Association Between the Subtypes of Stroke and the Various Risk Factors of Cerebrovascular Accidents: A Cross-Sectional Study.
Stroke is an amalgamate disease with two subtypes: ischemic and hemorrhagic . It is estimated that 6.8 million American adults have suffered from stroke, and that 610,000 people experienced it for the first time during 2013. Stroke is the second most common debilitating disease in the United States and financially is a massive burden on the health system . A recent largescale study has revealed that>90% of the burden of stroke is attributed to the modifiable risk factors, including behavioral (e.g., smoke), metabolic (hypertension, diabetes, hypercholesterolemia, low glomerular filtration rate, and high body mass index), and environmental (air pollution and lead exposure) factors .
Arterial hypertension (AH) causes hyaline degeneration and fibrinoid necrosis in the weak and short arteries supplying the base of the brain, including the thalamus, basal ganglia, brain stem, cerebellum, and internal capsule. Other different mechanisms of hypertension contributing to stroke are likewise well-discussed [4, 5]. The patients with diabetes mellitus (DM) are also at an increased risk of recurrent and disabling/fatal lacunar infarcts, which makes them susceptible to ischemic and hemorrhagic strokes [6, 7]. Also, according to two recent meta-analyses, DM and smoking habits differently affect gender in terms of an increase in the risk of stroke. Female diabetic or smoker patients are predisposed to a higher risk of stroke in contrast to males [8, 9]. As another metabolic factor the elevated levels of low-density lipoprotein particles are related to an increased risk of ischemic strokes . Smoking is implicated in higher stroke mortality functional disability, and experiencing stroke at younger ages . A meta-analysis reporting on 11,658 stroke patients has shown newly diagnosed atrial fibrillation (AF)  in nearly 25% of all the patients, detected by the combination of sequential cardiac monitoring . The patients with AF have a 5-fold increased risk for embolic strokes .
Considering the high prevalence of emergency referrals and hospitalizations due to stroke, it seems that a vast evaluation of the relevant risk factors and their demography is valuable . To the best of our knowledge, there is limited evidence in this field, and it is not well understood if all risk factors contribute as much to the different subtypes of stroke. Understanding the different patterns of the risk factors could benefit policy makers in constructing measures to accurately address the needs of the patients at high risk of stroke. Herein, we have investigated the relation among the above-mentioned risk factors, central and peripheral vascular syndromes, and the subtypes of stroke.
Materials and Methods
In this retrospective cross-sectional study, we assessed all patients with diagnosed stroke admitted to a referral medical educational hospital. The inclusion period was from January 2015 to January 2017. A total of 846 patients were detected; of which, we excluded those who left the hospital untreated (discharged with personal consent) or who had incomplete documents, i.e., the items of our study After the exclusion, a total of 827 patients were assessed. The collected data were extracted from the patients' documents according to the variables predetermined in our questionnaire. The variables comprised the demographic data of the patients such as sex, age, stroke subtype (ischemic or hemorrhagic), risk factors (hypertension, diabetes, hyperlipidemia, smoking habits, alcohol consumption, Atrial fibrillation (AF), oral contraceptive use, a history of previous transient ischemic attacks, cerebrovascular accidents (CVAs), acute coronary syndromes, familial predisposition), and the presence of central or peripheral vascular syndromes (strokes, limb arterial thrombosis, and mesenteric artery thrombosis). The risk factors and vascular syndromes were determined by the results of a physical examination during the period in which the patient was hospitalized and by referring to the patient's medical records
The data were analyzed using SPSS[R] (version 23.0.0, IBM Corp.; Armonk, New York, USA). To describe the sample population, we used mean[+ or -]standard deviation, frequency cumula tive frequency, frequency distribution table, and cluster bar graphs. For the evaluation of our assumptions regarding the differences among the independent groups, chi-square test, Student t-test, and Pearson correlation coefficient were used. In all items, p<0.05 was considered statistically significant. Power of the study was set at 80%.
The present study was approved by the Ethical Board of the University of Medical Sciences wherein the study was conducted. The collected data were anonymously entered in this study. No personal information was extracted from the files; we have provided only general data (not individualized) about our study population. The collected data were recorded in real and non-perverted forms, without selecting particular individuals, to achieve the desired results. To avoid any bias, the assumptions were written in a double-sided layout.
In the present study, of the 846 patients, 827 patients with diagnosed stroke from January 2015 to January 2017 were included.
