Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools

Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools

Effect of antihypertensive treatment at different blood pressure levels

Background High 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. Methods We 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. Results Forty-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.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

Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus : systematic review and meta-analyses

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

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Benefits and harms of lower blood pressure treatment targets : systematic review and meta-analysis of randomised placebo-controlled trials

Objectives To assess the effect of antihypertensive treatment in the 130-140mm Hg systolic blood pressure range. Design Systematic review and meta-analysis. Information sources PubMed, CDSR and DARE were searched for the systematic reviews, which were manually browsed for clinical trials. PubMed and Cochrane Central Register of Controlled Trials were searched for trials directly in February 2018. Eligibility criteria Randomised double-blind trials with >= 1000 patient-years of follow-up, comparing any antihypertensive agent against placebo. Data extraction and risk of bias Two reviewers extracted study-level data, and assessed risk of bias using Cochrane Collaborations risk of bias assessment tool, independently. Main outcomes and measures Primary outcomes were all-cause mortality, major cardiovascular events and discontinuation due to adverse events. Secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, heart failure, hypotension-related adverse events and renal impairment. Results Eighteen trials, including 92 567 participants (34% women, mean age 63 years), fulfilled the inclusion criteria. Primary preventive antihypertensive treatment was associated with a neutral effect on all-cause mortality (relative risk 1.00, 95% CI 0.95 to 1.06) and major cardiovascular events (1.01, 0.96 to 1.06), but an increased risk of discontinuation due to adverse events (1.23, 1.03 to 1.47). None of the secondary efficacy outcomes were significantly reduced, but the risk of hypotension-related adverse events increased with treatment (1.71, 1.32 to 2.22). In coronary artery disease secondary prevention, antihypertensive treatment was associated with reduced risk of all-cause mortality (0.91, 0.83 to 0.99) and major cardiovascular events (0.85, 0.77 to 0.94), but doubled the risk of adverse events leading to discontinuation (2.05, 1.62 to 2.61). Conclusion Primary preventive blood pressure lowering in the 130-140mm Hg systolic blood pressure range adds no cardiovascular benefit, but increases the risk of adverse events. In the secondary prevention, benefits should be weighed against harms

Effect of antihypertensive treatment in isolated systolic hypertension (ISH) : systematic review and meta-analysis of randomised controlled trials

BACKGROUND: Isolated systolic hypertension (ISH) in middle-aged and elderly is associated with high cardiovascular risk, but no randomised controlled trial has assessed the effect of antihypertensive treatment in ISH using today's definition, i.e. systolic blood pressure (SBP) ≥140 mmHg and diastolic blood pressure (DBP) <90 mmHg. METHODS: A systematic review and meta-analysis of randomised controlled trials was performed. Studies with ≥1000 patient-years of follow-up, comparing more intensive versus less intensive BP targets, or active drug versus placebo, were included if the mean baseline SBP was ≥140 mmHg and the mean baseline DBP was <90 mmHg. The primary outcome was major adverse cardiovascular events (MACE). Relative risks from each trial were pooled in random-effects meta-analyses, stratified by baseline and attained SBP level. RESULTS: Twenty-four trials, including 113,105 participants (mean age 67 years; mean blood pressure 149/83 mmHg) were included in the analysis. Overall, treatment reduced the risk of MACE by 9% (relative risk 0.91, 95% confidence interval 0.88-0.93). Treatment was more effective if baseline SBP was ≥160 mmHg (RR 0.77, 95% CIs 0.70-0.86) compared to 140-159 mmHg (RR 0.92, 95% CIs 0.89-0.95; p = 0.002 for interaction), but provided equal additional benefit across all attained SBP levels (RR 0.80, 95% CIs 0.70-0.92 for <130 mmHg, RR 0.92, 95% CIs 0.89-0.96 for 130-139 mmHg, and RR 0.87, 95% CIs 0.82-0.93 for ≥140 mmHg; p = 0.070 for interaction). CONCLUSIONS: These findings support antihypertensive treatment of isolated systolic hypertension, regardless of baseline SBP, to target SBP <140 mmHg and even <130 mmHg if well tolerated

Comparative efficacy and acceptability of different antihypertensive drug classes for cardiovascular disease prevention: Protocol for a systematic review and network meta-analysis

Introduction Clinical practice guidelines differ in their recommendations on first-line antihypertensive drug classes. No adequately powered randomised controlled trial have assessed all major drug classes against each other, and previous meta-analyses have mainly relied on pairwise meta-analyses for treatment comparisons. Methods and analysis A systematic review and network meta-analysis will be carried out to assess the efficacy and acceptability of all major antihypertensive drug classes. PubMed and CENTRAL were searched on 21 February 2020 to identify randomised controlled trials with at least 1000 person-years of follow-up, assessing any antihypertensive agent against other agents or placebo. All trials fulfilling the inclusion criteria will be assessed for risk of bias using the second version of Cochrane's risk of bias assessment tool. The study selection process, risk of bias assessment and data extraction are done by two authors in duplicate. Relative risks from individual trials will be combined in pairwise meta-analyses; in the absence of important intransitivity, random-effects network meta-analysis will be performed. The primary outcome for efficacy will be major adverse cardiovascular events, whereas the primary acceptability outcome will be treatment discontinuation for any reason. Additional outcomes include all-cause mortality, cardiovascular mortality, stroke, myocardial infarction, heart failure and acute renal failure. The impact of differences within drug classes will be explored through alternative networks, including analysing thiazide-like and thiazide-type diuretics separately. Ethics and dissemination This review will only process aggregated study level data and does not require ethical approval. The findings will be published in a peer-reviewed medical journal. PROSPERO registration number CRD42020205482

Blood pressure treatment levels and choice of antihypertensive agent in people with diabetes mellitus : an overview of systematic reviews

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