Abstract:
BACKGROUND:There is evidence from genome wide association study that single-nucleotide polymorphisms (SNPs) in the 5' end of the uromodulin gene (UMOD) affect uromodulin excretion and blood pressure (BP). Uromodulin is almost exclusively expressed in the thick ascending limb of the loop of Henle (TAL) and its effect on BP appear to be mediated via the TAL sodium transporter, NKCC2. Loop-diuretics block NKCC2 but are not commonly used in hypertension management. As volume overload is considered as one of the primary drivers for uncontrolled hypertension, targeting loop-diuretics to individuals who are more likely to respond to this drug class, using UMOD genotype, could be an efficient precision medicine strategy. METHODS:A genotype-blinded, multi-centre trial comparing the BP response to torasemide between individuals possessing the AA genotype of the SNP rs13333226 and those possessing the G allele. 240 participants with uncontrolled BP aged ≥18 years, on ≥1 antihypertensive agent for ≥3 months, will be included. Uncontrolled BP is average systolic BP (SBP) >135mmHg and/or diastolic BP >85mmHg on home monitoring. Torasemide, 5mg daily, is taken for 16 weeks. The primary outcome is the change in 24h ambulatory SBP area under the curve between baseline and end of treatment. Sample size was calculated to detect a 4mmHg difference between groups at 90% power. Approval by West of Scotland Research Ethics Committee 5 (16/WS/0160). Registration at https://clinicaltrials.gov/ct2/show/NCT03354897. RESULTS:The study should conclude August 2021. CONCLUSIONS:If hypothesis confirmed, a targeted strategy will improve BP control and could reduce the burden of uncontrolled hypertension.
journal_name
Am J Hypertensjournal_title
American journal of hypertensionauthors
McCallum L,Brooksbank K,McConnachie A,Aman A,Lip S,Dawson J,MacIntyre IM,MacDonald TM,Webb DJ,Padmanabhan Sdoi
10.1093/ajh/hpaa166subject
Has Abstractpub_date
2020-10-21 00:00:00eissn
0895-7061issn
1941-7225pii
5934425pub_type
杂志文章abstract:BACKGROUND:The mechanism of left atrial (LA) remodeling is poorly understood. The aim of this longitudinal study was to investigate whether changes in NT-proBNP levels relate to alterations of LA structure and function over time in a multi-ethnic population. METHODS:From the prospective cohort study, the Multi-Ethnic ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpab018
更新日期:2021-01-25 00:00:00
abstract:BACKGROUND:Although insulin resistance and metabolic syndrome are often used synonymously, concordance is not established. METHODS:Metabolic, hemodynamic, and hormonal data were analyzed on 141 patients in the Trial of Preventing Hypertension (TROPHY) Sub-Study with high-normal blood pressure (BP) (130 to 139/85 to 89...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2004.08.008
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:Salt sensitivity of blood pressure (SSBP) increases the risk of cardiovascular complications, and the heritability of SSBP is about 50% in Chinese population. However, studies identifying genes involved in BP responses to acute sodium loading and diuresis shrinkage are still limited. METHOD:A total of 342 e...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpx179
更新日期:2018-03-10 00:00:00
abstract::The stimulation of autocrine and paracrine factors such as basic fibroblast- (bFGF) and platelet-derived (PDGF) growth factors mediates many of the growth-promoting actions of angiotensin II. The aim of this study was to evaluate the effect of chronic AT1-receptor blockade on plasma endothelin-1 (ET-1) and growth fact...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(98)00027-2
更新日期:1998-05-01 00:00:00
abstract::The effect of fish oil on potassium efflux and basal tension in aortas from stroke prone spontaneously hypertensive rats (SHRSP) was evaluated. Four-week-old male Wistar-Kyoto rats (WKY) and SHRSP were divided into two groups: one received a 5% corn oil diet; the other a 5% menhaden oil diet. After 15 weeks, mean syst...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/5.7.473
更新日期:1992-07-01 00:00:00
abstract:BACKGROUND:The association between hypertension (HTN) and inflammatory biomarkers (interleukin-6 [IL-6] and high-sensitivity C-reactive protein [hsCRP]) in HIV-positive persons with CD4+ count >500 cells/mm3 is unknown. METHODS:We studied HTN in participants of the Strategic Timing of AntiRetroviral Treatment (START) ...
