Heart failure (HF) with reduced ejection fraction is a progressive, systemic disease resulting from systolic dysfunction, an often enlarged left ventricle, with low, insufficient cardiac output to meet tissue demands. In many cases, reduced myocardial contractility is a result of ischaemic heart disease associated with the other systemic process of atherosclerosis [
Abnormalities in the oxidative and antioxidant states causing oxidative stress were found in heart failure of various aetiologies. Furthermore, increasing experimental evidence supports the concept that oxidative stress is increased in the failing heart and contributes to the pathogenesis of myocardial remodelling [
Systolic heart dysfunction leads to tissue hypoxia. In these conditions, we observed an imbalance in mitochondrial electron transport, which leads to increased oxidative stress, intracellular Ca2+ overload, and cell death. The formation of reactive oxygen species (ROS) in the heart and other tissues occurs as a result of several mechanisms. They can be produced by xanthine oxidase (XO), NAD(P)H oxidases, and cytochrome P450, by autoxidation of catecholamines and by the uncoupling of NO synthase (NOS) [
One of the methods to detect oxidative stress is a measurement of organic molecules that are products of harmful ROS effects on the integrity of biological tissue, e.g., malondialdehyde (MDA). MDA arises as a result of the fragmentation of polyunsaturated fatty acids undergoing attack by ROS and is a generally accepted index of lipid peroxidation [
Systemic oxidative stress can also be measured as a depletion of free thiol in the serum [
Both protein modifications and coexisting increased lipid oxidation confirm the existence of systemic oxidative stress in heart failure patients [
Uric acid is considered as an important component of the antioxidant system. It is a final product of the enzymatic degradation of purines, and it is released from hypoxic tissues [
Due to the fact that xanthine oxidase produces uric acid (UA) in proportion to the production of ROS, the uric acid would be a very valuable and readily available biomarker of oxidative stress in the cardiovascular system. Serum levels of UA probably present an adaptive response against oxidative stress [
Another metabolic transformation, which probably affects the redox status, is heme degradation with reduction of biliverdin to bilirubin by biliverdin reductase, with subsequent oxidation of bilirubin to biliverdin by ROS [
Because of the large number of different antioxidants in the serum, we decided to assess the total antioxidant capacity (TAC), total oxidant status (TOS), and TOS/TAC ratio, also called the oxidative stress index (OSI), in heart failure patients depending on ischaemic (ICM) and nonischaemic (nICM) aetiologies [
In our study, we used data collected in the prospective registry of heart failure (PR-HF), undertaken since 2003, and the SICA-HF (Studies Investigating Comorbidities Aggravating Heart Failure) study described elsewhere [
Noninvasive clinical assessments included physical examination, ECG, and echocardiography. The NYHA classification and cardiopulmonary exercise testing (CPX) were used to assess functional capacity [
Blood samples for laboratory assessments were obtained from the patients at the study inclusion. Serum was separated by centrifugation at 1500 g for 10 minutes and frozen at −70°C. Uric acid, bilirubin, and albumin concentrations were measured using the colorimetric method (Roche, Cobas 6000e501). NT-proBNP was measured with the use of the chemiluminescence method (Roche, Cobas 6000e501). Additionally, we determined lipid parameters, blood haemoglobin, and serum creatinine concentrations using routine techniques. The total oxidant status (TOS) was measured by the spectrophotometric method developed by Erel [
Malondialdehyde was measured according to the method described by Ohkawa et al., using the reaction with thiobarbituric acid with spectrofluorimetric detection: excitation 515 nm and emission 552 nm. MDA concentration was calculated from the standard curve, prepared from 1,1,3,3-tetraethoxypropane and expressed in
Statistical analysis was performed using STATISTICA 13.1 PL (StatSoft, Poland, Cracow). A normal distribution of all variables was evaluated by the Shapiro-Wilk test. The continuous data was presented as a median with the first and fourth quartiles (because of the abnormal distribution of the data). In the case of a normal distribution, continuous variables were compared using the Mann-Whitney
The statistical correlation between the variables was determined using Spearman’s rank correlation coefficient, and a
774 patients with reduced ejection fraction heart failure (HFrEF), 479 due to ischaemic cardiomyopathy (ICM) (mean age 56.44 years, 86,8% male), and 295 with nonischaemic cardiomyopathy (mean age 47,40 years, 84,4% male) were enrolled into the final study. The ICM group was significantly older. Comorbidities like arterial hypertension and diabetes were more frequent in ICM group. The mean duration of symptoms was similar in both groups and was around four years (Table
Clinical and laboratory characteristics of patients included into the study with comparison of study groups. Categorical variables are shown as percentages and numerical variables as medians with lower and upper quartiles where appropriate.
