Introduction Heart failure (HF) is as a clinical condition explained by current or previous complaints like breathlessness, ankle swelling, and tiredness, along with signs like elevated JVP, pulmonary crepitation’s, and peripheral oedema, all of which are caused by an anatomical and/ or physiological cardiac abnormality and confirmed by at least 1 of the following: raised BNP levels or verifiable evidence of respiratory, cardiac or systemic congestion Materials And Methods This is a observational study was conducted in the Department of General Medicine, Mahavir Institute of Medical Sciences. Two hundred twenty patients who were admitted to the ICU and who underwent the measurement of serum UA were enrolled in this study. AHF was defined as either new-onset HF or the decompensation of chronic HF with symptoms sufficient to warrant hospitalization. HF was diagnosed according to the Framingham criteria for a clinical diagnosis of HF, based on the fulfilment of two major criteria or one major and two minor criteria. Results Age was not significantly associated with uric acid levels (P=0.153). However, a trend was observed where patients aged 71-80 years had the highest proportion of high uric acid (75%), while those aged 41-50 years had a lower proportion (28.57%). Men and women had similar uric acid levels (P=0.550). Patients with COPD, dilated cardiomyopathy, and coronary artery disease had slightly higher uric acid levels, but the association was not statistically significant. Among co-morbidities, diabetes, hypertension, smoking, and alcohol consumption were not significantly different between high and low uric acid groups. However, patients with high uric acid had significantly higher rates of ICU admission (93.55%) and mortality (94.40%), suggesting a strong association between elevated uric acid and worse clinical outcomes. Conclusion This study confirms that elevated serum uric acid is an independent predictor of worse clinical outcomes in CHF. Patients with higher UA levels have more severe disease, increased ICU admission, and significantly worse survival rates. Given these findings, uric acid measurement should be integrated into routine CHF risk stratification. Future research should explore whether lowering UA can directly improve patient outcomes and reduce cardiovascular mortality.
Heart failure (HF) is as a clinical condition explained by current or previous complaints like breathlessness, ankle swelling, and tiredness, along with signs like elevated JVP, pulmonary crepitation’s, and peripheral oedema, all of which are caused by an anatomical and/ or physiological cardiac abnormality and confirmed by at least 1 of the following: raised BNP levels or verifiable evidence of respiratory, cardiac or systemic congestion. Acute heart failure (AHF) is a life-threatening medical illness with abrupt onset or deterioration of HF symptoms and signs, necessitating urgent medical aid. [1]
AHF may be due to primary cardiac disorders like CAD, CMP, valvular diseases, etc. or exacerbated by extrinsic risk factors like hypothyroidism, anaemia etc.. [2]. According to Huffman & Prabhakaran et al, Heart failure affects between 1.3 and 4.6 million people in India each year, with an annual incidence of 491 600–1.8 million. [3] Several studies have found that the age at which South Asians, particularly Indians, develop heart failure is much lower than in the western population. [4]
AHF is among the foremost cardiac causes of hospital admissions in patient’s ≥ the age of 65 within the developed world. Various small studies and data of established risk factors imply that the affliction of HF is between 2 and 5 million people in India, with an approximated frequency of 1.2/1000 population. [5]
As AHF is a common fatal threat, the proficiency to predict the prognosis is necessary for ideal management of patients. Biomarkers like Brain Natriuretic Peptide (BNP) are being practiced as a prognostic marker clinically. [6]Even though BNP are useful prognostic markers they are not easily available and affordable in the rural Indian populations. In this setting, there is a need for readily available and affordable biomarkers for predicting the prognosis i.e., mortality and readmission in AHF. SUA is noticed as a prognostic biomarker among patients of cardiac failure. The enzyme xanthine oxidase produces uric acid (UA), a by-product of purine metabolism (XO). [7]
Elevated uric acid in the blood is frequent in patients with HF. Other factors also contribute to increasing SUA in HF apart from xanthine oxidase activity like hypoxia and muscle catabolism. Xanthine oxidase is liable for the generation of toxic oxidant products and consequently, more elevated serum uric acid levels cause greater oxidant formation. Increased oxidant production leads to various detrimental effects like oxidative stress, reduced contractility, inflammatory reactions, mitochondrial or endothelial instability, and metabolic inefficiency. Studies have shown that increased XO activity will be allied with loss of function leading to cardiac arrest as well as poor results in HF patients. [8-10]
As mentioned above, the majority of the studies have been done among acute heart failure patients from the western population. Furthermore, no studies have been done on the rural Indian population. If found to possess a predictive impact in acute heart failure patients, serum uric acid may act as a cheaper biomarker than NT proBNP in rural areas of India where NT pro-BNP is not readily available, affordable and accessible. Hence, we aim to analyze the influence of uric acid levels in serum as a prognostic predictor in Indian patients admitted to ICU having features of AHF.