Of the 827 patients, 432 (52.2%) were males and the remaining 395 (47.8%) were females (sex ratio of 1.09:1), and the difference was not statistically significant (p=0.21).
The mean [+ or -] standard deviation of age was 68.16 [+ or -] 12.38 y with a median of 68 and a mode of 65 y (min=26 and max=95). The age distribution examined with the Kolmogorov-Smirnov test showed that the data distribution was not normal (p<0.01) and had a negative skew (skewness=-0.041), showing a higher incidence rate in older patients (Figure 1).
The mean [+ or -] standard deviation of age in male patients was 68.41 [+ or -] 12.46 y and 67.89 [+ or -] 11.85 y for female patients, respectively, showing no statistically significant difference (p=0.29).
A total of 672 patients had ischemic stroke (81.3%), leaving the prevalence of hemorrhagic strokes at 18.7% (155 of 872 patients). There was no statistically significant correlation in terms of sex and the subtype of stroke (p=0.47). More information is presented in Figure 2.
The mean age of the patients having ischemic stroke was 68.64 [+ or -] 12.41 y and it was 66.11 [+ or -] 12.06 y in patients with hemorrhagic stroke. The difference was statistically significant (p=0.02).
The most common risk factor for stroke was hypertension (66.7%). The other risk factors are presented in Figure 3.
The determination of a relation between the risk factors and the subtypes of stroke showed that there was a significant relation between AH, AF age, and family history and the subtype of stroke. The other risk factors had no significant relation. More information is presented in Table l.
Of all the patients, 123 (14.9%) and 26 (3.1%) had peripheral and central vascular syndromes (PVS and CVS), respectively CVS is defined as the involvement of the vasculature of the central nervous system by any means. Further analysis of the CVSs showed that the most prevalent etiology was the previous episodes of stroke (14.9%). While studying the PVSs, we found that the thromboses of extremity and mesenteric veins with a prevalence of 19 (2.3%) and 7 (0.8%), respectively were the main causes of PVSs in these patients.
A history of previous stroke(s) was more common in patients with hemorrhagic strokes than that in the patients with ischemic strokes (20.6% vs. 13.4%; p=0.02). The incidence of thrombosis in the extremities was 2.4% in ischemic strokes and l.9% in hemorrhagic strokes (p=0.73), respectively; further the incident rate of mesenteric veins thrombosis was 0.7% and 1.3% in the ischemic and hemorrhagic strokes, respectively (p=0.5). There was no statistically significant correlation between the PVSs incidents and the subtype of stroke (p=0.9)
The frequency of ischemic and hemorrhagic strokes was 81.2% and 18.8%, respectively. These findings were in compliance to those of various previous studies, including Andersen et al. , Hajat et al. , and Zhang et al.  who stated that the prevalence of hemorrhagic strokes was between 5% and 25%.
In the study of the stroke risk factors, 64.4% and 20.1% of patients had AH and DM, respectively The most common risk factors among the patients in Zhang's study were AH and hyperlipidemia. According to these results, the controlling and preventing chronic illnesses such as AH and DM are of high importance while controlling CVAs, particularly now that the prevalence of these conditions is increasing in different societies .
According to our study, old age, a history of AF (15.7% vs 3%), and a familial history of CVAs (13.6% vs. 5.2%) were more common among the patients with ischemic strokes. There was no significant difference between the subtype of stroke in terms of sex and the other risk factors. Other studies such as Anderson et al. found that the risk factors such as age, sex, and blood pressure were not predictive of the subtype of stroke . On the other hand, Hajat et al., in a study of 1254 stroke patients that reviewed the risk factors and subtypes of strokes, found that there is a correlation between increased age and the incidence of ischemic strokes . The same results were obtained in the studies performed by Zhang et al. and Grysiewicz et al. [18, 20]. Bilic et al. , studying the differences between hemorrhagic and ischemic strokes, found a higher prevalence of AH, an older age, atherosclerotic diseases, and AF in patients suffering from ischemic strokes. The results of the study conducted by Kimura et al. show the predictive value of old age in the occurrence of a second ischemic stroke . All these studies show a positive relation between older age and the incidence of stroke, which is aligned with the findings of the current study, although there were some studies failing to show a correlation among these two factors.
