Ethnic differences in acute myocardial infarction in Singapore

K.-H. Maka,*, K.-S. Chiab, J.D. Karkc, T. Chuaa, C. Tana, B.-H. Foongd, Y.-L. Lima and S.-K. Chewd

a Department of Cardiology, National Heart Centre, Singapore
b Department of Community, Family and Occupational Medicine, National University of Singapore, Singapore
c Department of Social Medicine, Hadassah Medical Organization and Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel
d Division of Epidemiology and Disease Control, Ministry of Health, Singapore

Received May 13, 2002; accepted June 12, 2002 * Correspondence: Koon-Hou Mak, MBBS, FESC, Department of Cardiology, National Heart Centre, 17 Third Hospital Avenue, Singapore 168752


    Abstract
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Aims We compare the myocardial infarction (MI) event and mortality rates among Chinese, Malay and Indian residents of Singapore.

Methods Residents, aged 20 to 64 years, with an MI event were identified from hospital discharge listings, postmortem reports, and the Registry of Births and Deaths. All pathology laboratories flagged patients with elevated creatine phosphokinase (CPK) levels. Modified MONICA (multinational monitoring of trends and determinants in cardiovascular disease) criteria were used for determining MI events.

Results From 1991 to 1999, 12 481 MI events were identified. Chinese patients were older and less likely to have typical symptoms or previous MI. Malays had the highest peak CPK level. Among all three ethnic groups, MI event and age-adjusted case-fatality rates declined. Compared with Chinese, MI event rates were >2-fold and >3-fold higher, and age-standardized coronary mortality rates were 2.4 and 3.0 higher times for Malays and Indians, respectively. Malays have the highest 3.1-year case-fatality, with an adjusted hazard ratio of 1.26 (95% confidence interval, 1.14 to 1.38) compared with Chinese.

Conclusion We found strong ethnic differences in MI event, case-fatality and coronary mortality rates among the three ethnic groups in Singapore. While Indians have the greatest MI event rates, Malays have the highest case-fatality.

Key Words: Case-fatality • coronary • gender • incidence • mortality • race


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Substantial disparities exist in the occurrence and mortality of cardiovascular disease across geographical regions.1 The World Health Organization (WHO), MONICA (multinational monitoring of trends and determinants in cardiovascular disease) project that assessed age-standardized coronary event rates of myocardial infarction and coronary heart disease death among 38 populations, between the ages of 35 and 64 years, from 21 countries found 12- and 8.5-fold differences for men and women, respectively.2 There were also differences in case-fatality rates but these were not correlated with event rates. Variations in incidence and mortality rates of myocardial infarction have also been observed among ethnic origins. In particular, South Asian migrants in severalcountries were more prone to suffer from a myocardial infarction or coronary death.3–9 A similar association was observed in Singapore based on mortality data.10 From 1980 to 1984, among those aged 30 and 69 years, Indians had the highestrates compared with Chinese and Malays for both sexes. However, these data were based largely on death or hospital registries where the diagnosis of myocardial infarction had not been verified.2

Singapore is a small tropical city-state of 647.5 square kilometres with a resident population of 3.22 million (http://www.singstat.gov.sg). There are three major ethnic groups: 77.0% Chinese, 13.9% Malays and 7.7% Indians. The SingaporeMyocardial Infarction Register (SMIR) set up in 1987 to monitor myocardial infarction trends enables exploration of these differences. Basically, the procedures of the register were adapted, with some modifications, from the WHO MONICA Project protocol.11 The aims of our study are to describe ethnic variation in myocardial infarction event ratesand case-fatality over 28 days, 1 year and the long-term, and coronary mortality in the entire Singapore resident population between the ages of 20 to 64 years.


    Methods
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Case identification and determination
The method adopted by the SMIR has been previously described.12 In brief, this is a comprehensive population-based register for all Singapore residents, aged 20 to 64 years. Potential cases of myocardial infarction were identified from discharge listings from all hospitals in Singapore (based on the international classification of disease, 9th edition (ICD9), codes 410), creatine phosphokinase (CPK) listings, the Registry of Births and Deaths, and postmortem reports. All pathology laboratories in Singapore submitted a quarterlylisting of patients with CPK400 IU.l–1. Trained investigators using the MONICA protocol2 thenrigourously evaluated all potential cases.

