The impact of body composition on functional recovery, mortality, and survival: a systematic review of research conducted in a cohort of stroke survivors

Abstract

Background

The phrase obesity paradox after stroke appears to be a recent phenomenon and was first coined in the early 2000s; thereafter, there has been a growing controversy about the phenomenon, with many studies in favor and a few others against it. Notably, obesity a major risk factor for stroke is now regarded as global pandemic. The purpose of this study was to carry out a systematic review on the impact of body weight on functional recovery, mortality, and survival among stroke survivors.

Methods

We searched PubMed and Google scholar from January 2011 to 2022. Studies were recruited if they reported the impact of body weight on functional recovery, mortality, and survival among stroke survivors.

Results

A total of 284,699 subjects (30-studies) were included, and 2 were RCTs and a nested case–control study. Seventeen (n = 197,833, two on intravenous thrombolysis-IVT), and two studies (n = 2565) on body weight and outcome among stroke patients receiving insulin were in support of the obesity paradox. Nine studies (n = 79,451, four on IVT) were against the obesity paradox. For body weight and outcome of ischemic stroke patients treated with IVT, a total of six studies (n = 2940) four against and two in support of the obesity paradox. In addition, two studies (n = 4124) reported on WHR, WC, and BMI on mortality and outcome.

Conclusions

Overall, the odds were in favor of the obesity paradox among stroke patients with their first-time stroke with no report on second-time stroke. The underweight patients showed the worst unfavorable outcome and mortality. Insulin resistance is a major factor underpinning the presence of a paradox among stroke patients with diabetes receiving treatment with insulin therapy. We recommend that the nutritional status of stroke patients be taken into consideration during management. More studies especially on RCT should be conducted to determine the impact of body weight other that BMI on mortality and functional recovery among stroke survivor of African descent.

Background

Stroke is the foremost cause of disability the world over [1]. Exceed only cancer and cardiovascular disease, and ranked as the third most cause of mortality globally [2]. It is a “neurological deficit attributed to an acute focal injury of the central nervous system by a vascular cause, including cerebral infarction, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH)” [3]. Obesity, diabetes, hypertension, and hyperlipidemia are among the modifiable risk factor associated with stroke. To reduce the risk associated with chronic diseases like heart disease, diabetes, and obesity which is current regarded as a worldwide pandemic, recent studies have suggested that individuals should reduce weight by partaking in exercise and health-enhancing physical activity [4]. Body mass index (BMI) is the most widely used measure to determine body composition in clinical settings and hospital-based clinical research. Findings of such research have led to a consensus that “there is” on the one hand and on the other hand that “there is” no paradox in obesity following an index stroke event or other lifestyle diseases. At best, there are few RCTs on the impact of BMI on treatment outcome, one with a beneficial effect of higher BMI and the other with opposing findings [5, 6]. Hence, one could wonder why most clinicians and exercise instructors recommend that patients with stroke should participate in health-enhancing physical activity to promote weight loss. This has led to a controversy as to whether there is a positive favorable effect associated with obesity post-stroke and if so if this benefit could outweigh the risk in the long run following an index event. A previous letter to the editor by Nishioka et al. [7] has faulted the findings of Kalichman et al. [8] that there was an inverse relationship between BMI on admission and independence in function (insinuating no paradox in obesity) in stroke patients; however, there is no reply yet to this criticism. In addition, Dohner and Aubert [9] faulted the conclusion arrived by Dehlendroff et al. [10] to refute their previous finding that a lower mortality was linked with a an increase in body weight following an indexed stroke event and concluded that there was no basis to recommend that patient should lose weight or strife towards achieving a normal weight, since this was not supported by the data that was presented; hear their reply: rather than the reverse obesity has no survival advantage and also clarified that their report that patient within normal BMI at upper end range and overweight at low end range survived better than the obese should not be misrepresented as a paradox [10]. Although they agreed with existence of an inverse association between BMI and severity of stroke which means that stroke associated with obesity is less severe than stroke of other causes [9]. The word obesity paradox first came to light from cardiology when it was first discovered that there was a better prognosis among overweight patients with heart disease compared with those with lower BMI [11,12,13]. In stroke patients, the phrase first came to bear from the study of Olsen et al. [14], and since then, other researchers have confirmed its existence among stroke survivors. For example, one such study reported that stroke mortality was higher in underweight and normal weight compared to overweight and obese [9], and another by Burke et al. reported that functional outcome was highest in the overweight followed by obese and other weight categories [15]. More so, other phrases and words often used after a stroke occurrence include; sarcopenic obesity, sarcopenia, or cachexia. For example, muscle wasting with the associated increase in fat mass as a result of reduced muscle strength (sarcopenia) was coined sarcopenic obesity [16, 17], while cachexia is labeled as a global weight reduction with associated degradation of body tissue [18]. Weight loss post-stroke is easily noticed by the rehabilitation team and is often associated with a more serious form of stroke. For instance, post-index stroke loss of weight is noticed as a clinically overt summary effect of negative nitrogen and caloric balance resulting from impaired feeding, lack of activity, paraplegia, and metabolic balance which is controlled by extant factors including fever, cytokines, loss of appetite, neuroendocrine sympathetic firing, and accumulation of free radical [19]. On the contrary, it has been noticed that patients with increased weight post-stroke may have less stroke severity, however, may pose a great challenge in terms of cost of management and burden both to themselves, their caregivers, and the rehabilitation team. For example, the major burden associated with stroke include, long-term care and rehabilitation, which result in higher treatment costs [20].

