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Background: We previously reported increased plasma XO (xanthine oxidase) activity in patients with resistant hypertension. Increased XO can cause mitochondrial DNA damage and promote release of fragments called mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs). Here, we report racial differences in XO activity and mtDNA DAMPs in Black and White adults with resistant hypertension. Methods: This retrospective study includes 91 resistant hypertension patients (44% Black, 47% female) with blood pressure >140/90 mm Hg on ≥4 medications and 37 normotensive controls (30% Black, 54% female) with plasma XO activity, mtDNA DAMPs, and magnetic resonance imaging of left ventricular morphology and function. Results: Black-resistant hypertension patients were younger (mean age 52±10 versus 59±10 years; P =0.001), with higher XO activity and left ventricular wall thickness, and worse diastolic dysfunction than White resistant hypertension patients. Urinary sodium excretion (mg/24 hour per kg) was positively related to left ventricular end-diastolic volume ( r =0.527, P =0.001) and left ventricular mass ( r =0.394, P =0.02) among Black but not White resistant hypertension patients. Patients with resistant hypertension had increased mtDNA DAMPs versus controls ( P P Conclusions: These data warrant a large study to examine the role of XO and mitochondrial mtDNA DAMPs in cardiac remodeling and heart failure in Black adults with resistant hypertension.

BACKGROUND Obstructive sleep apnoea (OSA) episode related blood pressure (BP) surge may mediate the association of OSA with cardiovascular disease. However, BP is not measured during a clinical sleep study. METHOD We tested the feasibility of incorporating the Caretaker physiological monitor, which utilizes a novel continuous beat-to-beat (b-b) BP monitoring technology, into polysomnography (PSG) and aimed to characterize BP surges related to obstructive respiratory events. B-b BP was concurrently collected and merged with PSG data on a posthoc basis. We compared BP surge between mean respiratory (apnoea, hypopnea and desaturation-alone events) and nonrespiratory events (spontaneous or leg movement-related arousals). We examined the association of the degree of oxygen desaturation with BP surge in a given respiratory event combining all events. A total of 17 consecutive patients (12 men, mean 52 years old, nine diagnostic and eight split-night PSGs) undergoing clinically indicated PSG were included after excluding one patient with poor signal quality due to excessive movement. RESULTS Caretaker was well tolerated. Mean respiratory BP surge ranged from 5 to 19 mmHg [Median (IQR) = 13.9 (9.5--16.2)]. Mean BP surge between the respiratory and nonrespiratory events was similar [13.8 (4.5) vs. 14.9 (5.3) mmHg, P = 0.13]. Accounting for the count distribution of desaturation/BP surge data pair events, there was a linear correlation between the degree of oxygen desaturation and BP surge (R = 0.57, P

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

Resistant hypertension, defined as blood pressure levels above goal while taking ≥3 classes of antihypertensive medication or ≥4 classes regardless of blood pressure level, is associated with increased cardiovascular disease risk. The 2018 American Heart Association Scientific Statement on Resistant Hypertension recommends healthy lifestyle habits and thiazide-like diuretics and mineralocorticoid receptor antagonists for adults with resistant hypertension. The term apparent treatment-resistant hypertension (aTRH) is used when pseudoresistance cannot be excluded. We estimated the use of healthy lifestyle factors and recommended antihypertensive medication classes among US Black adults with aTRH. Data were pooled for Black participants in the JHS (Jackson Heart Study) in 2009 to 2013 (n=2496) and the REGARDS study (Reasons for Geographic and Racial Differences in Stroke) in 2013 to 2016 (n=3786). Outcomes included lifestyle factors (not smoking, not consuming alcohol, ≥75 minutes of vigorous-intensity or ≥150 minutes of moderate or vigorous physical activity per week, and body mass index 2 ) and recommended antihypertensive medications (thiazide-like diuretics and mineralocorticoid receptor antagonists). Overall, 28.3% of participants who reported taking antihypertensive medication had aTRH. Among participants with aTRH, 14.5% and 1.2% had ideal levels of 3 and 4 of the lifestyle factors, respectively. Also, 5.9% of participants with aTRH reported taking a thiazide-like diuretic, and 9.8% reported taking a mineralocorticoid receptor antagonist. In conclusion, evidence-based lifestyle factors and recommended pharmacological treatment are underutilized in Black adults with aTRH. Increased use of lifestyle recommendations and antihypertensive medication classes specifically recommended for aTRH may improve blood pressure control and reduce cardiovascular disease–related morbidity and mortality among US Black adults. Graphic Abstract A graphic abstract is available for this article.

