中西医结合治疗缺血性脑血管病研究
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摘要
1研究目的及选题思路
缺血性脑血管病具有发病率高、致残率高、死亡率高、复发率高等特点,成为危害人类健康的重要疾病。缺血性脑血管病主要包括TIA和脑梗死,而动脉粥样硬化形成斑块并造成脑供血动脉狭窄是缺血性脑血管病的重要病因。脑动脉粥样硬化好发于颅内、外大中动脉分叉部及弯曲部,东西方人脑血管病的发病特点、危险因素和远期预后存在很多差异,颅内外动脉粥样硬化发生的部位、病理特点等也不完全相同。美国每年新发作的卒中与颅外段颈动脉狭窄有关,占35%～70%,而亚洲国家报道颅内动脉狭窄是引起脑梗死和TIA的重要原因,但国内此方面较大样本的研究尚少。中医诊治中风有悠久的历史。在中风病整个疾病进程中,从急性期到后遗症期,随着病机的变化,中风病的证候随之发生动态变化。只有把握其证候的动态演变规律,才能全面完整的认识中风,在临床采取果断准确的处方用药,因此了解国人缺血性脑血管病患者的血管学资料及中医证候特点,可以更好的认识和防治缺血性脑血管病。症状性颅内外动脉狭窄病变是中风发作的主要原因,血管内治疗技术为颅内外动脉狭窄开辟了新的治疗方法,但是其安全性有效性仍处于探索阶段。现在另一个研究的热点就是支架后再狭窄。中医药防治动脉支架术后再狭窄,可以发挥中医药复方全面调节机体机能和多途径、多环节、多靶点干预的优势,有望开辟一条新的治疗途径。但是中医药如何干预,干预的时间窗、方法、结局等成为亟待解决的问题。解决这些问题的关键离不开中医的辨证论治,而辨证论治的核心在于对中医证候演变规律的认识和把握。因此,明确缺血中风患者脑供血动脉支架围手术期中医证候演变规律,可以为进一步深入研究脑供血动脉支架术后中长期中医证候演变规律奠定基础,为中医药防治缺血中风患者动脉支架术后再狭窄提供前期可靠的临床证候学依据。
2研究方法
回顾性分析我脑血管病中心缺血性脑血管病患者DSA资料,并填写中风病中医证候调查表,分三部分对以上问题进行探讨。
第一部分：通过分析数字减影血管造影(DSA)资料明确缺血性脑血管病患者脑动脉狭窄病变特点。
第二部分：分析缺血性脑血管病患者急性期中医证候分布规律,结合DSA结果分析脑动脉狭窄病变与中医证候的相关性。
第三部分：评价颅内外支架治疗脑动脉粥样硬化性狭窄病变的安全性、有效性,分析支架围手术期中医证候演变规律。
3研究结果
第一部分：缺血性脑血管病患者362例,其中334例患者存在脑动脉狭窄,占总数的92.3%。所有存在脑动脉狭窄患者中单纯颅内动脉狭窄病变患者143例(42.8%),单纯颅外动脉狭窄病变患者84例(25.2%),颅内颅外动脉均存在狭窄病变患者107例(32%)；单纯前循环狭窄病变患者173例(51.8%),单纯后循环狭窄病变患者58例(17.4%),前后循环联合狭窄病变103例(30.8%)。颅外动脉狭窄好发位置：颈内动脉颅外段185处(61.7%),椎动脉颅外段96处(32%),锁骨下动脉19处(6.3%)；颅内动脉狭窄好发位置：颈内动脉颅内段55处(13.2%),大脑前动脉55处(13.2%),大脑中动脉171处(41.2%),大脑后动脉29处(7%),椎动脉颅内段54处(12.9%),基底动脉52处(12.5%)。
334例脑动脉狭窄病变的患者中共有84例(25.1%)存在侧枝循环,主要为Willis环代偿及邻近软脑膜动脉代偿。脑动脉闭塞且有侧枝循环的患者NIHSS评分明显低于无侧枝循环者,经过统计学分析,P=0.01,差异有统计学意义。
362例缺血性脑血管病患者,共有299例存在责任血管。脑梗塞与TIA患者责任血管狭窄分布与程度经统计学分析P>0.05,均无统计学意义。
在颅外动脉狭窄中高血压(p=0.025)与动脉狭窄有关,危险度为5.046；不同年龄分组颅内外动脉狭窄分布发生比例与程度明显不同,P<0.01,有统计学意义。
第二部分：急性缺血性中风患者247例,其中230例患者存在脑动脉狭窄病变,占总数的93.1%；而存在脑动脉狭窄患者中198例可以确认责任血管狭窄病变。
单纯颅内动脉狭窄患者51例(45.7%),单纯颅外动脉狭窄患者51例(22.2%),颅内颅外动脉均存在狭窄患者74例(32.2%)；单纯前循环狭窄病变147例(63.9%),单纯后循环狭窄病变24例(10.4%),前后循环均狭窄59例(25.7%)。
缺血性中风急性期中医证候分布以风证最多,其次为痰湿证,再次为血瘀证、气虚证、火热证,阴虚阳亢证最少。证候组合以三证组合为最多,共145例(58.7%)其次为两证组合,共52例(20.6%),再次为四证组合,共48例(19.4%),单证(2例,占0.8%)和五证(1例,0.4%)组合少见。缺血性中风急性期证候以风、痰、瘀为主证,兼加虚证、火热证、阴虚阳亢等,组成了各种证候组合。
危险因素与中医证候相关性多因素Logistic回归分析,高血压史是痰湿证的相关因素；糖尿病史与吸烟是火热证的相关因素；吸烟史、冠心病史和既往中风史是气虚证的相关因素,均有统计学意义。
单纯颅内动脉狭窄病变痰湿证的发生率明显高于单纯颅外动脉狭窄病变,差异有统计学意义(P=0.027)；单纯颅外动脉狭窄病变血瘀证发生率明显高于单纯颅内狭窄病变,差异有显著统计学意义(P=0.007)。颅外动脉狭窄程度与血瘀证明显相关(P<0.01),且秩相关提示等级相关系数rs值为0.975(P<0.01),呈明显正相关。颅内动脉狭窄程度与痰湿证明显相关(P<0.01),且秩相关提示等级相关系数rs值为0.896(P=0.004),呈明显正相关,颅内动脉狭窄程度与血瘀证也相关(P=0.05)。
第三部分：颅外动脉支架前后及支架2周后,风证在支架前后有显著差异(P=0.001),有统计学意义；痰湿证在支架前后有显著差异(P=0.01),有统计学意义,火热证在支架前后有明显差异(P=0.018),有统计学意义；血瘀证在支架前后有明显差异(P=0.011),有统计学意义；且根据Ranks结果提示,以上四证在支架后及支架后2周均明显减少。气虚证在支架前后有显著差异(P=0.003),有统计学意义,且根据Ranks结果提示,气虚证在支架后及支架后2周明显增多。
颅内动脉支架前后及支架2周后,风证在支架前后有显著差异(P=0.007),有统计学意义,血瘀证在支架前后有明显差异(P=0.042),有统计学意义,且根据Ranks结果提示,以上2证在支架后及支架后2周均明显减少。
颅外动脉支架前后证候组合差异明显,P=0.001,有统计学意义,即术前两证组合、三证组合最多,术后单证、两证组合增多,而三证、四证组合减少；虚实组合P=0.000<0.01,有统计学意义,即术前实证最多,虚证最少,术后实证减少,虚证及本虚标实证增多。
颅内动脉支架前后证候组合P>0.05,无统计学意义。虚实组合,P=0.001,差异有统计学意义,即术前实证最多,虚证最少,术后实证减少,虚证增多。
64例行颅外动脉支架患者,共有4例发生手术相关并发症,占6.2%,均为颈内动脉起始部支架后并发症。36例成功放置颅内动脉支架患者,共有5例(13.9%)发生手术相关并发症。2例为大脑中动脉支架,3例为基底动脉支架。
DSA随访：颅外动脉支架患者59例共有3名患者随访DSA发现支架内再狭窄,椎动脉开口处支架再狭窄2例,再狭窄发生率12.5%；锁骨下动脉再狭窄1例,再狭窄发生率11.1%。颅内动脉支架患者27例共有4例患者随访DSA发现支架内再狭窄,均为大脑中动脉支架,均为Winspan支架,再狭窄发生率30.8%。
中医证候随访：颅外动脉支架后再狭窄随访,1例再狭窄50%,中医证候为痰湿+气虚证；2例再狭窄70%,中医证候分别为痰湿+气虚+血瘀、痰湿+血瘀；颅内动脉支架后再狭窄随访,1例狭窄20%,中医证候为痰湿+火热证；1例狭窄23%,中医证候为血瘀证；2例均狭窄50%,1例中医证候为血瘀证,1例中医证候为痰湿+气虚证。
4研究结论
第一部分缺血性脑血管病患者DSA动脉狭窄病变特点
1缺血性脑血管病患者颅内外动脉狭窄病变发生率较高,且本研究病例中单纯颅内动脉狭窄病变发生率高于单纯颅外狭窄病变。
2脑梗塞组与TIA组责任血管狭窄病变比较无统计学差异,提示我们更应该重视TIA的快速病因诊断,及时给与治疗,防止其进展为脑梗塞。
3脑动脉狭窄程度是引起神经功能缺损的主要因素,但侧枝循环起了非常重要的保护作用,尤其是Willis环和邻近脑软膜支代偿。
4各种危险因素中,颅外动脉狭窄与高血压(P=0.025)有关,危险度为5.046；不同年龄分组颅内外动脉狭窄分布发生比例与程度明显不同,P<0.01,有统计学意义。中青年组易发生颅内狭窄,而老年组易发生颅外动脉狭窄。
