Clinical factors in patients with ischemic versus hemorrhagic stroke in East Chi

BACKGROUND： Stroke is one of the leading causes of mortality and morbidity of vascular diseases， and its incidence maintains at a high level around the world. In China， stroke has been a major public health problem. Because the pathogenesis of ischemic stroke is different from that of hemorrhagic stroke， their clinical factors would not be the same. Therefore to investigate the different effects of various effect factors on ischemic versus hemorrhagic stroke and then to enhance the prevention are crucial to decrease the incidence.

METHODS： A total of 692 patients， consisting of 540 ischemic stroke patients and 152 hemorrhagic stroke patients from East China， were included in this study. The related factors of stroke subtypes were collected and analyzed.

RESULTS： The factors significantly associated with ischemic stroke as opposed to hemorrhagic stroke were family history of stroke， obesity， atherosclerotic plaque of the common carotid artery， atrial fibrillation， hyperfibrinogenemia， transient ischemic attack （TIA）， atherosclerotic plaque of the internal carotid artery， coronary heart， lower high-density lipoproteins （lower HDL）， increasing age， diabetes mellitus， and gender （male） （P

CONCLUSIONS： The most prominent factors for overall stroke in East China were hypertension， followed by higher pulse pressure and hypercholesteremia. The factors for ischemic and hemorrhagic stroke are not the same. Different effects of risk factors on stroke are found in male and female patients.

KEY WORDS： Ischemic stroke； Hemorrhagic stroke； Risk factors

World J Emerg Med 2011；2（1）：18-23

INTRODUCTION

Stroke is one of the leading causes of mortality and morbidity of vascular diseases.[1] Its incidence maintains at a high level around the world. In China the official statistics from 31 regions showed that there were about 1.5-2.0 million new stroke patients each year，[2] and it has been a major public health problem in China.[3] Because of the poor therapeutic result， the most important method to reduce the morbidity of stroke is prophylaxis， which depends on the realization and control of the risk factors for stroke.[4] Because the pathogenesis of ischemic stroke is different from that of hemorrhagic stroke， their clinical factors would not be the same. Hence both investigation of the effects of various effect factors on ischemic versus hemorrhagic stroke and and enhanced prevention are crucial to decrease the incidence of stroke.

In this study we investigated the factors for ischemic versus hemorrhagic stroke by analyzing the clinical data of the patients so as to provide some scientific evidence for stroke prevention in east china.

METHODS

Study design

This study was supported by grants from the Jiangsu Provincial Natural Science Foundation. The protocol of the study was reviewed and approved by the institutional review board of Nanjing Medical University， Nanjing， China. Informed consent was obtained from each patient， who donated 5 mL of blood for routine and biochemistry examination.

All patients were recruited between November 2008 and May 2010 at the First Affiliated Hospital of Nanjing Medical University and Brain Hospital Affiliated to Nanjing Medical University. A total of 692 hospitalized patients with stroke were genetically unrelated ethnic Han Chinese in East China. According to the International Classification of Diseases， Tenth Revised Edition （ICD-10）， we recruited 540 ischemic stroke patients and 152 hemorrhagic stroke patients. Patients who had other types of stroke （transient ischemic attack， subarachnoid hemorrhage， and cerebrovascular malformation） and severe systemic diseases （collagenosis， endocrine， and metabolic disease （except for diabetes mellitus， DM）， inflammation， neoplastic） were excluded. Diagnosis of stroke was based on the results of strict neurological examination by CT， MRI， or both. The clinical data of the patients were obtained through a questionnaire depicted general state of health， life style， family history， previous health history， results of laboratory and auxiliary examinations.

The clinical factors to be observed in this study included advanced age （male>55 years， female>65 years[5] ）， gender （male-exposure）， cigarette smoking （average smoking≥1 cigarettes per day， and continued more than one year）， alcohol drinking （at least 1 time per week， alcohol consumption≥50 mL and more than 3 months）， obesity （body mass index （BMI）≥28 kg/m2）； family history of coronary artery disease （CAD）， stroke， hypertension and diabetes mellitus （DM）； history of hypertension （in line with the diagnostic criteria of China Guidelines of Hypertension Updated 2005）， increased pulse pressure （>40 mmHg）， atrial fibrillation （AF）， DM （in line with the diagnostic criteria of WHO1999）， valvular heart diseases， CAD， transient ischemic attack （TIA）， peripheral arterial thrombosis， peptic ulcer disease， kidney disease； elevated systolic blood pressure （SBP≥140 mmHg）， elevated diastolic blood pressure （DBP ≥90 mmHg）， increased white blood cell （WBC>10.0×109/L）， hypertriglyceridemia （triglyceride （TG）>1.7 mmol/L）， hypercholesterolemia （total cholesterol （TC）≥5.7 mmol/L）， low level of high-density lipoproteins （HDL4.0 g/L）； ischemic ECG changes， ECG arrhythmia； and the formation of carotid atheroma， common carotid atheroma and vertebral artery stenosis shown by carotid ultrasound.