Background Primary aldosteronism is a nonsuppressible renin-independent aldosterone production that causes hypertension and cardiovascular disease. Objective To characterize the prevalence of nonsuppressible renin-independent aldosterone production, as well as biochemically overt primary aldosteronism, in relation to blood pressure. Design Cross-sectional study. Setting 4 U.S. academic medical centers. Participants Participants with normotension (n = 289), stage 1 hypertension (n = 115), stage 2 hypertension (n = 203), and resistant hypertension (n = 408). Measurements Participants completed an oral sodium suppression test, regardless of aldosterone or renin levels, as a confirmatory diagnostic for primary aldosteronism and to quantify the magnitude of renin-independent aldosterone production. Urinary aldosterone was measured in participants in high sodium balance with suppressed renin activity. Biochemically overt primary aldosteronism was diagnosed when urinary aldosterone levels were higher than 12 μg/24 h. Results Every blood pressure category had a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher blood pressure, kaliuresis, and lower serum potassium levels. Mean adjusted levels of urinary aldosterone were 6.5 μg/24 h (95% CI, 5.2 to 7.7 μg/24 h) in normotension, 7.3 μg/24 h (CI, 5.6 to 8.9 μg/24 h) in stage 1 hypertension, 9.5 μg/24 h (CI, 8.2 to 10.8 μg/24 h) in stage 2 hypertension, and 14.6 μg/24 h (CI, 12.9 to 16.2 μg/24 h) in resistant hypertension; corresponding adjusted prevalence estimates for biochemically overt primary aldosteronism were 11.3% (CI, 5.9% to 16.8%), 15.7% (CI, 8.6% to 22.9%), 21.6% (CI, 16.1% to 27.0%), and 22.0% (CI, 17.2% to 26.8%). The aldosterone-renin ratio had poor sensitivity and negative predictive value for detecting biochemically overt primary aldosteronism. Limitation Prevalence estimates rely on arbitrary and conventional thresholds, and the study population may not represent nationwide demographics. Conclusion The prevalence of primary aldosteronism is high and largely unrecognized. Beyond this categorical definition of primary aldosteronism, there is a prevalent continuum of renin-independent aldosterone production that parallels the severity of hypertension. These findings redefine the primary aldosteronism syndrome and implicate it in the pathogenesis of "essential" hypertension. Primary funding source National Institutes of Health.

BACKGROUND Obstructive sleep apnea (OSA), nocturnal hypertension, and nondipping systolic blood pressure (BP) are each highly prevalent among African Americans. However, few data are available on the association between OSA and nighttime BP in this population. METHODS We examined the association of OSA with nighttime BP among African Americans who completed 24-hour ambulatory BP monitoring (ABPM) at Exam 1 (2000–2004) of the Jackson Heart Study (JHS) and subsequently participated in the JHS Sleep Study (2012–2016). Type 3 home sleep apnea testing was used to assess OSA measures, including respiratory event index (REI4%) and percent sleep time RESULTS Among 206 participants who completed ABPM and participated in the Jackson Heart Sleep Study, 50.5% had nocturnal hypertension and 26.2% had moderate to severe OSA (REI4% ≥15 events/hour). After multivariable adjustment, each SD (13.3 events/hour) increase in REI4% was associated with 1.75 mm Hg higher nighttime DBP (95% confidence interval (CI): 0.38, 3.11) and a prevalence ratio of 1.11 (95% CI: 1.00, 1.24) for nocturnal hypertension. Each SD (10.4%) increase in nocturnal hypoxemia was associated with a 1.91 mm Hg higher nighttime SBP (95% CI: 0.15, 3.66). CONCLUSIONS Severity of OSA and nocturnal hypoxemia were associated with high nighttime BP in African American participants in the JHS.

Hypertension is a highly common condition with well-established adverse consequences. Ambulatory blood pressure monitoring has repeatedly been shown to better predict cardiovascular outcomes and mortality, compared to single office visit blood pressure. Non-dipping of sleep-time blood pressure is an independent marker for increased cardiovascular risk. We review blood pressure variability and the challenges of blood pressure monitoring during sleep. Although pathological sleep such as obstructive sleep apnea has been associated with non-dipping of sleep-time blood pressure, blood pressure is not routinely measured during sleep due to lack of unobtrusive blood pressure monitoring technology. Second, we review existing noninvasive continuous blood pressure monitoring technologies. Lastly, we propose including sleep-time blood pressure monitoring during sleep studies and including sleep studies in patients undergoing ambulatory blood pressure monitoring.

Refractory hypertension (RfHTN) is a phenotype of antihypertensive treatment failure defined as uncontrolled BP despite the use of effective doses of ≥5 antihypertensive medications including a long-acting thiazide-like diuretic (chlorthalidone) and a mineralocorticoid receptor antagonist. The degree of medication nonadherence is unknown among patients with RfHTN. In this prospective evaluation, 54 patients with apparent RfHTN were recruited from the University of Alabama at Birmingham Hypertension Clinic after having uncontrolled BP at 3 or more clinic visits. All patients’ BP was evaluated by automated office BP and 24-hour ambulatory BP monitoring (n=49). Antihypertensive medication adherence was determined by measuring 24-hour urine specimens for antihypertensive medications and their metabolites by high-performance liquid chromatography-tandem mass spectrometry (n=45). Of the 45 patients who completed 24-hour ambulatory BP monitoring, 40 (88.9%) had confirmed RfHTN based on an elevated automated office BP (≥130/80 mm Hg), mean 24-hour ABP (≥125/75 mm Hg), and mean awake (day-time) ABP (≥130/80 mm Hg). Out of the 40 fully evaluated patients with RfHTN, 16 (40.0%) were fully adherent with all prescribed medications. Eighteen (45.0%) patients were partially adherent and 6 (15.0%) had none of the prescribed agents detected in their urine. Of 18 patients who were partially adherent, 5 (12.5%) were adherent with at least 5 medications, including chlorthalidone and the mineralocorticoid receptor antagonist, consistent with true RfHTN. Of patients identified as having apparent RfHTN, 52.5% were adherent with at least 5 antihypertensive medications, including chlorthalidone and a mineralocorticoid receptor antagonist, confirming true RfTHN. These findings validate RfHTN as a rare, but true phenotype of antihypertensive treatment failure.

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.