第二部分缺血性脑血管病患者急性期中医证候分布与DSA结果相关性
1缺血中风急性期中医证候分布
以风证出现概率最高(87.4%),证候组合以三证组合为最多,共145例(58.7%),证候组合分别以风证、痰湿证、血瘀证为主证,相互组合并兼加气虚、火热、阴虚阳亢证,组成了各种证候组合。
2危险因素与中医证候相关性分析
高血压史与痰湿证呈负相关；糖尿病史与火热证呈负相关,吸烟史与火热证呈正相关；吸烟史、冠心病史与气虚证呈负相关,既往中风史与气虚证呈正相关。这些结果提示我们在临床工作中对于无证可辨的中风病患者,可以将患者的危险因素和临床某些客观检查加以联系,参考本研究结果以辨证施治。
3脑动脉狭窄病变部位、程度与中医证候相关性分析
主要表现为颅外动脉狭窄分布及程度与血瘀证呈明显正相关,颅内动脉狭窄分布及程度与痰湿证明显相关。
第三部分脑动脉支架围手术期中医证候特点
1脑动脉支架治疗前后中医证候演变有规律可循,主要表现为实证的减少和虚证的增加,本研究结果提示支架介入治疗相当于中医清热化痰除瘀的作用,可以改变甚至逆转中风病自然证候演变规律,但支架易引起出血、乏力加重等证,所以在支架介入术后应以扶正培元为主,兼以祛痰化瘀,清热解毒。
2颅外动脉支架尤其是颈动脉支架是安全有效的,颅内动脉支架风险较高,应谨慎开展。
3中西医结合防治颅内外支架后再狭窄是可行的,应开展更深入的研究。
1 Background and Objective:
Ischemic cerebrovascular disease with high incidence and high morbidity, high mortality and high recurrence rate has become a major disease harm human health. It includes TIA and cerebral infarction, the formation of atherosclerotic plaques and cerebral artery stenosis is an important cause of ischemic cerebrovascular disease.Cerebral artery atherosclerosis offen occurs in intracranial and extracranial, medium and large arteries and the bifurcation of the Department of bending, there are many differences between East and West patients in the characteristics of cerebrovascular disease, risk factors and long-term prognosis. The position and pathological characteristics of intracranial and extracranial atherosclerosis are not exactly the same In United States, the new onset of stroke is mainly caused by extracranial carotid artery stenosis, accounting for 35% to 70%, but in Asian, it reported that intracranial arterial stenosis is an important reason which caused cerebral infarction and TIA. However, a larger sample of domestic research in china is still less. Traditional Chinese Medicine has a long history of stroke treatment. Throughout the process of stroke, from the acute phase to the Sequela, the stroke syndrome changes while the pathogenesis changes occurring. Only by understanding the dynamic evolution of TCM syndromes law, we could fully and completely understand the stroke.Then take decisive and accurate drugs. Therefore, By finding out the features of vascular information and TCM Syndrome in Chinese patients, we can have a better understanding and can prevent the ischemic cerebrovascular disease. Symptoms of cerebral artery stenosis is the main reasons of stroke, endovascular treatment of cranial arterial stenosis technology opens up a new treatment. However, the effectiveness and their safety are still at the exploratory stage. Another research focus in the stent restenosis, TCM prevent the stent restenosis, which can play a Superiority of Chinese medicine compound regulate the body functions and multi-channel, multi-link, and the advantages of multi-target interference is expected to open up a new therapeutic approach. However, how Chinese medicine to intervene, The time window of intervention, methods, outcomes have become pressing problem. The key to solving these problems can not do without TCM syndrome, understanding the syndrome differentiation and grasp of the law is the core of the evolution of the TCM. Therefore, defining the TCM Syndrome perioperative cerebral artery stent, it can provide early and reliable basis for clinical symptoms and signs for TCM prevention of restenosis after stenting.
2 Research methods
A retrospective analysis of patients'DSA information who suffered ischemic cerebrovascular disease, and fill stroke TCM syndromes questionnaire, It divided into three sections to discuss above issues:
PartⅠ:Analysis of digital subtraction angiography (DSA) to define cerebral artery stenosis characteristics in patients with cerebral artery stenosis.