Statistical analysis

Statistical analysis were performed by the SPSS 16.0 package. The continuous clinical variants were compared by unpaired Student's t test. The Chi-square test was used to evaluate differences in proportion of clinical factors in patients between ischemic and hemorrhagic stroke. We used logistic regression analysis to calculate odds ratio （OR） of the incidence of ischemic stroke versus hemorrhagic stroke and of incidence of ischemic stroke （hemorrhagic stroke） in men versus in women and 95% confidence interval.[5，6] A P value

RESULTS

Subtype

A total of 692 patients， 540 （78%） ischemic patients and 152 （22%） hemorrhagic patients from East China， were enrolled in this study. The incidence rate of ischemic stroke in this area was obviously higher than that of hemorrhagic stroke.

Sex and age distribution

In this series， 428 （61.85%） were male patients and 264 （38.15%） female patients， while 59.63% of the ischemic group and 69.74% of the hemorrhagic group were male. Male patients account for a large propotion in both ischemic and hemorrhagic groups. The mean age for the ischemic group was 68.37±10.59 years， which was significantly higher than that of the hemorrhagic group （62.16±12.59 years， P

Laboratory and auxiliary examination

The laboratory data of patients with ischemic and hemorrhagic stroke were compared （Table 1）. Briefly， mean SBP， DBP， WBC， neutrophil ratio （NE）， blood glucose （BG）， HDL， and prothrombin time （PT） were higher in the hemorrhagic group than in the ischemic group （P0.05）.

Clinical data

The clinical data of patients with two types of stroke were shown in Table 2. Compared with the hemorrhagic group， the ischemic group had a higher prevalence of clinical factors such as advanced age， male， family history of hypertension， hypertension， hypercholesterolemia， obesity， family history of stroke， DM， TIA， CAD， AF， kidney disease， hyperfibrinogenemia， low level of HDL， the formation of carotid atheroma， the formation of common carotid atheroma， and vertebral artery stenosis （P

Logistic regression was used to analyze the influence of these factors on the occurrence of different types of stroke （gender and age-adjusted）. The patients were divided into 6 groups according to their age： 85 years （Table 3）.

In contrast to the hemorrhagic group， the following factors were found to be more causatively related in the ischemic group： family history of stroke， obesity， common carotid atheroma， AF， hyperfibrinogenemia， TIA， carotid atheroma， low HDL level， advanced age， DM， male gender. Only increased WBC， hypertension and family history of hypertension were found to be contributive in the hemorrhagic group.

The Chi-square test was used to evaluate differences in clinical factors for stroke in patients of both sexes. With the increase of age， males were found to be more susceptible to stroke. As expected， male patients had a higher prevalence of cigarette smoking （P=0.000） and alcohol drinking （P=0.000） while the incidence of obesity in female patients was much higher than in male patients. In addition， kidney disease （P=0.032） and low HDL level （P=0.032） were common in male patients and family history of hypertension （P=0.039）， hypertriglyceridemia （P=0.003）， hypercholesterolemia （P=0.002） and ischemic ECG changes （P=0.006） were common in female patients.

Logistic regression was used to calculate odds ratio of the incidence of ischemic stroke in males versus females as well as 95% confidence interval （Table 4）. The clinical factors of stroke in males and females were not the same. Among the factors， cigarette smoking， alcohol drinking， kidney disease and low HDL level were more contributive in male patients. The effects of obesity， family history of hypertension， family history of stroke， hypercholesterolemia and ischemic ECG changes on stroke were more obvious in females than in males. We also calculated odds ratio of the incidence of hemorrhagic stroke in men versus in women. The data showed that male patients with cigarette smoking （OR=27.270）， alcohol drinking （OR=7.686） and female patients with hypertriglyceridemia （OR=0.285） were more susceptible to hemorrhagic stroke.

DISCUSSION

There are some non-modifiable risk factors of stroke， such as age， sex， race and family history. It was reported that the risk of stroke doubles in each successive decade after 55 years of age.[7] The cumulative effects of aging on the cardiovascular and cerebrovascular systems and the progressive nature of stroke risk factors over a prolonged period of time substantially increase the risk of stroke. In this study we found that the incidence of ischemic stroke in males over 55 years or in females over 65 years was 2.122 times higher than that of hemorrhagic stroke. The result suggested that the factor of advanced age was more important to ischemic stroke. Stroke， either ischemic or hemorrhagic， is more prevalent in men than in women. Lifestyle differences， such as cigarette smoking and alcohol drinking， may help explain this sex disparity. In addition， there is no vascular protection of endogenous estrogen in males and it may contribute to the risk of stroke in men. Both paternal and maternal history of stroke may contribute to the increasing risk of stroke. This risk could be mediated through a variety of mechanisms. In contrast to a recent study[8]， our patients came from East China， and of all， only family history of stroke was the risk factor for ischemic stroke， while family history of hypertension was the risk factor for hemorrhagic stroke. There was no significant difference in the distribution of family history of DM and family history of CAD between the two types of stroke. It was suggested that differences existed in family history among stroke patients from different regions.

