Role of sub-clinical inflammation and defective cholesterol efflux in myocardial infarction patients without standard modifiable risk factors

Abstract Background and Aims Sub-clinical inflammation and defective high-density lipoprotein (HDL) function have emerged as potential risk factors for a first cardiovascular event. We evaluated their role in the pathogenesis of ST-segment elevation myocardial infarction (STEMI) patients with no standard modifiable cardiovascular risk factors (SMuRF). Methods Using our STEMI biobank registry, we compared baseline characteristics and markers of sub-clinical inflammation (interleukin (IL)-1β, high sensitivity C Reactive Protein (hsCRP) and defective HDL function using serum cholesterol efflux capacity) in patients with and without SMuRF. Determinants of 1-year all-cause mortality were assessed using multivariable Cox regression analyses. Results Among the 1604 patients included, 178 (11.1%) were SMuRF-less. Compared to patients with SMuRF, SMuRF-less patients had lower serum cholesterol efflux capacity (0.79 ± 0.16 vs 0.83 ± 0.16, respectively, p<0.001), were more often in the highest tertile of IL-1β (28.7% vs 18.9%, respectively, p=0.002) with a trend towards more patients within the highest hs-CRP level tertile (24.7% vs 19.1%, respectively, p=0.077). Crude rates of mortality were higher in the SMuRF-less group (18.5% vs 7.7%, p<0.001). After multivariable adjustment with traditional prognostic risk factors, high tertiles of hs-CRP (HR 1.83 (1.28-2.63), p=0.001) or of IL-1β (HR 1.54 (1.06-2.24), p=0.024), and SMuRF-less status (HR 1.56 (1.05-2.38), p=0.029) were associated with mortality while higher serum cholesterol efflux capacity was protective (HR 0.27 (0.09-0.87); p=0.028). Conclusion Sub clinical inflammation and defective cholesterol efflux were associated with SMuRF-less status of STEMI patients and had prognostic impact. This highlights the need to explore new therapeutic strategies in this high-risk population.