The U -shape relationship between free fatty acid level and adverse outcomes in coronary artery disease patients with hypertension: evidence from a large prospective cohort study

Evidence is scarce on the effect of free fatty acid (FFA) level in the prognosis of coronary artery disease (CAD) patients with hypertension. This study. A large prospective cohort study with a follow-up period of average 2 years was conducted at Xinjiang Medical University Affiliated First Hospital from December 2016 to October 2021. A total of 10,395 CAD participants were divided into groups based on FFA concentration and hypertension status, and then primary outcome mortality and secondary endpoint ischemic events were assessed in the different groups. A total of 222 all-cause mortality (ACMs), 164 cardiac mortality (CMs), 718 major adverse cardiovascular events (MACEs) and 803 major adverse cardiovascular and cerebrovascular events (MACCEs) were recorded during follow-up period. A nonlinear relationship between FFA and adverse outcomes was observed only in CAD patients with hypertension. Namely, a “U -shape” relationship between FFA levels and long-term outcomes was found in CAD patients with hypertension. Lower FFA level (< 310 µmol/L), or higher FFA level (≥ 580 µmol/L) at baseline is independent risk factors for adverse outcomes. After adjustment for confounders, excess FFA increases mortality (ACM, HR = 1.957, 95%CI(1.240–3.087), P = 0.004; CM, HR = 2.704, 95%CI(1.495–4.890, P = 0.001) and MACE (HR = 1.411, 95%CI(1.077–1.848), P = 0.012), MACCE (HR = 1.299, 95%CI (1.013–1.666), P = 0.040) prevalence. Low levels of FFA at baseline can also increase the incidence of MACE (HR = 1.567,95%CI (1.187–2.069), P = 0.002) and MACCE (HR = 1.387, 95%CI (1.070–1.798), P = 0.013). Baseline FFA concentrations significantly associated with long-term mortality and ischemic events could be a better and novel risk biomarker for prognosis prediction in CAD patients with hypertension. The details of the design were registered on https://www.chictr.org.cn/ (Identifier NCT05174143). What is known on this topic? • Free fatty acid (FFA) plays an essential role in hepatic triglyceride synthesis . Several studies have shown that plasma FFA concentration is a modifiable risk factor for metabolic disease. However, no evidence is currently available regarding the link between FFA and prognosis in CAD patients with hypertension. What does this paper add? • We observed a “U -shape” relationship between FFA and adverse outcomes in CAD patients with hypertension, which address a novel knowledge gap in the risk classification of CAD patients with hypertension.