Demographic characteristics and clinical presentation were documented systematically. The ethnic group of the patient was obtained from the source of notification. There are three major ethnic groups, Chinese, Malays, and Indians, who aredescendants of immigrants from China, theMalaysian Archipelago, and the Indian subcontinent, respectively. While there has been limited intermarriage between ethnic groups, the practice is becoming more common. Generally, among Asians, offspring report the ethnic group of the father. An additional group known as Eurasians, descendents of European settlers and Asian immigrants, are small in number, and were grouped together with other small ethnic groups under a heterogenous category of Others. This category, comprising only 1.7% of myocardial infarction events, was excluded from analysis.

Symptoms were classified as typical if chest pain, or any similar description, such as pressure, tightness, discomfort or ache, was the principal symptom of a myocardial infarction and it lasted for 20 min without other non-cardiac cause. The duration was assumed to be 20 min if something else happened, such as the patient deteriorated into ventricular arrhythmia or shock, or words, such as ‘protracted’ or ‘continuous’, were used to describe the symptom. Symptoms were considered as atypical if the site or nature of the pain was unusual, or when it lasted <20 min. Previous history of myocardial infarction was obtained from patient history or medical records. Electrocardiograms weresystemically read using the Minnesota criteria.13

These data were entered into a computer program and analysed using the modified MONICA algorithm.2 Patients were classified under one of nine diagnostic categories. Cases with the diagnostic categories; definite or clinical acute myocardial infarction, death from myocardial infarction with or without necropsy, were considered to be a myocardial infarction. Patients classified under other categories; possible myocardial infarction, cardiac arrest not attributable to myocardial infarction, non-acute myocardial infarction or insufficient data, were not considered to have suffered from a myocardial infarction event. This paper reports the findings from the year 1991 to 1999.

Registry of Births and Deaths
The SMIR is linked to the Registry of Births and Deaths to determine case-fatality. It is a statutory requirement that death must be registered within 24 h of its occurrence. Previous studies have documented the completeness of this information source.10 The last date of follow-up for this report was 31 December 2000. In addition, coronary deaths were also obtained from the Registry of Births and Deaths based on ICD9 codes 410 to 414.

Statistical analysis
Data management and analysis were performed using Statistical Package for Social Sciences (SPSS) Windows version 10 (Chicago, IL). Several internal checks were set-up in the database to ensure the quality of the information.

Event and coronary mortality rates were first computed as crude rates. The mid-year population was used as the denominator for age.14 Direct age standardisation was performed using the WHO MONICA Project procedures15 with the Segi Old World Standard Population.16 For computation of case-fatality, deaths occurring within 28 days and1 year of onset were analysed. The rates were adjusted to the baseline year (1991). These rates were stratified according to gender and ethnic groups. The annual change in age-standardized rates was estimated from the slope in linear regression analysis. Testing for the rate of change in rates was performed using GraphPad Prism version 3.00 for Windows (San Diego, CA).

Chi-square tests were used to analyse differences in categorical variables and analysis of variance for continuous variables. Kaplan-Meier estimates were performed for long-term survival, with the log-rank test for comparison among groups. Multivariable analysis was performed using Cox proportional hazard modelling to determine ethnic associations with time to event, adjusting for covariates. The variables included in the models were gender, age, ethnic group, typical symptoms and history of previous myocardial infarction.


    Results
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Throughout the years, the overall median age of patients with myocardial infarction was 55 years. Even among this group of relatively young patients, the median age of onset has decreased from 56 in 1991 to 53 years in 1999 (P<0.001). The majority (>80%) of patients were male. There were 7753 (62.1%) Chinese, 2291 (18.4%) Malays, 2224 (17.8%) Indians and 213 (1.7%) belonged to other ethnic groups (Table 1). Chinese patients were slightly older, less likely to have had a previous myocardial infarction or to have typical symptoms. Indians were most likely to have had a prior myocardial infarction and to have a Q-wave myocardial infarction, but had the lowest CPK levels.


