Abstract
Objectives
Our purpose was to evaluate interaction of green tea consumption and abdominal obesity as related factors for lacunar infarction in Korean women.
Designs
A hospital-based, incident case-control study.
Settings
The Prevention and Managements of Stroke in Women study.
Participants
Cases (n=233) of first incident lacunar infarction were enrolled and matched by age to stroke-free hospital controls (n=204).
Measurements
The data were collected through face-to-face interviews by well trained research assistants to assess demographic, medical, lifestyle, marital status, religions status, green tea consumptions, family history of stroke, smoking status, alcohol consumption, meat and vegetable intake frequency, and past history of hypertension. Biochemical analysis, fasting blood specimens for lipid, glucose, and cholesterol level were acquired.
Results
Compared with the non green tea consumer and obese women group, only the green tea consumption and non obese women group had a protective effect of lacunar infarction when adjusted for age, and age plus diet factors (OR, 0.23; 95% CI, 0.09, 0.59; OR, 0.21; 95% CI, 0.08, 0.56 respectively), but lost their significance after adjustment for age, diet factors, vascular risk factors and full model included atherogenic index factors (OR, 0.32; 95% CI, 0.09 to 1.01; OR, 0.49; 95% CI, 0.12, 1.89 respectively).
Conclusions
The interaction of green tea consumption and non obesity have reduced risk of lacunar infarction, but not after adjustment for age, diet factors, vascular risk factors and atherogenic index. Also individually green tea consumption and abdominal obesity have failed to find an independent relationship with lacunar infarction after adjustment by all risk factors. Green tea consumption and green tea consumption with non obese group seemed to have a protective effect for lacunar infarction. In the results of our study, these results still remain controversial, and then we need further and larger study to get at the root of real causal effect of both relationships.
Key words: Case-control study, ischemic stroke, lacunar infarction, green tea consumption, abdominal obesity
Introduction
Stroke is annually accounting for approximately 10%, 5 million people, of the total death in worldwide (1) and ischemic stroke contributes over 70% of all stroke patients in Western worlds. The proportion of ischemic stroke among all stroke patients in China and Japan is approximately 60% 2, 3, 4, 5. In Korea also stroke is the second largest leading cause of death, and a leading cause of chronic disability and morbidity in Korean (6).
Interest and consumption of the green tea is growing and recently several studies showed that green tea consumption is inversely associated with death from stroke and cardiovascular diseases 7, 8. Some experimental studies showed that green tea had a potent antioxidant property and could reduce free radical-induced lipid peroxidation and prevent cardiovascular disease 9, 10, 11. Also systemic administration of green tea immediately after ischemia inhibited the hippocampal neuronal damage in the gerbil model of global ischemia (12).
Early case-control studies of tea consumption found no association with CHD, MI or Stroke because of the low prevalence of heavy tea consumption 13, 14. Cohort studies conducted in Japan investigated the association between green tea consumption and cardiovascular disease mortality, but the results were inconsistent 15, 16, 17.
The prevalence of Korean adult women who had abdominal obesity was rapidly increased and reached to 42% in 2003, in the same manner the prevalence of Americans women who were overweight or obese rapidly increased from 47% to 61% 18, 19. The impact of obesity on public health is a growing concern because obesity is well recognized to be related to many diseases including cardiovascular disease 20, 21. The information about abdominal obesity as a risk factor for ischemic stroke, especially lacunar infarcts, is very limited and the relationship between abdominal obesity and lacunar infarction remains less clear.
In stroke subtypes, cerebral infarction is the most common subtypes and the incidence and prevalence have been increasing in Korea women (1). Cerebral infarction is categorized into three subtypes, atherosclerotic disease, embolism from the heart and intracranial small vessel occulsion (lacunar infarcts) on the basis of the size, location of the affected cerebral arteries and their pathogenesis (22). Small vessel occlusion, lacunar infarction, accounts for up to 25% of all ischemic strokes and is the most frequent subtype 23, 24.
Although there were several experimental and human studies on the relationship between tea or green tea and stroke, the stroke of these studies encompassed a wide range of stroke subtypes. To date, there were no studies on the relationship between just green tea consumption and lacunar infarction. So we tried this study to determine whether green tea consumptions and abdominal obesity, which have been on the increase in South Korea, were independently associated with increased or decreased risk of lacunar infarction, a large proportion of ischemic stroke, among Korean women. We also examined about the effect to the lacunar infarction of interaction between green tea consumptions and abdominal obesity.
Subjects and Methods
Participants
The Prevention and Management of Stroke in Women (PAMOS-W) Study is a hospital-based case-control study that examines risk factors for ischemic stroke in Korean women. This case-control study was conducted at the department of neurology, distributed nationwide three University Hospital, South Korea. The period of investigation was from April 1, 2003 to August 31, 2009.
Selection of Cases
This hospital-based case-control study was undertaken in 3 university teaching hospitals in South Korea (Seoul, Incheon, Wonju). Consecutive 233 female hospitalized incident cases were prospectively enrolled between April 1, 2003 and August 31, 2009. Only the patients with a first-ever lacunar infarction were included. Research assistants majoring neurology of each hospital were trained to guarantee intra reliability of diagnosis with CT, MRI or MRA, neurologic examination, face to face interview, and anthropometric assessment among individuals. The patients with past history of hypertension, diabetes mellitus or dyslipidemia were included when they confirmed with lacunar infaction. This study was approved by the Institutional Review Board at each hospital and all participants provided written informed consents.
