Low Serum Cholesterol Is a Biomarker of Advanced Disease and Poor Outcomes in Myeloproliferative Neoplasms

Myeloproliferative neoplasms (MPNs), including essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF), are a diverse group of hematopoietic stem cell neoplasms associated with an increased risk of hematologic progression to secondary MF or leukemia and cardiovascular disease (CVD). Elevated total cholesterol levels are traditional CVD risk factors. Patients with MPNs may have reduced cholesterol levels, potentially reflecting an underlying hypermetabolic state. The impact of serum total cholesterol on clinical outcomes in patients with MPNs has not yet been evaluated. We performed a multicenter retrospective cohort study of patients with MPNs who had undergone transthoracic echocardiography (TTE) with available serum lipid levels at time of TTE not on statin therapy. Patients were categorized by total cholesterol level (≥ 150, 120 - 149, and < 120 mg/dL). Outcomes evaluated were MPN disease progression to secondary MF or acute leukemia, major adverse cardiovascular events (MACE), and death. Multivariable competing-risk regression modeling was performed. A total of 305 patients were included of whom 54.4% had total cholesterol ≥ 150, 21.3% 120 - 149, and 24.3% < 120 mg/dL. After a median follow-up of 50.8 months, total cholesterol < 120 was associated with increased risk of MPN disease progression (aSHR 3.00, 95% CI 1.36 - 6.63), heart failure hospitalization (aSHR 3.76, 95% CI 1.77 - 7.96), and all-cause death (aHR 1.87, 95% CI 1.06 - 3.30) vs ≥ 150 mg/dL. Among patients with MPN, low total cholesterol levels were associated with increased risk of MPN disease progression.