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Table 1 Baseline demographic characteristics

 
Age-standardized coronary event rates (Table 2)
The overall age-standardized event rates of myocardial infarction in Singapore decreased from 98.2 to 83.0 per 100 000 residents from 1991 to 1999. This change translated to an average annual reduction of 2.26 (95% confidence interval [CI], 0.80 to 3.71) per 100 000 residents, or 2.3%. The decline was greater from 1991 to 1995.


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Table 2 Age-standardized myocardial infarction event rates per 100 000 Singapore residents aged 20 to 64 years, 1991 to 1999

 
Comparing the three ethnic groups, the MI event rates for Malays and Indians were much higher than Chinese, with overall rate ratios of 2.1 (95% CI, 2.0 to 2.2) and 3.1 (95% CI, 2.9 to 3.2), respectively.To stabilize the estimates of Malays and Indians, moving 3-year averages were used (Fig. 1). For Chinese, the fall in events was fairly consistent, at an annual rate of 1.55 (95% CI, 0.46 to 2.65) per100 000 residents or 2.0%. The absolute and relative rates of decline were most pronounced for Indians, at 5.85 (95% CI, 0.39 to 11.31) per 100 000 residents or 2.6% annually. Malays had the lowest rate of average annual fall at 1.14 per 100 000 residents or 0.8%, with a less precise estimate (95% CI, –4.90 to 2.63). Overall, the slopes were not statistically different among the three ethnic groups. While there was little difference in the slopes of decline in MI event rates among men, Indian women had the steepest rate of fall among female patients (P=0.017).



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Figure 1 Moving 3-year average age-standardized coronary event rates for men (panel A) and women (panel B) residents, aged 20 to 64 years, among the three ethnic groups in Singapore, 1991–1999. 1992=1991 to 1993, 1993=1992 to 1994, 1994=1993 to 1995, 1995=1994 to 1996, 1996=1995 to 1997, 1997=1996 to 1998, 1998=1997 to 1999.

 
The overall age-standardized MI event rate for men was 4.1 (95% CI, 3.8 to 4.5) times higher than women. This discrepancy was greatest amongChinese, with a relative risk of 4.3 (95% CI, 3.9 to 4.8), compared with Malays, 3.9 (95% CI, 3.6 to 4.2) and Indians, 3.5 (95% CI, 3.0 to 4.1).

Twenty-eight-day age-adjusted case-fatality (Table 3)
From 1991 to 1999, the age-adjusted 28-day case-fatality rates fell from 27.8% to 22.0%, constituting a relative reduction of 20.9%. Among the three major ethnic groups, the overall age-adjusted28-day case-fatality rate was lowest for the Indians (22.2%), highest for the Malays (26.8%) and intermediate for the Chinese (24.2%). To stabilize the rates for Malays and Indians, moving 3-year averages are presented (Fig. 2). The average annual decline was greatest among Malays, at 1.41 (95% CI, 0.84 to 2.04) percentage points, followed byChinese, at 0.89 (95% CI, 0.28 to 1.51) percentage points, and then the Indians, at 0.74 (95% CI, –1.76 to 0.28) percentage points. However, the differences in the rate of change were not statistically different among the three ethnic groups.


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Table 3 Age-adjusted 28-day case-fatality rates, 1991 to 1999

 


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Figure 2 Moving 3-year average age-adjusted 28-day case-fatality rates following acute myocardial infarction for men (panel A) and women (panel B) residents aged 20 to 64 years, among the three ethnic groups in Singapore, 1991-1999. 1992=1991 to 1993, 1993=1992 to 1994, 1994=1993 to 1995, 1995=1994 to 1996, 1996=1995 to 1997, 1997=1996 to 1998, 1998=1997 to 1999.

