Showing papers by "Luis M. Ruilope published in 2011"

Reappraisal of European guidelines on hypertension management:: A European Society of Hypertension Task Force document

Abstract: ACEangiotensin-converting enzymeBPblood pressureDBPdiastolic blood pressureeGFRestimated glomerular filtration rateESCEuropean Society of CardiologyESHEuropean Society of HypertensionETendothelinIM...

Clinical Features of 8295 Patients With Resistant Hypertension Classified on the Basis of Ambulatory Blood Pressure Monitoring

Abstract: We aimed to estimate the prevalence of resistant hypertension through both office and ambulatory blood pressure monitoring in a large cohort of treated hypertensive patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. In addition, we also compared clinical features of patients with true or white-coat-resistant hypertension. In December 2009, we identified 68 045 treated patients with complete information for this analysis. Among them, 8295 (12.2% of the database) had resistant hypertension (office blood pressure ≥140 and/or 90 mm Hg while being treated with ≥3 antihypertensive drugs, 1 of them being a diuretic). After ambulatory blood pressure monitoring, 62.5% of patients were classified as true resistant hypertensives, the remaining 37.5% having white-coat resistance. The former group was younger, more frequently men, with a longer duration of hypertension and a worse cardiovascular risk profile. The group included larger proportions of smokers, diabetics, target organ damage (including left ventricular hypertrophy, impaired renal function, and microalbuminuria), and documented cardiovascular disease. Moreover, true resistant hypertensives exhibited in a greater proportion a riser pattern (22% versus 18%; P<0.001). In conclusion, this study first reports the prevalence of resistant hypertension in a large cohort of patients in usual daily practice. Resistant hypertension is present in 12% of the treated hypertensive population, but among them more than one third have normal ambulatory blood pressure. A worse risk profile is associated with true resistant hypertension, but this association is weak, thus making it necessary to assess ambulatory blood pressure monitoring for a correct diagnosis and management.

Olmesartan for the Delay or Prevention of Microalbuminuria in Type 2 Diabetes

Abstract: A b s t r ac t Background Microalbuminuria is an early predictor of diabetic nephropathy and premature cardiovascular disease. We investigated whether treatment with an angiotensin-receptor blocker (ARB) would delay or prevent the occurrence of microalbuminuria in patients with type 2 diabetes and normoalbuminuria. Methods In a randomized, double-blind, multicenter, controlled trial, we assigned 4447 patients with type 2 diabetes to receive olmesartan (at a dose of 40 mg once daily) or placebo for a median of 3.2 years. Additional antihypertensive drugs (except angiotensin-converting–enzyme inhibitors or ARBs) were used as needed to lower blood pressure to less than 130/80 mm Hg. The primary outcome was the time to the first onset of microalbuminuria. The times to the onset of renal and cardiovascular events were analyzed as secondary end points. Results The target blood pressure (<130/80 mm Hg) was achieved in nearly 80% of the patients taking olmesartan and 71% taking placebo; blood pressure measured in the clinic was lower by 3.1/1.9 mm Hg in the olmesartan group than in the placebo group. Microalbuminuria developed in 8.2% of the patients in the olmesartan group (178 of 2160 patients who could be evaluated) and 9.8% in the placebo group (210 of 2139); the time to the onset of microalbuminuria was increased by 23% with olmesartan (hazard ratio for onset of microalbuminuria, 0.77; 95% confidence interval, 0.63 to 0.94; P = 0.01). The serum creatinine level doubled in 1% of the patients in each group. Slightly fewer patients in the olmesartan group than in the placebo group had nonfatal cardiovascular events — 81 of 2232 patients (3.6%) as compared with 91 of 2215 patients (4.1%) (P = 0.37) — but a greater number had fatal cardiovascular events — 15 patients (0.7%) as compared with 3 patients (0.1%) (P = 0.01), a difference that was attributable in part to a higher rate of death from cardiovascular causes in the olmesartan group than in the placebo group among patients with preexisting coronary heart disease (11 of 564 patients [2.0%] vs. 1 of 540 [0.2%], P = 0.02). Conclusions Olmesartan was associated with a delayed onset of microalbuminuria, even though blood-pressure control in both groups was excellent according to current standards. The higher rate of fatal cardiovascular events with olmesartan among patients with preexisting coronary heart disease is of concern. (Funded by Daiichi Sankyo; ClinicalTrials.gov number, NCT00185159.)

