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OBJECTIVE To determine whether serum urate reduction with allopurinol lowers blood pressure (BP) in young adults and the mechanisms mediating this hypothesized effect. METHODS We conducted a single-center, randomized, double-blind, crossover clinical trial. Adults ages 18-40 years with baseline systolic BP ≥120 and

The purpose of the current study was to determine whether aortic blood pressure (BP) and arterial stiffness are greater in patients with controlled resistant hypertension (RHTN) than controlled non‐resistant hypertension (non‐RHTN) despite similar clinic BP level. Participants were recruited from University of Alabama at Birmingham (UAB) Hypertension Clinic. Controlled hypertension was defined as automated office BP measurement with BP

Background Aortic stiffness is an independent predictor of cardiovascular events in patients with arterial hypertension. Resistant hypertension is often linked to hyperaldosteronism and associated with adverse outcomes. Spironolactone, a mineralocorticoid receptor antagonist, has been shown to reduce both the arterial blood pressure (BP) and aortic stiffness in resistant hypertension. However, the mechanism of aortic stiffness reduction by spironolactone is not well understood. We hypothesized that spironolactone reduces aortic stiffness in resistant hypertension independently of BP change. Methods and Results Patients with uncontrolled BP (≥140/90 mm Hg) despite use of ≥3 antihypertensive medications (including diuretics) were prospectively recruited. Participants were started on spironolactone at 25 mg/d, and increased to 50 mg/d at 4 weeks while other antihypertensive medications were withdrawn to maintain constant mean BP. Phase‐contrast cardiac magnetic resonance imaging of the ascending aorta was performed in 30 participants at baseline and after 6 months of spironolactone treatment to measure aortic pulsatility, distensibility, and pulse wave velocity. Pulse wave velocity decreased (6.3±2.3 m/s to 4.5±1.8 m/s, P P P Conclusions Our results suggest that spironolactone improves aortic properties in resistant hypertension independently of BP, which may support the hypothesis of an effect of aldosterone on the arterial wall. A larger prospective study is needed to confirm our findings.

Apparent treatment-resistant hypertension (aTRH), nocturnal hypertension, and nondipping blood pressure (BP) have shared risk factors. The authors studied the association between aTRH and nocturnal hypertension and aTRH and nondipping BP among 524 black Jackson Heart Study participants treated for hypertension. Nocturnal hypertension was defined by mean nighttime systolic BP ≥120 mm Hg or diastolic BP ≥70 mm Hg. Nondipping BP was defined by mean nighttime to daytime systolic BP ratio >0.90. aTRH was defined by mean clinic systolic BP ≥140 mm Hg and/or diastolic BP ≥90 mm Hg with three medication classes or treatment with four or more classes. The risk for developing aTRH associated with nondipping BP and nocturnal hypertension was estimated. After multivariable adjustment, participants with aTRH were more likely to have nocturnal hypertension (prevalence ratio, 1.20; 95% confidence interval, 1.03-1.39) and nondipping (prevalence ratio, 1.25; 95% confidence interval, 1.09-1.43). Over a median 7.3 years of follow-up, nocturnal hypertension and nondipping BP at baseline were not associated with developing aTRH after adjustment.

Background and objective We directly compared sleep apnoea (SA) rates and risk of cardiovascular and mortality outcomes among SA patients with resistant hypertension (RH) and non-RH within a large diverse hypertension population. Methods A retrospective cohort study between 1 January 2006 and 31 December 2010 among hypertensive adults (age ≥ 18 years) was performed within an integrated health system. Rates of SA in RH and non-RH were determined. Multivariable logistic regression analyses were used to calculate OR for SA. Cox proportional hazard modelling was used to estimate hazard ratios (HRs) for cardiovascular and mortality outcomes between SA in RH versus SA in non-RH adjusting for age, gender, race, BMI, chronic kidney disease and other comorbidities. Results SA was identified in 33 682 (7.2%) from 470 386 hypertensive individuals. SA in RH accounted for 5806 (9.6%) compared to SA in non-RH 27 876 individuals (6.8%). Multivariable OR (95% CI) for SA was 1.16 (1.12, 1.19), 3.57 (3.47, 3.66) and 2.20 (2.15, 2.25) for RH versus non-RH, BMI ≥ 30, and males, respectively. Compared to SA in non-RH individuals, SA in RH had a multivariable adjusted HR (95% CI) of 1.24 (1.13, 1.36), 1.43 (1.28, 1.61), 0.98 (0.85, 1.12) and 1.04 (0.95, 1.14) for ischaemic heart event (IHE), congestive heart failure (CHF), stroke and mortality, respectively. Conclusion We observed a modest increase in likelihood for SA among RH compared to non-RH patients. Risks for IHE and CHF were higher for SA in RH compared to SA in non-RH patients; however, there were no differences in risk for stroke and mortality.

