Long-Term Prognosis of Spontaneous Intracerebral Hemorrhage on the Tibetan Plateau: A Prospective Cohort Study at 2 Hospitals

Accepted Manuscript Long-term Prognosis of Spontaneous Intracerebral Hemorrhage on the Tibetan Plateau: A Prospective Cohort study at Two Hospitals Ruozhen Yuan, MD, Deren Wang, MD, PhD, Ming Liu, MD, PhD, Junfeng Liu, MD, Yongqiao He, MD, Yongyi Deng, MD, Chunyan Lei, MD, Zilong Hao, MD, PhD, Wendan Tao, MD, PhD, Bian Liu, MD, Xueli Chang, MD, Qiuxiao Wang, MD, Ge Tan, MD PII:

S1878-8750(16)30338-2

DOI:

10.1016/j.wneu.2016.05.064

Reference:

WNEU 4125

To appear in:

World Neurosurgery

Received Date: 26 February 2016 Revised Date:

20 May 2016

Accepted Date: 21 May 2016

Please cite this article as: Yuan R, Wang D, Liu M, Liu J, He Y, Deng Y, Lei C, Hao Z, Tao W, Liu B, Chang X, Wang Q, Tan G, Long-term Prognosis of Spontaneous Intracerebral Hemorrhage on the Tibetan Plateau: A Prospective Cohort study at Two Hospitals, World Neurosurgery (2016), doi: 10.1016/j.wneu.2016.05.064. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Long-term Prognosis of Spontaneous Intracerebral Hemorrhage on the Tibetan Plateau: A Prospective Cohort study at Two Hospitals Ruozhen Yuan1, MD‡; Deren Wang1, MD, PhD‡*; Ming Liu1, MD, PhD*; Junfeng

RI PT

Liu1, MD; Yongqiao He2, MD; Yongyi Deng2, MD; Chunyan Lei1, MD; Zilong Hao1, MD, PhD; Wendan Tao1, MD, PhD; Bian Liu1, MD; Xueli Chang1, MD; Qiuxiao Wang1, MD; Ge Tan1, MD

Stroke Clinical Research Unit, Department of Neurology, West China Hospital,

SC

1

2

M AN U

Sichuan University, Chengdu, P.R. China

Department of Neurology, People’s Hospital of Garzê, Garzê, P.R. China

*Correspondence to Deren Wang, Stroke Clinical Research Unit, Department of

TE D

Neurology, West China Hospital, Sichuan University, No 37, GuoXue Xiang, Chengdu, 610041, Sichuan Province, PR China. E-mail address: [email protected]. Tel: +86 15608231902. or Professor Ming Liu, Stroke Clinical Research Unit,

EP

Department of Neurology, West China Hospital, Sichuan University, No. 37, GuoXue

AC C

Xiang, Chengdu, 610041, Sichuan Province, PR China. E-mail address: [email protected]. Tel: +86 18980601671, Fax: +86 28 85423551 .

Running title: ICH on the Tibetan Plateau Keywords: Intracerebral hemorrhage, High-altitude, Tibetan plateau, Long-term outcomes, Comparative study.

1

ACCEPTED MANUSCRIPT ‡Ruozhen Yuan and Deren Wang contributed equally to this study Tables: 2 Figures: 1

RI PT

Abbreviations: CI, confidence interval; CT, computed tomography; DBP, diastolic blood pressure; GCS, Glasgow Coma Scale; ICH, intracerebral hemorrhage; IQR,

interquartile range; MR, magnetic resonance; mRS, modified Rankin Scale; NIHSS,

AC C

EP

TE D

M AN U

systolic blood pressure; WCH, West China Hospital.

