Abstract
The purpose of this study was to classify factors of symptoms and signs, which is the same implication with items of factor, from patients with stroke based on the Traditional Korean Medicine (TKM) theory by using factor analysis, and to find out the inter-relations between factors and patterns. A cross-sectional study was conducted among 2905 patients with stroke in 11 Oriental Medicine hospitals of Korea. Outcome measures comprised patterns decided by TKM doctors considering 44 items and 44 items that were based on inspection, listening and smelling, inquiry, and palpation. Factor analysis was used as statistical method for classifying 44 items, and dominant pattern of the four patterns [Qi deficiency (QD), Fire-heat (FH), Yin deficiency (YD), Dampness-phlegm (DP)] for each factor was determined by Chi-square test. Thirty-three items belonged to some factors, but 11 items did not. 14 factors were extracted. Six factors which had a negative loading were separated, and distinguished using hyphen. The fourteen factors accounted for 9.42%, 6.97%, 5.75%, 4.22%, 4.15%, 3.82%, 3.32%, 3.14%, 2.95%, 2.65%, 2.62%, 2.47%, 2.37% and 2.29% of total variance respectively, and totally 56.14%. In conclusion, there are 10 factors which belong to exclusive pattern, and 9 factors which belong to inter-related pattern. It was statistically found out that there are inter-relation between DP and QD, between DP and FH, between FH and YD, and between YD and QD for stroke patients.
Keywords: Stroke, symptoms and signs, factor analysis, Korean Medicine
Introduction
Cerebrovascular disease is the second leading cause of death worldwide. It is a disease that predominantly occurs in mid-age and older adults. WHO estimated that in 2005, stroke accounted for 5.7 million deaths worldwide, equivalent to 9.9% of all death [1].
Stroke is caused by the interruption of the blood supply to the brain, usually because a blood vessel bursts or is blocked by a clot. This cuts off the supply of oxygen and nutrients, causing damage to the brain tissue [2]. The most common symptom of stroke is sudden weakness or numbness of the face, arm or leg, most often on one side of the body [2]. Approximately half of the stroke survivors in the United States and Korea engage in some form of CAM therapy [3,4]. The estimated direct and indirect cost of stroke for 2010 in the United States is $73.7 billion [5]. In addition, sequelae of stroke, acute stroke and pre-symptoms of stroke ranked No. 2, No. 6 and No. 19 respectively, when being arranged in order of frequently treated diseases in Traditional Korean Medicine (TKM) [6]. However, diagnosis of stroke by Traditional Eastern-Asia Medicine (TEAM) including TKM, has not been fully standardized. Although there are many symptoms and signs required to be considered by clinician, TKM theory behind stroke has never been quantitatively supported by data. Therefore, there is a strong need to examine underlying factors of this condition so that TKM research on this disease could be carried out in the future.
When certain symptoms and signs co-appear, they may show certain underlying pathophysiology. In addition, factor analysis is statistically able to play a role in showing classification and association of underlying pathophysiology [7]. Generally, a factor must be loaded with more than one item, an item can be loaded to more than one factor. Items that are not loaded to any factor are said to have high uniqueness [7-9]. Factor analysis is performed to identify these factors and unique items. Also we investigate inter-relations displaying dominant patterns for each factor in diagram form by using Chi-square test.
The aim of this study was to identify underlying factors for patient with stroke in TKM theory, to classify dominant pattern of factors, and to detect the inter-relation of dominant pattern. The knowledge from this study is expected to allow TKM doctors to understand the TKM theory of stroke discerningly.
Material and methods
Extraction process of pattern identification questionnaire
An Expert Committee (EC), which was composed of 19 professors who specialized in stroke from 11 Oriental Medicine hospitals, was organized for The Fundamental Study for the Standardization and Objectification of Pattern Identification in TKM for Stroke (SOPI-Stroke) [10]. After the EC and Korean Institute of Oriental Medicine (KIOM) had several meetings, 5 patterns (Fire-heat pattern, Dampness-Phlegm pattern, Qi deficiency pattern, Yin deficiency pattern, Blood-Stasis pattern) and 122 pattern indicators for stroke were derived from 10 books in the literature focused on stroke in TEAM including TKM [11-20]. The principle of pattern indicators extraction was as follows [10].
1) To reflect the characteristic of stroke symptoms and to exclude its own symptoms such as hemiparesis, dysphagia, dysarthria, facial palsy and so on.
2) To identify stroke patterns based on the present state of TKM clinically.
3) To consider the association with the previous studies.
4) To reflect the recent trend of stroke in TKM literature.
After these pattern indicators were applied to a clinical field and modified repetitively, Korean standard PI for stroke I (K-SPI-Stroke I) [10], Korean standard PI for stroke II (K-SPI-Stroke II) [21] and Korean standard PI for stroke III (K-SPI-Stroke III) [22] were developed successively. As a result of these procedures, Blood-Stasis pattern was excluded due to rare diagnosis (n = 89 [23], thus K-SPI-Stroke III composed of 4 pattern and 44 pattern indicators was adopted as the Pattern Identification Questionnaire (PIQ). 44 pattern indicators were used as items for factor analysis. It was then reexamined by the EC and adjusted to maximize its validity. Descriptions of grading the severity for each pattern indicators (described below as symptoms and signs or items for factor) were scored as follows: 1 = not significant, 2 = significant and 3 = very significant.