Introduction: Masked uncontrolled hypertension (MUCH) in treated patients is defined as controlled office BP but uncontrolled out-of-clinic ambulatory BP (ABP). In contrast, patients with true controlled hypertensive (CHTN) have controlled BP by both office BP and out-of-clinic ABP. Previously, we have shown that patients with MUCH have increased out-of-clinic catecholamines/metanephrines (indicative of SNS activity) and aldosterone levels (indicative of RAAS activity). The current study tested the hypothesis that MUCH patients have higher cortisol levels (corticotropin-glucocorticoid axis) compared to patients with true CHTN. Methods: 222 patients with controlled office BP at ≥3 clinic visits were recruited. Patients taking glucocorticoid-containing medications were excluded. All patients were evaluated by automated office BP. Out-of-clinic ABP monitoring and 24-hour-urinary cortisol, cortisone, aldosterone, catecholamines and metanephrines levels were also measured. 115 patients had MUCH and remaining 75 patients had true CHTN. Results: MUCH patients had significantly higher out-of-clinic levels of 24-hour-urinary cortisol, catecholamines, metanephrines and aldosterone compared to true CHTN. Further, in correlation matrix analysis higher urinary cortisol was associated with higher catecholamines, metanephrines and aldosterone in MUCH patients.BP. Conclusions: Patients with MUCH had higher out-of-clinic urinary cortisol levels compared to patients with true CHTN. These findings suggest that patients with MUCH have higher out-of-clinic cortisol, aldosterone secretion and SNS tone that may contribute to their higher out-of-clinic BP.

Objective. We developed a method using cardiovascular magnetic resonance imaging to model the untwisting of the left ventricle (LV) as a damped torsional harmonic oscillator to estimate shear modulus (intrinsic myocardial stiffness) and frictional damping, then applied this method to evaluate the torsional stiffness of patients with resistant hypertension (RHTN) compared to a control group. Approach. The angular displacement of the LV during diastole was measured. Myocardial shear modulus and damping constant were determined by solving a system of equations modeling the diastolic untwisting as a damped, unforced harmonic oscillator, in 100 subjects with RHTN and 36 control subjects. Main Results. Though overall torsional stiffness was increased in RHTN (41.7 (27.1–60.7) versus 29.6 (17.3–35.7) kdyn*cm; p = 0.001), myocardial shear modulus was not different between RHTN and control subjects (0.34 (0.23–0.50) versus 0.33 (0.22–0.46) kPa; p = 0.758). RHTN demonstrated an increase in overall diastolic frictional damping (6.13 ± 3.77 versus 3.35 ± 1.70 kdyn*cm*s; p < 0.001), but no difference in damping when corrected for the overlap factor (74.3 ± 25.9 versus 68.0 ± 24.0 dyn*s/cm3; p = 0.201). There was an increase in the polar moment (geometric component of stiffness; 11.47 ± 6.95 versus 7.58 ± 3.28 cm4; p Significance. We have developed a phenomenological method, estimating the intrinsic stiffness and relaxation properties of the LV based on restorative diastolic untwisting. This model finds increased overall stiffness in RHTN and points to hypertrophy, rather than tissue- level changes, as the major factor leading to increased stiffness.

Resistant hypertension is defined as uncontrolled blood pressure despite the use of 3 or more antihypertensive agents of different classes, including a diuretic, usually thiazide-like, a long-acting calcium channel blocker, and a blocker of the renin- angiotensin system, either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, at maximal or maximally tolerated doses. Antihypertensive medication non-adherence and the white coat effect, defined as elevated blood pressure when measured in clinic but controlled when measured outside of clinic, must be excluded to make the diagnosis. Resistant hypertension is a high risk phenotype, leading to increased all-cause mortality and cardiovascular disease (CVD) outcomes. Healthy lifestyle habits are associated with reduced CV risk in patients with resistant hypertension. Aldosterone excess is common in patients with resistant hypertension, and addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen is effective at getting the blood pressure to goal in most of these patients. Refractory hypertension is defined as uncontrolled blood pressure despite use of 5 or more antihypertensive agents of different classes, including a long acting thiazide-like diuretic and a mineralocorticoid receptor antagonist, at maximal or maximally tolerated doses. Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying resistant hypertension, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity.

Background: Blacks have a high prevalence of hypertension and uncontrolled blood pressure (BP), each of which may be partially explained by untreated sleep apnea. We investigated the association of sleep apnea with uncontrolled BP and resistant hypertension in blacks. Methods: Between 2012 and 2016, Jackson Heart Sleep Study participants (N=913) underwent an in-home Type 3 sleep apnea study, clinic BP measurements, and anthropometry. Moderate or severe obstructive sleep apnea (OSA) was defined as a respiratory event index ≥15, and nocturnal hypoxemia was quantified as percent sleep time with > 80mm Hg, use of antihypertensive medication, or self-report of a diagnosis of hypertension. Controlled BP was defined as systolic BP Results: The analytic sample with hypertension (N=664) had a mean age of 64.0 (SD,10.6) years, and were predominately female (69.1%), obese (58.6%), and college educated (51.3%). Among the sample, 25.7% had OSA, which was untreated in 94% of participants. Overall, 48% of participants had uncontrolled hypertension and 14% had resistant hypertension. After adjustment for confounders, participants with moderate or severe OSA had a 2.0 times higher odds of resistant hypertension (95% confidence interval [CI], 1.14–3.67). Each standard deviation higher than Conclusion: Untreated moderate or severe OSA is associated with increased odds of resistant hypertension. These results suggest that untreated OSA may contribute to inadequate BP control in blacks.