There appears to be a serious controversy on the report related to the impact of obesity on stroke functional recovery. This study, therefore, seeks to resolve this controversy and explored existing studies on this debated topic. A previous systematic review carried out by Oesch and colleagues in 2017 [21] to inquire if “the stroke obesity paradox” was a myth or a reality, at best only included studies from inception to 2015, and found no RCT as regards the link between functional outcome and body weight, lacks report on the impact on patient body weight on functional recovery, mortality, and survival among stroke patient receiving additional treatment such as insulin although, explored on some studies on stroke patient treated with endovascular/intravenous thrombolysis (EVT/IVT). To bridge this gap in existing literature we intend to search extensively on the impact of the body weight of stroke patients on functional recovery, mortality, and survival among stroke patients including those receiving EVT/IVT or insulin treatment. Second, we intend to explore the psychometric properties of the instrument used to measure functional recovery post-stroke and how they differ in studies that would be explored.

Methodology

Criteria for eligibility

The criteria for study inclusion are: (1) studies that classified obesity as either underweight, normal weight, overweight or obese; (2) studies on body composition such as BMI, WHR, or WC; (3) studies whose subjects are stroke patients (hemorrhagic ischemic or undefined); (4) both community and hospital base studies; (5) studies in favor or against a paradox in obesity; (6) cross-sectional and retrospective studies; (7) studies published in the English language whose full text can be freely assessed; and (8) studies with a reliable outcome measure to determine functional recovery, mortality, or survival with body weight in stroke or stroke patients after treatment with IVT.

The criteria for exclusion are: (1) studies whose subjects are not stroke patients (cancer and sleep apnea); (2) studies that could not clearly define obesity as stated above; (3) systematic review and studies on meta-analysis; and (4) studies published in French and Arabic with no English language translation or with only abstract whose full text is not openly assessed.

Include sources information

The idea to commence this study came to bears in 2019 but the actual systematic search for relevant studies was carried out on June 15, 2022, and included studies from January 2011 to date. To retrieve relevant studies on the impact of body composition on rehabilitation outcome/functional recovery, mortality, or survival among stroke patients, search engines such as Google Scholar and PubMed (MEDLINE) were employed.

The strategy utilized in searching

A prior search method on PubMed was devised using keywords and Boolean operators (AND; OR) and this was then applied to the other database. A researcher (PAE) searches keywords linked to the impact of body composition on functional recovery/functional outcome, mortality, and survival among stroke patients. Therefore, the search (MeSH) term include; “Impact” OR “association” OR “relationship” AND “obesity” “BMI” “body composition” OR “obesity paradox” AND “functional recovery” OR “mortality” OR “survival” AND “stroke patients”.

Selection of study

To ascertain whether the title or abstract of the prospective included studies met the inclusion criteria, the researchers (PAE, ID) independently review the articles, Fig. 1. Only full-text articles that certified inclusion criteria were selected for this systematic review. In addition, a discussion between the authors was used to reconcile any misconceptions in choosing an appropriate article. A detail of the included studies  was presented in Table 1.

