Fraser D Russell

Abdominal aortic aneurysm (AAA) is an important cause of death in older adults which has no current drug therapy. Inflammation and abnormal redox status are believed to be key pathogenic mechanisms for AAA. In light of evidence correlating inflammation with aberrant fatty acid profiles, this study compared erythrocyte fatty acid content in 43 AAA patients (diameter 3.0-4.5 cm) and 52 healthy controls. In addition, the effect of omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation on erythrocyte fatty acid content was examined in a cohort of 30 AAA patients as part of a 12-week randomised placebo-controlled clinical trial. Blood analyses identified associations between AAA and decreased linoleic acid, and AAA and increased Δ6-desaturase activity and biosynthesis of arachidonic acid from linoleic acid. n-3 PUFA supplementation (1.5g DHA+0.3g EPA/day) decreased red blood cell distribution width (RDW, 14.8±0.4% to 13.8±0.2%, p=0.003) and levels of pro-inflammatory n-6 PUFAs (arachidonic acid, 12.46±0.23% to 10.14±0.3%, P<0.001; adrenic acid 2.12±0.13% to 1.23±0.09%, p<0.001). In addition, Δ4-desaturase activity increased (docosahexaenoic/docosapentaenoic acid ratio, 1.85±0.14 to 3.93±0.17, P<0.001) and elongase 2/5 activity decreased (adrenic acid/arachidonic acid ratio, 0.17±0.01 to 0.12±0.01, P<0.01) following supplementation. The findings suggest n-3 PUFAs improve fatty acid profiles and ameliorate factors associated with inflammation in AAA patients.

Objective/background: Elevated arterial stiffness is a characteristic of abdominal aortic aneurysm (AAA), and is associated with AAA growth and cardiovascular mortality. A bout of exercise transiently reduces aortic and systemic arterial stiffness in healthy adults. Whether the same response occurs in patients with AAA is unknown. The effect of moderate- and higher intensity exercise on arterial stiffness was assessed in patients with AAA and healthy adults. Methods: Twenty-two men with small diameter AAAs (36±5 mm; mean age 74±6 years) and 22 healthy adults (mean age 72±5 years) were included. Aortic stiffness was measured using carotid to femoral pulse wave velocity (PWV), and systemic arterial stiffness was estimated from the wave reflection magnitude (RM) and augmentation index (Alx75). Measurements were performed at rest and during 90 min of recovery following three separate test sessions in a randomised order: (i) moderate intensity continuous exercise; (ii) higher intensity interval exercise; or (iii) seated rest. Results: At rest, PWV was higher in patients with AAA than in healthy adults (p < .001), while AIx75 and RM were similar between groups. No differences were observed between AAA patients and healthy adults in post-exercise aortic and systemic arterial stiffness after either exercise protocol. When assessed as the change from baseline (delta, Δ), post-exercise ΔAIx75 was not different to the seated rest protocol. Conversely, post-exercise ΔPWV and ΔRM were both lower at all time points than seated rest (p < .001). ΔPWV was lower immediately after higher intensity than after moderate intensity exercise (p = .015). Conclusion: High resting aortic stiffness in patients with AAA is not exacerbated after exercise. There was a similar post-exercise attenuation in arterial stiffness between patients with AAA and healthy adults compared with seated rest. This effect was most pronounced following higher intensity interval exercise, suggesting that this form of exercise may be a safe and effective adjunctive therapy for patients with small AAAs.

Markers of chronic inflammation increase with aging, and are associated with cardiovascular disease prevalence and mortality. Increases in fitness with exercise training have been associated with lower circulating concentrations of cytokines known to have pro-inflammatory actions (such as interleukin-6 [IL-6]) and higher circulating concentrations of anti-inflammatory cytokines (interleukin-10 [IL-10]). However, the effect of cardiorespiratory fitness on acute cytokine responses to a single bout of exercise in healthy older individuals is unknown. We compared the response of plasma cytokines IL-6, tumor necrosis factor-alpha (TNF-α) and IL-10 to a bout of moderate-intensity continuous and higher-intensity interval exercise between older individuals with higher and lower levels of cardiorespiratory fitness. Sixteen lower-fit (VO2peak: 22.6±2.8 mL.kg-1.min-1) and fourteen higher-fit participants (VO2peak: 37.4±5.9 mL.kg-1.min-1) completed three 24 min experimental protocols in a randomized order: (1) moderate-intensity continuous exercise (40% of peak power output [PPO]); (2) higher-intensity interval exercise (12 × 1 min intervals at 70% PPO separated by 1 min periods at 10% PPO); or (3) non-exercise control. Plasma cytokines were measured at rest, immediately after, and during 90 min of recovery following exercise or control. Plasma IL-6 concentrations at baseline were greater in the higher-fit compared to the lower-fit group (P = 0.02), with no difference in plasma IL-10 or TNF-α concentrations at baseline between groups. Plasma IL-6 and IL-10 concentrations in both groups increased immediately after all protocols (IL-6: P = 0.02, IL-10: P < 0.01). However, there was no difference in the IL-6 and IL-10 response between the exercise and non-exercise (control) protocols. After all protocols, no changes in plasma TNF-α concentrations were observed in either the higher- or lower-fit groups. In this study, basal concentrations of circulating IL-6 were elevated in older individuals with higher levels of cardiorespiratory fitness. However, changes in plasma cytokine concentrations after exercise were not different to changes after non-exercise control in both the lower- and higher-fit groups.

Purpose: Inflammation and extracellular matrix degeneration contribute to abdominal aortic aneurysm (AAA) development. We aimed to assess the effect of exercise intensity on circulating biomarkers of inflammation and extracellular matrix degeneration in patients with AAA and healthy older adults. Methods: Twenty patients with AAA (74±6y) and twenty healthy males (72±5y) completed moderate-intensity cycling at 40% peak power output (PPO), higher-intensity intervals at 70% PPO, and control (rest) on separate days. Circulating matrix metalloproteinase-9 (MMP-9), transforming growth factor beta 1 (TGF-β1), interleukin-6 (IL-6), IL-10 and tumour necrosis factor alpha (TNF-α) were analysed at rest, and 0 to 90 min post. Results: Biomarkers at baseline were similar between groups. IL-6 responses to exercise were similar between groups, with a greater increase in ΔIL-6 after moderate-intensity compared to higher-intensity exercise (P<0.001). Delta MMP-9 showed a 118 ng/ml (95% CI, 23 to 214, P=0.02) greater increase immediately after higher-intensity exercise compared to changes in control in both groups. Delta MMP-9 then decreased by 114 ng/ml (18 to 211, P=0.02) 90 min after higher-intensity exercise compared to the changes in control. Delta TNF-α was not different between protocols in healthy adults. In patients with AAA, delta TNF-α showed a greater decrease after higher-intensity compared to moderate-intensity exercise (-6.1 pg/ml, -8.5 to -3.6, P<0.001) and control (-4.9 pg/ml, -7.4 to -2.4, P<0.001). IL-10 and TGF-β1 did not change in either group. Conclusions: These findings suggest that a bout of higher-intensity exercise elicits a greater anti-inflammatory response compared to moderate-intensity exercise, which may be further augmented in patients with AAA. Exercise-induced reductions in biomarkers associated with AAA progression may represent a protective effect of exercise in patients with AAA.