SC

National Institutes of Health Stroke Scale; PHG, People’s Hospital of Garzê; SBP,

2

ACCEPTED MANUSCRIPT Abstract Background and purpose: Patterns of intracerebral hemorrhage (ICH) and outcomes in Tibetans are poorly understood. We aimed to investigate the long-term outcomes of

RI PT

Tibetan ICH patients. Methods: This prospective study involved a consecutive series of ICH patients admitted within 1 month of onset to West China Hospital (WCH) on the Chengdu

SC

Plain or People’s Hospital of Garzê (PHG) on the Tibetan Plateau between January

M AN U

2013 and December 2013. Basic characteristics and functional outcomes were compared between PHG and WCH groups.

Results: Of the 843 cases included, 105 (12.5%) were from PHG and 738 (87.5%) were from WCH. Compared to patients from WCH, patients from PHG were older

TE D

and had higher blood pressure on admission, and a greater proportion had hypertension (all P<0.001). Among patients from PHG, the 1-year death rate was 30.5%, similar to that in WCH (P=0.987), and the adjusted 3-month disability risk

EP

was 2.0-fold higher than for WCH patients, while the adjusted 1-year disability risk

AC C

was 2.5-fold higher than for WCH patients (both P≤0.05). The adjusted 3-month risk of disability/death was 2.1-fold higher in PHG patients than in WCH patients, while the adjusted 1-year risk was 2.4-fold higher (both P≤0.05). Conclusions: Most cases of ICH on the Tibetan Plateau involve concomitant hypertension. Tibetan patients are at higher risk of disability or disability/death on follow-up than are patients from Chengdu Plain.

3

ACCEPTED MANUSCRIPT Introduction Stroke is the second leading cause of death and third leading cause of disability-adjusted life-years (DALYs) worldwide,1 with spontaneous intracerebral

RI PT

hemorrhage (ICH) being the most fatal and least treatable form. In China, ICH accounts for a larger proportion of all strokes than in Western countries,2 though the frequency of ICH varies across the country, likely reflecting variation in the

SC

prevalence of cardiovascular risk factors.3 In Tibet, which is located on the so-called

M AN U

Tibetan Plateau in western China, the local diet is rich in meat and salt, increasing the risk of hypertension, hyperlidemia and therefore stroke. As a result, Tibet forms part of the “stroke belt” in China.4 Our previous work has shown that ICH is the most

TE D

frequent stroke subtype on the Plateau, accounting for 74.1% of all cases.5

Detailed information on the clinical profile of ICH among patients on the Tibetan Plateau is scarce, making it difficult to understand prognosis in this part of the stroke

EP

belt and to design effective prevention and management strategies. We conducted a

AC C

prospective cohort study at two hospitals in order to help clarify the prognostic features of ICH in Tibetans and compare long-term functional outcomes of Tibetan and non-Tibetan ICH patients.

Subjects and methods Study design This prospective study was supported by the National Key Technology R&D Program 4

ACCEPTED MANUSCRIPT of the 12th Five-Year Plan entitled “Study on Etiology and Minimally Invasive Neurosurgery for Hemorrhagic Stroke”. The study protocol was approved by the Scientific Research Department of West China Hospital and it conformed to local

RI PT

ethics criteria for human research.6 Informed consent was obtained from patients or their relatives.

SC

The study was carried out at two hospitals. One was the People’s Hospital of Garzê

M AN U

(PHG) in the Tibetan Autonomous Prefecture of Garzê, located on the southeastern Tibetan Plateau (27°58″-34°20″, 97°22″-102°29″) near the Hengduan Mountains, at altitudes ranging from 2280 to 4540 m. PHG is the only tertiary medical center of the prefecture. The other hospital was West China Hospital (WCH), a comprehensive

TE D

teaching and research hospital on the Chengdu Plain that serves the residents mainly from Sichuan Province, together with some surrounding provinces from southwest China. Both hospitals enroll patients from urban, suburban and rural areas, who

EP

present for the first time or after referral by a local physician. The most recent census

AC C

figures (from 2010) indicate a total population of 1.09 million and a population density of 7 people/km2 in the Tibetan Autonomous Prefecture of Garzê, compared to a total population of 80.4 million and population density of 166 people/km2 in Sichuan Province.7

