| 1. |
- Alvarez-Madrazo, S., et al.
(författare)
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Common Polymorphisms in the CYP11B1 and CYP11B2 Genes: Evidence for a Digenic Influence on Hypertension
- 2013
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Ingår i: Hypertension. - : Ovid Technologies (Wolters Kluwer Health). - 0194-911X .- 1524-4563. ; 61:1, s. 232-239
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Tidskriftsartikel (refereegranskat)abstract
- The locus encompassing the corticosteroidogenic genes CYP11B2 and CYP11B1 is of potential importance in essential hypertension. We analyzed the association of polymorphisms at this locus with risk of essential hypertension, using 2 white case-control collections for discovery (n = 3340) and confirmation (n = 2929). Single-marker and haplotype analyses were performed, with the CYP11B2 Intron 2 Conversion polymorphism showing strongest association with hypertension in both cohorts and in combined analysis (odds ratio = 1.16, P = 8.54x10(-5)). The CYP11B1 ACA haplotype associated with increased risk of hypertension relative to the alternative, GTC (odds ratio = 1.11; P = 7.4x10(-3)), whereas the CYP11B2 TWtC haplotype seemed protective relative to the contrasting CConvT (odds ratio = 0.88, P = 2.2x10(-3)). Analysis spanning the whole CYP11B1/CYP11B2 locus showed that haplotypes associated with raised risk of hypertension tend to coexist. Functional analysis of heterozygous human adrenal tissue demonstrated decreased CYP11B2 expression and increased CYP11B1 expression for those alleles associating with reduced risk of hypertension. These results confirm the hypertensive influence of this locus, with data suggesting a complex digenic mechanism whereby altered relative CYP11B1 and CYP11B2 gene expression could have a chronic effect on enzyme activity and corticosteroid synthesis.
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| 2. |
- Asayama, Kei, et al.
(författare)
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Setting Thresholds to Varying Blood Pressure Monitoring Intervals Differentially Affects Risk Estimates Associated With White-Coat and Masked Hypertension in the Population
- 2014
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 64:5, s. 935-942
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Tidskriftsartikel (refereegranskat)abstract
- Outcome-driven recommendations about time intervals during which ambulatory blood pressure should be measured to diagnose white-coat or masked hypertension are lacking. We cross-classified 8237 untreated participants (mean age, 50.7 years; 48.4% women) enrolled in 12 population studies, using >= 140/>= 90, >= 130/>= 80, >= 135/>= 85, and >= 120/>= 70 mm Hg as hypertension thresholds for conventional, 24-hour, daytime, and nighttime blood pressure. White-coat hypertension was hypertension on conventional measurement with ambulatory normotension, the opposite condition being masked hypertension. Intervals used for classification of participants were daytime, nighttime, and 24 hours, first considered separately, and next combined as 24 hours plus daytime or plus nighttime, or plus both. Depending on time intervals chosen, white-coat and masked hypertension frequencies ranged from 6.3% to 12.5% and from 9.7% to 19.6%, respectively. During 91 046 person-years, 729 participants experienced a cardiovascular event. In multivariable analyses with normotension during all intervals of the day as reference, hazard ratios associated with white-coat hypertension progressively weakened considering daytime only (1.38; P=0.033), nighttime only (1.43; P=0.0074), 24 hours only (1.21; P=0.20), 24 hours plus daytime (1.24; P=0.18), 24 hours plus nighttime (1.15; P=0.39), and 24 hours plus daytime and nighttime (1.16; P=0.41). The hazard ratios comparing masked hypertension with normotension were all significant (P<0.0001), ranging from 1.76 to 2.03. In conclusion, identification of truly low-risk white-coat hypertension requires setting thresholds simultaneously to 24 hours, daytime, and nighttime blood pressure. Although any time interval suffices to diagnose masked hypertension, as proposed in current guidelines, full 24-hour recordings remain standard in clinical practice.
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| 3. |
- Bakris, George L, et al.