All hospitalized cerebral infarction patients were divided into subtypes and confirmed lacunar infarction on the basis of the Classification of Cerebrovascular disease III proposed by the National Institute of Neurological Disorders and Stroke. The definition of lacunar infarction of our study was cerebral infarction cases lack evidence of cerebral cortical impairment, cerebellar dysfunction and disturbance of consciousness. Classification into this lacunar infarction also requires the presence of a relevant brain stem or subcortical hemispheric lesions with a diameter of <1.5 cm as demonstrated on CT or MRI brain scan (25). The diagnosis of stroke was made if reported on computed tomography (CT), magnetic resonance imaging (MRI), or cerebral angiography carried out within 3 weeks of the clinical event. Green tea consumption were obtained almost subjects, 231 cases, only two missing, but waist and hip circumferences were not obtained 56 subjects; therefore 177 cases were included in this analysis.
Selection of Controls
AS Control group, 203 consecutive subjects were identified from among those patients hospitalizing in the same hospitals for Orthopedic, ear, nose, throat, skin and Ophthalmic disorders unrelated to lacunar infaction and recruited during same period with case subjects. For the enrollment for control subject, we recruited female controls matched to 1 control by 5-year age band, hospital, and time of admission. Control subjects were eligible if they had never been diagnosed with a stroke. When a subject was recruited, the research objectives were explained and interviewed briefly to record age, and social economic status, life styles, green tea consumption, anthropometric measurements, convention vascular disease risk factors. Green tea consumption were obtained all participants, 204 controls, and waist and hip circumferences were not obtained 80 controls; therefore 124 controls were included in this final analysis.
Ascertainments of Exposure to Related Factors of Cases and Controls
The study parameters were obtained from the both case patients and control participants, and the data were collected through face-to-face interviews by well trained research assistants who got the three times of workshop for reviewer education with well documented SOPs. Demographic, medical, lifestyle, marital status, religions status, green tea consumptions, family history of stroke, smoking status, alcohol consumption, meat and vegetable intake frequency, and past history of hypertension were collected. Past history of hypertension was confirmed by history of use of antihypertensive drug, and through biochemical analysis, fasting blood specimens for lipid, glucose, and cholesterol level were acquired. Total cholesterol and HDL cholesterol were measured according to standard practices 26, 27. Total cholesterol, LDL cholesterol, and HDL cholesterol was analyzed with classification criteria of Adult Treatment Panal III (ATP III) of National Cholesterol Education Program (NCEP), NHLBI (28). Fasting glucose was measured with a Hitachi 747 automated spectrometer (Boehringer) and lipid panels (including total cholesterol, LDL, HDL, and triglyceride) were measured with a Hitachi 705 automated spectrometer (Boehringer).
Green tea consumption and other data were also assessed through structured interviews using questions according to questionnaire adapted and revised by PAMOSW study group. Inquiries were made about consumptions of green tea both during the past year and on average during the participant's drinking lifetime. The defined responses regarding frequency allowed 6 possibilities ranging from never to 2 or more drinks per day. The unit of drinks was a cup and one cup or unit means 150ml of liquid with one gram of green tea bag. The volume of 500ml of green tea bottles equals with 3 cups of green tea, it was calculated the green tea extract contents. The responses for green tea consumption were then summed to obtain a total overall quantity. Inter and intra reliability was raised by training of researchers. Stroke-free controls were interviewed in person and evaluated in the same manner as cases. Standardized questions were developed and revised several times by PAMOS study meeting regarding the variables.
Anthropometric Assessment
Case and controls had waist and hip circumference measurements performed by trained research assistants. Participants were measured with standing and relaxed without heavy outer garments and among those cases who were unable to stand, measurements were done supine. Waist circumference was measured with the participant standing with abdomen relaxed, arms at sides, and feet together without footwear. The research assistant faced the participant and measured with a tape to the nearest 0.5 cm in the horizontal plane on the bare skin at the level of the natural waist, the narrowest part of the torso at the end of a normal expiration. Hip circumference was measured with the participant standing in the same position around the buttocks in the horizontal plane at the largest circumference between the waist and thigh. The measurement was usually over the greater trochanters. Weight was measured to the nearest 0.5 kg, and height, to the nearest 0.5 cm. Participants did not wear shoes during height measurements. WHR was defined as waist divided by hip circumference.
Statistical Analyses
As an initial comparison of case patients and controls, status of green tea consumption, and status of abdominal obesity, univariate testing was done continuous variables using the Student t-test for comparisons between means and on categorical variables using chi-square tests for comparisons between values for categorical variables. The relationship between green tea consumption or WHR quartiles classified by control distributions and lacunar infarction was analyzed by simple and multiple conditional logistic regression models for matched case-control data and were used to calculate the odds ratio (OR) and 95% confidence interval (CI). Adjusted ORs were calculated after adjustment for potential confounding factors. For the logistic regression analyses, four models were estimated; model 1 adjusted only age factor; model 2, age and diet factors, model 3 included all of the variables in model 2 as well as conventional vascular risk factors, and model 4, included all factors, age, diet factors, conventional vascular risk factors and atherogenic index, LDL/HDL ratio.
