http://informahealthcare.com/bij ISSN: 0269-9052 (print), 1362-301X (electronic) Brain Inj, Early Online: 1–6 ! 2015 Informa UK Ltd. DOI: 10.3109/02699052.2015.1004752
ORIGINAL ARTICLE
Incidence and survival of lacunar infarction in a southern Chinese population: A 7-year prospective study Xin-Gang Sun1, Te Wang2, Ning Zhang3, Qi-Dong Yang3, & Yun-Hai Liu3 Department of Neurology, the Second Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, PR China, 2Department of Neurology, the First People’s Hospital, Xiangtan, Hunan Province, PR China, and 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
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1
Abstract
Keywords
Objective: Little attention has been paid to the epidemiological characteristics of lacunar infarction (LAC) in China before. This study aimed to examine the incidence and survival of LAC in a southern Chinese population. Methods: From 2004–2010 in Changsha, two communities with a registered population of 100 000 were selected and data from first-ever ischaemic stroke (IS) cases were prospectively collected. Then the epidemiological characteristics of LAC and non-LAC were evaluated. Results: During the study period, the age-standardized incidence increased at an annual rate of 0.7% (p50.001) for LAC and 2.0% (p50.001) for non-LAC. The mean annual age-standardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively. Compared with non-LAC patients, the prevalence of hypertension, diabetes and hyperlipidemia was significantly higher in patients with LAC (p50.05). Although the 30-day fatality rate was significantly lower in patients with LAC than non-LAC (0.5% vs. 14.9%, p50.001), there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p ¼ 0.203) after excluding the patients who died within 1 year of stroke onset. Conclusion: LAC is a common stroke sub-type in southern China and the long-term prognosis is not benign.
Incidence, lacunar infarct, risk factors, survival
Introduction Stroke is ranked as the third highest cause of mortality in urban and the first highest in rural China [1–3]. Surveillance and prevention efforts have been made and an increasing trend of ischaemic stroke (IS) incidence has been found in the Chinese population [1]. Lacunar infarction (LAC) was a common sub-type of IS in Asian populations. However, little attention has been paid to LAC in China to date [3]. Epidemiological studies showed a north–south gradient, with an obviously higher stroke incidence in the north of China compared with the south [4, 5], which may be caused by the difference of risk factor’s prevalence between northern and southern cities [6]. However, Changsha, a city in the south of China, had an unexpectedly high stroke incidence [1, 4, 7]. In previous studies conducted in Changsha, epidemiological research of stroke sub-types was limited to Xin-Gang Sun and Te Wang work equally to this study. Correspondence: Yun-Hai Liu, MD, Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China. Tel: +86 15873142321. Fax: +86 731 4327401. E-mail: [email protected]
History Received 27 June 2014 Revised 17 November 2014 Accepted 4 January 2015 Published online 31 March 2015
ischaemic and haemorrhagic stroke. In this study, a population-based study was conducted in Changsha aiming to examine the incidence and long-term prognosis of patients with LAC. This is the first study in a southern Chinese population to describe the epidemiological characteristics of LAC, which will be helpful for treatment and prevention of these patients.
Patients and methods Study population The Ethics Review Board of the institution examined and approved the research protocol in accordance with the Declaration of Helsinki before the study. In January 2004, two old communities with a registered population of 100 000 in Changsha were typically selected as the demographic characteristics were stable. The study areas were well-defined communities and the study population included all the registered residents. Persons who were not registered in the local administrative office but only resided in these areas were excluded. Annual demographic characteristics of the residents were obtained from the census
2
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Brain Inj, Early Online: 1–6
register of the local administrative office during the study period. The study areas included three integrated hospitals (the Third Hospital of Changsha, Hunan Provincial Finance Hospital, Hunan Provincial People’s Hospital) and seven daily clinics.
interview at 15, 30, 60, 90, 120 days and then at 60 day intervals until 780 days after stroke onset. The starting point was the date of stroke onset and the end-point of follow-up was the death event. For the patients who migrated out of the two communities during the study, the information was obtained by other methods (i.e. telephone and mail).
Brain Inj Downloaded from informahealthcare.com by Rutgers University on 04/09/15 For personal use only.