Ischaemic ( |
Nonischaemic ( |
||
---|---|---|---|
General characteristics | |||
Male ( |
416 (86,8) | 249 (84,4) | NS |
Age (years) | 56,00 (52,00–61,00) | 50,00 (39,00–56,00) | 0,001 |
BMI (kg/m2) | 26,45 (23,88-29,29) | 25,77 (22,32-29,07) | 0,01 |
Duration of symptoms before inclusion (months) | 33,87 (13,6-66,27) | 33,83 (2,17-73,1) | NS |
NYHA class | 3 (2-3) | 3 (2-3) | NS |
Measured VO2 (ml/min) | 1,10 (0,82-1,38) | 1,16 (0,92-1,43) | 0,05 |
Maximum measured VO2 (ml/min/kg b.m.) | 14,6 (11,9-17,9) | 15,6 (12,6-19,5) | 0,01 |
Measured VCO2 (l/min) | 1,07 (0,77-1,38) | 1,13 (0,86-1,39) | 0,01 |
LVEDD (mm) | 69,00 (63,00-75,00) | 71,00 (64,00-78,00) | 0,05 |
LVEDV (ml) | 209,0 (167,0-271,0) | 245,0 (181,0-314,0) | 0,001 |
LVEF (%) | 24,00 (20,00-30,00) | 23,00 (20,00-29,00) | NS |
Basic biochemistry | |||
Haemoglobin (mmol/l) | 14,02 (13,05-14,83) | 14,18 (13,05-15,31) | 0,05 |
Creatinine ( |
88,00 (73,00–108,0) | 83,00 (71,0–99,0) | 0,01 |
Serum protein concentration (g/l) | 71,00 (67,00–75,00) | 71,0 (67,00–76,00) | NS |
Albumin (g/l) | 42,00 (39, 00–44,00) | 42,00 (39,00–45,00) | NS |
Fasting glucose (mmol/l) | 5,60 (5,00-6,40) | 5,50 (4,90-6,10) | 0,05 |
Total cholesterol (mmol/l) | 4,26 (3,65-5,23) | 4,32 (3,62-5,19) | NS |
Triglycerides (mmol/l) | 1,21 (0,88-1,74) | 1,21 (0,91-1,71) | NS |
Cholesterol HDL (mmol/l) | 1,16 (0,95-1,41) | 1,14 (0,91-1,40) | NS |
Cholesterol LDL (mmol/l) | 2,43 (1,87 - 3,16) | 2,48 (1,94-3,19) | NS |
NT-proBNP (pg/ml) | 1317 (628,4-2863) | 1601 (658,6-3562) | NS |
Comorbidities | |||
Diabetes ( |
162 (33,8) | 57 (19,3) | 0,001 |
Arterial hypertension ( |
287 (59,9) | 136 (46,1) | 0,001 |
Atrial fibrillation ( |
85 (17,7) | 98 (33,2) | 0,001 |
ICD presence ( |
75 (15,7) | 47 (15,9) | NS |
Smoker ( |
361 (75,4) | 202 (68,5) | 0,05 |
Pharmacotherapy | |||
Beta-blockers ( |
472 (98,5) | 287 (97,3) | NS |
ACE inhibitors ( |
417 (87,2) | 251 (85,1) | NS |
Angiotensin-2 receptor blockers ( |
48 (10,0) | 34 (11,5) | NS |
Loop diuretics ( |
403 (84,1) | 276 (93,6) | 0,05 |
Thiazide diuretics ( |
52 (10,9) | 47 (15,9) | 0,05 |
Aldosterone receptor antagonist ( |
433 (90,4) | 281 (95,3) | NS |
Statins ( |
364 (76,0) | 142 (48,1) | 0,001 |
Fibrates ( |
17 (3,55) | 11 (3,73) | NS |
Digitalis ( |
193 (40,3) | 159 (53,9) | 0,001 |
XOi ( |
142 (29,6) | 133 (45,1) | 0,001 |
BMI: body mass index; NYHA: New York Heart Association functional class; VO2: maximum oxygen output; LVEDD: left ventricle end-diastolic diameter; LVEDV: left ventricle end-diastolic volume; LVEF: left ventricle ejection fraction; NT-proBNP: N-terminal pro-B-type natriuretic peptide; ICD: implantable cardioverter defibrillator; ACE-inhibitor: angiotensin-converting enzyme inhibitor; XOi: xanthine oxidase inhibitors; NS: nonsignificant.