Neurological physicians at PHG and WCH prospectively reviewed medical records of consecutive patients admitted to the two hospitals between January 1, 2013 and 5

ACCEPTED MANUSCRIPT December 31, 2013 with a diagnosis of ICH, corresponding to code I61 of the International Classification of Diseases (10th Revision). To be included in the study, patients had to meet the WHO definition of stroke8 within 30 days of onset, and their

RI PT

hemorrhage had to be confirmed by computed tomography (CT) and/or magnetic resonance (MR). Patients were excluded if they had primary subarachnoid hemorrhage, primary subdural/epidural hematoma, hemorrhagic transformation of

SC

ischemic stroke, and hemorrhage due to trauma or brain tumor. Patients were also

Data collection and outcomes

M AN U

excluded if they were transferred from Tibetan regions to WCH.

Data were recorded at admission about demographics, past medical history, time of

TE D

onset, stroke severity and vital signs. Laboratory and imaging data were obtained within 24 h of admission. Hypertension, hyperlipidemia, and diabetes mellitus were defined as in our previous study.9 Stroke severity on admission was measured using

EP

the National Institutes of Health Stroke scale (NIHSS)10 and Glasgow Coma scale

AC C

(GCS)11. At 3, 6, and 12 months after stroke onset, patients were followed up by telephone, when well-trained neurologists assessed functional outcomes using the modified Rankin Scale (mRS)12. Functional outcomes were death, disability, and death/disability. Disability was defined as an mRS score of 3-5. Dates of death were recorded.

Statistical analysis 6

ACCEPTED MANUSCRIPT All statistical analyses were performed using SPSS 19.0 (IBM, USA). Intergroup differences on continuous variables were assessed for significance using analysis of variance or Mann-Whitney U tests, while differences on categorical variables were

RI PT

assessed using χ2 or Fisher’s exact tests as appropriate. Multivariate logistic regression was performed to explore possible associations between hospitalization at PHG and outcomes. Survival rates in the two regions were compared using the Kaplan–Meier

SC

product limit method and log rank test. A two-sided P<0.05 was considered

Results Baseline patient characteristics

M AN U

statistically significant.

TE D

A total of 843 patients were included; 65.6% (553/843) were male, and median age was 56 years. The PHG cohort comprised 105 patients (12.5%), of whom 69.5% were male, and median age at stroke onset was 61 years. A total of 19 Tibetan patients were

EP

transferred to WCH during the study period, and they were excluded from the analysis.

AC C

Their demographics and ICH severity on admission did not differ from those of the rest of the PHG cohort (data not shown). Baseline characteristics of ICH patients admitted to PHG or WCH are shown in Table 1.

Compared to patients at WCH, patients at PHG were older (median age, 61 vs 55 years; P<0.001), were admitted with a longer delay from stroke onset (median, 24 vs 10 h; P=0.002), and showed a significantly higher proportion of hypertension (98.1% 7

ACCEPTED MANUSCRIPT vs 67.2%; P<0.001) and diabetes mellitus (21.9% vs 12.7%; P=0.011). On admission, patients at PHG had significantly higher systolic blood pressure (176.20±31.65 vs 159.62±34.11 mmHg; P<0.001), diastolic blood pressure (108.17±19.36 vs

RI PT

93.65±19.42 mmHg; P<0.001), platelet count (median, 194 vs 155 x 109/L; P<0.001), total cholesterol (median, 4.81 vs 4.33 mmol/L; P<0.001), and lower albumin (median, 39.8 vs 42.8 g/L; P<0.001). Based on CT or MR imaging, PHG patients

SC

showed a significantly higher proportion of midline shift (49.5% vs 33.6%; P=0.001)

M AN U

and lower proportions of infratentorial hemorrhage (4.8% vs 16.8%; P=0.001) and intraventricular hemorrhage (30.5% vs 42.1%; P=0.023).

