resistant hypertension ( rh ) is defined when blood pressure remains high ( 140  90  mm  hg ) despite the use of three antihypertensive drug classes , including a diuretic and all prescribed in appropriate doses . in addition , the blood pressure controlled with the use of four or more medications is also considered rh . since these patients are under greater risk of presenting reversible and/or secondary causes of hypertension , they may be benefited by therapeutical approach for this diagnosis . it is important to know the difference between arterial hypertension ( ah ) , noncontrolled , and rh because the first one includes patients with low adherence to treatment or under inappropriate treatment . although its prevalence is not known for sure , it is a common clinical problem mainly due to the increase in life expectancy and the prevalence of chronic diseases such as diabetes , obesity , and kidney disease . according to the vi brazilian guidelines of ah , a brazilian study revealed that 59.1% of adult individuals are known to be hypertensive ; 67.3% of them were in treatment and only 26.1% had their blood pressure controlled ( 140  90  mm  hg ) . the same source also highlights that approximately 70.6% of deaths in 2007 in brazil were a result of cardiovascular disease and stroke which was the leading cause of death throughout the country . the ah is an important risk factor to the development of cardiovascular diseases and complications like cerebral vascular disease , coronary artery disease , heart failure , chronic kidney disease and peripheral vascular disease . in this context , it is estimated that 40% of the deaths by stroke are secondary to ah , as well as 25% of the deaths by coronary artery disease . the prognosis of patients with rh compared with patients with ah easily controlled was specifically evaluated in a recent study that demonstrated a higher cardiovascular risk among rh patients . however considering the significant reduction of the risk achieved with the effective treatment of ah , it is estimated that the effective control of rh promotes more significant benefits . it is a condition of multifactorial origin including genetic factors , lifestyle , use of certain drugs , and secondary causes , namely , obstructive sleep apnea , primary hyperaldosteronism , cushing 's syndrome , pheochromocytoma , renal parenchymal disease , renal artery stenosis , hypothyroidism , hyperthyroidism , acromegaly , hyperparathyroidism , and aortic coarctation . as has been shown in the literature and in medical practice , the rh is a relevant clinical problem found in the general population . given the risk that the maintenance of very high blood pressure represents for the development of diseases with significant mortality , it is assumed that the rh increases the susceptibility to these conditions , exposing the resistant hypertensives to a higher risk . furthermore , in this set of patients , we can identify a unique opportunity to prevent diseases associated with ah . however , the rh is currently little studied , is necessary and more knowledge of this clinical condition in order to improve the prognosis of its bearers . in addition , this is a study of resistant hypertension in a brazilian population that is an emergent country . these reports from this kind of population are uncommon in the literature .    in view of the assumptions made above , we proposed the analysis of specific causes of rh by using a standardized protocol in brazilian patients diagnosed in a center for evaluation and treatment of hypertension . the current study has monitored patients diagnosed with resistant hypertension treated by a university center for management of ah ( cha ) in botucatu medical school ( botucatu sp brazil ) . the management of these patients was conducted in an outpatient resistant hypertension clinic linked to cha , with application of a preformulated protocol which aimed at the identification of the causes of resistant hypertension in each patient through the management standardization ( figure 1 ) . the clinical protocol was composed of.ambulatory blood pressure monitoring ( abpm ) to the exclusion of pseudo - resistance by white coat effect.measurement of arterial stiffness by evaluation of aortic pulse wave velocity , central blood pressure measurement , and augmentation index.analysis of proteinuria urinary sediment and estimation of glomerular filtration rate to check the presence of parenchymatous renal disease.perform a clinical score of renovascular disease .verification of lifestyle factors : quantifying 24 hours urinary sodium ; calculation of body mass index ( bmi ) ; survey of hypertensive drugs use ; application of questionnaires of compliance ( morisky survey )   and obstructive sleep apnea ( berlin questionnaire ) [ 57 ] ; reminder of daily intake of alcohol and application of cage questionnaire [ 8 , 9].tsh and t4 dosage for search of hyper and hypothyroidism.determination of renin , aldosterone , and adrenal tomography for the investigation of primary aldosteronism when applicable . ambulatory blood pressure monitoring ( abpm ) to the exclusion of pseudo - resistance by white coat effect . measurement of arterial stiffness by evaluation of aortic pulse wave velocity , central blood pressure measurement , and augmentation