Background: The multicenter, international, randomized, blinded, sham-controlled RADIANCE-HTN SOLO trial (A Study of the ReCor Medical Paradise System in Clinical Hypertension) demonstrated a 6.3 mm Hg greater reduction in daytime ambulatory systolic blood pressure (BP) at 2 months by endovascular ultrasound renal denervation (RDN) compared with a sham procedure among patients not treated with antihypertensive medications. We report 6-month results after the addition of a recommended standardized stepped-care antihypertensive treatment to the randomized endovascular procedure under continued blinding to initial treatment. Methods: Patients with a daytime ambulatory BP ≥135/85 mm Hg and Results: A total of 69/74 RDN patients and 71/72 sham patients completed the 6-month ambulatory BP measurement. At 6 months, 65.2% of patients in the RDN group were treated with the standardized stepped-care antihypertensive treatment versus 84.5% in the sham group ( P =0.008), and the average number of antihypertensive medications and defined daily dose were less in the RDN group than in the sham group (0.9±0.9 versus 1.3±0.9, P =0.010 and 1.4±1.5 versus 2.0±1.8, P =0.018; respectively). Despite less intensive standardized stepped-care antihypertensive treatment, RDN reduced daytime ambulatory systolic BP to a greater extent than sham (−18.1±12.2 versus −15.6±13.2 mm Hg, respectively; difference adjusted for baseline BP and number of medications: −4.3 mm Hg, 95% confidence interval, −7.9 to −0.6, P =0.024). There were no major adverse events in either group through 6 months. Conclusions: The BP-lowering effect of endovascular ultrasound RDN was maintained at 6 months with less prescribed antihypertensive medications compared with a sham control. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02649426.

In 2015, the American Heart Association awarded 4-year funding for a Strategically Focused Research Network focused on hypertension composed of 4 Centers: Cincinnati Children’s Hospital, Medical College of Wisconsin, University of Alabama at Birmingham, and University of Iowa. Each center proposed 3 integrated (basic, clinical, and population science) projects around a single area of focus relevant to hypertension. Along with scientific progress, the American Heart Association put a significant emphasis on training of next-generation hypertension researchers by sponsoring 3 postdoctoral fellows per center over 4 years. With the center projects being spread across the continuum of basic, clinical, and population sciences, postdoctoral fellows were expected to garner experience in various types of research methodologies. The American Heart Association also provided a number of leadership development opportunities for fellows and investigators in these centers. In addition, collaboration was highly encouraged among the centers (both within and outside the network) with the American Heart Association providing multiple opportunities for meeting and expanding associations. The area of focus for the Cincinnati Children’s Hospital Center was hypertension and target organ damage in children utilizing ambulatory blood pressure measurements. The Medical College of Wisconsin Center focused on epigenetic modifications and their role in pathogenesis of hypertension using human and animal studies. The University of Alabama at Birmingham Center’s areas of research were diurnal blood pressure patterns and clock genes. The University of Iowa Center evaluated copeptin as a possible early biomarker for preeclampsia and vascular endothelial function during pregnancy. In this review, challenges faced and successes achieved by the investigators of each of the centers are presented.

Masked uncontrolled hypertension (MUCH) in treated patients is defined as controlled office blood pressure (BP) but uncontrolled out-of-clinic ambulatory BP. Previously, we have shown that patients with MUCH have evidence of heightened out-of-clinic sympathetic nervous system activity. The aim is to test the hypothesis that MUCH patients have higher aldosterone secretion compared with patients with true controlled hypertension. Two hundred twenty-two patients were recruited after having controlled office BP readings at ≥3 clinic visits. Patients taking MR (mineralocorticoid receptor) antagonists and epithelial sodium channel blockers were excluded. All patients were evaluated by clinic automated office BP and morning serum aldosterone and plasma renin activity. Out-of-clinic ambulatory BP monitoring and 24-hour urinary aldosterone, catecholamines, and metanephrines were also measured. Sixty-four patients had MUCH, and the remaining 48 patients had true controlled hypertension. MUCH patients had significantly higher out-of-clinic levels of 24-hour urinary aldosterone, catecholamines, and metanephrines compared with true controlled hypertension. The 2 groups did not differ in serum aldosterone, plasma renin activity, or aldosterone-renin ratio collected in clinic. In addition, 32.8% of MUCH patients had high out-of-clinic 24-hour urinary aldosterone (≥12 µg) but normal clinic serum aldosterone (

OBJECTIVES Obstructive sleep apnea (OSA) is associated with treatment-resistant hypertension (RHTN) and may contribute to refractory hypertension (RfHTN). The objective of the current study was to test the hypothesis that patients with RfHTN have more severe OSA compared with patients with controlled RHTN. METHODS Patients (n = 187) referred to the University of Alabama at Birmingham Hypertension Clinic for evaluation and treatment of RHTN, defined as uncontrolled blood pressure (BP) (SBP ≥ 130 mmHg or DBP ≥ 80 mmHg) despite the use of at least three antihypertensive medications including a diuretic, were enrolled following completion of at least three follow-up clinic visits. RfHTN was defined as uncontrolled high BP despite treatment with five or more antihypertensive agents of different classes, including a long-acting thiazide-type diuretic and a mineralocorticoid receptor antagonist. Following enrollment, all patients (n = 130) completed 24-h ambulatory BP measurement and overnight diagnostic polysomnography during normal nightly use of continuous positive airway pressure. Analyses examined the severity of OSA and related sleep characteristics among patients with RfHTN versus controlled RHTN. RESULTS Of the 130 evaluated patients, 37 (28.5%) had RfHTN and 93 (71.5%) had controlled RHTN. In unadjusted analyses, there was not a significant difference in OSA severity, oxygen saturation, or hypoxemia time in patients with RfHTN versus controlled RHTN (P > 0.05). Men with RfHTN had more severe OSA compared with men with controlled RHTN (P = 0.044). In adjusted analyses, OSA severity was associated with sex (P

A case of episodic hypertension related to changes in position with the biochemical diagnosis of pheochromocytoma confirmed on imaging. The positional hypertension due to pheochromocytoma was treated by right open adrenalectomy, but the episodic hypertension recurred after 1 year and remained unresolved.