A double-blind, randomized study comparing the antihypertensive effect of eplerenone and spironolactone in patients with hypertension and evidence of primary aldosteronism.

Abstract: BackgroundEplerenone is claimed to be a more selective blocker of the mineralocorticoid receptor than spironolactone being associated with fewer antiandrogenic side-effects. We compared the efficacy, safety and tolerability of eplerenone versus spironolactone in patients with hypertension associated

Renal function and target organ damage in hypertension

Abstract: Chronic kidney disease (CKD) is frequently observed in patients with arterial hypertension. The same factors that promote the appearance and progression of atherosclerosis can also promote the development of CKD. Two parameters are usually measured to estimate alterations in renal function, the presence of albuminuria, and the estimation of glomerular filtration rate (GFR). Microalbuminuria and a decreased estimated GFR (<60 mL/min/1.73 m(2)) are both accompanied by a significant increase in cardiovascular (CV) risk. Chronic kidney disease can develop all over the cardiorenal continuum and its presence in hypertensive patients with already developed CV disease contributes to a further increase in the development of events and death. Renal protection will in turn obtain CV protection and the treatment to be used is similar to that employed to prevent or to treat established CV disease.

Urinary Albumin Excretion Is Associated With Nocturnal Systolic Blood Pressure in Resistant Hypertensives

Abstract: Microalbuminuria is a known marker of subclinical organ damage. Its prevalence is higher in patients with resistant hypertension than in subjects with blood pressure at goal. On the other hand, some patients with apparently well-controlled hypertension still have microalbuminuria. The current study aimed to determine the relationship between microalbuminuria and both office and 24-hour ambulatory blood pressure. A cohort of 356 patients (mean age 64 ± 11 years; 40.2% females) with resistant hypertension (blood pressure ≥ 140 and/or 90 mm Hg despite treatment with ≥ 3 drugs, diuretic included) were selected from Spanish hypertension units. Patients with estimated glomerular filtration rate <30 mL/min/1.73 m(2) were excluded. All patients underwent clinical and demographic evaluation, complete laboratory analyses, and good technical-quality 24-hour ambulatory blood pressure monitoring. Urinary albumin/creatinine ratio was averaged from 3 first-morning void urine samples. Microalbuminuria (urinary albumin/creatinine ratio ≥ 2.5 mg/mmol in males or ≥ 3.5 mg/mmol in females) was detected in 46.6%, and impaired renal function (estimated glomerular filtration rate <60 mL/min/1.73 m(2)) was detected in 26.8%. Bivariate analyses showed significant associations of microalbuminuria with older age, reduced estimated glomerular filtration rate, increased nighttime systolic blood pressure, and elevated daytime, nighttime, and 24-hour diastolic blood pressure. In a logistic regression analysis, after age and sex adjustment, elevated nighttime systolic blood pressure (multivariate odds ratio, 1.014 [95% CI, 1.001 to 1.026]; P=0.029) and reduced estimated glomerular filtration rate (multivariate odds ratio, 2.79 [95% CI, 1.57 to 4.96]; P=0.0005) were independently associated with the presence of microalbuminuria. We conclude that microalbuminuria is better associated with increased nighttime systolic blood pressure than with any other office and 24-hour ambulatory blood pressure monitoring parameters.

Abnormalities in ambulatory blood pressure monitoring in hypertensive patients with diabetes

Abstract: Our aim was to assess the ambulatory blood pressure monitoring (ABPM) characteristics or patterns in hypertensive patients with diabetes compared with non-diabetic hypertensives. We performed a cross-sectional analysis of a 68 045 patient database from the Spanish Society of Hypertension ABPM Registry, a nation-wide network of >1200 primary-care physicians performing ABPM under standardized conditions in daily practice. We identified 12 600 (18.5%) hypertensive patients with diabetes. When compared with patients without diabetes, diabetic hypertensives exhibited higher systolic blood pressure (BP) levels in every ABPM period (daytime 135.4 vs. 131.8, and nighttime 126.0 vs. 121.0 mm Hg, P<0.001 for both) despite they were receiving more antihypertensive drugs (mean number 1.71 vs. 1.23, P<0.001). Consequently, diabetic patients suffered from lack of control of BP more frequently than non-diabetic subjects particularly during the night (65.5% vs. 57.4%, P<0.001). Prevalence of a non-dipping BP profile (64.2% vs. 51.6%, P<0.001) was higher in diabetic patients. In the other hand, prevalence of ‘white-coat’ hypertension in diabetic patients was 33.0%. We conclude that there was a remarkably high prevalence of alterations in ABPM in patients with diabetes. Abnormalities in systolic BP, particularly during the night, and in circadian BP pattern could be linked with the excess of BP-related cardiovascular risk of diabetes. A wider use of ABPM in diabetic patients should be considered.

