Greater Reduction of Blood Pressure with Exercise Intervention Than Standard Care After Recent Ischaemic Atroke: A Randomized Clinical Trial

Context and Objectives: Ischaemic stroke (IS) causes disability and uses massive public health 38 resources. Cumulative disability from recurrence may be reduced with cardiometabolic risk reduction 39 strategies e.g., lowering blood pressure (BP). We hypothesized that intensive exercise plus best 40 available care in adults with recent IS improves fitness, glucose metabolism; muscle protein synthesis 41 in paretic limbs compared to controls. BP changes were compared between intervention (INT) and 42 controls (CON). 43 Research Design and Setting: A randomised, interventional clinical trial conducted in Jamaican adults 44 Subjects: We investigate 103 adults with recent IS and residual weakness. Forty-nine subjects (24 45 women: mean age 61.5; 25 men: mean age 63.8) received task-oriented exercise training (TEXT) plus 46 best available care. Fifty-four subjects (23 women: mean age 60.2; 31 men: mean age 61.3) received 47 best care, including exercise advice. 48 Measurements: We measured baseline, 3-month and 6-month BP. 49 Results: After recent IS, TEXT plus best available care reduced systolic BP by 21 mmHg and diastolic 50 by 12 mmHg compared to controls, independent of medication adherence, body composition; stroke 51 severity. Men in the TEXT group had increased lean mass (P < 0.007), VO2 max (P = 0.03); 6-minute 52 walk distance (P = 0.003). Leg press on paretic (P = 0.004) and non-paretic (P < 0.001) increased 53 with TEXT vs CON over 6 months, in both sexes ( P -values for sex difference > 0.2). Time-to-chair-rise 54 decreased in both sexes who received intervention vs controls (P <0.04) 55 Conclusions: TEXT results in significant blood pressure reduction in adults with recent ischaemic stroke 56 and residual weakness when compared with best available medical care only.


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Ischaemic heart disease and stroke cause more than 27% of worldwide deaths i and are major 61 categories of the non-communicable diseases (NCDs) (7 of 10 leading causes of death in 2019). This 62 equates to 44% of deaths globally. Non-communicable diseases account for 80% of deaths in 63 Jamaica ii ; regionally, heart disease, cancer, stroke, and diabetes accounted for 47% of deaths in the 64 Caribbean in 1980. This mortality rate increased to 51% by 2000 iii . Globally and in the Caribbean,

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NCDs are leading causes of death; stroke being a major contributor.

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Overall, 20 to 50% of people with incident stroke die within a month iv ; survivors are often significantly 68 disabled v , requiring massive public health expenditures. Up to 50% of survivors are chronically 69 disabled posing a health care burden. Risk factors for stroke include hypertension, diabetes obesity, 70 prevalent globally, in Jamaica and the Caribbean vi .

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Risk of recurrent stroke is 30% within 5 years; highest within the first year (13%), 15 times that of the 73 general population vii . Mortality after recurrence is twice that associated with first-time events viii . About 74 80% of survivors die within 10 years and 50% die from recurrent stroke or cardiovascular (CV) 75 disease ix . Glucose intolerance and CV events increase after thrombotic strokes x and contribute to the 76 increased mortality. Increased CV risk is largely due to hypertension and diabetes, exacerbated by 77 associated low physical activity xi and high sedentary time xii .

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Recurrence can be reduced by optimising cardio-metabolic risk status. Lowering blood pressure (BP), 81 or treating hypertension, reduces recurrence, the effect primarily due to systolic blood pressure (SBP) 82 reduction xiii . In patients with a history of ischaemic stroke (IS) or transient ischaemic attack, 9/4 mmHg 83 BP reduction over 4 years reduces recurrence in patients with and without hypertension xiv . A 5 mmHg 84 5 and 10 mmHg BP reduction reduces odds of stroke recurrence by 22% and 31% respectively. Despite 85 the magnitude of the contribution of cerebrovascular disease to stroke-associated mortality/disability, 86 there is little emphasis on secondary prevention.

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Stroke rehabilitation can improve these adverse sequelae and may ameliorate cardiometabolic risk 89 and future CV or cerebrovascular events. The American Stroke Association (ASA) recommends stroke 90 survivors increase physical activity and participate in aerobic exercise to reduce risk of recurrence and 91 lower CV risk xv . Modifying post-stroke exercise regimens with harness support for body weight allows 92 participants to exercise safely at higher intensity to improve VO2max and cardiometabolic health. Body 93 weight support and task-oriented treadmill ™ exercise training [TEXT] cause greater improvement in 94 muscle strength, fitness and reduced inflammatory markers in hemiparetic stroke xvi .

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We conducted a randomized trial to investigate the hypothesis that in African-origin Jamaican adults 97 recent (preceding 3 months) hemiparetic stroke, 6 months of specialized exercise intervention across 98 sub-acute into chronic post-event phase will improve cardiometabolic health compared to controls 99 (CON) receiving best available medical care. We report on effects of this intervention on BP response.

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Subjects engaged in sit-to-stand repeats, dynamic balance, leg-strengthening exercises. These 177 consisted of weight shifting (non-Paretic to paretic), forward, sideways, backward steps, and squats at 9 ballet bar. Walking course duration was progressed from 3-15 minutes. Sit-to-stand and ballet bar 179 exercises were advanced from 6 repetitions per side x 1 set to 15 repetitions x 2 sets, as tolerated, vs. 17%, ∆ VO2 peak, p<0.01), and we report improved indices of insulin sensitivity were related to 218 change in fitness levels with exercise after stroke, these sample sizes were considered conservative.

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Sample sizes for fitness for TEXT were based on mean and SD of differences between intra-individual 220 VO2 peak measures in chronic stroke patients (n=17)

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were no differences in prevalence of these conditions/factors or medications by intervention group.

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254 Table 1 provides the baseline and 6-month data for subject characteristics and metabolic health. Body 255 weight, BMI, waist circumference, fat mass, and pulse did not change. In men, lean mass increased 256 after TEXT (P=0.007). Lean mass tended to increase in the combined (women and men) intervention 257 group, compared to CON (P = 0.05). VO2 max (P = 0.03), distance walked in 6 minutes (P= 0.003),

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leg press paretic (P = 0.004) and non-paretic (P < 0.001) increased with TEXT compared to CON over 259 the 6 months, in men and women (P-values for sex difference > 0.2). Time to chair rise decreased in

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TEXT men and women vs CON (P <0.04) There were no changes in TM time and grip. Stroke severity, 261 depression score and medication adherence did not change between baseline and 6 months in either 262 group.

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In age-and sex-adjusted regression analyses with SBP as outcome variable, baseline BP and treatment 265 effect were independent predictors ( Summary Table   337 338 What is known about the topic • Up to 50% of stroke survivors are rendered chronically disabled.
• Lowering blood pressure significantly reduces recurrent ischaemic stroke.
• A 5.1 mmHg and 10 mmHg reduction in BP reduces the odds of stroke recurrence by 22% and 31% respectively.