OBJECTIVES We compared the prevalence of apparent treatment-resistant hypertension (aTRH) according to the seventh report of the Joint National Committee (JNC 7) and the 2017 American College of Cardiology/American Heart Association (ACC/AHA) guideline in an integrated healthcare delivery system. METHODS We identified individuals aged at least 18 years with hypertension from Kaiser Permanente Southern California between 1 July 2014 and 30 June 2015. aTRH was defined as either blood pressure (BP) above goal (≥140/90 mmHg per JNC7, and ≥130/80 mmHg per 2017 ACC/AHA for most adults with hypertension) while taking at least 3 classes of antihypertensive medication or taking at least four classes regardless of BP level. A secondary analysis was conducted requiring use of a diuretic for the definition of aTRH. Patient clinical characteristics and antihypertensive medication use were described using electronic health records. RESULTS We included 469 509 patients with treated hypertension [mean (SD) age 65 years (12), 46% white, 26% Hispanic, 13% black, and 12% Asian]. The prevalence of aTRH was 16.9 and 21.8% according to the JNC 7 and the 2017 ACC/AHA guidelines, respectively [Δ = 4.9% (95% CI: 4.7--5.1%)]. By requiring a diuretic to be considered as aTRH, the prevalence of aTRH decreased to 13.4 and 17.2% according to the JNC 7 and the 2017 ACC/AHA guidelines, respectively. Among patients with aTRH, 1.9% received a long-acting thiazide-like diuretic, and 5.6% received a mineralocorticoid receptor blocker. CONCLUSION The prevalence of aTRH increased using the more stringent BP goals of the 2017 ACC/AHA guideline. The use of recommended therapy for aTRH was suboptimal suggesting a potential area for improvement.

BACKGROUND Refractory hypertension (RfHTN), a phenotype of antihypertensive treatment failure, is defined as uncontrolled automated office blood pressure (AOBP) ≥130/80 mm Hg and awake ambulatory blood pressure (ABP) ≥130/80 mm Hg on ≥5 antihypertensive medications, including chlorthalidone and a mineralocorticoid receptor antagonist. Previous studies suggest that RfHTN is attributable to heightened sympathetic tone. The current study tested whether reserpine, a potent sympatholytic agent, lowers blood pressure (BP) in patients with RfHTN. METHODS Twenty-one out of 45 consecutive patients with suspected RfHTN were determined to be fully adherent with their antihypertensive regimen. Seven patients agreed to participate in the current clinical trial with reserpine and 6 patients completed the study. Other sympatholytic medications, such as clonidine or guanfacine, were tapered and discontinued before starting reserpine. Reserpine 0.1 mg daily was administered in an open-label fashion for 4 weeks. All patients were evaluated by AOBP and 24-hour ABP at baseline and after 4 weeks of treatment. RESULTS Reserpine lowered mean systolic and diastolic AOBP by 29.3 ± 22.2 and 22.0 ± 15.8 mm Hg, respectively. Mean 24-hour systolic and diastolic ABPs were reduced by 21.8 ± 13.4 and 15.3 ± 9.6 mm Hg, mean awake systolic and diastolic ABPs by 23.8 ± 11.8 and 17.8 ± 9.2 mm Hg, and mean asleep systolic and diastolic ABPs by 21.5 ± 11.4 and 13.7 ± 6.4 mm Hg, respectively. CONCLUSIONS Reserpine, a potent sympatholytic agent, lowers BP in patients whose BP remained uncontrolled on maximal antihypertensive therapy, lending support to the hypothesis that excess sympathetic output contributes importantly to the development of RfHTN.

Blacks have a high prevalence of hypertension and uncontrolled blood pressure (BP), each of which may be partially explained by untreated sleep apnea. We investigated the association of sleep apnea with uncontrolled BP and resistant hypertension in blacks.Between 2012 and 2016, Jackson Heart Sleep Study participants (N=913) underwent an in-home Type 3 sleep apnea study, clinic BP measurements, and anthropometry. Moderate or severe obstructive sleep apnea (OSA) was defined as a respiratory event index ≥15, and nocturnal hypoxemia was quantified as percent sleep time with90% oxyhemoglobin saturation. Prevalent hypertension was defined as either a systolic BP ≥130 mm Hg or diastolic BP80mm Hg, use of antihypertensive medication, or self-report of a diagnosis of hypertension. Controlled BP was defined as systolic BP130 mm Hg and diastolic BP80 mm Hg; uncontrolled BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with use of 1 to 2 classes of antihypertensive medication; and resistant BP as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg with the use of ≥3 classes of antihypertensive medication (including a diuretic) or use of ≥4 classes of antihypertensive medication regardless of BP level. Multinomial logistic regression models were fit to determine the association between OSA severity and uncontrolled BP or resistant hypertension (versus controlled BP) after multivariable adjustment.The analytic sample with hypertension (N=664) had a mean age of 64.0 (SD,10.6) years, and were predominately female (69.1%), obese (58.6%), and college educated (51.3%). Among the sample, 25.7% had OSA, which was untreated in 94% of participants. Overall, 48% of participants had uncontrolled hypertension and 14% had resistant hypertension. After adjustment for confounders, participants with moderate or severe OSA had a 2.0 times higher odds of resistant hypertension (95% confidence interval [CI], 1.14-3.67). Each standard deviation higher than90% oxyhemoglobin saturation was associated with an adjusted odds ratio for resistant hypertension of 1.25 (95% CI 1.01-1.55). OSA and90% oxyhemoglobin saturation were not associated with uncontrolled BP.Untreated moderate or severe OSA is associated with increased odds of resistant hypertension. These results suggest that untreated OSA may contribute to inadequate BP control in blacks.

