Acute ST-elevation myocardial infarction (STEMI) remains an important cause of cardiovascular morbidity and mortality worldwide. Ischemic heart disease continues to be a leading cause of death globally, accounting for a substantial proportion of cardiovascular deaths.1 The burden of ischemic heart disease is particularly relevant in developing countries such as India, where cardiovascular diseases have emerged as a leading cause of mortality. Epidemiological transition, rapid urbanization, changes in lifestyle, and the increasing prevalence of conventional cardiovascular risk factors have contributed substantially to the growing burden of coronary heart disease in the Indian population.2,3 Despite major advances in early diagnosis, reperfusion strategies, and contemporary management of acute myocardial infarction, early mortality following STEMI remains an important clinical concern. Hyponatremia, generally defined as a serum sodium concentration <135 mmol/L, is one of the most frequently encountered disorders of fluid and electrolyte balance in clinical practice and is common among hospitalized patients.4 It has also been recognized as an important prognostic marker in cardiovascular disease, particularly among patients with heart failure, in whom persistent or more severe hyponatremia is associated with increased mortality and rehospitalization.5 Acute myocardial infarction is accompanied by neurohormonal activation, including activation of the sympathetic nervous system and renin–angiotensin–aldosterone system and increased release of vasopressin, which may promote water retention and contribute to disturbances in sodium and water homeostasis.6,7 Consequently, hyponatremia present at admission or developing during the early course of STEMI may serve as a marker of greater neurohormonal activation, physiological stress, and severity of myocardial dysfunction.6 Although the adverse prognostic significance of hyponatremia has been well established in heart failure, evidence also indicates an important prognostic role in acute STEMI.5 Goldberg et al.6, in a study of 1,047 consecutive patients with acute STEMI, demonstrated that both hyponatremia present at admission and hyponatremia developing during the first 72 hours following admission were independent predictors of 30-day mortality. Furthermore, mortality increased with increasing severity of hyponatremia. Subsequent evidence demonstrated that hyponatremia occurring during acute STEMI was also associated with increased long-term mortality among survivors of the acute event.7 These findings suggest that the timing and severity of hyponatremia may provide clinically useful prognostic information in patients presenting with STEMI. Therefore, the present study was undertaken to determine the association between hyponatremia and 30-day all-cause mortality among patients with acute STEMI. The study also aimed to determine the occurrence of hyponatremia at admission and within 72 hours, compare 30-day mortality according to sodium-status groups, assess the association between the severity of hyponatremia and mortality, and explore the association of demographic and clinical characteristics with 30-day mortality.

This prospective observational study was conducted for 2 years at B.L.D.E.A.’s Shri B.M. Patil Medical College and Research Centre, Bijapur. The sample size was estimated based on a previous study by Goldberg et al.6, which reported an incidence of hyponatremia of 32% among patients with acute ST-elevation myocardial infarction (STEMI). Considering an expected proportion of 32% and an allowable relative error of 30%, the minimum required sample size was calculated to be approximately 94 participants. A total of 100 consecutive eligible patients presenting with acute STEMI during the study period were included. Patients presenting with acute myocardial infarction characterized by chest pain lasting more than 20 minutes, diagnostic electrocardiographic changes consistent with acute myocardial infarction, and elevated creatine kinase-MB or cardiac troponin T levels were considered eligible. Patients presenting with acute coronary syndrome without ST-segment elevation were excluded. Eligible participants underwent detailed clinical history and physical examination. Demographic and clinical characteristics, including age, sex, smoking status, diabetes mellitus, hypertension, infarct location, Killip class, and left ventricular ejection fraction, were recorded. Patients received thrombolytic therapy with either tissue-type plasminogen activator or streptokinase as part of the management of acute myocardial infarction. Plasma sodium concentration was measured at admission and subsequently at 24, 48, and 72 hours using an ion-selective electrode autoanalyser (Roche OMNI C). Hyponatremia was defined as a plasma sodium concentration <135 mmol/L. Based on serial sodium measurements, patients were categorized as having normal sodium levels, hyponatremia at admission, or hyponatremia developing within 72 hours. The severity of hyponatremia was also evaluated according to the observed sodium concentrations. The primary outcome was all-cause mortality within 30 days following myocardial infarction. Mortality occurring during hospitalization and after discharge was ascertained up to 30 days. For patients discharged before completion of follow-up, mortality status was obtained through returned postcards from patients or their families and, when these were unavailable, by telephone contact or a home visit. Sodium-status groups were compared for baseline demographic and clinical characteristics and 30-day mortality. The relationship between the severity of hyponatremia and 30-day mortality was also assessed. Categorical variables were expressed as frequencies and percentages, while continuous variables were summarized as mean ± standard deviation. Comparisons across the three sodium-status groups were performed using one-way ANOVA for continuous variables and chi-square or Fisher’s exact test for categorical variables, as appropriate. Thirty-day mortality was compared using Fisher’s exact test, and unadjusted odds ratios with 95% confidence intervals were calculated using the normal-sodium group as reference. Survivor and non-survivor characteristics were similarly compared. All tests were two-tailed, and p<0.05 was considered statistically significant.

