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    Factors Predicting High Estimated 10-Year Stroke Risk: ThaiEpidemiologic Stroke Study

    Suchat Hanchaiphiboolkul, MD,*Pimchanok Puthkhao, MSc,*Somchai Towanabut, MD,*Tasanee Tantirittisak, MD,*

    Khwanrat Wangphonphatthanasiri, MD,*Thanes Termglinchan, MD,*

    Samart Nidhinandana, MD,Nijasri Charnnarong Suwanwela, MD,

    and Niphon Poungvarin, MD, FRCPx

    Background:The purpose of the study was to determine the factors predicting highestimated 10-year stroke risk based on a risk score, and among the risk factors

    comprising the risk score, which factors had a greater impact on the estimated

    risk. Methods: Thai Epidemiologic Stroke study was a community-based cohortstudy, which recruited participants from the general population from 5 regions of

    Thailand. Cross-sectional baseline data of 16,611 participants aged 45-69 years

    who had no history of stroke were included in this analysis. Multiple logistic regres-

    sion analysis was used to identify the predictors of high estimated 10-year stroke

    risk basedon therisk score of theJapanPublic HealthCenter Study, which estimated

    the projected 10-year risk of incident stroke. Results:Educational level, low personalincome, occupation, geographic area, alcohol consumption, and hypercholesterole-

    mia were significantly associated with high estimated 10-year stroke risk. Among

    these factors, unemployed/house work class had the highest odds ratio (OR, 3.75;

    95% confidence interval [CI], 2.47-5.69) followed by illiterate class (OR, 2.30; 95%

    CI, 1.44-3.66). Among risk factors comprising the risk score, the greatest impact asa stroke risk factor corresponded to age, followed by male sex, diabetes mellitus, sys-

    tolic blood pressure, and current smoking. Conclusions: Socioeconomic status, inparticular, unemployed/house work and illiterate class, might be good proxy to

    identify the individuals at higher risk of stroke. The most powerful risk factors

    were older age, male sex, diabetes mellitus, systolic blood pressure, and current

    smoking. Key Words: Thailandepidemiologystrokerisk factors10-year

    stroke risk.

    2014 by National Stroke Association

    From the *Prasat Neurological Institute, Department of Medical

    Services, Ministry of Public Health, Bangkok; Division of Neurology,

    Department of Medicine, Phramongkutklao Hospital, Bangkok;

    Division of Neurology, Department of Medicine, Chulalongkorn

    University, Bangkok; and xDivision of Neurology, Department of

    Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.

    Received January 16, 2014; accepted January 26, 2014.

    This study was supported by grants from the Prasat Neurological

    Institute, the National Neurological Institute of Thailand, and the

    Department of Medical Services, Ministry of Public Health, Thailand.

    Address correspondence to Suchat Hanchaiphiboolkul, MD, Prasat

    Neurological Institute, Department of Medical Services, Ministry of

    Public health, 312 Rajavithi Road, Bangkok 10400, Thailand. E-mail:

    [email protected].

    1052-3057/$ - see front matter

    2014 by National Stroke Association

    http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.025

    Journal of Stroke and Cerebrovascular Diseases, Vol. -, No. - (---), 2014: pp 1-6 1

    http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-mailto:[email protected]://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.025http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2014.01.025mailto:[email protected]://-/?-http://-/?-http://-/?-http://-/?-http://-/?-http://-/?-
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    Introduction