The majority of patients were treated with
Redox biomarkers of patients included into a study with comparison of study groups. Variables are shown as medians with lower and upper quartiles where appropriate.
Ischaemic ( |
Nonischaemic ( |
||
---|---|---|---|
TAC (mmol/l) | 1,14 (1,04-1,26) | 1,11 (0,98-1,22) | 0,001 |
TOS (mmol/l) | 4,75 (4-6,1) | 5,10 (4,3-6,2) | NS |
OSI (TOS/TAC) | 4,27 (3,31-5,65) | 4,60 (3,68-5,89) | 0,01 |
Uric acid ( |
407,0 (333,0–505,0) | 413,0 (326,0-506,0) | NS |
Uric acid ( |
406,0 (336,0–491,0) | 423,5 (344,5–497,5) | NS |
Uric acid ( |
410,5 (324,0–541,0) | 403,0 (308,0–519,0) | NS |
Bilirubin ( |
12,70 (9,20-19,10) | 15,40 (10,60-21,90) | 0,001 |
Albumin (g/l) | 42,00 (39,00–44,00) | 42,00 (39,00–45,00) | NS |
PSH ( |
4,10 (3,1-5,1) | 4,75 (3,65-5,6) | 0,001 |
MDA ( |
1,80 (1,40-2,20) | 1,70 (1,40-2,10) | 0,05 |
MDA/PSH ratio | 0,435 (0,314-0,647) | 0,358 (0,269–0,527) | 0,001 |
TAC: total antioxidant capacity; TOS: total oxidant status; OSI: oxidative stress index; MDA: malondialdehyde; PSH: sulfhydryl groups; XOi: xanthine oxidase inhibitors; NS: nonsignificant.
In the ICM patients, we observed a statistically significant higher concentration of TAC (
Comparison of oxidative stress parameters in groups of patients depending on heart failure aetiology.
There were significant positive correlations between the NYHA class and TOS (
VO2 max correlated inversely with MDA (
Correlation between redox parameters and clinical characteristic of heart failure in ischaemic and nonischaemic cardiomyopathy.