Among the 100 patients with acute STEMI, 71% maintained normal sodium levels, while 29% developed hyponatremia. Hyponatremia was present at admission in 11% of patients, whereas 18% developed hyponatremia within 72 hours of admission. (Figure 1) Diabetes mellitus differed significantly across the sodium-status groups (p=0.009), with the highest proportion among patients developing hyponatremia within 72 hours (44.4%). Age, sex, smoking, hypertension, anterior infarction, Killip class, and LVEF did not differ significantly between the groups. (Table 1). Figure 1: Distribution of patients with acute STEMI according to sodium status Table 1: Baseline demographic and clinical characteristics of patients with acute STEMI according to sodium status Characteristic Normal sodium (n=71) Hyponatremia at admission (n=11) Hyponatremia in 72 hours (n=18) p-value Age, years, mean ± SD 57.8 ± 11.7 64.9 ± 13.1 56.61 ± 11.54 0.145† Male sex, n (%) 57 (80.3) 9 (81.8) 14 (77.8) 0.960# Diabetes mellitus, n (%) 9 (12.7) 3 (27.3) 8 (44.4) 0.009#* Smoking, n (%) 50 (70.4) 9 (81.8) 11 (61.1) 0.493# Hypertension, n (%) 14 (19.7) 2 (18.2) 4 (22.2) 0.960# Anterior infarction, n (%) 45 (63.4) 8 (72.7) 15 (83.3) 0.252# Killip class, mean ± SD 1.06 ± 0.23 1.18 ± 0.40 1.06 ± 0.24 0.312† LVEF, %, mean ± SD 44.63 ± 11.19 40.36 ± 6.14 50.11 ± 13.26 0.060† † One Way ANOVA test; # Chi-square test; * Statistically significant at p<0.05. LVEF, left ventricular ejection fraction; SD, standard deviation; STEMI, ST-elevation myocardial infarction. Of the 100 patients with acute STEMI included in the study, 92 (92.0%) survived through 30 days, while 8 (8.0%) died, resulting in an overall 30-day all-cause mortality rate of 8.0%. (Figure 2) Figure 2: Distribution of patients with acute STEMI according to sodium status Thirty-day all-cause mortality was 8.0% overall. Mortality was 2.8% among patients with normal sodium, compared with 27.3% among those with hyponatremia at admission and 16.7% among those developing hyponatremia within 72 hours. Admission hyponatremia was associated with significantly higher odds of 30-day mortality compared with normal sodium levels (OR 12.94, 95% CI 1.87–89.42; p=0.016). Delayed hyponatremia showed higher mortality odds, although the pairwise comparison did not reach statistical significance (p=0.054). (Table 2) Table 2: Association of sodium status with 30-day all-cause mortality among patients with acute STEMI Sodium status Survivors n (%) Deaths n (%) OR (95% CI)† p-value# Normal sodium (n=71) 69 (97.2) 2 (2.8) Reference - Hyponatremia at admission (n=11) 8 (72.7) 3 (27.3) 12.9 (1.8–89.4) 0.016* Hyponatremia in 72 hours (n=18) 15 (83.3) 3 (16.7) 6.9 (1.1–44.9) 0.054 † Unadjusted odds ratio calculated using the normal-sodium group as the reference category. # Fisher's exact test; * Statistically significant at p<0.05. CI, confidence interval; OR, odds ratio; STEMI, ST-elevation myocardial infarction. Among 29 patients who developed hyponatremia, 3 had serum sodium <130 mmol/L and 26 had levels of 131–134 mmol/L. All three patients with sodium <130 mmol/L died within 30 days, compared with 3 (11.5%) deaths among those with sodium levels of 131–134 mmol/L. The association between severity of hyponatremia and 30-day mortality was statistically significant (p=0.005), indicating substantially higher mortality among patients with more severe hyponatremia. (Table 3) Table 3: Association between severity of hyponatremia and 30-day all-cause mortality among patients with acute STEMI Serum sodium level Survivors, n (%) Deaths, n (%) p-value# <130 mmol/L (n=3) 0 (0.0) 3 (100.0) 0.005* 131–134 mmol/L (n=26) 23 (88.5) 3 (11.5) # Fisher's exact test; *Statistically significant at p<0.05. STEMI, ST-elevation myocardial infarction. Table 4: Demographic and clinical characteristics according to 30-day survival status among patients with acute STEMI Characteristic Survivors (n=92) Non-survivors (n=8) p-value Age, years, mean ± SD 57.7 ± 12.1 65.5 ± 7.58 0.025†* Sex, n (%) Male 76 (82.6) 4 (50.0) 0.042#* Female 16 (17.4) 4 (50.0) Serum sodium, mmol/L, mean ± SD 136.96 ± 1.92 134.09 ± 3.53 0.057† Smoking, n (%) 66 (71.7) 4 (50.0) 0.238# Diabetes mellitus, n (%) 16 (17.4) 4 (50.0) 0.046#* Hypertension, n (%) 16 (17.4) 4 (50.0) 0.046#* Infarct location, n (%) Anterior 63 (68.5) 5 (62.5) 0.999# Inferior 29 (31.5) 3 (37.5) Killip class, n (%) I 88 (95.7) 5 (62.5) 0.013#* II 4 (4.3) 3 (37.5) LVEF, %, mean ± SD 47.7 ± 12.7 38.6 ± 10.9 0.050† † Independent t-test; # Fisher's exact test; * Statistically significant at p<0.05. LVEF, left ventricular ejection fraction; SD, standard deviation; STEMI, ST-elevation myocardial infarction. Among 100 patients with acute STEMI, 8 died within 30 days. Non-survivors were older and had higher proportions of diabetes mellitus, hypertension, and Killip class II compared with survivors. Female sex was also more frequent among non-survivors. Mean serum sodium was lower among non-survivors (134.09 ± 3.53 vs 136.96 ± 1.92 mmol/L), although the reported difference did not reach statistical significance (p=0.057). LVEF was lower among non-survivors, with a borderline p-value of 0.050. Infarct location and smoking were not significantly associated with survival status. (Table 4)

Hyponatremia is a recognized prognostic marker in cardiovascular disease, but its relationship with early mortality following acute STEMI, particularly according to its timing and severity, requires further evaluation. This prospective observational study included 100 consecutive STEMI patients admitted to B.L.D.E.A.’s Shri B.M. Patil Medical College, Bijapur, for the duration of 2 years. Eligible patients had typical chest pain, diagnostic ECG changes, and elevated cardiac biomarkers. Demographic and clinical variables, including cardiovascular risk factors, infarct location, Killip class, and LVEF, were recorded. Serum sodium was measured at admission and at 24, 48, and 72 hours. Hyponatremia was defined as sodium <135 mmol/L, and patients were categorized by sodium status. In the present study, hyponatremia occurred in 29.0% of 100 acute STEMI patients, with 11.0% having hyponatremia at admission and 18.0% developing it within 72 hours. These findings were comparable to Pasha G et al.8, who reported 27.0% overall hyponatremia (13.0% at admission and 14.0% within 72 hours), Vikas et al.9 with 34.0% (14.0% and 20.0%, respectively), Chandrasekaran SP et al.10 with 35.4%, and Patil GS et al.11 with 42.0% (29.0% at admission and 13.0% within 72 hours). In contrast, Jeyaraman S et al.12 reported a substantially higher prevalence of 