Abstract Body (Do not enter title and authors here): Introduction
Heart failure with preserved ejection fraction (HFpEF) shows clear sex differences in pathophysiology and outcomes, but it is unknown circulating biomarkers major adverse cardiovascular events (MACE) risk differently between men and women.

Hypothesis
Circulating biomarkers predict MACE differently in female and male HFpEF patients with coronary artery disease (CAD).

Methods
We retrospectively analyzed patients with HFpEF and CAD from the Emory Cardiovascular Biobank. After imputing missing data, we screened a broad panel of clinical variables and biomarkers (ejection fraction, eGFR, lipid profile, renal function tests, blood counts, CRP, BNP/NTproBNP, suPAR, troponin, C-peptide, B12, lipoprotein(a), Gal3, vitamin D, ApoA1, ApoB, insulin, homocysteine, testosterone, and DHEAS). We used ElasticNet to select pertinent predictors for 5-year MACE and CV death. Selected features were entered into a non-penalized Cox model, adjusting for race, age, BMI, ACE/ARB use, statin/beta-blocker use, smoking history, hypertension, hyperlipidemia, diabetes, prior myocardial infarction, ejection fraction, and eGFR.

Results
We included 760 patients with HFpEF and CAD (315 women, 445 men). Men were younger (median 67 vs. 73 years; p < 0.001), with more CKD (40.0% vs. 29.2%; p = 0.003) and prior MI (26.9% vs. 20.1%; p = 0.039). In men, ElasticNet selected hemoglobin and suPAR as key variables associated with 5-year MACE. In adjusted Cox models, hemoglobin (HR 0.62; 95% CI 0.47-0.82; p = 0.001) and suPAR (HR 1.37; 95% CI 1.13-1.64; p = 0.001) independently predicted MACE (Table 1); hemoglobin also predicted CV death. In women, ElasticNet did not identify any biomarker as a predictor of MACE or CV death. Instead, adjusted Cox models identified age ≥75 years (HR 3.59; 95% CI 1.23-10.49; p = 0.020), BMI <18.5 kg/m2 (HR 4.66; 95% CI 1.30-16.73; p = 0.018), obesity (BMI ≥30 kg/m2; HR 3.02; 95% CI 1.33-6.85; p = 0.008), and smoking (HR 1.98; 95% CI 1.18-3.31; p = 0.009) as independent predictors of 5-year MACE, while age, underweight BMI, obesity, and smoking increased CV death risk, with ACEI/ARB use and higher hemoglobin protective (Table 2). Adjusted Kaplan-Meier curves demonstrate clear separation by suPAR level for men but not for women (Figure 1).

Conclusions
In HFpEF and CAD, lower hemoglobin and higher suPAR predict 5 year MACE in men only. In women, MACE risk was predicted by age, underweight or obese BMI, and smoking rather than circulating biomarkers.