ICM | nICM | |
---|---|---|
Spearman |
Spearman | |
NYHA | NYHA | |
PSH ( |
||
TAC (mmol/l) | ||
TOS (mmol/l) | ||
OSI (TOS/TAC) | ||
MDA ( |
||
MDA/PSH ratio | ||
Uric acid ( |
||
Uric acid ( |
||
Uric acid ( |
||
Bilirubin ( |
||
Albumin (g/l) | ||
LVEF | LVEF | |
PSH ( |
||
TAC (mmol/l) | ||
TOS (mmol/l) | ||
OSI (TOS/TAC) | ||
MDA ( |
||
MDA/PSH ratio | ||
Uric acid ( |
||
Uric acid ( |
||
Uric acid ( |
||
Bilirubin ( |
||
Albumin (g/l) | ||
NT-proBNP | NT-proBNP | |
PSH ( |
||
TAC (mmol/l) | ||
TOS (mmol/l) | ||
OSI (TOS/TAC) | ||
MDA ( |
||
MDA/PSH ratio | ||
Uric acid ( |
||
Uric acid ( |
||
Uric acid ( |
||
Bilirubin ( |
||
Albumin (g/l) | ||
VO2 maks. | VO2 maks. | |
PSH ( |
||
TAC (mmol/l) | ||
TOS (mmol/l) | ||
OSI (TOS/TAC) | ||
MDA ( |
||
MDA/PSH ratio | ||
Uric acid ( |
||
Uric acid ( |
||
Uric acid ( |
||
Bilirubin ( |
||
Albumin (g/l) |
ICM: ischaemic cardiomyopathy; nICM: nonischaemic cardiomyopathy; NYHA: New York Heart Association functional class; LVEF: left ventricle ejection fraction; NT-proBNP: N-terminal pro-B-type natriuretic peptide; VO2max: maximum oxygen output; TAC: total antioxidant capacity; TOS: total oxidant status; OSI: oxidative stress index; MDA: malondialdehyde; PSH: sulfhydryl groups; XOi: xanthine oxidase inhibitors.
There were significantly positive correlations between the NYHA class and TOS (
An inverse correlation between TAC and TOS (
Correlation between redox parameters in ischaemic heart failure patients.
ICM | PSH ( |
TAC (mmol/l) | TOS (mmol/l) | OSI (TOS/TAC) | MDA ( |
MDA/SH | Uric acid ( |
Uric acid (XOi -) ( |
Uric acid (XOi +) ( |
Bilirubin ( |
Albumin (g/l) |
---|---|---|---|---|---|---|---|---|---|---|---|
PSH ( |
1,000 | -0,265 ( |
-0,012 NS | 0,099 ( |
-0,207 ( | -0,059 (NS) | -0,086 (NS) | -0,016 (NS) | -0,049 (NS) | 0,096 ( | |
TAC (mmol/l) | -0,265 ( | -0,139 ( | 0,204 ( |
0,292 ( |
0,324 ( |
0,282 ( |
0,399 ( |
0,004 (NS) | 0,102 ( | ||
TOS (mmol/l) | -0,012 (NS) | -0,139 ( | 0,032 (NS) | 0,062 (NS) | -0,025 (NS) | -0,054 (NS) | 0,040 (NS) | -0,052 (NS) | -0,065 (NS) | ||
OSI (TOS/TAC) | 0,099 ( | -0,072 (NS) | -0,078 (NS) | -0,150 ( |
-0,162 ( |
-0,125 (NS) | -0,056 (NS) | -0,081 (NS) | |||
MDA ( |
-0,207 ( |
0,204 ( |
0,032 (NS) | -0,072 (NS) | 0,120 ( |
0,125 ( |
0,105 (NS) | 0,078 (NS) | 0,060 (NS) | ||
MDA/PSH ratio | 0,292 ( |
0,062 (NS) | -0,078 (NS) | 0,115 ( |
0,143 ( |
0,066 (NS) | 0,081 (NS) | -0,043 (NS) | |||
Uric acid ( |
-0,059 (NS) | 0,324 ( |
-0,025 (NS) | -0,150 ( |
0,120 ( |
0,115 ( | 0,164 ( |
0,146 ( | |||
Uric acid (XOi -) ( |
-0,086 (NS) | 0,282 ( |
-0,054 (NS) | -0,162 ( |
0,125 ( |
0,143 ( | 0,191 ( |
0,148 ( | |||
Uric acid (XOi +) ( |
-0,016 (NS) | 0,399 ( |
0,040 (NS) | -0,125 (NS) | 0,105 (NS) | 0,066 (NS) | 0,102 (NS) | 0,124 (NS) | |||
Bilirubin ( |
-0,049 (NS) | 0,004 (NS) | -0,052 (NS) | -0,056 (NS) | 0,078 (NS) | 0,081 (NS) | 0,164 ( |
0,191 ( |
0,102 (NS) | 0,009 (NS) | |
Albumin (g/l) | 0,096 ( |
0,102 ( |
-0,065 (NS) | -0,081 (NS) | 0,060 (NS) | -0,043 (NS) | 0,146 ( |
0,148 ( |
0,124 (NS) | 0,009 (NS) |
ICM: ischaemic cardiomyopathy; TAC: total antioxidant capacity; TOS: total oxidant status; OSI: oxidative stress index; MDA: malondialdehyde; PSH: sulfhydryl groups; XOi: xanthine oxidase inhibitors.