Results
The basic characteristics of the 233 stroke patients and the 204 controls were shown Table 1. There was no significant difference in age distribution between the controls and the cases, mean ages of controls and cases were 65.15+11.76 and 66.49 (10.72 years, respectively. Table 1, also showed the unadjusted odds ratios for the development of lacunar infarction for the two groups characteristics of particular interest, green tea consumption and waist hip ratio. Green tea consumptions were analyzed into three categorization methods, yes or no, above or below of one cup per day, and none, <1 cup a week, <1 cup a day, >=1 cup a day, and all classifications of green tea consumption had protective effects of lacunar infarction, the odds ratio were 0.58, 0.49 and 0.43~0.67 (95% CI, 0.37~0.93, 0.26~0.94, and 0.19~1.43) respectively. In waist hip ratio, cases were more common than controls significantly, as a risk factor, the odds ratio of waist hip ratio was 1.97 (95% CI, 1.23~3.17), but in our study population, BMI was not significantly associated with lacunar infartion, in fact, BMI had a slight inverse association with ischemic stroke. These patterns of findings had been noted by others (29). Coffee consumption, meat intake frequency, vegetable intake frequency were not different their frequencies between two groups, but current smoking, current drinking, family history of stroke, marital status of separated by death, past history of hypertension, high total cholesterol, high low density lipoprotein were more common, and atherogenic index was higher among the case subjects, while religious status were more prevalent among the controls.
Table 1.
Distributions of Basic Characteristics of Cases and Controls in PAMQS-W Study
| Variable | Controls (n=233) | Cases (n=204) | ORs $ (95% CI) | P value |
|---|---|---|---|---|
| Age at screening, mean(SD), y | 65.15 (11.76) | 66.49 (10.72) | 1.01(0.00~1.03) | 0.118 |
| Green tea consumption (n, %) No | 169(73.1) | 168(82.4) | 0.58(0.37~0.93) | 0.023 |
| Yes | 62(26.1) | 36(17.6) | ||
| Green tea consumption/day (n, %) < 1 | 199(86.1) | 189(92.6) | 0.49(0.26~0.94) | 0.032 |
| >= 1 | 32(13.9) | 15(7.4) | ||
| Green tea consumption (n, %) None | 169(73.2) | 168(82.4) | 0.051 | |
| <1 cup a day | 30(13.0) | 21(10.3) | 0.70(0.38~1.27) | 0.250 |
| >=1 cup a day | 32(14.8) | 15(7.3) | 0.47(0.24~0.90) | 0.023 |
| WHR # (n, %) Non obese women | 89(50.3) | 42(31.6) | 1.97(1.23~3.17) | 0.005 |
| Obese women | 88(49.7) | 82(69.4) | ||
| BMI (n, %) Non obese women | 94(52.5) | 60(47.6) | 1.22(0.77~1.92) | 0.400 |
| Obese women | 85(47.5) | 66(52.4) | ||
| Coffee consumption (n, %) No | 109(47.2) | 99(48.7) | 0.97(0.66~1.44) | 0.888 |
| Yes | 122(52.8) | 104(51.3) | ||
| Meat intake frequency, day (n, %) < 1 | 124(54.6) | 106(52.2) | 1.10(0.75~1.61) | 0.617 |
| >= 1 | 103(45.4) | 97(47.7) | ||
| Vegetables intake frequency, day(n, %) < 1 | 32(14.0) | 36(17.6) | 0.76(0.45~1.27) | 0.295 |
| >= 1 | 197(86.0) | 68(82.4) | ||
| Smoking (n, %) Never | 202(87.5) | 170(84.2) | 0.617 | |
| Past | 13(5.6) | 14(6.9) | 1.28(0.59~2.80) | 0.535 |
| Current | 16(6.9) | 18(8.9) | 1.34(0.66~2.70) | 0.419 |
| Drinking (n, %) Never | 182(78.8) | 135(66.2) | 0.007 | |
| Past | 21(9.0) | 22(10.8) | 1.41(0.75~2.67) | 0.289 |
| Current | 28(12.2) | 47(23.0) | 2.26(1.35~3.80) | 0.002 |
| Family history of Stroke (n, %) No | 195(85.2) | 127(62.6) | 3.43(2.16~5.44) | <0.001 |
| Yes | 34(14.8) | 76(37.4) | ||
| Marital status Current marriage | 141(63.2) | 100(49.8) | 1.74(1.18~2.56) | 0.005 |
| Separated by death | 82(36.8) | 101(50.1) | ||
| Religion (n, %) No | 56(24.5) | 69(35.4) | 0.59(0.38~0.90) | 0.014 |
| Yes | 173(75.5) | 126(64.6) | ||
| Past history of Hypertension (n, %) No | 107(74.8) | 55(27.0) | 8.01(4.57~13.09) | <0.001 |
| Yes | 36(25.2) | 137(73.0) | ||
| TC, mean±SD, mg/dL ~ <200 | 78(62.4) | 94(47.0) | 0.002 | |
| 200~<240 | 38(30.4) | 63(31.5) | 1.38(0.83~2.27) | 0.213 |
| 240 ~ | 9(7.2) | 43(21.5) | 3.96(1.82~8.64) | 0.001 |
| LDLC, mean±SD, mg/dL ~ <100 | 47(38.5) | 32(16.1) | <0.001 | |
| 100~<130 | 39(32.0) | 73(36.7) | 2.75(1.52~4.98) | 0.001 |
| 130~<160 | 25(20.5) | 54(27.1) | 3.17(1.65~6.10) | 0.001 |
| 160~<190 | 8(6.6) | 29(14.6) | 5.32(2.16~13.13) | 0.015 |
| 190 ~ | 3(2.5) | 11(5.5) | 5.39(1.39~20.84) | <0.001 |
| HDLC, mean±SD, mg/dL ~ <40 | 53(42.7) | 78(39.2) | 0.799 | |
| 40~<60 | 62(50.0) | 107(53.8) | 1.17(0.73~1.87) | |
| 60 ~ | 9(7.3) | 14(7.0) | 1.06(0.43~2.62) | 0.505 0.905 |
| LDL-C/HDL-C €, mean(SD) |
2.71(0.87) |
3.13(1.06) |
1.57(1.22~2.02) |
<0.001 |
# WHR, Waist-Hip Ratio = circumference of waist over hip, based on the distributions of controls. Non obese < 0.9157, obese > 0.9158. BMI, Body Mass Index, Non obese < 25kg/m2, obese >=25kg/m2. $ ORs = Odds Ratios, & p-value of Chi-square test, student t-test, linear trend, € LDL-C/HDL-C, Atherogenic index = Low density lipoprotein cholesterol/High density lipoprotein cholesterol. TC=Total cholesterol, LDL-C=Low density lipoprotein cholesterol, HDLC=High density lipoprotein cholesterol.
