Rosuvastatin Decreases Mean Platelet Volume in Patients With Diabetes Mellitus
Angiology 1-5 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715584725 ang.sagepub.com
Aydın Akyu¨z, MD1, Dursun C ¸ ayan Akkoyun, MD1, 1 Hasan Deg˘irmenci, MD , and Mustafa Oran, MD2
Abstract Statins have multiple effects (also known as pleiotropic effects) on inflammation, plaque stabilization, endothelial function, and hemostasis. We evaluated the effects of rosuvastatin on mean platelet volume (MPV)—a marker for platelet activity—in patients with diabetes mellitus (DM) on rosuvastatin medication. Patients (n ¼ 178) who were to be prescribed high-intensity rosuvastatin were retrospectively enrolled according to their medical records. Baseline and 6-month biochemical tests, automated blood count, cell-volume analysis, and their cardiovascular risk factors were recorded. Rosuvastatin significantly reduced the MPV and the lipid parameters including total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C). However, there was no correlation between MPV and LDL-C before (r ¼ .66; P ¼ .383) and after (r ¼ .112; P ¼ .135) rosuvastatin treatment or between DMPV and DLDL-C after 40 mg rosuvastatin daily therapy (r ¼ .155; P ¼ .073). Rosuvastatin significantly decreases the MPV as well as cholesterol levels. The antiplatelet activation properties of high-dose rosuvastatin treatment in patients with DM are not lipid dependent. Keywords rosuvastatin, mean platelet volume, diabetes mellitus, cholesterol
Introduction Statins inhibit cholesterol synthesis by inhibiting 3-hydroxy-3methylglutaryl coenzyme A reductase in the mevalonate pathway. They have pleiotropic effects, irrespective of their cholesterol-lowering effects. These pleiotropic effects include decreasing low-density lipoprotein (LDL) oxidation, inhibiting platelet aggregation, inhibiting vascular smooth muscle cell proliferation, and reducing vascular inflammation.1-8 Statins are the most commonly used drugs for patients with atherosclerosis and hyperlipidemia, with or without coronary artery disease (CAD).9,10 Statin therapy obviously decreases LDL cholesterol (LDL-C) and triglyceride (TG) levels while increasing high-density lipoprotein cholesterol (HDL-C) levels. Larger platelets are more active, leading to increased platelet activity,11 and thus, an increased mean platelet volume (MPV) is accepted as an independent predictor of vascular events.12,13 Increased MPV is also associated with atherosclerosis, hypertension,14 dyslipidemia,15-17 diabetes mellitus (DM),18 smoking,19 obesity,20 and atrial fibrillation.21 Some studies showed that statin therapy inhibits platelet function.22,23 However, there are limited studies on MPV following statin therapy in the literature,24,25 and 2 studies suggested that there is an effect from mild to moderate-intensity rosuvastatin treatment on the MPV, and this effect is irrespective of cholesterol lowering following 4 to 12 weeks of therapy. However, there are no studies in the literature about the effects of high-
intensity rosuvastatin treatment in patients with DM over a longer duration. Hence, we determined the effect of rosuvastatin treatment on the MPV in patients with DM by evaluating whether there is such an effect, irrespective of its cholesterollowering effect.
Materials and Methods We enrolled 178 patients with dyslipidemia and type 2 DM retrospectively from our cardiology outpatient clinic during the period between January 2013 and September 2014 after we had screened their biochemical data. Patients with DM who had been on medication with high-intensity statin treatment according to the American College of Cardiology/American Heart Association joint recommendations26 were chosen based on their medical records. All of baseline medications and 40 mg daily rosuvastatin therapy did not change during the 6-month trial. At baseline and 6 months later, biochemical tests, 1
Department of Cardiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey 2 Department of Internal Medicine, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey Corresponding Author: Aydın Akyu¨z, Department of Cardiology, Faculty of Medicine, Namik Kemal University, 59100, Tekirdag˘, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at FLORIDA ATLANTIC UNIV on May 21, 2015
2
Angiology
complete blood count data, and cardiovascular risk factors were recorded. We defined risk factors and treatment goals as described previously.27 Diabetes mellitus was evaluated according to the American Diabetes Association.28 The body mass index (BMI) was calculated as weight in kg divided by height in m2. Smoking was defined as current smokers. Coronary artery disease (CAD) was defined as >50% luminal stenosis of epicardial coronary arteries. Peripheral artery disease (PAD) was considered ankle brachial index values 40 kg/m2), acute infection, thyroid and liver disorders, history of malignancy, renal failure, and hematological diseases (eg, polycythaemia vera and thrombophilia). One hundred and two (57.3%) patients were receiving aspirin and 19 (10.6%) patients were taking clopidogrel at enrollment.