 
After adjusting for baseline characteristics, the hazard ratio for 28-day case-fatality was 1.14 (95% CI, 1.03 to 1.25) for Malays compared with Chinese. There was little difference between Chinese and Indians. Throughout this period, the proportion of patients who died within the first hour of onset remained stable at about 5.5% of events.

Although the age-adjusted case fatality rate was declining for both genders, the decrease was greater for men (0.99% per year; 95% CI, 0.39 to 1.59) than women (0.67% per year; 95% CI, –1.67 to +0.33), resulting in an overall higher 28-day case-fatality rate for women (P<0.001). There was no significant difference in the rate of decline for men and women among the three ethnic groups. The likelihood of women dying within 28 days was 1.1, 1.3 and 1.1 times more than men for Chinese, Malays and Indians, respectively.

One-year case-fatality (Table 4)
Similar to 28-day case-fatality, there was a significant fall in age-adjusted 1–year mortality, ranging from 31.6% in 1991 to 25.6% in 1999, constituting a relative reduction of 19.0%. Among the three ethnic groups, there were significant differences in age-adjusted 1–year mortality (P<0.001), with Indians continuing to be the lowest (26.7%), followed by the Chinese (28.2%) and then the Malays (33.0%). After adjusting for baseline characteristics, the hazard ratio was 1.20 (95% CI, 1.10 to 1.31) for Malays compared with Chinese. The adjustedhazard ratio for 1–year mortality was 1.2 times (95% CI, 1.1 to 1.3) for women (32.6% vs 27.9%; P<0.001). This trend was observed among the three ethnic groups, particularly with the Malays.


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Table 4 Age-adjusted 1-year case-fatality rates, 1991 to 1999

 
Long-term follow-up (Fig. 3)
The median follow-up period for all patients was 3.1 years (interquartile range, 0.2 to 6.2). At the end of 10 years, the likelihood for survival was 54.2% for Malays, 56.7% for Chinese and 57.9% for Indians (P<0.0001). After adjusting for baseline characteristics, case fatality among Malaysremained highest, with a hazard ratio of 1.26(95% CI, 1.14 to 1.38) compared with Chinese. There was little difference between Chinese and Indians.



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Figure 3 Kaplan-Meier plot for long-term survival among the three ethnic groups.

 
Coronary mortality (Table 5)
The overall age-standardized coronary mortality rate declined from 60.8 to 47.2 per 100 000 residents. This change translated to an average annual fall of 1.61 (95% CI, 1.23 to 1.94) per 100 000 residents or 2.6%. All three ethnic groups experienced a significant decline in coronary mortality. The Indians have the largest absolute and relative reduction, with the age-standardized coronary mortality rate falling from 149.9 in 1991 to 109.1 per 100 000 residents in 1999, constituting an average annual decrease of 5.90 (95% CI, 3.56 to 8.24) per 100 000 residents or 3.9%. Among Malays, coronary mortality was lowered at a rate of 2.23 (95% CI, 0.00 to 4.51) per 100 000 residents or 2.3% yearly. Coronary mortality reduction for theChinese was lowest at 0.79 (95% CI, 0.31 to 1.28) per 100 000 residents or 1.7% annually. Both men and women experienced a reduction in coronary mortality over this period. However, the rate of decline was higher for men (2.47 (95% CI, 1.39 to 3.56) per 100 000 residents, or 2.8%) than women (0.72 (95% CI, 0.17 to 1.26) per 100 000 residents, or 2.1%).


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Table 5 Age-standardized coronary mortality rates per 100 000 residents aged 20 to 64 years, 1991 to 1999

 
Throughout the study period, Indians consistently had the highest age-standardized coronary mortality, followed by Malays and then Chinese. Among the three ethnic groups, coronary mortality for Malays and Indians were 2.38 (95% CI, 2.23 to 2.52) and 2.99 (95% CI, 2.77 to 3.20) times higher, respectively, than Chinese.

We also found a discrepancy in the gender gap among the three ethnic groups, with the Chinese having the largest difference between men and women in the age-standardized coronary mortality rate. Chinese men were 3.1 (95% CI, 2.9 to 3.2) times more likely to die from coronary death than Chinese women. In contrast, coronary mortality for Malay men was 1.8 (95% CI, 1.6 to 2.0) and for Indian men was 2.3 (95% CI, 2.0 to 2.6) times greater than for women of their respective ethnic groups.