(författare)
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Divergent results using clinic and ambulatory blood pressures report of a darusentan-resistant hypertension trial
- 2010
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 56:5, s. 824-830
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Tidskriftsartikel (refereegranskat)abstract
- Patients with resistant hypertension are at increased risk for cardiovascular events. The addition of new treatments to existing therapies will help achieve blood pressure (BP) goals in more resistant hypertension patients. In the current trial, 849 patients with resistant hypertension receiving ≥3 antihypertensive drugs, including a diuretic, at optimized doses were randomized to the selective endothelin A receptor antagonist darusentan, placebo, or the central α-2 agonist guanfacine. The coprimary end points of the study were changes from baseline to week 14 in trough, sitting systolic BP, and diastolic BP measured in the clinic. Decreases from baseline to week 14 in systolic BP for darusentan (−15±14 mm Hg) were greater than for guanfacine (−12±13 mm Hg; P<0.05) but not greater than placebo (−14±14 mm Hg). Darusentan, however, reduced mean 24-hour systolic BP (−9±12 mm Hg) more than placebo (−2±12 mm Hg) or guanfacine (−4±12 mm Hg) after 14 weeks of treatment (P<0.001 for each comparison). The most frequent adverse event associated with darusentan was fluid retention/edema at 28% versus 12% in each of the other groups. More patients withdrew because of adverse events on darusentan as compared with placebo or guanfacine. We conclude that darusentan provided greater reduction in systolic BP in resistant hypertension patients as assessed by ambulatory BP monitoring, in spite of not meeting its coprimary end points. The results of this trial highlight the importance of ambulatory BP monitoring in the design of hypertension clinical studies.
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| 4. |
- Barnes, J. N., et al.
(författare)
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Aging enhances autonomic support of blood pressure in women
- 2014
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 63:2, s. 303-308
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Tidskriftsartikel (refereegranskat)abstract
- The autonomic nervous system plays a central role in both acute and chronic blood pressure regulation in humans. The activity of the sympathetic branch of the autonomic nervous system is positively associated with peripheral resistance, an important determinant of mean arterial pressure in men. In contrast, there is no association between sympathetic nerve activity and peripheral resistance in women before menopause, yet a positive association after menopause. We hypothesized that autonomic support of blood pressure is higher after menopause in women. We examined the effect of ganglionic blockade on arterial blood pressure and how this relates to baseline muscle sympathetic nerve activity in 12 young (25±1 years) and 12 older postmenopausal (61±2 years) women. The women were studied before and during autonomic blockade using trimethaphan camsylate. At baseline, muscle sympathetic nerve activity burst frequency and burst incidence were higher in the older women (33±3 versus 15±1 bursts/min; 57±5 versus 25±2 bursts/100 heartbeats, respectively; P<0.05). Muscle sympathetic nerve activity bursts were abolished by trimethaphan within minutes. Older women had a greater decrease in mean arterial pressure (-29±2 versus-9±2 mm Hg; P<0.01) and total peripheral resistance (-10±1 versus-5±1 mm Hg/L per minute; P<0.01) during trimethaphan. Baseline muscle sympathetic nerve activity was associated with the decrease in mean arterial pressure during trimethaphan (r=-0.74; P<0.05). In summary, our results suggest that autonomic support of blood pressure is greater in older women compared with young women and that elevated sympathetic nerve activity in older women contributes importantly to the increased incidence of hypertension after menopause. © 2013 American Heart Association, Inc.
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| 5. |
- Boggia, Jose, et al.