The two groups were similar in terms of gender distribution (P=0.366), stroke

TE D

severity on admission (GCS score, P=0.127; NIHSS score, P=0.754) and proportion

Outcomes

EP

of hyperlipidemia (37.1% vs 35.0%; P=0.661).

AC C

Patients at PHG showed a death rate of 25.8% at 3 months, 29.5% at 6 months, and 30.5% at 1 year; these values were similar to those of patients at WCH, with respective P values of 0.950, 0.760 and 0.987. The two cohorts did not show significant differences in 1-year survival curves (P=0.943, log rank test; Figure 1).

Patients at PHG showed a significantly higher proportion of disability, defined as an mRS score of 3-5, at 3 months (55.6% vs 39.5%; P=0.010), 6 months (44.8% vs 8

ACCEPTED MANUSCRIPT 31.8%; P=0.034), and 1 year (42.4% vs 24.8%; P=0.003; Table 2). After adjusting for age, gender, admission delay, GCS score on admission, infratentorial hemorrhage, intraventricular hemorrhage and midline shift, risk of disability in PHG patients was

RI PT

higher than that in WCH patients by 2.0-fold (95% confidence interval [CI], 1.096-3.582; P=0.024) at 3 months and by 2.5-fold (95% CI, 1.310-4.735; P=0.005)

M AN U

(OR 1.866, 95% CI 0.998-3.489, P=0.051).

SC

at 1 year. Adjusted risk of disability was similar between the two groups at 6 months

Similarly, the combined frequency of death/disability was significantly higher among PHG patients than WCH patients at 3 months (67.0% vs 55.3%; P=0.029) and 1 year (60.0% vs 47.8%; P=0.027) (Table 2), but not at 6 months (61.1% vs 50.9%;

TE D

P=0.063). After adjustment for age, gender, admission delay, GCS score on admission, infratentorial hemorrhage, intraventricular hemorrhage and midline shift, risk of death/disability in PHG patients was higher than that in WCH patients by 2.1-fold

EP

(95% CI, 1.194-3.640; P=0.010) at 3 months and by 2.4-fold (95% CI, 1.382-4.206;

AC C

P=0.002) at 1 year.

Discussion

Located on the Qinghai-Tibetan Plateau and poorly studied, Tibet has an annual stroke incidence (450.4 per 100,000) that is triple the incidence in mainland China as a whole (135.6/100,000)4. ICH is the leading subtype of all strokes.4,5 In the present prospective study based on a large hospital on the Tibetan Plateau (PHG) and another 9

ACCEPTED MANUSCRIPT on the Chengdu Plain (WCH), we found that most PHG patients had concomitant hypertension, and they had higher blood pressure but similar stroke severity on admission as WCH patients. Risk of disability or disability/death was about 2.5-fold

RI PT

higher among PGH patients than WCH patients at 1 year after stroke onset, even after adjustment. Our findings provide insights that may help guide stroke prevention and

SC

management strategies targeting the Tibetan population.

M AN U

The two populations of ICH patients differed at baseline primarily in vascular risk factors. In particular, Tibetan patients showed a higher prevalence of hypertension, consistent with what our group reported previously.5 Living at high altitudes with reduced oxygen levels and intense radiation, Tibetans have increased hemoglobin

TE D

levels, a condition known as high-altitude polycythemia, which together with the high-sodium, low-potassium Tibetan diet increases the risk of hypertension. Hypertension, in turn, is a well-documented risk factor for intracerebral

EP

hemorrhage.4,13-16 Awareness, treatment and control of hypertension in Tibet are

AC C

poor.15 The high prevalence of hypertension among Tibetans likely helps explain why they show elevated prevalence of ICH.5 Together, the results of the present study and the available literature17,18 indicate that many cases of ICH among Tibetans could be prevented every year with more timely diagnosis and adequate treatment of hypertension.