    Stroke is the second most common cause of death after

    myocardial infarction and is a leading cause of acquired

    disability worldwide.1 More than 85% of fatal stroke

    occur in low- and middle-income countries,2 with a

    greater than 100% increase in stroke incidence over the

    past 4 decades.3 Without intervention, the number of

    global deaths is projected to rise to 6.5 million in 2015and 7.8 million in 2030.2 Despite the advent of treatment

    of selected patients with stroke, the best approach to

    reduce the burden of stroke remains prevention by modi-

    fication or control of stroke risk factors.2,4 However,

    reliable data on stroke risk factors in developing

    countries including Thailand are lacking.5,6 In Thailand,

    stroke is a major health problem and the leading cause

    of death for both males and females.7 Although the data

    on stroke incidence in Thailand is not currently available,

    a study in 2011 showed that the stroke prevalence in

    Thailand is 1.88% in people aged 45-80 years,8 which

    has increased from previous study in the elderly (1.12%)in 1998.9

    For primary stroke prevention, it seems intuitively

    appropriate to identify specific risk-reducing interven-

    tions for those individuals who have not yet had symp-

    toms of vascular disease, but are at highest risk.10

    The American Heart Association recommends that all

    asymptomatic adults receive a global cardiovascular

    risk screening.11 Similarly, the United Kingdom National

    Screening Committee recommends cardiovascular risk

    screening for all adults aged 40-74 years who are free of

    cardiovascular disease and known cardiovascular risks.12

    However, these strategies particularly might not be prac-

    tical in the context of developing countries, which often

    have limited resources. Therefore, the identification of

    people who have factors predicting high estimated 10-

    year stroke risk is required, and further risk screening,

    evaluation, and treatment, when appropriate, might be

    warranted. In the present study, individuals 10-year

    stroke risk was estimated by using a risk score developed

    from the Japan Public Health Center Study13, which esti-

    mated the projected 10-year risk of incident stroke.

    Furthermore, each risk factor comprising the risk score

    may have a different impact on the estimated risk, so if

    we understand more on this relationship, the manage-

    ment of stroke prevention could be improved.The purpose of the present study was to determine the

    factors predicting high estimated 10-year stroke risk, and

    among the risk factors comprising the risk score, which

    factors had a greater impact on the estimated risk.

    Methods

    Participants

    The Thai Epidemiologic Stroke Study is a community-

    based cohort study, an ongoing process to investigate the

    relationship between various risk factors, lifestyles, and

    stroke in Thailand. A general population cohort aged 45-

    80 years (n 5 19,997) was enrolled on the voluntary basis

    from the following 5 geographic regions of the country:

    Bangkok (capital city), Chiang Mai province (northern re-

    gion), Khon Kaen province (northeastern region), Cha-

    choengsao province (central region), and Nakhon Si

    Thammarat province (southern region). Although ourstudy sample was not established by random sampling

    but it covers all major demographic strata of the Thai gen-

    eral population aged 45-80 years.8 In the present study,

    baseline survey data were studied as cross-sectional ana-

    lyses. We limited our analyses to participants aged 45-

    69 years (n 5 16,611) and excluded those with a history

    of stroke (n 5292) because the risk score13 that we used

    was developed from participants aged 40-69 years, who

    were free of stroke at baseline. The study was approved

    by the Ethical Review Committee for Research in Human

    Subjects, Ministry of Public Health, Thailand. Signed

    informed consent was obtained from all participants.

    Baseline Survey

    Baseline health survey data were collected at a commu-

    nity place during 2004 and 2006. Measurement of blood

    pressure and anthropometric data, collection of blood sam-

    ple after overnight fast, and face-to-face interview assess-

    ing demographic information and medical history were

    performed under standard operating procedures by a

    well-trained staff. The amount of alcohol consumption

    was estimated usingresponsesto thequestion items on fre-

    quency, average daily amount, and type of alcohoic bever-

    ages. On the basis of stroke screening questionnaire,

    participants who were suspected to have a stroke were in-

    terviewed and examined by board-certified neurologists

    for determining stroke status. The details of stroke

    screening questionnaire and the method for verification

    of stroke status have been described in our previous pub-

    lication.8 Blood pressure was measured in a sitting position

    with the use of an automated blood pressure device (Om-

    ron HEM-907; Omron Healthcare Singapore Pte Ltd,

    Singapore) after participants had rested at least for 5 mi-

    nutes. Height and weight were measured in light clothes

    without shoes to the nearest .1 cm and .1 kg, respectively.