Fig. 1

Flow chart

Table 1 Review table of include studies

Measures of outcome

Several tools such as body composition (BMI, WHR, WC) were utilized in the selected articles to measure obesity/adiposity and in most studies, adiposity was classified using BMI as obese/overweight as (> 30.0 kg/m² vs 25–29.9 kg/m²) and normal weight/underweight (18.5–24.9 kg/m² vs < 18.5 kg/m²). Parameters used in measuring functional recovery/outcome include; FIM, delta FIM, FIM efficiency, Fulg-Meyer, Modified Ashworth Scale, Barthel index, and stroke severity/neurological assessment (NIHSS, modified Ranking Scale [mRS]). PRISMA guidelines for systematic review were adopted (Fig. 1).

Results

Our search yielded 3,513 hits on PubMed and 16,900 hits on Google scholar. Following an elaborate checking, about 100 relevant articles were identified and out of this, only 30 relevant studies carried out in 284,699 subjects that met the criteria for inclusion were documented (Fig. 1). A majority of the studies were conducted in Korea (6), USA (6), and China (5), while only a few found in African (Nigeria, 1), Tables 1 and 2.

Table 2 Search strategy and studies by country

Characteristic of the selected article in favor of a paradox in obesity post-stroke

Seventeen studies in 198,326 patients (2 on IVT) were found to be in favor of the obesity paradox. Two studies were found to be conducted in 2011. The study by Ovbiagele et al. [22] in 20,246 patients looked at the association of future vascular risk among patients with ischemic stroke with obesity, this study was undertaken in multiple centers (n = 695 centers) in about 35 different countries. The association between obesity and survival in patients hospitalized for an acute first-ever stroke (n = 2785, 1735 males and 1050 females) was carried out by Vemmos et al. [23] in Alexandra hospital in Greece. While Doehner et al. [24] assessed the association between BMI and non-fatal functional outcome and mortality among acute ischemic and hemorrhagic stroke patients (n = 2785) in a trial called Telemedical Project for Integrative Stroke (TEMPiS) Care in Germany. In a prospective cohort study in acute first-ever ischemic stroke (n = 365, 246 males and 119 females), the association between obesity and hemorrhagic transformation was assessed at Seoul university hospital Korea [25]. Two studies conducted by Burke et al. [15] and Skolarus et al. [26] assessed the association between BMI and functional progress among stroke patients (n = 819) in a freestanding rehabilitation stroke center in Atlanta, USA, and the association between BMI and mortality and severity in ischemic stroke (n = 1791), respectively. In a study conducted by Jang et al. [27] among Koreans with acute ischemic stroke (n = 2057), the association between obesity and functional recovery after stroke was assessed. In a nested case–control community-based study among first-time ischemic stroke subjects in Boston, USA (n = 782), Aparicioe et al. [28] assessed the effect of body weight and survival after an index event. The wake of 2019 saw a lot of studies (n = 5), Choi et al. [29], in a retrospective cohort design assess the relationship between BMI and mortality among ischemic stroke patients in a hospital in Korea. While, the association between adiposity and stroke outcome in acute ischemic stroke patient at a web-based multicenter registry in Korea (n = 127) being managed with IVT was assessed prospectively by Kim et al. [30]. In addition, Park et al. and Xu et al. assessed the impact of BMI and incidence of an adverse cardiovascular event among acute ischemic stroke diabetic patients in South Korea and the contribution of insulin resistance to the association between BMI and stroke outcome in a national prospective study among ischemic diabetic stroke patient in China, respectively [31, 32]. In a post hoc analysis in the Netherlands, following EVT, the association between BMI and outcome among acute ischemic stroke patients (n = 366) in a hospital-based study (CLEAN trial) was assessed [6]. In another study carried out in the department of neurology in the west of China, Wang et al. [33], prospectively look at the association between dynamic obesity and mortality among patients with first-time ischemic stroke (n = 754). Two studies by Chaudhary et al. and Kinter et al. were identified in 2021, they assessed the relationship between BMI and the cause of all mortality in a cohort of male and female ischemic stroke (n = 6703), in 4-data based in Pennsylvania and the effect of BMI on in-hospital mortality following first-ever ischemic stroke (n = 150,153, male and female) from the Agency for Health Care Administration (AHCA) of Florida hospital USA, respectively [34, 35].

