Background/Introduction

Industrially processed TFA (IP-TFA) from partially hydrogenated oils, but not naturally occurring dairy-derived TFA, have been linked to altered lipoprotein metabolism, endothelial dysfunction, increased biomarkers of inflammation and increased NTproBNP. In patients with heart failure with preserved ejection fraction (HFpEF), associations of TFA blood levels with phenotypic traits/patient characteristics are not known.

Purpose

To evaluate associations of whole blood TFA with cardiometabolic risk markers, aerobic capacity and cardiac function/morphology in patients with HFpEF.

Methods

This is a cross-sectional analysis of data from the Aldo-DHF-RCT. From 422 patients, individual blood TFA 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; 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 blood TFA with metabolic phenotype, functional capacity, echocardiographic markers for LVDF, and neurohumoral activation at baseline and after 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

Blood levels of the naturally occurring TFA trans-palmitoleic acid C16:1n-7t were inversely associated with triglycerides-to-HDL-C ratio (β=-11.375,p=0,001), triglycerides (β=-447.468,p<0,001), body-mass-index (β=-9.605,p=0,026), waist circumference (β=-26.961,p=0,022), and liver enzymes (alanine transaminase (β=-35.362,p=0,043) and γ-glutamyltransferase (β=-110.187,p=0,022)) at baseline and predictive of lower triglycerides (β=-337.067,p=0,022), body-mass-index (β=-11.441,p=0,014), waist circumference (β=-31.563,p=0,013), waist-to-height ratio (β=-0.228,p=0,003), and γ-glutamyltransferase (β=-150.272,p=0,001) after 12 months follow-up.

Conversely, the blood IP-TFA C18:1n9t was positively associated with triglycerides-to-HDL-C ratio (β=0.442,p=0,002), triglycerides (β=19.688,p<0,001), non-HDL-C (β=7.890,p=0,001), and LDL-C (β=5.4,p=0,011) at baseline. Higher IP-TFA C18:2n6tt and C18:2n6ct were associated with higher HbA1c (β=14.59,p=0,003 and β=4.183,p=0,014 respectively) at baseline while C18:2n6tc was positively associated with non-HDL-C (β=151.154,p=0,029) and LDL-C (β=151.8,p=0,015). C18:2n6tt, C18:2n6ct, and C18:2n6tc were all significantly inversely associated with submaximal aerobic capacity (i.e., distance covered in the 6MWT) at baseline and/or follow-up.

No association was found between naturally occurring and/or blood IP-TFA with echocardiographic markers for left ventricular filling pressures, left ventricular relaxation or neurohumoral activation.

Conclusions

In HFpEF patients, higher blood levels of industrially processed TFA, but not of the naturally occurring dairy-derived TFA C16:1n-7t, were associated with adverse effects on cardiometabolic risk factors and predictive of lower submaximal/maximal aerobic capacity. Our findings further support efforts to remove IP-TFA from the food supply for improving cardiometabolic health.