Jorgensen et al.  found no correlation between AF and the occurrence of stroke, but there were studies stating that there is a higher risk of having an ischemic stroke, particularly among the patients with a history of AF and another study showed an overall higher risk of suffering from strokes regardless of the subtype in patients with a history of AF [17, 18, 21, 22, 24]. Focusing on these results and the fact that AF has a prevalence of 19% in patients with a history of stroke and that this rate increases to 40% with an increase in age, we notice the importance of an early diagnosis and the treatment of AF in preventing strokes, particularly the ischemic subtype .
Age, sex, race, and a familial history of stroke are all risk factors of ischemic strokes, which cannot be changed, cured, or prevented .
In a study performed by Zhang et al., it was shown that having a familial history of stroke was suggestive of experiencing an ischemic stroke rather than a hemorrhagic stroke (9.8% vs. 3.3%) . The results of the current recent study show a correlation between ischemic strokes and a familial history of strokes. These results were proven by Yamada et al. at a cellular and molecular level, suggesting a genetic basis for ischemic strokes.
An evaluation of the PVSs and CVSs showed a history of these conditions in 3.1% and 14.9% of the cases, respectively. Zhang et al.  reported only a history of peripheral vascular diseases equivalent to 1.8% in patients with ischemic strokes. A history of past strokes in patients suffering from hemorrhagic strokes was more common as compared with that in patients suffering from ischemic ones (20.6% vs. 13.4%) with a p-value of 0.02. No correlations were found between the incidence of PVSs and the subtypes of stroke. In a study Skaf et al.  showed that the prevalence of venous thromboembolism was higher in the patients with hemorrhagic strokes than that in the patients with ischemic strokes. Another study performed by Turnipseed et al.  reported five cases of stroke and two cases of transient ischemic attacks in 160 patients referred with peripheral vascular problems .
There is also a study that showed a 22.5% risk of experiencing a second episode of stroke in 5 years after experiencing the first stroke, which risk is particularly higher in the first 6 months following the initial incident. According to this study the incidence rate of the second stroke is in correlation with the hemorrhagic index , and Baily et al.  claimed that 75% of the strokes in the patients experiencing a second episode were hemorrhagic rather than ischemic.
The present study aimed to address the differences between the two main subtypes of stroke and their different risk factor patterns. A limitation of this study is that the sample population was not large enough to make definite conclusion on the risk factors and the subtypes; it rather provides preliminary information on the subject. Also, all patients in the present study were from a single tertiary care, referral center Multicenter studies would be of more merit. Needless to say, cohort studies focusing on the risk factors would help in constructing a definite correlation.
Most of the patients had an ischemic-subtype stroke. The age difference between the ischemic and hemorrhagic stroke group was statis tically significant, suggesting a need for intense public health measures in the elderly. The most common risk factor among the patients was AH, emphasizing the importance of tight control of this factor The only factors associated with the stroke subtype were AH, AF age, and family history The other risk factors were not significantly associated with a particular subtype of stroke.
Ethics Committee Approval: Ethics committee approval was received for this study from the ethics board of research deputy of Azad University School of Medicine, Tabriz branch.
Informed Consent: Written informed consent was obtained from patients who participated in this study.
Peer-review: Externally peer-reviewed.
Author Contributions: Concept--S.S.V., A.A.; Design --S.S.V., A.A.; Supervision--S.S.V, A.A.; Resources --FA., A.A.; Materials--S.S.V, FA.; Data Collection and/or Processing--M.M.A.A., A.A.; Analysis and/or Interpretation--S.A.M.A., A.A.; Literature Search M.M.A.A., FA.; Writing Manuscript--M.M.A.A., A.A., S.A.M.A.; Critical Review--A.A., S.S.V; M.M.A.A.
Acknowledgements: The Authors would like to thank the deputy of research of Tabriz University of Medical Sciences for their support.
Conflict of Interest: Authors have no conflict of interest to declare.
Financial Disclosure: The authors declared that this study has received no financial support.
[1.] Amarenco P Bogousslavsky J, Caplan L, Donnan G, Hennerici M. Classification of stroke subtypes. Cerebrovasc dis 2009; 27: 493-501. [CrossRef]
[2.] Ma VY Chan L, Carruthers KJ. Incidence, prevalence, costs, and impact on disability of common conditions requiring rehabilitation in the United States: stroke, spinal cord injury, traumatic brain injury, multiple sclerosis, osteoarthritis, rheumatoid arthritis, limb loss, and back pain. Archnof Phys Med Rehabil 2014; 95: 986-95.el. [CrossRef]
[3.] Feigin VL, Roth GA, Naghavi M, et al. Global burden of stroke and risk factors in 188 countries, during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet Neurol 2016;5: 913-24. [CrossRef]
[4.] Spence JD, Hammond R. Hypertension and the Brain as an End-Organ Target. Girouard H, editor Hypertension and Stroke. Cham: Springer International Publishing; 2016.p.39-54.