    Digital weight measurement machine (TANITA BWB-

    800; TANITA Corporation, Japan) was used. Venous bloodsamples were obtained after a 12-hour overnight fast. An-

    alyses for glucose and lipid profile were performed at the

    Division of Clinical Chemistry, Faculty of Medicine Rama-

    thibodi Hospital, which was certified by the Centers for

    Disease Control, USANational Heart, Lung and Blood

    Institute Lipid Standardization Program.

    Definitions

    Education, personal income, and occupation were used

    as indicators of socioeconomic status (SES). Education

    S. HANCHAIPHIBOOLKUL ET AL.2

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    was classified as illiterate, primary, secondary, and uni-

    versity levels. Personal income was categorized using

    monthly income cutoffs at less than 5000 Thai baht as

    low personal income (35 Thai baht z 1 US dollar in

    2009 and 32 Thai baht z 1 US dollar in 2013). Occupation

    was classified as follows: nonmanual, manual class, agri-

    cultural class, and unemployed/house work class. Non-

    smokers were those who had never smoked at all orhad smoked less than 100 cigarettes in their lifetime. Cur-

    rent smoker was defined as having smoked 100 or more

    cigarettes in a lifetime and smokes cigarettes currently.

    Participants who smoked 100 or more cigarettes in their

    lifetime but currently do not smoke at all were defined

    as ex-smokers. Hypertension was defined as blood pres-

    sure of 140/90 mm Hg or more or self-reported use of

    antihypertensive medication. Fasting plasma glucose of

    7.0 mmol/L (126 mg/dL) or more or history of treatment

    for diabetes was defined as diabetes. Hypercholesterole-

    mia was defined as fasting total cholesterol of

    5.2 mmol/L (200 mg/dL) or more or self-reported use

    of medication for hypercholesterolemia.Assessment of 10-year stroke risk of each individual

    was based on the risk score of the Japan Public Health

    Center Study13 (n 5 15,672), which was developed to pre-

    dict 10-year risk of onset of stroke (hemorrhagic and

    ischemic stroke). The risk score was developed from the

    following variables: age, sex, current smoking, body

    mass index, blood pressure, antihypertensive medication,

    and diabetes mellitus. The 10-year stroke risk of each in-

    dividual was reclassified as low (,10%) and high risk

    ($10%). This classification is arbitrary, as it has not been

    defined what is low or high 10-year risk for stroke.

    Statistical Analysis

    Continuous variables were presented as the mean and

    standard deviation. Categorical variables were described

    as percentages. The differences in baseline characteristics

    between men and women were analyzed using an inde-

    pendent sample t test for continuous variables and the

    chi-square test for categorical variables.

    Multiple logistic regression analyses were used to iden-

    tify the predictors of high estimated 10-year stroke risk.

    The independent or predictor variables included in

    model 1 were educational level, low personal income,

    occupation, geographic area, alcohol consumption. and

    hypercholesterolemia. Odds ratios (ORs) and 95% confi-

    dence intervals (CIs) were used to illustrate the asso-

    ciation.

    To compare the impact of each risk comprising the risk

    score on high estimated 10-year stroke risk, model 2 was

    fitted by including variables as model 1 plus variables,

    which included in the risk score, that is, age, sex, current

    smoking, body mass index, systolic blood pressure, dia-

    stolic blood pressure, antihypertensive treatment and dia-

    betes mellitus. Standardized beta coefficients of the

    variables, which included in the risk score, were obtained

    by multiplying each unstandardized beta coefficient by

    the standard deviation of the predictor to which the coef-

    ficient refers.14

    All probability values were 2 sided, and the level of sig-

    nificance was set at a value ofP less than .05. All statistical

    analyses were performed using SPSS for Windows

    version 16.0 (IBM, Armonk, NY)

    Results

    Table 1 summarizes the characteristics of the study

    sample. A total of 16,611 participants (5406 men, 11,205

    women) who were free of stroke, with mean age of

    56.3 years (standard deviation, 6.9 years) and range of

    45-69 years, were included in the study. The average

    age was 56.7 years for men and 56.0 years for women

    (P , .001). Educational level, low personal income, and

    occupation were of significant difference between men

    and women (P , .001). Higher prevalence of agricultural

    class was found in men, whereas women have higherprevalence of illiterate, low personal income, unem-

    ployed/house work and living in Bangkok (capital city).