Characteristic of the selected article not in favor of a paradox in obesity post-stroke

Nine studies in 79,451 subjects in 10 studies were found not to be in favor of the obesity paradox in stroke patients. The study by Adeniyi et al. [37] conducted in northern Nigeria, to assess the correlation between BMI, and other adiposity measures on gait among stroke (n = 94; mean age 57 ± 5.2, duration = 1 year) and health subjects (n = 94). The mean BMI of stroke patients was in the overweight range (28.3 ± 4.26 kg/m²), they found a direct relationship between BMI and gait cycle (0.61r); however, BMI was inversely significantly related to step length (− 0.56r) and gait velocity (− 0.72r), a similar result was found with WC. Their conclusion was that obesity triples the odds of a patient having a low gait velocity. The study by Sheffler et al. [5] conducted among chronic stroke subjects (n = 109) in the USA on the relationship between BMI and change in motor impairment and functional mobility found that higher BMI was less likely to demonstrate enhancement of impairments of motor and performance of functional mobility following ambulation training. Dehlendorff et al. [10] conducted a prospective study on hospitalized ischemic and hemorrhagic stroke patients (n = 71,617; mean age = 71 years) in Demark to assess the relationship between BMI and survival. They found no change in the risk of dying 1 month after stroke among normal, obese, and overweight patients, hence concluded that there was no evidence of obesity paradox among this cohort of patients, although stroke occurred at a younger age in patients having a higher BMI and recommended that obese patient with stroke should strive toward achieving a normal weight. In a prospective study by Sun et al. [38], which consecutively collected data from the national multicenter registry from hospitalized Chinese patients with acute ischemia/ hemorrhagic stroke (n = 4782, 37.8% female) to assess the association between BMI on mortality and functional outcome. They found that being obese or overweight was not associated with lower mortality or enhance recovery of function, however, being underweight was associated with an unfavorable outcome. The death and cause of death were said to be reported by a health professional (18.4%), family members (64.7%), medical/police records (11.8%), other sources (1.5%), or death certificate (3.5%). Another prospective study conducted at Emory University USA was carried out to compare the BMI at baseline characteristics, procedural radiological as well as outcome parameters of ischemic stroke patients (n = 926) with large vessel occlusion stroke (LVOS) after EVT found that BMI was not associated with good outcomes or mortality and that overweight and obese patient has greater stroke risk and comorbidities than the normal weight and recommended that obese and overweight patient with stroke should strive to achieve normal weight [39]. Finally, Leszczak et al. [2], carried out a follow-up study from June 2015 to March 2017 in Poland to assess the relationship between BMI and results of rehabilitation among stroke patients (n = 403), they found a greater functional status in daily life among patient with normal body weight compared to those that are either obese or overweight.

BMI and all-cause of stroke mortality

A prospective cohort study by Ng et al. [40] was carried out in Singapore/China to assess the age-dependent association of BMI with all-cause of CVD disease and mortality. They found no significant association between obese and overweight patient categories with increased mortality all-cause; however, an increase in CVD and stroke mortality was linked with patients in the Obese/Overweight subgroup. With BMI showing a U-shape relationship with mortality. They concluded that in patients who are 65 years and older and having body weight in the overweight-obese, BMI was not related with an increase in mortality all-cause.

Body mass on functional recovery among ischemic stroke patients treated with endovascular/intravenous thrombolysis

We found about 2940 stroke patients being treated using EVT/IVT. The severity of stroke was measured using NIHSS and modified Ranking Scale (mRs). For mRs, a score of 0–2 was regarded as a favorable outcome, while 3–6 was an unfavorable outcome. In addition, Cox proportional hazard analysis and Kaplan Meier survival curve were conducted to determine mortality and survival after stroke.