Background Sleep characteristics and disorders are associated with higher blood pressure ( BP ) when measured in the clinic setting. Methods and Results We tested whether self‐reported sleep characteristics and likelihood of obstructive sleep apnea ( OSA ) were associated with nocturnal hypertension and nondipping systolic BP ( SBP ) among participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who completed 24‐hour ambulatory BP monitoring during the year 30 examination. Likelihood of OSA was determined using the STOP ‐Bang questionnaire. Global sleep quality, habitual sleep duration, sleep efficiency, and midsleep time were obtained from the Pittsburgh Sleep Quality Index. Nocturnal hypertension was defined as mean asleep SBP ≥120 mm Hg or diastolic BP ≥70 mm Hg. Nondipping SBP was defined as a decline in awake‐to‐asleep SBP SBP was 41.3% and 32.5%, respectively. After multivariable adjustment including cardiovascular risk factors, the prevalence ratios (PRs) for nocturnal hypertension and nondipping SBP associated with high versus low likelihood of OSA were 1.32 (95% CI, 1.00–1.75) and 1.31 (95% CI, 1.02–1.68), respectively. The association between likelihood of OSA and nocturnal hypertension was stronger for white participants (PR: 2.09; 95% CI, 1.23–3.48) compared with black participants (PR: 1.11; 95% CI, 0.79–1.56). The PR for nondipping SBP associated with a 1‐hour later midsleep time was 0.92 (95% CI, 0.85–0.99). Global sleep quality, habitual sleep duration, and sleep efficiency were not associated with either nocturnal hypertension or nondipping SBP . Conclusions These findings suggest that addressing OSA risk and sleep timing in a clinical trial may improve BP during sleep.

