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. 2013 Nov 5;8(31):2923–2931. doi: 10.3969/j.issn.1673-5374.2013.31.005

Synergistic effects of elevated homocysteine level and abnormal blood lipids on the onset of stroke

Lu Hao 1,1, Liming Chen 1,#, Xiaoyong Sai 2,3,#, Zhefeng Liu 1, Guang Yang 1, Rongzeng Yan 1, Lili Wang 1, Caiyun Fu 1, Xuan Xu 1, Zhenzhen Cheng 1, Qiang Wu 1, Shuzhang Li 1,✉
PMCID: PMC4146172  PMID: 25206613

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Keywords: neural regeneration, stroke, cysteine, risk factor, case-control study, abnormal blood lipids, medication, inpatients, cardiovascular disease, paired analysis, grants-supported paper, neuroregeneration

Abstract

Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether both factors exert a synergistic effect in the onset of stroke remains unclear. The present study is a retrospective analysis of 2 089 cases of stroke and 2 089 control cases of simple intervertebral disk protrusion using a paired multivariate logistic regression method. Adjusting for known confounding variables including the patients’ age, gender, smoking status, alcohol consumption status, patient and family medical history, and clinical biochemical indices, elevated homocysteine level was related to the onset of stroke. Patients with elevated homocysteine levels and abnormal blood lipids showed a 40.9 % increase in the risk for stroke compared to patients with normal homocysteine levels and blood lipids (odds ratio 1.409; 95% confidence interval 1.127–1.761). These results indicate that elevated homocysteine and abnormal blood lipids exert synergistic effects in the onset of stroke. Patients with elevated homocysteine levels and abnormal blood lipids are predisposed to stroke.

INTRODUCTION

Hyperhomocysteinemia and abnormal blood lipids are independent risk factors for stroke. However, whether they exert a synergistic effect in the onset of stroke remains poorly understood. There is evidence that a family history of abnormal blood pressure and blood lipids increases the risk for ischemic stroke in stroke patients compared to those without stroke, and the pathological mechanisms underlying the different subtypes of ischemic stroke are varied[1,2,3]. Elevated blood pressure/blood lipids is correlated with ischemic stroke risk[4,5]. Large artery atherosclerotic ischemic stroke is particularly closely related to blood lipids[6,7,8].

Hyperhomocysteinemia is an independent risk factor for atherosclerosis. Ten percent of coronary heart disease patients have hyperhomocysteinemia, and slightly or moderately elevated homocysteine levels can increase the risk of cardiovascular disease four to sixfold[9,10,11,12].

Many studies have investigated risk factors for stroke, but there is a lack of studies addressing the association between homocysteine, blood lipids, and stroke risk. The present study is a retrospective analysis of inpatients across a 5 year period from the Chinese PLA General Hospital, based on a matched pairs case control design.

RESULTS

Quantitative analysis of subjects

A total of 7 802 questionnaires were handed out and 6 203 were completed, with an effective rate of 79.51%. 2 089 stroke patients (case group) and 2 089 simple intervertebral disk protrusion patients (control group) were paired, and their data were analyzed. All 4 179 cases were included in the final analysis, without loss.

Baseline subject characteristics

Number of patients presenting with known risk factors and mean values of biochemical indices are provided in Table 1.

Table 1.

Baseline subject characteristics

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Multivariate analysis of stroke-related risk factor

With the exception of age, triglycerides, and history of coronary heart disease and diabetes mellitus, all other variables differed significantly between the case and control groups (P < 0.05).

Adjusting for age, gender, smoking status, alcohol consumption, family medical history (coronary heart disease, hypertension, stroke and diabetes mellitus), patient history (coronary heart disease, hypertension, stroke, diabetes mellitus, and hyperlipidemia), body mass index, systolic pressure, total cholesterol, triglycerides, low- and high-density lipoprotein cholesterols, and fasting blood glucose, we found that homocysteine levels were related to the onset of stroke.