The clinical outcome and safety after IVT among AIS (n = 304) patients who are obese were prospectively assessed by Sarikaya et al. [41] at the university hospital of Zurich Switzerland. At 3 months, they found a lower rate of a favorable outcome in the obese than in the non-obese patients, the death rate in the obese patient was more although the rate of symptomatic intracranial hemorrhage was comparable; however, after a series of multivariate adjustments, unfavorable outcome and mortality was still found to be more in the obese patient treated EVT. In an 8-year retrospective study by Seo et al. [42], carried out in Busan Korea to assess the association between BMI and mortality in acute ischemic stroke patients (n = 781) treated with IVT, it was found that the long term and 90-day mortality seemed to be greater in the underweight, hence mortality at long-term was only linked with the underweight, therefore, compared with normal weight the underweight may be independently associated with worse survival. Another prospective multicenter study in Swiss was carried out on ischemic stroke patients (n = 896) who underwent IVT to ascertain how body weight is related to outcome of stroke after treatment with IVT, it was found that the mortality at 3 months was not different among the non-obese and obese group and also was not varied across BMI classes, suggesting that for various group of body weight the current dosage scheme adapted for IV alteplase is appropriate, hence questioned the obesity paradox existence post-stroke [43]. In another study by Bouslama et al. [39] that look at BMI and outcomes among ischemic stroke patients after treatment with EVT in a tertiary academic institution, they found that the overweight subjects had a higher rate of diabetes/dyslipidemia, level of glucose, and were younger than the normal weight subjects, while subjects who were obese had higher rates of diabetes/hypertension/level of glucose, smoke less and were younger than the normal weight. Other baselines/procedural characteristics such as the parenchymal hematomas, rates of successful reperfusion, mortality, and good clinical outcome at day 90 were similar. However, BMI was not associated with mortality or outcome but subjects who are obese/overweight have a greater risk of stroke and comorbidities hence, should make effort to attain normal weight. The 90-day mortality and “European Cooperative Acute Stroke Study (ECASS)” criteria, were used to determine the Safety endpoint. While the study by Kim et al. [30], reported that subjects who were obese (BMI ≥ 25) had better outcome than those who were not; however, a decrease in the proportion of visceral fat was associated with and a favorable and excellent outcome among stroke survivor in the acute phase who were been treated with IVT. In this study, the subject's BMI was categorized using WHO Asia–pacific guidelines, and trichotomous and dichotomous analysis was utilized to assess the mRS score distribution and also adjusted for cofounders. Finally, Pirson et al. [6], in a post hoc analysis of multicenter acute ischemic stroke (n = 366) in the Netherlands looked at the association between BMI and outcome after EVT and found no interaction between EVT effect and BMI on functional outcome, mortality, and other safety outcomes. Hence better functional outcome, lesser risk of stroke progression, and lesser mortality for higher BMI patients and inversely relation between mortality and BMI, higher BMI associated with lesser risk progression of stroke seen with safety analysis.

Body composition on functional recovery and mortality among ischemic stroke patients receiving insulin

Two studies in 2565 subjects in 2019 that reported the contribution of body weight on functional outcomes among stroke patients with diabetes were identified. In a nationwide prospective study carried out by Xu et al. [32], in China to assess the insulin resistance contribution to the association between BMI and stroke outcome among first-ever acute ischemic stroke diabetic (n = 1227). They found that, overweight/obese (BMI, ≥ 23) subjects show one-half of the post stroke risk of death than their normal/low weight contemporaries among insulin-resistant patients; however, no significant change in risk of mortality was seen among the body weight categories in insulin-sensitive subjects. Although after adjusting for confounders the result was similar. In addition, a significant association between BMI and insulin resistance-homeostasis model assessment on poor functional outcome and the risks of mortality. This result suggests that there was the presence of an obesity paradox for functional outcome and mortality among patients with insulin resistance; however, there was no obesity paradox in patients with insulin sensitivity. Hence, one of the mechanisms underpinning a paradox with obesity outcomes in patients with ischemic stroke may be insulin resistance. In the other study by Park et al. [31], a retrospective study with a follow up of 3.6 years which prospectively sample about 133 subjects with acute ischemic stroke and diabetes type 2 in South Korea to assess whether BMI will differentially show an impact on major advance event (MACE) incidence. The survival curves were plotted using Kaplan–Meier method; survival time was analyzed using a log-rank test. The occurrence of MACE was more in the underweight patients than the normal weight but less frequently in the overweight/obese group than the normal weight. An L- and a U-shaped pattern of association was found between BMI and MACE, cardiovascular mortality and stroke. An inverse pattern was indicated for fatal/nonfatal stroke, and a reversed J-shaped pattern was shown for fatal or non-fatal cardiovascular events. The result suggests the presence of an “obesity paradox” in T2DM stroke patients. Albeit, there were different risks of cardiovascular events and stroke among obese subjects.