Data collection The Hunan Neurological Institute and the Institute of Neurology at Xiangya Hospital were responsible for designing the study. The doctors from the three integrated hospitals and seven clinics conducted the study. An active surveillance network was established to register new stroke cases that occurred from 1 January 2004 to 31 December 2010 in the study communities. The details of this system are described in Figure 1. The diagnosis and classification of stroke sub-types were defined according to the Atherosclerosis Risk in Communities Study [8, 9]. In this study, only first-ever IS cases analysed by both clinical symptoms and neuroimaging were included. Silent brain infarctions and transient ischaemic attacks were excluded. The IS were further classified as either LAC or non-LAC on the basis of lesion size and neuroimaging reports. The stroke cases were defined as LAC if the following two criteria were met: (I) an estimated infarct size of 2 cm; and (II) anatomic findings typical of LAC (basal ganglia, thalamus, cerebral white matter, internal capsule or brain stem). The other cases were defined as non-LAC. If the diagnostic criteria for both LAC and non-LAC were met for a patient with multiple cerebral infarctions, the classification of non-LAC would be assigned. All LAC and non-LAC patients were followed-up for death information by door-to-door
Definition of risk factors The risk factors were defined as follows [7, 10]: hypertension (reported systolic blood pressure 140 mmHg, reported diastolic blood pressure 90 mmHg, patients’ self-report of hypertension or use of anti-hypertension drugs), cardiac disease (history of myocardial infarction, coronary artery disease, arrhythmia, congestive heart failure or valvular heart disease), diabetes mellitus (fasting blood glucose level 7.0 mmol L1, patients’ self-report of diabetes or use of anti-diabetes drugs) and hyperlipidemia (reported fasting total cholesterol 5.72 mmol L1, reported low-density lipoprotein 3.64 mmol L1, reported triglyceride 1.70 mmol L1, reported high-density lipoprotein 0.91 mmol L1, selfreport of hyperlipidemia or use of anti-hyperlipidemic drugs). Being consistent with previous study, age 60 years was defined as one of the risk factors [10]. Quality control A manual of operations was compiled to standardize the research procedures. All staff members had to be trained annually according to the standard operating manual before the study started. Only those who had passed the examination on completion of the training were permitted to participate in the
Patients with new onset of suspected stroke
Patients presenting to a daily outpatient clinic
Patients presenting to an integrated hospital
Patients died before going to hospitals
Clinical and neuroimaging examinations were performed
Patients unable to visit an integrated hospital
Mild stroke
Severe or moderate cases stay in hospital
Treatment and rehabilitation Survivors, discharged
Participating doctors made home visits to identify stroke cases
Participating doctors reviewed the patients’ medical records weekly and advised suspicious stroke cases to visit integrated hospitals
Died
Participating doctors reviewed the medical records of integrated hospital weekly for stroke cases.
Reported to government with death certificate
Participating doctors reviewed the death certificates annually and identified stroke cases.
Figure 1. Clinical flowchart for cases with suspected diagnosis of stroke.
Lacunar infarction in a southern city of China
DOI: 10.3109/02699052.2015.1004752
research work. Researchers from the Hunan Neurological Institute, the Institute of Neurology at Xiangya Hospital and the three integrated hospitals met monthly to review research progress and to resolve problems encountered during the study.
Brain Inj Downloaded from informahealthcare.com by Rutgers University on 04/09/15 For personal use only.
Data analysis The incidence was directly standardized to the 1996 World Segi’s population [11]. The average annual incidence change was calculated by a regression model: log(Rt) ¼ + t. Age-adjusted incidence was used in this analysis. Annual percentage change equals 100 (exp 1), where is the maximum likelihood estimate of the slope parameter and exp approximates the relative risk associated with 2 consecutive years. 100 per cent of the incidence rate at time t is given to denote the instantaneous change rate per year at time point t because (exp 1) estimates for small changes [1]. Comparison of distribution of risk factor profiles between LAC and non-LAC were performed using 2 univariate analysis and multivariable logistic regression models. Relative risk (RR) of risk factors for LAC vs. nonLAC as determined by univariate and multivariate logistic regression was estimated. Risk factors were predictors and IS including LAC and non-LAC was the response variable in the logistic regression model. Survival or death was the response in survival analysis and Kaplan–Meier method was used to calculate the survival rates. The 95% confidence interval (CI) for survival rates was also calculated. Comparison of the Kaplan-Meier curve for LAC and non-LAC groups was performed by the log-rank test.