Similarly to the ICM group, positive correlations between TAC and uric acid (
Additionally, bilirubin correlated positively with MDA/PSH (
Correlation between redox parameters in nonischaemic heart failure patients.
nICM | PSH ( |
TAC (mmol/l) | TOS (mmol/l) | OSI (TPS/TAC) | MDA ( |
MDA/SH | Uric acid ( |
Uric acid (XOi -) ( |
Uric acid (XOi +) ( |
Bilirubin ( |
Albumin (g/l) |
---|---|---|---|---|---|---|---|---|---|---|---|
PSH ( | -0,267 ( |
-0,021 (NS) | 0,078 (NS) | -0,230 ( | -0,178 ( |
-0,193 ( |
-0,194 ( |
-0,179 ( |
0,049 (NS) | ||
TAC (mmol/l) | -0,267 ( | -0,087 (NS) | 0,278 ( |
0,366 ( |
0,546 ( |
0,383 ( |
0,706 ( |
0,195 ( |
0,051 (NS) | ||
TOS (mmol/l) | -0,021 (NS) | -0,087 (NS) | 0,112 (NS) | 0,081 (NS) | 0,050 (NS) | 0,149 (NS) | -0,040 (NS) | 0,098 (NS) | 0,015 (NS) | ||
OSI (TOS/TAC) | 0,078 (NS) | -0,017 (NS) | -0,072 (NS) | -0,191 ( |
-0,062 (NS) | -0,307 ( |
0,007 (NS) | 0,013 (NS) | |||
MDA ( |
-0,230 ( |
0,278 ( |
0,112 (NS) | -0,017 (NS) | 0,067 (NS) | 0,013 (NS) | 0,149 (NS) | 0,205 ( |
0,061 (NS) | ||
MDA/PSH ratio | 0,366 ( |
0,081 (NS) | -0,072 (NS) | 0,145 ( |
0,092 (NS) | 0,232 ( |
0,250 ( |
0,010 (NS) | |||
Uric acid ( |
-0,178 ( |
0,546 ( |
0,050 (NS) | -0,191 ( |
0,067 (NS) | 0,145 ( | 0,151 ( |
0,028 (NS) | |||
Uric acid (XOi -) ( |
-0,193 ( |
0,383 ( |
0,149 (NS) | -0,062 (NS) | 0,013 (NS) | 0,092 (NS) | 0,092 (NS) | -0,046 (NS) | |||
Uric acid (XOi +) ( |
-0,194 ( |
0,706 ( |
-0,040 (NS) | -0,307 ( |
0,149 (NS) | 0,232 ( | 0,165 ( |
0,089 (NS) | |||
Bilirubin ( |
-0,179 ( |
0,195 ( |
0,098 (NS) | 0,007 (NS) | 0,205 ( |
0,250 ( |
0,151 ( |
0,092 (NS) | 0,165 ( | -0,022 (NS) | |
Albumin (g/l) | 0,049 (NS) | 0,051 (NS) | 0,015 (NS) | 0,013 (NS) | 0,061 (NS) | 0,010 (NS) | 0,028 (NS) | -0,046 (NS) | 0,089 (NS) | -0,022 (NS) |
nICM: nonischaemic cardiomyopathy; TAC: total antioxidant capacity; TOS: total oxidant status; OSI: oxidative stress index; MDA: malondialdehyde; PSH: sulfhydryl groups; XOi: xanthine oxidase inhibitors.