Stroke mortality/functional recovery and waist circumference, waist–hip ratio, and body mass index

Two studies in 4124 subjects compared the impact of WHR, WC, and BMI on functional recovery among stroke survivors. The study by Yu et al. [44], a multi-center prospective cohort study in China with a 1-year follow-up assessed the relationship between the WHR and all-cause mortality and functional outcome among acute ischemic stroke patient (n = 2076). They reported that a worse functional outcome was linked with higher WHR, but not predictive of an outcome as regards mortality of the patient. However, abdominal fat accumulation may not be associated with mortality post-stroke but linked with functional recovery. Patient weight was categorized into quartiles, when compared with the lowest quartile, the highest quartile of WHR at admission was likely associated with worse functional recovery post-acute ischemic stroke. A retrospective cohort study report by Bembenek et al. [45] on first-ever acute ischemic stroke (n = 2048) collected from a stroke registry in Warsaw Poland, to assess whether WHR, WC, or improper BMI may differently predict short-term outcome. They reported that the odds of dependency at discharge or death in males and females but not in-hospital death alone was increased by a high WHR. Lower odds of either death or dependency at discharge or death in only females were significantly associated with increased WC. While no clear predictive value was shown by BMI in either sex. Hence concluded that being overweight (determine with WC) is a strong predictor of good outcomes in female but not in male. However, the consistency in predicting stroke outcome with WHR is less, since it is not linked with mortality at discharge alone.

Obesity at admission and weight loss after stroke and mortality

In a prospective study, a total of 736 patients hospitalize for first-time IS at Thomayer Hospital, Prague and Charles University Medical, Czech Republic to assess the association of obesity at the time of admission of patients and loss weight post-stroke with total mortality carried by Wohlfahrt et al. [46]. It was found that there was an independent association between increased mortality and normal weight at admission and loss of weight post-ischemic stroke, however, being obese or overweight at base value does not reduce the risk associated with weight loss. In this study to compare the difference in mortality risk among BMI categories and weight-loss groups. Survival was estimate with “Kaplan–Meier survival curves and log-rank test,” while “Cox proportional hazard model “was utilized to ascertain whether categories of BMI and loss of weight loss are linked with mortality risk independent of other factors. Finally, Kishimoto et al. [36], probed to determine if maintaining weight or increasing it during clinical rehabilitation in the early phase is related to enhanced recovery in function in patients with high BMI among hemorrhagic stroke patients (n = 293) in a 4-bed hospital in Japan.

Discussion

The finding of this study is that there are an overwhelming majority of studies confirm the presence of an obesity paradox among stroke patients with their first-ever event. Therefore, the odds are in favor of a paradox with obesity in stroke patients. This means that patients who are either overweight or obese after a stroke episode showed a lower rate of mortality, and higher functional recovery and survived better than those with normal weight, with the worst unfavorable outcome associated with being underweight. Further studies on the impact of body weight on recovery and mortality in patients with a recurring episode of stroke are recommended. Our findings from studies on body weight on mortality in stroke patients receiving insulin treatment also confirmed the existence of the obesity paradox in an ischemic stroke patient with insulin resistance. One will begin to wonder if there is any basis for a recommendation from a few studies that stroke patients who are obese/overweight should strive toward achieving a normal weight. One common general reason that may warrant such recommendation from our experience is that stroke patients who are obese pose a major burden to the rehabilitation expert, caregivers, and nurses who are often faced with a need to move the patient around during treatment when compared to other weight categories. The term obesity paradox in stroke was first reported by Olsen et al. [14], and since then, many other researchers have conducted studies to confirm its existence among stroke patients [6, 9, 15, 34]. The explanation of how obesity results in lower mortality or better recovery are yet to be fully understood; however, it has been suggested that having a broader view of the mechanism underpinning this phenomenon may be implicated for future strategies during rehabilitation and management [47]. In addition, at best, it has been hypothesized that for individuals who are in fragile metabolic state, fat could serve as a metabolic buffer or reservoir of protection [48, 49].

