Chu Yuguang (褚瑜光), Hu Yuanhui (胡元會)

Department of Cardiology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing 100053, China

ABSTRACT OBJECTIVE: To explore the difference of body mass index (BMI) and insulin sensitivity index (ISI) in saltsensitive hypertension patients of different traditional Chinese medicine (TCM) syndrome types, so as to elucidate the effect of the distribution of each syndrome on the degree of insulin resistance in salt-sensitive hypertension patients. METHODS: A total of 131 patients with salt-sensitive hypertension were included in the study. Factor analysis and cluster analysis were used to study the characteristics of TCM viscera, syndrome elements and syndrome differentiation. Furthermore, the following parameters were observed and corresponding differences were analyzed, including BMI, waist circumference, abdominal circumference, neck circumference and insulin sensitivity index among groups of different TCM syndrome types. RESULTS: There were 131 cases of saltsensitive hypertension. The results of factor analysis showed that the total variance contribution of F1-5 common factors was 75.8%. According to the pattern differentiation of zang-fu organs, a basic theory of traditional Chinese medicine (TCM), the main zang-fu organs involved in the five common factors are: liver, spleen, and kidney.The main syndrome factors that had been extracted include yin deficiency, fire, qi stagnation, yang hyperactivity,dampness, phlegm, qi reversal, heat, retained fluid, essence deficiency, qi descending, qi deficiency, and yang deficiency. Among them, factor 1 accounted for 18.32%, factor 2 accounted for 21.37%, factor 3 accounted for 20.43%, factor 4 accounted for 20.61%, and factor 5 accounted for 22.14%. The proportion of zang-fu organs involvement was: 21.37% of the spleen, 17.56% of the kidney, 18.32% of the liver and spleen, and 42.75% of the spleen and kidney. Syndrome elements: yin deficiency 18.32%, phlegm-dampness 21.37%, qi stagnation 39.69%, qi deficiency 42.75%, retained fluid 20.61%, yang deficiency 60.31%, essence deficiency 17.56%, qi sinking 17.56%,heat 21.37%, qi reversal 21.37%. Results of cluster analysis: there were 3 categories when the distance variance was 20 - Category 1: Factor 1; Category 2: Factor 2; Category 3: Factor 3, Factor 4, Factor 5. Combined with the clinical practice of TCM, the classification based on TCM syndromes was：Category 1, yin deficiency and yang hyperactivity pattern (accounting for 18.32%); Category 2, excessive accumulation of phlegm-dampness (accounting for 21.37%); Category 3, spleen-kidney yang deficiency and pattern of water-rheum collecting internally (accounting for 60.31%), including 24 cases of yin-deficiency and yang-hyperactivity (YDYH), 28 cases of excessive phlegmdampness syndrome (EPDS), 79 cases of spleen and kidney yang-deficiency and fluid retention stagnating in the interior (SKFR). There was no difference in the distribution of age and sex among groups. In addition, no significant difference was found regarding BMI, waist circumference, abdominal circumference, neck circumference among groups of salt-sensitive hypertension of different TCM syndrome types. Meanwhile, ISI was significantly lower in cases of spleen and kidney yang-deficiency and fluid retention stagnating in the interior than in the other 2 groups,with statistical difference. CONCLUSION: Insulin resistance is the most serious in salt-sensitive hypertension patients with spleen and kidney yang-deficiency and fluid retention stagnating in the interior. Besides, obesity is not a critical factor in determining the distribution of TCM syndrome types in patients with salt-sensitive hypertension.

KEYWORDS: Salt-sensitive hypertension; Research of TCM Syndrome; Body mass index; Insulin sensitivity index

Salt-sensitive hypertension is a subgroup of essential hypertension. Previous studies[1,2]have shown that the body mass index (BMI) of patients with salt-sensitive hypertension is significantly higher than those of nonsalt-sensitive hypertension patients. Moreover, the blood pressure of patients will be reduced with the decrease of body weight if treated with metformin. Simultaneously,sodium metabolism disorder in salt-sensitive hypertension has a close relationship with insulin resistance[3,4]. Studies on traditional Chinese medicine (TCM) syndrome types of salt-sensitive hypertension suggest that these patients with phlegm-dampness syndrome are most susceptible to insulin resistance[3]. Therefore, the present study was carried out to explore the difference of BMI and insulin sensitivity index (ISI) in salt-sensitive hypertension patients with different TCM syndrome types.

OBJECT AND METHODS

Object of study

The object of the study was a total of 131 hospitalized patients with salt-sensitive hypertension in the Department of Cardiology of Guang'anmen Hospital from August 2015 to August 2016.