(författare)
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Ambulatory Blood Pressure Monitoring in 9357 Subjects From 11 Populations Highlights Missed Opportunities for Cardiovascular Prevention in Women
- 2011
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 57:3, s. 397-405
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Tidskriftsartikel (refereegranskat)abstract
- To analyze sex-specific relative and absolute risks associated with blood pressure (BP), we performed conventional and 24-hour ambulatory BP measurements in 9357 subjects (mean age, 52.8 years; 47% women) recruited from 11 populations. We computed standardized multivariable-adjusted hazard ratios for associations between outcome and systolic BP. During a course of 11.2 years (median), 1245 participants died, 472 of cardiovascular causes. The number of fatal combined with nonfatal events was 1080, 525, and 458 for cardiovascular and cardiac events and for stroke, respectively. In women and men alike, systolic BP predicted outcome, irrespective of the type of BP measurement. Women compared with men were at lower risk (hazard ratios for death and all cardiovascular events=0.66 and 0.62, respectively; P<0.001). However, the relation of all cardiovascular events with 24-hour BP (P=0.020) and the relations of total mortality (P=0.023) and all cardiovascular (P=0.0013), cerebrovascular (P=0.045), and cardiac (P=0.034) events with nighttime BP were steeper in women than in men. Consequently, per a 1-SD decrease, the proportion of potentially preventable events was higher in women than in men for all cardiovascular events (35.9% vs 24.2%) in relation to 24-hour systolic BP (1-SD, 13.4 mm Hg) and for all-cause mortality (23.1% vs 12.3%) and cardiovascular (35.1% vs 19.4%), cerebrovascular (38.3% vs 25.9%), and cardiac (31.0% vs 16.0%) events in relation to systolic nighttime BP (1-SD, 14.1 mm Hg). In conclusion, although absolute risks associated with systolic BP were lower in women than men, our results reveal a vast and largely unused potential for cardiovascular prevention by BP-lowering treatment in women.
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| 6. |
- Boggia, Jose, et al.
(författare)
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Risk Stratification by 24-Hour Ambulatory Blood Pressure and Estimated Glomerular Filtration Rate in 5322 Subjects From 11 Populations
- 2013
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 61:1, s. 18-
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Tidskriftsartikel (refereegranskat)abstract
- No previous study addressed whether in the general population estimated glomerular filtration rate (eGFR [Chronic Kidney Disease Epidemiology Collaboration formula]) adds to the prediction of cardiovascular outcome over and beyond ambulatory blood pressure. We recorded health outcomes in 5322 subjects (median age, 51.8 years; 43.1% women) randomly recruited from 11 populations, who had baseline measurements of 24-hour ambulatory blood pressure (ABP(24)) and eGFR. We computed hazard ratios using multivariable-adjusted Cox regression. Median follow-up was 9.3 years. In fully adjusted models, which included both ABP(24) and eGFR, ABP(24) predicted (P <= 0.008) both total (513 deaths) and cardiovascular (206) mortality; eGFR only predicted cardiovascular mortality (P=0.012). Furthermore, ABP(24) predicted (P <= 0.0056) fatal combined with nonfatal events as a result of all cardiovascular causes (555 events), cardiac disease (335 events), or stroke (218 events), whereas eGFR only predicted the composite cardiovascular end point and stroke (P <= 0.035). The interaction terms between ABP(24) and eGFR were all nonsignificant (P >= 0.082). For cardiovascular mortality, the composite cardiovascular end point, and stroke, ABP(24) added 0.35%, 1.17%, and 1.00% to the risk already explained by cohort, sex, age, body mass index, smoking and drinking, previous cardiovascular disease, diabetes mellitus, and antihypertensive drug treatment. Adding eGFR explained an additional 0.13%, 0.09%, and 0.14%, respectively. Sensitivity analyses stratified for ethnicity, sex, and the presence of hypertension or chronic kidney disease (eGFR <60mL/min per 1.73 m(2)) were confirmatory. In conclusion, in the general population, eGFR predicts fewer end points than ABP(24). Relative to ABP(24), eGFR is as an additive, not a multiplicative, risk factor and refines risk stratification 2-to14-fold less.
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| 7. |
- Carlsson, Axel C, et al.