The risk for stroke was 1.297 times higher in females than males, and 2.739 times higher in smokers than non-smokers; compared with cases with no family history of cardiovascular events, stroke risk was 10.515, 2.830 and 5.145 times higher in cases who had a family history of coronary heart disease, hypertension or stroke, respectively; 2.161 times higher in cases who had a previous history of hypertension than those who did not. Risk was 1.220 and 2.335 times higher in cases in the low body weight or obese groups, respectively, than those in the normal body mass index (BMI) group. Compared with the normal blood pressure group, the risk for stroke was increased by 2.7% for each increase of 1 mmHg (0.133 kPa) in systolic pressure. The risk for stroke was 3.082 times higher in the elevated total cholesterol group than in the normal cholesterol level group, and lower in the elevated triglycerides group than in the normal triglycerides, although this may be a result of interaction between risk factors.

The risk for stroke was 1.539 times higher in the elevated high-density lipoprotein cholesterol group than the normal high-density lipoprotein cholesterol group, increased by 14.6% for each increase of 1 mmol/L fasting blood glucose compared with the normal fasting blood glucose group, and increased by 1.8% for each increase of 1 μmol/L homocysteine compared with the normal homocysteine level group. These data are summarized in Table 2.

Table 2.

Stroke risk factors

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Synergistic effect of homocysteine level and abnormal blood lipids on the onset of stroke

Taking into account age, gender, smoking status, alcohol consumption, body mass index, systolic pressure, family history of hypertension, stroke or coronary heart disease, and patient history of hypertension or coronary heart disease, odds ratio (OR) was 1.409 with a 95% confidence interval (CI) of 1.127 to 1.761 in the group with combined abnormal homocysteine and blood lipid levels compared to patients with normal levels.

This means that the risk for stroke in the group with elevated homocysteine levels complicated by abnormal blood lipids was increased by 40.9% (P = 0.003) compared with the group in which both factors were normal, indicating that elevated homocysteine level and abnormal blood lipid promote the onset of stroke.

Table 3.

Synergistic effect of elevated homocysteine level and abnormal blood lipid on the onset of stroke

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DISCUSSION

The present study correlated stroke with two important risk factors, elevated homocysteine and abnormal blood lipids. Both factors were significantly correlated with stroke onset. Further analysis revealed that stroke risk was higher in the group in which both factors were present together than in the groups presenting with elevated homocysteine or abnormal blood lipids alone. These findings indicate that the combined effect of elevated homocysteine and abnormal blood lipids should be taken into consideration in the clinical treatment of stroke.

Evidence for the effect of abnormal blood lipids and elevated homocysteine levels on the onset of stroke has previously been inconclusive, highlighting the need for further analysis of the pathological mechanisms and the prevention and treatment strategy of stroke. In the present study, the conventional risk factors of stroke were further evaluated.

The results show that total cholesterol, low- and high-density lipoprotein cholesterols, and triglycerides are related to the onset of stroke; smoking correlates positively with stroke; and systolic pressure is an independent stroke risk factor. Results from this study also showed that BMI is related to stroke; further study is required to elucidate the pathological mechanism behind this. Surprisingly, we found no correlation between family or patient history of diabetes mellitus and stroke. To our knowledge, the present study is the first to examine the relationship between stroke risk and elevated homocysteine levels complicated by abnormal blood lipids. To our knowledge, the present study is the first to examine the relationship between stroke risk and elevated homocysteine levels complicated by abnormal blood lipids[13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. Total cholesterol, low- and high-density lipoprotein cholesterols, and triglycerides are known risk factors for ischemic stroke[40,41,42,43].

The correlation between triglycerides and stroke remains disputed[43,44,45,46]. Chyou and Eaker[47] reported that total cholesterol is a risk factor for all-cause mortality in patients aged > 65 years. Wells et al[48] concluded that low-density lipoprotein cholesterol is an important predictor of cardiovascular disease. Similarly, the effects of blood lipid components are also affected by many other factors; for example, the effects of total serum cholesterol on all-cause mortality are correlated with smoking, drinking and hypertension[49]. The correlation between each factor and stroke has yet to be fully evaluated.