Results
3
Association of risk factors of LAC and non-LAC The risk of LAC was significantly higher than that of nonLAC in hypertension, hyperlipidemia and diabetes (p50.05). After adjusting for age and gender, the risk of LAC remained obviously higher than that of non-LAC in hypertension, diabetes and hyperlipidemia. Risk factors with a p value 50.05 in the univariate analysis were entered into multivariable logistic regression models. The risk of LAC was found to be significantly higher than that of non-LAC in hypertension after adjusting for confounding factors of age, gender, diabetes and hyperlipidemia (p ¼ 0.022) (Table II). Survival of LAC and non-LAC After 2 years’ follow-up, 16 LAC patients and 129 non-LAC patients died. Survival of LAC and non-LAC groups was shown in Table III. The 30 days fatality rates were 0.3% (1/ 278) in the LAC group and 14.1% (72/512) in the non-LAC group (p50.001). Not surprisingly, increased survival of patients with LAC was dependent on low death rates shortly after stroke onset, whilst trends in survival curves were parallel between the two groups 1 month after stroke onset (Figure 2). After excluding the seven LAC patients and 109 non-LAC patients who died within 1 year of stroke onset, there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p ¼ 0.203). Log-rank test of the Kaplan-Meier curve showed that the survival rate was significantly lower in patients with non-LAC than LAC (p50.001) (Figure 2), while no significant difference in survival between the two groups was found after excluding the cases who died within 1 year of stroke onset (p ¼ 0.299) (Figure 3).
Incidence and trends of LAC and non-LAC A total of 790 IS patients were identified, including 278 cases (35.2%) of LAC and 512 (64.8%) cases of non-LAC. From 2004–2010, an annually increasing trend was found for both LAC and non-LAC. The crude incidence increased at an annual rate of 1.0% (p50.001) for LAC and 5.1% (p50.001) for non-LAC. The age-standardized incidence increased at an annual rate of 0.7% (p50.001) for LAC and 2.0% (p50.001) for non-LAC. During the study period, the mean annual agestandardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively (Table I).
Discussion LAC is caused by small and deep cerebral infarcts, which is a common sub-type of IS. The crude incidence rates of LAC in western populations has been reported to range from 16–33/ 100 000 and the proportion of LAC that accounts for IS is between 16–28% [12–14]. Epidemiological studies conducted in a Japanese population 440 years of age found that the incidence of LAC was 280/100 000 for men and 200/ 100 000 for women [15, 16]. In this study, the individuals with LAC and non-LAC were classified as non-LAC to exclude the
Table I. The incidence rates (per 100 000/year) of LAC and non-LAC during 2004–2010. LAC
non–LAC
Year
Case
CIR (95% CI)
AIR (95% CI)
Case
CIR (95% CI)
AIR (95% CI)
2004 2005 2006 2007 2008 2009 2010 2004–2010 100 , p
32 36 42 39 56 38 35 278
31.6 (26.0–37.2) 35.6 (29.7–41.5) 41.5 (35.1–47.9) 38.2 (32.1–44.3) 54.5 (47.2–61.8) 36.9 (30.9–42.9) 33.8 (28.1–39.5) 38.9 (36.6–41.2) 1.0 50.001
22.7 (16.7–28.6) 23.8 (17.5–30.1) 28.5 (19.3–37.6) 27.5 (18.6–36.3) 36.7 (26.1–47.2) 27.0 (18.2–35.7) 23.2 (19.1–37.3) 28.2 (19.1–37.3) 0.7 50.001
59 65 63 77 66 93 89 512
58.3 (50.7–65.9) 64.2 (56.2–72.2) 62.2 (54.4–70.0) 75.5 (66.9–84.1) 64.2 (56.3–72.1) 90.3 (80.9–99.7) 86.0 (76.9–95.1) 71.6 (68.4–74.8) 5.1 50.001
39.1 (34.7–43.5) 44.8 (37.5–52.1) 40.8 (35.4–46.2) 52.0 (41.2–62.8) 41.4 (36.3–46.5) 57.6 (49.7–65.5) 47.9 (39.1–56.7) 45.0 (37.6–52.4) 2.0 50.001
LAC, lacunar infarction; CIR, crude incidence rate; AIR, age-adjusted incidence rate; CI, confidence interval; , maximum likelihood estimate of the slope parameter.
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Table II. Crude and adjusted relative risk and 95% confidence intervals of risk factors for LAC versus non-LAC as determined by univariate and multivariate logistic regression. Univariate analysis Risk factor
LAC n (%)
Non-LAC n (%)
Average age Men Age (60 years) Hypertension Cardiac diseases Diabetes Hyperlipidemia
278 146 216 220 66 126 101
512 315 409 356 132 185 151
(65.2 ± 10.3) (52.5) (77.7) (79.2) (23.6) (45.4) (36.2)
(66.1 ± 10.7) (61.5) (79.9) (69.5) (25.7) (36.1) (29.5)
Crude RR and 95% CI 1.2 1.0 1.5 1.3 1.4 1.3
(1.1–1.4) (0.8–1.2) (1.2–1.8) (1.0–1.5) (1.2–1.6) (1.1–1.5)
p 0.158 0.013 0.647 50.001 0.214 0.003 0.005
Multivariate analysis Adjusted RR and 95% CIa
1.3 1.0 1.5 1.3
— — — (1.1–1.5) (0.9–1.1) (1.1–1.9) (1.2–1.4)
p
Adjusted RR and 95% CI
p
— — — 0.001 0.238 0.005 0.002
— — — 1.5 (1.3–1.7)b — 1.3 (1.0–1.6)c 1.4 (0.9–1.9)d
— — — 0.022 — 0.273 0.141
LAC, lacunar infarction; CI, confidence interval; RR, relative risk. Adjusted for age and gender. b Adjusted for age, gender, diabetes and hyperlipidemia. c Adjusted for age, gender, hypertension and hyperlipidemia. d Adjusted for age, gender, hypertension and diabetes.