PartⅡ:Analysis the TCM syndrome distribution laws of patients with ischemic cerebrovascular disease, Combining with DSA results, analysis of the correlation between cerebral artery stenosis and TCM Syndrome.
PartⅢ:Evaluation of safety and effectiveness of cerebral artery stent, analysis of TCM Syndrome evolution rule perioperative stent
3 results
PartⅠ:362 cases of patients with ischemic cerebrovascular disease, of which 334 cases had cerebral artery stenosis, accounting for 92.3%. In all patients with cerebral artery stenosis,143 patients (42.8%) only had intracranial artery stenosis; 84 patients (25.2%) only had extracranial artery stenosis; there were 107 cases (32%) of patients had intracranial and extracranial artery stenosis.173 patients (51.8%) with anterior circulation stenosis; 58 patients (17.4%) with posterior circulation stenosis; 103 cases (30.8%) of patients with combined stenosis. Extracranial artery stenosis often occurred in:extracranial internal carotid artery 185 (61.7%) extracranial vertebral artery 96 (32%), subclavian artery 19 (6.3%); intracranial arterial stenosis made better position:intracranial internal carotid artery 55 (13.2%), anterior cerebral artery 55 (13.2%), middle cerebral artery 171 (41.2%), posterior cerebral artery 29 (7%), intracranial vertebral artery 54 (12.9%), basilar artery 52 (12.5%).
334 cases of cerebral artery stenosis in patients with a total of 84 patients (25.1%) had collateral circulation, mainly for the Willis ring and adjacent pial artery compensatory compensation. Cerebral artery occlusion and collateral circulation in patients with NIHSS score was significantly lower than those without collateral circulation, through statistical analysis, P = 0.01, the difference was statistically significant.
362 cases of ischemic cerebrovascular disease, a total of 299 vessels of responsibility. Cerebral infarction and TIA in patients with vascular stenosis distribution and extent of responsibility for the statistical analysis P> 0.05, not statistically significant.
For extracranial artery stenosis, hypertensive is related to arterial stenosis (p= 0.025), risk is 5.046; different age group distribution different cranial artery stenosis occurrence and degree, P<0.01, statistically significant.
Part II:247 cases of patients suffer acute ischemic stroke, of which 230 cases of patients had cerebral artery stenosis, accounting for 93.1%; 198 cases of patients can be confirmed responsibility vascular stenosis. Alone in patients with intracranial arterial stenosis in 51 cases (45.7%), extracranial artery stenosis alone,51 patients (22.2%), intracranial and extracranial arteries stenosis exist in 74 cases (32.2%); 147 cases of anterior circulation stenosis (63.9%), pure posterior circulation stenosis in 24 patients (10.4%),59 patients unite cycling are narrow (25.7%).
Distribution of TCM syndrome evidence with acute ischemic stroke:The most is wind, followed by phlegm, blood stasis again, qi deficiency,the least is syndrome of yin deficiency and yang hyperactivity. In syndrome combine, three-syndrome combination is the most with total of 145 cases (58.7%), followed by the combination of two cards, a total of 52 cases (20.6%), again syndrome for the four combinations, a total of 48 cases (19.4%), document (2 cases, accounting for 0.8%) and five-card (1 case,0.4%), rare combination.
The main syndrome of acute ischemic stroke are wind, phlegm, blood stasis, and additional deficiency of qi deficiency and yin deficiency and yang hyperactivity, to form various combinations of syndrome.