Study subjects and data collection
This study was a cross-sectional, multi-centered and community-based study conducted for inpatient with stroke at the department of Circulatory Internal Medicine (CIM) in the 11 Korean Oriental Medicine Hospitals (KOMH). Data were collected by each of TKM doctors who has worked for more than three years at the department of CIM in each KOMH. A total of 105 TKM doctors were included, and the number of TKM doctors ranged from 2-25 TKM doctors at each hospital. The TKM doctors took regular training courses for standard operating procedure (SOP) twice a year to increase the objectivity of diagnosis.
Subject inclusion criteria were the following: (1) stroke patients within 30 days of the onset of their symptoms, (2) confirmed by imaging diagnosis such as computerized tomography (CT) or magnetic resonance imaging (MRI). Exclusion criteria included the following: (1) traumatic stroke patients such as subarachnoid, subdural, and epidural hemorrhage.
After receiving of informed consent from all subjects, the K-SPI-Stroke III was performed, which included general information about patients such as diagnosis, medical history, and 44 symptoms and signs that were related to Pattern Identification (PI). The patients were diagnosed as one of four patterns by two TKM doctors. Patients were considered as having an identical pattern when the pattern decision of the two TKM doctors using the K-SPI-Stroke III were in agreement. A total of 2,905 stroke patients from September 2006 to December 2010, who have an identical pattern as a result of diagnostic decision of two TKM doctors, were analyzed in this study. This study was approved by the Institutional Review Boards of KIOM and each of the KOMHs involved.
Decision of dominant pattern for the items and factors
Dominant pattern of each items, which explain the representative characteristic of each items, was decided by these principles: to choose any two patterns (A and B) which has the most high frequency of 4 patterns (Fire-heat pattern, Dampness-Phlegm pattern, Qi deficiency pattern, Yin deficiency pattern) in each items, to compare the frequency of two patterns (A and B) by Chi-square test, to analyze the p-value of two patterns, to adopt [(A + B)] as the dominant pattern of item due to no statistical difference when the p-value is more than 0.01, to adopt [(A) or (B)] as the dominant pattern of item due to statistical difference when the p-value is less than 0.01. For instance, in case of mirror tongue which is an item in Factor 1, Yin deficiency and Fire-heat pattern were chosen as the most high frequency patterns, and the p-value between Yin deficiency and Fire-heat is less than 0.01, and frequency percentage of Yin deficiency is more than one of Fire-heat, therefore Yin deficiency was adopted as the dominant pattern of mirror tongue. In case of red tongue, Yin deficiency and Fire-heat pattern were chosen as the most high frequency patterns, and the p-value between Yin deficiency and Fire-heat is more than 0.01, therefore Yin deficiency + Fire-heat was adopted as the dominant pattern of red tongue.
Decision principles of dominant pattern in each factor are as follows:
1. When a certain factor (A) has 3 or 4 (N) items, and there are more than 2 or 3 (N-1) same dominant patterns (B), B is regarded as the dominant pattern of A factor. (Examples: factor 1, factor 2, factor 4).
2. When a certain factor (A) has 2 items, and there is the expression of 2 same dominant patterns (B), B is regarded as the dominant pattern of A factor. (Examples: factor 5, factor 7).
3. When a certain factor (A) has 2 items, and there is the appearance of 2 different dominant patterns (B, C), B + C is regarded as the dominant pattern in A factor. (Example: factor 6).
4. When a certain factor (A) has 2 items, and there are 2 different dominant patterns (B, B + C), B + C is regarded as the dominant pattern in A factor. (Example: factor 3, factor 13).
5. When a certain factor (A) has 2 items, and there are 2 different dominant patterns (A + B, B + C), A was excluded from pattern distribution. (Example: factor 9).
6. When some items have a negative loading in one factor (A), the negative factors were separated from positive factors. These were expressed differently from the positive factors using hyphen (A-1).
7. When a certain factor (A) has 1 item, dominant pattern of 1 item was regarded as dominant pattern of A. (Example: factor 3-1, factor 8, factor 8-1, factor 10, factor 10-1, factor 11, factor 11-1, factor 12, factor 12-1, factor 14, factor 14-1).
Statistical analysis
Continuous variables were summarized as mean ± standard deviation (SD). For categorical variables, the percentages of patients in each category were calculated. Principal component analysis with varimax rotation was used to determine the construct validity of the Pattern Identification Questionnaire (PIQ). “Eigenvalues” reflect the amount of the variance in the data that is explained by successive numbers of factors, and the traditional “eigenvalues > 1” rule was used as an indicator of the number of factors [8]. This was supplemented by “scree plots,” in which a bend or “elbow” in the plot is assumed to indicate the level at which increasing the number of factors is only introducing noise [24,25]. The output from factor analysis provides “factor loadings,” and these show the contribution of an item to each factor; by convention, loadings < 0.50 are usually ignored as being unimportant. Also, high rank two patterns for each item were compared using the chi-square test. Results with a two-sided P < 0.01 were considered statistically significant. All statistical analyses were carried out using SAS version 9.1.3 (SAS Institute, Cary, NC, USA).
Results
Demographiccharacteristics
Table 1 summarizes characteristics of patients included. A total of 2,905 patients were interviewed. The mean age of the interviewed patients was 66.98 ± 11.55 years. The number of men and women were 1,530 (52.67%) and 1,375 (47.33%) respectively. The number of patients who had a drinking history and smoking history is much more than the number of ones who didn’t. The proportion of diabetes, hyperlipidemia and hypertension accounted for 26.73%, 12.63% and 60.54% respectively. Additionally, weight, height, marriage state, anticoagulant treatment and NIHSS score are presented in Table 1.