To assess for other confounding factors that may have affected green tea consumptions and the level of waist hip ratio in our study subjects, we simply performed analyses of association of green tea consumption and other risk factors and between abdominal obesity and other risk factors. The associations of green tea consumptions classified by yes or no with other risk factors were shown in Table 2. A significant association of green tea consumption with meat intake frequency, vegetable intake frequency, smoking status, drinking status, marital status, and high HDL cholesterol were observed. But WHR, BMI, and other factors were also not different significantly. In Table 3, we analyzed our data according to abdominal obesity important risk factors of lacunar infarction. Participants were divided into two groups, abdominal obesity group and non obesity group by median based on the waist-hip ratio of the distribution of control group, none obese was defined below of 0.9157, obese was above 0.9158. Among the 170 abdominal obese group, vegetable intake frequency, drinking, past history of hypertension, high total cholesterol, high LDL cholesterol levels and LDL-C/HDL-C ratio were higher than controls significantly, and green tea consumptions, coffee consumptions, meat intake frequency, smoking, marital status, family history of stroke, religion status were similar between two groups.
Table 2.
General Characteristics and Conventional Vascular Risk Factors by Green Tea Consumption
| Variable | Green tea No (n=337) | Green tea Yes (n=98) | P value |
|---|---|---|---|
| Age at screening, mean(SD), y | 66.70(10.20) | 63.59(12.44) | 0.025 |
| WHR (n, %) Non obese women | 95(41.7) | 36(49.3) | 0.279 |
| Obese women | 133(58.3) | 37(50.7) | |
| BMI (n, %) Non obese women | 108(46.8) | 46(62.2) | 0.023 |
| Obese women | 123(53.2) | 28(37.8) | |
| Coffee consumption (n, %) No | 215(63.8) | 55(56.7) | 0.204 |
| Yes | 122(36.2) | 42(43.3) | |
| Meat intake frequency, day (n, %) < 1 | 190(57.0) | 40(41.2) | 0.006 |
| >= 1 | 143(43.0) | 57(58.8) | |
| Vegetables intake frequency, day(n, %) < 1 | 44(13.1) | 24(24.7) | 0.005 |
| >= 1 | 292(86.9) | 73(75.3) | |
| Smoking (n, %) Never | 293(87.5) | 79(80.6) | 0.004 |
| Past | 14(4.2) | 13(13.3) | |
| Current | 28(8.3) | 6(6.1) | |
| Drinking (n, %) Never | 248(73.6) | 69(70.4) | 0.037 |
| Past | 27(8.0) | 16(16.3) | |
| Current | 62(18.4) | 13(13.3) | |
| Family history of Stroke (n, %) No | 252(75.2) | 70(72.2) | 0.543 |
| Yes | 83(24.8) | 27(27.8) | |
| Marital status Current marriage | 179(59.7) | 62(66.6) | 0.043 |
| Separated by death | 151(40.3) | 32(34.0) | |
| Religion (n, %) No | 103(31.3) | 22(23.2) | 0.125 |
| Yes | 226(68.7) | 73(76.8) | |
| Past history of Hypertension (n, %) No | 124(48.1) | 38(49.4) | 0.897 |
| Yes | 134(51.9) | 39(50.6) | |
| TC, mean±SD, mg/dL ~ <200 | 133(52.4) | 39(54.9) | 0.870 |
| 200~<240 | 79(31.1) | 22(31.0) | |
| 240 ~ | 42(16.5) | 10(15.1) | |
| LDLC, mean±SD, mg/dL ~ <100 | 60(23.9) | 19(27.1) | 0.923 |
| 100~<130 | 86(34.3) | 26(37.1) | |
| 130~<160 | 64(25.5) | 15(21.4) | |
| 160~<190 | 30(12.0) | 7(10.0) | |
| 190 ~ | 11(4.6) | 3(5.4) | |
| HDLC, mean±SD, mg/dL ~ <40 | 103(40.9) | 28(39.4) | 0.033 |
| 40~<60 | 136(54.0) | 33(46.5) | |
| 60 ~ | 13(5.1) | 10(14.1) | |
| LDL-C/HDL-C, mean(SD) |
3.00(1.03) |
2.86(0.94) |
0.306 |
Table 3.