Digital, The Lancet Commission on Hypertension identified that a key action to address the worldwide burden of high blood pressure (BP) was to improve the quality of BP measurements by using BP devices that have been validated for accuracy. Currently, there are over 3 000 commercially available BP devices, but many do not have published data on accuracy testing according to established scientific standards. This problem is enabled through weak or absent regulations that allow clearance of devices for commercial use without formal validation. In addition, new BP technologies have emerged (e.g. cuffless sensors) for which there is no scientific consensus regarding BP measurement accuracy standards. Altogether, these issues contribute to the widespread availability of clinic and home BP devices with limited or uncertain accuracy, leading to inappropriate hypertension diagnosis, management and drug treatment on a global scale. The most significant problems relating to the accuracy of BP devices can be resolved by the regulatory requirement for mandatory independent validation of BP devices according to the universally-accepted International Organization for Standardization Standard. This is a primary recommendation for which there is an urgent international need. Other key recommendations are development of validation standards specifically for new BP technologies and online lists of accurate devices that are accessible to consumers and health professionals. Recommendations are aligned with WHO policies on medical devices and universal healthcare. Adherence to recommendations would increase the global availability of accurate BP devices and result in better diagnosis and treatment of hypertension, thus decreasing the worldwide burden from high BP., La Comisión Lancet de Hipertensión determinó que una medida clave para responder a la carga mundial que representa la hipertensión arterial era mejorar la calidad de las mediciones de la presión arterial, mediante la utilización de dispositivos cuya exactitud haya sido validada. En la actualidad existen 3000 dispositivos comercializados, pero muchos no tienen datos publicados sobre pruebas de exactitud conformes a las normas científicas establecidas. La falta de regulación o su ineficiencia, que permiten la autorización de dispositivos para uso comercial sin una validación oficial, posibilitan este problema. Además, han surgido tecnologías nuevas de medición de la presión arterial (por ejemplo, los sensores sin brazalete) sobre las cuales no existe unanimidad en la comunidad científica con respecto a las normas de exactitud de la medición. En conjunto, estos aspectos contribuyen a la disponibilidad generalizada de tensiómetros de consultorio o domiciliarios que ofrecen una exactitud limitada o incierta, que llevan a diagnósticos, manejo y farmacoterapia inapropiados de la hipertensión a escala mundial. Los problemas más importantes relacionados con la exactitud de los dispositivos de medición de la presión arterial se pueden resolver mediante el requisito regulatorio de una validación independiente obligatoria de los dispositivos, en consonancia con la norma ISO universalmente aceptada. Esta es una recomendación básica y constituye una necesidad internacional acuciante. Otras recomendaciones clave son la elaboración de normas de validación específicas para las tecnologías nuevas de medición de la presión arterial y la publicación en línea de listas de los dispositivos nuevos exactos que están a la disposición de los usuarios y los profesionales de salud. Las recomendaciones están en consonancia con las políticas de la Organización Mundial de la Salud sobre los dispositivos médicos y la atención universal de la salud. El cumplimiento de las recomendaciones aumentará la disponibilidad mundial de dispositivos de medición de la presión arterial que sean exactos y tendrá como efecto un mejor diagnóstico y tratamiento, reduciendo así la carga mundial de la hipertensión., A Comissão Lancet sobre Hipertensão Arterial identificou que uma iniciativa central para enfrentar a carga mundial da hipertensão arterial seria a melhoria na qualidade da mensuração da pressão arterial pelo uso aparelhos de pressão arterial validados quanto à acurácia. Atualmente, existem mais de 3 000 aparelhos de pressão arterial disponíveis comercialmente; entretanto, muitos não têm dados publicados sobre testes de acurácia realizados de acordo com padrões científicos estabelecidos. Este problema resulta de regulamentação fraca ou inexistente, o que permite a aprovação para uso comercial de dispositivos sem validação formal. Além disso, surgiram novas tecnologias de mensuração da pressão arterial (por exemplo, sensores sem algemas) sem consenso científico quanto aos padrões de acurácia. No conjunto, essas questões contribuem para a oferta generalizada de dispositivos de pressão arterial clínica e domiciliar com acurácia limitada ou incerta, levando a diagnóstico, gerenciamento e tratamento inadequados da hipertensão em escala global. Os problemas mais significativos relacionados com a acurácia dos dispositivos de pressão arterial podem ser resolvidos por regulamentação que imponha a obrigatoriedade de validação independente dos aparelhos de pressão arterial, de acordo com a norma universalmente aceita pela Organização Internacional de Normalização. Esta é uma recomendação fundamental para a qual existe uma necessidade internacional urgente. Outras recomendações essenciais incluem o desenvolvimento de padrões de validação especificamente para novas tecnologias de mensuração da pressão arterial e listas on-line de aparelhos com acurácia adequada que sejam acessíveis aos consumidores e profissionais de saúde. As recomendações estão alinhadas com as políticas da Organização Mundial da Saúde (OMS) sobre dispositivos médicos e atenção universal à saúde. A adesão às recomendações aumentaria a oferta global de dispositivos de pressão arterial com acurácia adequada e resultaria em melhor diagnóstico e tratamento da hipertensão arterial, diminuindo assim a carga mundial dessa doença., Traducción oficial al español del artículo original en inglés efectuada por la Organización Panamericana de la Salud. En caso de discrepancia, prevalecerá la versión original en inglés. Wolters Kluwer Health, Inc. y sus sociedades no se hacen responsables de la exactitud de la traducción del original inglés ni de los eventuales errores que esta pueda contener. Cita del artículo original: Sharman JE, O'Brien E, Alpert B, Schutte AE, Delles C, Hecht Olsen M et al. Lancet commission on hypertension group position statement on the global improvement of accuracy standards for devices that measure blood pressure. J Hypertens. 2020:38:21-29.doi: https://doi. org/10.1097/HJH.0000000000002246, Ciencias Médicas y de la Salud

Refractory hypertension (RfHTN) is an extreme phenotype of antihypertensive treatment failure defined as lack of blood pressure control with ≥5 medications, including a long-acting thiazide and a mineralocorticoid receptor antagonist. RfHTN is a subgroup of resistant hypertension (RHTN), which is defined as blood pressure >135/85 mm Hg with ≥3 antihypertensive medications, including a diuretic. RHTN is generally attributed to persistent intravascular fluid retention. It is unknown whether alternative mechanisms are operative in RfHTN. Our objective was to determine whether RfHTN is characterized by persistent fluid retention, indexed by greater intracardiac volumes determined by cardiac magnetic resonance when compared with controlled RHTN patients. Consecutive patients evaluated in our institution with RfHTN and controlled RHTN were prospectively enrolled. Exclusion criteria included advanced chronic kidney disease and masked or white coat hypertension. All enrolled patients underwent biochemical testing and cardiac magnetic resonance. The RfHTN group (n=24) was younger (mean age, 51.7±8.9 versus 60.6±11.5 years; P =0.003) and had a greater proportion of women (75.0% versus 43%; P =0.02) compared with the controlled RHTN group (n=30). RfHTN patients had a greater left ventricular mass index (88.3±35.0 versus 54.6±12.5 g/m 2 ; P P =0.001), and septal wall thickness (14.5±3.8 versus 10.0±2.2 mm; P

A 78-year-old black man presented to the Hypertension Clinic at the University of Alabama at Birmingham for uncontrolled blood pressure (BP). His BP remained uncontrolled (automated office, ≥135/85 mm Hg) from August 2011 to August 2016 in spite of use of 6 antihypertensive agents in adequate doses (Figure 1). During this time period, his average systolic BP was 167.1 mm Hg and average diastolic BP was 68.7 mm Hg. Figure 1. Blood pressure (BP) and antihypertensive medications before and after surgery. CABG indicates coronary artery bypass grafting. The patient was on 3 antihypertensive medications on initial presentation to University of Alabama at Birmingham in 2011, including an angiotensin receptor blocker (irbesartan), a calcium channel blocker (amlodipine), and a long-acting thiazide-like diuretic (chlorthalidone). Spironolactone was added as a fourth antihypertensive agent. Eventually, hydralazine—a vasodilator—and clonidine—a centrally acting sympatholytic—were added as the fifth and sixth antihypertensive agents. The patient’s BP remained uncontrolled on 6 different classes of antihypertensive medications (Figure 1). Comorbidities and secondary causes of hypertension were evaluated by biochemical analysis and imaging. ### Biochemical Analysis The patient was diagnosed with mild chronic kidney disease. Mean serum creatinine was 1.35 mg/dL with an estimated glomerular filtration rate of 58 mL/min per 1.73 m2. Diabetes mellitus was excluded (HbA1c was 5.5%), primary aldosteronism was excluded as the plasma aldosterone–renin ratio was

