Subclinical inflammation in very old and long-living patients with coronary artery disease

BACKGROUND . With aging, the concentration of proinflammatory mediators increases even in the absence of signs of inflammation (“inflammaging”). AIM. To determine the serum concentration of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) and to analyze the relationships of these proinflammatory cytokines with a number of pathological conditions in very old and long-living patients with coronary artery disease (CAD). MATERIALS AND METHODS . The study enrolled patients over 75 years of age. The study on TNF-α enrolled 130 patients (102 with CAD in the main group, 28 without CAD in the control group). The mean age of patients was 89.3 ± 4.6 years (77–101 years); more than half (56.2%) were over 90 years old. The study on IL-6 enrolled 128 patients (94 patients with CAD in the main group, 34 without CAD in the control group). The mean age of patients was 88.3 ± 5.3 years (76–98 years); 49.2% were over 90 years old. The concentration of TNF-α (N < 8.1 pg/mL) and IL-6 (N < 7.0 pg/mL) was determined by enzyme-linked immunosorbent assay. RESULTS . The mean TNF-α concentration was 9.2 ± 4.7 pg/mL (3.9– 31.9 pg/mL). Increased TNF-α was found in 54.6% of patients. In patients with CAD, mean TNF-α concentration reached 10.0 ± 4.9 pg/mL, while in the control group it was 6.1 ± 1.8 pg/mL (p = 0.000001). The probability of detecting an elevated TNF-α level in patients with CAD increased by 16.6 times compared with patients without CAD (odds ratio (OR) = 16.6; p < 0.00001). The TNF-α concentration was higher in patients with chronic heart failure (CHF) (p = 0.002). In patients with hyperuricemia, mean TNF-α level was 10.9 ± ± 5.3 pg/mL, while in patients with normal uric acid levels it was 7.5 ± 2.5 pg/mL (p = 0.000006). Direct correlations were found between the concentrations of TNF-αand uric acid (r = 0.45; p < 0.000001), creatinine (r = 0.26; p = 0.002), urea (r = = 0.37; p = 0.00004), type I collagen degradation products (β-CrossLaps) (r = 0.53; p = 0.0001) and IL-6 (r = 0.39; p = 0.007). Inverse correlations were found between the concentration of TNF-α and HDL-cholesterol (r = -0.38; p = 0.00005). In patients under 90 years of age, mean TNF-α concentration reached 10.5 pg/mL, while in long-living patients it was 8.1 pg/mL (p = 0.003). Elevated IL-6 levels were found in 45.3% of patients. Mean IL-6 concentration was 8.2 ± 6.3 pg/mL (1.5–36.2 pg/mL). In patients with CAD, mean IL-6 concentration reached 9.0 pg/mL, while in those without coronary artery disease it was 5.8 pg/mL (p = 0.001). The probability of detecting elevated IL-6 concentrations in patients with CHF increased by 3.1 times, compared with the group without heart failure (OR = 3.1; p = 0.005). Among patients with asymptomatic hyperuricemia, mean blood concentration of IL-6 reached 10.8 ± 4.8 pg/mL, while in patients with normal uric acid levels it comprised 6.9 ± 4.5 pg/mL (p = 0.001). Patients with elevated IL-6 levels had lower values of baseline functional activity according to the Barthel index (70.7 and 80.7, p = 0.003) and instrumental activity according to the IADL scale (3.4 and 5.0, p = 0.0002). CONCLUSIONS . The study results indicate a frequent increase in the blood concentration of TNF-α and IL-6 in very old and long-living patients with CAD. Higher levels of TNF-α and IL-6 are associated with CHF and hyperuricemia.