Racial Differences in XO (Xanthine Oxidase) and Mitochondrial DNA Damage-Associated Molecular Patterns in Resistant Hypertension.

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<0.001), with Black mtDNA DAMPS greater than Whites (P<0.001). Transmission electron microscopy of skeletal muscle biopsies in resistant hypertension patients demonstrates mitochondria cristae lysis, myofibrillar loss, large lipid droplets, and glycogen accumulation. 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.

Effect of Serum Urate Lowering With Allopurinol on Blood Pressure in Young Adults: A Randomized, Controlled, Crossover Trial.

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 <160 mm Hg or diastolic BP ≥80 and <100 mm Hg, and serum urate ≥5.0 mg/dl for men or ≥4.0 mg/dl for women were enrolled. Main exclusion criteria included chronic kidney disease, gout, or past use of urate-lowering therapies. Participants received oral allopurinol (300 mg daily) or placebo for 1 month followed by a 2-4 week washout and then were crossed over. Study outcome measures were change in systolic BP from baseline, endothelial function estimated as flow-mediated dilation (FMD), and high-sensitivity C-reactive protein (hsCRP) levels. Adverse events were assessed. RESULTS: Ninety-nine participants were randomized, and 82 completed all visits. The mean ± SD age was 28.0 ± 7.0 years, 62.6% were men, and 40.4% were African American. In the primary intent-to-treat analysis, systolic BP did not change during the allopurinol treatment phase (mean ± SEM -1.39 ± 1.16 mm Hg) or placebo treatment phase (-1.06 ± 1.08 mm Hg). FMD increased during allopurinol treatment periods compared to placebo treatment periods (mean ± SEM 2.5 ± 0.55% versus -0.1 ± 0.42%; P < 0.001). There were no changes in hsCRP level and no serious adverse events. CONCLUSION: Our findings indicate that urate-lowering therapy with allopurinol does not lower systolic BP or hsCRP level in young adults when compared with placebo, despite improvements in FMD. These findings do not support urate lowering as a treatment for hypertension in young adults.

Uric Acid Is Not Associated With Blood Pressure Phenotypes and Target Organ Damage According to Blood Pressure Phenotypes.

BACKGROUND: Hypertensive patients with increased serum uric acid (SUA) are at increased cardiovascular (CV) risks. Both the European and American hypertension guidelines endorse the utilization of 24 h-ambulatory blood pressure monitoring (24 h-ABPM) for hypertensive patients with increased CV risk. While there is difference in identifying uric acid as a CV risk factor between the European and American guidelines. Therefore, it is unknown whether 24 h-ABPM should be used routinely in hypertensive patients with increased SUA. METHODS: To address this knowledge gap, we investigated (i) the correlation between SUA and 24 h-ABP; (ii) the association between SUA and blood pressure (BP) phenotypes (controlled hypertension [CH], white-coat uncontrolled hypertension [WCUH], masked uncontrolled hypertension [MUCH], and sustained uncontrolled hypertension [SUCH]); (iii) the association between SUA and target organ damage (TOD: microalbuminuria, left ventricular hypertrophy [LVH], and arterial stiffness) according to BP phenotypes. RESULTS: In 1,336 treated hypertensive patients (mean age 61.2 and female 55.4%), we found (i) there was no correlation between SUA and 24 h, daytime, and nighttime systolic blood pressure/diastolic blood pressure, respectively; (ii) in reference to CH, SUA increase was not associated WCUH (odds ratio [OR] 0.968, P = 0.609), MUCH (OR 1.026, P = 0.545), and SUCH (OR 1.003, P = 0.943); (iii) the overall prevalence of microalbuminuria, LVH, and arterial stiffness was 2.3%, 16.7%, and 23.2%, respectively. After adjustment for covariates, including age, sex, smoking, body mass index, diabetes mellitus, and estimated glomerular filtration rate, there was no association between SUA and TOD in all BP phenotypes. CONCLUSIONS: These preliminary findings did not support routine use of 24 h-ABPM in treated hypertensive patients with increased SUA.

Underutilization of Treatment for Black Adults With Apparent Treatment-Resistant Hypertension: JHS and the REGARDS Study.

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 <25 kg/m2) 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.

Prediction of improved therapeutics for fabry disease patients generated by mutagenesis of the α-galactosidase A active site, dimer interface, and glycosylation region.