Table 1.
Demographic characteristics of patients with stroke
| variables | Mean (SD), n (%) | |
|---|---|---|
| Age (yrs), Mean (SD) | 66.98 (11.55) | |
| Gender, n (%) | ||
| Male | 1530 | 52.67% |
| Female | 1375 | 47.33% |
| Drinking history, n (%) | ||
| No | 1041 | 35.91% |
| Yes | 1858 | 64.09% |
| Smoking history, n (%) | ||
| No | 862 | 29.74% |
| Yes | 2036 | 70.26% |
| Weight (kg), Mean (SD) | 57.05 (9.62) | |
| Height (cm), Mean (SD) | 157.92 (8.50) | |
| Marriage | ||
| Single | 62 | 2.16% |
| Married | 2049 | 71.37% |
| Divorce | 62 | 2.16% |
| Bereavement | 698 | 24.31% |
| Diabetes | ||
| No | 2113 | 73.27% |
| Yes | 771 | 26.73% |
| Hyperlipidemia | ||
| No | 2498 | 87.37% |
| Yes | 361 | 12.63% |
| Hypertension | ||
| No | 1140 | 39.46% |
| Yes | 1749 | 60.54% |
| Anticoagulant treatment | ||
| No | 1913 | 67.86% |
| Yes | 906 | 32.14% |
| NIHSS score | 4.32 (3.78) | |
SD: standard deviation.
Factor analysis
Figure 1 shows the eigenvalue from scree plot. The diamond dots are from actual values, making a classical scree plot. The number of diamond dots, which are “eigenvalues > 1”, were fourteen. Therefore fourteen factors were derived from “eigenvalues > 1” rule.
Figure 1.
Scree plot of eigenvalues for factor retention.
Table 2 displays a sum of squares according to the number of factors. The fourteen factors explained 56.28% of the total variance. Varimax rotation with maximum likelihood method was used to recompute these loadings on multiple factors. The results are shown in Table 3. There was no item loaded on more than one factors. Strong pulse, yellow fur, overweight, reddened complexion, insomnia due to vexation and slow pulse had a negative loading: -0.73 from factor 3, -0.85 from factor 8, -0.73 from factor 10, -0.54 from factor 11, -0.78 from factor 12 and -0.68 from factor 14 respectively. For instance, theoretically it may mean that increase in strong pulse correlates with decrease in factor 3 problem.
Table 2.
Sum of Squares of Loading, Proportion of Variance, and Cumulative Variance Explained by the Loading
| Factor 1 | Factor 2 | Factor 3 | Factor 4 | Factor 5 | Factor 6 | Factor 7 | Factor 8 | Factor 9 | Factor 10 | Factor 11 | Factor 12 | Factor 13 | Factor 14 | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SS loading | 4.17552 | 3.10092 | 2.53973 | 1.84787 | 1.83053 | 1.68017 | 1.4597 | 1.38269 | 1.30433 | 1.16641 | 1.14747 | 1.08228 | 1.04553 | 1.00046 |
| Proportion variance | 0.0949 | 0.0705 | 0.0577 | 0.042 | 0.0416 | 0.0382 | 0.0332 | 0.0314 | 0.0296 | 0.0265 | 0.0261 | 0.0246 | 0.0238 | 0.0227 |
| Cumulative variance | 0.0949 | 0.1654 | 0.2231 | 0.2651 | 0.3067 | 0.3449 | 0.3781 | 0.4095 | 0.4391 | 0.4656 | 0.4917 | 0.5163 | 0.5401 | 0.5628 |
SS, sum of squares.
Table 3.
Mean and standard deviation (SD) and standardized scoring coefficients in every variable
| Variables | Mean ± SD | Factor 1 | Factor 2 | Factor 3 | Factor 4 | Factor 5 | Factor 6 | Factor 7 | Factor 8 | Factor 9 | Factor 10 | Factor 11 | Factor 12 | Factor 13 | Factor 14 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mirror tongue | 0.23 ± 0.53 | 0.281 | -0.026 | -0.009 | 0.018 | 0.018 | -0.016 | -0.105 | 0.010 | 0.002 | 0.051 | 0.068 | 0.024 | 0.003 | -0.005 |
| Underweight-Thin | 0.41 ± 0.76 | 0.286 | 0.025 | -0.014 | 0.115 | -0.025 | -0.097 | -0.043 | 0.026 | -0.091 | 0.107 | 0.070 | -0.021 | -0.056 | 0.008 |
