LAUSR

I n this article entitled ‘Plasma renin activity to plasma aldosterone concentration ratio correlates with nighttime and pulse pressures in essential hypertensive patients treated with angiotensin-converting enzyme inhibitors/AT1blockers’, Spannella et al. [1] summarize their conclusions referring to plasma renin activity (PRA)-to-plasma aldosterone concentration (PAC) ratio (RAR) as a potential ‘useful biomarker in the management of essential hypertensive patients treated with angiotensin converting enzyme inhibitors (ACE-I) or AT1 blockers (ARB)’. We acknowledge the authors’ significant contribution with their current well designed work to the clarification of the association of RAR with uncontrolled hypertension and pulse pressures. We would like tohighlight fewpoints thatmerit further attention. The ‘classic’ biomarker refers to a measurable parameter that can be used to fairly assess a particular disease state or the effects of treatment. However, in hypertensive patients, RAR may be affected by multiple factors, including age, sex, dietary sodium and potassium levels, time of day, posture, and lengthof time in that posture [2].Moreover, hypertension frequently coexists with diabetes, which is a common cause of hyporeninemic hypoaldosteronism [3]. More importantly, hypertensive patients in the real-world practice are usually under treatment with a combination of different antihypertensive classes, which exert divergent and often contrasting effects on RAR; diuretics and inhibitors of the renin–angiotensin–aldosterone system (RAAS) increase whereas beta blockers decrease renin, alpha blockers are considered to exert a neutral effect while inter-class variations exist for calcium channel blockers, which either do not affect or may upregulate renin. For all these reasons, it is currently recommended to change accordingly and washout all interfering antihypertensive medications before the evaluation of PRA and PAC tests in suspected cases of primary aldosteronism [2]. In the present study, patients in the first tertile (with the lowest RAR values), which was associated with poor blood pressure control and increased pulse pressures, compared with the third tertile, were older and exhibited a nonsignificant higher rate of diabetes and treatment with beta-blockers. Collectively, the above three factors might account for the lowest RAR values and contribute to the lower blood pressure control and increased pulse pressures. Another important limitation regarding the RAR measurement concerns the assay reliability, in combination with the need for laboratories to report individual values for both PAC and PRA plasma renin concentration [4]. The cost-effectiveness of an additional laboratory evaluation for hypertension management needs to be taken into account. Therefore, it might at present be somewhat optimistic to consider high RAR values as an indicator of effective management of hypertension in the real-life clinical practice, at least not before specific age-related and sex-related ‘normative values’ are determined, that additionally would take into consideration various antihypertensive combinations. Altogether, we would like to stress that physicians need to be extremely cautious regarding the evaluation of RAR in the typical hypertension setting, especially among patients under various antihypertensive combinations. It is plainly true that office and 24-h blood pressure measurements will define or uncover uncontrolled hypertension. Consequently,we are grateful to the authors for their novel and interestingobservations regardingbloodpressure control and pulse pressures in essential hypertensive patients treated with RAAS inhibitors, by assessing different tertiles of RAR. An arising question would be whether PRA, PAC and RAR differed according to the status of blood pressure control in the study population. Either way, the present study provides significant insight on the potential usefulness of PRA and PAC measurement in cases other than detection of primary aldosteronism, but the results need to be interpreted with caution whenever addressing the typical, multitreated hypertensive patient sharing several risk factors and comorbidities.