General Characteristics and Conventional Vascular Risk Factors by Waist Hip Ratio
| Variable | Non obese women(n=131) | Obese women (n=170) | P value |
|---|---|---|---|
| Age at screening, mean(SD), y | 62.08(12.18) | 67.80(9.68) | <0.001 |
| Green tea consumption (n, %) No | 95(73.1) | 133(82.4) | 0.279 |
| Yes | 36(26.1) | 37(17.6) | |
| Green tea consumption/day (n, %) < 1 | 109(83.2) | 151(88.8) | 0.177 |
| >= 1 | 22(16.8) | 19(11.2) | |
| Green tea consumption (n, %) None | 95(72.5) | 133(78.2) | 0.362 |
| <1 cup a day | 14(10.7) | 18(10.6) | |
| >=1 cup a day | 22(15.8) | 19(11.2) | |
| Coffee consumption (n, %) No | 73(55.7) | 98(58.0) | 0.695 |
| Yes | 58(44.3) | 71(42.0) | |
| Meat intake frequency, day (n, %) < 1 | 70(54.7) | 78(45.9) | 0.132 |
| >= 1 | 58(45.3) | 92(54.1) | |
| Vegetables intake frequency, day(n, %) < 1 | 13(10.1) | 37(22.8) | 0.007 |
| >= 1 | 116(89.9) | 133(78.2) | |
| Smoking (n, %) Never | 118(90.0) | 141(83.4) | 0.251 |
| Past | 6(4.7) | 13(7.7) | |
| Current | 7(5.3) | 15(8.9) | |
| Drinking (n, %) Never | 96(73.3) | 133(78.2) | 0.071 |
| Past | 8(6.1) | 17(10.0) | |
| Current | 27(20.6) | 20(11.8) | |
| Family history of Stroke (n, %) No | 103(78.6) | 126(75.5) | 0.519 |
| Yes | 28(21.4) | 41(24.5) | 0.099 |
| Marital status Current marriage | 76(62.3) | 90(65.2) | 0.309 |
| Separated by death | 46(37.7) | 48(34.8) | |
| Religion (n, %) No | 32(25.6) | 50(30.0) | |
| Yes | 98(75.4) | 117(70.0) | |
| Past history of Hypertension (n, %) No | 56(62.2) | 50(41.0) | 0.003 |
| Yes | 34(37.8) | 72(59.0) | |
| TC, mean±SD, mg/dL ~ <200 | 56(66.7) | 48(41.7) | 0.001 |
| 200~<240 | 21(25.0) | 42(36.6) | |
| 240 ~ | 7(8.3) | 25(21.7) | |
| LDLC, mean±SD, mg/dL ~ <100 | 27(32.1) | 16(14.2) | 0.001 |
| 100~<130 | 34(40.5) | 38(33.6) | |
| 130~<160 | 18(21.4) | 33(29.2) | |
| 160~<190 | 2(2.4) | 19(16.8) | |
| 190 ~ | 3(3.6) | 7(6.2) | |
| HDLC, mean±SD, mg/dL ~ <40 | 37(35.7) | 50(43.9) | 0.749 |
| 40~<60 | 42(50.0) | 54(47.4) | |
| 60 ~ | 5(14.3) | 10(8.7) | |
| LDL-C/HDL-C €, mean(SD) |
2.75(1.06) |
3.23(1.04) |
0.002 |
# WHR, Waist-Hip Ratio = circumference of waist over hip, based on the distributions of controls. Non obese < 0.9157, obese > 0.9158.
We also analyzed of the associations between the green tea consumptions and risks of lacunar infarction in Table 4. The methods of adjustment were analyzed separately with four models for analysis, for age (Model 1), age plus diet factors, such as coffee consumptions, meat and vegetable intake frequencies (Model 2), and Model 3 was added conventional vascular risk factors, such as, smoking status, drinking status, family history of stroke, religion status, marital status, past history of hypertension to Model 2, and Model 4, also adjusted for age, diet factors, vascular risk factors and atherogenic index (low density lipoprotein cholesterol/high density lipoprotein cholesterol. Engaging in any green tea consumptions were independently related to a reduced risk of lacunar infarction after adjustment for age, diet factors, cardiovascular factors, and athrogenic index (LDL-C/HDL-C) even though, not significant, but the trends of ORs for green tea consumptions were in the protective direction. Especially, when we used the no-consumption group as a reference, heavy green tea consumption groups, above one cup a day, seen protective effects in unadjusted model and model 1 and 2 (ORs=0.47, 0.48, and 0.43; CIs=0.24~0.90, 0.25~0.93, and 0.22~0.84 respectively). In all models, except for model 3, heavy green tea consumption group appeared significant protective than light-moderate green tea consumption groups, below one cup a day, suggesting a dose-response relationship between the intensity of green tea consumptions and lacunar infarction.
Table 4.
Associations of Green Tea Consumption Status with Other Risk Factors
| Models | none | Level of Green tea intake <1 cup per day ORs (95% CIs) | >= 1 cup per day ORs (95% CIs) |
|---|---|---|---|
| 1.0 | 0.70 (0.38, 1.27) | 0.47 (0.24, 0.90) | |
| Age a | 1.0 | 0.72 (0.39, 1.32) | 0.48 (0.25, 0.93) |
| Age+diet factors b | 1.0 | 0.66 (0.36, 1.24) | 0.43 (0.22, 0.84) |
| Age+diet factors +vauscular risk factors c | 1.0 | 0.30 (0.08, 1.19) | 0.66 (0.22, 1.96) |
| Age+diet factors+vascular risk factors+LDL/HDL ratio d |
1.0 |
0.56 (0.10, 3.38) |
0.30 (0.16, 1.77) |
Model 1, the odds ratio adjusted for age, the 95% confidence interval is for this odds ratio; b Model 2, the odds ratio also adjusted for age, and diet factors, such as, coffee consumption, meat and vegetable intake frequencies; c Mode 3, the odds ratio also adjusted for age, diet factors, and vascular risk factors, such as, smoking status, drinking status, family history of stroke, religion status, marital status, past history of hypertension; d Model 4, the odds ratio also adjusted for age, diet factors, vascular risk factors and atherogenic index (low density lipoprotein cholesterol/high density lipoprotein cholesterol).