| Red tongue | 0.73 ± 0.97 | 0.323 | 0.003 | -0.002 | -0.027 | -0.308 | -0.034 | 0.022 | 0.022 | -0.093 | 0.004 | -0.028 | 0.016 | 0.056 | -0.068 |
| Pale face and red zygomatic site | 0.34 ± 0.69 | 0.248 | -0.022 | 0.047 | -0.030 | -0.046 | 0.016 | 0.015 | 0.072 | 0.027 | 0.020 | -0.012 | 0.019 | -0.067 | 0.028 |
| Look powerless & lazy | 1.55 ± 0.63 | 0.017 | 0.411 | -0.051 | -0.008 | -0.038 | -0.006 | -0.034 | -0.007 | -0.078 | -0.022 | -0.012 | -0.032 | -0.060 | 0.021 |
| Feel powerless & lazy | 1.54 ± 0.66 | -0.045 | 0.364 | -0.093 | -0.015 | -0.058 | 0.018 | -0.026 | 0.025 | 0.041 | -0.059 | -0.053 | 0.039 | 0.007 | 0.020 |
| Reluctance to speak | 1.32 ± 0.58 | 0.028 | 0.355 | -0.051 | 0.007 | 0.004 | 0.029 | 0.058 | -0.013 | -0.129 | 0.050 | 0.032 | -0.039 | -0.042 | 0.002 |
| Weak pulse | 0.76 ± 0.95 | 0.041 | -0.029 | 0.369 | -0.055 | 0.077 | 0.068 | 0.080 | -0.025 | -0.021 | 0.026 | 0.025 | 0.011 | -0.020 | -0.047 |
| Fine pulse | 1.19 ± 0.48 | -0.001 | -0.039 | 0.415 | 0.050 | 0.007 | -0.061 | 0.075 | -0.003 | -0.049 | -0.005 | 0.020 | -0.024 | 0.017 | 0.226 |
| Strong pulse | 0.94 ± 1 | 0.069 | 0.102 | -0.398 | 0.039 | 0.106 | -0.025 | -0.038 | 0.020 | -0.125 | 0.029 | -0.012 | -0.020 | 0.057 | 0.072 |
| Vexing heat in the extremities | 1.01 ± 0.46 | 0.021 | -0.018 | 0.001 | 0.397 | 0.055 | 0.102 | -0.041 | 0.009 | -0.076 | 0.055 | 0.035 | 0.036 | -0.086 | 0.022 |
| Heat in the palms and soles | 1.02 ± 0.47 | 0.015 | -0.009 | -0.005 | 0.389 | 0.011 | 0.160 | -0.020 | -0.006 | -0.107 | -0.006 | 0.035 | 0.008 | -0.087 | -0.097 |
| Aphtha or sore tongue | 0.98 ± 0.41 | 0.029 | -0.021 | -0.025 | 0.308 | -0.095 | -0.105 | -0.032 | 0.022 | 0.129 | 0.025 | -0.003 | 0.049 | 0.056 | -0.091 |
| Pale tongue | 0.62 ± 0.91 | -0.058 | -0.003 | -0.042 | 0.068 | 0.419 | 0.001 | 0.048 | 0.050 | -0.004 | 0.175 | 0.021 | -0.006 | -0.069 | -0.038 |
| Teeth-marked tongue | 0.46 ± 0.77 | -0.052 | -0.062 | 0.039 | -0.059 | 0.375 | 0.038 | -0.006 | -0.025 | -0.130 | -0.079 | 0.026 | -0.027 | 0.154 | 0.087 |
| Heat vexation and aversion to heat | 1.5 ± 0.66 | -0.081 | -0.002 | -0.020 | 0.053 | 0.083 | 0.389 | 0.021 | -0.006 | -0.082 | 0.025 | -0.019 | -0.017 | 0.032 | 0.013 |
| Afternoon tidal fever | 1.08 ± 0.36 | 0.013 | 0.012 | -0.009 | 0.060 | -0.017 | 0.329 | -0.151 | -0.029 | 0.076 | -0.047 | 0.086 | -0.002 | -0.059 | 0.007 |
| Thick fur | 1.01 ± 1.02 | -0.082 | -0.011 | 0.015 | -0.050 | 0.023 | 0.026 | 0.448 | -0.063 | 0.011 | -0.032 | -0.064 | -0.004 | -0.061 | -0.055 |
| Fetid mouth odor | 1.19 ± 0.57 | 0.008 | -0.007 | 0.099 | 0.098 | -0.091 | -0.092 | 0.410 | 0.111 | -0.066 | 0.089 | 0.051 | -0.029 | 0.083 | 0.062 |
| White fur | 1.15 ± 1.02 | 0.039 | -0.012 | -0.038 | -0.014 | 0.028 | 0.037 | 0.134 | 0.562 | -0.015 | -0.022 | -0.032 | 0.021 | 0.010 | -0.021 |
| Yellow fur | 0.75 ± 0.98 | -0.024 | -0.005 | 0.002 | -0.007 | 0.076 | -0.010 | 0.108 | -0.535 | 0.033 | -0.007 | 0.016 | 0.008 | -0.064 | -0.044 |
| Headache accompanied by hot flush | 0.31 ± 0.56 | -0.053 | -0.045 | 0.016 | -0.013 | -0.092 | -0.054 | -0.006 | 0.027 | 0.439 | 0.041 | -0.067 | -0.053 | 0.012 | 0.018 |
| Dizziness with nausea | 1.15 ± 0.46 | -0.084 | -0.080 | 0.046 | -0.018 | 0.069 | 0.056 | -0.034 | -0.051 | 0.382 | -0.083 | 0.105 | 0.133 | 0.055 | 0.112 |