journal_title:American journal of hypertension
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1093/ajh/hpz132
更新日期:2020-01-01 00:00:00
abstract::Sodium ions markedly decreased in vitro renal alpha 2-adrenoceptor affinity for epinephrine in Sabra hypertensive (SBH) but not in normotensive (SBN) rats. Under these conditions, affinity of alpha 1-adrenoceptor for epinephrine was unchanged in SBH and SBN rats. If these data could be confirmed in vivo, the sodium io...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/4.3.267
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND:Ionized magnesium levels are elevated in fetal blood compared with maternal blood, suggesting that the placenta may possess an active transport mechanism for magnesium. In the present study, we sought to determine the existence of an active transport mechanism for magnesium in the placenta using cultured tro...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(02)02272-0
更新日期:2002-06-01 00:00:00
abstract::Although the most direct way to interfere with the renin-angiotensin system (RAS) is at the level of the angiotensin II (AII) receptor, the currently available AII receptor antagonists are peptides still retaining significant agonistic properties with the obvious drawbacks of limited stability and lack of oral activit...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1093/ajh/3.8.599
更新日期:1990-08-01 00:00:00
abstract:BACKGROUND:The aim of this study was to test the hypothesis that angiotensin converting enzyme inhibition or angiotensin II antagonism can counteract cardiac human vascular endothelial growth factor-A165 (phVEGF-A165) induced angiogenesis. METHODS:Mice were given a single intramyocardial injection of phVEGF-A165. Eith...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.04.023
更新日期:2005-10-01 00:00:00
abstract::Molecular evidence, using DNA fingerprint analyses, of extensive genetic heterogeneity between spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) and even within some of the WKY colonies has been reported. Thus we investigated the genetic relations between Dahl S and R rats newly inbred by Dr. Iwai. Gen...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:
更新日期:1997-05-01 00:00:00
abstract:OBJECTIVES:Central blood pressure (BP) can be used to define hypertension. A central BP approach may be more sensitive than a conventional brachial BP approach in detecting hypertension. We aimed to compare the 2 approaches in estimating the prevalence hypertension in a nationally representative population. METHODS:A ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpx178
更新日期:2018-02-09 00:00:00
abstract:BACKGROUND:Differences between the antihypertensive responses to drug therapy measured by office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) techniques have been noted but rarely analyzed. We studied whether the OBP and 24-h ABPM responses to hydrochlorothiazide differ and, if so, the relevance...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1016/j.amjhyper.2004.10.021
更新日期:2005-03-01 00:00:00
abstract:BACKGROUND:Azilsartan medoxomil (AZL-M), an angiotensin II receptor blocker, demonstrates antihypertensive and organ protective effects in hypertension. We investigated the efficacy of AZL-M to ameliorate metabolic syndrome and kidney damage associated with type 2 diabetes using Zucker diabetic fatty (ZDF) rats. METHO...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu016
更新日期:2014-08-01 00:00:00
abstract:BACKGROUND:The direct renin inhibitor aliskiren is known to exhibit a strong antihypertensive effect. However, the organoprotective potential of aliskiren beyond its antihypertensive properties is less clear. This study investigates the antifibrotic nephroprotective effects of aliskiren in a nonhypertensive mouse model...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2010.231
更新日期:2011-03-01 00:00:00
abstract::Recent publications purporting to show that calcium antagonists, when used for the treatment of hypertension or in the post myocardial infarction patient, would paradoxically increase the rate of heart attack and mortality have cast doubts on the safety and efficacy of this drug class. All three studies are retrospect...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(96)00387-1
更新日期:1996-12-01 00:00:00
abstract:BACKGROUND:Previous autopsy studies suggested that a reduced nephron number is associated with increased risk of hypertension and chronic kidney disease. However, the significance of the nephron number estimated from a renal biopsy in patients with hypertensive nephrosclerosis (HNS) has not yet been elucidated. METHOD...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpu267
更新日期:2015-09-01 00:00:00
abstract:BACKGROUND:Apelin is an adipokine directly associated with adiposity, insulin resistance, and decreased blood pressure. Urinary 8-isoprostane is a marker of chronic oxidative endothelial stress. Visfatin, an adipokine that acts by binding and activating the insulin receptor, has been associated with hypertension. As se...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpw007
更新日期:2016-07-01 00:00:00
abstract:BACKGROUND:We determined the prognostic value of the Cornell/strain [C/S] index, a simple electrocardiographic (ECG) index for left ventricular hypertrophy (LVH) defined by the presence of either a classic strain pattern or a Cornell voltage (sum of R in aVL + S in V(3)) >2.0 mV in women or 2.4 mV in men, or both. MET...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章
doi:10.1016/s0895-7061(03)00912-9
更新日期:2003-08-01 00:00:00
abstract::The purpose of this double-blind, forced titration study was to compare the antihypertensive effect duration of candesartan cilexetil, which has a longlasting binding to the human AT1-receptor, to that of losartan on ambulatory BP (ABP) not only during the 24-h dosing interval but also during the day of a missed dose ...
