Response to “Effective” Plasma Renin Activity: A Derived Measure for Assessing Residual Plasma Renin Activity in Patients Taking Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers
We thank Sealey et al1 for their interest in our article and their comments. They point out that plasma renin activity (PRA) in our study likely overestimated the true activity of circulating PRA and, by calculating the effective PRA, our results would be predictable. Suppressed PRA is a marker of volume overload and can occur with high dietary salt ingestion. Theoretically, patients with suppressed PRA might achieve greater blood pressure (BP) reductions with a low-salt diet than patients with high PRA because of greater salt sensitivity.
Some investigators, but not all, have reported that low levels of renin predict the magnitude of BP reduction secondary to sodium depletion.2,3 As discussed in our report,4 Gavras et al5 demonstrated extreme BP reductions during a low-salt diet (10 mmol) and high doses of diuretics. They reported that a small percentage of rise in PRA was a better predictor of BP reduction than initial renin levels alone. In the same study, 1 patient in whom PRA at baseline was 70 ng/mL per hour had his BP decreased by 38/18 mm Hg after sodium reduction of 206 mmol. In another patient, PRA was 0.58 ng/mL per hour, and BP decreased by 21/1 mm Hg after a 404-mmol reduction in sodium. These individual results highlight that PRA is not the only determinant of BP response, and even patients with high renin levels can achieve large BP reductions with a low-salt diet.
In our study, the interpretation of PRA (or effective PRA) is affected by multiple antihypertensive medications. Nine of 12 participants were taking β-blockers, and 1 was taking a centrally acting α2-agonist at baseline. These medications are well known to suppress PRA. Furthermore, low PRA levels at baseline also support our previous findings that patients with resistant hypertension are characterized by aldosterone excess and intravascular volume expansion.6 However, BP reduction achieved in our study far exceeded our expectations, although all of the patients were receiving hydrochlorothiazide at the recommended dose, suggesting persistent fluid retention in spite of conventional diuretic treatment.
In conclusion, we agree that, in general, low PRA levels may predict BP response to salt intake but feel that, on an individual basis, benefit is not necessarily limited to patients with suppressed PRA. A treatment strategy on the basis of calculation of effective PRA to guide treatment is an exciting idea, but additional studies are needed to evaluate the efficacy of this approach.
Sources of Funding
This work was supported by National Heart, Lung, and Blood Institute grants HL075614 and SCCOR P50HL077100 received by D.A.C. and National Institutes of Health grant M01-RR00032 received by the Pittman General Clinical Research Center.
Sealey JE, Parra D, Rosenstein R, Laragh JH. “Effective” plasma renin activity: a derived measure for assessing residual plasma renin activity in patients taking angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Hypertension. 2010; 55: e16.
Pimenta E, Gaddam KK, Oparil S, Aban I, Husain S, Dell'Italia LJ, Calhoun DA. Effects of dietary sodium reduction on blood pressure in subjects with resistant hypertension: results from a randomized trial. Hypertension. 2009; 54: 475–481.
Gavras H, Waeber B, Kershaw GR, Liang CS, Textor SC, Brunner HR, Tifft CP, Gavras I. Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension. Hypertension. 1981; 3: 441–447.