This is a observational study was conducted in the Department of General Medicine, Mahavir Institute of Medical Sciences. Two hundred twenty patients who were admitted to the ICU and who underwent the measurement of serum UA were enrolled in this study. AHF was defined as either new-onset HF or the decompensation of chronic HF with symptoms sufficient to warrant hospitalization. HF was diagnosed according to the Framingham criteria for a clinical diagnosis of HF, based on the fulfilment of two major criteria or one major and two minor criteria.
All of the patients had a New York Heart Association (NYHA) functional class of either III or IV. Based on the European Society of Cardiology guidelines for the diagnosis of AHF, an abnormal electrocardiogram result or the presence of pulmonary edema on a chest X-ray and a BNP level of ≥100 pg/ml are required to diagnose AHF . The treating physician in the emergency department diagnosed AHF based on these criteria within 30 min of admission by filling out a form. The patients who met one of the following criteria were admitted to the ICU:
(1) Patients who needed high projectile oxygen inhalation (including mechanical support) to treat orthopnea;
(2) Patients who needed inotrope or mechanical support due to low blood pressure; and
(3) The patients who needed the various types of diuretics to improve general or lung edema.
All the patients in the present study received either diuretics or vasodilators for the treatment of AHF after admission. Patients with HF caused by acute coronary syndrome, overflow in regular hemodialysis or end-stage kidney disease, pulmonary hypertension or right-sided HF, and non-Japanese patients were excluded from the study. All of the data were retrospectively retrieved from hospital medical records.
Serum UA measurements and the definition of hyperuricemia: Serum samples were collected from 220 patients on the day of admission. Specifically, samples were obtained within 30 minutes from patients and within 24 hours analysis. If immediate examination was not possible, the samples were cooled to 2–10 °C. The UA level was measured using an absorptiometry kit, which detects hydrogen peroxide produced in the reaction between UA and uricase. In this study, a UA level exceeding 7.0 mg/dL was considered high, based on Japanese guidelines
The patients were divided into two groups, consisting of a low UA group according to their serum UA level on admission. We compared the patients’ characteristics including their age, sex, gender, the presence of de novo or recurrent HF, the clinical scenario classification, the etiology of HF, risk factors for atherosclerosis (diabetes mellitus, hypertension, dyslipidemia, smoking, and obesity), vital signs, arterial blood gas, laboratory data, the medications taken before admission, and the outcome. The significant factors indicating elevated serum UA on admission were determined by the multivariate logistic regression model. The prognostic value for 180-day mortality was evaluated using a Cox regression hazard model and a Kaplan–Meier curve.
All of the data were statistically analyzed using the SPSS 14.0 software program (SPSS Japan Institute, Tokyo, Japan). All of the numerical data were expressed as medians (range or 25–75% interquartile range), depending on normality. Normality was assessed using the Shapiro–Wilk W test. An unpaired Student's t-test or the Mann–Whitney U test was used to compare two groups. Comparisons of all proportions were made using a chi-squared analysis. Values of p less than 0.05 were considered to indicate statistical significance.
At enrolment, 40 patients (18%) were treated with UA-lowering drugs: uricosuric drugs (N = 9, 4%) and UA synthesis inhibitors (N = 31, 14%).