Shinton and Beevers[50] performed a meta-analysis on smoking and stroke and found that the risk for stroke in smokers was 1.2 times higher than that in non-smokers. Wolf et al[51] concluded that heavy smokers had very high risk of stroke. Another study revealed that OR (95% CI) for stroke was 2.10 (1.33–3.32) and 1.66 (1.07–2.57) in male and female passive smokers, respectively[52], which further implicates the effect of smoking.

Hypertension has been shown by many studies to be the most important risk factor for stroke; several multi-center, large-sample clinical trials have investigated the treatment of isolated systolic hypertension in the elderly[53,54,55]. Lida et al[56] performed a 14 year study confirming that hypertension is an important risk factor not only for stroke but also for all-cause mortality. The unavoidable risk factors for stroke include age, family history, gender and race[57,58,59,60,61]. Recent evidence also implicates elevated homocysteine level[62], inflammatory markers such as C reactive protein[63], and blood clotting factors such as fibrinogen[64].

The present study investigates a large, representative sample with a high response rate and good subject cooperation. However, the fact that it is a single-center study may have introduced selection bias. Moreover, patients suffered from various diseases and thereby many risk factors coexist, which likely has certain effects on the assessment of results. This case-controlled study provides level 3 evidence and as such the conclusions require further validation by large, prospective studies. The study was designed to investigate the synergistic effect of elevated homocysteine levels and abnormal blood lipids in stroke patients, an approach that differs from previous studies that examined the effect of a single risk factor in elderly stroke patients or from a selection of community populations[65,66]. Nevertheless, the results from this study suggest that elevated homocysteine and abnormal blood lipids likely have a synergic effect on the onset of stroke, and provide evidence to inform the prevention and treatment of stroke.

SUBJECTS AND METHODS

Design

A single-center, 1:1 matched, case-control study.

Time and setting

This study was performed in the Institute of Geriatrics, Chinese PLA General Hospital, Beijing, China, between January 2007 and December 2012.

Subjects

2 089 stroke patients (case group) and 2 089 patients with simple intervertebral disk protrusion (control group) who received treatment between January 2007 and December 2012 in the Chinese PLA General Hospital were included in this study. These subjects were 1:1 matched by age (difference < 1 year). After 1 month of medical records checks, 2 089 pairs of cases and controls were included in the final analysis. To ensure representative sampling, subjects were selected consecutively over the same time period.

Diagnostic criteria of stroke

Cerebrovascular diseases were categorized and diagnosed according to The International Classification of Diseases, Edition 9 (ICD-9.0; CVD430-438) and Classification of Cardiovascular Disease issued by the Second National Cerebrovascular Disease Chinese Physician Association[67]. A diagnosis of cerebrovascular disease was confirmed by CT examination and by the provincial (municipal) hospital (both necessary for final diagnosis) and in some cases by an experienced neurologist.

Inclusion criteria of case group: (1) stroke inpatients at the Chinese PLA General Hospital who met the diagnostic criteria for stroke; (2) full medical record information and related examination data.

Exclusion criteria of case group: (1) incomplete medical records or examination data; (2) clinical examination that did not correspond to the medical record; (3) patients who were not willing to participate.

Inclusion criteria of control group: (1) inpatients with simple intervertebral disk protrusion at the Chinese PLA General Hospital; (2) complete medical record information and related examination data.

Exclusion criteria of control group: (1) other medical conditions; (2) incomplete medical record or examination data; (3) clinical examination that did not correspond to the medical record; (4) subjects not willing to participate.

Related indices

Smoking: According to World Health Organization criteria (1984), at least one cigarette per day for a period of 1 year or longer.

Drinking: Consumption of alcohol once a week for 1 year or longer.

BMI: body weight (kg)/body height (m)2. According to the normal distribution of Chinese adults, BMI was divided into four groups: (1) normal: 18.50–23.99 kg/m2; (2) low: < 18.50 kg/m2; (3) overweight: 24.00–27.99 kg/m2; (4) obese: ≥ 28.00 kg/m2.

