The main result of the present study is that Zangfu patterns were strongly or moderately associated with clinical manifestations of TOD in subjects with hypertension. Moreover, clinical manifestations were at most (all r < 0.40) weakly associated with hemodynamic variables.
Relationship between Chinese medicine patterns and TOD in hypertension
The results of this study indicated that all Zangfu patterns were strongly (up to r = 0.718) or moderately associated with two or three target-organs due to hypertension by the amount of available information N%. These results were much less (up to r = 0.424) pronounced when association was tested with the explained information F% criterion. More interestingly, those results occurred in spite of the negligible similarity between theoretical descriptions in both ZFHD and TODD datasets. Altogether, these results indicate that the amount of information that explains a single pattern is directly proportional to the amount of information explained by the investigated target-organs for any quantity of manifestations in either clinical history or pattern. In other words, although patterns share no significant amount of manifestations with target-organs, the quantity of manifestations explained by a pattern is almost linearly proportional to the quantity of explained manifestations compatible with TOD in the same patient. The present study investigates such integrative relationship whereas other studies on morbidity of patterns in hypertension focused on descriptive statistics of patterns , therapeutic interventions [23–25] and proteomic analysis of dichotomous classes of patterns .
Chinese medicine pattern differentiation considers the presence or absence of manifestations in the exterior of the body, together with the individual constitutional characteristics, to differentiate the pattern inside the body, ie the internal organs and viscera. A pattern indicates the progress of a morbid condition at a certain phase, as well as the cause, nature, location, manifestation and prognosis of the condition. That is why different diseases may be associated with the same pattern and the same disease may be associated with different patterns [7–12]. The strength of this association is expected to vary with the similarity between descriptions of each pattern and disease (ie co-occurrence of manifestations)  and other factors such as relations to tissues, organs and systems functional interdependency, family history and environmental etiology .
In Chinese medicine, the amount of manifestations is a measure of the severity and progression of patterns , ie patterns under development are described by a small amount of manifestations (low N% values) while severe patterns usually presents with a large amount of manifestations (high N% values). The explained information criterion is based on the holistic approach that 'all manifestations must be interpreted collectively' [9, 54] and thus is more influenced by co-occurrence than N%, which explains the strong correlation found between patterns and TOD with N% but not with F%.
By contrast, in conventional medicine, subclinical findings of diseases must be assessed with clinical and laboratorial examinations. The presence of 'silent', asymptomatic TOD (eg left ventricle hypertrophy, carotid atherosclerosis, diminished glomerular filtration rate, increased serum creatinine and microalbuminuria) in subjects with hypertension is already an indicator of disease progression. Silent TOD is estimated to occur in in 61.3% (any TOD) of subjects with hypertension while 50.3% of the hypertensive patients presented a single silent TOD, 31.0% two TOD and 18.7% presented three or more . If left untreated, subclinical hypertension may lead to localized microvascular lesions (atherosclerosis) which can progress into diffuse (arteriosclerosis) lesions, affecting target-organs and producing various manifestations , ie silent TOD slowly progresses to symptomatic TOD. Because of the progression of structural damages, hypertension can be undiscovered for 10-20 years  and the overall prevalence of clinically manifested TOD can be as high as 95% for stroke (CVD), 89% for left ventricular hypertrophy (HD) and 95% for kidney failure (KD) . Although this study does not present data regarding silent TOD to guarantee that patients actually present any degree of TOD - in fact, for some manifestations is not quite necessary (eg stroke) - the collective results of this first study strongly indicate that the five Zangfu patterns commonly used for pattern differentiation in patients with hypertension are indeed related to hypertension-induced TOD. Further studies should focus on subclinical findings in hypertension and their relationship with symptomatic hypertensive patients and Chinese medicine patterns.
Frequency distribution of patterns and manifestations
The frequency distribution of patterns observed in this sample is in agreement with previously studies. Maklin et al.  reported that Kidney-yin deficiency and Liver-yang rising (shen yin xu gan yang shang yan) was the most prevalent pattern (47-63%), followed by obstruction of phlegm and dampness of Heart/Liver/Gallbladder (xin gan dan shi tan bi) (19-30%), Liver-fire blazing upwards (gan huo shang yan) (13-17%), qi and blood deficiency leading to Liver yang rising (qi xue xu gan yang shang yan) (2-6%) and Kidney-yin/yang deficiency (shen yin yang xu) (0-3%). Gu et al.  found stagnation of phlegm-dampness (zhi shi tan) to be the most prevalent pattern (27%), followed by hyperactivity of the Liver-yang (gan yang shang yan) (24%), deficiency of Heart/Kidney-Qi (xin shen qi xu) (10%), blood stasis obstructing the collaterals (luo xue yu bi) (9%), deficiency of yin and yang (yin yang xu) (8%) while other syndromes accounted for 21% of the sample. Why patterns related to Liver-yang and phlegm-dampness are the most prevalent is still unknown. Emotional states, family history and food habits play important roles in the etiology of these patterns and are considered as major risk factors to hypertension by both Chinese medicine [9, 11] and conventional medicine .
Association between manifestations, patterns, and hemodynamic data
High blood pressure levels should be symptomless; however, patients and physicians usually attribute symptoms to increased levels of blood pressure. The weak significant association between manifestations and blood pressure variables observed in this study were not held under adjustment for age, sex and BMI. These results agree with the physiologic knowledge on blood pressure control and with other epidemiologic reports according to which symptoms were not significantly correlated to hypertension [63, 64], patterns  or proved uncorrelated when adjusted to confounding variables  or awareness of hypertension . In the present study, association tests were performed with the entire sample of hypertensive subjects. It is possible that predominance of Kidney-yin deficiency and Liver-yang rising pattern lead to biased results. Further studies may search for such correlations with the sample divided into equally distributed subgroups regarding all identified patterns and subsample sizes.
Using manifestations to bridge the gap between Chinese medicine and conventional medicine
The present study regards the patient as the common element to both medical practices. Chinese medicine practitioners and physicians interpret clinical manifestations according to their medical training and may not rely on information provided by laboratories and medical imaging. Conventional medicine considers the manifestations of hypertension-induced TOD as consequences of progressive, structural lesions to arteries that progressively compromise blood flow to and cell metabolism of vital organs. Chinese medicine interprets the same manifestations as due to chronic, functional imbalances of organs and viscera that result in Zangfu deficiency states and obstruction or rebellion of qi, yin, yang or blood (xue). Risk factors for hypertension are quite identical in these two medical systems and stress the observed strong association between TOD with manifestations and Zangfu patterns.
Implications for proper antihypertensive agents selection
While current pharmacological treatment for hypertension is based on the level of SBP and DBP and the level of total cardiovascular risk , however, Chinese medicine diagnosis with disease subtyping may provide insights into optimization of classes of antihypertensive medications for TOD management. For instance, research suggests that specific agents work better in treating hypertension with particular patterns, eg calcium channel blockers for phlegmatic damp excess pattern and blood stasis; β-blockers for liver-yang rising; angiotensin converting enzyme inhibitors for yin-deficiency and yang-hyperactivity or combined liver-yin and kidney-yin deficiency . The therapeutic potential of several antihypertensive agents (diuretics, angiotensin converting enzyme inhibitors, angiotensin II receptor antagonists, β-blockers, calcium channel blockers and aldosterone antagonism) have been shown to also improve hypertension-induced TOD . However, the efficacy of antihypertensive agents, acupuncture and herbs as well as the effects of such interventions on TOD is yet to be determined.