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 Glomerular hyperfiltration may contribute to the high incidence of renal disease in Obese African Americans essential hypertensive (ObAAEH) patients, but the precise mechanisms responsible for renal injury have not been elucidated. Mitochondria are important determinants of renal injury in hypertension, and increased levels of mitochondrial DNA (mtDNA) in the urine may indicate renal mitochondrial injury. We hypothesized that urine mtDNA copy numbers would be higher in ObAAEH compared to Caucasian essential hypertensive (CEH) patients. Methods We prospectively measured systemic, renal vein (RV), inferior vena cava (IVC), and urinary copy number of the mtDNA genes COX3 and ND1 by quantitative-PCR in CEH and ObAAEH patients during constant sodium intake and antihypertensive regimens, and compared them with healthy volunteers (HV) (n = 23 each). Results Blood pressure was similarly elevated in CEH and ObAAEH, while glomerular filtration rate (GFR) was higher and age lower in ObAAEH. Urinary (but not plasma) COX3 and ND1 were higher in CEH compared to HV, and further elevated in ObAAEH patients. COX3 and ND1 renal gradients (RV-IVC) were higher in ObAAEH vs. CEH, and their urinary levels directly correlated with GFR. In multivariate analysis, GFR remained the only predictor of elevated urinary COX3 and ND1 levels. Conclusions Urinary fragments of the mitochondrial genome are elevated in ObAAEH patients and correlate with glomerular hyperfiltration. A positive gradient across the kidney in ObAAEH suggests selective renal release. These results are consistent with mitochondrial injury that may aggravate renal damage and accelerate hypertension-related morbidity/mortality rates in ObAAEH.

Resistant hypertension, defined as blood pressure >140/90 mm Hg despite using ≥3 antihypertensive medications, is a well-recognized clinical entity. Patients with resistant hypertension are at an increased risk of cardiovascular disease compared with those with more easily controlled hypertension. Coronary heart disease mortality rates of younger adults are stagnating or on the rise. The purpose of our study was to characterize the phenotype and risk factors of younger patients with resistant hypertension, given the dearth of data on cardiovascular risk profile in this cohort. We conducted a cross-sectional analysis with predefined age groups of a large, ethnically diverse cohort of 2170 patients referred to the Hypertension Clinic at the University of Alabama at Birmingham. Patients (n=2068) met the inclusion criteria and were classified by age groups, that is, ≤40 years (12.7% of total cohort), 41 to 55 years (32.1%), 56 to 70 years (36.1%), and ≥71 years (19.1%). Patients aged ≤40 years compared with those aged ≥71 years had significantly earlier onset of hypertension (24.7±7.4 versus 55.0±14.1 years; P P P =0.005), plasma renin activity (4.9±10.2 versus 2.5±5.0 ng/mL per hour; P =0.001), 24-hour urinary aldosterone (13.4±10.0 versus 8.2±6.2 µg/24 h; P P

Face-to-face comparison of major large scale HPC interconnects.Review of challenges and solutions for increased use of optics in HPC.Description of optical switching, in terms of principle, limitations, technical requirements and benefits. Large-scale high performance computing is permeating nearly every corner of modern applications spanning from scientific research and business operations, to medical diagnostics, and national security. All these communities rely on computer systems to process vast volumes of data quickly and efficiently, yet progress toward increased computing power has experienced a slowdown in the last number of years. The sheer cost and scale, stemming from the need for extreme parallelism, are among the reasons behind this stall. In particular, very large-scale, ultra-high bandwidth interconnects, essential for maintaining computation performance, represent an increasing portion of the total cost budget.Photonic systems are often cited as ways to break through the energy-bandwidth limitations of conventional electrical wires toward drastically improving interconnect performance. This paper presents an overview of the challenges associated with large-scale interconnects, and reviews how photonic technologies can contribute to addressing these challenges. We review some important aspects of photonics that should not be underestimated in order to truly reap the benefits of cost and power reduction.

Refractory hypertension is a recently proposed phenotype of antihypertensive treatment failure. As such it represents an extreme subtype of resistant or difficult-to-treat hypertension. Resistant hypertension is relatively common with an estimated prevalence of 10-20% of treated hypertensive patients. It is typically defined as having an uncontrolled blood pressure on three or more antihypertensive medications, including a diuretic. Refractory hypertension is rare with a prevalence of approximately 5% of patients with uncontrolled resistant hypertension. It is defined as an uncontrolled blood pressure with the use of five or more antihypertensive medications, including a long-acting thiazide diuretic, such as chlorthalidone, and a mineralocorticoid receptor antagonist such as spironolactone.Persistent excess fluid retention is thought to commonly underlie development of resistant hypertension, recent studies suggest that refractory may be more likely attributable to heightened sympathetic output as opposed to inappropriate fluid retention.Treatment recommendations for resistant hypertension are generally based on intensification of diuretic therapy, especially with combined use of chlorthalidone and spironolactone. Although fuller elucidation is needed, such an approach may not be appropriate for refractory hypertension, which instead, may require effective sympathetic inhibition, either with medications or device-based approaches.