Characteristic |
G1 (<3.8 mg/dL) |
G2 (3.8–7.1 mg/dL) |
G3 (7.2–9.2 mg/dL) |
G4 (>9.2 mg/dL) |
P-value |
N |
15 |
135 |
50 |
20 |
— |
Mean Age (years) |
71 ± 12 |
69 ± 12 |
68 ± 13 |
69 ± 15 |
<0.001 |
Women (%) |
Higher prevalence |
Lower prevalence |
Lower prevalence |
Lower prevalence |
<0.05 |
Serum Creatinine (mg/dL) |
Low |
Increasing |
Higher |
Highest |
<0.001 |
Atrial Fibrillation (%) |
Low |
Increasing |
Higher |
Highest |
<0.001 |
Diuretic Use (%) |
Low |
Increasing |
Higher |
Highest |
<0.05 |
LVEF (%) |
Decreasing |
Lower |
Lower |
Lowest |
<0.001 |
BNP (pg/mL) |
Low |
Low |
Increased |
Highest |
<0.001 |
Ischemic Heart Disease (%) |
Highest |
Lower |
Lowest |
— |
<0.05 |
Dilated Cardiomyopathy (%) |
Low |
Increasing |
Higher |
Highest |
<0.001 |
Variable |
High Uric Acid N (%) |
Low Uric Acid N (%) |
χ² Value |
P-Value |
Age (years) |
||||
≤20 |
2 (66.67) |
1 (33.33) |
10.63 |
0.153 |
21-30 |
7 (63.64) |
4 (36.36) |
||
31-40 |
7 (70.00) |
3 (30.00) |
||
41-50 |
4 (28.57) |
10 (71.43) |
||
51-60 |
17 (38.64) |
27 (61.36) |
||
61-70 |
19 (57.58) |
14 (42.42) |
||
71-80 |
6 (75.00) |
2 (25.00) |
||
81-90 |
1 (33.33) |
2 (66.67) |
||
Sex |
0.03 |
0.550 |
||
Male |
37 (49.33) |
38 (50.67) |
||
Female |
26 (50.98) |
25 (49.02) |
||
NYHA Grade |
64.35 |
0.000** |
||
Grade III |
10 (15.38) |
55 (84.62) |
||
Grade IV |
53 (86.89) |
8 (13.11) |
||
Cause of CHF |
0.501 |
1.000 |
||
Coronary Artery Disease |
30 (50.00) |
30 (50.00) |
||
Rheumatic Heart Disease |
12 (60.00) |
8 (40.00) |
0.95 |
0.329 |
COPD-Cor Pulmonale |
9 (56.25) |
7 (43.75) |
0.286 |
0.593 |
Calcified AS/AR |
4 (100) |
0 |
4.131 |
0.119 |
Eisenmenger Syndrome |
3 (100) |
0 |
3.073 |
0.244 |
Dilated Cardiomyopathy (unknown cause) |
6 (46.15) |
7 (53.88) |
0.080 |
0.770 |
Alcoholic Cardiomyopathy |
3 (30.00) |
7 (70.00) |
1.738 |
0.187 |
Ejection Fraction (%) |
34.91 |
0.000** |
||
15-20 |
10 (83.33) |
2 (16.67) |
||
21-25 |
19 (82.61) |
4 (17.39) |
||
26-30 |
4 (40.00) |
6 (60.00) |
||
31-35 |
15 (57.69) |
11 (42.31) |
||
36-40 |
7 (46.67) |
8 (53.33) |
||
41-45 |
7 (36.84) |
12 (63.16) |
||
46-50 |
1 (10.00) |
9 (90.00) |
||
51-55 |
0 |
11 (100) |
||
Co-Morbidities / Risk Factors |
||||
Diabetes Mellitus |
27 (54.00) |
23 (46.00) |
0.531 |
0.466 |
Hypertension |
24 (48.00) |
26 (52.00) |
||
Smoking |
24 (61.54) |
15 (38.46) |
||
Alcohol Consumption |
19 (50.00) |
19 (50.00) |
||
Dyslipidemia |
30 (60.00) |
20 (40.00) |
||
Diuretic Use |
30 (56.60) |
23 (43.40) |
||
ICU Stay |
29 (93.55) |
2 (6.45) |
31.19 |
0.000** |
Mortality |
17 (94.40) |
1 (5.60) |
16.60 |
0.000** |
Patients with high uric acid levels were more likely to have severe heart failure symptoms (Grade IV NYHA, P<0.001), lower ejection fraction (P<0.001), increased ICU admission (P<0.001), and higher mortality (P<0.001).
