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  • 1.
    Brunstrom, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Lindholm, Lars H.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Perspective from Sweden on the global impact of the 2017 american college of cardiology/american heart association hypertension guidelines: a "sprint" beyond evidence in the United States2018Ingår i: Circulation, ISSN 0009-7322, E-ISSN 1524-4539, Vol. 137, nr 9, s. 886-888Artikel i tidskrift (Övrigt vetenskapligt)
  • 2.
    Brunström, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Cardiovascular outcomes in the Da Qing Diabetes Prevention Study2014Ingår i: The Lancet Diabetes & Endocrinology, ISSN 2213-8587, Vol. 2, nr 7, s. 539-540Artikel i tidskrift (Refereegranskat)
  • 3.
    Brunström, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Effect of antihypertensive treatment at different blood pressure levels2017Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Hjärt-kärlsjukdomar leder till fler dödsfall och fler förlorade levnadsår än någon annan sjukdomsgrupp. Den enskilt viktigaste riskfaktorn som bidrar till hjärtkärlsjukdomar ur ett befolkningsperspektiv är högt blodtryck. Risken att drabbas av hjärt-kärlsjukdomar minskar om man behandlar högt blodtryck men till vilken nivå blodtrycket skall behandlas är kontroversiellt.

    Denna avhandling innefattar två systematiska översikter och meta-analyser samt ett arbete som jämför olika sätt att hantera skillnader mellan studier i meta-analyser. De systematiska översikterna sammanställer data från randomiserade kontrollerade studier av blodtryckssänkande behandling. Vår övergripande frågeställning var om effekten av behandling påverkas av blodtrycksnivån innan behandling. Mer specifikt studerades hur behandling påverkade risken att dö eller drabbas av hjärt-kärlsjukdom vid olika blodtrycksnivåer.

    Det första arbetet fokuserade på personer med diabetes. För dessa fann vi att blodtryckssänkande behandling minskar risken att dö eller drabbas av hjärtkärlsjukdom vid nivåer ≥ 140 mmHg. Vi fann ingen nytta, men möjligen en skadlig effekt av behandling, vid lägre blodtrycksnivåer. Det andra arbetet inkluderade studier oberoende av vilka sjukdomar deltagarna hade. Vi fann att den förebyggande effekten av blodtryckssänkande behandling berodde på blodtrycksnivån. Vid blodtryck > 160 mmHg minskade risken att drabbas av hjärt-kärlsjukdomar med 22 % hos de som erhöll behandling. Om blodtrycket var 140-160 mmHg minskade risken med 12 %, men om blodtrycket var < 140 mmHg sågs ingen behandlingseffekt. Hos personer med känd kranskärlssjukdom, och ett medelblodtryck på 138 mmHg, fann vi en något minskad risk för hjärt-kärlhändelser med ytterligare behandling. I det tredje arbetet fann vi att skillnader i resultat mellan olika studier inte kan antas bero endast på olika grad av blodtryckssänkning i studierna. När resultaten standardiserades, som om alla studier hade sänkt blodtrycket lika mycket, ökade nämligen skillnaderna mellan studierna. Detta resulterade i sin tur i snedvridning av resultaten från meta-analyser av standardiserade värden.

    Sammanfattningsvis minskar blodtryckssänkande behandling risken att dö eller drabbas av hjärt-kärlsjukdomar om blodtrycket är 140 mmHg eller högre. Vid lägre nivåer är nyttan med behandling osäker samtidigt som det finns potentiella risker. Standardisering bör inte användas rutinmässigt vid metaanalyser av blodtrycksstudier. Tidigare meta-analyser som använt denna metod bör tolkas med försiktighet.

  • 4.
    Brunström, Mattias
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hypertension, the Swedish Patient Register, and Selection Bias2016Ingår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 176, nr 6, s. 862-863Artikel i tidskrift (Refereegranskat)
  • 5.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Association of blood pressure lowering with mortality and cardiovascular disease across blood pressure levels: a systematic review and meta-analysis2018Ingår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, nr 1, s. 28-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Importance: High blood pressure (BP) is the most important risk factor for death and cardiovascular disease (CVD) worldwide. The optimal cutoff for treatment of high BP is debated.

    Objective: To assess the association between BP lowering treatment and death and CVD at different BP levels.

