Neuroimmune and endocrine mechanisms of unfavorable geriatric status in patients with acute coronary syndrome

Background: Acute coronary syndrome (ACS) is the cause of above 70% of deaths in patients of older age. Frailty that develops in elderly patients provokes pro-inflammatory and neuroimmune inflammatory responses in the body that promote deterioration of the ACS course.

Aim: To study neuroimmunoendocrine alterations in elderly patients with ACS depending on the presence or absence of the frailty syndrome.

Materials and methods: The study was performed by retrospective, cross-sectional and prospective evaluation of the ACS patient registries within an international project GIRAFFE (Gerontological Research International Against Frailty: Fit Experience) in 2011–2015. We analyzed the results of measurement of serum tumor necrosis factor alfa (TNF-α) and the interleukin family (IL-1β, IL-4, IL-6, IL-10) in 633 patients with non-ST ACS (n = 270) and with ST-ACS (n = 363) at days 5, 12, and 26 from the beginning of the pain syndrome. From those, 265 patients were non-frail, 97 were pre-frail, and 271 patients had the frailty syndrome. The control group included 116 patients without significant somatic disease.

Results: In all study groups of patients with non-ST ACS, there was an increase in IL-4, IL-6 and IL-10 levels, compared to their reference ranges, at day 5 from the beginning of the pain syndrome. Subsequently, these parameters were changing with therapy, similarly in all groups: IL-4 level gradually decreased by the end of the follow-up, IL-10 level increased by day 12 from the beginning of the pain syndrome and decreased by day 26. The lowest IL-10 levels compared to the reference range (1.5 ± 0.2 pg/mL) were seen in the elderly frail patients: 2.9 ± 0.6 pg/mL at day 5 from the beginning of the pain syndrome, 7.2 ± 1.2 pg/mL at day 12, and 1.9 ± 0.3 pg/mL at day 26, compared to 8 ± 1.2, 15.5 ± 1.6 and 6.2 ± 1.1 pg/mL in the isolated ACS group, respectively (all p < 0.05). In the group with non-ST ACS, higher TNF-α and IL-1β levels, compared to the control, were registered only in the elderly frail patients. Under treatment, these parameters did not reached the reference ranges, being 187.7 ± 6.5 and 310.2 ± 29.5 pg/mL at day 5 from the beginning of the pain syndrome, 165 ± 6 and 299.5 ± 29.4 pg/mL at day 12 and 154 ± 5.9 and 265.9 ± 27.9 at day 26, respectively, compared to 68.7 ± 3 pg/mL (p < 0.05 for all comparisons to the control group). In the ST-ACS patients, TNF-α, IL-1β, IL-4, IL-6, and IL-10 levels exceeded the reference ranges in all groups studied for the whole study duration. In the patients with the elderly frailty syndrome the serum concentrations of TNF-α, IL-1β, IL-6 and IL-10 were higher than in the non-frail and pre-frail patients with ST-ACS. The IL-4 levels were not informative for the assessment of the contribution of the elderly frailty to the ST-ACS course.

Conclusion: The frailty syndrome of the elderly provokes the activation of the pro-inflammatory system that is confirmed by the consistent increase of serum pro-inflammatory mediators associated to the degree of the frailty syndrome in ACS patients.