Blood pressure control by the nifedipine GITS-telmisartan combination in patients at high cardiovascular risk: the TALENT study

Abstract: BackgroundGuidelines on hypertension regard combinations between two antihypertensive drugs to be the most important treatment strategy. Because of the complementary mechanism of action and the evidence of cardiovascular protective effects they include the combination of a calcium antagonist and an

Twisting arms to angiotensin receptor blockers/antagonists: the turn of cancer.

Abstract: Treatment of cardiovascular disease has achieved spectacular targets in the last 30 years, significantly contributing to the dramatic increases in life expectancy. In contrast, in the recent years, very few pharmacological innovations have been proposed, most likely because of the escalating costs of drug clinical development and by the reduced needs of innovation in this field. Angiotensin receptor blockers/antagonists (ARBs) have represented one of the major novel class of drugs reaching the therapeutic use for cardiovascular disease indication. Given the extremely high prevalence of hypertension, the leading indication for ARBs, prescription of this class of drugs has increased to very high levels. It is calculated that about 200 million individuals are treated with ARBs on our planet and that this class covers ∼25% prescription of antihypertensive agents. Even though this may be due to intensive marketing activity, it is also related to their ‘friendly’ use recognized by both doctors and patients, being the best tolerated class among cardiovascular drugs,1,2 and to rigorous and impressive clinical development. In fact, beyond the 15-year clinical experience by physicians and the consequent long-term drug surveillance by the authorities of healthcare systems worldwide, until today more than 300 000 patients have been strictly monitored for periods averaging from 3 to 5 years in clinical trials performed in numerous different clinical settings [including hypertension, high cardiovascular risk, diabetes, heart failure, myocardial infarction (MI), renal failure, stroke, and atherosclerosis].3,4 In all these studies, adverse reactions ascribed to ARBs have generally been less than any comparator, and similar to placebo. Besides the setting of clinical trials, these drugs have been extensively investigated as indicated by more than 12 100 scientific publications on PubMed at the date of 3 July 2010, using only the keywords Angiotensin Receptor Antagonists and Angiotensin Receptor blockers. During …

Telmisartan for the management of patients at high cardiovascular risk.

Abstract: Background:Cardiovascular disease (CVD) places a significant burden on healthcare providers. High blood pressure (BP) is the single most prevalent risk factor for CVD worldwide and is responsible for more deaths than any other risk factor. ‘Cardiovascular (CV) high-risk patients’ make up the broad cross-section of patients in the middle of the risk spectrum for CVD progression that is referred to as the CV continuum and includes those with atherothrombotic disease, those with target organ damage associated with type 2 diabetes and those with multiple risk factors. Angiotensin II is involved in CVD progression at every stage of the CV continuum, making the renin–angiotensin system a rational target for pharmacologic intervention. Angiotensin II receptor blockers (ARBs) offer a better tolerated alternative to angiotensin converting enzyme inhibitors, with greater long-term adherence. The ARB telmisartan recently received an indication for CV prevention.Scope:A PubMed literature search was conducted ...

Validation of a therapeutic scheme for the treatment of resistant hypertension.

Abstract: We tested the hypothesis that a therapeutic strategy of substituting the diuretic (most commonly hydrochlorothiazide) with chlorthalidone (50 mg/day), and, if needed, the calcium channel blocker with the highest dose of the most commonly used calcium antagonist (amlodipine 10 mg), and adding on top a direct renin inhibitor (aliskiren 300 mg) is effective to treat resistant hypertensive patients not responding to spironolactone. The scheme was tested in a group of 76 patients who had true treatment resistant hypertension (24-hour mean blood pressure ≥130/80 mm Hg while receiving three or more drugs). An effective response to spironolactone was defined as 24-hour ambulatory systolic blood pressure (SBP) drop by more than 20 mm Hg, and was obtained with 25–50 mg in 60 patients (78.9%). In patients with inadequate response to spironolactone (n = 16), we administered the triple combination plus the remaining therapy, a mean decrease of 29 mm Hg (95% CI 11–48; P = .004) for SBP and 12 mm Hg (95% CI: 4–20 mm Hg) for diastolic BP were observed. In only 1 of 16 patients (6%), the response was considered as insufficient. These data indicate the need for further testing this scheme that looks really promising to treat resistant hypertensive patients not responding to spironolactone.