| Red eyes | 1.53 ± 0.58 | -0.010 | -0.036 | -0.001 | -0.030 | 0.093 | 0.018 | 0.088 | -0.029 | 0.086 | 0.530 | 0.009 | 0.029 | 0.010 | 0.009 |
| Overweight-thick | 0.6 ± 0.91 | -0.090 | -0.008 | -0.010 | -0.059 | 0.009 | 0.111 | 0.044 | -0.010 | 0.067 | -0.514 | -0.050 | 0.033 | -0.023 | -0.010 |
| Sallow complexion | 0.77 ± 0.92 | 0.055 | -0.033 | -0.054 | 0.067 | 0.020 | -0.073 | -0.011 | -0.048 | -0.020 | 0.042 | 0.595 | -0.008 | 0.049 | -0.047 |
| Reddened complexion | 0.73 ± 0.98 | 0.087 | -0.088 | -0.056 | -0.050 | 0.018 | 0.117 | 0.140 | 0.038 | -0.025 | 0.055 | -0.345 | 0.066 | -0.041 | -0.042 |
| Like to lie in spite of well-sleeping | 1.02 ± 0.82 | 0.064 | 0.064 | -0.042 | 0.030 | 0.029 | -0.003 | -0.022 | 0.004 | 0.040 | -0.014 | -0.003 | 0.550 | 0.027 | 0.023 |
| Insomnia due to vexation | 0.54 ± 0.77 | 0.069 | 0.061 | -0.026 | -0.031 | 0.037 | 0.031 | 0.002 | -0.003 | 0.035 | -0.019 | -0.005 | -0.518 | -0.036 | -0.005 |
| Thirsty | 1.39 ± 0.64 | -0.052 | -0.079 | -0.029 | -0.001 | 0.095 | -0.012 | -0.022 | 0.006 | -0.025 | 0.044 | 0.001 | 0.063 | 0.560 | -0.070 |
| Dry mouth | 1.56 ± 0.68 | -0.012 | 0.017 | -0.001 | -0.037 | -0.057 | -0.057 | 0.014 | 0.062 | 0.032 | -0.035 | 0.009 | -0.014 | 0.513 | -0.010 |
| Rapid pulse | 0.82 ± 0.97 | 0.130 | 0.012 | 0.051 | -0.076 | 0.096 | 0.078 | -0.005 | 0.010 | -0.006 | 0.063 | 0.066 | 0.039 | -0.054 | 0.571 |
| Slow pulse | 0.53 ± 0.82 | 0.051 | 0.019 | -0.045 | 0.038 | 0.144 | -0.012 | 0.052 | -0.032 | -0.137 | 0.055 | 0.025 | -0.033 | 0.086 | -0.529 |
| Dry fur | 0.68 ± 0.88 | 0.084 | 0.004 | 0.041 | -0.126 | -0.044 | 0.018 | 0.202 | -0.012 | -0.097 | -0.136 | 0.005 | 0.004 | 0.161 | 0.000 |
| Slippery pulse | 1.46 ± 0.59 | -0.100 | 0.023 | -0.195 | -0.013 | -0.019 | -0.151 | 0.143 | 0.010 | 0.182 | -0.086 | 0.097 | 0.016 | -0.042 | 0.060 |
| Reversal cold of the extremities | 1.04 ± 0.48 | -0.081 | 0.003 | 0.112 | 0.198 | -0.037 | -0.278 | 0.063 | -0.009 | 0.158 | -0.053 | -0.030 | 0.013 | 0.100 | 0.080 |
| Surging pulse | 1.07 ± 0.36 | -0.114 | 0.075 | -0.050 | 0.199 | 0.154 | -0.120 | 0.123 | -0.059 | -0.132 | 0.036 | -0.066 | -0.106 | 0.062 | 0.231 |
| Pale complexion | 0.45 ± 0.78 | -0.068 | 0.142 | 0.048 | 0.004 | 0.246 | -0.097 | -0.090 | -0.077 | 0.057 | -0.062 | -0.251 | -0.070 | -0.032 | 0.033 |
| Wheezing in throat with sputum | 1.13 ± 0.62 | -0.029 | 0.067 | 0.041 | -0.009 | -0.229 | 0.043 | 0.242 | 0.098 | -0.079 | 0.119 | 0.019 | -0.100 | -0.008 | -0.052 |
| Night sweating | 1.2 ± 0.47 | -0.072 | 0.017 | 0.090 | -0.030 | -0.035 | 0.259 | 0.086 | 0.071 | 0.025 | -0.137 | -0.073 | -0.018 | 0.025 | 0.062 |
| Enlarged tongue | 0.46 ± 0.77 | 0.066 | -0.003 | -0.049 | -0.069 | -0.038 | -0.011 | 0.211 | 0.066 | 0.243 | 0.056 | -0.011 | 0.040 | -0.227 | -0.099 |
| Heat vexation in the chest | 0.51 ± 0.77 | 0.091 | 0.029 | -0.066 | -0.016 | -0.009 | 0.026 | -0.066 | -0.038 | 0.256 | 0.031 | 0.025 | -0.165 | -0.020 | -0.051 |
| Turbid urine | 1.12 ± 0.65 | 0.116 | -0.012 | -0.045 | -0.034 | -0.029 | 0.171 | -0.050 | -0.021 | 0.197 | 0.210 | 0.000 | 0.161 | -0.095 | -0.076 |
| Dark inferior palpebral | 1.17 ± 0.4 | 0.039 | -0.017 | 0.050 | -0.075 | -0.004 | 0.170 | 0.025 | 0.013 | -0.002 | 0.037 | 0.296 | 0.032 | -0.074 | 0.058 |
Bold character numbers signify factor loading higher than 0.5. SD, standard deviation.