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
Event rates for myocardial infarction
While the burden of cardiovascular disease is increasing in several countries in Asia,17 the incidence of myocardial infarction is decreasing in Singapore. The rate of decline in event rates of myocardial infarction was comparable to that observed in the WHO MONICA populations, with an average annual change of –2.1% (95% CI, –4.6% to 0.4%) for men and –1.4% (95% CI, –4.2% to 1.4%) for women.18 Although the reasons for this favourable trend are unclear, it may be partly attributed to extensive primary prevention strategies.19,20 Anaging population together with the fact that the reduction in mortality far exceeded the decrease in incidence, should lead to an increased prevalence of patients with coronary heart disease.

Our findings corroborated numerous studies showing that Indians have a higher incidence of myocardial infarction.3–8 On average, we found that Indians had a threefold risk and Malays a twofold risk compared with Chinese. These large differences within a single country with a flourishing economy and a freely accessible healthcare system raise major questions as to the other factors operative among the three major ethnic groups inSingapore. Several clinical studies attempted to determine the cause of these ethnic inequalities. Recently, the role of atherosclerotic risk factors was more extensively evaluated in the Study of Health Assessment and Risk in Ethnic groups (SHARE) in a Canadian context.21 South Asians were also found to have higher levels of low-density lipoprotein (LDL), triglyceride, fibrinogen, homocysteine, lipoprotein (a) and plasminogen activator inhibitor-1 levels. These adverse characteristics were shown to be strongly associated with a substantially greater proportion of patients with coronary artery disease among South Asians (10.7%) compared with Caucasians (4.6%) or Chinese (1.7%) (P=0.002). In contrast, the heightened occurrence of myocardial infarction among Indians in Singapore may be accounted for, in part, by the higher prevalence of diabetes mellitus and lower high-density lipoprotein levels.22,23 Indeed, the prevalence of diabetes was highest among Indians (14.5%, 95% CI, 12.4% to 16.7%) compared with the Chinese (7.0%, 95% CI, 6.2% to 7.9%) or Malays (10.7%, 95% CI, 8.9% to 12.5%). Furthermore, Indians were more likelyto have some features of syndrome X, including central obesity and insulin resistance.24 Theseunfavourable features could not be fully explained by dietary intake. Malays have the highest intake of saturated fats (31.6 g) followed by Indians (27.5 g) and Chinese (25.7 g), whereas Indians have the lowest cholesterol intake (211 mg) followed by the Malays (272 mg) and Chinese (283 mg).25 Other traditional risk factors such as smoking status,hypertension, and high LDL and triglyceride levels did not account for the higher risk of myocardial infarction among Indians. Although homocysteine levels were 6% higher among Indians compared with Europeans in the United Kingdom,26 there was little difference in homocysteine levels among the three ethnic groups in Singapore.27 The wide discrepancy in incidence of myocardial infarction among the three ethnic groups in a closely knit society is worthy of further focussed investigative efforts. Both the striking excess incidence in the Indians and protection of the Chinese from coronary heartdisease should be high priority targets forresearch directed to unravelling gene-environment interactions.

Myocardial infarction case-fatality and coronary mortality
Our age-adjusted case-fatality and age-standardized coronary mortality rates fell during the study period for all three ethnic groups. While the decline in age-adjusted case-fatality was greatest among the Malays, the reduction in coronary mortality was largest among Indians, corresponding to a drop in event rates. There was also a significant decrease in case-fatality and coronary mortality among men and women in Singapore. In fact, the rates of reduction in coronary mortality corresponded to the average decline in deaths from coronary heart disease reported by the WHO MONICA populations; with an annual change of –2.7% (range, –8.0 to 4.2) for men and –2.1% (–8.5 to 4.1) for women.18 While a similar rate of decline in coronary mortality was also found in theAtherosclerosis Risk in Communities (ARIC) in the United States,28 the incidence of hospitalisation for myocardial infarction was increasing.

