP levels was examined in blood freshly sampled in 235 cases of NVAF who were not receiving any antithrombotic therapy, 116 cases SBI who were not with NVAF and 120 cases healthy volunteers as control enrolled in the LPA and stroke prevention study. Plasma LPA was assayed by measuring its inorganic phosphorus after separation by chromatograph. Meanwhile, the platelet activation in NVAF or （and） SBI were observed. Results SBI was found in 31.5% of the participants with NVAF, and in 37. 6% of the elderly NVAF subjects （age 〉 60 years old）. LPA/AP levels were significantly increased in NVAF with SBI group（（3.78 ±0.61） μmol/L） compared with controls（（2.66 ±0.49） μmol/L, 95% CI 3.47-4.21, P = 0. 000）, NVAF without SBI group （ （ 3. 29 ±0. 57 ）μmo//L, 95% CI 3. 01-3. 76, P = 0. 008 ）, SBI without NVAF group（ （3. 17 ±0.54） μmo]/L, P=0. 004）. The platelet activation was significantly higher in NVAF with SBI group, the odds ratio （95% CI） was 21.39 （ 10. 17 to 45.02 ）, than those in NVAF without SBI group （ P 〈 0. 01 ）. Conclusion The plasma LPA/AP levels were significantly elevated in NVAF or NVAF with SBI, NVAF contributes to the risk of SBI. Platelet activation may play an important role in the pathogenesis of thromboembolism in NVAF and the measurement of LPA reflects activation of platelets in vivo and may be a useful marker for the diagnosis of thrombosis or prothrombotic states. Consideration of the role of antiplatelet therapy should be given when choosing antithrombotic therapy to NVAF-associated ischemic stroke.