In Table 5, the variable of one of two primary interests, WHR, quartiles based on the distributions among control participants, was also adjusted and analyzed separately with four models. Unadjusted for other risk factors, a risk effect was seen for lacunar infarction in obese women patient (OR, 1.97; 95% CI, 1.22~3.17). In multivariable analysis, adjusted for age only (Model 1), age and diet factors (Model 2) were similar to unadjusted analysis (ORs, 2.00, 1.74; 95% CIs, 1.22~3.26, 1.05~2.89), but adjusted age, diet factors, conventional vascular factors (Model 3), and age, diet factors, vascular risk factors, LDL/HDL ratio (Model 4) were not significant, but it shown the risk trends.
Table 5.
Associations of Abdominal Obesity Represented by WHR with Other Risk Factors
| Models | Abdominal Obesity Status Non obese, n=177 | Obese, n=124, ORs (95% CIs) |
|---|---|---|
| 1.0 | 1.97 (1.22, 3.17) | |
| Age a | 1.0 | 2.00 (1.22, 3.26) |
| Age + diet factors b | 1.0 | 1.74 (1.05, 2.89) |
| Age + diet factor + vascular risk factor c | 1.0 | 0.98 (0.45, 2.11) |
| Age+diet factor +v ascular risk factor + LDL-C/HDL-C ratio d |
1.0 |
0.68 (0.27, 1.66) |
Model 1, the odds ratio adjusted for age, the 95% confidence interval is for this odds ratio; b Model 2, the odds ratio also adjusted for age, and diet factors, such as, green tea consumption, coffee consumption, meat and vegetable intake frequencies; c Mode 3, the odds ratio also adjusted for age, diet factors, and vascular risk factors, such as, smoking status, drinking status, family history of stroke, religion status, marital status, past history of hypertension; d Model 4, the odds ratio also adjusted for age, diet factors, vascular risk factors and atherogenic index (low density lipoprotein cholesterol/high density lipoprotein cholesterol).
With the results of Table 1 to 5, we knew that waist hip ratio was a potential risk factor of lacunar infarction, and green tea consumption was a potential protective factor of lacunar infarction. So, we supposed that green tea consumption and waist hip ratio would have interaction, because the results of Table 2, Table 3 showed that they didn't have correlations and in Table 4, Table 5 they appeared to be a potential protective and risk factor of lacunar infarction. In table 6, we simply combined abdominal obesity status based on the waist-hip ratio of the distribution of control group and green tea intake status based on current consumer or non consumer, and simply analyzed the difference of frequencies by using cross tabs. Abdominal obesity was divided by two methods, one was by abdominal obese and non obese woman, the other was by quartiles of WHR based on the distribution of control group. The distribution of green tea intake status and abdominal obesity status combinations were significantly different. In control groups, current green tea consumer and non obese woman was more common, and in case groups, green tea non consumer and obese women combination was more frequent.
Table 6.
Distribution Divided by Green Tea Consumption and Abdominal Obesity Status of Cases and Controls Groups
| Variable | Controls (n=233) | Cases (n=204) | P value | |
|---|---|---|---|---|
| Green tea No | + WHR > 50% | 67 | 66 | 0.015 |
| Green tea No | + WHR < 50% | 61 | 34 | |
| Green tea Yes | + WHR > 50% + | 21 | 16 | |
| Green tea Yes | WHR < 50% | 28 | 8 | |
| Green tea No | + WHR 1st Q | 29 | 12 | 0.049 |
| Green tea No | + WHR 2nd Q | 32 | 22 | |
| Green tea No | + WHR 3rd Q | 34 | 38 | |
| Green tea No | + WHR 4th Q | 33 | 28 | |
| Green tea Yes | + WHR 1st Q | 15 | 2 | |
| Green tea Yes | + WHR 2nd Q | 13 | 6 | |
| Green tea Yes | + WHR 3rd Q | 10 | 9 | |
| Green tea Yes |
+ WHR 4th Q |
11 |
7 |
The interactive effects of current green tea intake and non obese women were analyzed simultaneously using a binary logistic regression analysis adjusted for age, diet factors, conventional vascular risk factors, and atherogenic index with each model 1 to 4. Especially our results showed statistical significance in case of current green tea consumer and non obese combination group compared to green tea non consumer and obese women combination group in unadjusted, adjusted model 1 and 2. Supposing that green tea consumer and obese women combination group showed decreased ORs, but not significant, in all models compared to non consumer, obese group. For model 3 and model 4, even if the trend of protective effect was seen, the protective effects were lost their statistical significance. A dose-response relationship was observed in current green tea consumer and obese combination group, but in the green tea consumer and non obese group lost their significance as well as increased the ORs.
Table 7.