78.3% among 60 patients. Thus, most studies indicate that approximately 27–42% of acute STEMI patients develop hyponatremia, with higher estimates likely reflecting differences in cohort characteristics and sample size. The overall 30-day all-cause mortality was 8.0% in the present study. Comparable mortality was reported by Pasha G et al.8 at 7.0%, Patil GS et al.11 at 10.0%, and Vikas et al.9 at 12.5%. In contrast, Jeyaraman S et al.12 reported a considerably higher mortality of 30.0%, possibly reflecting differences in patient severity, referral patterns, or management. Overall, short-term mortality across most tertiary-care STEMI cohorts appears to range between approximately 7.0% and 12.5%. Mean age across sodium groups was 57.8 ± 11.7, 64.9 ± 13.1, and 56.61 ± 11.54 years (p=0.145), while non-survivors were older (65.5 ± 7.58 vs. 57.7 ± 12.1 years; p=0.025). Vikas et al.9 reported corresponding ages of 56.95, 64.71, and 57.10 years (p=0.145) and 62.04 ± 7.12 vs. 57.50 ± 11.91 years among non-survivors and survivors (p=0.065). Pasha G et al.8 found 66.57 vs. 56.11 years (p=0.021), and Patil GS et al.11 58.9 ± 14.15 vs. 55.02 ± 12.78 years (p=0.370). Male proportions were 80.3%, 81.8%, and 77.8% (p=0.960), but female sex was more frequent among non-survivors (50.0% vs. 17.4%; p=0.042). Vikas et al.9 reported 40.0% vs. 19.4% females (p=0.020), while Pasha G et al.8 (p=0.743) and Patil GS et al.11 (4:1 male; mortality p=0.452) found no significant sex association. In the present study, diabetes differed significantly across sodium groups (12.7%, 27.3%, and 44.4%; p=0.009) and was more frequent among non-survivors (50.0% vs. 17.4%; p=0.046). Pasha G et al.8 similarly found associations with sodium status (53.8% diabetic in admission hyponatremia; p=0.016) and mortality (p=0.001), while Chandrasekaran SP et al.10 reported 42.7% vs. 27.0% (p<0.05). Conversely, Patil GS et al.11 found no association with sodium status (31.0% vs. 37.9%; p=0.106) or mortality (50.0% vs. 30.0%; p=0.190), consistent with Vikas et al.9 (p=0.083; p=0.711). Hypertension also showed no sodium-group association in the present study (19.7%, 18.2%, and 22.2%; p=0.960) but was higher among non-survivors (50.0% vs. 17.4%; p=0.046). Significant associations were reported by Pasha G et al.8 (p=0.031; mortality p=0.013), Vikas et al.9 (42.1% in admission hyponatremia; p=0.000; mortality 32.0% vs. 6.2%; p=0.000), and Chandrasekaran SP et al.10 (p<0.05), whereas Patil GS et al.11 found none (p=0.420; mortality 20.0% vs. 11.1%; p=0.412). Smoking was unrelated to sodium status (70.4%, 81.8%, and 61.1%; p=0.493) or mortality (50.0% vs. 71.7%; p=0.238). Similar findings were reported by Patil GS et al.11 (p=0.450; 50.0% vs. 72.0%; p=0.198) and Vikas et al.9 (p=0.148; p=0.955), whereas Pasha G et al.8 found an association with sodium status (p=0.003) but not mortality (p=0.051), and Chandrasekaran SP et al.10 reported an association with hyponatremia (p<0.05). Anterior wall infarction was not associated with sodium status (63.4%, 72.7%, and 83.3%; p=0.252) or mortality (62.5% vs. 68.5%; p=0.999) in the present study. Similar findings were reported by Patil GS et al.11 (p=0.100; mortality 60.0% vs. 68.9%; p=0.6972), Pasha G et al.8 (54.0%; p=0.786), and Chandrasekaran SP et al.10 (44.0% vs. 