Interestingly, we found similar 1-year death rates for ICH patients at PHG and WCH, 10

ACCEPTED MANUSCRIPT although PHG patients showed a higher 1-year disability rate. These results contrast with those of our previous study of early outcomes at discharge among Tibetan ICH patients and hospital different from those in the present study.5 In that previous work,

RI PT

we reported a higher mortality rate and a lower disability rate at discharge than among WCH patients. The discrepancy between our previous and present studies likely reflects variations in functional outcomes during the first year after ICH onset, not

SC

only between individuals but also over time.19 Another possible explanation is

M AN U

differences between the two Tibetan populations and hospitals in the two studies. The present work is, to our knowledge, the first study of long-term outcomes in Tibetan patients after ICH, so our findings should be verified in larger samples.

TE D

A key finding of the present study is that ICH patients on the Tibetan Plateau appear to be at about 2.5-fold higher risk of disability or disability/death at 1 year than patients on the Chengdu Plain. This higher risk may reflect inadequate systems for

EP

stroke rehabilitation as a result of poverty and/or culture-specific factors.20 It is also

AC C

possible that the extreme geographic conditions may compromise the natural ICH recovery process. Regardless of the underlying causes, our results suggest that improving stroke rehabilitation on the Tibetan Plateau may promote functional recovery of ICH patients and thereby reduce the disease burden on society.21

The prospective design of the present study and its year-round recruitment of a consecutive patient population for parallel comparison of Tibetan and non-Tibetan 11

ACCEPTED MANUSCRIPT medical centers strengthen our conclusions. In addition, we conducted follow-up out to 1 year and assessed functional outcomes, not just survival.

RI PT

At the same time, our study suffers from several weaknesses that limit its conclusions. First, the PGH population in our study (n=105) was much smaller than the WCH population (n=738), and the drop-out rate was higher among PGH patients [10 (9.5%)

SC

vs. 65 (8.8%) at 1 year]. These issues likely reflect the much lower population density

M AN U

in the PHG catchment area, as well as the lower education level and linguistic and cultural differences of Tibetans, which make follow-up difficult. Second, our study did not take into account ICH volume, which has been shown to be an independent prognostic factor.22 Third, we could not compare etiological subtypes between the two

TE D

hospitals because ICH patients admitted to PHG were not routinely analyzed by angiography. The major causes of ICH are hypertension, amyloid angiopathy, vascular structural abnormality, medication, and systematic disease.23,24 Compared to ICH

EP

caused by hypertension or amyloid angiopathy, ICH related to vascular structural

AC C

abnormality commonly occurs in younger patients, shows different clinical characteristics and is associated with better outcomes.25,26 Therefore, differences in the etiological proportions between the two hospitals may contribute to observed differences in baseline characteristics and outcomes. Fourth, this study compares two hospital populations, increasing the risk that the results may not be generalizable to the general population. The two populations come from quite different environments: Garzê has much lower population density and less developed transportation and 12

ACCEPTED MANUSCRIPT health infrastructure than the Chengdu area.27 The hospitals differed in some standard practices, which may help explain the different outcomes that we observed between the two medical centers, although the fact that we did not impose pre-specific

RI PT

treatment algorithms on both centers may make our observational study more reflective of clinical reality. The PHG patients in our study showed longer admission delay, higher prevalence of midline shift, and lower prevalence of intraventricular

SC

hemorrhage and infratentorial hemorrhage than WCH patients. These differences

M AN U

suggest that we may have missed a group of patients who did not, or could not, seek medical help. This highlights the need for large population- or community-based studies of the Tibetan region to understand the clinical characteristics of ICH.

TE D

In conclusion, our study provides important new information regarding long-term outcomes of ICH patients in Tibetans. We found that most cases of ICH in Tibetans had concomitant hypertension and Tibetan patients with ICH had poor prognosis in

EP

terms of disability and death/disability. Prevention and management of ICH in

AC C

Tibetans remain a challenge for local health systems.

Acknowledgments None.

