血脂異常對心臟電器生理及機械功能之影響

Abstract

許多動物實驗及人類研究結果顯示出,高膽固醇血症可以經由非動脈硬化的病生理機制 來增加心肌缺氧時的損害,例如改變心肌細胞膜上的鈉或鈣離子孔道,影響血小板的活性等 等。通常冠狀動脈粥狀硬化的過程需要數年的時間,而血脂異常所造成的心肌細胞功能上之 失全或“易感性”早在這以前便已發生。因此,臨床實驗所觀察到的降血脂藥物可以很快 的降低冠心病之併發症,其大部份的機轉應該是經由改善這些血脂異常所造成的非動脈粥狀 硬化因素而來。過去的研究顯示在誘發致死性的心室性纖維顫動時,一個“易感的”心肌 可能與“刺激 (比如心肌缺氧 )”或危險因子的存在同樣重要。心肌細胞膜的生理機制在 誘發心律不整的電氣生理機轉中佔有中心性之地位,因此改變心肌細胞膜的功能亦可改變心 肌的“易感度”。過去已有許多的研究顯示生物細胞膜的脂質成分改變是造成細胞功能變 化的基礎。我們過去的研究也顯示高膽固醇血症會降低心肌細胞膜上鈉離子流的活性。 由於原三年期之研究計劃被刪減為一年之經費,故本年度主要完成原第一年度欲達成之目 標。本研究選取58 位因急性心肌梗塞(AMI)住入本院加護病房中而在第一天併發心室性心律 不整(VT/VF)之病患(A 組),及另58 位性別、年齡及血栓溶解治療相稱的AMI 病患(B 組)。 吾人登錄其冠心病之危險因子,血壓,心跳及檢測其一週內及三個月後的血中總膽固醇(TC)、 高密度膽固醇(HDL-C)、低密度膽固醇(LDL-C)、三酸甘油酯(TG)含量。吾人發現,病人住院當 中的血中脂值濃度均較出院後三個月低。在急性期,A 組病人之LDL-C 較B 組高(137.6 ±35.6 對122.5 ±31.3mg/dl,p=0.002),其平均血壓較低(89.0 ±18.7 對99.8 ±17.4mmHg),而Killip 分類為Ⅲ或Ⅳ者亦較多(16 對5%,p=0.127)。在三個月之慢性期,A 組病患之TC (224.6 ±42.2 對198.2 ±33.2mg/dl,p<0.001),LDL-C (159.4 ±38.1 對128.3 ±30.0mg/dl,p<0.0001)及TG (179.8 ±102.3 對136.6 ±68.4mg/dl,p=0.009)均較B 組為高。以多變數分析法發現,慢性 期之LDL-C 值(p=0.0009),急性期之平均血壓(p=0.0029),慢性及急性期之TG 值差 (p=0.0466)與急性期病患是否會發生VT/VF 非常有關,為獨立之危險因子。 因此,吾人可據以結論,血脂異常可使急性心肌梗塞病患較易發生心室性心律不整。它可 部份解釋為何近年來發表的大型藥物研究報告中,降血脂藥物可以降低冠心病的猝死率。

Background Ventricular tachycardia/fibrillation (VT/VF) developing in the acute stage of myocardial infarction is a primary factor of sudden cardiac death that still remains as a major problem in contemporary cardiology. Several animal studies have shown that dyslipidemia can alter the lipid composition of myocardial membrane and subsequently increases the susceptibility of cardiac arrhythmia. To the best of our knowledge, there have been no previous human studies providing the longitudinal evidence of a relationship between plasma dyslipidemia and arrhythmia. The aim of this study is to determinate whether dyslipidemia is a predisposing factor of the occurrence of VT/VF during the acute stage of myocardial infarction. Methods and Results A total of 58 patients experiencing VT/VF within 24 hours after the onset of chest pain were matched to 58 patients without such clinical events. Sex (104 males), age (58+10 years), and the use of thrombolytic therapy (n=82) were required to matched in both groups initially. To diagnose a patient with dyslipidemia, the lipid profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were measured during patients’ hospitalization period (day 1 and day 7) and the outpatient follow up at the 3rd month after the index event. Other coronary risk factors, as well as clinical, hemodynamic, and angiographic characteristics were also included in our assessment. The mean serum levels of TC, HDL-C, LDL-C, and TG measured during hospitalization were all lower than those measured 3 months later (-9%, P=0.0003; -6%, P=0.08; -10%, P=0.004; and –9%, P=0.16, respectively). A unique and intriguing pattern was observed in the patients with incidence of VT/VF. During the acute stage, they had a higher level of LDL-C (137.6+35.6 vs. 122.5+31.3 mg/dl, P=0.02), a lower mean blood pressure (89.0 ±18.7 vs. 99.8 ±17.4 mmHg, P=0.002), and a higher percentage with Killip class III or IV (16 vs. 5%, P=0.127) on the initial arrival. At the 3-month follow up, these patients with experience of VT/VF had a higher level of TC (224.6+42.2 vs. 198.2+33.2 mg/dl, P<0.001), LDL-C (159.4+38.1 vs. 128.3+30.0 mg/dl, P<0.0001), and TG (179.8+102.3 vs. 136.6+68.4 mg/dl, P=0.009). In multivariate analysis, the LDL cholesterol ( P=0.0009) at the 3-month follow up, the mean blood pressure on arrival ( P=0.0025), and the difference in level of triglyceride between the first week and the third month ( P=0.0466) were all accounted the independent predictors for the occurrence of VT/VF in the acute stage of myocardial infarction. Conclusions This study suggested that dyslipidemia imposed a higher risk of developing VT/VF in the acute phase of myocardial infarction. It might partly explain the reason why the current treatment with lipid-lowering drugs could reduce the risk of major coronary events, including sudden cardiac death, in recently published large-scale study trials.