43.1%). Conversely, significant associations were observed by Vikas et al.9 (sodium status p=0.001; mortality 80.0% vs. 67.5%; p=0.001), and Jeyaraman S et al.12 (74.5% vs. 30.8%; p=0.0054). Baseline Killip class was comparable across sodium groups (1.06 ± 0.23, 1.18 ± 0.40, and 1.06 ± 0.24; p=0.312), but Killip class II was more frequent among non-survivors (37.5% vs. 4.3%; p=0.013). Higher Killip class was associated with hyponatremia and/or mortality in Vikas et al.9 (p=0.001; mortality p=0.000), Pasha G et al.8 (1.31 vs. 1.01; p<0.001; mortality p<0.001), Patil GS et al.11 (mortality p<0.0001), and Jeyaraman S et al.12 (p=0.0126). LVEF was 44.63 ± 11.19%, 40.36 ± 6.14%, and 50.11 ± 13.26% across sodium groups (p=0.060) and lower among non-survivors (38.6 ± 10.9% vs. 47.7 ± 12.7%; p=0.050). Similar associations were reported by Vikas et al.9 (40.1% vs. 46.5%; p=0.025; mortality 39.48 ± 8.65% vs. 47.11 ± 11.7%; p=0.002), Pasha G et al.8 (37.69% vs. 45.66%; p<0.001; mortality 37.57% vs. 44.30%; p<0.001), Patil GS et al.11 (sodium status p=0.073; survival p=0.008), and Jeyaraman S et al.12 (p<0.0001), supporting the relationship between ventricular dysfunction, hyponatremia, and adverse prognosis. In the present study, 30-day mortality was 2.8%, 27.3%, and 16.7% among patients with normal sodium, admission hyponatremia, and developing hyponatremia, respectively. Admission hyponatremia significantly increased mortality (OR 12.94; 95% CI 1.87–89.42; p=0.016), while developing hyponatremia showed a non-significant trend (OR 6.9; 95% CI 1.1–44.9; p=0.054). Pasha G et al.8 reported similar mortality rates (2.7%, 23.0%, 14.28%) and associations (admission: OR 10.650; p=0.015; delayed: OR 5.917; p=0.090). Vikas et al.9 reported 0.75%, 75.0%, and 7.5%, while Jeyaraman S et al.12 (36.2% vs. 7.7%; p=0.0434) demonstrated higher mortality with hyponatremia. Patil GS et al.11 reported 3.44%, 24.1%, and 7.69%, with significant associations for admission (OR 3.143; p=0.008) and delayed hyponatremia (OR 12.0; p=0.017). Severity also predicted mortality: in the present study, mortality was 100% (3/3) with sodium <130 mmol/L versus 11.5% (3/26) at 131–134 mmol/L (p=0.005). Corresponding rates were 57.14% vs. 16.11% in Patil GS et al.11, 65.38% vs. 16.6% in Vikas et al.9, while Pasha G et al.8 reported 66.6%, 10.0%, and 14.2% at <125, 125–130, and 131–135 mmol/L, respectively. Mean sodium was lower among non-survivors in the present study (134.09 ± 3.53 vs. 136.96 ± 1.92 mmol/L; p=0.057), consistent with Patil GS et al.11 (131.63 ± 4.24 vs. 136.96 ± 4.02; p<0.0001), Pasha G et al.8 (131.89 vs. 137.30 mmol/L), and Jeyaraman S et al.12 (129.1 ± 3.3 mmol/L in expired patients; cohort mean 131.3 mEq/L). Overall, admission and increasingly severe hyponatremia were consistently associated with poorer 30-day outcomes following acute STEMI. Strengths and Limitations The study’s strengths include its prospective observational design, consecutive inclusion of 100 acute STEMI patients, serial serum sodium measurements from admission through 72 hours, and complete assessment of 30-day all-cause mortality, enabling evaluation of both the timing and severity of hyponatremia. However, the single-centre design and relatively small sample, particularly the limited number of hyponatremic patients and deaths, restrict generalizability and statistical precision. Mortality associations were based on unadjusted analyses, limiting control for potential confounders such as age, diabetes, hypertension, Killip class, and ventricular function