Logistic regression analysis, history of hypertension is related phlegm; history of diabetes and smoking are fiery evidence related factors; smoking history, coronary heart disease history and previous history of stroke is related to qi deficiency, all were statistically significant.
Phlegm with intracranial arterial stenosis alone were significantly higher than that of extracranial artery stenosis, the difference was statistically significant (P= 0.027); pure extracranial artery stenosis incidence of blood stasis was significantly higher than intracranial stenosis, the difference was statistically significant (P= 0.007). Extracranial artery stenosis was significantly associated with blood stasis syndrome (P<0.01), and the rank correlation coefficient of rank correlation rs value prompted 0.975 (P<0.01), was positively correlated. Intracranial arterial stenosis significantly correlated with phlegm (P<0.01), and the rank correlation coefficient of rank correlation rs value prompted 0.896 (P= 0.004), positive correlation.
Part III:Before and after extracranial artery stents:the wind syndrome significantly different (P= 0.001), there was significant; phlegm syndrome significantly different (P= 0.01), there statistically significant; blood stasis before and after stent significantly difference (P= 0.011), there was significant; FHP significant difference before and after the stent (P= 0.018), statistically significant, and Ranks results suggest that these four cards significantly reduced after the stent and 2 weeks later, Qi deficiency before and after stent significantly different (P= 0.003), there was significant, and Ranks results suggest that Qi deficiency increased significantly after the stent and 2 weeks later.
Before and after intracranial artery stents:the wind permits were significantly different (P= 0.007), statistically significant, blood stasis before and after stent significantly difference (P= 0.042), with statistical significance, Ranks results suggest that these two cards significantly reduced after the stent and 2 weeks later
Before and after extracranial artery stent:the combination syndrome with significantly different, P= 0.001, statistically significant. Which means that two or three card combination are the most preoperative, after stenting, the two card combination increased, and the three cards, four cards combination reduced; deficiency-excess syndrome combine before and after stent statistically significant, Which means excess syndrome are the most before stent, reduced postoperative,;deficiency syndrome are the lesst,increased postoperative.
Stent complications:64 case of patients with extracranial artery stenting, 4 patients had surgical complications,6.2%, both the department of carotid artery stent complications.36 cases of intracranial artery stents were successfully placed, a total of 5 cases (13.9%) had surgery-related complications,2 cases of middle cerebral artery stent,3 cases of basilar artery stent.
Follow-up DSA,we found 3of 59 patients with extracranial artery stents restenosis, vertebral artery,2 cases, which restenosis rate is 12.5%; subclavian artery stenosis,1 case, which restenosis rate is 11.1%.27 patients with intracranial artery stents were followed up, for a total of four cases of restenosis was found, all were the middle cerebral artery stents, Winspan stent, the restenosis rate is 30.8%.
Syndromes of TCM follow-up:In extracranial artery stent restenosis, one case of restenosis by 50% with the phlegm syndromes + qi deficiency; two cases of restenosis 70%, respectively, with phlegm syndromes+Qi+Blood, phlegm +blood stasis;
Between intracranial artery stent restenosis, one case of restenosis of 20% with the phlegm syndromes+ FHP; one case of stenosis of 23% with the blood stasis syndromes; two cases of stenosis were 50%, 1 case with blood stasis Syndrome,1 case of TCM syndrome is phlegm+ qi deficiency.
4 Research conclusions
PartⅠThe characteristics of arterial stenosis in patients with ischemic cerebrovascular disease
1 Ischemic cerebrovascular disease had higher incidence of cranial stenosis and this study cases show pure intracranial stenosis higher than simple extracranial Stenosis.
2 Infarction group and TIA group responsibility vascular stenosis had no statistical difference, prompted us should put emphasis to TIA rapid etiological diagnosis, given treatment timely to prevent its progress as cerebral infarction.
3 Cerebral artery stenosis is main factors aroused neurologic impairment but collateral circulation played very important protection role,especially Willis ring and neighboring brain soft membrane compensatory.
4 Between various risk factors, extracranial artery stenosis has the relation with hypertension (P= 0.025), OR is 5.046; Between different age group, The distribution and degree of racranial artery stenosis significantly different, P<0.01, statistically significant. The young group prone to intracranial stenosis, but old age group prone extracranial artery stenosis.
Part II The Correlation between the distribution of Syndrome and cerebral artery stenosis in patient with acute ischemic cerebrovascular disease.
1 Characteristic of TCM syndromes with acute ischemic stroke
Wind syndrome probability highest (87.4%), three syndromes combination is highest in syndromes combination. Syndromes combination is mainly formed by wind、phlegm、blood stasis, which mutual combination and plus qi deficiency, fiery, YV and YHP, composition various syndromes combinations.
2 The correlation between TCM syndromes and risk factors
Hypertension History and phlegm had negative correlation; diabetes history and fiery syndrones had negative correlation, smoking history with fiery card correlated; smoking history, CHD history and Qi Deficiency negatively related, past stroke history and Qi Deficiency Syndrome correlated. These results prompt us in Clinical, For undocumented discernible stroke patients, patients'risk factors and clinical certain objective examination can be Contact, reference this study results syndrome differentiation.
3 TCM syndromes had relationship with cerebral artery stenosis lesion and extent
Distribution and extent of extracranial artery stenosis was positively correlated with blood stasis syndrome, Distribution and degree of intracranial arterial stenosis was positively associated with phlegm.
Part III TCM Syndrome Features of perioperative cerebral artery stent
1 Perioperative of cerebral artery stent, the rule of TCM syndrome can be found, mainly manifested that empirical reduce and deficiency increase.
2 Extracranial artery stent especially carotid stent is safe and effective, intracranial artery stent had higher risk which should cautiously conduct.