Our search also showed that the commonest outcome measure used in measuring stroke severity and neurological assessment include NIHSS, SSS, and mRS, while the documented outcome for physical functional recovery includes the modified Barthel index, functional independence measure, mEFAP and Fugl-Meyer and the most common analysis used to estimate first-time stroke survival and mortality include, Kaplan Meier Survival curve, Fine-Grey competing risk model and cox proportional hazards models, detailed in Table 3.

Table 3 Psychometric properties of some tools found among included studies

Finding from our included studies also showed that a vast majority of the studies used BMI as a measure of body weight among stroke patients. A recent research conducted by Bako et al. [50], suggested that between WHR, WC, and BMI, BMI might not be a good measure of obesity as it showed the least ability in discriminating the presence of obesity among diabetes and hypertensive patient which are a risk factor of stroke, insinuating that there could be some flaws as regards to method used in assessing body weight using BMI alone as seen in most of the studies.

The inability to discriminate between body fat from muscle tissue as well as reflect body composition and mass distribution has been indicated as the most important limitation of BMI [34, 51], more so, BMI cannot discriminate Visceral abdominal fat [detrimental fat] from subcutaneous abdominal fat [beneficial fat].

All-cause mortality risk and CVD with BMI were age-dependent, higher at middle age for all weight categories, the hazard ratio for obese and overweight was similar to that of the underweight, although the hazard ratio for normal weight was lowest at older age only the underweight was significantly associated with “all-cause”, the obese and overweight was not associated with “all-cause” [40]. We inferred that the underpinning factor for the obesity paradox among stroke patients was age with a reflection at older age and absence at a younger age. This finding shows the limiting ability of BMI as an estimator of body fat, since at comparable BMI, older subjects present with higher body fat than their younger contemporaries, with higher BMI likely reflecting relatively higher fat-free mass, instead of higher body fat [40]. Obese subjects are at a higher risk of dying younger, hence those that survived into old age are likely metabolically healthy leading to a survival bias [40]. The diagnostic accuracy of BMI flattens out with increasing age [6], hence a piece of caution should be emphasized when interpreting the result of this study.

At best, we identified two studies with a report comparing WHR, WC, and BMI on mortality and functional recovery. The association of obesity and functional outcome/mortality shows a differing trend when body weight determinants other than BMI was utilized and was influenced by sex, hence BMI obesity paradox in stroke may have a sex bias. For example, Yu et al. [44] reported that the worst functional outcome was linked with a higher WHR but not predictive of mortality. That accumulation of abdominal fat may be linked with recovery of function but not with mortality after stroke and the study by Bembenek et al. [45], found that in both sexes the odd of death or dependence at discharge was increased with higher WHR but not the in-hospital death alone; however, WC increase was significantly linked to lower odd either of death alone or dependency and death at discharge among female patient but no clear predictive value was found in either sex with BMI. These studies clearly showed that BMI may not be a good predictor of obesity when compared to WHR and WC. Our findings as regards this are in tandem with a previous review study carried out by Oesch et al. [21], contrariwise, while they did not include any RCT this study found two studies [5, 6] on RCT and nested case–control study [28] and additional two studies on acute ischemic stroke patient with diabetes receiving insulin therapy which Oesch et al. [21] did not report due to their eligibility criteria.

