High‐Intensity Statin Treatment Is Associated With Reduced Growth Differentiation Factor‐15 in Patients With Coronary Artery Disease

BACKGROUND: Growth differentiation factor-15 (GDF-15) is upregulated in coronary artery disease (CAD). The relationship of intensive statin therapy with circulating GDF-15 levels has not been explored yet. In the current secondary analysis of an observational cohort, we investigated whether high-intensity statin treatment is associated with GDF-15 in patients with advanced CAD. METHODS: In 102 CAD patients we measured GDF-15 levels before and after median 7 [6-8] months from initiation atorvastatin 80 mg/day (n = 63, 61.8%) or rosuvastatin 40 mg/day (n = 39, 38.2%). At the two time points we also determined C-reactive protein (CRP), thrombin generation and fibrinolysis inhibitors. There was no concurrent control group. RESULTS: At baseline GDF-15 levels (median 942; interquartile range 639-1284 pg/mL) were associated solely with age (R = 0.567, p < 0.001) and CRP (R = 0.464, p < 0.001), but not with lipid profile. On high-intensity statin therapy GDF-15 reduction by 17.8% was observed (p = 0.006), which was associated with CRP lowering by 46.4% (R = 0.788, p < 0.001), but not with changes in total cholesterol (by 17.6%) and low-density lipoprotein cholesterol (LDL-C) (by 28.1%). However, GDF-15 levels were lower by 28.5% (p < 0.001) and 18.9% (p = 0.013) in 43 patients (42.2%) who achieved the target LDL-C < 1.8 mmol/L and 19 (18.6%) with LDL-C < 1.4 mmol/L, respectively, as compared to the remainder. The type of statin was not associated with follow-up GDF-15. Age (p = 0.029), baseline GDF-15 (p < 0.001) and CRP (p < 0.001), but not LDL-C, were independently associated with follow-up GDF-15. CONCLUSIONS: We demonstrated that high-dose statin therapy is associated with lower GDF-15 in CAD patients and this effect is largely related to the anti-inflammatory properties of statins.