Pharmacological Research 54 (2006) 442–446 Simvastatin improves the attenuated heart rate recovery of type 2 diabetics G¨ oknur Tekin a,∗ , Abdullah Tekin a , Taner Canatar b , ˙ Ilke Sipahi c , Aydan ¨ Unsal b , Tuna Katırcıbas ¸ı a , Tolga Koc ¸um a , Tansel Erol a , Fatma Yi˘ git a ,S ¸ enol Demircan a , Necip Ermis ¸ a , Alpay Turan Sezgin a , Haldun M ¨ uderriso˘ glu a a Department of Cardiology, Faculty of Medicine, Ba¸ skent University, Adana, Turkey b Department of Family Medicine, Faculty of Medicine, Ba¸ skent University, Adana, Turkey c Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA Accepted 12 September 2006 Abstract Heart rate recovery at 1 min (HRR1) is a strong predictor of all-cause mortality. The effects of statins on the autonomic nervous system may account for their beneficial effects in survival. Our aim was to determine if statin therapy improves heart rate recovery in hypercholesterolemic patients with type 2 diabetes mellitus. Thirty type 2 diabetic patients without known coronary artery disease and low density lipoprotein cholesterol > 100 mg/dl and 30 age and sex matched non-diabetic controls were included in a prospective study. Patients with diabetes were treated with simvastatin 40 mg/day for 1 year. No lipid-lowering therapy was administered to the control group. Exercise testing with 2 min cool-down period was performed at baseline, 6, 12 weeks and at 1 year. The diabetics had significantly lower HRR1 compared with non-diabetics at baseline (19.2 ± 5.4 bpm versus 24.2 ± 4 bpm, p < 0.0001). Simvastatin therapy significantly improved HRR1 after 12 weeks compared to baseline (19.2 ± 5.4 bpm versus 24 ± 5 bpm, p < 0.0001) and this improvement remained significant at 1 year (26 ± 4.4 bpm, p < 0.0001 compared to baseline). HRR1 did not change in the control group (p =0.39 by ANOVA). This study demonstrates that treatment with simvastatin might improve the attenuated heart rate recovery of diabetic subjects. In patients with diabetes, the mortality benefit provided by statins might involve their effects on the autonomic nervous system. © 2006 Elsevier Ltd. All rights reserved. Keywords: Simvastatin; Heart rate recovery; Statin; Autonomic nervous system; Diabetes mellitus 1. Introduction Attenuated heart rate recovery (HRR) after exercise, a marker of reduced parasympathetic activity [1,2], has been shown to be associated with increased long-term mortality [3,4]. The pre- dictive ability of HRR has been shown to be independent of the angiographic severity of coronary disease [5]. Although the prognostic significance of HRR is well known, less is known about its modification [6]. Statins may evoke salutary neural effects [7]. Some data suggest the concept of statin effects on the autonomic nervous system as part of their pleiotropic efficacy [8,9]. For instance, statin treatment has been related to higher ∗ Corresponding author at: Department of Cardiology, Faculty of Medicine, Bas ¸kent University, Dadalo˘ glu Mahallesi, 39 Sok. No. 6, 01250 Yuregir/Adana, Turkey. Tel.: +90 322 231 07 91; fax: +90 322 327 12 76. E-mail address: goknurtek@yahoo.com (G. Tekin). heart rate variability in a retrospective study of patients with a previous myocardial infarction [10]. It has been also demonstrated that diabetes mellitus is associ- ated with an abnormal heart rate recovery after maximum-graded exercise testing in a cohort of patients without known coronary artery disease [11]. Therefore, in the present study, we have examined whether simvastatin therapy has any effect on the heart rate recovery of diabetic patients. 2. Materials and methods 2.1. Study population Thirty diabetic statin-naive subjects with low density lipopro- tein (LDL) cholesterol > 100 mg/dl, triglycerides < 250 mg/dl and HgbA1 c < 8 mg/dl were included. Diabetes mellitus was determined on the basis of history and use of medications. The 1043-6618/$ – see front matter © 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.phrs.2006.09.002