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.