Background: Circulating long-chain (LCSFAs) and very long-chain saturated fatty acids
(VLSFAs) have been differentially linked to risk of incident heart failure (HF). In patients with
heart failure with preserved ejection fraction (HFpEF), associations of blood SFA levels with patient
characteristics are unknown. Methods: From the Aldo-DHF-RCT, whole blood SFAs were
analyzed at baseline in n = 404 using the HS-Omega-3-Index methodology. Patient characteristics
were 67 8 years, 53% female, NYHA II/III (87%/13%), ejection fraction 50%, E/e’ 7.1 1.5;
and median NT-proBNP 158 ng/L (IQR 82–298). Spearman´s correlation coefficients and linear
regression analyses, using sex and age as covariates, were used to describe associations of blood
SFAs with metabolic phenotype, functional capacity, cardiac function, and neurohumoral activation
at baseline and after 12-month follow-up (12 mFU). Results: In line with prior data supporting a
potential role of de novo lipogenesis-related LCSFAs in the development of HF, we showed that
baseline blood levels of C14:0 and C16:0 were associated with cardiovascular risk factors and/or
lower exercise capacity in patients with HFpEF at baseline/12 mFU. Contrarily, the three major
circulating VLSFAs, lignoceric acid (C24:0), behenic acid (C22:0), and arachidic acid (C20:0), as well as
the LCSFA C18:0, were broadly associated with a lower risk phenotype, particularly a lower risk lipid
profile. No associations were found between cardiac function and blood SFAs. Conclusions: Blood
SFAs were differentially linked to biomarkers and anthropometric markers indicative of a higher-
/lower-risk cardiometabolic phenotype in HFpEF patients. Blood SFA warrant further investigation
as prognostic markers in HFpEF. One Sentence Summary: In patients with HFpEF, individual circulating
blood SFAs were differentially associated with cardiometabolic phenotype and aerobic capacity