To our knowledge, this is one of few studies assessing the oxidative stress index (OSI) as a TAC to TOS ratio, the products of lipid peroxidation, and the protein sulfhydryl group PSH in relation to heart failure due to ischaemic and nonischaemic aetiologies.
Additionally, we focused on the differences between redox-state compounds in the ischaemic and nonischaemic groups depending on the patient’s clinical status and therapy.
In the present study, we evaluated a large group of 479 patients with ischaemic heart failure and 295 patients with nonischaemic heart failure. It should be emphasised that the patients were clinically stable and they received the optimal treatment for heart failure.
We have found significantly higher TAC concentrations in ischaemic patients which was accompanied by a significant decrease in OSI. In our study, TOS was similar in ischaemic and nonischaemic patients. Additional studies compared ischaemic or nonischaemic patients with a control group. Karabacak et al. studied 37 patients with nonischaemic HF. They observed that OSI levels were significantly higher in the patients with nonischaemic HF compared to the control subjects; uric acid and the TOS level were also higher in nonischaemic HF patients compared to the control group [
In our study, ICM patients were statistically older and had higher incidences of hypertension or diabetes. In addition, this group was characterised by higher fasting glycaemia, higher creatinine, and a lower haemoglobin level. The aforementioned differences may be partially explained by metabolic disorders, leading to the development and propagation of the atherosclerotic process at the base of ischaemic HF.
Both groups were comparable in terms of values of parameters such as LVEF, NT-proBNP concentration, and NYHA functional class. However, lower maximal minute oxygen consumption was indicated in the ICM group. An impaired metabolic profile and lower haemoglobin level may explain the lower peak of oxygen consumption in ICM. The concentration of uric acid and lipids was similar in both groups, but it may be the effect of more frequent use of allopurinol in nICM groups and statins in the ICM group. Referring to the clinical state of patients, both bilirubin and albumin correlated with the exercise tolerance of patients assessed by NYHA or cardiopulmonary exercise testing and NTproBNP in both groups. However, UA, especially in patients not treated with allopurinol, showed a positive correlation only to the ICM group.
Moreover, significantly lower PSH and a higher MDA concentration and MDA/SH ratio were found in the ICM group. It is very important to highlight that a negative correlation between the maximum oxygen consumption and the MDA concentration and a positive correlation with PSH were indicated. In addition, the concentration of MDA in both subgroups positively correlated with the NYHA functional class, while in the nICM group, it correlated negatively with PSH.
At the same time, there was no correlation between the LVEF and oxidative stress parameters such as PSH, MDA, TAC, TAS, OSI, and the MDA/SH ratio, in both groups. The association of LVEF with potential antioxidant activity compounds such as UA, bilirubin, and albumin has been demonstrated only in the group of patients with ICM. This supports the hypothesis that the reduction of LVEF is less important for oxidative stress generation than tissue hypoxia and neurohormonal activation as consequence of low cardiac output and maybe atherosclerotic lesions. The results obtained confirm the previous observation that disturbances of reduction and oxidative balance in patients with systolic heart failure are rather a result of heart failure than its cause [
Our results are partially consistent with data presented by Keith et al., who reported a correlation between the severity of heart failure and elevated lipid peroxides and MDA in both ischaemic heart disease and dilated cardiomyopathy patients with end-stage heart failure [
In ICM patients, MDA correlated with uric acid concentration positively too. A negative correlation between PSH and the concentration of uric acid and bilirubin was expressed only in the nICM group. This may be in favour of PSH consumption in the ROS inactivation reaction generated by the xanthine oxidase reaction and in the cyclic bilirubin oxidation to biliverdin reaction. The nICM and ICM groups are also different in terms of the degree of correlation between MDA and uric acid and bilirubin. In the ICM group, a significantly positive correlation occurs between uric acid and MDA, while in the nICM group, MDA correlates with uric acid and bilirubin. This suggests that in patients with ischaemic HF, the oxidation of purines to uric acid is a dominant source of ROS. In patients with nICM, ROS comes from reactions associated with heme degradation. The increase in uric acid levels under oxidative stress, as well as its reducing properties in vitro and in vivo, is well documented.