3 Peventing cranial external stent restenosis by integrative medicine is feasiblea and should undertake further studies.
缺血性脑血管病具有发病率高、致残率高、死亡率高、复发率高等特点,成为危害人类健康的重要疾病。缺血性脑血管病主要包括TIA和脑梗死,而动脉粥样硬化形成斑块并造成脑供血动脉狭窄是缺血性脑血管病的重要病因。脑动脉粥样硬化好发于颅内、外大中动脉分叉部及弯曲部,东西方人脑血管病的发病特点、危险因素和远期预后存在很多差异,颅内外动脉粥样硬化发生的部位、病理特点等也不完全相同。美国每年新发作的卒中与颅外段颈动脉狭窄有关,占35%～70%,而亚洲国家报道颅内动脉狭窄是引起脑梗死和TIA的重要原因,但国内此方面较大样本的研究尚少。中医诊治中风有悠久的历史。在中风病整个疾病进程中,从急性期到后遗症期,随着病机的变化,中风病的证候随之发生动态变化。只有把握其证候的动态演变规律,才能全面完整的认识中风,在临床采取果断准确的处方用药,因此了解国人缺血性脑血管病患者的血管学资料及中医证候特点,可以更好的认识和防治缺血性脑血管病。症状性颅内外动脉狭窄病变是中风发作的主要原因,血管内治疗技术为颅内外动脉狭窄开辟了新的治疗方法,但是其安全性有效性仍处于探索阶段。现在另一个研究的热点就是支架后再狭窄。中医药防治动脉支架术后再狭窄,可以发挥中医药复方全面调节机体机能和多途径、多环节、多靶点干预的优势,有望开辟一条新的治疗途径。但是中医药如何干预,干预的时间窗、方法、结局等成为亟待解决的问题。解决这些问题的关键离不开中医的辨证论治,而辨证论治的核心在于对中医证候演变规律的认识和把握。因此,明确缺血中风患者脑供血动脉支架围手术期中医证候演变规律,可以为进一步深入研究脑供血动脉支架术后中长期中医证候演变规律奠定基础,为中医药防治缺血中风患者动脉支架术后再狭窄提供前期可靠的临床证候学依据。
2研究方法
回顾性分析我脑血管病中心缺血性脑血管病患者DSA资料,并填写中风病中医证候调查表,分三部分对以上问题进行探讨。
第一部分：通过分析数字减影血管造影(DSA)资料明确缺血性脑血管病患者脑动脉狭窄病变特点。
第二部分：分析缺血性脑血管病患者急性期中医证候分布规律,结合DSA结果分析脑动脉狭窄病变与中医证候的相关性。
第三部分：评价颅内外支架治疗脑动脉粥样硬化性狭窄病变的安全性、有效性,分析支架围手术期中医证候演变规律。
3研究结果
第一部分：缺血性脑血管病患者362例,其中334例患者存在脑动脉狭窄,占总数的92.3%。所有存在脑动脉狭窄患者中单纯颅内动脉狭窄病变患者143例(42.8%),单纯颅外动脉狭窄病变患者84例(25.2%),颅内颅外动脉均存在狭窄病变患者107例(32%)；单纯前循环狭窄病变患者173例(51.8%),单纯后循环狭窄病变患者58例(17.4%),前后循环联合狭窄病变103例(30.8%)。颅外动脉狭窄好发位置：颈内动脉颅外段185处(61.7%),椎动脉颅外段96处(32%),锁骨下动脉19处(6.3%)；颅内动脉狭窄好发位置：颈内动脉颅内段55处(13.2%),大脑前动脉55处(13.2%),大脑中动脉171处(41.2%),大脑后动脉29处(7%),椎动脉颅内段54处(12.9%),基底动脉52处(12.5%)。
334例脑动脉狭窄病变的患者中共有84例(25.1%)存在侧枝循环,主要为Willis环代偿及邻近软脑膜动脉代偿。脑动脉闭塞且有侧枝循环的患者NIHSS评分明显低于无侧枝循环者,经过统计学分析,P=0.01,差异有统计学意义。
362例缺血性脑血管病患者,共有299例存在责任血管。脑梗塞与TIA患者责任血管狭窄分布与程度经统计学分析P>0.05,均无统计学意义。
在颅外动脉狭窄中高血压(p=0.025)与动脉狭窄有关,危险度为5.046；不同年龄分组颅内外动脉狭窄分布发生比例与程度明显不同,P<0.01,有统计学意义。
第二部分：急性缺血性中风患者247例,其中230例患者存在脑动脉狭窄病变,占总数的93.1%；而存在脑动脉狭窄患者中198例可以确认责任血管狭窄病变。
单纯颅内动脉狭窄患者51例(45.7%),单纯颅外动脉狭窄患者51例(22.2%),颅内颅外动脉均存在狭窄患者74例(32.2%)；单纯前循环狭窄病变147例(63.9%),单纯后循环狭窄病变24例(10.4%),前后循环均狭窄59例(25.7%)。
缺血性中风急性期中医证候分布以风证最多,其次为痰湿证,再次为血瘀证、气虚证、火热证,阴虚阳亢证最少。证候组合以三证组合为最多,共145例(58.7%)其次为两证组合,共52例(20.6%),再次为四证组合,共48例(19.4%),单证(2例,占0.8%)和五证(1例,0.4%)组合少见。缺血性中风急性期证候以风、痰、瘀为主证,兼加虚证、火热证、阴虚阳亢等,组成了各种证候组合。
危险因素与中医证候相关性多因素Logistic回归分析,高血压史是痰湿证的相关因素；糖尿病史与吸烟是火热证的相关因素；吸烟史、冠心病史和既往中风史是气虚证的相关因素,均有统计学意义。
单纯颅内动脉狭窄病变痰湿证的发生率明显高于单纯颅外动脉狭窄病变,差异有统计学意义(P=0.027)；单纯颅外动脉狭窄病变血瘀证发生率明显高于单纯颅内狭窄病变,差异有显著统计学意义(P=0.007)。颅外动脉狭窄程度与血瘀证明显相关(P<0.01),且秩相关提示等级相关系数rs值为0.975(P<0.01),呈明显正相关。颅内动脉狭窄程度与痰湿证明显相关(P<0.01),且秩相关提示等级相关系数rs值为0.896(P=0.004),呈明显正相关,颅内动脉狭窄程度与血瘀证也相关(P=0.05)。
第三部分：颅外动脉支架前后及支架2周后,风证在支架前后有显著差异(P=0.001),有统计学意义；痰湿证在支架前后有显著差异(P=0.01),有统计学意义,火热证在支架前后有明显差异(P=0.018),有统计学意义；血瘀证在支架前后有明显差异(P=0.011),有统计学意义；且根据Ranks结果提示,以上四证在支架后及支架后2周均明显减少。气虚证在支架前后有显著差异(P=0.003),有统计学意义,且根据Ranks结果提示,气虚证在支架后及支架后2周明显增多。
颅内动脉支架前后及支架2周后,风证在支架前后有显著差异(P=0.007),有统计学意义,血瘀证在支架前后有明显差异(P=0.042),有统计学意义,且根据Ranks结果提示,以上2证在支架后及支架后2周均明显减少。
颅外动脉支架前后证候组合差异明显,P=0.001,有统计学意义,即术前两证组合、三证组合最多,术后单证、两证组合增多,而三证、四证组合减少；虚实组合P=0.000<0.01,有统计学意义,即术前实证最多,虚证最少,术后实证减少,虚证及本虚标实证增多。
颅内动脉支架前后证候组合P>0.05,无统计学意义。虚实组合,P=0.001,差异有统计学意义,即术前实证最多,虚证最少,术后实证减少,虚证增多。
64例行颅外动脉支架患者,共有4例发生手术相关并发症,占6.2%,均为颈内动脉起始部支架后并发症。36例成功放置颅内动脉支架患者,共有5例(13.9%)发生手术相关并发症。2例为大脑中动脉支架,3例为基底动脉支架。
DSA随访：颅外动脉支架患者59例共有3名患者随访DSA发现支架内再狭窄,椎动脉开口处支架再狭窄2例,再狭窄发生率12.5%；锁骨下动脉再狭窄1例,再狭窄发生率11.1%。颅内动脉支架患者27例共有4例患者随访DSA发现支架内再狭窄,均为大脑中动脉支架,均为Winspan支架,再狭窄发生率30.8%。
中医证候随访：颅外动脉支架后再狭窄随访,1例再狭窄50%,中医证候为痰湿+气虚证；2例再狭窄70%,中医证候分别为痰湿+气虚+血瘀、痰湿+血瘀；颅内动脉支架后再狭窄随访,1例狭窄20%,中医证候为痰湿+火热证；1例狭窄23%,中医证候为血瘀证；2例均狭窄50%,1例中医证候为血瘀证,1例中医证候为痰湿+气虚证。
4研究结论
第一部分缺血性脑血管病患者DSA动脉狭窄病变特点
1缺血性脑血管病患者颅内外动脉狭窄病变发生率较高,且本研究病例中单纯颅内动脉狭窄病变发生率高于单纯颅外狭窄病变。
2脑梗塞组与TIA组责任血管狭窄病变比较无统计学差异,提示我们更应该重视TIA的快速病因诊断,及时给与治疗,防止其进展为脑梗塞。
3脑动脉狭窄程度是引起神经功能缺损的主要因素,但侧枝循环起了非常重要的保护作用,尤其是Willis环和邻近脑软膜支代偿。