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a
Table III. Survival rates of LAC and non-LAC patients at different time point after stroke onset. Daysa 15 30 60 90 120 180 240 300 360 420 480 540 600 660 720
LAC (95% CI) 99.6 99.6 98.6 98.2 98.2 97.8 97.8 97.5 97.5 97.1 97.1 96.4 95.7 94.6 94.2
(98.9–100.0) (98.9–100.0) (97.2–100.0) (96.6–99.8) (96.6–99.8) (96.1–99.5) (96.1–99.5) (95.6–99.3) (95.6–99.3) (95.2–99.1) (95.2–99.1) (94.2–98.6) (93.3–98.1) (91.9–97.3) (91.5–97.0)
non-LAC (95% CI) 91.2 85.9 84.85 84.4 84.4 84.2 82.4 80.7 78.7 77.7 77.2 76.6 76.2 75.4 74.8
(88.8–93.7) (82.9–89.0) (81.7–87.9) (81.2–87.5) (81.2–87.5) (81.0–87.3) (79.1–85.7) (77.2–84.1) (75.2–82.3) (74.1–81.3) (73.5–80.8) (72.9–80.2) (72.5–79.9) (71.7–79.1) (71.0–78.6)
LAC (95% CI)b
99.6 99.6 98.9 98.2 97.1 96.7
— — — — — — — — — (98.7–100.0) (98.7–100.0) (97.6–100.0) (96.5–99.8) (95.0–99.1) (94.5–98.8)
non-LAC (95% CI)b
98.8 98.0 97.3 96.8 95.8 95.0
— — — — — — — — — (97.7–99.8) (96.6–99.4) (95.7–98.9) (95.0–98.5) (93.8–97.7) (92.9–97.2)
LAC, lacunar infarction; CI, confidence interval. a After stroke onset. b Excluding the cases who died within 1 year of stroke onset.
effect of non-LAC for the LAC group’ prognosis. Even so, the proportion of LAC in IS was higher in this study than those observed in western populations and was similar to results from Japanese studies. These findings confirm that LAC is more common in Asian populations than Caucasian populations [17, 18]. Although there are many reports on the epidemiology of stroke from China, reports on the incidence of LAC are limited. A recent hospital-based study conducted in China showed that the proportion of LAC was 42.3% amongst IS patients [19]. Another population-based study, conducted in the northern Chinese city of Beijing, showed that the proportion of LAC accounted for IS was 36.9% [10]. To the authors’ knowledge, this study is the first population-based report of LAC in Southern China. The proportion of LAC in IS is similar to the results observed in Beijing (35.2% vs. 36.9%), while the average annual age-standardized incidence of LAC is relatively low (28.2/100 000 vs. 35.3/100 000) [10]. This may be partly explained by the fact that IS is the most prevalent sub-type in Beijing, while haemorrhagic stroke is the major stroke sub-type in Changsha [1].
