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

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 [11‐13]. 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.

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.

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.

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, 41‐43] 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, 41‐43]. 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.

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.

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.