When analysing the relationship between UA and TAC, a positive correlation was found in both groups but it was stronger in nICM. Interestingly, both in ICM and in nICM, stronger correlations were demonstrated for patients treated with allopurinol.
Strong positive correlations between TAC and uric acid are not surprising, since these small molecules (like albumin, vitamin E, and vitamin C) are TAC components [
It is possible that the plasma level of UA (also a significant component of TAC) represents an adaptive response to protect an organism against oxidative stress [
Fabbrini et al. showed, in an “in vivo” experiment, that total uric acid degradation by recombinant urate oxidase in insulin-resistant patients with elevated UA concentration caused a 45-95% decrease in TAC, with a parallel increase of muscle and systemic markers of oxidative stress by 25-40% [
Preliminary results of the study [
Unfortunately, large clinical trials have not demonstrated the benefits of inhibiting xanthine oxidase activity with allopurinol in patients with heart failure [
Kittleson et al. showed that serum uric acid levels correlate with plasma NT-proBNP and are associated with worse haemodynamic function in patients with HF [
The study by Anker et al. documents and validates that high serum UA levels are strong, independent markers of a worse prognosis in patients with moderate to severe CHF [
Our research suggests that bilirubin has similar properties to UA in the ischaemic group HF patient observation. The positive correlations between bilirubin and NT-proBNP and uric acid were observed. Higher bilirubin and lower albumin concentrations were associated with an increased severity of heart failure both in ICM and in nICM patients. These results, on the one hand, are likely to reflect the impairment of liver function in advanced heart failure. On the other hand, the demonstrated correlations between bilirubin and SH (negative) and MDA (positive) concentrations suggest that they are related to the oxidation reduction balance. Interestingly, these relationships only occur in the nICM patients. Is difficult to explain that the lipid peroxidation process is connected with higher bilirubin in nICM, in contrast to higher UA in the ICM group. The facts that bilirubin and uric acid correlated positively with TAC and that increased bilirubin or uric acid concentrations are related to adverse outcomes make it difficult to view these parameters as beneficial antioxidants [
It seems that TAC is not protective in the literal sense. We cannot interpret the increase in TAC as a super defensive mechanism against ROS action in patients with heart failure, because of the fact that there were positive correlations between TAC and MDA in both groups.
We emphasise that the negative correlation between the final products of lipid peroxidation—MDA and PSH—were detected in both examined groups. In heart failure patients, Koning et al. showed that the concentration of PSH groups above the mean, was associated with better renal function, lower levels of NT-proBNP, and with a decreased rehospitalisation rate and increased patient survival [
These complement the results obtained by us. The presented study showed a positive correlation between the magnitude of maximum oxygen consumption and the concentration of SH groups. We also detected a negative correlation between PSH and NT-proBNP and the NYHA class in n-ICM patients. The negative correlation between TAC and PSH (part of TAC) speaks over the active growth of TAS components generated in oxidation reactions (uric acid) and consumption of others such as PSH, perhaps in a reaction with ROS generated in the synthesis of TAC components.
PSH negatively correlates with the concentration of uric acid and bilirubin. This is particularly expressed in the nICM group. This may be in favour of PSH consumption in the ROS inactivation reaction generated by the xanthine oxidase reaction and in the cyclic bilirubin oxidation to biliverdin reaction.
An important advantage of the study is the large size of the study group. In both groups of patients, we have demonstrated the relationship between the heart failure aetiology and oxidative stress. These findings are in favour of the dominant concept of the role of oxidative stress in CHF in the last decade [
The data used to support the findings of this study are available from the corresponding author upon request.
The authors declare that there is no conflict of interests regarding the publication of this paper.
This work was founded by the Medical University of Silesia grant no. KNW-1/096/K/8/0, Poland.