An annually increasing trend was found for both LAC and non-LAC in this study. Previous studies demonstrated that body mass index and high serum cholesterol increased the risk of IS [20–23]. In recent years China has been experiencing fast economic development, which has been a major driving force in greatly changing the population’s lifestyle and resulting in increased prevalence of diabetes, hypertension, obesity and hypercholesterolemia [24]. These changes are likely to be related to the increasing trend of LAC and non-LAC in this study. Being consistent with the results reported in a Beijing population [10], differences in risk factor profiles between LAC and non-LAC were found in this study. It was interesting that hypertension, diabetes and hyperlipidemia was significant in the univariate analysis but only hypertension was significant in the multivariate model. These results support the hypothesis that LAC may be due to segmental arterial disorganization with lipohyalinosis secondary to the effects of hypertension and that all of the risk factors were related [25]. So management of hypertension, hyperlipidemia and diabetes is the most important measure for LAC patients in China. However, in Jackson et al.’s [26]
Lacunar infarction in a southern city of China
DOI: 10.3109/02699052.2015.1004752
5
1.00
cumulative survival rates
0.75
LAC N-LAC
0.50
c 2 = 45.456 p
ORIGINAL ARTICLE
Incidence and survival of lacunar infarction in a southern Chinese population: A 7-year prospective study Xin-Gang Sun1, Te Wang2, Ning Zhang3, Qi-Dong Yang3, & Yun-Hai Liu3 Department of Neurology, the Second Hospital, Shanxi Medical University, Taiyuan, Shanxi Province, PR China, 2Department of Neurology, the First People’s Hospital, Xiangtan, Hunan Province, PR China, and 3Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China
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1
Abstract
Keywords
Objective: Little attention has been paid to the epidemiological characteristics of lacunar infarction (LAC) in China before. This study aimed to examine the incidence and survival of LAC in a southern Chinese population. Methods: From 2004–2010 in Changsha, two communities with a registered population of 100 000 were selected and data from first-ever ischaemic stroke (IS) cases were prospectively collected. Then the epidemiological characteristics of LAC and non-LAC were evaluated. Results: During the study period, the age-standardized incidence increased at an annual rate of 0.7% (p50.001) for LAC and 2.0% (p50.001) for non-LAC. The mean annual age-standardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively. Compared with non-LAC patients, the prevalence of hypertension, diabetes and hyperlipidemia was significantly higher in patients with LAC (p50.05). Although the 30-day fatality rate was significantly lower in patients with LAC than non-LAC (0.5% vs. 14.9%, p50.001), there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p ¼ 0.203) after excluding the patients who died within 1 year of stroke onset. Conclusion: LAC is a common stroke sub-type in southern China and the long-term prognosis is not benign.
Incidence, lacunar infarct, risk factors, survival
Introduction Stroke is ranked as the third highest cause of mortality in urban and the first highest in rural China [1–3]. Surveillance and prevention efforts have been made and an increasing trend of ischaemic stroke (IS) incidence has been found in the Chinese population [1]. Lacunar infarction (LAC) was a common sub-type of IS in Asian populations. However, little attention has been paid to LAC in China to date [3]. Epidemiological studies showed a north–south gradient, with an obviously higher stroke incidence in the north of China compared with the south [4, 5], which may be caused by the difference of risk factor’s prevalence between northern and southern cities [6]. However, Changsha, a city in the south of China, had an unexpectedly high stroke incidence [1, 4, 7]. In previous studies conducted in Changsha, epidemiological research of stroke sub-types was limited to Xin-Gang Sun and Te Wang work equally to this study. Correspondence: Yun-Hai Liu, MD, Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, PR China. Tel: +86 15873142321. Fax: +86 731 4327401. E-mail: [email protected]
History Received 27 June 2014 Revised 17 November 2014 Accepted 4 January 2015 Published online 31 March 2015
ischaemic and haemorrhagic stroke. In this study, a population-based study was conducted in Changsha aiming to examine the incidence and long-term prognosis of patients with LAC. This is the first study in a southern Chinese population to describe the epidemiological characteristics of LAC, which will be helpful for treatment and prevention of these patients.
Patients and methods Study population The Ethics Review Board of the institution examined and approved the research protocol in accordance with the Declaration of Helsinki before the study. In January 2004, two old communities with a registered population of 100 000 in Changsha were typically selected as the demographic characteristics were stable. The study areas were well-defined communities and the study population included all the registered residents. Persons who were not registered in the local administrative office but only resided in these areas were excluded. Annual demographic characteristics of the residents were obtained from the census
2
X.-G. Sun et al.
Brain Inj, Early Online: 1–6
register of the local administrative office during the study period. The study areas included three integrated hospitals (the Third Hospital of Changsha, Hunan Provincial Finance Hospital, Hunan Provincial People’s Hospital) and seven daily clinics.
interview at 15, 30, 60, 90, 120 days and then at 60 day intervals until 780 days after stroke onset. The starting point was the date of stroke onset and the end-point of follow-up was the death event. For the patients who migrated out of the two communities during the study, the information was obtained by other methods (i.e. telephone and mail).
Brain Inj Downloaded from informahealthcare.com by Rutgers University on 04/09/15 For personal use only.
