Renin System Analysis: A Rational Method for the Diagnosis and Treatment of the Individual Patient with Hypertension

Hypertension afflicts 43 million people in the U.S. and is a leading risk factor for cardiovascular morbidity and mortality.1 Accordingly, blood pressure measurement is one of the most common reasons for a visit to the doctor's office. Nevertheless, there is considerable evidence that the current strategies used to diagnose and treat hypertension are inadequate. The recent National Health and Nutrition Examination Survey (NHANES III) reported that fewer than half of treated hypertensives are controlled and fewer than 30% of all hypertensives in the U.S. have their blood pressure 3.0 ng/mL/h).8,9 Therefore, these disorders are clearly distinguishable by the accompanying PRA, but not by the blood pressure or other clinical and laboratory features. Furthermore, the failure to appropriately suppress renin secretion in patients with essential hypertension has been associated with an increased risk of myocardial infarction.6 The benefits of measuring the PRA level are not limited to identification of curable forms of hypertension and assessment of cardiovascular risk. In essential hypertension, the PRA level is a marker for the primary pressor mechanism and, therefore, can often guide the selection of effective antihypertensive medication and enable monotherapy for most patients.7 In those with renin-dependent vasoconstriction, blood pressure can be lowered most effectively by antirenin and antiangiotensin therapies (eg, ACE inhibitors, β-blockers, Type 1 angiotensin II receptor blockers). By contrast, when PRA activity is low, blood pressure reduction is accomplished more effectively by sodium-volume reduction (eg, dietary sodium restriction, diuretics), α1-adrenergic receptor blockers, and calcium channel blockers. The benefits of measuring the PRA level for guiding drug selection are not limited to the previously untreated patient, but also encompass the patient who is refractory to antihypertensive treatment. For example, the reactive rise in renin-angiotensin-aldosterone during diuretic therapy attenuates the natriuretic and antihypertensive effects of thiazide-type diuretics. This accounts for the complementary effects of antirenin therapy in patients resistant to diuretic monotherapy.7 These salutary effects of PRA measurement were further reinforced by an analysis of 73 outpatients (39 men, 34 women) with hypertension resistant to treatment with one or more agents (systolic > 140, diastolic > 90) who were referred recently to the Hypertension Center at The New York Hospital-Cornell Medical Center (Table 1; Figure 1). At the initial visit, patients were being treated with 2.1 ± 0.1 antihypertensive medications. While on the medication regimen at the time of referral, their mean systolic pressure was 163 ± 3 mm Hg (> 170 mm Hg in 42%) and diastolic pressure 95 ± 1 mm Hg (> 100 mm Hg in 36%). The mean PRA at entry, obtained during treatment, was 5.0 ± 1.2 ng/mL/h). Blood Pressure and Drug Costs Fall During Renin-Based Treatment Blood Pressure and Drug Costs Fall During Renin-Based Treatment Patients were subsequently assessed using a renin-based analysis and treatment modified according to the principles described above. During a 1-year follow-up period, blood pressure improved when compared with the initial visit: systolic 140 ± 2 mm Hg (P < .0001; < 140 mm Hg in 60%) and diastolic 84 ± 1 mm Hg (P < .0001; < 90 mm Hg in 86%). Furthermore, the mean number of medications decreased to 1.5 ± 0.1 per patient (P < .0001; ≤ 2 drugs in 92%). Of note, there was a 20% reduction in total cost of medication per patient. In addition, secondary etiologies of hypertension were newly detected in 17.8% of this study population, with renovascular hypertension and primary aldosteronism each accounting for about half of those diagnoses. The results of this study support the larger body of data that reinforces the concept that antihypertensive treatment based on PRA measurement improves the accuracy of selecting antihypertensive medications, facilitates detection of secondary hypertension, and increases the efficacy of treating patients with resistant hypertension. In summary, the current strategies for antihypertensive therapy are inadequate and reflect the older view that hypertension is a homogenous disorder that can be treated with a single therapeutic recipe. Treatment efficacy can be improved by an analysis of the volume vasoconstriction mechanisms based on plasma renin profiling and has been confirmed by sequential use of single antihypertensive agents that have specific pharmacologic targets.