Prevalencia de lesión de órganos diana y alteraciones metabólicas en la hipertensión arterial refractaria

Abstract: Resumen Fundamento y objetivo La hipertension arterial refractaria o resistente (HTR) es frecuente en las unidades especializadas de hipertension arterial (HTA). El objetivo de este trabajo fue valorar la prevalencia de afectacion de organos diana y alteraciones metabolicas asociadas en una serie de pacientes con HTR que se incluyeron de forma consecutiva en el registro de HTR de la Sociedad Espanola de Hipertension/Liga Espanola para la Lucha contra la Hipertension arterial (SEH-LELHA). Pacientes y metodo Estudio epidemiologico, transversal, multicentrico, en condiciones de practica clinica habitual. La HTR fue definida como la persistencia de cifras de presion arterial (PA) sistolica ≥ 140 mmHg o PA diastolica ≥ 90 mmHg en pacientes tratados con al menos 3 farmacos, a dosis plenas, uno de ellos diuretico. Se recogieron los datos demograficos y antropometricos, la presencia de otros factores de riesgo y condiciones clinicas asociadas. A todos los sujetos se les practico una monitorizacion ambulatoria de la presion arterial durante 24 horas (MAPA). La afectacion de organos diana se determino mediante la realizacion de ecocardiograma, electrocardiograma basal y excrecion urinaria de albumina. Resultados Se incluyeron 513 sujetos con una edad media (DE) de 64 (11) anos; un 47% eran mujeres. Un 65,7% (intervalo de confianza del 95% [IC 95%] 61,6-69,9) tenian obesidad central, un 38,6% (IC 95% 34,4-42,8) presentaban diabetes mellitus y un 63,8% (IC 95% 59,4-67,9) sindrome metabolico. La prevalencia de hipertrofia ventricular izquierda medida ecocardiograficamente fue del 57,1% (IC 95% 50,8-63,5) y la de dilatacion de auricula izquierda del 10,0% (IC 95% 6,3-13,7). Se observo microalbuminuria en un 46,6% de los sujetos (IC 95% 41,4-51,8). Los pacientes con sindrome metabolico fueron significativamente mayores (media de 65,4 [11] frente a 62,5 [ 12] anos; p = 0,0052), presentaron una mayor prevalencia de diabetes (52,0 frente a 16,6%, p Conclusiones La prevalencia de alteraciones metabolicas y de afectacion de organos diana es muy elevada en los sujetos con HTR.

Dual-Acting Angiotensin Receptor–Neprilysin Inhibition

Abstract: Lowering blood pressure by pharmacologic intervention reduces the incidence of cardiovascular events. Nevertheless, despite the widespread availability of effective antihypertensive medications, the vast majority of hypertensive patients worldwide continue to have inadequate blood pressure control. The development of new antihypertensive drugs could contribute to improving the hypertension control rate, and the blockade of new pathophysiologic pathways involved in blood pressure regulation would offer additional benefits. The dual inhibition of the angiotensin II receptor and neprilysin could provide clinical benefits in a range of cardiovascular diseases, including hypertension and heart failure.

Cardiovascular and Renal Links along the Cardiorenal Continuum.

Abstract: The cardiorenal syndrome includes the widely known relationship between kidney function and cardiovascular disease. A large number of patients have various degrees of heart and kidney dysfunction worldwide, both in developed and developing countries. Disorders affecting one of them mostly involve the other. Such interactions represent the pathogenesis for a clinical condition called cardiorenal syndrome. Renal and cardiovascular disease shares similar etiologic risk factors. The majority of vascular events are caused by accelerated atherosclerosis. Moreover, cardiovascular events rarely occur in patients without underlying disease; rather, they typically take place as the final stage of a pathophysiological process that results in progressive vascular damage, including vital organ damage, specifically the kidney and the heart if these factors are uncontrolled. Chronic kidney disease is a novel risk factor included at this stage that accelerates both vascular and cardiac damage.