Data collection The Hunan Neurological Institute and the Institute of Neurology at Xiangya Hospital were responsible for designing the study. The doctors from the three integrated hospitals and seven clinics conducted the study. An active surveillance network was established to register new stroke cases that occurred from 1 January 2004 to 31 December 2010 in the study communities. The details of this system are described in Figure 1. The diagnosis and classification of stroke sub-types were defined according to the Atherosclerosis Risk in Communities Study [8, 9]. In this study, only first-ever IS cases analysed by both clinical symptoms and neuroimaging were included. Silent brain infarctions and transient ischaemic attacks were excluded. The IS were further classified as either LAC or non-LAC on the basis of lesion size and neuroimaging reports. The stroke cases were defined as LAC if the following two criteria were met: (I) an estimated infarct size of 2 cm; and (II) anatomic findings typical of LAC (basal ganglia, thalamus, cerebral white matter, internal capsule or brain stem). The other cases were defined as non-LAC. If the diagnostic criteria for both LAC and non-LAC were met for a patient with multiple cerebral infarctions, the classification of non-LAC would be assigned. All LAC and non-LAC patients were followed-up for death information by door-to-door
Definition of risk factors The risk factors were defined as follows [7, 10]: hypertension (reported systolic blood pressure 140 mmHg, reported diastolic blood pressure 90 mmHg, patients’ self-report of hypertension or use of anti-hypertension drugs), cardiac disease (history of myocardial infarction, coronary artery disease, arrhythmia, congestive heart failure or valvular heart disease), diabetes mellitus (fasting blood glucose level 7.0 mmol L1, patients’ self-report of diabetes or use of anti-diabetes drugs) and hyperlipidemia (reported fasting total cholesterol 5.72 mmol L1, reported low-density lipoprotein 3.64 mmol L1, reported triglyceride 1.70 mmol L1, reported high-density lipoprotein 0.91 mmol L1, selfreport of hyperlipidemia or use of anti-hyperlipidemic drugs). Being consistent with previous study, age 60 years was defined as one of the risk factors [10]. Quality control A manual of operations was compiled to standardize the research procedures. All staff members had to be trained annually according to the standard operating manual before the study started. Only those who had passed the examination on completion of the training were permitted to participate in the
Patients with new onset of suspected stroke
Patients presenting to a daily outpatient clinic
Patients presenting to an integrated hospital
Patients died before going to hospitals
Clinical and neuroimaging examinations were performed
Patients unable to visit an integrated hospital
Mild stroke
Severe or moderate cases stay in hospital
Treatment and rehabilitation Survivors, discharged
Participating doctors made home visits to identify stroke cases
Participating doctors reviewed the patients’ medical records weekly and advised suspicious stroke cases to visit integrated hospitals
Died
Participating doctors reviewed the medical records of integrated hospital weekly for stroke cases.
Reported to government with death certificate
Participating doctors reviewed the death certificates annually and identified stroke cases.
Figure 1. Clinical flowchart for cases with suspected diagnosis of stroke.
Lacunar infarction in a southern city of China
DOI: 10.3109/02699052.2015.1004752
research work. Researchers from the Hunan Neurological Institute, the Institute of Neurology at Xiangya Hospital and the three integrated hospitals met monthly to review research progress and to resolve problems encountered during the study.
Brain Inj Downloaded from informahealthcare.com by Rutgers University on 04/09/15 For personal use only.
Data analysis The incidence was directly standardized to the 1996 World Segi’s population [11]. The average annual incidence change was calculated by a regression model: log(Rt) ¼ + t. Age-adjusted incidence was used in this analysis. Annual percentage change equals 100 (exp 1), where is the maximum likelihood estimate of the slope parameter and exp approximates the relative risk associated with 2 consecutive years. 100 per cent of the incidence rate at time t is given to denote the instantaneous change rate per year at time point t because (exp 1) estimates for small changes [1]. Comparison of distribution of risk factor profiles between LAC and non-LAC were performed using 2 univariate analysis and multivariable logistic regression models. Relative risk (RR) of risk factors for LAC vs. nonLAC as determined by univariate and multivariate logistic regression was estimated. Risk factors were predictors and IS including LAC and non-LAC was the response variable in the logistic regression model. Survival or death was the response in survival analysis and Kaplan–Meier method was used to calculate the survival rates. The 95% confidence interval (CI) for survival rates was also calculated. Comparison of the Kaplan-Meier curve for LAC and non-LAC groups was performed by the log-rank test.
Results
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Association of risk factors of LAC and non-LAC The risk of LAC was significantly higher than that of nonLAC in hypertension, hyperlipidemia and diabetes (p50.05). After adjusting for age and gender, the risk of LAC remained obviously higher than that of non-LAC in hypertension, diabetes and hyperlipidemia. Risk factors with a p value 50.05 in the univariate analysis were entered into multivariable logistic regression models. The risk of LAC was found to be significantly higher than that of non-LAC in hypertension after adjusting for confounding factors of age, gender, diabetes and hyperlipidemia (p ¼ 0.022) (Table II). Survival of LAC and non-LAC After 2 years’ follow-up, 16 LAC patients and 129 non-LAC patients died. Survival of LAC and non-LAC groups was shown in Table III. The 30 days fatality rates were 0.3% (1/ 278) in the LAC group and 14.1% (72/512) in the non-LAC group (p50.001). Not surprisingly, increased survival of patients with LAC was dependent on low death rates shortly after stroke onset, whilst trends in survival curves were parallel between the two groups 1 month after stroke onset (Figure 2). After excluding the seven LAC patients and 109 non-LAC patients who died within 1 year of stroke onset, there was no significant difference in survival between the two groups (96.7% vs. 95.2%, p ¼ 0.203). Log-rank test of the Kaplan-Meier curve showed that the survival rate was significantly lower in patients with non-LAC than LAC (p50.001) (Figure 2), while no significant difference in survival between the two groups was found after excluding the cases who died within 1 year of stroke onset (p ¼ 0.299) (Figure 3).