    Men showed significantly higher prevalence of smoking

    and alcohol consumption and significantly higher values

    for diastolic blood pressure, whereas women had higher

    values for body mass index and higher prevalence of hy-

    pertension, antihypertensive treatment, and hypercholes-

    terolemia. Prevalence of high estimated 10-year stroke

    risk was 9.2% (19.0% in men, 4.4% in women,P , .001).

    In multiple logistic regression analysis (model 1),

    educational level (P , .001), low personal income

    (P 5 .012), occupation (P , .001), geographic area(P , .001), alcohol consumption (P 5 .004), and hypercho-

    lesterolemia (P 5 .002) were significantly associated with

    high estimated 10-year stroke risk. Among these factors,

    unemployed/house work class had the highest OR

    (3.75; 95% CI, 2.47-5.69) followed by illiterate class (OR,

    2.30; 95% CI, 1.44-3.66) (Table 2).

    To evaluate the specific impact of each variable

    included in the risk score on the high estimated 10-year

    stroke risk in the study population, a multiple logistic

    model (model 2) was constructed including the variables

    as model 1 plus variables, which included in the risk

    score, that is, age, sex, current smoking, body mass index,

    systolic blood pressure, diastolic blood pressure, antihy-

    pertensive treatment, and diabetes mellitus. In the result-

    ing model, the greatest impact as stroke risk factor

    corresponded to age, followed by male sex, diabetes mel-

    litus, systolic blood pressure, and current smoking

    (Table 3).

    Discussion

    In this community-based cross-sectional study per-

    formed in Thai general population (n 5 16,611) aged

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    45-69 years, enrolled from 5 geographic regions of

    Thailand, the prevalence of high estimated 10-year stroke

    risk ($10%) was 9.2% (19.0% in men, 4.4% in women). In

    multiple logistic regression analysis, educational level,

    low personal income, occupation, geographic area,

    alcohol consumption, and hypercholesterolemia were

    significantly associated with high estimated 10-year

    stroke risk (Table 2). Among these associated factors, un-

    employed/house work (OR, 3.75; 95% CI, 2.47-5.69) and

    illiterate (OR, 2.30; 95% CI, 1.44-3.66) had the higher

    odds ratio. When risk factors comprising the risk score

    were added to the model, we found that age, followed

    by male sex, diabetes mellitus, systolic blood pressure,

    and current smoking had the greatest impact on the

    high estimated 10-year stroke risk ($10%) (Table 3).