4各种危险因素中,颅外动脉狭窄与高血压(P=0.025)有关,危险度为5.046；不同年龄分组颅内外动脉狭窄分布发生比例与程度明显不同,P<0.01,有统计学意义。中青年组易发生颅内狭窄,而老年组易发生颅外动脉狭窄。
第二部分缺血性脑血管病患者急性期中医证候分布与DSA结果相关性
1缺血中风急性期中医证候分布
以风证出现概率最高(87.4%),证候组合以三证组合为最多,共145例(58.7%),证候组合分别以风证、痰湿证、血瘀证为主证,相互组合并兼加气虚、火热、阴虚阳亢证,组成了各种证候组合。
2危险因素与中医证候相关性分析
高血压史与痰湿证呈负相关；糖尿病史与火热证呈负相关,吸烟史与火热证呈正相关；吸烟史、冠心病史与气虚证呈负相关,既往中风史与气虚证呈正相关。这些结果提示我们在临床工作中对于无证可辨的中风病患者,可以将患者的危险因素和临床某些客观检查加以联系,参考本研究结果以辨证施治。
3脑动脉狭窄病变部位、程度与中医证候相关性分析
主要表现为颅外动脉狭窄分布及程度与血瘀证呈明显正相关,颅内动脉狭窄分布及程度与痰湿证明显相关。
第三部分脑动脉支架围手术期中医证候特点
1脑动脉支架治疗前后中医证候演变有规律可循,主要表现为实证的减少和虚证的增加,本研究结果提示支架介入治疗相当于中医清热化痰除瘀的作用,可以改变甚至逆转中风病自然证候演变规律,但支架易引起出血、乏力加重等证,所以在支架介入术后应以扶正培元为主,兼以祛痰化瘀,清热解毒。
2颅外动脉支架尤其是颈动脉支架是安全有效的,颅内动脉支架风险较高,应谨慎开展。
3中西医结合防治颅内外支架后再狭窄是可行的,应开展更深入的研究。
1 Background and Objective:
Ischemic cerebrovascular disease with high incidence and high morbidity, high mortality and high recurrence rate has become a major disease harm human health. It includes TIA and cerebral infarction, the formation of atherosclerotic plaques and cerebral artery stenosis is an important cause of ischemic cerebrovascular disease.Cerebral artery atherosclerosis offen occurs in intracranial and extracranial, medium and large arteries and the bifurcation of the Department of bending, there are many differences between East and West patients in the characteristics of cerebrovascular disease, risk factors and long-term prognosis. The position and pathological characteristics of intracranial and extracranial atherosclerosis are not exactly the same In United States, the new onset of stroke is mainly caused by extracranial carotid artery stenosis, accounting for 35% to 70%, but in Asian, it reported that intracranial arterial stenosis is an important reason which caused cerebral infarction and TIA. However, a larger sample of domestic research in china is still less. Traditional Chinese Medicine has a long history of stroke treatment. Throughout the process of stroke, from the acute phase to the Sequela, the stroke syndrome changes while the pathogenesis changes occurring. Only by understanding the dynamic evolution of TCM syndromes law, we could fully and completely understand the stroke.Then take decisive and accurate drugs. Therefore, By finding out the features of vascular information and TCM Syndrome in Chinese patients, we can have a better understanding and can prevent the ischemic cerebrovascular disease. Symptoms of cerebral artery stenosis is the main reasons of stroke, endovascular treatment of cranial arterial stenosis technology opens up a new treatment. However, the effectiveness and their safety are still at the exploratory stage. Another research focus in the stent restenosis, TCM prevent the stent restenosis, which can play a Superiority of Chinese medicine compound regulate the body functions and multi-channel, multi-link, and the advantages of multi-target interference is expected to open up a new therapeutic approach. However, how Chinese medicine to intervene, The time window of intervention, methods, outcomes have become pressing problem. The key to solving these problems can not do without TCM syndrome, understanding the syndrome differentiation and grasp of the law is the core of the evolution of the TCM. Therefore, defining the TCM Syndrome perioperative cerebral artery stent, it can provide early and reliable basis for clinical symptoms and signs for TCM prevention of restenosis after stenting.
2 Research methods
A retrospective analysis of patients'DSA information who suffered ischemic cerebrovascular disease, and fill stroke TCM syndromes questionnaire, It divided into three sections to discuss above issues:
PartⅠ:Analysis of digital subtraction angiography (DSA) to define cerebral artery stenosis characteristics in patients with cerebral artery stenosis.