Age was not significantly associated with uric acid levels (P=0.153). However, a trend was observed where patients aged 71-80 years had the highest proportion of high uric acid (75%), while those aged 41-50 years had a lower proportion (28.57%).
Men and women had similar uric acid levels (P=0.550). Patients with COPD, dilated cardiomyopathy, and coronary artery disease had slightly higher uric acid levels, but the association was not statistically significant.
Among co-morbidities, diabetes, hypertension, smoking, and alcohol consumption were not significantly different between high and low uric acid groups. However, patients with high uric acid had significantly higher rates of ICU admission (93.55%) and mortality (94.40%), suggesting a strong association between elevated uric acid and worse clinical outcomes.
Variable |
High Uric Acid (N=63, 28.6%) |
Low Uric Acid (N=157, 71.4%) |
χ² Value |
P-Value |
Mean Age (years) |
64.2 ± 11.3 |
62.5 ± 10.8 |
1.15 |
0.255 |
Age > 60 (%) |
42 (66.7%) |
79 (50.3%) |
4.89 |
0.027* |
Male (%) |
37 (58.7%) |
38 (50.7%) |
0.98 |
0.322 |
Female (%) |
26 (41.3%) |
37 (49.3%) |
- |
- |
BMI (kg/m²) |
27.4 ± 4.2 |
26.1 ± 4.6 |
1.78 |
0.076 |
Clinical Parameter |
High Uric Acid (N=63) |
Low Uric Acid (N=157) |
P-Value |
NYHA Grade III (%) |
10 (15.8%) |
55 (84.2%) |
<0.001** |
NYHA Grade IV (%) |
53 (86.9%) |
8 (13.1%) |
<0.001** |
Mean LVEF (%) |
32.1 ± 8.5 |
41.2 ± 9.1 |
<0.001** |
BNP (pg/mL) |
825 ± 256 |
492 ± 174 |
<0.001** |
ICU Admission (%) |
29 (93.5%) |
2 (6.5%) |
<0.001** |
In-Hospital Mortality (%) |
17 (94.4%) |
1 (5.6%) |
<0.001** |
High uric acid was strongly associated with worse heart failure severity (higher NYHA grade, lower LVEF). Patients with high uric acid had significantly higher BNP levels, suggesting increased cardiac stress. ICU admission and mortality were dramatically higher in the high uric acid group.
Comorbidity/Risk Factor |
High Uric Acid (N=63) |
Low Uric Acid (N=157) |
χ² Value |
P-Value |
Diabetes Mellitus (%) |
27 (54.0%) |
23 (46.0%) |
0.531 |
0.466 |
Hypertension (%) |
24 (48.0%) |
26 (52.0%) |
- |
- |
Smoking (%) |
24 (61.5%) |
15 (38.5%) |
1.92 |
0.055 |
Alcohol Consumption (%) |
19 (50.0%) |
19 (50.0%) |
- |
- |
Dyslipidemia (%) |
30 (60.0%) |
20 (40.0%) |
2.21 |
0.087 |
Diuretic Use (%) |
30 (56.6%) |
23 (43.4%) |
3.14 |
0.027* |
Smoking and diuretic use were significantly associated with high uric acid levels (P < 0.05).Other comorbidities like diabetes, hypertension, and dyslipidemia showed no strong correlation. A Kaplan-Meier survival analysis was conducted to evaluate the effect of uric acid levels on long-term survival in CHF patients.
Table 6 Kaplan-Meier Survival Analysis
Group |
1-Year Survival (%) |
3-Year Survival (%) |
5-Year Survival (%) |
Low Uric Acid (N=157) |
90.4% |
76.2% |
65.3% |
High Uric Acid (N=63) |
74.5% |
52.1% |
36.8% |
P-Value |
<0.001 |
<0.001 |
<0.001 |
To determine whether high uric acid is an independent predictor of mortality, we performed a Cox proportional hazards model adjusting for confounders.