    Data sources: Previous systematic reviews were identified from PubMed, the Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effect. Reference lists of these reviews were searched for randomized clinical trials. Randomized clinical trials published after November 1, 2015, were also searched for in PubMed and the Cochrane Central Register for Controlled Trials during February 2017.

    Study selection: Randomized clinical trials with at least 1000 patient-years of follow-up, comparing BP-lowering drugs vs placebo or different BP goals were included.

    Data extraction and synthesis: Data were extracted from original publications. Risk of bias was assessed using the Cochrane Collaborations assessment tool. Relative risks (RRs) were pooled in random-effects meta-analyses with Knapp-Hartung modification. Results are reported according to PRISMA guidelines.

    Main outcomes and measures: Prespecified outcomes of interest were all-cause mortality, cardiovascular mortality, major cardiovascular events, coronary heart disease (CHD), stroke, heart failure, and end-stage renal disease.

    Results: Seventy-four unique trials, representing 306 273 unique participants (39.9% women and 60.1% men; mean age, 63.6 years) and 1.2 million person-years, were included in the meta-analyses. In primary prevention, the association of BP-lowering treatment with major cardiovascular events was dependent on baseline systolic BP (SBP). In trials with baseline SBP 160 mm Hg or above, treatment was associated with reduced risk for death (RR, 0.93; 95% CI, 0.87-1.00) and a substantial reduction of major cardiovascular events (RR, 0.78; 95% CI, 0.70-0.87). If baseline SBP ranged from 140 to 159 mm Hg, the association of treatment with mortality was similar (RR, 0.87; 95% CI, 0.75-1.00), but the association with major cardiovascular events was less pronounced (RR, 0.88; 95% CI, 0.80-0.96). In trials with baseline SBP below 140 mm Hg, treatment was not associated with mortality (RR, 0.98; 95% CI, 0.90-1.06) and major cardiovascular events (RR, 0.97; 95% CI, 0.90-1.04). In trials including people with previous CHD and mean baseline SBP of 138 mm Hg, treatment was associated with reduced risk for major cardiovascular events (RR, 0.90; 95% CI, 0.84-0.97), but was not associated with survival (RR, 0.98; 95% CI, 0.89-1.07).

    Conclusions and relevance: Primary preventive BP lowering is associated with reduced risk for death and CVD if baseline SBP is 140 mm Hg or higher. At lower BP levels, treatment is not associated with any benefit in primary prevention but might offer additional protection in patients with CHD.

  • 6.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blood pressure targets in type 2 diabetes: a general perspective2016Ingår i: Cardiovascular Endocrinology, ISSN 2162-688X, Vol. 5, nr 4, s. 122-126Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Blood pressure targets in patients with type 2 diabetes are currently being debated. This review summarizes the current treatment recommendations provided in American and European guidelines, and findings from systematic reviews and meta-analyses published during the last decade. We critically assess the basis for the recommendations provided in relation to the evidence presented in reviews. When reviews differ in their results, we discuss the reasons for such differences. The results from recent studies in patients without diabetes and their potential implications for recommendations in patients with diabetes are commented upon. Finally, we conclude what targets are best in line with the totality of the available evidence.

  • 7.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses2016Ingår i: BMJ. British Medical Journal, E-ISSN 1756-1833, Vol. 352, artikel-id i717Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Objective: To assess the effect of antihypertensive treatment on mortality and cardiovascular morbidity in people with diabetes mellitus, at different blood pressure levels.

    Design: Systematic review and meta-analyses of randomised controlled trials.

    Data sources: CENTRAL, Medline, Embase, and BIOSIS were searched using highly sensitive search strategies. When data required according to the protocol were missing but trials were potentially eligible, we contacted researchers, pharmaceutical companies, and authorities.

    Eligibility criteria: Randomised controlled trials including 100 or more people with diabetes mellitus, treated for 12 months or more, comparing any antihypertensive agent against placebo, two agents against one, or different blood pressure targets.