Hyponatremia was observed in 29% of patients with acute STEMI and was associated with increased 30-day mortality, particularly when present at admission. Mortality was 27.3% with admission hyponatremia compared with 2.8% among patients with normal sodium levels. Increasing severity of hyponatremia was significantly associated with mortality, with 100% mortality among patients with serum sodium <130 mmol/L. Older age, female sex, diabetes mellitus, hypertension, and higher Killip class were also associated with mortality. Thus, hyponatremia, especially severe and admission hyponatremia, may serve as an important prognostic marker for 30-day mortality following acute STEMI. Acknowledgement: We sincerely thank the faculty of the institute for helping us in each aspect of the study. Funding: None Conflict of interest: None declared Ethical approval: The study was approved by the Institutional Ethics Committee.

1. World Health Organization. The top 10 causes of death [Internet]. Geneva: World Health Organization; 2024 [cited 2025 Aug 8]. Available from: https://www.who.int/news-room/fact-sheets/detail/the-top-10-causes-of-death 2. Gupta R, Joshi P, Mohan V, Reddy KS, Yusuf S. Epidemiology and causation of coronary heart disease and stroke in India. Heart. 2008;94(1):16-26. 3. Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India: current epidemiology and future directions. Circulation. 2016;133(16):1605-20. 4. Spasovski G, Vanholder R, Allolio B, Annane D, Ball S, Bichet D, et al. Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014;170(3):G1-G47. 5. Gheorghiade M, Rossi JS, Cotts W, Shin DD, Hellkamp AS, Piña IL, et al. Characterization and prognostic value of persistent hyponatremia in patients with severe heart failure in the ESCAPE Trial. Arch Intern Med. 2007;167(18):1998-2005. 6. Goldberg A, Hammerman H, Petcherski S, Zdorovyak A, Yalonetsky S, Kapeliovich M, et al. Prognostic importance of hyponatremia in acute ST-elevation myocardial infarction. Am J Med. 2004;117(4):242-8. 7. Goldberg A, Hammerman H, Petcherski S, Nassar M, Zdorovyak A, Yalonetsky S, et al. Hyponatremia and long-term mortality in survivors of acute ST-elevation myocardial infarction. Arch Intern Med. 2006;166(7):781-6. 8. Pasha G, Marulashresta GD, Vagesh Kumar SR. A study on prognostic significance of hyponatremia in acute ST-elevation myocardial infarction. Int J Adv Res Med. 2021;3(2):440-4. 9. Vikas, Kaur G. Prognostic importance of hyponatremia in acute ST elevation myocardial infarction (STEMI). J Med Sci Clin Res. 2018;6(8):142-51. 10. Chandrasekaran SP, Chandrasekaran S, Jambulingam S, Senthilvel N. The prognostic significance of hyponatremia in acute STEMI. Int J Dent Med Sci Res. 2021;3(5):688-706. 11. Patil GS, Devareddy S. Study of hyponatremia as prognostic indicator in acute ST elevation myocardial infarction. MedPulse Int J Med. 2019;10(2):74-8. 12. Jeyaraman S, Rajan S, Retnadas P, Dayaladurai A. Hyponatraemia as a prognostic indicator in acute ST elevation myocardial infarction. J Evid Based Med Healthc. 2016;3(64):3490-3