Diagnostic criteria

Diagnostic criteria for essential hypertension

According to the criteria mentioned in Guidelines for Chinese Hypertension (2010), systolic blood pressure140 mmHg and diastolic blood pressure90 mmHg were considered as hypertension under the premise of no administration of antihypertensive drugs[6].

Diagnostic criteria for salt-sensitive hypertension

The determination of salt-sensitive hypertension was performed via the modified Sullivan's acute oral saline loading method[7].

Diagnostic criteria for TCM syndrome types

Diagnostic criteria for TCM syndrome types referred to Diagnostics of Traditional Chinese Medicine[8],and Clinical Diagnosis and Treatment Term of TCM &Syndrome Part in State Standard of the People's Republic of China[9].

Inclusion criteria

Inclusion criteria: ① Conformed to the standard of Western medicine and traditional Chinese medicine for hypertension, and in accordance with the diagnostic criteria for salt-sensitive hypertension; ② Age16 years old and no limitation of gender; ③ Patients who agreed to provide signed informed consent in advance.

Exclusion criteria

Exclusion criteria: ① Patients with secondary hypertension; ② Patients who had previous history of cerebral hemorrhage, acute cerebral infarction, acute myocardial infarction, severe heart failure, severe trauma or major operations; ③ Patients who had severe liver damage, acute kidney injury (AKI), chronic kidney disease (CKD3-5 stage); ④ Psychiatric patients;⑤ Patients with malignant tumors; ⑥ Patients with tuberculosis and other infectious diseases.

Calculation of fasting insulin (FINS) and ISI

The determination of FINS was achieved by applying radioimmunoassay with a standard radioimmunoassay counter (GC1200, Zhongke Zhongjia Co. Ltd. China) to measure the level of fasting insulin.The radioimmunoassay kit was provided by Wuhan Booute Biotechnology Co. Ltd. (Wuhan, China). ISI = ln(1/fasting blood glucose*fasting insulin)[10].

Measurement

Measurement of BMI and waist circumference(WC), hips circumference (HC) abdominal circumference(AC), neck circumference (NC) was conducted according to the industry standard[11].

Statistical methods

SPSS 13.0 statistical software was used for data analysis. Measurement data were expressed as mean ±standard deviation (X ± SD), and categorical data were tested using chi-square test. P0.05 meant that the statistical difference was significant. The comparison of measurement data among multiple groups was performed via one-way analysis of variance. Syndrome research uses factor analysis and R-type system clustering for statistics.

RESULTS

Results of Study on the Distribution of TCM Syndromes in Patients with Salt-Sensitive Hypertension

Analysis results of TCM Syndrome Factors of Salt-Sensitive Hypertension

Basic Variable Information.

From the initial 131 scales of TCM clinical symptoms, after the elimination of low-frequency symptoms, 59 main symptoms remained and were analyzed.

Factor Analysis and Condition Selection

Factor analysis: single-variable descriptive analysis; correlation matrix: KMO and Bartlett sphericity test, significant level and coefficient;method: principal component analysis (PCA); analysis:correlation matrix, unrotated factor solution, scree plot; extraction: based on eigenvalues; maximum convergence iterations: 25; rotation method: varimax,output rotation diagram, and load diagram; factor score: regression.

Results of Factor Analysis KOM and Barlett sphericity test

The KMO was 0.93, which indicates that the data was very suitable for factor analysis; Bartlett sphericity test: P ＜ 0.01, which indicates that the factor analysis can be done.

Results of Factor Analysis Common Factor Information

According to the results of factor analysis, we selected the common factor with the eigenvalue greater than 0.8. The results showed that the cumulative contribution of the variances of F1-5 common factors contributed to 75.8%, which means that the five common factors can explain 75.8% of the total variance.See Table 1.

Table 1. The characteristic root of factor analysis and the common factor contribution rate of the total variance

Syndrome Analysis of Cluster Results

According to the theories of TCM and the definition of national standard basic syndromes, combined with the clinical practices of TCM, there are 3 categories of TCM syndromes. See Table 2.

General information of salt-sensitive hypertension patients with different TCM syndrome types

There were 131 cases of salt-sensitive hypertension,including 24 cases of yin-deficiency and yanghyperactivity, 28 cases of excessive phlegm-dampnesssyndrome, 79 cases of spleen and kidney yang-deficiency and fluid retention stagnating in the interior. There was no difference in the distribution of age and sex among groups. See Table 3.

Table 2. Clustering Collection of TCM Syndrome

Table 3. General information of salt-sensitive hypertension patients with different TCM syndrome types (X ± S)

Comparison of obesity index in salt-sensitive hypertension patients with different TCM syndrome types

There was no significant difference of BMI,waist circumference, hips circumference, abdominal circumference, neck circumference among groups of saltsensitive hypertension with different TCM syndrome types. See Table 4 and Figure 1.

