renin profiling in selection of initial antihypertensive drug

Conditions: Hypertension

Summary: the purpose of this research study is to determine whether a simple blood test measuring a hormone called renin can better determine which first drug would be most effective in controlling blood pressure, in comparison with the more traditional approach recommended by jnc7 (joint national committee on prevention, detection, evaluation, and treatment of high blood pressure).

hypothesis: that antihypertensive drug selection guided by activity of the renin angiotensin system will be superior to the strategy advocated in jnc 7 in achieving blood pressure control on monotherapy. background: the national heart, lung, and blood institute, through the joint national committee on the detection, treatment and control of hypertension (jnc 7) has recommended that most hypertensive patients begin therapy with a diuretic and sequentially add other classes of drugs until blood pressure is controlled. this approach appears to assume homogeneity in the mechanism by which bp is controlled in different patients. when this standardized strategy has been rigidly applied in clinical trials, a majority of patients generally require 2 or more agents to achieve blood pressure control. the pioneering work of laragh, sealey and their colleagues, widely confirmed by others, suggests instead that heterogeneity, in fact, characterizes patterns of blood pressure control in populations. this heterogeneity can be exposed through assessment of the activity of the renin angiotensin system (ras). specifically, volume and vasoconstriction determine blood pressure control. patients in whom volume predominates have suppressed ras, and, conversely, those in whom vasoconstriction predominates will have an activated ras. this can be simply and accurately determined by estimation of plasma renin activity (pra). it has been demonstrated that volume and vasoconstriction dependent hypertensive patients respond best to different drugs. by exploitation of the ras it is possible to provide rational therapy to each patients according to the mechanism by which blood pressure is controlled. the result is that appropriate therapy can be both more effective and more efficient. a specific system the laragh method has been designed to translate this physiologically based paradigm into a practical scheme or patient management. the purpose of this trial is to determine whether the laragh method will lead to better and more efficient blood pressure control in a general population of hypertensive patients than does the existing treatment strategy. the measure by which this hypothesis will be tested is percentage of hypertensive patients achieving blood pressure control on monotherapy. the significance of this trial is enormous for both individuals and society. some 50 million americans have hypertension and more than 25 million are currently in treatment. if the laragh method leads to more parsimonious and effective care, it will mean literally millions of individual patients will be spared the burden of unnecessary polypharmacy. moreover, the strain on health care costs associated with antihypertensive therapy will be redu

Eligibility criteria:
inclusion criteria: * males and females, 40 to 85 years of age * sustained systolic blood pressure between 140-180 mm hg * free of antihypertensive therapy at randomization for at least 4 weeks exclusion criteria: * ages \ 85 years * systolic blood pressure \>180 mm hg * blood pressure \>180/105 mm hg during the washout period * require antihypertensive agents for non-blood pressure indications * taking clonidine * on a beta-blocker drug and have known or suspected coronary artery disease * documented history of a heart attack, new onset of chest pain, or a coronary revascularization procedure within the past year, congestive heart failure * serious intercurrent illness * an active ulcer * have certain abnormal laboratory tests (elevated serum creatinine \>1.5 mg/dl, transaminase \> 2 times upper limit of normal or active liver disease), * hypersensitivity, allergy or have an intolerance to angiotensin ii receptor blockers (olmesartan), hydrochlorothiazide or amlodipine * mentally or legally unable to participate * have or are currently abusing alcohol, have abused drugs within the past 2 years * have been in another drug study in the past month.