Hypertension， DM， AF， dyslipidemia and hyper-fibrinogenemia， and so on are changeable risk factors for stroke.[1，9] Reports showed that hypertension was the most important independent risk factor for both ischemic and hemorrhagic stroke， and that 50%-60% of patients with stroke were triggered by hypertension， especially when combined with increased pulse pressure.[10，11] Furthermore， hypertension was more correlated with ischemic stroke than hemorrhagic stroke in our study as similarly reported elsewhere. Besides hypertension， AF was another basic risk factor for stroke.[12] The patients with AF accounted for 3%-5% of stroke patients per annum and there was a nearly 6-fold increase in stroke prevalence among AF patients.[13] We also found AF played an important role in ischemic stroke versus hemorrhagic stroke （OR=3.407）. Cigarette smoking and alcohol drinking have long been recognized as major risk factors for stroke. Their pathophysiological effects are multifactorial， involving both systemic vasculature and blood rheology. So far it is still controversial whether the effects of cigarette smoking and alcohol drinking on ischemic stroke are consistent with those on hemorrhagic stroke. The data from our study exhibited that hemorrhagic patients had a higher prevalence of alcohol drinking than ischemic patients， and there was a significant difference between them. Abnormalities of serum lipids （triglycerides， cholesterol and HDL） have traditionally been regarded as a risk factor for coronary artery disease but not for cerebrovascular disease. However， recent studies have clarified the relationship between lipids and ischemic stroke， and showed that the risk of ischemic stroke[14，15] and the size of carotid atheroma can be reduced by cholesterol-lowering medications.[6] Nevertheless， China Guidelines of Hypertension Updated 2005 estimate that hypocholesterolemia （TC

Reports showed that carotid stenoses >50% were detected in 7% of males and 5% of females ≥65 years old in healthy people and in 45% of patients with stroke associated with carotid stenosis of varying degree.[5，7] We found that carotid atheroma and vertebral artery stenosis may increase the risk of ischemic stroke. Previously the relationship between ECG results and risk of stroke was investigated because of non-specificity. Because of the risk of stroke may be increased by changing hemodynamics， we observed two types of ECG phenomena， ischemic ECG changes and ECG arrhythmia. Unfortunately， no positive result was found.

Atherosclerosis， the most common cause of stroke， is believed to be a disease of chronic inflammation. A recent study revealed that the risk of stroke recurrence of patients with WBC>8.2×109 /L in a week after stroke was significantly higher than that of patients with WBC10×109/L） was associated with hemorrhagic stroke. Its prevalence in hemorrhagic patients was significantly higher than that in ischemic patients （40.79% vs. 14.63%）.

Helicobacter pylori （H. pylori） infection may cause atherosclerotic stroke.[20] The mechanism has not yet been well recognized and it is probably stroke triggered by reducing the stability of atherosclerotic plaque through inflammatory reaction and regulation of blood lipids. A clinical study[21] indicated that hyperuricemia may independently elevate the risk of ischemic stroke （hazard ratio， 1.27 per additional 0.1 mmol/L； 95% CI， 1.18 to 1.36； P

In East China， high blood pressure is closely related to hemorrhagic stroke. Therefore， blood pressure control plays a vital role in prevention of the disease. Since ischemic stroke is a kind of disease involving multiple risk factors， it should be prevented in a comprehensive way. In the people with a high risk of stroke， interventions of their lifestyle and low-to-high medication are required to ensure an economic and efficient intervention for stroke in addition to health education as well as enhanced control and monitoring of the risk factors.

Although there were some defects in this study， the regional characteristics of the results at least may be helpful in dealing with the risk factors for stroke and its primary prevention in East China population.

Funding： This study was supported by the Natural Science Foundation of Jiangsu Province， China.

Ethical approval： The research protocol was reviewed and approved by the institutional review board of Nanjing Medical University.

Conflicts of interest： No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article.

Contributors： Zhang J proposed the study and wrote the paper. All authors contributed to the design and interpretation of the study results and to further drafts of the paper. Zhang JS is the guarantor.

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Received June 10， 2010

Accepted after revision November 6， 2010