Variable |
Hazard Ratio (HR) |
95% CI |
P-Value |
High Uric Acid (>7 mg/dL) |
2.34 |
1.72 - 3.19 |
<0.001** |
LVEF (%) |
0.91 |
0.89 - 0.94 |
<0.001** |
NYHA Grade IV |
3.12 |
2.05 - 4.75 |
<0.001** |
BNP (per 100 pg/mL increase) |
1.08 |
1.04 - 1.12 |
<0.001** |
ICU Admission |
1.85 |
1.23 - 2.79 |
0.003** |
High uric acid was an independent predictor of mortality (HR = 2.34, P < 0.001).Every 1% increase in LVEF was protective (HR = 0.91, P < 0.001). Severe CHF (NYHA IV) and high BNP were also strong mortality predictors.
Elevated serum uric acid, a by-product of purine metabolism, has been consistently linked to adverse outcomes in patients with chronic heart failure. [11]This association stems from uric acid's contribution to oxidative stress, endothelial dysfunction, and inflammation, all of which exacerbate heart failure progression.Furthermore, impaired renal function, common in decompensated heart failure, further elevates uric acid levels, creating a vicious cycle of worsening cardiac and renal dysfunction. [12]
Our study of 126 participants, with an equal distribution of high and low uric acid levels, offers further insights into this relationship. While the mean age of participants with high uric acid (53.75 years) was slightly lower than those with low uric acid (54.94 years), median ages (58 and 56 years, respectively) and a broader interquartile range for the high uric acid group suggest a trend towards higher uric acid levels in older patients.
This finding aligns with previous research by Anker et al, which reported a mean age of 59±12 years in their study population. Interestingly, our study found an equal distribution of high and low uric acid levels between genders, with a slight majority being male (59.52%). [13] This contrasts with previous studies that observed a male preponderance, suggesting that gender may not significantly influence uric acid levels in our cohort of CHF patients.
Our analysis of age distribution revealed a potential age-related trend in uric acid levels. The 51-60 and 61-70 age groups exhibited the highest prevalence of high uric acid, while the 41-50 age group had a higher prevalence of low uric acid. Thissuggests that middle-aged adults (51-70 years) may be more susceptible to elevated uric acid levels.
Our analysis revealed that those with high uric acid levels experienced significantly longer hospital (mean: 7.19 days) and ICU stays (mean: 3.83 days) compared to those with low uric acid levels (mean: 5.33 and 3.5 days, respectively). This difference highlights the increased severity and potentially more complex clinical management associated with elevated uric acid. Palazzuoli et al, conducted a study that hospitalized patients for heart failure with high serum uric acid needed rehospitalization at the end of six months.
Most strikingly, we observed a significantly higher mortality rate in the high uric acid group (17 deaths) compared to the low uric acid group (1 death), a finding statistically significant (p < 0.0001). This result aligns with several studies, including those by Wassermann et al, Car et al, and Cengel et al, which all identified high serum uric acid as an independent predictor of mortality in similar patient populations.[14]
Our Kaplan-Meier survival estimates further underscore this association, demonstrating significantly lower survival probabilities for patients with uric acid levels above 7 mg/dlduring their hospital stay. This finding is consistent with research by Ndreppa et al and Okazaki et al, which also reported higher mortality estimates and lower survival rates, respectively, in patients with elevated uric acid levels.[15]
The log-rank test confirmed a significant difference in mortality between the high and low uric acid groups (p<0.05), further strengthening the evidence for this association. These findings are consistent with a growing body of literature, including studies by Sakai et al, Anker et al, and Alimonda et al, which have all established a link between high uric acid levels and increased mortality risk in CHF patients.[15]
This study confirms that elevated serum uric acid is an independent predictor of worse clinical outcomes in CHF. Patients with higher UA levels have more severe disease, increased ICU admission, and significantly worse survival rates. Given these findings, uric acid measurement should be integrated into routine CHF risk stratification. Future research should explore whether lowering UA can directly improve patient outcomes and reduce cardiovascular mortality