Funding This study was sponsored by research grants from the National Natural Science 13

ACCEPTED MANUSCRIPT Foundation of China (grant nos. 81371282 and 81400964) and the National Key Technology R&D Program of the 12th Five-Year Plan of the People’s Republic of China (grant no.

2011BAI08B05). These agencies did not have any role in the

RI PT

design or execution of the study; in the collection, management, analysis or

Disclosure of conflicts of interest statement

SC

interpretation of the data; or in the preparation, review or approval of the manuscript.

AC C

EP

TE D

M AN U

All the authors declare no financial or other conflicts of interest.

14

ACCEPTED MANUSCRIPT References 1.

Feigin VL, Forouzanfar MH, Krishnamurthi R, et al. Global and regional burden of stroke during 1990–2010: findings from the Global Burden of Disease Study 2010. The Lancet.

2.

RI PT

2014;383(9913):245-255. Liu M, Wu B, Wang W-Z, Lee L-M, Zhang S-H, Kong L-Z. Stroke in China: epidemiology, prevention, and management strategies. The Lancet Neurology. 2007;6(5):456-464.

Wei JW, Arima H, Huang Y, et al. Variation in the frequency of intracerebral haemorrhage and

SC

3.

diseases. 2010;29(4):321-327. 4.

Xu G, Ma M, Liu X, Hankey GJ. Is there a stroke belt in China and why? Stroke. 2013;44(7):1775-1783.

Fang J, Zhuo-Ga C, Zhao Y, et al. Characteristics of stroke in tibet autonomous region in

TE D

5.

M AN U

ischaemic stroke in China: a national, multicentre, hospital register study. Cerebrovascular

china: a hospital-based study of acute stroke. European neurology. 2011;66(3):151-158. 6.

Lei C, Wu B, Liu M, et al. VSARICHS: a simple grading scale for vascular structural

EP

abnormality-related intracerebral haemorrhage. Journal of neurology, neurosurgery, and

7.

AC C

psychiatry. 2014.

The Circular of the State Council on the Conduct of the 6th National Population Census,

Department of Population and Employment Statistics National Bureau of Statistics. Major

figures on 2010 population census of China. Beijing: China Statistical Press; 2011.

8.

Hatano S. Experience from a multicentre stroke register: a preliminary report. Bulletin of the World Health Organization. 1976;54(5):541-553.

9.

Kong FY, Tao WD, Hao ZL, Liu M. Predictors of one-year disability and death in Chinese

15

ACCEPTED MANUSCRIPT hospitalized women after ischemic stroke. Cerebrovascular diseases. 2010;29(3):255-262. 10.

Brott T, Adams HP, Olinger CP, et al. Measurements of acute cerebral infarction - A clinical examination scale. Stroke. 1989;20(7):864-870. Teasdale G, Jennett B. Assessment of coma and impaired consciousness - practical scale.

RI PT

11.

Lancet. 1974;2(7872):81-84. 12.

van Swieten JC, Koudstaal PJ, Visser MC, Schouten HJ, van Gijn J. Interobserver agreement

Zhang XF, Attia J, D'Este C, Yu XH. Prevalence and magnitude of classical risk factors for

M AN U

13.

SC

for the assessment of handicap in stroke patients. Stroke. 1988;19(5):604-607.

stroke in a cohort of 5092 Chinese steelworkers over 13.5 years of follow-up. Stroke. 2004;35(5):1052-1056. 14.

Okumiya K, Sakamoto R, Kimura Y, et al. Comprehensive geriatric assessment of elderly

diseases

among

TE D

highlanders in Qinghai, China II: the association of polycythemia with lifestyle-related the

three

ethnicities.

Geriatrics

&

gerontology

international.

2009;9(4):342-351.

Zhao X, Li S, Ba S, et al. Prevalence, awareness, treatment, and control of hypertension

EP

15.

AC C

among herdsmen living at 4,300 m in Tibet. American journal of hypertension. 2012;25(5):583-589.

