Cardiovascular risk markers in patients with spinal cord injury: the Austrian wheelchair dancer study

Coronary artery disease is the leading cause of death among patients with traumatic spinal cord injury (SCI).1 Due to the physical inactivity of the affected parts of the body, disruption of autonomic pathways, inflammation as well as vascular and endothelial dysfunction occur which all may lead to arterial stiffness. Further, individuals with SCI have an accelerated rate of decline in cardiovascular function compared to healthy individuals, and the damage to the spinal cord might mask early warning signs.2 Also, a sedentary lifestyle is associated with overweight and obesity, arterial hypertension, hyperglycaemia, and dyslipidaemia, which taken together result in a three to four times higher risk of cardiovascular disease compared to healthy individuals.3,4 As physical inactivity is a modifiable risk factor that contributes to the development and progression of cardiovascular diseases, regular physical exercise training exerts several anti-atherogenic effects5–7 and, in sum, reduces the risk of cardiovascular morbidity and mortality.8 Patients with SCI suffer from impaired motor control and sensation of the affected body parts. They are primarily dependent on a wheelchair and, therefore, more likely prone to an inactive, sedentary lifestyle. Nonetheless, patients with SCI can perform regular exercise regimes adapted to their condition.9,10 One option for wheelchair-based exercise is the performance of wheelchair dancing. However, no studies on its cardiovascular effects have been published, yet. In this study, we set out to analyse if different types of regular wheelchair-based exercises elicit anti-atherogenic effects in patients with traumatic SCI. Therefore, we analysed in this cross-sectional study on cardiovascular risk markers like exercise capacity, physical work capacity, blood lipids, pulse wave velocity, and pro-inflammatory endothelial blood markers in a healthy control group and three groups of patients with SCI: (i) wheelchair dancers (W-dance), (ii) patients conducting other wheelchair sports (wheelchair non-dancing athletes, W-ND-ex), and (iii) wheelchair non-exercising patients (W-no-ex). Patients with SCI between 18 and 80 years of age with no metal implants or additional neurological conditions besides SCI and no pregnancy were recruited. Age-matched healthy participants without neurological or psychiatric conditions were recruited as a control group. In total, 52 participants (50% males, 46.3 ± 13.5 years) including 8 wheelchair dancers, 7 wheelchair athletes of other sports (i.e. hand biking n = 3, basketball n = 3, and marathon n = 2), 8 non-exercising SCI patients, and 29 age-matched healthy participants were included. Clinical characteristics of the patients varied between an ASIA (American Spinal Injury Association) score from A to D, complete and incomplete lesions. All tests were performed at the University Institute for Sports Medicine, Prevention and Rehabilitation of the Paracelsus Medical University Salzburg, Austria. The study complied with the Declaration of Helsinki, and written informed consent was obtained from all participants before the beginning of the study (Ethics Committee of the State of Salzburg no. 415-E/1/2340-2016, ClinicalTrials.gov: NCT03352505). All participants underwent a blood draw and pulse wave analysis before maximal upper body cardiopulmonary exercise testing. For statistical analysis, based on distribution, a one-way analysis of variance (ANOVA) with Bonferroni post hoc test or the Kruskal–Wallis test with Dunn’s multiple comparison post hoc test was applied. The Student’s t-test or Mann–Whitney U test was performed to compare healthy participants from SCI patients. A χ² test was used to evaluate gender distribution and the location of the injury. Correlations were calculated using Spearman’s rho. All analyses were performed with IBM SPSS Statistics version 24.0. Statistical significance was assumed at P < 0.05. There were no significant differences between the three wheelchair groups or all four groups concerning age and anthropometric data (except for body height), age of injury, or location of injury. Between the four groups, there were significant differences for absolute (P = 0.003) and relative physical work capacities (PWCpeak; P = 0.001). Highest values were observed in healthy participants and the lowest levels within the non-exercising SCI group. Within the SCI groups, there were significantly higher values in the wheelchair non-dancing athletes than in the dance and non-exercising groups (all P < 0.01). Similar results were seen for absolute and relative PWCpeak. The highest values were found in the healthy participants and the lowest in the non-exercising SCI patients (all P < 0.001). Further, significantly lower