Hypertension in 2010: Blood pressure and the kidney.

Abstract: 2010 saw the publication of a number of papers that provide new information on the relationship between blood pressure and the kidney. The data reinforce the need for future studies to jointly consider cardiovascular and renal outcomes.

New clinical concepts after the ONTARGET trial

Abstract: Some aspects of the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) study are briefly commented on in this article. The three main topics of interest related to the study that require further analysis are the following: the influence of blood pressure control, and in particular, the target blood pressure for patients with established cardiovascular disease such as those admitted in the ONTARGET study, the renal aspects of the study, which are of great interest but do not adequately clarify, in particular, concerns over the dual blockade of the renin–angiotensin–aldosterone system (RAAS) with telmisartan and ramipril, and finally, and probably most importantly, the role of statins in the outcome of the study. A high percentage of patients receiving this type of therapy at the end of the study, which probably contributed to obtaining a residual risk similar to that in the Heart Outcomes Prevention Evaluation (HOPE) study in the absence of treatment with RAAS block...

RAS Blockade for Every Diabetic Patient: Pro and Con

Abstract: The first part of this manuscript offers an overview of clinical data supporting the use of renin-angiotensin system (RAS) inhibitors in every patient with type 1 or type 2 diabetes, based on the known role of the RAS in blood pressure regulation and organ protection. In the second part, a possible, relevant role of drugs other than RAS-active compounds in treating hypertension and preventing cardiovascular disease in type 2 diabetic patients is underlined, paying particular attention to calcium-channel blockers, either alone or, better, in combination with ACE inhibitors. The guidelines of the European Society of Hypertension and the European Society of Cardiology recognize that the first monotherapy to be given to a diabetic patient with elevated blood pressure is an RAS suppressor, either an ACE inhibitor or an angiotensin receptor blocker (ARB) when micro- or macroalbuminuria are present (1). They also recognize that in order to lower blood pressure, all effective and well tolerated drugs can be used. Having admitted the possibility of non-RAS suppression therapies as first line, the guidelines continue by saying that the great majority of diabetic patients will sooner or later present hypertension and that most of them will require combination therapy. In this case, they specify that a blocker of the RAS should be a regular component of the combination and the one preferred when monotherapy is sufficient. In summary, an RAS blocker should be used when an elevation of blood pressure, even within the high normal range, is detected. The recent reappraisal of European Society of Hypertension Guidelines (2) confirms that initiation of therapy in the high normal range is reserved for diabetic patients with some degree of target organ damage (TOD), in particular microalbuminuria. Are the guidelines wrong? Probably not, because RAS suppression has three different aspects: 1. Capacity to control blood pressure alone …

A review of renal, cardiovascular and mortality endpoints in antihypertensive trials in diabetic patients

Abstract: Renal disease is highly prevalent in people with type 2 diabetes, and co-existence with hypertension increases the risk of cardiac events and mortality. Despite many large randomized trials, controversies remain regarding optimal antihypertensive therapy in diabetic patients, including whether some classes of antihypertensive drugs have specific renal protective properties, and the relationships between renal, cardiovascular and mortality endpoints. In this article, we review landmark antihypertensive drug trials from the last two decades in patient populations composed, or including substantial proportions, of patients with type 2 diabetes. Several points emerge. Firstly, treatment effects can vary widely among different renal, cardiovascular and mortality endpoints. Secondly, combinations of antihypertensive drugs vary in their ability to prevent major renal and cardiovascular events, even if they produce similar reductions in blood pressure. Thirdly, simply adding further antihypertensive drugs may not improve outcomes, even if it produces further reductions in blood pressure. In most trials, a reduction in microalbuminuria was associated with evidence of renal protection, but further evidence is needed relating changes in proteinuria with cardiovascular risk. The study that aligns best with the current reappraisal of ESH guidelines, with regard to blood pressure goals, use of an adequate combination and simultaneously protecting the kidney and the cardiovascular system, is the ADVANCE study.