16.

Guo X, Long R, Kreuzer M, et al. Importance of functional ingredients in yak milk-derived

food on health of Tibetan nomads living under high-altitude stress: a review. Critical reviews

in food science and nutrition. 2014;54(3):292-302. 17.

Five-year findings of the hypertension detection and follow-up program. III. Reduction in stroke incidence among persons with high blood pressure. Hypertension Detection and

16

ACCEPTED MANUSCRIPT Follow-up Program Cooperative Group. Jama. 1982;247(5):633-638. 18.

Probstfield

JL.

PREVENTION

DRUG-TREATMENT

IN

OF

OLDER

STROKE

PERSONS

BY

WITH

ANTIHYPERTENSIVE ISOLATED

SYSTOLIC

RI PT

HYPERTENSION - FINAL RESULTS OF THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM (SHEP). Jama. 1991;265(24):3255-3264. 19.

Hemphill JC, III, Farrant M, Neill TA, Jr. Prospective validation of the ICH Score for

Scheidegger G, Lovelock L, Kinebanian A. The daily lives and occupations of Tibetan families

M AN U

20.

SC

12-month functional outcome. Neurology. 2009;73(14):1088-1094.

who have a child with disabilities. Scandinavian Journal of Occupational Therapy. 2010;17(4):286-298. 21.

Hemphill JC, 3rd, Greenberg SM, Anderson CS, et al. Guidelines for the Management of

TE D

Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015. 22.

Hemphill JC, 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC. The ICH score: a

Qureshi AI, Tuhrim S, Broderick JP, Batjer HH, Hondo H, Hanley DF. Spontaneous

AC C

23.

EP

simple, reliable grading scale for intracerebral hemorrhage. Stroke. 2001;32(4):891-897.

intracerebral hemorrhage. N Engl J Med. 2001;344(19):1450-1460.

24.

Meretoja A, Strbian D, Putaala J, et al. SMASH-U: a proposal for etiologic classification of

intracerebral hemorrhage. Stroke. 2012;43(10):2592-2597.

25.

Cordonnier C, Al-Shahi Salman R, Bhattacharya JJ, et al. Differences between intracranial vascular malformation types in the characteristics of their presenting haemorrhages: prospective, population-based study. Journal of neurology, neurosurgery, and psychiatry.

17

ACCEPTED MANUSCRIPT 2008;79(1):47-51. 26.

van Beijnum J, Lovelock CE, Cordonnier C, et al. Outcome after spontaneous and arteriovenous malformation-related intracerebral haemorrhage: population-based studies.

27.

RI PT

Brain. 2009;132(Pt 2):537-543. Garzê Statiscal Year Book 2013. Bureau of Statistics of Tibetan Autonomous Prefecture of

AC C

EP

TE D

M AN U

SC

Garzê; 2013.

18

ACCEPTED MANUSCRIPT Table 1. Demographic and clinical characteristics of ICH patients on the Tibetan Plateau (PHG) or Chengdu Plain (WCH)

Table 2. Death and disability of ICH patients on the Tibetan Plateau (PHG) or

RI PT

Chengdu Plain (WCH) [n/N (%)]

Figure 1. Kaplan-Meier survival curves for patients with ICH stratified by

AC C

EP

TE D

M AN U

SC

medical center. PHG, People’s Hospital of Garzê; WCH, West China Hospital.