Normal and high fasting levels of total serum homocysteine were 5–15 and > 15 μmol/L, respectively. Abnormal blood lipids refers to total cholesterol level < 3.1 or > 5.7 mmol/L and/or triglyceride < 0.44 or > 1.70 mmol/L and/or high density lipoprotein cholesterol < 1.0 or > 1.6 mmol/L and/or low density lipoprotein cholesterol > 3.4 mmol/L.

Methods

Retrospective analysis of medical records of included cases

Investigation was performed by neurology and epidemiology experts. Patient characteristics for analysis were obtained from the medical records as follows: age, gender, medical history, family medical history, body height, body weight, blood pressure, total serum cholesterol, triglyceride level, low density lipoprotein cholesterol level, high density lipoprotein cholesterol level, and fasting blood glucose.

Investigation was performed by 15 clinical physicians and postgraduates from the Chinese PLA General Hospital between January 2007 and December 2012. Prior to the study, all investigators were trained by the Institute of Gerontology, Chinese PLA General Hospital, to ensure consistent assessment methods and procedures. Twelve investigators were responsible for data quality control, medical checks, questionnaire management, and index standardization. The questionnaire was carefully designed and modified several times before use.

Statistical analysis

The subject database was created using Epidata 3.0 (The EpiData Association; http://www.epidata.dk/; Odense, Denmark). Statistical analysis was performed using SPSS 13.0 software (SPSS, Chicago, IL, USA). Ten percent of cases were randomly selected from the entire sample for double checking. The proportion of case numbers included for the final analysis in total number of hospitalized cases > 85% qualified for inclusion. Continuous data are presented as mean ± SD, and categorical data as constituent ratio (%). An independent samples t-test was used to compare normally-distributed data, and the Mann-Whitney U test was used for non-parametric data. The chi-square test was used for one-way analysis of categorical data, and 1:1 paired logistic regression for multivariate analysis of continuous data. A level of P < 0.05 was considered statistically significant.

Research background: Despite many studies evaluating risk factors for stroke, the association between elevated homocysteine, abnormal blood lipids, and stroke onset has not yet been investigated.

Research frontiers: Hyperhomocysteinemia is an independent risk factor for atherosclerosis and stroke. Abnormal blood lipids also increase the risk of ischemic stroke. However, whether abnormal blood lipids are associated with the onset of stroke remains unclear.

Clinical significance: This study investigated the impact of elevated homocysteine complicated by abnormal blood lipids on stroke risk and provides evidence to inform the prevention and treatment of stroke.

Academic terminology: Hyperhomocysteinemia refers to a condition in which the homocysteine level in the blood is abnormally elevated.

Peer review: This study investigates a large sample with complete record information and is scientifically designed and performed. Results of this investigation into the effects of elevated homocysteine levels and abnormal blood lipids on stroke onset are of significance in guiding further clinical studies and in stroke diagnosis and treatment.

Acknowledgments

We are grateful to the postgraduates in grade 2012 from the Chinese PLA General Hospital for their half-year endeavor in on-the-spot investigation. We also thank the medical record library of the Chinese PLA General Hospital for assistance in medical records checks.

Footnotes

Funding: This study was supported by a grant from Medical Science Data Sharing Network, Ministry of Science and Technology, China, No. 2005DKA32403, and Military Medical Scientific Research grants, No. 11BJZ32, No. 12BJZ271 and No. 10BJZ202.

Conflicts of interest: None declared.

(Reviewed by Slone-Murphy J, Stow A, Yang XH, Jang B)

(Edited by Wang J, Li CH, Song LP, Liu WJ, Zhao M)