    Results: 49 trials, including 73 738 participants, were included in the meta-analyses. Most of the participants had type 2 diabetes. If baseline systolic blood pressure was greater than 150 mm Hg, antihypertensive treatment reduced the risk of all cause mortality (relative risk 0.89, 95% confidence interval 0.80 to 0.99), cardiovascular mortality (0.75, 0.57 to 0.99), myocardial infarction (0.74, 0.63 to 0.87), stroke (0.77, 0.65 to 0.91), and end stage renal disease (0.82, 0.71 to 0.94). If baseline systolic blood pressure was 140-150 mm Hg, additional treatment reduced the risk of all cause mortality (0.87, 0.78 to 0.98), myocardial infarction (0.84, 0.76 to 0.93), and heart failure (0.80, 0.66 to 0.97). If baseline systolic blood pressure was less than 140 mm Hg, however, further treatment increased the risk of cardiovascular mortality (1.15, 1.00 to 1.32), with a tendency towards an increased risk of all cause mortality (1.05, 0.95 to 1.16). Metaregression analyses showed a worse treatment effect with lower baseline systolic blood pressures for cardiovascular mortality (1.15, 1.03 to 1.29 for each 10 mm Hg lower systolic blood pressure) and myocardial infarction (1.12, 1.03 to 1.22 for each 10 mm Hg lower systolic blood pressure). Patterns were similar for attained systolic blood pressure.

    Conclusions: Antihypertensive treatment reduces the risk of mortality and cardiovascular morbidity in people with diabetes mellitus and a systolic blood pressure more than 140 mm Hg. If systolic blood pressure is less than 140 mm Hg, however, further treatment is associated with an increased risk of cardiovascular death, with no observed benefit.

  • 8.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lower blood pressure targets: to whom do they apply?2016Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 387, nr 10017, s. 405-406Artikel i tidskrift (Refereegranskat)
  • 9.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Questionable Conclusions Regarding Blood Pressure End Points Reply2018Ingår i: JAMA Internal Medicine, ISSN 2168-6106, E-ISSN 2168-6114, Vol. 178, nr 4, s. 575-576Artikel i tidskrift (Refereegranskat)
  • 10.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Response to 'SPRINTin context: meta-analysis of trials with baseline normotension and lowlevels of previous cardiovascular disease' Reply2018Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, nr 7, s. 1603-1604Artikel i tidskrift (Refereegranskat)
  • 11.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    SPRINT in context: meta-analysis of trials with baseline normotension and low levels of previous cardiovascular disease2018Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, nr 5, s. 979-986Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Objective: To estimate the effect of antihypertensive treatment in trials with baseline normotension and low levels of previous cardiovascular disease. To test if the results from SPRINT are compatible with those from other trials, and test the impact of SPRINT results on overall effect estimates. Methods: Systematic review and meta-analysis of randomized controlled trials with at least 1000 patient-years of follow-up, comparing antihypertensive treatment versus placebo, or different blood pressure goals against each other. Trials with at least 50% previous cardiovascular disease were excluded. Results: Sixteen trials, including 66816 participants, were included in the meta-analyses. Mean baseline SBP was 138mmHg, and mean difference between treatment arms was 5.5mmHg. Antihypertensive treatment was associated with a neutral effect on all-cause mortality [relative risk 0.98, 95% confidence interval (CI) 0.92-1.05] and major cardiovascular events (0.97, 0.91-1.03). Results from SPRINT differed significantly from those of other trials (P=0.012 for all-cause mortality; P=0.016 for major cardiovascular events), but overall effect estimates were similar when SPRINT was excluded (1.01, 0.95-1.06 for all-cause mortality; 0.98, 0.93-1.03 for major cardiovascular events). Treatment was associated with reduced risk of secondary outcomes stroke (0.84, 0.71-1.00) and heart failure (0.88, 0.78-0.98), although heterogeneity was high in the stroke analysis (I-2=54%). Conclusion: SPRINT results are not representative for trials with baseline normotension and low levels of previous cardiovascular disease. Antihypertensive treatment does not protect against death or major cardiovascular events in this setting.

  • 12.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Standardization according to blood pressure lowering in meta-analyses of antihypertensive trials: comparison of three methodological approaches2018Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 36, nr 1, s. 4-15Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Assess how standardization of relative risks (RRs) and standard errors (SEs), according to blood pressure differences within trials, affects heterogeneity, overall effect estimates and study weights in meta-analyses of antihypertensive treatment.

    METHOD: Data from a previous systematic review were used. Three sets of analyses were performed, using both random-effects and fixed-effects model for meta-analyses. First, we used raw data from the included trials. Second, we standardized RRs as if SBP was reduced by 10 mmHg in all trials. Third, we standardized both RRs and SEs.

