Relationship between Levels of Pre-Stroke Physical Activity and Post-Stroke Serum Insulin-Like Growth Factor I

Physical activity (PA) and insulin-like growth factor I (IGF-I) have beneficial effects for patients who have suffered an ischemic stroke (stroke). However, the relationship between the levels of PA and IGF-I after stroke has not been explored in detail. We investigated the pre-stroke PA level in relation to the post-stroke serum IGF-I (s-IGF-I) level, at baseline and at 3 months after the index stroke, and calculated the change that occurred between these two time-points (ΔIGF-I). Patients (N = 380; 63.4% males; mean age, 54.7 years) with data on 1-year leisure-time pre-stroke PA and post-stroke s-IGF-I levels were included from the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS). Stroke severity was assessed using the National Institutes of Health Stroke Scale (NIHSS). Pre-stroke, leisure-time PA was self-reported as PA1–4, with PA1 representing sedentary and PA2–4 indicating progressively higher PA levels. Associations between s-IGF-I and PA were evaluated by multiple linear regressions with PA1 as the reference and adjustments being made for sex, age, history of previous stroke or myocardial infarctions, cardiovascular risk factors, and stroke severity. PA correlated with baseline s-IGF-I and ΔIGF-I, but not with the 3-month s-IGF-I. In the linear regressions, there were corresponding associations that remained as a tendency (baseline s-IGF-I, p = 0.06) or as a significant effect (ΔIGF-I, p = 0.03) after all the adjustments. Specifically, for each unit of PA, ΔIGF-I increased by 9.7 (95% CI 1,1−18.4) ng/mL after full adjustment. This supports the notion that pre-stroke PA is independently related to ΔIGF-I.

1. The Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS): The study population comprised adult Caucasian patients who presented with first-ever or recurrent ischemic stroke (IS) before reaching the age of 70 years (N=600). The patients were consecutively recruited between 1998 and 2003 at four stroke units in western Sweden. Caucasian population controls (N=600) were included as previously reported [1,2]. In the present study, a selection of patients with data available on prestroke physical activity and s-IGF-I levels is used (N=380). Blood samples were obtained in the acute phase, early (median of 4 days) and at 3 months (median of 101 days) after the index stroke [3]. Blood samples were drawn between 8.30 AM and 10.30 AM following overnight fasting. Serum was isolated within 2 h by centrifugation at 2000 × g at 4℃ for 20 min, and stored at -80℃ for 5-10 years before assay. Serum samples were analyzed for IGF-I in 2008 using a commercially available IGF-I binding protein (IGFBP)-blocked radioimmunoassay (RIA) (Mediagnost GmbH, Reutlingen, Germany) as described previously [3]. The intra-assay coefficient of variation (CV) was 5.1%, and the inter-assay CV was 4.7% in our sample range.
The lower detection limit allowed precise measurement of very low IGF-I concentrations (0.09 ng/ml) according to the manufacturer, well below the present concentrations. Because s-IGF-I is considered to be very stable [4], we did not specifically test long-term stability in our study. subjects' vascular risk factors was collected as described previously [1]. Hypertension was defined by pharmacological treatment for hypertension, systolic blood pressure ≥160 mm Hg, and/or diastolic blood pressure ≥90mm Hg. Diabetes mellitus was defined by diet or pharmacological treatment, fasting plasma glucose ≥7.0 mmol/L or fasting blood glucose ≥6.1 mmol/L. Smoking habits were coded as current, never or former. Concentrations of low-density lipoprotein (LDL, mmol/L) were measured as before [1,2]. The missing values (N=38, Table 1) were imputed using the mean of the baseline LDL levels to have complete LDL datasets when used as a covariate in the regression models.
3. Maximum stroke severity within the first 10 days after the stroke was scored using the Scandinavian Stroke Scale (SSS). SSS is a 58-point scale, in which a higher score represents better functionality. The SSS is highly (but inversely) correlated to the National Institutes of Health Stroke Scale (NIHSS). In this study, global SSS scores were transformed to NIHSS scores using a conversion algorithm [5], as described in the main text. Functional outcome 3 months and 2 years after IS was assessed according to the modified Rankin Scale (mRS) [6], later modified to seven steps (0-6) [7]. The mRS 0-2 scores represent functional independence, whereas scores 3-5 represent functional dependence, and mRS 6 designates death.
4. The Saltin-Grimby Physical Activity Level Scale (SGPALS) has four groups of selfreported physical activity (PA) levels. These are; PA1 (inactive group), which is defined as "almost completely inactive, reading, watching TV and movies, etc."; PA2 (active group), defined as "some physical activity during at least 4 hours per week: riding a bicycle or walking to work, walking or skiing with the family, gardening"; PA3 (intensive group), defined as "regular activity, such as heavy gardening, running, calisthenics, tennis, etc."; and PA4 (elite intensive group) defined as "regular hard physical training for competition in running events, soccer, racing, European handball, etc. several times per week." [8].
5. All participants provided informed consent prior to enrollment. For participants who were unable to communicate, consent was obtained from their next-of-kin. This study was approved by the Ethics Committee of the University of Gothenburg.