Traditional Chinese Medicine Syndromes for Essential Hypertension: A Literature Analysis of 13,272 Patients

Background. To simplify traditional Chinese medicine syndrome differentiation and allow researchers to master syndrome differentiation for hypertension, this paper retrospectively studied the literature and analyzed syndrome elements corresponding to hypertension syndromes. Methods. Six databases including PubMed, EMBASE, Chinese Bio-Medical Literature Database, Chinese National Knowledge Infrastructure, Chinese Scientific Journal Database, and Wan-fang Data were searched from 1/January/2003 to 30/October/2013. We included all clinical literature testing hypertension syndromes and retrospectively studied the hypertension literature published from 2003 to 2013. Descriptive statistics calculated frequencies and percentages. Results. 13,272 patients with essential hypertension were included. Clinical features of hypertension could be attributed to 11 kinds of syndrome factors. Among them, seven syndrome factors were excess, while four syndrome factors were deficient. Syndrome targets were mainly in the liver and related to the kidney and spleen. There were 33 combination syndromes. Frequency of single-factor syndromes was 31.77% and frequency of two-factor syndromes was 62.26%. Conclusions. Excess syndrome factors of hypertension patients include yang hyperactivity, blood stasis, phlegm turbidity, internal dampness, and internal fire. Deficient syndrome factors of hypertension patients are yin deficiency and yang deficiency. Yin deficiency with yang hyperactivity, phlegm-dampness retention, and deficiency of both yin and yang were the three most common syndromes in clinical combination.

Syndrome differentiation is a diagnostic and treatment method used in TCM [27,28]. It plays an important role in the therapeutic process and affects the therapeutic result of certain diseases [29][30][31]. The syndrome is not only the basic unit of TCM theory and syndrome differentiation, but also the bridge to associating disease and formula [32][33][34][35]. TCM syndrome, which is different from a disease or symptoms, is the abstraction of a major pathogenesis. Syndromes are identified from a comprehensive analysis of all symptoms and signs (including tongue appearance and pulse feeling) from the four main diagnostic TCM methods: observation, listening, questioning, and pulse analyses [36][37][38][39][40]. However, syndromes are the product of speculation in TCM. Therefore, they depend on medical experience, academic origins, and other factors. Therefore, the concept of syndromes is vague and broad, which makes clinical application difficult. Syndrome elements, which are the minimum units of syndromes, contribute to simplifying syndrome differentiation and understanding TCM syndromes. Each element has specific symptoms.
To simplify TCM syndrome differentiation and enable researchers not familiar with Chinese medicine to master the laws of hypertension syndrome differentiation, this paper

Description of Included Literature.
After a primary search of the databases, 503 articles were screened. After reading the titles and abstracts, 398 articles were excluded the reasons included; retrospective study that did not match the included criteria of this review ( = 42) and duplicated titles ( = 356). The full texts of 83 articles  were retrieved, and 22 articles were excluded for the following reasons: participants not meeting the inclusion criteria ( = 11), duplicated data ( = 5), patients having other diseases ( = 5), and no data for extraction ( = 1). In the end, 83 articles  were included, and all trials were conducted in China ( Figure 1). The characteristics of included trials are listed in Table 1.
Overall, 13,272 patients with essential hypertension were included, with an average of 160 per trial, ranging from 23 to 703. Among them, 7075 were men, accounting for 53.3%, while 6197 were women, accounting for 46.7%. There was a wide range in patient age (18-92 years). Sources of cases included 24 provinces and the number of papers in each region is shown in Table 2.

Extraction of Syndrome Elements of EH.
According to the definition of syndrome elements and classification criteria, syndrome elements were obtained and classified from the literature as follows: blood stasis (qi stagnation and blood stasis, qi deficiency with blood stasis, kidney deficiency and blood stasis, stasis blocking channels, phlegm and blood stasis resistance winding); qi stagnation (liver qi stagnation, qi stagnation and blood stasis); phlegm (phlegm turbidity resistance, phlegm-dampness retention); internal fire (intense liver fire, internal harassment of phlegm-heat); internal dampness (spleen deficiency with dampness encumbrance, phlegm-damp retention); internal wind (internal stirring of liver wind, wind-yang interference); qi deficiency (dual deficiency of qi and yin, dual deficiency of qi and blood, and qi deficiency with blood stasis); yang hyperactivity (ascendant hyperactivity of liver yang, yin deficiency with yang hyperactivity); yin deficiency (yin deficiency with yang hyperactivity, liver-kidney yin deficiency, dual deficiency of qi and yin, and deficiency of both yin and yang); yang deficiency (kidney yang deficiency, deficiency of both yin and yang); blood deficiency (dual deficiency of qi and blood).  As a result, 13,272 cases of hypertension syndrome were classified as 11 syndrome element types, which cover all cases.

Targets of Syndrome Elements of EH.
The targets of syndrome elements are the disease locations of individual syndrome elements. Disease location of syndrome elements was confirmed according to the five zang-organs and six fuorgans, chi heng fu, and meridians.
Internal fire is the most common in the single factor group, while yin deficiency with yang hyperactivity is the most common in the two-factor group. From highest to lowest frequency in the two-factor group are phlegm-damp retention, deficiency of both yin and yang, Liver-kidney yin deficiency, dual deficiency of qi and yin, qi stagnation and blood stasis, and qi deficiency with blood stasis. The syndrome, yin deficiency and wind-phlegm, is the most common in the three-factor category. There were no fourfactor combinations that reached a frequency of greater than 1%.

Pathogenesis of Hypertension.
Syndrome elements are the expression of pathogenesis of a disease [36]. According to the statistical results of syndrome elements, pathogenesis of EH can be summarized as simultaneous insufficiency and excess. Deficiency syndrome included yin deficiency, yang deficiency, qi deficiency, and blood deficiency. Excess  syndrome included blood stasis, phlegm turbidity, qi stagnation, yang hyperactivity, internal fire, internal dampness, and internal wind. Among them, yin deficiency was the most common, followed by yang hyperactivity. Other elements, included in descending order, were phlegm turbidity, internal fire, internal dampness, yang deficiency, blood stasis, qi deficiency, and internal wind. The main disease location is the liver, which is closely related to the kidney and spleen.

Characteristics of Combined Syndrome Elements of EH.
The combined forms of syndrome elements of hypertension have certain characteristics according to the literature, summarized as follows. (1) The combined forms of syndrome elements of hypertension have three forms, single-factor, two-factor, and three-factor forms.
(2) Excess syndromes are more common than deficiency syndromes for singlefactor syndromes, with internal fire, yang hyperactivity, blood stasis, and phlegm turbidity as the main syndrome factors.
(3) Deficiency syndrome and excess syndrome was the most common two-factor syndrome, followed by excess syndrome and excess syndrome and deficiency syndrome and deficiency syndrome, respectively. (4) Syndrome of yin deficiency and wind-phlegm was the most common threefactor syndrome.
In summary, the syndrome elements of hypertension are limited and are combined into syndromes. Single and the combined syndrome elements of hypertension are the basis of syndrome differentiation for EH and the key to the standardization of this syndrome. In this paper, we retrospectively confirmed the validity and reliability of the theory of syndrome elements and the combined forms of syndrome elements of hypertension. This study can provide new ideas and methods for the treatment of hypertension by syndrome differentiation, and has laid a foundation for researching syndrome standardization of hypertension.