In patients with hypercholesterolemia, simvastatin lowers C-reactive protein (CRP) within 14 days of treatment (Plenge et al., Circ., 2002). In patients presenting with an acute coronary event, a lower level of CRP soon after the event is associated with an improved long-term outcome. This may be even more important for patients who have a worse prognosis after an event, i.e. patients with type 2 diabetes. Our goal, therefore, was to determine whether or not the time course of CRP-lowering with simvastatin was slower in patients with type 2 diabetes.
Design Thirty-five subjects (13 male; 22 female; age 39 - 70 years; BMI = 32.8 ± 1 kg/m2; glycated hemoglobin A1C = 7.3 ± 0.2%, mean ± SEM) were studied using a randomized, cross-over, double-blind design. Patients were treated with simvastatin 40 mg/placebo for 28 days, with a minimum 28-day intervening washout. On entry, all subjects had a LDL cholesterol>100 mg/dL and/or a non-HDL cholesterol level>130 mg/dL, triglycerides<500 mg/dL, normal liver function, no chronic inflammatory diseases, and no active cardiovascular disease. High sensitivity CRP (hsCRP) was measured on days 0, 1, 3, 7, 14, 21, and 28 of each phase; fasting lipids were measured weekly. A repeated measures ANOVA was used to analyze values of hsCRP that were log-transformed.
Results The mean hsCRP was 4.2 ± 0.6 mg/L at baseline (> 3.0 mg/L = high risk). Levels of hsCRP were similar in women (4.1 ± 0.5 mg/L) and men (4.4 ± 1.5 mg/L). Following simvastatin, the main effect of treatment was a significant reduction in levels of hsCRP (p = 0.001). This effect of simvastatin was seen by day 7 (p = 0.008; hsCRP = 3.6 ± 0.5 mg/L on simvastatin, and 4.9 ± 1.1 mg/L on placebo), with maximal lowering seen at day 14 (p = 0.004, hsCRP = 3.1 ± 0.5 mg/L on simvastatin, and 4.1 ± 0.6 mg/L on placebo). As expected, LDL cholesterol was also lowered by simvastatin (p<0.001), but there was no relationship between the change in log (hsCRP) and the change in LDL cholesterol. Of interest, by day 28, hsCRP had returned to near baseline levels.
Conclusions In patients with type 2 diabetes, simvastatin lowered hsCRP within 7 days, an effect that was faster than that seen in hypercholesterolemic subjects without diabetes. However, this potentially beneficial effect was lost by 28 days. The implication of this surprising finding is unclear, but at the time of an acute coronary event might signify only transient cardioprotection of statin therapy in patients with type 2 diabetes.
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