REFERENCES

  • [1].Jiang HY, Zheng SC, Bai J, et al. Treatment progress of cerebral arterial thrombosis. Yixue Zongshu. 2009;15(18):2771–2774. [Google Scholar]
  • [2].An YT, Xia YY, Min Y. The pathogenesis of cerebral ischemia and its treatment. Shijie Linchuang Yaowu. 2010;31(1):35–39. [Google Scholar]
  • [3].Chen D, Zhao GD, Kao HS. New advances of ischemic cerebral stroke mechanism. Guowai Yixue (Shenjing-Bingxue Shenjingwaikexue Fence) 2001;28(1):32–34. [Google Scholar]
  • [4].Yin QX, Liu GQ. Metabolic syndrome and ischemic stroke. Zhonghua Zhongxiyixue Zazhi. 2009;10:42–43. [Google Scholar]
  • [5].Wang L, Xie YZ. Research progress of risk factors for ischemic stroke. Zhongguo Zhongyi Jizheng. 2012;21(10):1636–1637. 1639. [Google Scholar]
  • [6].Liu HY, Fang W. Progress in research on the pathogenesis of ischemic stroke. Zhongguo Xiandai Yisheng. 2010;48(25):11–12. [Google Scholar]
  • [7].Feng JQ. Study on the relationship between ischemic stroke and serum lipid levels. Shiyong Xin Nao Fei Xueguan Bing Zazhi. 2012;20(4):642–643. [Google Scholar]
  • [8].Zhao XG, Xu WW. Biology of coronary artery disease and its clinical significance. Zhonghua Zhongxiyi Zazhi. 2002;3:19. [Google Scholar]
  • [9].Liu R, Xiong Y, Wang XM. The cardiovascular research progress of disease risk factors and nursing intervention. Huli Shijian yu Yanjiu. 2013;10(6):126–129. [Google Scholar]
  • [10].Chen WM. Investigate the relationship between homocysteine and coronary heart disease patients. Zhongguo Laonian Baojian Yixue. 2004;2(2):35. [Google Scholar]
  • [11].Sun DM, Zhang ZJ. Research on risk factors between hyperhomocysteinemia and stoke. Dongnan Daxue Xuebao: Yixue Ban. 2012;31(6):732–735. [Google Scholar]
  • [12].Si XM, Zhu HG. Research progress of hyperhomocysteine and atherosclerosic obliterans. Anhui Yiyao. 2013;4:688–690. [Google Scholar]
  • [13].STEPwise Approach to Stroke Surveillance Manual. Chronic diseases and health promotion. 2006 [Google Scholar]
  • [14].WHO. The world health report 2000: Health systems: improving performance. 2000 [PubMed] [Google Scholar]
  • [15].Threapleton DE, Greenwood DC, Evans CE, et al. Dietary fiber intake and risk of first stroke: a systematic review and meta-analysis. Stroke. 2013;44(5):1360–1368. doi: 10.1161/STROKEAHA.111.000151. [DOI] [PubMed] [Google Scholar]
  • [16].Romero JR, Wolf PA. Epidemiology of stroke: legacy of the framingham heart study. Glob Heart. 2013;8(1):67–75. doi: 10.1016/j.gheart.2012.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [17].Sajjad A, Chowdhury R, Felix JF, et al. A systematic evaluation of stroke surveillance studies in low- and middle-income countries. Neurology. 2013;80(7):677–684. doi: 10.1212/WNL.0b013e318281cc6e. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Lichtman JH, Jones SB, Wang YL, et al. Seasonal variation in 30-day mortality after stroke: teaching versus nonteaching hospitals. Stroke. 2013;44(2):531–533. doi: 10.1161/STROKEAHA.112.670547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [19].Kluger BM, Krupp LB, Enoka RM. Fatigue and fatigability in neurologic illnesses: proposal for a unified taxonomy. Neurology. 2013;80(4):409–416. doi: 10.1212/WNL.0b013e31827f07be. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [20].Aburto NJ, Hanson S, Gutierrez H, et al. Effect of increased potassium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ. 2013;346:f1378. doi: 10.1136/bmj.f1378. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [21].Threapleton DE, Greenwood DC, Evans CE, et al. Dietary fiber intake and risk of first stroke: a systematic review and meta-analysis. Stroke. 2013;44(5):1360–1368. doi: 10.1161/STROKEAHA.111.000151. [DOI] [PubMed] [Google Scholar]