PartⅡ:Analysis the TCM syndrome distribution laws of patients with ischemic cerebrovascular disease, Combining with DSA results, analysis of the correlation between cerebral artery stenosis and TCM Syndrome.
PartⅢ:Evaluation of safety and effectiveness of cerebral artery stent, analysis of TCM Syndrome evolution rule perioperative stent
3 results
PartⅠ:362 cases of patients with ischemic cerebrovascular disease, of which 334 cases had cerebral artery stenosis, accounting for 92.3%. In all patients with cerebral artery stenosis,143 patients (42.8%) only had intracranial artery stenosis; 84 patients (25.2%) only had extracranial artery stenosis; there were 107 cases (32%) of patients had intracranial and extracranial artery stenosis.173 patients (51.8%) with anterior circulation stenosis; 58 patients (17.4%) with posterior circulation stenosis; 103 cases (30.8%) of patients with combined stenosis. Extracranial artery stenosis often occurred in:extracranial internal carotid artery 185 (61.7%) extracranial vertebral artery 96 (32%), subclavian artery 19 (6.3%); intracranial arterial stenosis made better position:intracranial internal carotid artery 55 (13.2%), anterior cerebral artery 55 (13.2%), middle cerebral artery 171 (41.2%), posterior cerebral artery 29 (7%), intracranial vertebral artery 54 (12.9%), basilar artery 52 (12.5%).
334 cases of cerebral artery stenosis in patients with a total of 84 patients (25.1%) had collateral circulation, mainly for the Willis ring and adjacent pial artery compensatory compensation. Cerebral artery occlusion and collateral circulation in patients with NIHSS score was significantly lower than those without collateral circulation, through statistical analysis, P = 0.01, the difference was statistically significant.
362 cases of ischemic cerebrovascular disease, a total of 299 vessels of responsibility. Cerebral infarction and TIA in patients with vascular stenosis distribution and extent of responsibility for the statistical analysis P> 0.05, not statistically significant.
For extracranial artery stenosis, hypertensive is related to arterial stenosis (p= 0.025), risk is 5.046; different age group distribution different cranial artery stenosis occurrence and degree, P<0.01, statistically significant.
Part II:247 cases of patients suffer acute ischemic stroke, of which 230 cases of patients had cerebral artery stenosis, accounting for 93.1%; 198 cases of patients can be confirmed responsibility vascular stenosis. Alone in patients with intracranial arterial stenosis in 51 cases (45.7%), extracranial artery stenosis alone,51 patients (22.2%), intracranial and extracranial arteries stenosis exist in 74 cases (32.2%); 147 cases of anterior circulation stenosis (63.9%), pure posterior circulation stenosis in 24 patients (10.4%),59 patients unite cycling are narrow (25.7%).
Distribution of TCM syndrome evidence with acute ischemic stroke:The most is wind, followed by phlegm, blood stasis again, qi deficiency,the least is syndrome of yin deficiency and yang hyperactivity. In syndrome combine, three-syndrome combination is the most with total of 145 cases (58.7%), followed by the combination of two cards, a total of 52 cases (20.6%), again syndrome for the four combinations, a total of 48 cases (19.4%), document (2 cases, accounting for 0.8%) and five-card (1 case,0.4%), rare combination.
The main syndrome of acute ischemic stroke are wind, phlegm, blood stasis, and additional deficiency of qi deficiency and yin deficiency and yang hyperactivity, to form various combinations of syndrome.