Fabry disease is an X-linked lysosomal storage disorder caused by the deficiency of the enzyme, α-galactosidase A that induces the accumulation of the substrate globotriaosylceramide. Currently approved enzyme replacement therapy using recombinant human α-galactosidase A improves patient symptoms but a majority of patients experience adverse events due to the multiple infusions required for full therapeutic efficacy. Our approach is to use medicinal chemistry and phylogenic comparisons to introduce mutations into the human enzyme to increase catalytic activity and/or stability to generate an improved therapeutic enzyme that may require fewer infusions. We designed mutations at three regions of the human α-galactosidase A: the active site, the dimer interface, and a site for glycosylation. The M208E mutation, adjacent to the Y207 active site residue, increased enzyme activity 3.01-fold. This mutation introduced a charged Glu residue that is adjacent to the Y207 active site residue and close to a site of N-glycosylation. The W277C mutation, designed to promote dimer stability, introduced a strong thiol-aromatic interaction (Cys-Phe) at the dimer interface and increased activity 2.31-fold. The W277C and M208E mutations modify the structure of the enzyme into forms with enhanced thermal stability 3.7- and 3.9-fold, respectively and positive cooperativity resulting in increased Hill coefficient from 1.0 to 4.60 and 3.47, respectively. Enhanced thermal stability and positive cooperativity predict improved in vivo activity and superior therapeutic properties. Our results demonstrate the value of in vitro mutagenesis for α-galactosidase A and support future perspectives to validate these results in Fabry disease patients.

Declaración de posición del Grupo de la Comisión Lancet de Hipertensión con respecto a la mejora mundial de las normas de exactitud para los dispositivos de medición de la presión arterial / Lancet Commission on Hypertension Group position statement on the global improvement of accuracy standards for devices that measure blood pressure / Posicionamento do Grupo da Lancet Commission on Hypertension sobre a melhoria global dos padrões de acurácia para aparelhos que medem a pressão arterial

Objetivos. El boletín de notas de México correspondiente al 2018 evalúa las oportunidades a disposición de la población infantil y joven mexicana para que puedan desarrollar niveles adecuados de actividad física y sueño, y disminuyan el sedentarismo.Métodos. El boletín es un sistema de vigilancia que recopila los datos obtenidos en las encuestas nacionales, censos, documentos gubernamentales, sitios web, literatura gris y estudios publicados con respecto al análisis de 16 indicadores en 4 categorías: comportamientos diarios, estado físico, entornos y fuentes influyentes, y estrategias e inversión. Los datos fueron cotejados con los puntos de referencia establecidos. A cada indicador se le asignó una calificación entre 1 y 10 (< 6 significa reprobado) o fue marcado como "incompleto" si los datos eran nulos o insuficientes. Resultados. Las calificaciones obtenidas para los comportamientos diarios fueron: actividad física en general: 4; participación en actividades deportivas organizadas: 5; juego activo: 3; modalidades de transporte activas: 5; sueño: 7; y sedentarismo: 3. El estado físico obtuvo un 7. Las calificaciones para los entornos y fuentes influyentes fueron: familiares y pares: "incompleto"; escuela: 3; comunidad y entorno: 4. Para las estrategias e inversión: estrategias gubernamentales: 6; entidades no gubernamentales: 2.Conclusiones. Las bajas calificaciones obtenidas en 11 de los 16 indicadores demuestran que las escuelas, las familias, las comunidades y el gobierno tienen que aunar esfuerzos para mejorar las oportunidades que tiene la población infantil y joven en México para desarrollar niveles de actividad física satisfactorios.(AU)

ABSTRACT 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.(AU)

RESUMO 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.(AU)

Racial Differences in Maintaining Optimal Health Behaviors Into Middle Age.