  • [22].Romero JR, Wolf PA. Epidemiology of Stroke: Legacy of the Framingham Heart Study. Glob Heart. 2013;8(1):67–75. doi: 10.1016/j.gheart.2012.12.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Morrison LJ, Neumar RW, Zimmerman JL, et al. Strategies for improving survival after in-hospital cardiac arrest in the United States: 2013 consensus recommendations: a consensus statement from the American Heart Association. Circulation. 2013;127(14):1538–1563. doi: 10.1161/CIR.0b013e31828b2770. [DOI] [PubMed] [Google Scholar]
  • [24].Richards A, Cheng EM. Stroke risk calculators in the era of electronic health5records linked to administrative databases. Stroke. 2013;44(2):564–569. doi: 10.1161/STROKEAHA.111.649798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [25].Noonan B, Bancroft RW, Dines JS, et al. Heat- and cold-induced injuries in athletes: evaluation and management. J Am Acad Orthop Surg. 2012;20(12):744–754. doi: 10.5435/JAAOS-20-12-744. [DOI] [PubMed] [Google Scholar]
  • [26].Zimmerman D, Sood MM, Rigatto C, et al. Systematic review and meta-analysis of incidence, prevalence and outcomes of atrial fibrillation in patients on dialysis. Nephrol Dial Transplant. 2012;27(10):3816–3822. doi: 10.1093/ndt/gfs416. [DOI] [PubMed] [Google Scholar]
  • [27].Yu HC, Tsai YF, Chen MC, et al. Underuse of antithrombotic therapy caused high incidence of ischemic stroke in patients with atrial fibrillation. Int J Stroke. 2012;7(2):112–117. doi: 10.1111/j.1747-4949.2011.00667.x. [DOI] [PubMed] [Google Scholar]
  • [28].Daneault B, Kirtane AJ, Kodali SK, et al. Stroke associated with surgical and transcatheter treatment of aortic stenosis: a comprehensive review. J Am Coll Cardiol. 2011;58(21):2143–2150. doi: 10.1016/j.jacc.2011.08.024. [DOI] [PubMed] [Google Scholar]
  • [29].Meltzer AJ, Shrikhande G, Gallagher KA, et al. Heart failure is associated with reduced patency after endovascular intervention for symptomatic peripheral arterial disease. J Vasc Surg. 2012;55(2):353–362. doi: 10.1016/j.jvs.2011.08.016. [DOI] [PubMed] [Google Scholar]
  • [30].Genuth S, Ismail-Beigi F. Clinical implications of the ACCORD trial. J Clin Endocrinol Metab. 2012;97(1):41–48. doi: 10.1210/jc.2011-1679. [DOI] [PubMed] [Google Scholar]
  • [31].Sadi L, Tønnessen T, Pillgram-Larsen J. Short- and long-term survival in type A aortic dissection justifies the operative risk and effort. Scand Cardiovasc J. 2012;46(1):45–50. doi: 10.3109/14017431.2011.626439. [DOI] [PubMed] [Google Scholar]
  • [32].Cognat E, Crassard I, Denier C, et al. Cerebral venous thrombosis in inflammatory bowel diseases: eight cases and literature review. Int J Stroke. 2011;6(6):487–492. doi: 10.1111/j.1747-4949.2011.00620.x. [DOI] [PubMed] [Google Scholar]
  • [33].Peacock JM, Keo HH, Duval S, et al. The incidence and health economic burden of ischemic amputation in Minnesota, 2005-2008. Prev Chronic Dis. 2011;8(6):A141. [PMC free article] [PubMed] [Google Scholar]
  • [34].Rocca WA, Grossardt BR, Miller VM, et al. Premature menopause or early menopause and risk of ischemic stroke. Menopause. 2012;19(3):272–277. doi: 10.1097/gme.0b013e31822a9937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Wang TY, Serletti JM, Cuker A, et al. Free tissue transfer in the hypercoagulable patient: a review of 58 flaps. Plast Reconstr Surg. 2012;129(2):443–453. doi: 10.1097/PRS.0b013e31823aec4d. [DOI] [PubMed] [Google Scholar]