Association of Lacunar Infarction With Interaction of Green Tea Consumption and Abdominal obesity
| Models | Level of Green tea intake and abdominal obesity Green tea No+ WHR > 50% Green tea Yes+ WHR > 50% ORs (95% CIs) | Green tea Yes+ WHR < 50% Ors (95% CIs) | |
|---|---|---|---|
| 0.77(0.37, 1.61) | 0.29(0.12, 0.68) | ||
| Age a | 1.0 | 0.75(0.35, 1.57) | 0.23(0.09, 0.59) |
| Age+diet factor b | 1.0 | 0.57(0.26, 1.27) | 0.21(0.08, 0.56) |
| Age+diet factors+vascular risk factors c | 1.0 | 0.42(0.12, 1.45) | 0.32(0.09,1.01) |
| Age+diet factors+vascular risk factors+LDL/HDL ratio d |
1.0 |
0.34(0.08, 1.42) |
0.49(0.12, 1.89) |
Model 1, the odds ratio adjusted for age, the 95% confidence interval is for this odds ratio; b Model 2, the odds ratio also adjusted for age, and diet factors, such as, coffee consumption, meat and vegetable intake frequencies; c Mode 3, the odds ratio also adjusted for age, diet factors, and vascular risk factors, such as, smoking status, drinking status, family history of stroke, religion status, marital status, past history of hypertension; d Model 4, the odds ratio also adjusted for age, diet factors, vascular risk factors and atherogenic index (low density lipoprotein cholesterol/high density lipoprotein cholesterol).
Discussion
In this hospital-based case-control study among Korean women, we studied the association between lacunar infarction and related factors. We particularly analyzed the association between green tea consumption and lacunar infarction, the relationship of waist-hip ratio and lacunar infarction, and then the interactive effects of green tea consumption and status of abdominal obesity by waist-hip ratio level based on the distribution of control participants to the lacunar infarction using multivariate analysis. Recent years, green tea consumption has been in an increase in quantity in South Korea due to the increase in number of persons interested in prevention of diseases and health promotion. In Korea, there are many kinds of tea, such as green tea, black tea and oolong tea, and different origination of tea. But the population of consumption of black and oolong tea is rare and only green tea has been getting the popularity. So we restricted on the green tea consumption in the data collection process. Green tea partly proved to be inversely associated with the risk of lacunar infarction with a significant reduction among higher green tea consumer, drinking >= 1 cup a day, when unadjusted, adjusted for age (model 1) and adjusted for age plus diet factors, such as coffee consumption, meat, and vegetable consumption (model 2), relative to the reference, non consumer. The odds ratio was 0.47 for univariate analysis (95% CI, 0.24, 0.90), 0.48 for model 1 (95% CI, 0.25, 0.93), 0.43 for model 2 (95% CI, 0.22, 0.84), while when it was adjusted for age, diet factors plus smoking status, drinking status, family history of stroke, marital status, religion status and past history of hypertension as conventional vascular risk factors (model 3) and adjusted for model 3 plus atherogenic index, Low density lipoprotein cholesterol/high density lipoprotein cholesterol ratio, (model 4), the OR were 0.66 (95% CI, 0.22,1.96), and OR=0.30 (95% CI=0.16,1.77. Supposing that significant associations of high green tea consumption and lacunar infarction were shown in unadjusted model and adjusted model 1 and 2, they were lost their significance after adjustment for model 3 and 4, but model 3 and model 4 showed to have the reduction of 28~70%, maintaining the trend of reduction of risk, even if they lost their significance. Among those green tea consumption <1 cup a day groups also appeared to have beneficial protective effects on lacunar infarction, in all models, 1 to 4, even if they didn't show statistically significant reduction of the risks of this disease. Abdominal obesity was appeared not to be associated with lacunar infarction in our data. Abdominal obesity was defined by a high waist hip ratio, well presenting abdominal obesity, based on the distributions among control participants. Our results had mixed outcomes, abdominal obesity showed risk effect significantly on the lacunar infarction in model 1 and 2, with 74~100% rise, but in model 3 and 4, they lost their significance and rather show protective tendencies than show risk tendency.
We found that green tea consumption and low waist hip ratio showed a significant synergistic interaction for the prevention of lacunar infarction, in univariate analysis (OR;0.29, 95% CI;0.12,0.68) and in multivariate analysis, when adjusted for age (model 1, OR;0.23, 95% CI;0.09,0.59), for age plus diet factors (model 2, OR;0.21, 95% CI;0.08-0.56). But after adjustment for age, diet factors plus smoking status, drinking status, family history of stroke, marital status, religion status and systolic and diastolic blood pressure as conventional vascular risk factors (model 3, OR;0.32, 95% CI;0.09,1.01), and full model, LDL/HDL addition to model 3 (model 4, OR;0.49, 95% CI;0.12,1.89), these data didn't show a statistical significance.
These investigations have lots of strengths compared with previous studies. Up to now, there were no studies on the interactive effects of green tea consumption and abdominal obesity as the related factors of the lacunar infarction. Most previous studies on the green tea consumption had an important limitation, which was imprecision of the exposure measurements. These studies referred simply to tea, including all kinds of teas, usually comprising a heterogeneous group of beverage, including fermented black tea, half fermented oolongs, unfermented green tea, and sweetened ice tea, and it might even be understood to include fruit tea or herbal teas (30). Just only study for association of green tea and stroke from Japan (31) included all subtypes of stroke, not for only lacunar infarction.
The measurement of waist circumference alone is a simple indicator of abdominal obesity but has not been found to be a good predictor of stroke in other studies (29), and these results were same with our results. Another obesity index, BMI have reported that they had a slight inverse association with ischemic stroke (32), but BMI was not significantly associated with ischemic stroke, in our outcomes, table 1 showed that there were no association between lacunar infarction and BMI. A measurement of WHR may be a more useful method to assess abdominal fat accumulation and a better predictor of an increased risk for stroke than BMI or waist circumference. Because WHR is a more difficult measure to standardize in the clinic compared with BMI and to measure in large persons, it has been used less extensively in practice. Despite these limitations, the value of WHR argues for adding this measurement to vascular risk assessments (33).