Logistic regression analysis, history of hypertension is related phlegm; history of diabetes and smoking are fiery evidence related factors; smoking history, coronary heart disease history and previous history of stroke is related to qi deficiency, all were statistically significant.
Phlegm with intracranial arterial stenosis alone were significantly higher than that of extracranial artery stenosis, the difference was statistically significant (P= 0.027); pure extracranial artery stenosis incidence of blood stasis was significantly higher than intracranial stenosis, the difference was statistically significant (P= 0.007). Extracranial artery stenosis was significantly associated with blood stasis syndrome (P<0.01), and the rank correlation coefficient of rank correlation rs value prompted 0.975 (P<0.01), was positively correlated. Intracranial arterial stenosis significantly correlated with phlegm (P<0.01), and the rank correlation coefficient of rank correlation rs value prompted 0.896 (P= 0.004), positive correlation.
Part III:Before and after extracranial artery stents:the wind syndrome significantly different (P= 0.001), there was significant; phlegm syndrome significantly different (P= 0.01), there statistically significant; blood stasis before and after stent significantly difference (P= 0.011), there was significant; FHP significant difference before and after the stent (P= 0.018), statistically significant, and Ranks results suggest that these four cards significantly reduced after the stent and 2 weeks later, Qi deficiency before and after stent significantly different (P= 0.003), there was significant, and Ranks results suggest that Qi deficiency increased significantly after the stent and 2 weeks later.
Before and after intracranial artery stents:the wind permits were significantly different (P= 0.007), statistically significant, blood stasis before and after stent significantly difference (P= 0.042), with statistical significance, Ranks results suggest that these two cards significantly reduced after the stent and 2 weeks later
Before and after extracranial artery stent:the combination syndrome with significantly different, P= 0.001, statistically significant. Which means that two or three card combination are the most preoperative, after stenting, the two card combination increased, and the three cards, four cards combination reduced; deficiency-excess syndrome combine before and after stent statistically significant, Which means excess syndrome are the most before stent, reduced postoperative,;deficiency syndrome are the lesst,increased postoperative.
Stent complications:64 case of patients with extracranial artery stenting, 4 patients had surgical complications,6.2%, both the department of carotid artery stent complications.36 cases of intracranial artery stents were successfully placed, a total of 5 cases (13.9%) had surgery-related complications,2 cases of middle cerebral artery stent,3 cases of basilar artery stent.
Follow-up DSA,we found 3of 59 patients with extracranial artery stents restenosis, vertebral artery,2 cases, which restenosis rate is 12.5%; subclavian artery stenosis,1 case, which restenosis rate is 11.1%.27 patients with intracranial artery stents were followed up, for a total of four cases of restenosis was found, all were the middle cerebral artery stents, Winspan stent, the restenosis rate is 30.8%.
Syndromes of TCM follow-up:In extracranial artery stent restenosis, one case of restenosis by 50% with the phlegm syndromes + qi deficiency; two cases of restenosis 70%, respectively, with phlegm syndromes+Qi+Blood, phlegm +blood stasis;
Between intracranial artery stent restenosis, one case of restenosis of 20% with the phlegm syndromes+ FHP; one case of stenosis of 23% with the blood stasis syndromes; two cases of stenosis were 50%, 1 case with blood stasis Syndrome,1 case of TCM syndrome is phlegm+ qi deficiency.
4 Research conclusions
PartⅠThe characteristics of arterial stenosis in patients with ischemic cerebrovascular disease
1 Ischemic cerebrovascular disease had higher incidence of cranial stenosis and this study cases show pure intracranial stenosis higher than simple extracranial Stenosis.
2 Infarction group and TIA group responsibility vascular stenosis had no statistical difference, prompted us should put emphasis to TIA rapid etiological diagnosis, given treatment timely to prevent its progress as cerebral infarction.
3 Cerebral artery stenosis is main factors aroused neurologic impairment but collateral circulation played very important protection role,especially Willis ring and neighboring brain soft membrane compensatory.
4 Between various risk factors, extracranial artery stenosis has the relation with hypertension (P= 0.025), OR is 5.046; Between different age group, The distribution and degree of racranial artery stenosis significantly different, P<0.01, statistically significant. The young group prone to intracranial stenosis, but old age group prone extracranial artery stenosis.
Part II The Correlation between the distribution of Syndrome and cerebral artery stenosis in patient with acute ischemic cerebrovascular disease.
1 Characteristic of TCM syndromes with acute ischemic stroke
Wind syndrome probability highest (87.4%), three syndromes combination is highest in syndromes combination. Syndromes combination is mainly formed by wind、phlegm、blood stasis, which mutual combination and plus qi deficiency, fiery, YV and YHP, composition various syndromes combinations.
2 The correlation between TCM syndromes and risk factors
Hypertension History and phlegm had negative correlation; diabetes history and fiery syndrones had negative correlation, smoking history with fiery card correlated; smoking history, CHD history and Qi Deficiency negatively related, past stroke history and Qi Deficiency Syndrome correlated. These results prompt us in Clinical, For undocumented discernible stroke patients, patients'risk factors and clinical certain objective examination can be Contact, reference this study results syndrome differentiation.
3 TCM syndromes had relationship with cerebral artery stenosis lesion and extent
Distribution and extent of extracranial artery stenosis was positively correlated with blood stasis syndrome, Distribution and degree of intracranial arterial stenosis was positively associated with phlegm.
Part III TCM Syndrome Features of perioperative cerebral artery stent
1 Perioperative of cerebral artery stent, the rule of TCM syndrome can be found, mainly manifested that empirical reduce and deficiency increase.
2 Extracranial artery stent especially carotid stent is safe and effective, intracranial artery stent had higher risk which should cautiously conduct.
3 Peventing cranial external stent restenosis by integrative medicine is feasiblea and should undertake further studies.
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