INTRODUCTION: Earlier development of cardiovascular disease risk factors in blacks versus whites may result from differences in maintaining health behaviors. Age-specific racial differences in maintaining health behaviors from ages 18 to 50 years were determined. METHODS: In 1985-1986, the population-based Coronary Artery Risk Development in Young Adults study enrolled 5,115 participants aged 18-30 years. In 2017, a total of 2,485 blacks and 2,407 whites with one or more optimal health behaviors at baseline who attended one or more of seven follow-up exams over 25 years (i.e., through 2010-2011) were analyzed. The primary outcome, maintaining four or more optimal health behaviors, included BMI <25; never smoking; ≥150 minutes/week of moderate to vigorous physical activity; no/moderate alcohol intake (women/men: zero to seven/zero to 14 drinks per week); and Dietary Approaches to Stop Hypertension diet adherence score ≥15 (i.e., baseline highest quartile). Hazard ratios comparing blacks with whites for maintaining optimal health behaviors were calculated among participants with each optimal behavior at baseline. RESULTS: From ages 18 to 50 years, 2.6% of blacks and 9.2% of whites maintained four or more optimal health behaviors (for optimal BMI: 16.0% and 30.1%, smoking status: 74.6% and 78.4%, physical activity: 17.7% and 21.4%, alcohol intake: 68.4% and 64.6%, diet adherence: 3.9% and 10.3%, respectively). The multivariable adjusted hazard ratio comparing blacks with whites was 0.63 (95% CI=0.56, 0.72) for maintaining four or more optimal health behaviors (for optimal BMI: 0.82 [95% CI=0.66, 1.01], smoking status: 0.57 [95% CI=0.52, 0.62], physical activity: 0.83 [95% CI=0.75, 0.91], alcohol intake: 1.19 [95% CI=1.03, 1.37], diet adherence: 0.71 [95% CI=0.61, 0.82]). CONCLUSIONS: Fewer blacks than whites maintained four or more optimal health behaviors until age 50 years, but maintenance was low among both races.

Use of Aldosterone Antagonists for Treatment of Uncontrolled Resistant Hypertension.

BACKGROUND: Multiple studies indicate that primary aldosteronism (PA) is common in patients with resistant hypertension, with an estimated prevalence of approximately 20%. Additional studies suggest that beyond this 20% of patients with classical PA, there is a larger proportion of patients with lesser degrees of hyperaldosteronism which contributes even more broadly to antihypertensive treatment resistance. Given these observations, it is intuitive that use of aldosterone antagonists will provide antihypertensive benefit in patients with resistant hypertension and evidence of aldosterone excess. Intriguingly, however, are clinical findings demonstrating substantive benefit of aldosterone antagonists in patients with resistant hypertension, but without demonstrative evidence of hyperaldosteronism, that is, with seemingly normal or even low aldosterone levels. CONCLUSION: Spironolactone is clearly established as the most effective fourth agent for treatment of uncontrolled resistant hypertension. Emerging observations suggest a further role of spironolactone for counteracting the effects of diet high in sodium, particularly in obese, hypertensive patients.

The effects of urate lowering therapy on inflammation, endothelial function, and blood pressure (SURPHER) study design and rationale.

BACKGROUND: The association between hyperuricemia and hypertension is controversial. Animal models, epidemiological data, and small clinical trials have favored a causative role for hyperuricemia in hypertension but more studies are necessary to elucidate putative mechanisms, population susceptibility, and potential for urate-lowering therapies (ULT) to decrease blood pressure (BP). PURPOSE: To describe the background and design of the Serum Urate Reduction to Prevent Hypertension (SURPHER) study. METHODS: SURPHER is a single center, double-blinded, crossover trial in which participants are randomly assigned to allopurinol (300mg) or placebo. Enrollment focused on adults 18-40years old with baseline systolic blood pressure≥120 and <160mmHg or diastolic blood pressure≥80 and <100mmHg, and serum urate ≥5.0mg/dL or ≥4.0mg/dL for men or women, respectively. SURPHER recruitment targets participants without chronic kidney disease (estimated glomerular filtration rate>60mL/min/1.73m2), and without prior diagnosis of gout or use of ULT to treat gout. The primary outcome is change from baseline in blood pressure assessed by 24hour ambulatory blood pressure monitoring and mechanistic outcomes include changes in endothelial function as measured by flow-mediated dilation, as well as C-reactive protein levels. RESULTS: Since June 16, 2014 until present, SURPHER is recruiting participants in the city of Birmingham, Alabama. LIMITATIONS: The study aims to enroll otherwise healthy young adults for a pharmacological intervention study with multiple study-related procedures. Challenges related to recruitment are anticipated and multiple strategies for increasing recruitment and retention are planned if necessary.

Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus.