    Knowledge of existing disparities in stroke risk is

    important for effective stroke prevention and manage-

    ment.15 SES is an individual s position relative to others

    based on income, education, and occupation.16 Our study

    showed that low SES was a strong predictor of high esti-

    mated 10-year stroke risk. These findings were consistent

    with the previous meta-analysis of 17 studies, which

    demonstrated an increased incidence of stroke in those

    of lower SES (pooled hazard ratio, 1.67; 95% CI, 1.46-

    1.91).16 The associations between lower SES and the

    incidence of stroke have generally been demonstrated

    across stroke subtypes.17,18 However, some studies have

    demonstrated nonsignificant or weaker associations

    with hemorrhagic stroke.19-21 It is not certain what

    causes the link between lower SES and stroke.22 However,

    classic vascular risk factors partly explain the increased

    risk of stroke among lower SES groups.16 A greater

    burden of vascular risk factors in lower SES groups has

    been shown in some studies19,21,23; however, the results

    Table 1. The characteristics of a study sample

    Variable Total (n 5 16,611) Men (n 5 5406) Women (n 5 11,205) Pvalue

    Age (y; mean, SD) 56.3, 6.9 56.7, 6.8 56.0, 6.8 ,.001

    Education level ,.001

    Illiterate (%) 1.9 .8 2.5

    Primary (%) 77.3 72.5 79.6

    Secondary (%) 12.9 19.2 9.8University (%) 7.9 7.5 8.0

    Low personal income (,5000 Thai baht*/mo; %) 67.4 58.4 71.7 ,.001

    Occupation ,.001

    Nonmanual class (%) 6.4 7.0 6.1

    Manual class (%) 38.0 36.8 38.6

    Agricultural class (%) 32.6 43.5 27.3

    Unemployed/house work (%) 23.0 12.7 28.0

    Geographic area ,.001

    Bangkok (%) 10.8 7.6 12.4

    Central region (%) 24.9 22.1 26.2

    Southern region (%) 12.1 13.9 11.2

    Northern region (%) 21.5 25.0 19.8

    Northeastern region (%) 30.7 31.4 30.3

    Body mass index (kg/m2; mean, SD) 24.7, 4.2 23.5, 3.8 25.3, 4.2 ,.001

    Smoking status ,.001

    Never (%) 72.2 26.1 94.3

    Ex-smoker (%) 13.8 36.0 3.2

    Current (%) 14.0 37.9 2.5

    Alcohol consumption (g/wk; %) ,.001

    ,150 96.1 89.3 99.3

    150 to ,300 2.2 5.9 .4

    $300 1.7 4.8 .2

    Hypertension (%) 39.6 37.7 40.6 ,.001

    Systolic blood pressure (mm Hg; mean, SD) 135.5, 21.9 135.5, 21.8 135.5, 21.9 .919

    Diastolic blood pressure (mm Hg; mean, SD) 76.2, 12.4 77.0, 13.0 75.9, 12.0 ,.001

    Antihypertensive treatment (%) 17.9 14.7 19.5 ,.001

    Diabetes mellitus (%) 15.7 15.1 16.0 .105Hypercholesterolemia (%) 66.2 56.1 71.1 ,.001

    High estimated 10-y risk of strokey(%) 9.2 19.0 4.4 ,.001

    *35 Thai bahtz 1 US dollar in 2009 and 32 Thai bahtz 1 US dollar in 2013.

    yDefined as estimated 10-years risk of stroke of 10% or more.

    S. HANCHAIPHIBOOLKUL ET AL.4

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    are inconsistent.24 In the present study, the association be-

    tween lower SES and stroke could be partly explained by

    a higher burden of conventional risk factors in the lowerSES group because high estimated 10-year stroke risk in

    this study was estimated based on conventional risk fac-

    tors comprising the risk score. In addition, our study

    showed that unemployed/house work and illiterate class

    were more related to increased stroke risk compared with

    low personal income.

    Geographic variation in stroke incidence has been

    observed in some regions such as the United States25

    and China.26 The present study also demonstrated that

    a geographic area was associated with high estimated

    10-year stroke risk with the highest OR (1.52; 95% CI,

    1.24-1.87) in northeastern region. Differences in risk fac-

    tors may explain this association.

    A meta-analysis based on 35 observational studiesdemonstrates that heavy alcohol consumption increases

    the relative risk of stroke, whereas light or moderate

    alcohol consumption may be protective against total

    and ischemic stroke.27 Our study found that alcoholic

    consumption was a significant predictor of high esti-

    mated 10-year stroke risk. Most but not all epidemiologic

    studies find an association between higher cholesterol

    levels and increased risk of ischemic stroke, and also be-

    tween lower cholesterol levels and increased risk of hem-

    orrhagic stroke.28 In the present study, the 10-year stroke

    risk was estimated by risk score, which predicts stroke

    including ischemic and hemorrhagic stroke, and it was

    found that hypercholesterolemia was a significant predic-tor of high 10-year stroke risk.