19

ACCEPTED MANUSCRIPT Table 1. Demographic and clinical characteristics of ICH patients on the Tibetan Plateau (PHG) or Chengdu Plain (WCH) p

PHG

WCH

(n=105)

(n=738)

Male, n (%)

73 (69.5)

480 (65.0)

Age, median (IQR)

61 (50-67)

55 (44-65)

<0.001

Hypertension

103 (98.1)

496 (67.2)

<0.001*

Hyperlipidemia

39 (37.1)

258 (35.0)

0.661*

Diabetes mellitus

23 (21.9)

Admission delay in hr, median (IQR) Characteristics on admission Stroke severity GCS, median (IQR)

RI PT

0.011*

67 (9.1)

0.139*

24 (6-72)

10 (4-30)

0.002

14 (9-14)

12 (6-15)

0.127

10 (3-13)

9 (3-20)

0.754

SBP in mmHg, mean (SD)

176.20 (31.65)

159.62 (34.11)

<0.001

DBP in mmHg, mean (SD)

108.17 (19.36)

93.65 (19.42)

<0.001

Hemoglobin, g/L

152 (133-166)

137 (124-148)

<0.001

Platelets, x109/L

194 (149-231)

155 (115-202)

<0.001

AC C

TE D

NIHSS, median (IQR)

94 (12.7)

M AN U

5 (4.8)

SC

Co-morbid conditions, n (%)

Prior stroke

0.366*

Albumin, g/L

39.8 (36.7-43.1)

42.8 (39.5-45.3)

<0.001

Triglycerides, mmol/L

1.12 (0.84-1.48)

1.08 (0.76-1.67)

0.895

Total cholesterol, mmol/L

4.81 (4.07-5.41)

4.33 (3.70-5.01)

<0.001

Cortical/subcortical/lobar

35 (33.3)

264 (35.8)

0.625*

Deep supratentorial

68 (64.8)

365 (49.5)

0.003*

5 (4.8)

124 (16.8)

0.001*

32 (30.5)

311 (42.1)

0.023*

EP

Laboratory results, median (IQR)

ICH location, n (%)

Infratentorial Intraventricular hemorrhage, n (%)

ACCEPTED MANUSCRIPT Midline shift, n (%)

52 (49.5)

248 (33.6)

0.001*

DBP, diastolic blood pressure; GCS, Glasgow Coma Scale; ICH, intracerebral hemorrhage; IQR, interquartile range; NIHSS, National Institutes of Health Stroke Scale; PHG, People’s Hospital of Garzê; SBP, systolic blood pressure; WCH, West

RI PT

China Hospital * χ2 test Analysis of variance

AC C

EP

TE D

M AN U

SC

Mann–Whitney U test

ACCEPTED MANUSCRIPT Table 2. Death and disability of ICH patients on the Tibetan Plateau (PHG) or Chengdu Plain (WCH) [n/N (%)] PHG

WCH

p

3 months

25/97 (25.8)

183/702 (26.1)

0.950

6 months

28/95 (29.5)

193/690 (28.0)

12 months

29/95 (30.5)

206/673 (30.6)

3 months

40/72 (55.6)

205/519 (39.5)

6 months

30/67 (44.8)

158/497 (31.8)

0.034

12 months

28/66 (42.4)

116/467 (24.8)

0.003

M AN U

SC

Disability

RI PT

Death

Death/Disability

0.760

0.987

0.010

3 months

65/97 (67.0)

388/702 (55.3)

0.029

6 months

58/95 (61.1)

351/690 (50.9)

0.063

12 months

57/95 (60.0)

322/673 (47.8)

0.027

AC C

EP

TE D

PHG, People’s Hospital of Garzê; WCH, West China Hospital

ACCEPTED MANUSCRIPT Figure 1. Kaplan-Meier survival curves for patients with ICH stratified by

AC C

EP

TE D

M AN U

SC

RI PT

medical center. PHG, People’s Hospital of Garzê; WCH, West China Hospital.

ACCEPTED MANUSCRIPT 1. Most Tibetan ICH patients had concomitant hypertension. 2. Similar death rates were observed between the Tibetan and non-Tibetan ICH patients.

RI PT

3. Tibetan ICH patients had worse functional outcomes than non-Tibetan patients on

AC C

EP

TE D

M AN U

SC

follow-ups.

ACCEPTED MANUSCRIPT

Conflicts of interest: All the authors declare no financial or other

AC C

EP

TE D

M AN U

SC

RI PT

conflicts of interest.