journal_title:American journal of hypertension
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/s0895-7061(99)00142-9
更新日期:1999-12-01 00:00:00
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journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/4.5.464
更新日期:1991-05-01 00:00:00
abstract:BACKGROUND:Blood pressure (BP) measured in the office setting increases from early through later adulthood. However, it is unknown to what extent out-of-office BP derived via ambulatory BP monitoring (ABPM) increases over time, and which participant characteristics and risk factors might contribute to these increases. ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1093/ajh/hpaa189
更新日期:2020-11-17 00:00:00
abstract:BACKGROUND:To clarify whether the double product (DP) (product of systolic blood pressure (SBP) and pulse rate (PR)) at rest based on home blood pressure (HBP) measurement has prognostic value for mortality. METHODS:HBP data of 2,583 participants from a Japanese general population (40% men) ≥35 years of age (mean, 59 ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2012.3
更新日期:2012-05-01 00:00:00
abstract:BACKGROUND:Increased sodium intake has been positively associated with high blood pressure (BP) and hypertensive target organ damage, but associations with cardiac structure in nonhypertensive individuals have yielded inconsistent results. We tested the hypothesis that sodium intake is associated with left ventricular ...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2004.06.008
更新日期:2004-10-01 00:00:00
abstract:BACKGROUND:Expression of matrix metalloproteinase (MMP) has been shown in aortic dissection and aneurysms indicating increased proteolysis compared with the normal aorta. However, its role in the development of aortic root dilatation has not been studied. We therefore attempted to determine the relationship between aor...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/j.amjhyper.2005.08.013
更新日期:2006-04-01 00:00:00
abstract::Left ventricular hypertrophy in patients with hypertension is an important condition. It is associated with significant mortality and carries increased risk for developing nonfatal cardiovascular complications, including coronary heart disease. The pathogenesis of left ventricular hypertrophy is linked to activation o...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(00)01257-7
更新日期:2001-02-01 00:00:00
abstract::Stroke-prone spontaneously hypertensive rats (SHRSP), subjected to high NaCl, show severe hypertension, organ damage, and early death. Preventive treatment with angiotensin II type 1 (AT1) receptor antagonists is known to be effective. Previously, we found that angiotensin converting enzyme (ACE) inhibition could redu...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(00)01231-0
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Obesity is a risk factor for the development of cardiovascular diseases that are associated with impaired angiogenesis. Nifedipine, a calcium-channel blocker, has a number of blood pressure (BP)-independent effects as well, such as improving endothelial function and decreasing oxidative stress. Here, we inve...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1038/ajh.2011.239
更新日期:2012-04-01 00:00:00
abstract::The association between obesity and hypertension is well recognized. However, the exact mechanisms whereby obesity causes hypertension are complex and multifactorial. The current article summarizes some of the known mechanisms responsible for obesity hypertension. ...
journal_title:American journal of hypertension
pub_type: 杂志文章,评审
doi:10.1016/s0895-7061(01)02299-3
更新日期:2002-02-01 00:00:00
abstract::To assess whether aerobic exercise training is an effective and an alternative method to control blood pressure (BP) in hypertension, 32 uncomplicated, never treated patients suffering from mild-to-moderate essential arterial hypertension (EAH) were included in an aerobic exercise training program using a regular stan...
journal_title:American journal of hypertension
pub_type: 杂志文章
doi:10.1016/s0895-7061(99)00265-4
更新日期:2000-06-01 00:00:00