The fourteen factors accounted for 9.49%, 7.05%, 5.77%, 4.20%, 4.16%, 3.82%, 3.32%, 3.14%, 2.96%, 2.65%, 2.61%, 2.46%, 2.38% and 2.27% of the total variance respectively. Each of factors has some items ranged from 2 to 4. Description of items according to each factor was as follows: Factor 1-mirror tongue, underweight, red tongue, pale face and red zygomatic site; Factor 2-look powerless & lazy, feel powerless & lazy, reluctance to speak; Factor 3-weak pulse, fine pulse, strong pulse; Factor 4-vexing heat in the extremities, heat in the palms and soles, aphtha or sore tongue; Factor 5-pale tongue, teeth-marked tongue; Factor 6-heat vexation and aversion to heat, afternoon tidal fever; Factor 7-thick fur, fetid mouth odor; Factor 8-white fur, yellow fur; Factor 9-headache accompanied by hot flush, dizziness with nausea; Factor 10-red eyes, overweight; Factor 11-sallow complexion, reddened complexion; Factor 12-ike to lie in spite of well-sleeping, insomnia due to vexation; Factor 13-thirsty, dry mouth; Factor 14-rapid pulse, slow pulse. However, there are 11 items which don’t belong to any factor: dry fur, slippery pulse, reversal cold of the extremities, surging pulse, pale complexion, wheezing in throat with sputum, night sweating, enlarged tongue, heat vexation in the chest, turbid urine and dark inferior palpebral.
Table 4 shows how the frequency, percentage and the p-value of Chi-square test between items and 4 patterns (Qi deficiency, Dampness-phlegm, Yin deficiency, Fire-heat) was related. In addition, the dominant pattern of each of items and each of factors was manifested.
Table 4.
Decision of dominant pattern
| Factor | Variables | P-value | Qi deficiency (630) | Dampnessphlegm (1037) | Yin deficiency (407) | Fire-heat (831) | Total (2905) | Dominant Pattern | |
|---|---|---|---|---|---|---|---|---|---|
| Factor 1 | Mirror tongue | <.0001 | 17 | 9 | 60 | 28 | 114 | Y | Y |
| 2.7 | 0.87 | 14.74 | 3.37 | ||||||
| Underweight-Thin | 0.0003 | 85 | 64 | 94 | 123 | 366 | Y | ||
| 13.49 | 6.17 | 23.1 | 14.8 | ||||||
| Red tongue | 0.8767 | 109 | 203 | 194 | 400 | 906 | FY | ||
| 17.3 | 19.58 | 47.67 | 48.13 | ||||||
| Pale face and red zygomatic site | <.0001 | 30 | 62 | 138 | 85 | 315 | Y | ||
| 4.76 | 5.98 | 33.91 | 10.23 | ||||||
| Factor 2 | Look powerless & lazy | <.0001 | 473 | 413 | 226 | 263 | 1375 | Q | Q |
| 75.08 | 39.83 | 55.53 | 31.65 | ||||||
| Feel powerless & lazy | <.0001 | 419 | 430 | 211 | 287 | 1347 | Q | ||
| 66.51 | 41.47 | 51.84 | 34.54 | ||||||
| Reluctance to speak | <.0001 | 308 | 234 | 117 | 154 | 813 | Q | ||
| 48.89 | 22.57 | 28.75 | 18.53 | ||||||
| Factor 3 | Weak pulse | <.0001 | 380 | 232 | 151 | 110 | 873 | Q | QY |
| 60.32 | 22.37 | 37.1 | 13.24 | ||||||
| Fine pulse | 0.4587 | 256 | 99 | 156 | 54 | 565 | QY | ||
| 40.63 | 9.55 | 38.33 | 6.5 | ||||||
| Strong pulse* | <.0001 | 110 | 420 | 100 | 516 | 1146 | F | F | |
| 17.46 | 40.5 | 24.57 | 62.09 | ||||||
| Factor 4 | Vexing heat in the extremities | 0.0008 | 30 | 98 | 30 | 120 | 278 | F | FY |
| 4.76 | 9.45 | 7.37 | 14.44 | ||||||
| Heat in the palms and soles | 0.8841 | 26 | 87 | 58 | 121 | 292 | FY | ||
| 4.13 | 8.39 | 14.25 | 14.56 | ||||||
| Aphtha or sore tongue | 0.5116 | 19 | 56 | 30 | 53 | 158 | FY | ||
| 3.02 | 5.4 | 7.37 | 6.38 | ||||||
| Factor 5 | Pale tongue | 0.1505 | 227 | 338 | 59 | 112 | 736 | DQ | DQ |
| 36.03 | 32.59 | 14.5 | 13.48 | ||||||
| Teeth-marked tongue | 0.0269 | 135 | 177 | 37 | 84 | 433 | DQ | ||
| 21.43 | 17.07 | 9.09 | 10.11 | ||||||
| Factor 6 | Heat vexation and aversion to heat | <.0001 | 211 | 383 | 176 | 476 | 1246 | F | FY |
| 33.49 | 36.93 | 43.24 | 57.28 | ||||||
| Afternoon tidal fever | <.0001 | 39 | 60 | 73 | 82 | 254 | Y | ||
| 6.19 | 5.79 | 17.94 | 9.87 | ||||||
| Factor 7 | Thick fur | 0.9655 | 149 | 469 | 87 | 375 | 1080 | DF | DF |
| 23.65 | 45.23 | 21.38 | 45.13 | ||||||