Glucagon-like peptide-1 receptor agonists, used to treat type 2 diabetes mellitus, are associated with small reductions in systolic blood pressure (SBP) and increases in heart rate. However, findings based on clinic measurements do not adequately assess a drug's 24-hour pharmacodynamic profile. The effects of dulaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, on BP and heart rate were investigated using ambulatory BP monitoring. Patients (n=755; 56±10 years; 81% white; 48% women), with type 2 diabetes mellitus, taking ≥1 oral antihyperglycemic medication, with a clinic BP between 90/60 and 140/90 mm Hg were randomized to dulaglutide (1.5 or 0.75 mg) or placebo subcutaneously for 26 weeks. Ambulatory BP monitoring was performed at baseline and at 4, 16, and 26 weeks. The primary end point was change from baseline to week 16 in mean 24-hour SBP, a tree gatekeeping strategy compared the effects of dulaglutide to placebo. Both doses of dulaglutide were noninferior to placebo for changes in 24-hour SBP and diastolic blood pressure, and dulaglutide 1.5 mg significantly reduced SBP (least squares mean difference [95% confidence interval]), -2.8 mm Hg [-4.6, -1.0]; P≤0.001). Dulaglutide 0.75 mg was noninferior to placebo (1.6 bpm; [0.3, 2.9]; P≤0.02) for 24-hour heart rate (least squares mean difference [95% confidence interval]), but dulaglutide 1.5 mg was not (2.8 bpm [1.5, 4.2]). Dulaglutide 1.5 mg was associated with a reduction in 24-hour SBP and an increase in 24-hour heart rate. The mechanisms responsible for the observed effects remain to be clarified.

Characterizing workers participating in a worksite wellness health screening program using blood pressure control, self-monitoring, medication adherence, depression, and exercise.

Blood pressure control remains a serious public health issue because hypertension is the most common risk factor for cardiovascular disease. Effective management of hypertension often requires lifestyle modification and medication adherence. The objective of this study was to identify the prevalence of blood pressure control, medication adherence, self-monitoring of blood pressure, depression, and exercise among workers with access to health resources. Faculty and staff (N = 484) from a university and health care institution in the southeastern United States participated in biometric and questionnaire screening. The researchers used initial screening data from this worksite wellness program to describe baseline blood pressure control (< 140/90 mm Hg), self-monitoring of blood pressure, medication adherence, depression, and exercise. Overall, 63% of the workers' blood pressure was controlled; however, 23% of the sample had been prescribed antihypertensive medication to control their blood pressure. Thirty percent of the sample reported practicing blood pressure self-monitoring, 72.2% reported that they exercised, and 22% reported feeling down and depressed. More than half (64.9%) who used prescribed antihypertensive medication reported adherence to these medications.

Healthy lifestyle factors and risk of cardiovascular events and mortality in treatment-resistant hypertension: the Reasons for Geographic and Racial Differences in Stroke study.

Few data exist on whether healthy lifestyle factors are associated with better prognosis among individuals with apparent treatment-resistant hypertension, a high-risk phenotype of hypertension. The purpose of this study was to assess the association of healthy lifestyle factors with cardiovascular events, all-cause mortality, and cardiovascular mortality among individuals with apparent treatment-resistant hypertension. We studied participants (n=2043) from the population-based Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with apparent treatment-resistant hypertension (blood pressure ≥140/90 mm Hg despite the use of 3 antihypertensive medication classes or the use of ≥4 classes of antihypertensive medication regardless of blood pressure control). Six healthy lifestyle factors adapted from guidelines for the management of hypertension (normal waist circumference, physical activity ≥4 times/week, nonsmoking, moderate alcohol consumption, high Dietary Approaches to Stop Hypertension diet score, and low sodium-to-potassium intake ratio) were examined. A greater number of healthy lifestyle factors were associated with lower risk for cardiovascular events (n=360) during a mean follow-up of 4.5 years. Multivariable-adjusted hazard ratios [HR (95% confidence interval)] for cardiovascular events comparing individuals with 2, 3, and 4 to 6 versus 0 to 1 healthy lifestyle factors were 0.91 (0.68-1.21), 0.80 (0.57-1.14), and 0.63 (0.41-0.95), respectively (P-trend=0.020). Physical activity and nonsmoking were individual healthy lifestyle factors significantly associated with lower risk for cardiovascular events. Similar associations were observed between healthy lifestyle factors and risk for all-cause and cardiovascular mortality. In conclusion, healthy lifestyle factors, particularly physical activity and nonsmoking, are associated with a lower risk for cardiovascular events and mortality among individuals with apparent treatment-resistant hypertension.

Effects of demographics on the antihypertensive efficacy of triple therapy with amlodipine, valsartan, and hydrochlorothiazide for moderate to severe hypertension.