index . analysis of proteinuria urinary sediment and estimation of glomerular filtration rate to check the presence of parenchymatous renal disease . verification of lifestyle factors : quantifying 24 hours urinary sodium ; calculation of body mass index ( bmi ) ; survey of hypertensive drugs use ; application of questionnaires of compliance ( morisky survey )   and obstructive sleep apnea ( berlin questionnaire ) [ 57 ] ; reminder of daily intake of alcohol and application of cage questionnaire [ 8 , 9 ] . determination of renin , aldosterone , and adrenal tomography for the investigation of primary aldosteronism when applicable . when identified the source of resistance , the necessary adjustments were made in the treatment of these patients aiming the at improvement of their condition . continuous variables of parametric distribution were expressed as mean  standard deviation and of nonparametric distribution in median ( first quartile and third quartile ) . eighty - six out of 209 patients from the outpatient hypertension clinic had resistant hypertension criteria , and 30 of them agreed to participate in this study . these thirty patients assessed were composed by seven male and twenty - three females , of whom six afrodescendants and twenty - four whites . the patients had a weight of 84  21.1  kg and 162  11.0  cm high , resulting in a bmi of 32  5.6  kg / m , 36 of them had a bmi over and 30  kg / m . the abpm systolic blood pressure ( sbp ) was 145  19.9  mm  hg , and diastolic blood pressure ( dbp ) was 87  13.4  mm  hg . the office sbp was 147  19.4  mm  hg , while the office dbp was 14.1  90  mm  hg . the sleep sbp was 139  22.4  mm  hg , and the sleep dbp was 11.8  79  mm  hg . the dip of sbp was 0.05  0.10 , and the dip of dbp was 0.11  0.10 during sleep . the percentage of nondipper patients was 31% dipper for sbp and was 44% dipper for dbp . used antihypertensive classes were calcium channel blockers in 64% ; converting enzyme inhibitors in 63% of patients ; angiotensin ii antagonist in 43% ; converting enzyme inhibitors or angiotensin ii antagonist or aliskiren in 96% ; beta - blockers in 36% ; alfa-2 adrenergic agonist in 36% ; spironolactone in 32% ; vasodilators in 11% ; aliskiren in 0.04% . after the beginning of this study , all the patients became adherent to the drug treatment , but only two of them had achieved an adequate blood pressure control . so , only two patients had pseudoresistance , which shows the representativeness of our approach . the application of berlin questionnaire pointed out a frequency of 44% patients with high risk of obstructive sleep apnea , and they were referred for expert evaluation . eighty percent of the patients presented either low compliance or high risk for sleep apnea . the application of cage questionnaire , referring to use of alcohol , obtained only a positive response . eight patients used hypertensive drugs four of these used chronically diclofenac , and one of them associated sibutramine with amfepramone . among patients who made use of hypertensive drugs , two patients presented a score higher than 10 points in the renovascular disease score ; these patients were referred to hemodynamic assessment . this patient was confirmed as having renal vascular disease in hemodynamic assessment .   among the laboratory tests performed , the 24 hours urinary was 204.41  98.79  meq/24  h. the excretion of sodium in 24 hours was above 150  meq/24  h in 53% of patients , and only one patient presented sodium excretion less than 100  meq/24  h.   the urinalysis pointed a proteinuria frequency of 7 in 30 patients . the 24 hours proteinuria was 0.35  0.66  g/24  h , one patient had proteinuria exceeding 2  g. this patient had all clinical criteria for diabetic nephropathy , and proteinuria remitted after tight control of blood pressure with intensive inhibition of renin angiotensin axis . the median of albuminuria was 20 ( 5523 ) , and the prevalence of albuminuria > 30  mg/24  h was 36% . all patients with albuminuria > 30  mg/24  h were nondipper or to sbp or to dbp . the aldosterone ( ng / dl)/renin ( ng / ml / h ) relationship was over 30 , and only one showed an abnormality in adrenal tomography ( hyperplasia ) . one patient had a reduction in serum potassium with normal aldosterone / renin relationship and responded satisfactorily to the use of amiloride . one patient presented a hematocrit of 68% and hemoglobin of 22  g / dl and was referred to hematological investigation , and an analysis of bone marrow confirm the diagnosis of polycythemia vera . so , seven patients had secondary hypertension of different causes ; 19 of the 23 remaining patients failed to reducing the blood pressure values by obstructive sleep apnea , high sodium intake , and a low compliance to drug treatment in the beginning of protocol . nevertheless only two patients of these achieved blood pressure target . only four patients could not find any obvious cause for resistant hypertension . all patients were evaluated as outpatients from the proposed protocol , and the appropriate therapeutics were implemented . resistant hypertension is a serious public health problem , and its treatment has sparked attention from experts in hypertension . these data bring the information about the causes of resistant hypertension in a hypertension clinic of an emergent country and are very uncommon in the literature . in this way furthermore , few studies used an algorithm for differential diagnosis in resistant hypertension highlighting the importance of our approach . . however , there are few studies that apply a standardized and broad algorithm and show the results as we do in this paper .   