Incidence and trends of LAC and non-LAC A total of 790 IS patients were identified, including 278 cases (35.2%) of LAC and 512 (64.8%) cases of non-LAC. From 2004–2010, an annually increasing trend was found for both LAC and non-LAC. The crude incidence increased at an annual rate of 1.0% (p50.001) for LAC and 5.1% (p50.001) for non-LAC. The age-standardized incidence increased at an annual rate of 0.7% (p50.001) for LAC and 2.0% (p50.001) for non-LAC. During the study period, the mean annual agestandardized incidence of LAC and non-LAC was 28.2/100 000 and 45.0/100 000, respectively (Table I).
Discussion LAC is caused by small and deep cerebral infarcts, which is a common sub-type of IS. The crude incidence rates of LAC in western populations has been reported to range from 16–33/ 100 000 and the proportion of LAC that accounts for IS is between 16–28% [12–14]. Epidemiological studies conducted in a Japanese population 440 years of age found that the incidence of LAC was 280/100 000 for men and 200/ 100 000 for women [15, 16]. In this study, the individuals with LAC and non-LAC were classified as non-LAC to exclude the
Table I. The incidence rates (per 100 000/year) of LAC and non-LAC during 2004–2010. LAC
non–LAC
Year
Case
CIR (95% CI)
AIR (95% CI)
Case
CIR (95% CI)
AIR (95% CI)
2004 2005 2006 2007 2008 2009 2010 2004–2010 100 , p
32 36 42 39 56 38 35 278
31.6 (26.0–37.2) 35.6 (29.7–41.5) 41.5 (35.1–47.9) 38.2 (32.1–44.3) 54.5 (47.2–61.8) 36.9 (30.9–42.9) 33.8 (28.1–39.5) 38.9 (36.6–41.2) 1.0 50.001
22.7 (16.7–28.6) 23.8 (17.5–30.1) 28.5 (19.3–37.6) 27.5 (18.6–36.3) 36.7 (26.1–47.2) 27.0 (18.2–35.7) 23.2 (19.1–37.3) 28.2 (19.1–37.3) 0.7 50.001
59 65 63 77 66 93 89 512
58.3 (50.7–65.9) 64.2 (56.2–72.2) 62.2 (54.4–70.0) 75.5 (66.9–84.1) 64.2 (56.3–72.1) 90.3 (80.9–99.7) 86.0 (76.9–95.1) 71.6 (68.4–74.8) 5.1 50.001
39.1 (34.7–43.5) 44.8 (37.5–52.1) 40.8 (35.4–46.2) 52.0 (41.2–62.8) 41.4 (36.3–46.5) 57.6 (49.7–65.5) 47.9 (39.1–56.7) 45.0 (37.6–52.4) 2.0 50.001
LAC, lacunar infarction; CIR, crude incidence rate; AIR, age-adjusted incidence rate; CI, confidence interval; , maximum likelihood estimate of the slope parameter.
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Table II. Crude and adjusted relative risk and 95% confidence intervals of risk factors for LAC versus non-LAC as determined by univariate and multivariate logistic regression. Univariate analysis Risk factor
LAC n (%)
Non-LAC n (%)
Average age Men Age (60 years) Hypertension Cardiac diseases Diabetes Hyperlipidemia
278 146 216 220 66 126 101
512 315 409 356 132 185 151
(65.2 ± 10.3) (52.5) (77.7) (79.2) (23.6) (45.4) (36.2)
(66.1 ± 10.7) (61.5) (79.9) (69.5) (25.7) (36.1) (29.5)
Crude RR and 95% CI 1.2 1.0 1.5 1.3 1.4 1.3
(1.1–1.4) (0.8–1.2) (1.2–1.8) (1.0–1.5) (1.2–1.6) (1.1–1.5)
p 0.158 0.013 0.647 50.001 0.214 0.003 0.005
Multivariate analysis Adjusted RR and 95% CIa
1.3 1.0 1.5 1.3
— — — (1.1–1.5) (0.9–1.1) (1.1–1.9) (1.2–1.4)
p
Adjusted RR and 95% CI
p
— — — 0.001 0.238 0.005 0.002
— — — 1.5 (1.3–1.7)b — 1.3 (1.0–1.6)c 1.4 (0.9–1.9)d
— — — 0.022 — 0.273 0.141
LAC, lacunar infarction; CI, confidence interval; RR, relative risk. Adjusted for age and gender. b Adjusted for age, gender, diabetes and hyperlipidemia. c Adjusted for age, gender, hypertension and hyperlipidemia. d Adjusted for age, gender, hypertension and diabetes.