OBJECTIVE: To compare the antihypertensive efficacy and safety of once-daily triple therapy with amlodipine (Aml) 10 mg, valsartan (Val) 320 mg, and hydrochlorothiazide (HCTZ) 25 mg versus dual-therapy combinations of these components in patients with moderate to severe hypertension. RESEARCH DESIGN: Subgroup analysis of a multinational, randomized, double-blind, parallel-group, active-controlled trial. METHODS: After antihypertensive washout and a placebo run-in of up to 4 weeks, 2271 patients were randomly allocated in a 1:1:1:1 ratio to receive Aml/Val/HCTZ triple therapy or dual therapy with Val/HCTZ, Aml/Val, or Aml/HCTZ for 8 weeks. Forced titration to the full dose was done over the first 2 weeks of treatment. Efficacy and safety parameters were determined by age group (<65 vs. ≥65 years), gender, race (White vs. Black), ethnicity (Hispanic/Latino vs. non-Hispanic/Latino), and body mass index (BMI, <30 vs. ≥30 kg/m²). MAIN OUTCOME MEASURES: Change from baseline to endpoint in mean sitting systolic blood pressure (MSSBP) and mean sitting diastolic blood pressure (MSDBP); blood pressure (BP) control rate <140/90 mmHg. RESULTS: Triple therapy was numerically superior and, for the majority of comparisons, statistically superior to each dual therapy in reducing MSSBP and MSDBP and in improving BP control rates in all subgroups. Across subgroups, triple therapy reduced MSSBP by 5.7-10.7 mmHg more than Val/HCTZ, 3.4-8.3 mmHg more than Aml/Val, and 4.4-9.4 mmHg more than Aml/HCTZ. Triple therapy was well tolerated across all subgroups. Limitations of our analysis included the lack of stratification of patients by subgroup at randomization and the small sample size of some subgroups (e.g., Blacks, elderly). CONCLUSIONS: Triple therapy with Aml/Val/HCTZ is effective and well tolerated in patients with moderate to severe hypertension regardless of age, gender, race, ethnicity, or BMI. TRIAL REGISTRATION NUMBER: NCT00327587.

The contributions of unhealthy lifestyle factors to apparent resistant hypertension: findings from the Reasons for Geographic And Racial Differences in Stroke (REGARDS) study.

OBJECTIVES: Unhealthy lifestyle factors may contribute to apparent treatment resistant hypertension (aTRH). We examined associations of unhealthy lifestyle factors with aTRH in individuals taking antihypertensive medications from three or more classes. METHODS: Participants (n = 2602) taking three or more antihypertensive medication classes were identified from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study. aTRH was defined as having SBP/DBP at least 140/90 mmHg despite the use of three or more antihypertensive medication classes or the use of four or more classes to achieve blood pressure control. Lifestyle factors included obesity, physical inactivity, current smoking, heavy alcohol consumption, a low Dietary Approaches to Stop Hypertension (DASH) diet score and high sodium-to-potassium (Na/K) intake. RESULTS: Among participants taking three or more antihypertensive medication classes, 1293 (49.7%) participants had aTRH. The prevalence of unhealthy lifestyle factors in participants with and without aTRH was 55.2 and 51.7%, respectively, for obesity, 42.2 and 40.5% for physical inactivity, 11.3 and 11.5% for current smoking, 3.1 and 4.0% for heavy alcohol consumption, 23.1 and 21.5% for low-DASH diet score, and 25.4 and 24.4% for high Na/K intake. After adjustment for age, sex, race, and geographic region of residence, none of the unhealthy lifestyle factors were associated with aTRH. The associations between each unhealthy lifestyle factor and aTRH remained nonsignificant after additional adjustment for education, income, depressive symptoms, total calorie intake, and comorbidities. CONCLUSIONS: Unhealthy lifestyle factors did not have independent associations with aTRH among individuals taking three or more antihypertensive medication classes.

Moderate waist circumference and hypertension prevalence: the REGARDS Study.

