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- Brunström, Mattias, 1988-
(författare)
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Effect of antihypertensive treatment at different blood pressure levels
- 2017
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundHigh blood pressure is associated with an increased risk of cardiovascular disease and premature death. The shape of association between blood pressure and the risk of cardiovascular events is debated. Some researchers suggest that the association is linear or log-linear, whereas others suggest it is J-shaped. Randomized controlled trials of antihypertensive treatment have been successful in hypertension, but ambiguous in the high normal blood pressure range. Previous systematic reviews have not found any interaction between baseline systolic blood pressure and treatment effect, with beneficial effects at systolic blood pressure levels well below what is currently recommended. These reviews, however, use a method to standardize treatment effects and study weights according to within-trial blood pressure differences that may introduce bias.MethodsWe performed two systematic reviews to assess the effect of antihypertensive treatment on cardiovascular disease and mortality at different blood pressure levels. The first review was limited to people with diabetes mellitus. The second review included all patient categories except those with heart failure and acute myocardial infarction. Both reviews were designed with guidance from Cochrane Collaborations Handbook for Systematic Reviews of Interventions, and are reported according to PRISMA guidelines. We included randomized controlled trials assessing any antihypertensive agent against placebo or any blood pressure targets against each other. Results were combined in random-effects meta-analyses, stratified by baseline systolic blood pressure. Non-stratified analyses were performed for coronary heart disease trials and post-stroke trials. Interaction between blood pressure level and treatment effect was assessed with Cochran’s Q in the first review, and multivariable-adjusted metaregression in the second review.The third paper builds on data from the second paper, and assesses the effect of standardization according to within-trial blood pressure differences on the results of meta-analyses. We performed non-standardized analyses, analyses with standardized treatment effects, and analyses with standardized treatment effects and standard errors. We compared treatment effect measures and heterogeneity across different methods of standardization. We also compared treatment effect estimates between fixed-effects and random-effects meta-analyses within each method of standardization. Lastly, we assessed the association between number of events and study weights, using linear regression.ResultsForty-nine trials assessed the effect of antihypertensive treatment in people with diabetes mellitus. Treatment effect on cardiovascular mortality and myocardial infarction decreased with lower baseline systolic blood pressure. Treatment reduced the risk of death and cardiovascular disease if baseline systolic blood pressure was 140 mm Hg or higher. If baseline systolic blood pressure was below 140 mm Hg, however, treatment increased the risk of cardiovascular death by 15 % (0-32 %).Fifty-one trials assessed the effect of antihypertensive treatment in primary prevention. Treatment effect on cardiovascular mortality, major cardiovascular events, and heart failure decreased with lower baseline systolic blood pressure. If baseline systolic blood pressure was 160 mm Hg or higher treatment reduced the risk of major cardiovascular events by 22 % (95 % confidence interval 13-30 %). If systolic blood pressure was 140-159 mm Hg treatment reduced the risk by 12 % (4-20 %), whereas if systolic blood pressure was below 140 mm Hg, treatment effect was neutral (4 % increase to 10 % reduction). All-cause mortality was reduced if systolic blood pressure was 140 mm Hg or higher, with neutral effect at lower levels.Twelve trials compared antihypertensive treatment against placebo in people with coronary heart disease. Mean baseline systolic blood pressure was 138 mm Hg. Treatment reduced the risk of major cardiovascular events by 10 % (3-16 %), whereas the effect on mortality was neutral (7 % increase to 11 % reduction).Standardization of treatment effects resulted in more extreme effect estimates for individual trials. This caused increased between-study heterogeneity, and different results with fixed- and random-effects model. Standardization of standard errors shifted weights from trials with many events to trials with large blood pressure differences. This caused biased overall effect estimates. Standardization of standard errors also resulted in wider confidence intervals, masking the previously increased heterogeneity. This reduced the possibility to find different treatment effects at different blood pressure levels.Conclusion The effect of antihypertensive treatment depends on blood pressure level before treatment. Treatment reduces the risk of death and cardiovascular disease if baseline systolic blood pressure is 140 mm Hg or higher. Below this level, treatment is potentially harmful in people with diabetes, has neutral effect in primary prevention, but might offer additional protection in people with coronary heart disease. Standardization should generally be avoided in meta-analyses of antihypertensive treatment. Previous meta-analyses using standardized methods should be interpreted with caution.
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- Hasvold, Pal, et al.
(författare)
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Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting
- 2016
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Ingår i: Clinical drug investigation. - : Springer Science and Business Media LLC. - 1173-2563 .- 1179-1918. ; 36:3, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). Methods Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased >= 0.1 mmol/L, unchanged +/- 0.1 or >= 0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. Results HDL-C decreased in 20 %, was unchanged in 58%, and increased in 22 % of patients initiated on statin treatment (96 % treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56 % higher MACE risk (hazard ratio 1.56; 95 % confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. Conclusions Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.
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| 3. |
- Heimark, Sondre, et al.