Clinical utility of fixed-combination telmisartan–amlodipine in the treatment of hypertension

Abstract: The majority of hypertensive patients, especially those with target organ damage, are likely to require multiple-drug therapy in order to reach blood pressure (BP) targets and reduce their risk of adverse vascular outcomes. The rationale for combination therapy with agents that block the renin-angiotensin system (RAS) and a calcium channel blocker (CCB) or diuretic is well founded in growing evidence. Recent published trials have shown that the combination of an RAS suppressor and a dihydropiridinic CCB would offer additional benefits independently of BP reduction. A telmisartan-amlodipine combination has demonstrated significantly greater BP reductions compared with each monotherapy component in the overall population, and in particular in patients with moderate to severe hypertension and high-risk patients. This combination is well tolerated with a safety profile similar to placebo and is consistent with the known safety profile of its monotherapy components.

Office and ambulatory pulse pressure--association with clinical characteristics and cardiovascular risk factors in normoalbuminuric patients with type 2 diabetes (ROADMAP study).

Abstract: To investigate the association of office and ambulatory 24-h pulse pressure (PP) with clinical characteristics and cardiovascular risk factors in normoalbuminuric type 2 diabetic patients enrolled to the Randomised Olmesartan and Diabetes Microalbuminuria Prevention study, 4449 patients (2054 male and 2395 female; mean age 57.7±8.7 years) with type 2 diabetes, normoalbuminuria and at least one additional cardiovascular risk factor were included into the analysis. After adjustment by age, there were significant correlations between office PP and presence of hypertension (r=0.24; P<0.001), presence of cardiac and vascular disorders (r=0.17; P<0.001), metabolic syndrome (r=0.10; P<0.001), duration of diabetes (r=0.09; P<0.001), fasting blood glucose (r=0.08; P<0.001), albumin/creatinine ratio (r=0.07; P<0.001), insulin treatment, glycosylated haemoglobin (HbA1c), male gender and current smoking. In the subgroup of 1234 patients with ambulatory blood pressure measurement performed, ambulatory PP adjusted for office PP correlated with fasting blood glucose (r=0.16; P<0.001), metabolic syndrome (r=0.14; P<0.001), albumin/creatinine ratio (r=0.11; P<0.001) and indices of glycemic control (HbA1c: r=0.11; P<0.001). In this group of normoalbuminuric type 2 diabetic patients, office and ambulatory PP were associated with duration of diabetes, indices of glycemic control and cardiovascular risk factors. There was relationship between office and ambulatory PP and albuminuria even within normal albuminuria range.

Normotension, blood pressure variability and early target organ damage

Abstract: Arterial hypertension is an important public health challenge. Worldwide, nearly 8 million premature deaths, 54% of stroke cases and 47% of ischemic heart disease cases were attributable to high blood pressure (BP, >115 mm Hg systolic) in 2001. About half of these cases develop in people with arterial hypertension (>140/90 mm Hg); the remaining cases affect patients with BP levels that are normal or high normal.1 Wide intra-individual variability in BP influences prognosis and contributes to the burden of cardiovascular (CV) disease. In fact, data collected over the past 50 years through ambulatory BP monitoring (ABPM)2 have shown that BP is a highly variable parameter in both normotensive and hypertensive subjects.

Response to Unmasking True Resistant Hypertension: Is the Real-World Resistance Just Revealed?

Abstract: We thank Thomopoulos and Tsioufis1 for their interest in our article2 and also for their positive feedback and criticism. We will try to answer directly to the 3 points raised in their letter. First, we would like to clarify our analyses regarding treatment posology. Although, in the protocol of the Spanish Ambulatory Blood Pressure Monitoring Registry, details of treatment posology were collected on a 3-category scheme, results from this cohort of patients with resistant hypertension indicated that only 41 patients (0.5% of the cohort) received part of their …

Response to Bedtime Hypertension Treatment Increases Ambulatory Blood Pressure Control and Reduces Cardiovascular Risk in Resistant Hypertension

Abstract: We have read with interest the letter from Ayala et al1 concerning our article on resistant hypertension (RH).2 The first comment concerns a possible overestimation of white-coat RH by using 24-hour blood pressure (BP) as the criteria for definition of true and white-coat RH. Ayala et al1 stated that patients on ≥4 medications were true RH, and they should not be considered as having white-coat RH, even if 24-hour BP was normal. As contained in the American Heart Association definition, RH is a condition where patients remain above BP target despite the use of ≥3 medications.3 The inclusion in the definition of patients on ≥4 medications with normal clinic BP understands that these patients have been uptitrated to 4 medications because of …