Association between Admission Total Cholesterol and In-Hospital Mortality in Acute Decompensated Heart Failure: A Prospective Cohort Study from Syria

Abstract Background An apparent inverse relationship between cholesterol levels and mortality — the "cholesterol paradox" — has been described in chronic heart failure, but data from Middle Eastern patients with acute decompensated heart failure (ADHF) are scarce. This study evaluated the association between admission lipid profile and in-hospital mortality in Syrian patients with ADHF. Methods A prospective cohort study was conducted at two tertiary university hospitals in Damascus, Syria (Al-Mouassat and Al-Watani) from March 2025 to March 2026, enrolling 166 consecutive adult patients with ADHF (2021 European Society of Cardiology [ESC] criteria). Lipid profiles were measured within 24 hours of admission. Receiver operating characteristic (ROC) curve, bivariate, and multivariate logistic regression analyses were performed; Firth's penalized likelihood regression was used as a sensitivity analysis given the limited number of events. Results In-hospital mortality was 15.1% (25/166). Non-survivors had significantly lower total cholesterol (TC) (142.8 ± 38.4 vs. 168.5 ± 42.6 mg/dL, P = 0.005) and low-density lipoprotein cholesterol (LDL-C) (78.4 ± 28.2 vs. 96.6 ± 32.8 mg/dL, P = 0.009). TC showed moderate discrimination (area under the curve [AUC] = 0.712; optimal cutoff ≤ 130 mg/dL); LDL-C showed fair discrimination (AUC = 0.632; optimal cutoff ≤ 88 mg/dL). In multivariate analysis, TC < 150 mg/dL was independently associated with mortality (adjusted odds ratio [AOR] = 2.38, 95% confidence interval [CI]: 1.12–5.06, P = 0.024); LDL-C was significant in bivariate analysis (P = 0.009) but did not retain independent significance after adjustment for TC and other covariates (AOR = 1.89, P = 0.069). Five independent predictors were identified: oxygen saturation < 90%, TC < 150 mg/dL, age ≥ 70 years, New York Heart Association (NYHA) Class IV, and sodium < 135 mEq/L (model AUC = 0.827). Firth's sensitivity analysis yielded consistent estimates. Conclusions Lower admission TC is independently associated with higher in-hospital mortality in Syrian ADHF patients, supporting the cholesterol paradox in this previously understudied population. LDL-C was associated with mortality only at the bivariate level. The cutoffs of 130 mg/dL (ROC-derived) and 150 mg/dL (multivariate-derived) should be externally validated in larger multicenter studies that include natriuretic peptides and apply propensity score methods.