Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography

AIMS: Sudden cardiac death (SCD) is the most common fatal cardiovascular event. Free fatty acids (FFAs) exert several harmful effects on the myocardium and may therefore contribute to SCD. We examined whether fasting FFA predict SCD in patients who had undergone coronary angiography. METHODS AND RESULTS: FFAs were measured at baseline (1997-2000) in 3315 patients scheduled for coronary angiography. Angiographic coronary artery disease was found in 2231 study participants. After a median time of follow-up of 6.85 years, 165 SCD occurred in the entire study population. In a Cox proportional hazards model, the unadjusted hazard ratio (HR) for SCD in the fourth when compared with the first FFA quartile was 2.95 (95% CI 1.84-4.73; P < 0.001). After adjustment for common and emerging cardiovascular risk factors, the HR remained significant at 1.76 (1.03-3.00; P = 0.038). High FFA levels were also significantly associated with all-cause and cardiovascular mortality, even after exclusion of patients with SCD. CONCLUSION: Our study shows that elevated plasma FFAs are an independent risk factor for future SCD in patients referred to coronary angiography. These results may suggest that modulation of myocardial fatty acid uptake and/or metabolism are a possible target of treatment, but it still remains to be clarified whether high FFA levels are a cause or a consequence of pathological processes that underlie the association between FFA and SCD.