(författare)
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Which Target Blood Pressure in Year 2018? Evidence from Recent Clinical Trials
- 2018
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Ingår i: High Blood Pressure and Cardiovascular Prevention. - : Springer Science and Business Media LLC. - 1120-9879 .- 1179-1985. ; 25:2, s. 151-158
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Forskningsöversikt (refereegranskat)abstract
- The Systolic Blood Pressure Intervention Trial (SPRINT) suggested a favourable effect of lowering blood pressure to < 120/80 mmHg in high-risk hypertensive patients; however, new American guidelines in 2017 have not followed SPRINT but lowered its recommended treatment target to < 130/80 mmHg. We aimed to review the latest research from large randomised controlled trials and observational analyses in order to investigate the evidence for new treatment targets. We assessed recent data from the Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD) study, the International Verapamil-Trandolapril Study (INVEST), the Telmisartan, Ramipril or Both in Patients at High Risk for Vascular Events trial (ONTARGET)/the Telmisartan Randomised AssessmenNt Study in aCE iNtolerant participants with cardiovascular Disease (TRANSCEND) study and The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study. These studies confirm a positive effect on cardiovascular protection with blood pressure lowering treatment to between 120–140 mmHg in patients with and without diabetes, but no additional effect of lowering blood pressure to < 120 mmHg; possibly too aggressive treatment may increase both cardiovascular morbidity and mortality. Thus, a target blood pressure < 130/80 mmHg appears appropriate in most high-risk hypertensive patients. Additionally, early and sustained BP control below this target is required for optimal cardiovascular protection.
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| 8. |
- Okin, Peter M., et al.
(författare)
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Digoxin use and risk of mortality in hypertensive patients with atrial fibrillation
- 2015
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 33:7, s. 1480-1486
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Tidskriftsartikel (refereegranskat)abstract
- Background: Digoxin is widely used for rate control of atrial fibrillation. However, recent studies have reported conflicting results on the association of digoxin with mortality when used in patients with atrial fibrillation. Moreover, the relationship of digoxin use to mortality in hypertensive patients with atrial fibrillation has not been examined.Methods and results: All-cause mortality was examined in relation to in-treatment digoxin use in 937 hypertensive patients with ECG left ventricular hypertrophy in atrial fibrillation at baseline (n = 134) or who developed atrial fibrillation during follow-up (n = 803), randomly assigned to losartan or atenolol-based treatment, in post-hoc analysis of a substudy of the Losartan Intervention For Endpoint Reduction in hypertension (LIFE) trial. During 4.7 ± 1.1 years of mean follow-up, 167 patients died (17.8%) and 372 (39.7%) were treated with digoxin. In univariate Cox analyses, in-treatment digoxin use, entered as a time-varying covariate, was associated with a 61% higher risk of dying (hazard ratio 1.61, 95% confidence interval 1.18–2.19, P = 0.003). After adjusting for other univariate predictors of death in this population, including age, diabetes, history of ischemic heart disease, stroke, or heart failure, baseline Cornell product, QRS duration, heart rate, serum glucose, creatinine and high-density lipoprotein cholesterol, and a propensity score for digoxin use entered as standard covariates, and for in-treatment heart rate, pulse pressure, and Sokolow–Lyon voltage treated as time-varying covariates, digoxin use was no longer a significant predictor of mortality (hazard ratio 1.04, 95% confidence interval 0.73–1.48, P = 0.839).Conclusion: In hypertensive patients with ECG left ventricular hypertrophy with existing or new atrial fibrillation, digoxin use is not associated with a significantly increased risk of all-cause mortality after adjusting for other independent predictors of death and for the factors associated with the propensity to use digoxin in this population. These findings suggest that factors other than digoxin use may account for the increased mortality found with digoxin use in some studies.
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| 9. |
- Vishram, Julie K.K., et al.
(författare)
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Blood pressure variability predicts cardiovascular events independently of traditional cardiovascular risk factors and target organ damage : a LIFE substudy
- 2015
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 33:12, s. 2422-2430
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Tidskriftsartikel (refereegranskat)abstract
- Background: Assessment of antihypertensive treatment is normally based on the mean value of a number of blood pressure (BP) measurements. However, it is uncertain whether high in-treatment visit-to-visit BP variability may be harmful in hypertensive patients with left ventricular hypertrophy (LVH).Methods: In 8505 patients randomized to losartan vs. atenolol-based treatment in the LIFE study, we tested whether BP variability assessed as SD and range for BP6-24months measured at 6, 12, 18 and 24 months of treatment was associated with target organ damage (TOD) defined by LVH on ECG and urine albumin/creatinine ratio at 24 months, and predicted the composite endpoint (CEP) of cardiovascular death, nonfatal myocardial infarction (MI) or stroke occurring after 24 months (CEP=630 events).Results: In multiple regression models adjusted for mean BP6-24months and treatment allocation, neither high BP6-24months SD nor wide range were related to TOD at 24 months, except for a weak association between Sokolow-Lyon voltage and DBP6-24months SD and range (both b=0.04, P<0.01). Independently of mean BP6-24months, treatment allocation, TOD and baseline characteristics in Cox regression models, CEP after 24 months was associated with DBP6-24months SD [hazard ratio per 1mmHg increase1.04, 95% confidence interval (95% CI) 1.01-1.06, P=0.005], range (hazard ratio 1.02, 95% CI 1.01-1.03, P=0.004), SBP6-24months SD (hazard ratio 1.01, 95% CI 0.99-1.02, P=0.07) and range (hazard ratio 1.006, 95% CI 1.001-1.01, P=0.04). Adjusted for the same factors, stroke was associated with DBP6-24months SD (hazard ratio 1.06, 95% CI 1.02-1.10, P=0.001), range (hazard ratio 1.03, 95% CI 1.01-1.04, P=0.001), SBP6-24months SD (hazard ratio 1.02, 95% CI 1.002-1.04, P=0.04) and range (hazard ratio 1.008, 95% CI 1.001-1.02, P=0.05), but MI was not.Conclusion: In LIFE patients, higher in-treatment BP6-24months variability was independently of mean BP6-24months associated with later CEP and stroke, but not with MI or TOD after 24 months.
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