This study was also at variance with Oesch et al. [21] as regards IVT. For example, while they reported a lack of obesity paradox with IVT we found two studies [6, 30] confirming the presence of obesity paradox with IVT; however, there were four studies [39, 41,42,43] with a report of a lack of obesity paradox with IVT. For instance, Kim et al. [30], found that there was an excellent outcome at 3 months for AIS patients being treated with IVT who are obese and have a lower visceral adipose tissue [VAT], than their non-obese counterparts, and explained that the major factor underpinning obesity paradox among patient treated with IVT is lower VAT, meaning that a good clinical outcome is linked to a reduced VAT proportion but not detrimental fat as implied by BMI only determine obesity paradox, this finding in IVT was strength by the study of Pirson et al. [6] who also found that a higher BMI was associated with lower mortality, better functional outcome and lower occurrence of stroke progression plus no interaction between EVT and BMI. This finding agrees with previous research reporting the association between obese stroke patients compared to normal weight and 3-month functional recovery [15, 52]. However, the prognostic implication of adiposity on clinical outcomes remains controversial with the availability of opposing findings [10, 39, 41,42,43]. The strength of Pirson et al. [6] finding lies in the use of an RCT design which helps in assessing the impact of treatment on BMI; however, their limitation includes; the use of BMI whose diagnostic performance vanishes with age and inclusion bias due to missing BMI. It should be noted that the study of Kim et al. [30] was carried out to resolve the BMI obesity paradox, they clarified that in the sense of a disorder, obese patients are not truly obese, but rather have reduced VAT proportion, hence may be labeled metabolically healthy obese. The findings of Kim et al. [30] should, however, be interpreted considering some limitations; an observational design that weakens a cause-and-effect association, only baseline VAT was used, selection bias, and a small sample with a report only on Asian descent. More so, it is pertinent to clarify that after adjusting for the stroke severity at baseline the association between BMI and outcome of stroke flattened out and was no longer significant in some studies [52], which was not the case in others [6, 30].

Among the two RCTs Sheffler et al. [5] found an inverse relationship between Fugl-Meyer (FM) score and pre-treatment BMI, they explain that irrespective of the intervention during treatment, improvement in up and go, motor impairment and performance of functional mobility was less likely to be noticed in patients with higher BMI having chronic stroke; however, Pirson et al. [6] found a shift towards a better functional outcome with higher BMI albeit on a patient with acute ischemic stroke (AIS) indicating that AIS patient with higher BMI receiving EVT are more likely to show a better outcome in function, lower risk of stroke progression and lesser mortality confirming obesity paradox. This finding was in tandem with a report from the nested case–control study by Aparicio et al. [28] with a report that overweight ischemic stroke patient with their first-time stroke had lower mortality than their normal-weight counterpart. From these two findings, we inferred that the phase of a stroke may be a major factor in underpinning the presence or absence of obesity paradox among stroke patients. Due to the a few numbers of RCT studies we recommend that more studies be conducted in this regard.

The finding of this study may also have been influenced by bias during treatment. Treatment bias may have two sides of a coin, one tending toward support of obesity paradox in stroke and the other to lack of a paradox. For example, due to the perceived view that obesity poses a greater risk of development of stroke and other non-communicable diseases, clinicians tend to use a more aggressive approach while managing overweight and obese subjects when compared to either underweight or normal weight which may invariably lead to a better outcome and lesser mortality both in terms of functional recovery or survival in the former compared to the later in favor of obesity paradox. On the other hand, obese and overweight patients are both burdens to the clinician, themselves, and their care-giver because of their size. For example, some MRI beds cannot contain a very large person, to manage a very large individual may require more than one health professional compared to smaller individuals, and it may be difficult to get the vein of an obese individual compared to normal weight. All of this may contribute to lower functional recovery and higher mortality in the obese compared to the normal weight patient with lack of obesity paradox as reported in some of the studies.

A majority of the studies were conducted in stroke patients of the white race (Korea, USA and China); however, we found studies with reports on few patients in African carried out by Adeniyi et al. [37]; therefore, more studies on stroke patients from this region are needed.

Finally, we also notice that apart from the severity of stroke which some of the studies that support the BMI obesity paradox did not adjust for, other confounders like age and sex may have influenced the result of their findings.

Limitation of the study

We could not carry out a meta-analysis of included studies due to the heterogeneity of included studies. However, we did a detailed review of articles on the debated topic among stroke patients 'the obesity paradox. Metanalysis of the included studies is, therefore, recommended.

Conclusion

The odds are in favor of the obesity paradox among stroke patients with their first-time stroke with no report on second-time stroke. The underweight patient showed the worst unfavorable outcome and mortality. Insulin resistance is a major factor underpinning the presence of a paradox among stroke patients with diabetes receiving treatment with insulin therapy. We recommend that the nutritional status of stroke patients be taken into consideration during management. More studies especially on RCT on body weight on outcome among stroke patients of African descent are warranted. Further studies on body weight other than BMI on mortality, and functional recovery are also warranted.