On the basis of several in vitro and in vivo studies, green tea and compounds of green tea catechins have shown considerable promise in reducing the risk of ischemic stroke by changes in polyamine levels (34), inhibition of ischemic damage (35), or estrogen-like activity (36), inhibiting H2O2 or ferrous ion-induced lipid peroxidation (37). By these in vitro, in vivo study results, we could offer two possible explanations for the inverse association between tea and the reduced risk of lacunar infarction of our study. First, flavonoids in green tea may reduce ischemic infarction by inhibiting low density lipoprotein cholesterol oxidation (38), reducing platelet aggregation (39), or reducing ischemic damage (35). Some mechanisms have been proposed for the association between abdominal obesity and cardiovascular risk factors. Increased peripheral concentrations of insulin (40) and increased triglyceride concentration (41), and associated with abdominal obesity, might be due to the direct deposition of free fatty acids into the portal vein from intra-abdominal adipocytes. Also elevated blood pressure (42) and metabolic syndrome may be associated with abdominal obesity (33). Uncomplicated abdominal obesity is related to endothelial dysfunction, an early marker of atherosclerotic disease (43) as well as platelet activation through enhanced lipid peroxidation and inflammation (44).
In human studies, the effects of green tea for prevention of ischemic stroke were not identical. Hertog et al (45) reported reductions in fatal and nonfatal stroke in 522 older Dutch men initially free of stroke in the highest tertile of flavonoid intake comprising 61% of black tea as the major food source. And another study of 10054 Finnish subjects indicated an association between higher flavonoid intake and a lower risk of cerebrovascular mortality (46). But as different reports, Sesso et al (47) study showed that increasing tea intake was not associated with the risk of CVD which including stroke, with a no significant linear trend (P=0.36), and another study of Sesso et al (48) showed only among highest tea intake consumer, >=4 cups a day, referent to none tea consumer, had protective effects of tea intake on vascular events, including stroke, the relative risks (RRs) was 0.33 (95% CI, 0.14, 0.80). Another population-based cohort form Finland showed no association between quercetin and stroke in women (49) with ORs in increasing quartiles of 1.00 (reference), 1.02, 1.18, and 0.33 for important vascular events, including stroke, in the Women's Health Study (WHS) - which indicate the lack of significant linear trend (P=0.07) (48). These results parallel the shape of reduction association noted for tea and lacunar infarction in our study, 0.56 and 0.30 in full model adjustment. Although our results didn't show significant difference between green tea consumption and lacunar infarction, a true inverse association may have been masked because of the low prevalence of heavy tea consumption of control 32, case 15, or because of potential recall, information, or selection biases. And another reason, we could guess that higher tea consumption might be a surrogate for a healthier lifestyle.
Because of the association of obesity with conventional risk factors for cardiovascular disease, many studies have found a positive association between obesity and the risk of fatal and nonfatal stroke, range from 1.5 to 2.0 of RRs and recent studies have also assessed measurements of the distribution of body fat as predictors of stroke, specially the waist-hip ratio 50, 51, 52, 53. But in some cohort studies, WHR was no longer an independent risk factor for stroke after adjustment for hypertension and blood lipid levels 54, 55, an association between metropolitan relative weight and atherothrombotic stroke was found in women but not in men (56). These previous study results were corresponding to our study results. But the number of events in these cohort studies and our case-control study were small, so we need to further and large human research to demonstrate our results authentically.
Several important limitations of this study should be considered. First, our study was a case-control study rather than prospective cohort study. The hospital-based approach of this case-control study design matched by age, and restricted to women, help to minimize the potential biases often associated with case-control studies. Some control selection bias could have existed, but the distribution of WHR and green tea consumption were similar to other study distribution in Korea, implying that control selection bias was less likely. Second, WHR as anthropometric measurement was performed after hospitalization, so might not accurately reflect the premorbid status of obesity because weight and waist and hip circumferences could be changed by inadequate nutritional intake after acute stroke. However, we made special efforts to collect anthropometric questionnaire data within 72 hours after stroke, and it is unlikely that significant changes in waist or hip measurements would have occurred in that time. Measurement error may also have occurred because WHR was measured in the supine position in some cases that were unable to stand. In a pilot study, waist circumferences measured when supine were slightly smaller than when measured standing, whereas hip circumferences did not differ by position measured. Therefore, measurement errors in WHR because some cases could not stand would have led to an underestimation of the OR. Third, misclassification on green tea consumption might have occurred, but in Korea, green tea producing districts were rare, the variance of tea content would not big. Finally, alternatively, higher tea consumption may be a surrogate for a healthy lifestyle. Our data suggest that tea consumers differ from nonconsumers in terms of health behaviors and medical conditions. Nevertheless, adjustment for neither coronary risk factors nor individual lipids changed the risk estimates.
In summary, in our results we got two results, the first was that the interaction of green tea consumer and low WHR group had significant protective effects when adjusted for only age, and age plus diet factors, while for full models, non significant reduction of the risk of lacunar infarction. In adjustment of full model, the insignificant interaction effect of green tea consumption and abdominal obesity was considered that the past history of hypertension and athreogenic index had affected the results because they had a possibility of mediator of lacunar infarction. The second, green tea consumption was seemed more strong protective effects than non obese women in the results of our study, both interaction analysis and individual multivariate analysis. More data from prospective cohort studies will help to distinguish whether the interaction of tea consumption and low WHR has a true biological effect or serve as a surrogate for a risk profile promoting lower lacunar infarction risk.
Acknowledgments
Acknowledgement: This work was supported by a grant from the Kyung Hee University in 2008 (KHU-20071497).
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