in this study , were identified seven patients with secondary resistant hypertension in 30 patients , two patients with primary hyperaldosteronism , renovascular disease in two , one with a renal parenchymatous disease , a liddle 's syndrome , and a polycythemia vera in one . almost all the 23 patients had some degree of noncompliance either to drug treatment or diet . however , after the beginning of the study , all patients became adherent and were using effectively at least 3 medications , but only two of them had achieved blood pressure control . thirty patients of 86 in the resistant hypertension criteria agreed to participate in the implementation of the protocol and accompaniment ; however , even with the limited number of patients , the current study allowed the evaluation of these individuals consistently . of the thirty patients studied , only seven have secondary causes of hypertension , showing a prevalence of 23.3% . the score for renovascular disease was 8.6 , which corresponds to an estimated frequency of approximately 9% according to the diagram of drastic study . this estimated prevalence is similar to the frequency of renovascular disease observed in this study ( 6.6% ) .    in the current study , of the thirty patients evaluated , 13 showed high risk for obstructive sleep apnea , which represents prevalence of 43.3% . in a recent study , calhoun and cols   suggested that there is a close relationship between the serum level of aldosterone and obstructive sleep apnea . according to these authors , elevated aldosterone levels both patients diagnosed with primary hyperaldosteronism presented a high risk for obstructive sleep apnea according to the berlin questionnaire . prospective studies have shown that the prevalence of primary hyperaldosteronism in patients with resistant hypertension reaches about 14%21% , which is too high in relation to the general hypertensive population . in our study , two patients had this diagnosis representing 6.6% of the studied sample .   in the set of patients studied , 68% did not have adequate compliance to drug treatment , highlighting that this is one of the main factors limiting the reduction of blood pressure in these patients . the lifestyle , associated with high sodium intake , a sedentary lifestyle , and obesity , is a factor that complicates even more the appropriate treatment of these patients . it is known that these drugs attenuate the antihypertensive effect of diuretics and converting enzyme inhibitors which may contribute to the resistance to treatment . surprisingly , the frequency of alcoholism was low , only one patient , which can be explained by a possible selection bias with a female predominance . it is due to the knowledge and the awareness of women in comparison with that of men to seek medical care for their problems , so we can speculate that alcoholics with resistant hypertension could be underdiagnosed . the data obtained suggest that among patients with resistant hypertension , there is a higher prevalence of secondary hypertension than that observed in general hypertensive ones and higher prevalence of sleep apnea . but there are a predominance of obesity , noncompliance either with diet or drugs and frequent use of hypertensive drugs . these latter factors are likely approachable at primary level health care , since that detailed anamnesis directed to the causes of resistant hypertension are applied .
resistant hypertension ( rh ) is characterized by blood pressure above 140  90  mm  hg , despite the use , in appropriate doses , of three antihypertensive drug classes , including a diuretic , or the need of four classes to control blood pressure . 
 resistant hypertension patients are under a greater risk of presenting secondary causes of hypertension and may be benefited by therapeutical approach for this diagnosis . however , the rh is currently little studied , and more knowledge of this clinical condition is necessary . 
 in addition , few studies had evaluated this issue in emergent countries . 
 therefore , we proposed the analysis of specific causes of rh by using a standardized protocol in brazilian patients diagnosed in a center for the evaluation and treatment of hypertension . 
 the management of these patients was conducted with the application of a preformulated protocol which aimed at the identification of the causes of resistant hypertension in each patient through management standardization . 
 the data obtained suggest that among patients with resistant hypertension there is a higher prevalence of secondary hypertension , than that observed in general hypertensive ones and a higher prevalence of sleep apnea as well . 
 but there are a predominance of obesity , noncompliance with diet , and frequent use of hypertensive drugs . 
 these latter factors are likely approachable at primary level health care , since that detailed anamneses directed to the causes of resistant hypertension are applied .