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a
Table III. Survival rates of LAC and non-LAC patients at different time point after stroke onset. Daysa 15 30 60 90 120 180 240 300 360 420 480 540 600 660 720
LAC (95% CI) 99.6 99.6 98.6 98.2 98.2 97.8 97.8 97.5 97.5 97.1 97.1 96.4 95.7 94.6 94.2
(98.9–100.0) (98.9–100.0) (97.2–100.0) (96.6–99.8) (96.6–99.8) (96.1–99.5) (96.1–99.5) (95.6–99.3) (95.6–99.3) (95.2–99.1) (95.2–99.1) (94.2–98.6) (93.3–98.1) (91.9–97.3) (91.5–97.0)
non-LAC (95% CI) 91.2 85.9 84.85 84.4 84.4 84.2 82.4 80.7 78.7 77.7 77.2 76.6 76.2 75.4 74.8
(88.8–93.7) (82.9–89.0) (81.7–87.9) (81.2–87.5) (81.2–87.5) (81.0–87.3) (79.1–85.7) (77.2–84.1) (75.2–82.3) (74.1–81.3) (73.5–80.8) (72.9–80.2) (72.5–79.9) (71.7–79.1) (71.0–78.6)
LAC (95% CI)b
99.6 99.6 98.9 98.2 97.1 96.7
— — — — — — — — — (98.7–100.0) (98.7–100.0) (97.6–100.0) (96.5–99.8) (95.0–99.1) (94.5–98.8)
non-LAC (95% CI)b
98.8 98.0 97.3 96.8 95.8 95.0
— — — — — — — — — (97.7–99.8) (96.6–99.4) (95.7–98.9) (95.0–98.5) (93.8–97.7) (92.9–97.2)
LAC, lacunar infarction; CI, confidence interval. a After stroke onset. b Excluding the cases who died within 1 year of stroke onset.
effect of non-LAC for the LAC group’ prognosis. Even so, the proportion of LAC in IS was higher in this study than those observed in western populations and was similar to results from Japanese studies. These findings confirm that LAC is more common in Asian populations than Caucasian populations [17, 18]. Although there are many reports on the epidemiology of stroke from China, reports on the incidence of LAC are limited. A recent hospital-based study conducted in China showed that the proportion of LAC was 42.3% amongst IS patients [19]. Another population-based study, conducted in the northern Chinese city of Beijing, showed that the proportion of LAC accounted for IS was 36.9% [10]. To the authors’ knowledge, this study is the first population-based report of LAC in Southern China. The proportion of LAC in IS is similar to the results observed in Beijing (35.2% vs. 36.9%), while the average annual age-standardized incidence of LAC is relatively low (28.2/100 000 vs. 35.3/100 000) [10]. This may be partly explained by the fact that IS is the most prevalent sub-type in Beijing, while haemorrhagic stroke is the major stroke sub-type in Changsha [1].
An annually increasing trend was found for both LAC and non-LAC in this study. Previous studies demonstrated that body mass index and high serum cholesterol increased the risk of IS [20–23]. In recent years China has been experiencing fast economic development, which has been a major driving force in greatly changing the population’s lifestyle and resulting in increased prevalence of diabetes, hypertension, obesity and hypercholesterolemia [24]. These changes are likely to be related to the increasing trend of LAC and non-LAC in this study. Being consistent with the results reported in a Beijing population [10], differences in risk factor profiles between LAC and non-LAC were found in this study. It was interesting that hypertension, diabetes and hyperlipidemia was significant in the univariate analysis but only hypertension was significant in the multivariate model. These results support the hypothesis that LAC may be due to segmental arterial disorganization with lipohyalinosis secondary to the effects of hypertension and that all of the risk factors were related [25]. So management of hypertension, hyperlipidemia and diabetes is the most important measure for LAC patients in China. However, in Jackson et al.’s [26]
Lacunar infarction in a southern city of China
DOI: 10.3109/02699052.2015.1004752
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1.00
cumulative survival rates
0.75
LAC N-LAC
0.50
c 2 = 45.456 p