Laboratory Measurements Hematological data including the red and white blood cell count, MPV, and platelet count were analyzed using a Roche Sysmex XT-2000i autoanalyzer (Roche Diagnostics, Paris, France), and the same commercial kits were used for analyses at both baseline and at the 6-month follow-up. First, we used vacutainer 2-mL tubes (Vacutainer, Becton, Dickinson and Company, Franklin Lakes, New Jersey) containing dipotassium EDTA to obtain the blood samples. Blood analysis was performed within 30 minutes, according to the protocol of the biochemistry department. Both the intra- and interassay coefficients of variation were
Angiology 1-5 ª The Author(s) 2015 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319715584725 ang.sagepub.com
Aydın Akyu¨z, MD1, Dursun C ¸ ayan Akkoyun, MD1, 1 Hasan Deg˘irmenci, MD , and Mustafa Oran, MD2
Abstract Statins have multiple effects (also known as pleiotropic effects) on inflammation, plaque stabilization, endothelial function, and hemostasis. We evaluated the effects of rosuvastatin on mean platelet volume (MPV)—a marker for platelet activity—in patients with diabetes mellitus (DM) on rosuvastatin medication. Patients (n ¼ 178) who were to be prescribed high-intensity rosuvastatin were retrospectively enrolled according to their medical records. Baseline and 6-month biochemical tests, automated blood count, cell-volume analysis, and their cardiovascular risk factors were recorded. Rosuvastatin significantly reduced the MPV and the lipid parameters including total cholesterol, triglyceride, and low-density lipoprotein cholesterol (LDL-C). However, there was no correlation between MPV and LDL-C before (r ¼ .66; P ¼ .383) and after (r ¼ .112; P ¼ .135) rosuvastatin treatment or between DMPV and DLDL-C after 40 mg rosuvastatin daily therapy (r ¼ .155; P ¼ .073). Rosuvastatin significantly decreases the MPV as well as cholesterol levels. The antiplatelet activation properties of high-dose rosuvastatin treatment in patients with DM are not lipid dependent. Keywords rosuvastatin, mean platelet volume, diabetes mellitus, cholesterol
Introduction Statins inhibit cholesterol synthesis by inhibiting 3-hydroxy-3methylglutaryl coenzyme A reductase in the mevalonate pathway. They have pleiotropic effects, irrespective of their cholesterol-lowering effects. These pleiotropic effects include decreasing low-density lipoprotein (LDL) oxidation, inhibiting platelet aggregation, inhibiting vascular smooth muscle cell proliferation, and reducing vascular inflammation.1-8 Statins are the most commonly used drugs for patients with atherosclerosis and hyperlipidemia, with or without coronary artery disease (CAD).9,10 Statin therapy obviously decreases LDL cholesterol (LDL-C) and triglyceride (TG) levels while increasing high-density lipoprotein cholesterol (HDL-C) levels. Larger platelets are more active, leading to increased platelet activity,11 and thus, an increased mean platelet volume (MPV) is accepted as an independent predictor of vascular events.12,13 Increased MPV is also associated with atherosclerosis, hypertension,14 dyslipidemia,15-17 diabetes mellitus (DM),18 smoking,19 obesity,20 and atrial fibrillation.21 Some studies showed that statin therapy inhibits platelet function.22,23 However, there are limited studies on MPV following statin therapy in the literature,24,25 and 2 studies suggested that there is an effect from mild to moderate-intensity rosuvastatin treatment on the MPV, and this effect is irrespective of cholesterol lowering following 4 to 12 weeks of therapy. However, there are no studies in the literature about the effects of high-
intensity rosuvastatin treatment in patients with DM over a longer duration. Hence, we determined the effect of rosuvastatin treatment on the MPV in patients with DM by evaluating whether there is such an effect, irrespective of its cholesterollowering effect.
Materials and Methods We enrolled 178 patients with dyslipidemia and type 2 DM retrospectively from our cardiology outpatient clinic during the period between January 2013 and September 2014 after we had screened their biochemical data. Patients with DM who had been on medication with high-intensity statin treatment according to the American College of Cardiology/American Heart Association joint recommendations26 were chosen based on their medical records. All of baseline medications and 40 mg daily rosuvastatin therapy did not change during the 6-month trial. At baseline and 6 months later, biochemical tests, 1
Department of Cardiology, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey 2 Department of Internal Medicine, Faculty of Medicine, Namik Kemal University, Tekirdag, Turkey Corresponding Author: Aydın Akyu¨z, Department of Cardiology, Faculty of Medicine, Namik Kemal University, 59100, Tekirdag˘, Turkey. Email: [email protected]
Downloaded from ang.sagepub.com at FLORIDA ATLANTIC UNIV on May 21, 2015
2
Angiology
complete blood count data, and cardiovascular risk factors were recorded. We defined risk factors and treatment goals as described previously.27 Diabetes mellitus was evaluated according to the American Diabetes Association.28 The body mass index (BMI) was calculated as weight in kg divided by height in m2. Smoking was defined as current smokers. Coronary artery disease (CAD) was defined as >50% luminal stenosis of epicardial coronary arteries. Peripheral artery disease (PAD) was considered ankle brachial index values 40 kg/m2), acute infection, thyroid and liver disorders, history of malignancy, renal failure, and hematological diseases (eg, polycythaemia vera and thrombophilia). One hundred and two (57.3%) patients were receiving aspirin and 19 (10.6%) patients were taking clopidogrel at enrollment.
Laboratory Measurements Hematological data including the red and white blood cell count, MPV, and platelet count were analyzed using a Roche Sysmex XT-2000i autoanalyzer (Roche Diagnostics, Paris, France), and the same commercial kits were used for analyses at both baseline and at the 6-month follow-up. First, we used vacutainer 2-mL tubes (Vacutainer, Becton, Dickinson and Company, Franklin Lakes, New Jersey) containing dipotassium EDTA to obtain the blood samples. Blood analysis was performed within 30 minutes, according to the protocol of the biochemistry department. Both the intra- and interassay coefficients of variation were