Although the reasons for this observation are unclear, they may be attributed to a complex interplay of issues in methodology, reduction in severity of the disease and improvement in treatment.29 Furthermore, previous estimates have shown that 25% of the reduction in coronary mortality may be attributed to primary prevention programmes.30 Indeed, extensive health education campaigns may have resulted in greater awareness of symptoms leading to earlier diagnosis and treatment of previously unrecognized events in the community.Certainly, physicians were also better informed and armed with more effective diagnostic techniques and therapeutic modalities for myocardial infarction.31–33 Not surprisingly, we observed that the decline in coronary mortality (2.6%) marginally exceeded the fall in incidence (2.2%) of myocardial infarction among Singapore residents.

Despite the favourable trend, mortality among Indians remained high, which was entirely due to their higher event rate, whereas their case fatality rate is lower. Conversely, South Asian men with a first myocardial infarction experienced a poorer outcome compared with white men in the Harrow study from the United Kingdom.34 The investigators attributed their observation to a larger myocardial infarction size, resulting in a lower left ventricular systolic function, and a greater proportion ofpatients with multivessel coronary atherosclerotic disease (81% vs 58%, P<0.001). However, we found that Indian patients had the lowest CPK levels, consistent with their lower case fatality. Understandably, there are limitations when using peak CPK levels to estimate infarct size.35,36

Long-term survival
In contrast with previous beliefs, we found that Malays have the highest long-term case-fatality following myocardial infarction, consistent with the 28-day and 1-year case-fatality rates. The determinants of this ethnic difference are unclear. We found that Malays were least likely to undergo invasive cardiac procedures within 28 days of onset and had the largest infarct size. While the benefit of routine revascularization after myocardialinfarction is unknown, elective angioplasty for an occluded vessel may prevent ventricular dilatation after anterior myocardial infarction.37 Progressive dilatation of the left ventricle after a myocardial infarction is associated with adverse cardiovascular events.[38,39] Similarly, larger infarct size isassociated with left ventricular enlargement and scarring.40

Beyond the usual clinical factors, cultural, educational, and socio-economic factors may impact on the outcome of patients with myocardial infarction.41,42 Education may also enhance the understanding of illness, care seeking, behavioural modification, control of risk factors and adherence to efficacious treatment regimens. In Singapore, only 4.9% of Malays received tertiary education compared with 19.6% for Chinese and Indians inthe year 2000.43 Similarly, other socio-economic factors may also play an important role.44 While household income has been increasing in Singapore from 1990 to 2000, differences among the three ethnic groups have also been observed. The monthly median for Malays of SGD 2708 (USD 1504) was lower than for Indians (SGD 3387 or USD 1882) and Chinese (SGD 3848 or USD 2138).45 However,as the healthcare financing system for Singapore residents is largely subsidised by the government, economic considerations alone should not serve as a barrier to care. Detailed study of the role of socio-economic factors, as well as cultural and education characteristics in affecting case-fatality in Singapore, will throw more light on thesevariations.


    Conclusion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 
We found strong ethnic differences in myocardial infarction event rates, with a substantial excess in Indians and Malays compared with Chinese. Overall, there has been a decline in myocardial infarction event rates, most strikingly among Indian women. We also found that while an Indian in our population is more likely to die from myocardial infarction (due to the high incidence rate), a Malay patient is most likely to die after a myocardial infarction. In fact, Malay patients have the lowest long-term survival. Although the reason for this observation is unclear, it is probably the result of a complex interplay of biological, social and cultural factors. The excess in event rates among Indians, the protection enjoyed by the Chinese population and the higher case-fatality among Malays remain a major aetiologic and public health challenge.


    Acknowledgments
 
We would like to thank Ms Ling-Ling Sm and Lay- Yong Tan for their invaluable contribution to this manuscript. The Singapore Myocardial Infarction Register was funded, in part, by the Singapore National Heart Association.


    References
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 Conclusion
 References
 

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