Table 4. Obesity index in salt-sensitive hypertension patients with different TCM syndrome types (X±S)

Figure 1. Obesity index in salt-sensitive hypertension patients with different TCM syndrome types

Comparison of ISI in salt-sensitive hypertension patients with different TCM syndrome types

ISI was significantly lower in cases of spleen and kidney yang-deficiency and fluid retention stagnating in the interior than in the other 2 groups, with statisticaldifference. See Table5.

Table 5. Results of ISI in salt-sensitive hypertension patients with different TCM syndrome types (X ± S)

DISCUSSION

The perspective of salt-sensitive hypertension in TCM mainly focuses on the relationship between salty flavor and kidney. It is recorded in Plain Questions that "salty (flavor] enters the kidney". According to the "five ways of entrance", the salty flavor enters and nourishes the kidney. The nourishment of the acquired five-flavors is that underlies the functions of the kidney. The relatively insufficient salt intake will lead to the lack of nourishment of the kidney. Since the kidney is the root of the body, if the foundation is weak, people will manifest as lack of strength,anergia, flaccidity, headache, lethargy, which is similar to the symptoms of hyponatremia. As the old saying goes, too much water drowned the miller, too much of salty flavor will cause hyperactivity, which eventually leads to the depletion of kidney qi, kidney yang, and kidney essence. The manifestations are the insufficiency of kidney yang and the breakdown of qi transformation. As kidney governs water,the breakdown of qi transformation will lead to the occurrence of retained fluid. Kidney essence deficiency，hyperactivity of the liver-yang and waterrheum collecting internally are the main symptoms of salt-sensitive hypertension from the perspective of TCM[12]. Excessive accumulation of phlegmdampness is the main manifestation of salt-sensitive hypertension complicated with insulin resistance[13].

In the research of the level of obesity of different TCM syndromes of essential hypertension, most studies suggest that the level of obesity is most serious in patients with phlegm-dampness syndrome. However,the type and standard of TCM syndromes are actually not the same due to different clinical observations.For example, Shang Yangxiu[14]conducted a study by involving 333 EH patients, and 9 subgroups were divided according to TCM syndrome differentiation,corresponding results concerning the relationship between each syndrome and BMI indicated that BMI was highest in patients with the syndrome of phlegmblood stasis blocking and in those with the syndrome of deficiency of both qi and yin, with statistical difference. Furthermore, with the inclusion of 471 hypertension patients in the study conducted by Chen Guangliang[15], patients with excessive phlegmdampness (27%) accounted for the highest proportion of the overall cases, followed by overabundant liverfire type (20.9%) and yin-deficiency and yanghyperactivity (14.9%), and the lowest was yin-yang deficiency type (9.6%). The results showed that the level of BMI was highest in patients with excessive phlegm-dampness. At present, there are few studies focused on TCM syndromes and the level of obesity in salt-sensitive hypertension. In our study, no significant difference was found of BMI, waist circumference,abdominal circumference, neck circumference among groups of salt-sensitive hypertension with different TCM syndrome types, suggesting that obesity might not be an important factor in determining the distribution of TCM syndrome types in in salt-sensitive hypertension patients.

In prior studies of insulin resistance in saltsensitive hypertension patients, Wu Qifeng incorporated 84 hypertension patients and then divided 4 syndrome types of overabundant liver- fire type, yindeficiency and yang-hyperactivity type, excessive phlegm-dampness type and yin-yang deficiency type.Corresponding results revealed that the salt-sensitive ratio of phlegm dampness syndrome was highest in patients with excessive phlegm-dampness type among the above-mentioned types. Furthermore, the level of ISI was compared in each syndrome, and it was found that the excessive phlegm-dampness type had the lowest ISI, and the insulin resistance was the most serious. These findings proved that there was a strongest relationship between excessive phlegm dampness and insulin resistance in patients with saltsensitive hypertension. On the other hand, due to the highest proportion of salt-sensitive hypertension in excessive phlegm dampness type, it also illustrated the intimate relationship between salt-sensitive hypertension and insulin resistance.

In the study, there was obvious statistical difference that ISI was significantly lower in cases of spleen and kidney yang-deficiency and fluid retention stagnating in the interior than in the other 2 groups, suggesting the highest degree of insulin resistance in the former type of syndrome. It is well-known that insulin resistance is the main pathogenesis of type 2 diabetes, besides, spleen and kidney yang-deficiency type in TCM pathogenesis of diabetes is also one of the main syndromes in patients with longer course of diabetes. In the event of diabetic nephropathy, fluid retention stagnating in the interior is the main clinical syndrome. With respect to the above, we believed that this was an intrinsic connection of spleen and kidney yang-deficiency and fluid retention stagnating in the interior with insulin resistance in patients with saltsensitive hypertension.