[5.] Yu JG, Zhou RR, Cai GJ. From hypertension to stroke: mechanisms and potential prevention strategies. CNS Neurosci Ther 2011, 17: 577-84. [CrossRef]
[6.] Palacio S, McClure LA, Benavente OR, et al. Lacunar strokes in patients with diabetes mel litus: risk factors, infarct location, and prognosis. Stroke 2014; 45: 2689-94. [CrossRef]
[7.] Chen R, Ovbiagele B, Feng W. Diabetes and stroke: epidemiology, pathophysiology, pharmaceuticals and outcomes. Am J Med Sci 2016; 351: 380-6. [CrossRef]
[8.] Peters SAE, Huxley RR, Woodward M. Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12539 strokes. Lancet 2014; 383: 1973-80. [CrossRef]
[9.] Peters SAE, Huxley RR, Woodward M. Smoking as a risk factor for stroke in women compared with men. a systematic review and meta-analysis of 81 cohorts, including 3,980,359 individuals and 42,401 strokes. Stroke 2013; 44: 2821-8. [CrossRef]
[10.] Kim Y-J, Fan W, Budoff MJ, et al. Abstract WP219: the relationship of low-density lipoprotein (ldl) particle number (ldl-p) and ldl particle size and incident stroke events: the multi-ethnic study of atherosclerosis. Stroke 2017; 48 AWP219.
[11.] Edjoc RK, Reid RD, Sharma M, Fang J. The prognostic effect of cigarette smoking on stroke severity, disability, length of stay in hospital, and mortality in a cohort with cerebrovascular disease. J Stroke and Cerebrovasc Dis 203; 22: e446-54. [CrossRef]
[12.] Urban RR, He H, Alfonso-Cristancho R, Hardesty MM, Goff BA. The cost of initial care for Medicare patients with advanced ovarian cancer. J Natl Canc Netw 201 6; 14: 429-37. [CrossRef]
[13.] Sposato LA, Cipriano LE, Saposnik G, et al. Diagnosis of atrial fibrillation after stroke and transient ischaemic attack: a systematic review and meta-analysis. Lancet Neurol 2015; 14: 377-87. [CrossRef]
[14.] January CT Wann LS, Alpert JS, et al. 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society. J AM Coll Cardiol 2014; 64: el-76. [CrossRef]
[15.] Edlow JA, Kim S, Pelletier AJ, Camargo CA. National study on emergency department visits for transient ischemic attack, 1992-2001. Acad Emerg Med. 2006; 13: 666-72. [CrossRef]
[16.] Andersen KK, Olsen TS, Dehlendorff C, Kammersgaard LP Hemorrhagic and ischemic strokes compared. Stroke 2009; 40: 2068-72. [CrossRef]
[17.] Hajat C, Dundas R, Stewart JA, et al. Cerebrovascular risk factors and stroke subtypes. Stroke 2001; 32: 37-42. [CrossRef]
[18.] Zhang J, Wang Y, Wang G, et al. Clinical factors in patients with ischemic versus hemorrhagic stroke in East China. World J Emerg Med 2011; 2: 18-23. [CrossRef]
[19.] Rahimi K, Emdin CA, MacMahon S. The epidemiology of blood pressure and its worldwide management. Circulation research 2015; 116: 925-36. [CrossRef]
[20.] Grysiewicz RA, Thomas K, Pandey DK. Epidemiology of ischemic and hemorrhagic stroke: incidence, prevalence, mortality, and risk factors. Neurol Clin 2008; 26: 871-95. [CrossRef]
[21.] Bilic I, Dzamonja G, Lusic I, Matijaca M, Caljkusic K. Risk factors and outcome differences between ischemic and hemorrhagic stroke. Acta Clin Croat 2009; 48: 399-403.