| Fetid mouth odor | 0.0210 | 84 | 234 | 63 | 226 | 607 | DF | ||
| 13.33 | 22.57 | 15.48 | 27.2 | ||||||
| Factor 8 | White fur | 0.2816 | 377 | 648 | 165 | 320 | 1510 | DQ | DQ |
| 59.84 | 62.49 | 40.54 | 38.51 | ||||||
| Yellow fur* | <.0001 | 106 | 300 | 95 | 381 | 882 | F | F | |
| 16.83 | 28.93 | 23.34 | 45.85 | ||||||
| Factor 9 | Headache accompanied by hot flush | 0.3729 | 21 | 21 | 19 | 49 | 110 | FY | Exclusion |
| 3.33 | 2.03 | 4.67 | 5.9 | ||||||
| Dizziness with nausea | 0.4787 | 89 | 197 | 64 | 115 | 465 | DY | ||
| 14.13 | 19 | 15.72 | 13.84 | ||||||
| Factor 10 | Red eyes | 0.0007 | 367 | 500 | 196 | 410 | 1473 | Q | Q |
| 58.25 | 48.22 | 48.16 | 49.34 | ||||||
| Overweight-Thick* | <.0001 | 72 | 347 | 52 | 190 | 661 | D | D | |
| 11.43 | 33.46 | 12.78 | 22.86 | ||||||
| Factor 11 | Sallow complexion | <.0001 | 147 | 538 | 83 | 117 | 885 | D | D |
| 23.33 | 51.88 | 20.39 | 14.08 | ||||||
| Reddened complexion* | <.0001 | 63 | 186 | 97 | 527 | 873 | F | F | |
| 10 | 17.94 | 23.83 | 63.42 | ||||||
| Factor 12 | Like to lie in spite of well-sleeping | 0.0006 | 230 | 216 | 107 | 151 | 704 | Q | Q |
| 36.51 | 20.83 | 26.29 | 18.17 | ||||||
| Insomnia due to vexation* | 0.1595 | 40 | 91 | 60 | 149 | 340 | FY | FY | |
| 6.35 | 8.78 | 14.74 | 17.93 | ||||||
| Factor 13 | Thirsty | 0.3053 | 167 | 288 | 159 | 350 | 964 | FY | FY |
| 26.51 | 27.77 | 39.07 | 42.12 | ||||||
| Dry mouth | <.0001 | 292 | 431 | 260 | 417 | 1400 | Y | ||
| 46.35 | 41.56 | 63.88 | 50.18 | ||||||
| Factor 14 | Rapid pulse | 0.2264 | 115 | 322 | 165 | 367 | 969 | FY | FY |
| 18.25 | 31.05 | 40.54 | 44.16 | ||||||
| Slow pulse* | <.0001 | 198 | 199 | 51 | 75 | 523 | Q | Q | |
| 31.43 | 19.19 | 12.53 | 9.03 | ||||||
| Non-groupable Items | Dry fur | 89 | 155 | 131 | 210 | 585 | |||
| 14.13 | 14.95 | 32.19 | 25.27 | ||||||
| Slippery pulse | 135 | 746 | 97 | 323 | 1301 | ||||
| 21.43 | 71.94 | 23.83 | 38.87 | ||||||
| Reversal cold of the extremities | 109 | 123 | 58 | 62 | 352 | ||||
| 17.3 | 11.86 | 14.25 | 7.46 | ||||||
| Surging pulse | 17 | 61 | 14 | 154 | 246 | ||||
| 2.7 | 5.88 | 3.44 | 18.53 | ||||||
| Pale complexion | 272 | 80 | 40 | 37 | 429 | ||||
| 43.17 | 7.71 | 9.83 | 4.45 | ||||||
| Wheezing in throat with sputum | 88 | 237 | 79 | 180 | 584 | ||||
| 13.97 | 22.85 | 19.41 | 21.66 | ||||||
| Night sweating | 94 | 141 | 102 | 156 | 493 | ||||
| 14.92 | 13.6 | 25.06 | 18.77 | ||||||
| Enlarged tongue | 98 | 219 | 41 | 102 | 460 | ||||
| 15.56 | 21.12 | 10.07 | 12.27 | ||||||
| Heat vexation in the chest | 56 | 96 | 65 | 136 | 353 | ||||
| 8.89 | 9.26 | 15.97 | 16.37 | ||||||
| Turbid urine | 129 | 210 | 96 | 208 | 643 | ||||
| 20.48 | 20.25 | 23.59 | 25.03 | ||||||
| Dark inferior palpebral | 99 | 225 | 52 | 86 | 462 | ||||
| 15.71 | 21.7 | 12.78 | 10.35 | ||||||
indicates items which had a negative loading.
Bold character numbers signify that P-values were calculated by chi-square test between high rank two patterns for each item is lower than 0.01. Q: Qi deficiency, D: Dampness-phlegm, Y: Yin deficiency, F: Fire-heat, DY: Dampness-phlegm and Yin deficiency, QY: Qi deficiency and Yin deficiency, FY: Fire-heat and Yin deficiency, DF: Dampness-phlegm and Fire-heat, DQ: Dampness-phlegm and Qi deficiency.
Figure 2 displays dominant patterns for each factor in diagram form. Factor 10-1 and Factor 11 belong to Dampness-phlegm pattern, Factor 7 belongs to Dampness-phlegm + Fire-heat pattern, Factor 5 and Factor 8 belong to Dampness-phlegm + Qi deficiency. In addition, Fire-heat pattern include Factor 3-1, Factor 8-1, Factor 11-1 that are totally negative loadings, and Fire-heat + Yin deficiency include Factor 4, Factor 6, Factor 12-1, Factor 13, Factor 14. The only factor which belongs to Yin deficiency is Factor 1. Factor 3 belongs to Yin deficiency + Qi deficiency. Qi deficiency includes Factor 2, Factor 10, Factor 12, Factor 14-1. However, Factor 9 did not belong to any factor.