  • [36].Zhang H, Sun M, Sun T, et al. Association between angiotensin II type 1 receptor gene polymorphisms and ischemic stroke: a meta-analysis. Cerebrovasc Dis. 2011;32(5):431–438. doi: 10.1159/000330655. [DOI] [PubMed] [Google Scholar]
  • [37].Varas-Lorenzo C, Riera-Guardia N, Calingaert B, et al. Stroke risk and NSAIDs: a systematic review of observational studies. Pharmacoepidemiol Drug Saf. 2011;20(12):1225–1236. doi: 10.1002/pds.2227. [DOI] [PubMed] [Google Scholar]
  • [38].O’Brien EC, Rose KM, Shahar E, et al. Stroke Mortality, Clinical Presentation and Day of Arrival: The Atherosclerosis Risk in Communities (ARIC) Study. Stroke Res Treat 2011. 2011 doi: 10.4061/2011/383012. 383012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [39].Foody J, Huo Y, Ji L, et al. Unique and Varied Contributions of Traditional CVD Risk Factors: A Systematic Literature Review of CAD Risk Factors in China. Clin Med Insights Cardiol. 2013;7:59–86. doi: 10.4137/CMC.S10225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [40].The Atlas of Heart Disease and Stroke. Indian J Med Sci. 2004;58(9):405–406. [PubMed] [Google Scholar]
  • [41].Kurth T, Everett BM, Buring JE, et al. Lipid levels and the risk of ischemic stroke in women. Neurology. 2007;68(8):556–562. doi: 10.1212/01.wnl.0000254472.41810.0d. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [42].Tirschwell DL, Smith NL, Heckbert SR, et al. Association of cholesterol with stroke risk varies in stroke subtypes and patient subgroups. Neurology. 2004;63(10):1868–1875. doi: 10.1212/01.wnl.0000144282.42222.da. [DOI] [PubMed] [Google Scholar]
  • [43].Sacco RL, Benson RT, Kargman DE, et al. High-density lipoprotein cholesterol and ischemic stroke in the elderly: the Northern Manhattan Stroke Study. JAMA. 2001;285(21):2729–2735. doi: 10.1001/jama.285.21.2729. [DOI] [PubMed] [Google Scholar]
  • [44].Dyker AG, Weir CJ, Lees KR. Influence of cholesterol on survival after stroke: a retrospective study. BMJ. 1997;314(5):1584–1588. doi: 10.1136/bmj.314.7094.1584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [45].Weir CJ, Sattar N, Walters MR, et al. Low triglyceride, not low Cholesterol concentration, independently predicts poor outcome following acute stroke. Cerebrovasc Dis. 2003;16(1):76–82. doi: 10.1159/000070119. [DOI] [PubMed] [Google Scholar]
  • [46].Dziedzic T, Slowik A, Gryz EA, et al. Lower serum triglyceride Level is associated with increased stroke severity. Stroke. 2004;35(6):151–152. doi: 10.1161/01.STR.0000128705.63891.67. [DOI] [PubMed] [Google Scholar]
  • [47].Chyou PH, Eaker ED. Serum cholesterol concentrations and all-cause mortality in older people. Age Ageing. 2000;29(1):69–74. doi: 10.1093/ageing/29.1.69. [DOI] [PubMed] [Google Scholar]
  • [48].Wells BJ, Mainous AG, 3rd, King DE, et al. The combined effect of transferrin saturation and low density lipoprotein on mortality. Fam Med. 2004;36(5):324–329. [PubMed] [Google Scholar]
  • [49].Iribarren C, Reed DM, Burchfiel CM, et al. Serum total cholesterol and mortality. Confounding factors and risk modification in Japanese-American men. JAMA. 1995;273(24):1926–1932. [PubMed] [Google Scholar]
  • [50].Shinton R, Beevers G. Meta-analysis of relation between cigarette smoking and stroke. BMJ. 1989;298(6676):789–794. doi: 10.1136/bmj.298.6676.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [51].Wolf PA, D’Agostino RB, Kannel WB, et al. Cigarette smoking as a risk factor for stroke. The Framingham Study. JAMA. 1988;259(7):1025–1029. [PubMed] [Google Scholar]
