| 1. |
- 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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| 2. |
- Brunström, Mattias, et al.
(författare)
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Methodological Aspects of Meta-Analyses Assessing the Effect of Blood Pressure-Lowering Treatment on Clinical Outcomes
- 2022
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 79:3, s. 491-504
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Tidskriftsartikel (refereegranskat)abstract
- Systematic reviews and meta-analyses are often considered the highest level of evidence, with high impact on clinical practice guidelines. The methodological literature on systematic reviews and meta-analyses is extensive and covers most aspects relevant to the design and interpretation of meta-analysis findings in general. Analyzing the effect of blood pressure-lowering on clinical outcomes poses several challenges over and above what is covered in the general literature, including how to combine placebo-controlled trials, target-trials, and comparative studies depending on the research question, how to handle the potential interaction between baseline blood pressure level, common comorbidities, and the estimated treatment effect, and how to consider different magnitudes of blood pressure reduction across trials. This review aims to address the most important methodological considerations, to guide the general reader of systematic reviews and meta-analyses within our field, and to help inform the design of future studies. Furthermore, we highlight issues where published meta-analyses have applied different analytical strategies and discuss pros and cons with different strategies.
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| 4. |
- 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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| 5. |
- Devereux, Richard B., et al.
(författare)
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Left Ventricular Wall Stress-Mass-Heart Rate Product and Cardiovascular Events in Treated Hypertensive Patients LIFE Study
- 2015
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 66:5, s. 945-953
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Tidskriftsartikel (refereegranskat)abstract
- In the Losartan Intervention for End Point Reduction in Hypertension (LIFE) study, 4.8 years' losartan- versus atenolol-based antihypertensive treatment reduced left ventricular hypertrophy and cardiovascular end points, including cardiovascular death and stroke. However, there was no difference in myocardial infarction (MI), possibly related to greater reduction in myocardial oxygen demand by atenolol-based treatment. Myocardial oxygen demand was assessed indirectly by the left ventricular massxwall stressxheart rate (triple product) in 905 LIFE participants. The triple product was included as time-varying covariate in Cox models assessing predictors of the LIFE primary composite end point (cardiovascular death, MI, or stroke), its individual components, and all-cause mortality. At baseline, the triple product in both treatment groups was, compared with normal adults, elevated in 70% of patients. During randomized treatment, the triple product was reduced more by atenolol, with prevalences of elevated triple product of 39% versus 51% on losartan (both P0.001). In Cox regression analyses adjusting for age, smoking, diabetes mellitus, and prior stroke, MI, and heart failure, 1 SD lower triple product was associated with 23% (95% confidence interval 13%-32%) fewer composite end points, 31% (18%-41%) less cardiovascular mortality, 30% (15%-41%) lower MI, and 22% (11%-33%) lower all-cause mortality (all P0.001), without association with stroke (P=0.34). Although losartan-based therapy reduced ventricular mass more, greater heart rate reduction with atenolol resulted in larger reduction of the triple product. Lower triple product during antihypertensive treatment was strongly, independently associated with lower rates of the LIFE primary composite end point, cardiovascular death, and MI, but not stroke.
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| 6. |
- Donat-Vargas, Carolina, et al.
(författare)
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Persistent Organochlorine Pollutants in Plasma, Blood Pressure, and Hypertension in a Longitudinal Study
- 2018
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Ingår i: Hypertension. - 0194-911X .- 1524-4563. ; 71:6, s. 1258-1268
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Tidskriftsartikel (refereegranskat)abstract
- Persistent organochlorine pollutants (POPs) have shown to be involved in the atherosclerotic process and to cause endothelial cell dysfunction. To assess longitudinally whether plasma concentrations of different POPs were associated with blood pressure and risk of hypertension in middle-aged women and men. Study subjects were 850 participants in the VIP (Västerbotten Intervention Programme) with 2 blood samples and blood pressure measurements, 10 years apart, during 1990 to 2003 (baseline) and during 2000 to 2013 (follow-up). Dioxin-like and nondioxin-like polychlorinated biphenyls (DL-PCBs, NDL-PCBs) and p,p'-dichlorodiphenyldichloroethylene (DDE) were measured. Associations were assessed using generalized estimating equations. At baseline sampling 49% and at follow-up 64% had hypertension. DL-PCBs and DDE, but not NDL-PCBs or hexachlorobenzene, were associated with hypertension. Only the association for DL-PCBs remained statistically significant after lipid-standardization and adjustment for body mass index and total serum lipids. The multivariable-adjusted odds ratio of hypertension based on repeated measurements were 1.52 (95% confidence interval, 1.08-2.13) for DL-PCBs (third versus first tertile of lipid-standardized POPs). In stratified adjusted analyses, odds ratio for those born after 1950 increased to 3.99 (95% confidence interval, 2.15-7.43), whereas no association was observed among those born earlier. Based on repeated measurements, the accumulated exposure to DL-PCBs and DDE, although less clear for the latter, may disrupt the normal blood pressure levels and increase the odds of hypertension. Moreover, individuals experiencing early-life POP exposure may be at elevated risk of vascular POP effects.
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| 7. |
- Eriksson, Jan W., et al.
(författare)
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Hydrochlorothiazide, but not Candesartan, aggravates insulin resistance and causes visceral and hepatic fat accumulation : the mechanisms for the diabetes preventing effect of Candesartan (MEDICA) Study
- 2008
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Ingår i: Hypertension. - : American Heart Association. - 0194-911X .- 1524-4563. ; 52:6, s. 1030-1037
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Tidskriftsartikel (refereegranskat)abstract
- Treatment with angiotensin II receptor blockers is associated with lower risk for the development of type 2 diabetes mellitus compared with thiazide diuretics. The Mechanisms for the Diabetes Preventing Effect of Candesartan Study addressed insulin action and secretion and body fat distribution after treatment with candesartan, hydrochlorothiazide, and placebo. Twenty-six nondiabetic, abdominally obese, hypertensive patients were included in a multicenter 3-way crossover trial, and 22 completers (by predefined criteria; 10 men and 12 women) were included in the analyses. They underwent 12-week treatment periods with candesartan (C; 16 to 32 mg), hydrochlorothiazide (H; 25 to 50 mg), and placebo (P), respectively, and the treatment order was randomly assigned and double blinded. Intravenous glucose tolerance tests and euglycemic hyperinsulinemic (56 mU/m(2) per minute) clamps were performed. Intrahepatic and intramyocellular and extramyocellular lipid content and subcutaneous and visceral abdominal adipose tissue were measured using proton magnetic resonance spectroscopy and MRI. Insulin sensitivity (M-value) was reduced following H versus C and P (6.07+/-2.05, 6.63+/-2.04, and 6.90+/-2.10 mg/kg of body weight per minute, mean+/-SD; P
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