[22.] Kimura K, Minematsu K, Yamaguchi T Atrial fibrillation as a predictive factor for severe stroke and early death in 15 831 patients with acute ischaemic stroke. J Neurol Neurosurg Psychiatry 2005; 76: 679-83. [CrossRef]
[23.] Jorgensen HS, Nakayama H, Raaschou HO, Olsen TS. Intracerebral hemorrhage versus infarction: stroke severity, risk factors, and prognosis. Ann Neurol 1995; 38: 45-50. [CrossRef]
[24.] Liu X-F van Melle G, Bogousslavsky J. Analysis of risk factors in 3901 patients with stroke. Chin Med Sci J 2005; 20: 35-9.
[25.] Wolf PA, Abbott RD, Kannel WB. Atrial fibrillation: a major contributor to stroke in the elderly: the Framingham Study. Arch Intern Med. 1987; 147: 1561-4. [CrossRef]
[26.] Yamada Y Metoki N, Yoshida H, et al. Genetic risk for ischemic and hemorrhagic stroke. Arterioscler Thromb Vasc Biol 2006; 26: 19205. [CrossRef]
[27.] Skaf E, Stein PD, Beemath A, et al. Venous thromboembolism in patients with ischemic and hemorrhagic stroke. The American journal of cardiology. 2005; 96: 1731-3. [CrossRef]
[28.] Turnipseed W, Berkoff H, Belzer F Postoperative stroke in cardiac and peripheral vascular disease. Ann Surg 1980; 192: 365-8. [CrossRef]
[29.] Bailey RD, Hart RG, Benavente O, Pearce LA. Recurrent brain hemorrhage is more frequent than ischemic stroke after intracranial hemorrhage. Neurology 2001; 56: 773-7. [CrossRef]
Samad Shams Vahdati (1), Alireza Ala (2), Seyed Ali Mousavi Aghdas (3), Ali Adib (2), Mohammad Mirza-Aghazadeh-Attari (4), Fatemeh Aliar (2)
ORCID IDs of the authors: S.S.V. 0000-0002-4831-6691; A.A. 0000-0001-8231-2937; SA.MA. 0000-0001-9408-3596; A.A. 0000-0003-1613-7653; MMAA. 0000-0001-7927-6912; FA. 0000-0002-3544-132X.
(1) Department of Emergency, Emergency Medicine Research Team, Tabriz University of Medical Sciences, Iran
(2) Department of Emergency Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
(3) Students Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
(4) Institute of Aging Research, Tabriz University of Medical Sciences, Tabriz, Iran
Received: October 27, 2017
Accepted: December 6, 2017
Correspondence to: Mohammad Mirza-Aghazadeh-Attari E-mail: email@example.com
Caption: Figure 1. Distribution of age in patients included in the study
Caption: Figure 2. Distribution of patients based on the subtype of stroke separated according to sex
Caption: Figure 3. Prevalence of different risk factors in the included patients
Table 1. Relevance of stroke risk factors in accordance with the subtypes of stroke B S.E. Wald DF Variables DM -.290 .264 1.203 1 AH .680 .220 9.555 1 HLP -.418 .330 1.607 1 Smoke .348 .278 1.569 1 Alcohol .910 .598 2.318 1 Family History -2.243 .520 18.627 1 IHD -.066 .587 .013 1 AF -1.442 .415 12.092 1 TIA -.360 .254 2.006 1 Age -.035 .008 17.346 1 Sex .171 .201 .725 1 Constant .698 .572 1.491 1 Sig. Exp[B] Variables DM .273 .749 AH .002 1.974 HLP .205 .658 Smoke .210 1.417 Alcohol .128 2.485 Family History .000 .106 IHD .910 .936 AF .001 .236 TIA .157 .698 Age .000 .966 Sex .395 1.187 Constant .222 2.010 Variable(s) entered on step 1: DM (Diabetes mellitus), AH (Arterial Hypertension), HLP (Hyperlipidemia), Smoke, Alcohol, Familial history, IHD (Ischemic heart disease), Atrial fibrillation (AF), TIA (Transient ischemic attack), age, sex
|Printer friendly Cite/link Email Feedback|
|Title Annotation:||Original Article|
|Author:||Vahdati, Samad Shams; Ala, Alireza; Aghdas, Seyed Ali Mousavi; Adib, Ali; Mirza-Aghazadeh-Attari, Mo|
|Publication:||The Eurasian Journal of Medicine|
|Date:||Jun 1, 2018|
|Previous Article:||The Role of Ionic Homeostasis in Cisplatin-Induced Neurotoxicity: A Preliminary Study.|
|Next Article:||Computed Tomography-Based Diagnosis of Gastric Vein Invasion in Patients with Gastric Cancer.|