  • [52].Bonita R, Duncan J, Truelsen T, et al. Passive smoking as well as active smoking increases the risk of acute stroke. Tob Control. 1999;8(2):156–160. doi: 10.1136/tc.8.2.156. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [53].Li PX, Wu XJ, Liu GZ, et al. Epidemiology and harm of isolated systolic hypertension. Zhonghua Laonian Yixue Zazhi. 1995;14(1):52–59. [Google Scholar]
  • [54].Wang JG, Staessen JA, Gong LS, et al. Chinese trial on isolated systolic hypertension in the elderly. Arch Intern Med. 2000;160(2):211–220. doi: 10.1001/archinte.160.2.211. [DOI] [PubMed] [Google Scholar]
  • [55].Bowman TS, Sesso HD, Gaziano JM. Effect of age on blood pressure parameters and risk of cardiovascular death in men. Am J Hypertens. 2006;19(1):47–52. doi: 10.1016/j.amjhyper.2005.06.024. [DOI] [PubMed] [Google Scholar]
  • [56].Lida M, Ueda K, Okayama A, et al. Impact of elevated blood pressure on mortality from all causes, cardiovascular diseases, heart disease and stroke among Japanese: 14 year follow-up of randomly selected population from Japanese--Nippon data 80. J Hum Hypertens. 2003;17(12):851–857. doi: 10.1038/sj.jhh.1001602. [DOI] [PubMed] [Google Scholar]
  • [57].Isozumi K. Obesity as a risk factor for cerebrovascular disease. Keio J Med. 2004;53(1):7–11. doi: 10.2302/kjm.53.7. [DOI] [PubMed] [Google Scholar]
  • [58].Zhou B, Wu Y, Yang J, et al. Overweight is an independent risk factor for cardiovascular disease in Chinese populations. Obes Rev. 2002;3(3):147–156. doi: 10.1046/j.1467-789x.2002.00068.x. [DOI] [PubMed] [Google Scholar]
  • [59].Gil de Castro R, Gil-Nunez AC. Risk factors for ischemic stroke. I. Conventional risk factors. Rev Neurol. 2000;31(4):314–323. [PubMed] [Google Scholar]
  • [60].Stover Hertzberg V, Weiss P, Stern BJ, et al. Family history associated with improved functional outcome following ischemic stroke. Neuroepidemiology. 2006;27(2):74–80. doi: 10.1159/000094977. [DOI] [PubMed] [Google Scholar]
  • [61].Connor MD, Walker R, Modi G, et al. Burden of stroke in black populations in sub-Saharan Africa. Lancet Neurol. 2007;6(3):269–278. doi: 10.1016/S1474-4422(07)70002-9. [DOI] [PubMed] [Google Scholar]
  • [62].Zee RY, Mora S, Cheng S, et al. Homocysteine, 5,10- methylenetetrahydrofolate reductase 677C>T polymorphism, nutrient intake,and incidentcardiovascular disease in 24,968 initially healthy women. Clin Chem. 2007;53(5):845–851. doi: 10.1373/clinchem.2006.083881. [DOI] [PubMed] [Google Scholar]
  • [63].Angerio AD, Bialko MF, White BM. C-reactive protein, stroke, and statins. Crit Care Nurs Q. 2007;30(2):161–165. doi: 10.1097/01.CNQ.0000264259.82875.c0. [DOI] [PubMed] [Google Scholar]
  • [64].Aono Y, Ohkubo T, Kikuya M, et al. Plasma fibrinogen, ambulatory blood pressure, and silent cerebrovascular lesions: the Ohasama study. Arterioscler Thromb Vasc Biol. 2007;27(4):963–968. doi: 10.1161/01.ATV.0000258947.17570.38. [DOI] [PubMed] [Google Scholar]
  • [65].Sai XY, Sun YF. Prevalence of chronic kidney disease in China (letter) Lancet. 2012;380(9838):214–216. doi: 10.1016/S0140-6736(12)61210-0. [DOI] [PubMed] [Google Scholar]
  • [66].Sai XY, He Y, Men K, et al. All-cause mortality and risk factors in a cohort of retired military male veterans, Xi’an, China: an 18-year follow up study. BMC Public Health. 2007;7:290. doi: 10.1186/1471-2458-7-290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [67].Liu AM. Beijing: People's Military Publishing House; 2008. The International Classification of Diseases. [Google Scholar]

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