Elevated fasting triglyceride levels are associated with adverse molecular profiles and impaired functional imaging measures in patients with suspected myocardial ischemia

Introduction Metabolic dysfunction is increasingly recognised as a key driver of cardiovascular mortality and morbidity. We have previously demonstrated that coronary flow reserve (CFR), a physiological index of coronary vascular function, is a strong predictor of future cardiovascular events in patients with suspected myocardial ischemia undergoing myocardial perfusion scintigraphy (MPS). Purpose This study investigated the relationship between fasting triglyceride (TG) levels and cardiovascular biomarker profiles, stress-induced cardiac function, peripheral endothelial function and CFR in patients with suspected myocardial ischemia. Methods We enrolled 461 patients (mean age: 62±9 years, 46% male) with suspected myocardial ischemia undergoing MPS. In addition to the MPS examination, all patients attended a dedicated study visit comprising adenosine stress echocardiography including CFR, peripheral endothelial function assessment using Endo-PAT and fasting blood sampling for biomarker analysis. Cardiovascular biomarkers were quantified using the Olink Target 96 Cardiovascular I panel. Pearson correlations were used to assess the relationship between fasting TG levels and both biomarkers and physiological variables. Multiple linear regression models were then applied to the functional imaging results to evaluate the independent association with TG levels, adjusting for age, sex, diabetes and hypertension. Results Elevated TG levels were significantly associated with biomarkers of inflammation (IL-6, GDF-15 and CHI3L1), endothelial activation (E-selectin), fibrosis (Gal-3 and CTSD) and metabolic dysregulation (HbA1c and HOMA-IR). In addition to these molecular biomarker associations, higher TG levels were independently linked to reduced cardiac contractility under stress (ejection fraction during stress), more extensive stress-induced perfusion defect (higher summed stress score), impaired peripheral endothelial function (lower reactive hyperaemia index) and lower CFR. Conclusions In patients with suspected myocardial ischemia, fasting TG levels are consistently and broadly associated with a pro-inflammatory and dysmetabolic biomarker profile, impaired peripheral endothelial function, reduced coronary flow reserve and greater stress-induced perfusion defect. Taken together, these findings establish TG as a clinically significant marker of cardiovascular risk in symptomatic cardiovascular patients. Ongoing trials of novel therapies that lower TG levels are well-placed to clarify whether elevated TG plays a causal role in cardiovascular pathophysiology.