Diabetology & Metabolic Syndrome | |
Effect of single tablet of fixed-dose amlodipine and atorvastatin on blood pressure/lipid control, oxidative stress, and medication adherence in type 2 diabetic patients | |
Hiroshi Itoh1  Yoshifumi Saisho1  Junichiro Irie1  Shu Meguro1  Toshihide Kawai1  Takeshi Nishimura1  Risa Nishimura1  Masami Tanaka1  | |
[1] Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan | |
关键词: Combination tablet; Medication adherence; Atherosclerosis; Dyslipidemia; Hypertension; Diabetes mellitus; Atorvastatin; Amlodipine; Oxidative stress; Malondialdehyde-modified low-density lipoprotein; | |
Others : 803669 DOI : 10.1186/1758-5996-6-56 |
|
received in 2013-11-20, accepted in 2014-05-12, 发布年份 2014 | |
【 摘 要 】
Background
Oxidized low-density lipoprotein (LDL) plays central roles in the formation and progression of atherosclerotic lesions. Malondialdehyde (MDA)-modified LDL (MDA-LDL) is speculated to be generated as a result of oxidative stress in the human body. Because both amlodipine and atorvastatin have been reported to reduce oxidative stress, it is expected that both drugs would have a favorable influence to reduce oxidative stress.
Objective
The objective of this study was to investigate the effects of a single pill of amlodipine (5 mg)/atorvastatin (10 mg) on oxidative stress, blood pressure/lipid control and adherence to medication in patients with type 2 diabetes.
Methods
This combination tablet was administered to 29 patients (16 male), and MDA-LDL, blood pressure, lipid profile, renal/liver function, CPK, hs-CRP, adiponectin, BNP, and HbA1c were measured at baseline, 6, and 12 months, and baPWV and mean IMT were measured at baseline and 12 months. Medication adherence was examined using a questionnaire at 6 months.
Results
MDA-LDL was decreased significantly. LDL-C, TG, and Cr were significantly decreased at 6 and 12 months compared with baseline. eGFR was increased at 6 months, and urinary albumin/creatinine ratio was decreased at 12 months. BNP was decreased at 6 and 12 months, and adiponectin was increased at 12 months. Both mean IMT and baPWV were significantly decreased. The results of the questionnaire showed that 93% of patients were satisfied with this medication. No severe adverse event was observed.
Conclusion
This combination tablet controlled both hypertension and dyslipidemia well in type 2 diabetic patients. The deceases in mean IMT and baPWV might suggest the improvement of atherosclerosis by this medication, which could be caused by the reduction of oxidative stress measured by MDA-LDL. In addition, this medication is expected to improve medication adherence.
【 授权许可】
2014 Tanaka et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20140708044228787.pdf | 427KB | download | |
Figure 3. | 21KB | Image | download |
Figure 2. | 21KB | Image | download |
Figure 1. | 24KB | Image | download |
【 图 表 】
Figure 1.
Figure 2.
Figure 3.
【 参考文献 】
- [1]Witztum JL, Steinberg D: Role of oxidized low density lipoprotein in atherogenesis. J Clin Invest 1991, 88:1785-1792.
- [2]Kotani K, Maekawa M, Kanno T, Kondo A, Toda N: Manabe: Distribution of immunoreactive malondialdehyde-modified low-density lipoprotein in human serum. Biochim Biophys Acta 1994, 17:121-125.
- [3]Berliner JA, Heinecke JW: The role of oxidized lipoproteins in atherosclerosis. Free Radic Biol Med 1996, 20:707-727.
- [4]Steinberg D: Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem 1997, 272:20963-20966.
- [5]Tanaga K, Bujo H, Inoue M, Mikami K, Kotani K, Takahashi K, Kanno T, Saito Y: Increased circulating malondialdehyde-modified LDL levels in patients with coronary artery diseases and their association with peak sizes of LDL particles. Arterioscler Thromb Vasc Biol 2002, 22:662-666.
