Effects of adding exercise to usual care in patients with either hypertension, type 2 diabetes or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis

Abstract

ObjectiveTo assess the beneficial and harmful effects of adding exercise to usual care for people with hypertension, type 2 diabetes mellitus and/or cardiovascular disease.DesignSystematic review with meta-analysis and trial sequential analysis of randomised clinical trials.Data sourcesThe CENTRAL, MEDLINE, EMBASE, Science Citation Index Expanded on Web of Science and BIOSIS searched from inception to July 2020.Eligibility criteria for selecting studiesWe included all randomised clinical trials adding any form of trialist defined exercise to usual care versus usual care in participants with either hypertension, type 2 diabetes or cardiovascular disease irrespective of setting, publication status, year and language.Outcome and measuresThe primary outcomes were all-cause mortality, serious adverse events and quality of life.Data extraction and synthesisFive independent reviewers extracted data and assessed risk of bias in pairs. Our methodology was based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses, Grading of Recommendations Assessment, Development and Evaluation and Cochrane Risk of Bias-version 1.ResultsWe included 950 trials, of which 248 trials randomising 21 633 participants reported on our predefined outcomes. All included trials were at high risk of bias. The major types of exercise reported were dynamic aerobic exercise (126/248 trials), dynamic resistance exercise (25/248 trials), and combined aerobic and resistance exercise (58/248 trials). The study participants were included due to cardiovascular diseases (189/248 trials), type 2 diabetes (41/248 trials) or hypertension (16/248 trials). The median intervention period was 3 months (IQR: 2–4 months) and the median follow-up period was 6 months (IQR: 3–8 months) after randomisation. Meta-analyses and trial sequential analyses showed evidence of a beneficial effect of adding exercise to usual care when assessing all-cause mortality (risk ratio (RR) 0.82; 95% CI 0.73 to 0.93; I2=0%, moderate certainty of evidence) and serious adverse events (RR 0.79; 95% CI 0.71 to 0.88; I2=0%, moderate certainty of evidence). We did not find evidence of a difference between trials from different economic regions, type of participants, type of exercise or duration of follow-up. Quality of life was assessed using several different tools, but the results generally showed that exercise improved quality of life, but the effect sizes were below our predefined minimal important difference.ConclusionsA short duration of any type of exercise seems to reduce the risk of all-cause mortality and serious adverse events in patients with either hypertension, type 2 diabetes or cardiovascular diseases. Exercise seems to have statistically significant effects on quality of life, but the effect sizes seem minimal.PROSPERO registration numberCRD42019142313.

Effects of adding exercise to usual care on blood pressure in patients with hypertension, type 2 diabetes, or cardiovascular disease: a systematic review with meta-analysis and trial sequential analysis

“…Thus, the exerciseinduced lowering of BP, though statistically significant, may have minimal individual clinical importance. However, we have to consider that the individual minimal importance in this review is based on conventional Cohen's d definition, that is, the observed SD divided by ''2'' in the control group, which is arbitrary and may not be optimal for continuous outcomes such as blood pressure in large cohorts [22]. In large cohorts, much lower and modest reductions in blood pressure have been associated with cardioprotective benefits [31,32] questioning the calculated minimal differences of 6 and 3 mmHg.…”

“…A random effects model meta-regression analysis [34] was performed to evaluate the association between degree of SBP and DBP reduction and all-cause mortality, reported previously [22]. The logarithm of relative risk (RR) of each trail was regressed against the difference in mean SBP/DBP for participants assigned to exercise intervention and participants assigned to usual care at the end of maximum follow-up.…”

“…Likewise, no prior systematic review has attempted to assess whether the blood pressure reducing effect of adding exercise varies between cohorts from high-income countries (HICs) versus LMICs, where the majority of the hypertensive population lives [4] despite the population generally are more physically active [20,21]. It is also unclear whether the exercise induced blood pressure reduction can explain the reduction in all-cause mortality reported in our previously published article [22].…”

“…Primary outcomes (all-cause mortality, serious adverse events, quality of life) and other secondary outcomes from this review have been published elsewhere [22].…”

“…Thus, the implication of our findings should be considered from both an individual and public health perspective. In addition, for participants with resistant hypertension (non-responders to antihypertensive medication) [1,38], modest exercise, shown to be completely well tolerated [22], may be an important supplement in the hypertension management. Our results underline that exercise intervention could be viable complementary strategy alongside usual care to reduce blood pressure in larger groups of participants with hypertension and/or type 2 diabetes with the aim to prevent associated cardiovascular events and reduce all-cause mortality.…”