    In this study, among factors comprising the risk score,

    age, male sex, diabetes mellitus, systolic blood pressure,

    and current smoking were factors of a greater impact on

    stroke risk estimation in our population. Although older

    age and male sex are nonmodifiable, people in these

    groups could get benefit from rigorous prevention or

    treatment of other modifiable risk factors; additionally,

    appropriate control of diabetes mellitus, systolic blood

    pressure, and current smoking could lead to substantial

    reduction in stroke risk.

    The main limitations of the present study are the use ofrisk score to estimate the 10-year stroke risk. Participants

    were recruited on the voluntary basis, so the study sam-

    ple was not established by random sampling but it

    covered all major demographic strata of the Thai general

    population.8 However, the study was large sample

    size and participants were enrolled from the general

    Table 2. Factors predicting high estimated 10-years risk of

    stroke ($10%) in multiple logistic regression analysis

    Variable OR 95% CI Pvalue

    Education level ,.001

    Illiterate 2.30 1.44-3.66

    Primary 1.44 1.02-2.03

    Secondary 2.00 1.42-2.84University 1.00

    Low personal income

    (,5000 Thai baht*/mo)

    1.20 1.04-1.39 .012

    Occupation ,.001

    Nonmanual class 1.00

    Manual class 1.52 1.00-2.33

    Agricultural class 1.99 1.29-3.06

    Unemployed/house work 3.75 2.47-5.69

    Geographic area ,.001

    Southern region 1.00

    Northern region 1.19 .94-1.50

    Bangkok 1.38 1.07-1.78

    Northeastern region 1.52 1.24-1.87

    Central region 1.40 1.12-1.75

    Alcohol consumption (g/wk) .004

    ,150 1.00

    150 to ,300 1.48 1.04-2.11

    $300 1.68 1.14-2.48

    Hypercholesterolemia 1.21 1.07-1.37 .002

    *35 Thai bahtz 1 US dollar in 2009 and 32 Thai bahtz 1 US

    dollar in 2013.

    Table 3. Impact of a risk score component on high estimated 10-years risk of stroke ($10%) in multiple logistic regression analysis

    Variable

    Nonstandardized coefficients

    Standardized beta coefficients PvalueBeta Standard error

    Age .690 .025 4.733 ,.001

    Sex (male) 5.896 .235 2.763 ,.001

    Diabetes mellitus 6.710 .239 2.442 ,.001

    Systolic blood pressure .088 .004 1.920 ,.001

    Current smoking 4.045 .199 1.402 ,.001

    Antihypertensive treatment 3.197 .161 1.226 ,.001

    Body mass index .221 .017 .921 ,.001

    Diastolic blood pressure .026 .007 .325 ,.001

    Educational level, low personal income, occupation, geographic area, alcohol consumption, and hypercholesterolemia were also included in

    the model.

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    population from 5 regions around the country rather than

    selected population.

    Conclusions

    To sum up, SES, geographic area, alcohol consumption,

    and hypercholesterolemia were significant predictors of

    high estimated 10-year stroke risk. Unemployed/house

    work and illiterate class were strong predictors. Among

    factors comprising the risk score, age, male sex, diabetes

    mellitus, systolic blood pressure, and current smoking

    were of a greater impact on stroke risk. These findings

    suggest that SES, in particular, unemployed/house

    work, and illiterate class are good proxy to identify the in-

    dividuals at higher risk of stroke. Clinical preventive

    focus targeting these disadvantaged population groups

    may reduce the high burden of stroke in the population.

    Acknowledgment: The authors thank the neurologists

    and staff of the Prasat Neurological Institute for their cooper-

    ation in this study. Appreciation is extended to staff of San-kampang Hospital, Khon Kaen Provincial Health Office,

    Buddha-Sothorn Hospital, and Nakhon Si Thammarat

    Provincial Health Office for their participation in the survey.

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