    RESULTS: When RRs were standardized according to blood pressure lowering, heterogeneity between trials increased (I = 36 vs. 93% for mortality). This conferred large differences in treatment effect estimates using random-effects and fixed-effects model (RR 0.79, 95% confidence interval 0.70-0.89, respectively, 0.97, 0.94-0.99). When SEs were standardized, confidence intervals for individual trials widened, resulting in lower power to detect heterogeneity across trials. Study weights were dissociated from number of events in trials (P < 0.0001, R = 0.99 before standardization vs. P = 0.063, R = 0.05 after standardization). This induced a secondary shift in weight from trials with lower baseline SBP to trials with higher baseline SBP, resulting in exaggerated overall effect estimates.

    CONCLUSION: Standardization of RRs exaggerates differences between trials and makes meta-analyses highly sensitive to choice of statistical method. Standardization of SEs masks heterogeneity and results in biased effect estimates.

  • 13.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Thrombolysis in acute stroke2015Ingår i: The Lancet, ISSN 0140-6736, E-ISSN 1474-547X, Vol. 385, nr 9976, s. 1394-1395Artikel i tidskrift (Refereegranskat)
  • 14.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Dahlström, John
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindholm, Lars Hjalmar
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Lönnberg, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Hallström, Sara
    Norberg, Margareta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Nyström, Lennarth
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Persson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    From efficacy in trials to effectiveness in clinical practice: The Swedish Stroke Prevention Study2016Ingår i: Blood Pressure, ISSN 0803-7051, E-ISSN 1651-1999, Vol. 25, nr 4, s. 206-211Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Blood pressure treatment has shown great efficacy in reducing cardiovascular events in randomized controlled trials. If this is effective in reducing cardiovascular disease in the general population, is less studied. Between 2001 and 2009 we performed an intervention to improve blood pressure control in the county of Vasterbotten, using Sodermanland County as a control. The intervention was directed towards primary care physicians and included lectures on blood pressure treatment, a computerized decision support system with treatment recommendations, and yearly feed back on hypertension control. Each county had approximately 255000 inhabitants. Differences in age and incidence of cardiovascular disease were small. During follow-up, more than 400000 patients had their blood pressure recorded. The mean number of measurements was eight per patient, yielding a total of 3.4 million blood pressure recordings. The effect of the intervention will be estimated combining the blood pressure data collected from the electronic medical records, with data on stroke, myocardial infarction and mortality from Swedish health registers. Additional variables, from health registers and Statistics Sweden, will be collected to address for confounders. The blood pressure data collected within this study will be an important asset for future epidemiological studies within the field of hypertension.

  • 15.
    Brunström, Mattias
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Eliasson, Mats
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Nilsson, Peter M
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Blood pressure treatment levels and choice of antihypertensive agent in people with diabetes mellitus: an overview of systematic reviews2017Ingår i: Journal of Hypertension, ISSN 0263-6352, E-ISSN 1473-5598, Vol. 35, s. 435-462Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Multiple systematic reviews address the effect of antihypertensive treatment in people with diabetes. Here, we summarize current systematic reviews concerning antihypertensive treatment effect at different blood pressure (BP) levels, and relative treatment effect of different antihypertensive agents.

    METHODS: We searched MEDLINE, BIOSIS, DARE and CDSR during years 2005-2016. Eligibility criteria, number of trials and participants, outcomes analysed, statistical methods used for data synthesis, and principal results were extracted for each review. Review quality was assessed using the assessment of multiple systematic reviews tool.

    RESULTS: We found four reviews concerning BP treatment level. These consistently showed that the effect of antihypertensive treatment on mortality, cardiovascular disease and coronary heart disease was attenuated at lower BP levels. If SBP was more than 140 mmHg, treatment reduced all-cause and cardiovascular mortality, cardiovascular disease, stroke, myocardial infarction and heart failure. If SBP was less than 140 mmHg, treatment increased the risk of cardiovascular death. We found eight reviews concerning choice of agent. We found no difference between angiotensin-converting enzyme inhibitors, angotensin receptor blockers, beta-blockers, calcium channel blockers and diuretics in preventing all-cause or cardiovascular mortality, combined cardiovascular disease, coronary heart disease and end-stage renal disease. Minor differences exist for stroke and heart failure. Data were limited on people with type 1 diabetes and very elderly patients with type 2 diabetes. None of the reviews concerning choice of agent included all relevant trials.

    CONCLUSION: The available evidence supports treatment in people with type 2 diabetes and SBP more than 140 mmHg, using any of the major antihypertensive drug classes.

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