Low medication adherence may explain part of the high prevalence of apparent treatment-resistant hypertension (aTRH). The authors assessed medication adherence and aTRH among 4026 participants taking ≥ 3 classes of antihypertensive medication in the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) trial using the 4-item Morisky Medication Adherence Scale (MMAS). Low adherence was defined as an MMAS score ≥ 2. Overall, 66% of participants taking ≥ 3 classes of antihypertensive medication had aTRH. Perfect adherence on the MMAS was reported by 67.8% and 70.9% of participants with and without aTRH, respectively. Low adherence was present among 8.1% of participants with aTRH and 5.0% of those without aTRH (P

Among patients with resistant hypertension (RHTN), there are those whose blood pressure (BP) remains uncontrolled in spite of maximal medical therapy. This retrospective analysis aims to characterize these patients with refractory hypertension. Refractory hypertension was defined as BP that remained uncontrolled after ≥3 visits to a hypertension clinic within a minimum 6-month follow-up period. Of the 304 patients referred for RHTN, 29 (9.5%) remained refractory to treatment. Patients with refractory hypertension and those with controlled RHTN had similar aldosterone levels and plasma renin activity (PRA). Patients with refractory hypertension had higher baseline BP (175±23/97±15 mm Hg vs 158±25/89±15 mm Hg; P=.001/.005) and heart rate, and higher rates of prior stroke and congestive heart failure. During follow-up, the BP of patients with refractory hypertension remained uncontrolled (168.4±14.8/93.8±17.7 mm Hg) in spite of use of an average of 6 antihypertensive medications, while those of patients with controlled RHTN decreased to 129.3±11.2/77.6±10.8 mm Hg. Spironolactone reduced the BP by 12.9±17.8/6.6±13.7 mm Hg in patients with refractory hypertension and by 24.1±16.7/9.2±12.0 mm Hg in patients with controlled RHTN. In patients with RHTN, approximately 10% remain refractory to treatment. Similar aldosterone and PRA levels and a diminished response to spironolactone suggest that aldosterone excess does not explain the treatment failure.

Spironolactone, a nonselective mineralocorticoid receptor (MR) antagonist, has been in clinical use for several decades. A selective MR antagonist (eplerenone) has also been developed and is now in clinical use. Before proceeding to review the use of these drugs in clinical practice, we will briefly review how the aldosterone paradigm and current concepts of the mineralocorticoid receptor have changed.

Treatment of resistant hypertension requires confirmation of true resistance, diagnosis and treatment of secondary causes of hypertension, adoption of appropriate lifestyle modifications, and effective use of multidrug antihypertensive regimens. Excessive volume retention often underlies resistant hypertension, so diuretics are generally necessary to achieve blood pressure (BP) goals. Although treatment regimens consisting of 3 or more agents have not been systematically evaluated, the author has found a triple regimen consisting of a thiazide diuretic, a calcium channel blocker, and an angiotensin‐converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) to be generally effective and well tolerated. Although hydrochlorothiazide is more widely used, chlorthalidone provides better BP reduction and should be preferentially used in patients with resistant hypertension, particularly if the patient remains uncontrolled on hydrochlorothiazide. Recent studies have demonstrated that low doses of aldosterone antagonists, when added to multi‐drug regimens that include a thiazide diuretic and an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker, provide significant additional BP reduction, seemingly exceeding what would be expected with addition of alternative classes of agents. The degree of BP reduction induced by aldosterone blockade has been similar in patients with and without evidence of aldosterone excess. Aldosterone antagonists are generally safe and well tolerated. The most common adverse effect of low‐dose spironolactone has been breast tenderness, occurring in about 10% of men. Hyperkalemia is uncommon, but can occur, necessitating biochemical monitoring. Risk of hyperkalemia is increased in patients with chronic kidney disease or diabetes, elderly patients, and patients already receiving an angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker.

Recent studies have indicated a higher prevalence of primary aldosteronism (PA) than reported historically. Aldosterone excess induces sodium and fluid retention with consequential increases in blood pressure. Patients with PA are at an increased risk of developing left ventricular hypertrophy, chronic kidney disease, and endothelial dysfunction. Measurement of the plasma aldosterone/plasma renin activity ratio is an effective screening test for PA. The majority of patients with PA do not have a discernable aldosterone-producing adenoma (APA), and the aldosterone excess is considered idiopathic in etiology and/or attributed to adrenal hyperplasia. Treatment of PA includes medical therapy with mineralocorticoid receptor antagonists and adrenalectomy for patients with a unilateral APA. A reasonable treatment strategy is to attempt medical therapy in all patients with a high plasma aldosterone/PRA ratio and reserve the extensive workup needed to identify an APA for those patients whose hypertension or hypokalemia cannot be controlled medically.