Background

Circulating blood levels of de novo lipogenesis-(DNL)related monounsaturated fatty acids (MUFAs) have been linked to risk of incident heart failure (HF). Biological plausibility underlying this observation may be conferred by the potential of DNL-related FAs to directly induce proinflammatory pathways, endoplasmic reticulum stress, cellular apoptosis, and insulin resistance which are involved in the pathophysiology of heart failure with preserved ejection fraction (HFpEF).

Purpose

To evaluate associations of circulating MUFAs with cardiometabolic phenotype, aerobic capacity and cardiac function/morphology in patients with HFpEF.

Methods

This is a cross-sectional analysis of data from the Aldosterone in Diastolic Heart Failure (Aldo-DHF) trial. From 422 patients, individual blood MUFAs were analyzed at baseline in n=404 using the HS-Omega-3-Index® methodology which is unbiased by recent dietary intake and reflects long-term tissue fatty acid composition. Patient characteristics were; 67±8 years, 53% female, NYHA II/III (87/13%), ejection fraction ≥50%, E/e´ 7.1±1.5; median NT-proBNP 158 ng/L (IQR 82-298). Multiple linear regression analyses, using sex and age as covariates, were used to describe associations of MUFAs with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline/12 months follow-up. A significance level of α=5% was used for all tests. As all tests were hypothesis generating without confirmatory interpretation, no correction was applied to counteract the problem of multiple comparisons.

Results

Individual blood MUFAs were differentially related with phenotypic traits in patients with HFpEF. In line with prior data supporting a potential role of DNL-related MUFAs in HF, higher baseline blood levels of palmitoleic acid (C16:1n7 cis) and oleic acid (C18:1n9 cis), both biomarkers for DNL, were associated with significantly higher HbA1c, markers for atherogenic dyslipidemia (triglycerides-to-HDL-C ratio, triglycerides, non-HDL-C), body-mass-index, markers for truncal adiposity (waist circumference, waist-to-height ratio), and biomarkers indicative of non-alcoholic fatty liver disease (alanine transaminase and γ-glutamyltransferase). These associations persisted after 12mFU. Furthermore, blood levels of both DNL-related MUFAs were inversely associated with submaximal aerobic capacity (denoted distance covered in 6MWT) and maximal aerobic capacity (VO2peak) at baseline/12mFU.

Contrarily, higher blood levels of not-DNL-related MUFAs eicosenoic acid (C20:1n9) and nervonic acid (C24:1n9), were broadly associated with a lower risk metabolic phenotype and higher functional capacity at baseline/12mFU.

No association was found between individual MUFAs with echocardiographic markers for left ventricular filling pressures or left ventricular relaxation.

Conclusions

In patients with HFpEF, higher circulating levels of DNL-related MUFAs palmitoleic- and oleic acid were associated with dyslipidemia, dysglycemia, truncal adiposity and predictive of lower functional capacity. In contrast, the MUFAs eicosenoic- and nervonic acid were broadly associated with a lower-risk cardiometabolic phenotype. Our findings support further investigation of circulating MUFAs as prognostic markers in HFpEF and speak against the use of umbrella terms such as MUFAs to categorize fatty acids based on physicochemical properties.