BACKGROUND: High waist circumference (WC) (women: >88 cm; men: >102 cm) increases cardiovascular risk. Less is known about moderate WC (women: 80-88 cm; men: 94-102 cm). Therefore, we examined the association between moderate WC and hypertension prevalence, independent of body mass index (BMI). METHODS: Among 24,247 eligible adults 45-84 years old, when recruited from January 2003 to October 2007 in the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) cohort, we examined hypertension prevalence (systolic blood pressure (BP) ≥140 mm Hg, or diastolic BP ≥90 mm Hg, or self-reported antihypertensive medication use) by WC before and after stratification by BMI (normal: 18.5-24.9; overweight: 25-29.9; obese class I: 30-34.9). Logistic regression adjusted associations between WC, BMI, and hypertension prevalence for age, race, sex, region, income, education, cigarette smoking, glomerular filtration rate, alcohol use, and physical activity. RESULTS: Overall, hypertension prevalence was 44% among those with low WC (n = 8,068), 55% with moderate WC (n = 6,488), and 66% with high WC (n = 9,691). After full adjustment, moderate WC was independently associated with hypertension prevalence among persons with normal BMI, (adjusted odds ratio (aOR), 1.49; 95% confidence interval (CI), 1.31-1.70), overweight BMI (aOR, 1.80; 95% CI, 1.64-1.98), and obese class I BMI (aOR, 2.28; 95%CI, 1.96-2.65) (referent: low WC-normal BMI). The moderate WC-hypertension association was observed in blacks and whites and in men and women. CONCLUSION: Moderate WC is associated with hypertension prevalence independent of BMI and several hypertension risk factors in middle-aged and older adults.

Geographic and demographic variability in 20-year hypertension incidence: the CARDIA study.

Although the variability of cardiovascular disease mortality by geography, race, and sex is well known, less is known about risk factor variation. We assessed 20-year incidence of hypertension, a cardiovascular disease risk factor, across 4 US urban areas and by race-sex. Among 3436 eligible adults 18 to 30 years of age when recruited in 1985 to 1986 in the community-based Coronary Artery Risk Development in Young Adults (CARDIA) cohort, we examined 20-year cumulative incidence of hypertension (systolic blood pressure ≥ 140 mm Hg or diastolic blood pressure ≥ 90 mm Hg or antihypertensive medication use at any examination) by site and race-sex, adjusting for baseline and time-dependent covariates with Cox regression. Twenty-year incidence, when the mean age was ≈ 45 years, was 34.5% in black men (n = 617), 37.6% in black women (n = 965), 21.4% in white men (n = 856), and 12.3% in white women (n = 998; P<0.001). Incidence was 33.6% in Birmingham, Ala, 23.4% in Chicago, Ill, 19% in Minneapolis, Minn, and 27.4% in Oakland, Calif (P<0.001). After adjustment for age, race, sex, heart rate, body mass index, smoking, family history, education, uric acid, alcohol use, physical activity, and baseline systolic blood pressure, hazard ratios (95% CI) compared with Birmingham were 0.72 (0.59 to 0.87) for Chicago, 0.60 (0.50 to 0.74) for Minneapolis, and 0.73 (0.61 to 0.87) for Oakland. Race-sex differences persisted after adjustment for site, especially for black women. From young adulthood to middle age, hypertension incidence varies significantly across urban areas. Independent of geography, blacks, especially women, are at markedly higher risk of hypertension. Hypertension incidence may contribute to geographic and racial differences in cardiovascular disease mortality, including stroke.

Resistant hypertension, secondary hypertension, and hypertensive crises: diagnostic evaluation and treatment.

Hypertension is a very common modifiable risk factor for cardiovascular morbidity and mortality. Patients with hypertension represent a diverse group. In addition to those with primary hypertension, there are patients whose hypertension is attributable to secondary causes, those with resistant hypertension, and patients who present with a hypertensive crisis. Secondary causes of hypertension account for less than 10% of cases of elevated blood pressure (BP), and screening for these causes is warranted if clinically indicated. Patients with resistant hypertension, whose BP remains uncontrolled in spite of use of 3 or more antihypertensive agents, are at increased cardiovascular risk compared with the general hypertensive population. After potentially correctible causes of uncontrolled BP (pseudoresistance, secondary causes, and intake of interfering substances) are eliminated, patients with true resistant hypertension are managed by encouraging therapeutic lifestyle changes and optimizing the antihypertensive regimen, whereby the clinician ensures that the medications are prescribed at optimal doses using drugs with complementary mechanisms of action, while adding an appropriate diuretic if there are no contraindications. Mineralocorticoid receptor antagonists are formidable add-on agents to the antihypertensive regimen, usually as a fourth drug, and are effective in reducing BP even in patients without biochemical evidence of aldosterone excess. In the setting of a hypertensive crisis, the BP has to be reduced within hours in the case of a hypertensive emergency (elevated BP with evidence of target organ damage) using parenteral agents, and within a few days if there is hypertensive urgency, using oral antihypertensive agents.