Figure 2.
Classification of factors into each pattern.
Discussion
Of the 44 tested items (symptoms and signs) in 2905 patients with stroke, 14 underlying factors were identified and distributed as “Yin deficiency”, “Qi deficiency” and “Fire-heat”, “Dampness-phlegm”, “Dampness-phlegm + Fire-heat”, “Dampness-phlegm + Qi deficiency”, “Fire-heat + Yin deficiency”, “Yin deficiency + Qi deficiency”. Each of four patterns was defined by World Health Organization as follows [26]: “Qi deficiency” is a pattern leading to decreased visceral functions and lowered body resistance. “Dampness-phlegm” is a pattern due to accumulation of dampness phlegm in the lung, marked by cough with profuse expectoration, heaviness sensation of the limbs, feeling of stuffiness in the chest, reduced food intake, stickiness of the mouth, white slimy tongue coating and slippery pulse. “Yin deficiency” is a pattern resulting from deficiency of yin fluid and essence, incapable of restraining yang and usually manifested by emaciation, dizziness, tinnitus, dryness of the mouth and throat, constipation, dark-colored urine, afternoon tidal fever, malar flush, night sweating, reddened tongue with scanty coating and rapid fine pulse. “Fire-heat” is a pattern of heat and fire, either contracted externally or engendered internally.
Because there is no overlapped area between Dampness-phlegm and Yin deficiency, and between Qi deficiency and Fire-heat, it could be interpreted that their relation is mutually exclusive in terms of pathophysiology. However, Dampness-phlegm is partly overlapped with Qi deficiency and Fire-heat considering each of areas such as factor 5, 8 and factor 7. Similarly Yin deficiency is partly associated with Qi deficiency and Fire-heat regarding each of areas such as factor 3 and factor 4, factor 6, factor 13, factor 14.
Some items of the heat condition such as red tongue, heat in the palms and soles, aphtha or sore tongue, headache accompanied by hot flush, insomnia due to vexation, thirsty and rapid pulse were expressed as Yin deficiency + Fire-heat within the framework of dominant items. Although the pathological causes and their treatments of Yin deficiency and Fire-heat are so different each other, external symptoms and signs of Yin deficiency and Fire-heat are similarly expressed as heat condition, so it is thought that TKM doctors have had difficulties to identify the difference of external expressions between two patterns. Because these difficulties were reflected to TKM doctors clinically, it was supposed that the domain of Yin deficiency + Fire-heat including factor 4, factor 6, factor 13 and factor 14 were generated. Therefore, it was recommended that clinically exclusive factors that represent Fire-heat or Yin deficiency are requisite to draw a sharp line between Fire-heat and Yin deficiency.
Factor 7 which has thick fur and fetid mouth odor were found out to belong to Dampness-phlegm + Fire-heat. In pathophysiology having congested the flow of Qi and Blood for a long time, Dampness-phlegm tends to generate heat and often be combined with heat for itself [27]. For this reason, it was thought that the overlapped area of Dampness-phlegm and Fire-heat exists. Therefore exclusive factors that represent Dampness-phlegm or Fire-heat are requisite to distinguish Dampness-phlegm from Fire-heat. Additionally heat-typed Taeeum constitution in Sasang Constitution Medicine which is originated from only Korea [28] would clinically be able to be recommended as representative type of Dampness-phlegm + Fireheat.
Factor 3 including weak pulse and fine pulse were expressed as Qi deficiency + Yin deficiency. Pulse indicators from Yin deficiency or Qi deficiency have in common in that they all belong to Deficiency pattern. However, the differentiation between Qi which is power to boost pulse and Yin which is a volume of pulse is not quite easy clinically, indicating that exclusive clinical factors from Qi deficiency and Yin deficiency are essential for us to tell Qi deficiency from Yin deficiency.
Factor 5 including pale tongue and teeth-marked tongue, and Factor 8 which has white fur were expressed as Qi deficiency + Dampness-phlegm. Further consideration of the reasons why the area of Qi deficiency + Dampness-phlegm generates is below: Lowering the speed of metabolism; discharging waste from a body and charging nutrition into a body, Qi deficiency induces the formation of Dampness-phlegm in human body [12]. Therefore exclusive factors that represent Qi deficiency or Dampness-phlegm are requisite to differentiate Qi deficiency from Dampness-phlegm. In addition, cold-typed Taeeum constitution in Sasang Constitution Medicine [28] would clinically be able to be suggested as representative type of Dampness-phlegm + Qi deficiency.
Conclusion
Fourteen factors were detected among 44 items (symptoms and signs) for stroke. 11 items were non-groupable. Dominant patterns of each factor were manifested, constructing 8 classification areas: Yin deficiency, Qi deficiency, Fire-heat, Dampness-phlegm, Dampness-phlegm + Fire-heat, Dampness-phlegm + Qi deficiency,Yin deficiency + Fire-heat, Yin deficiency + Qi deficiency. Therefore, it was statistically investigated that there are inter-relation between Dampness-phlegm and Qi deficiency, between Dampness-phlegm and Fire-heat, between Fire-heat and Yin deficiency, and between Yin deficiency and Qi deficiency for stroke patients.
Acknowledgements
We are grateful to TKM doctors in the study from 11 oriental medical hospitals. This study was supported by a grant from the Korea Institute of Oriental Medicine (K13130 and K14281).
Disclosure of conflict of interest
None.
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