relative PWCpeak was observed in the sedentary SCI group compared to wheelchair dancers and wheelchair non-dancing athletes (P = 0.001). Results are shown in Table 1. There were no differences between any groups with regard to parameters of pulse wave velocity. Exercise, pulse wave analyses, and blood parameter of individuals with traumatic SCI and healthy controls Values are means ± standard deviation or median and range when not normally distributed; significance levels are calculated using one-way ANOVA over all four groups, respectively, and only the three wheelchair user groups for normally distributed. Statistical significance was set at P < 0.05. W-dance, wheelchair dancers; W-ND-ex, wheelchair non-dancing athletes; W-no-ex, wheelchair non-exercising patients; VO2max, maximal oxygen uptake; mL, millilitre; min, minute; kg, kilogram; HRmax, maximal heart rate; Pmax, maximal power in Watt (W); Pmax-rel, maximal power in relation to the bodyweight; SBP, systolic blood pressure; DBP, diastolic blood pressure; mmHg, millimetre of mercury; PWV, pulse wave velocity; cSBP, central systolic blood pressure; cDBP, central diastolic blood pressure; cPP, central pulse pressure; AIx@75, augmentation index corrected to a normative heart rate of 75 beats per minute; Pb, amplitude of reflection wave; Pf, amplitude of ejection wave; vCAM, vascular cell adhesion molecule-1; iCAM, intercellular adhesion molecule-1; BDNF, brain derived neurotrophic factor; VEGF, vascular endothelial growth factor; NO, nitric oxide; TNFα, tumour necrosis factor α; IL-6, interleukin 6; HDL, high-density lipoprotein; LDL, low-density lipoprotein; CK, creatine kinase; CRP, C-reactive protein; m/s, metre per second; %, per cent; mg, milligram; dL, decilitre; ng, nanogram; pg, picogram; L, litre; U/L, units per litre. aKruskal–Wallis test when not normally distributed. bSignificant post hoc differences between healthy and W-no-ex. cSignificant post hoc differences between W-ND-ex and W-no-ex. dPost hoc differences between healthy and W-ND-ex. eSignificant post hoc differences between W-no-ex and W-dance. fSignificant post hoc differences between W-ND-ex and W-dance. In wheelchair non-dancing athletes, the vascular cell adhesion molecule-1 (vCAM-1) was significantly lower than in non-exercising SCI patients (P = 0.030), and the intercellular adhesion molecule-1 (iCAM-1) was significantly lower than in all other groups (P = 0.003). Highest values for triglycerides were detected in the non-exercising SCI patients (P = 0.032) and for high-density lipoprotein in the healthy group (P = 0.001). Association between blood markers, age, and exercise parameters in all study participants are shown in the Supplementary material online, File. In brief, we found significant indirect correlations for absolute and relative PWCpeak, with iCAM-1 (P < 0.05), vCAM-1 (only PWCpeak P = 0.03), IL-6 (P < 0.01), and TNF-α (P < 0.01). Also, a direct correlation was found between the same absolute and relative exercise parameters and NO levels (P < 0.01).Taken together, our data suggest that good physical fitness might result in lower expression levels of pro-inflammatory endothelial blood markers. The differences between SCI patients and healthy controls independent of their exercise behaviour are shown in the Supplementary material online, File. Taken together, we report beneficial effects of regular physical exercise in SCI patients on objective measures of exercise capacity, markers of inflammation, and endothelial health. We also report that low-grade inflammation and endothelial activation were more commonly found in sedentary SCI patients. We conclude that it is important also for SCI patients to provide opportunities for life-long physical activity and physical exercise training. Nonetheless, more research is needed to assess whether these beneficial effects translate into attenuating if not halting atherogenesis and thus coronary artery disease—the leading cause of death also in patients with SCI. B.M., E.T., and J.N. contributed to the conception or design of the work. B.M., M.F., V.F., N.R., and K.S. contributed to the acquisition, analysis, or interpretation of data for the work. B.M. drafted the manuscript. M.F., V.F., N.R., K.S., E.T., and J.N. critically revised the manuscript. All gave final approval and agree to be accountable for all aspects of work ensuring integrity and accuracy. Supplementary material is available at European Journal of Preventive Cardiology online. The authors would like to thank all subjects for their enthusiasm and their time dedicated to the study. The Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS) support its cooperation partners financially (like the department of Neurology Salzburg). The data that support the findings of this study are available from the corresponding author upon reasonable request.