(författare)
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Association Between Circulating Endostatin, Hypertension Duration, and Hypertensive Target-Organ Damage
- 2013
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Ingår i: Hypertension. - : Lippincott Williams & Wilkins. - 0194-911X .- 1524-4563. ; 62:6, s. 1146-1151
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Tidskriftsartikel (refereegranskat)abstract
- Our aim is to study associations between circulating endostatin, hypertension duration, and hypertensive target-organ damage. Long-term hypertension induces cardiovascular and renal remodeling. Circulating endostatin, a biologically active derivate of collagen XVIII, has been suggested to be a relevant marker for extracellular matrix turnover and remodeling in various diseases. However, the role of endostatin in hypertension and hypertensive target-organ damage is unclear. Serum endostatin was measured in 2 independent community-based cohorts: the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS; women 51%; n=812; mean age, 75 years) and the Uppsala Longitudinal Study of Adult Men (ULSAM; n=785; mean age, 77.6 years). Retrospective data on blood pressure measurements and antihypertensive medication (PIVUS >5 years, ULSAM >27 years), and cross-sectional data on echocardiographic left ventricular mass, endothelial function (endothelium-dependent vasodilation assessed by the invasive forearm model), and urinary albumin/creatinine ratio were available. In PIVUS, participants with 5 years of history of hypertension portrayed 0.42 SD (95% confidence interval, 0.23-0.61; P<0.001) higher serum endostatin, compared with that of normotensives. This association was replicated in ULSAM, in which participants with 27 years hypertension duration had the highest endostatin (0.57 SD higher; 95% confidence interval, 0.35-0.80; P<0.001). In addition, higher endostatin was associated with higher left ventricular mass, worsened endothelial function, and higher urinary albumin/creatinine ratio (P<0.03 for all) in participants with prevalent hypertension. Circulating endostatin is associated with the duration of hypertension, and vascular, myocardial, and renal indices of hypertensive target-organ damage. Further studies are warranted to assess the prognostic role of endostatin in individuals with hypertension.
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| 8. |
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| 9. |
- Carlström, Mattias, et al.
(författare)
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Superoxide Dismutase 1 Limits Renal Microvascular Remodeling and Attenuates Arteriole and Blood Pressure Responses to Angiotensin II via Modulation of Nitric Oxide Bioavailability
- 2010
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 56:5, s. 907-913
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Tidskriftsartikel (refereegranskat)abstract
- Oxidative stress is associated with vascular remodeling and increased preglomerular resistance that are both implicated in the pathogenesis of renal and cardiovascular disease. Angiotensin II induces superoxide production, which is metabolized by superoxide dismutase (SOD) or scavenged by NO. We investigated the hypothesis that SOD1 regulates renal microvascular remodeling, blood pressure, and arteriolar responsiveness and sensitivity to angiotensin II using SOD1-transgenic (SOD1-tg) and SOD1-knockout (SOD1-ko) mice. Blood pressure, measured telemetrically, rose more abruptly during prolonged angiotensin II infusion in SOD1-ko mice. The afferent arteriole media: lumen ratios were reduced in SOD1-tg and increased in SOD1-ko mice. Afferent arterioles from nontreated wild types had graded contraction to angiotensin II (sensitivity: 10(-9) mol/L; responsiveness: 40%). Angiotensin II contractions were less sensitive (10(-8) mol/L) and responsive (14%) in SOD1-tg but more sensitive (10(-13) mol/L) and responsive (89%) in SOD1-ko mice. Arterioles from SOD1-ko had 4-fold increased superoxide formation with angiotensin II at 10(-9) mol/L. N-G-nitro-L-arginine methyl ester reduced arteriole diameter of SOD1-tg and enhanced angiotensin II sensitivity and responsiveness of wild-type and SOD1-tg mice to the level of SOD1-ko mice. SOD mimetic treatment with Tempol increased arteriole diameter and normalized the enhanced sensitivity and responsiveness to angiotensin II of SOD1-ko mice but did not affect wild-type or SOD1-tg mice. Neither SOD1 deficiency nor overexpression was associated with changes in nitrate/nitrite excretion or renal mRNA expression of NO synthase, NADPH oxidase, or SOD2/SOD3 isoforms and angiotensin II receptors. In conclusion, SOD1 limits afferent arteriole remodeling and reduces sensitivity and responsiveness to angiotensin II by reducing superoxide and maintaining NO bioavailability. This may prevent an early and exaggerated blood pressure response to angiotensin II.
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| 10. |
- Conen, David, et al.
(författare)
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Age-Specific Differences Between Conventional and Ambulatory Daytime Blood Pressure Values
- 2014
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 64:5, s. 1073-1079
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Tidskriftsartikel (refereegranskat)abstract
- Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and 24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and >= 70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001). The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged >= 70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.
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