- [6]Shigematsu S, Takahashi N, Hara M, Yoshimatsu H, Saikawa T: Increased incidence of coronary in-stent restenosis in type 2 diabetic patients is related to elevated serum malondialdehyde-modified low-density lipoprotein. Circ J 2007, 71:1697-1702.
- [7]Uno M, Kitazato KT, Nishi K, Itabe H, Nagahiro S: Raised plasma oxidized LDL in acute cerebral infarction. J Neurol Neurosurg Psychiatry 2003, 74:312-316.
- [8]Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998, 339:229-234.
- [9]Mason RP, Walter MF, Day CA, Jacob RF: Intermolecular differences of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors contribute to distinct pharmacologic and pleiotropic actions. Am J Cardiol 2005, 96(Suppl):11F-23F.
- [10]Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH: CARDS investigators: Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicenter randomized placebo-controlled trial. Lancet 2004, 364:685-696.
- [11]Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, Sillesen H, Simunovic L, Szarek M, Welch KM, Zivin JA: Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators: High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med 2006, 355:549-559.
- [12]Dahlöf B, Sever PS, Poulter NR, Wedel H, Beevers DG, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Ostergren J: ASCOT Investigators: Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005, 366:895-906.
- [13]Sever PS, Dahlöf B, Poulter NR, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen SE, Kristinsson A, McInnes GT, Mehlsen J, Nieminen M, O’Brien E, Ostergren J: ASCOT investigators: Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003, 361:1149-1158.
- [14]Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S, Egusa G, Hiro T, Hirobe K, Iida M, Kihara S, Kinoshita M, Maruyama C, Ohta T, Okamura T, Yamashita S, Yokode M, Yokote K: Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan -2012 version. J Atheroscler Thromb 2013, 20:517-523.
- [15]Ogihara T, Kikuchi K, Matsuoka H, Fujita T, Higaki J, Horiuchi M, Imai Y, Imaizumi T, Ito S, Iwao H, Kario K, Kawano Y, Kim-Mitsuyama S, Kimura G, Matsubara H, Matsuura H, Naruse M, Saito I, Shimada K, Shimamoto K, Suzuki H, Takishita S, Tanahashi N, Tsuchihashi T, Uchiyama M, Ueda S, Ueshima H, Umemura S, Ishimitsu T, Rakugi H: Japanese Society of Hypertension Committee: The Japanese Society of Hypertension Guidelines for the Management of Hypertension (JSH 2009). Hypertens Res 2009, 32:3-107.
- [16]Kondo A, Muranaka Y, Ohta I, Notsu K, Manabe M, Kotani K, Saito K, Maekawa M, Kanno T: Relationship between triglyceride concentrations and LDL size evaluated by malondialdehyde-modified LDL. Clin Chem 2001, 47:893-900.
- [17]Nishimura A, Sawai T: Determination of adiponectin in serum using a latex particle-enhanced turbidimetric immunoassay with an automated analyzer. Clin Chim Acta 2006, 371:163-168.
- [18]Irie Y, Katakami N, Kaneto H, Kasami R, Sumitsuji S, Yamasaki K, Tachibana K, Kuroda T, Sakamoto K, Umayahara Y, Ueda Y, Kosugi K, Shimomura I: Maximum carotid intima-media thickness improves the prediction ability of coronary artery stenosis in type 2 diabetic patients without history of coronary artery disease. Atherosclerosis 2012, 221:438-444.
- [19]Hirano M, Nakamura T, Kitta Y, Takishima I, Deyama J, Kobayashi T, Fujioka D, Saito Y, Watanabe K, Watanabe Y, Kawabata K, Obata JE, Kugiyama K: Short-term progression of maximum intima-media thickness of carotid plaque is associated with future coronary events in patients with coronary artery disease. Atherosclerosis 2011, 215:507-512.
- [20]Sever PS, Dahlöf B, Poulter N, Wedel H, Beevers G, Caulfield M, Collins R, Kjeldsen S, Kristinsson A, Mclnnes G, Mehlsen J, Nieminem M, O’brien E, Ostergren J: ASCOT Steering Committee members: Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial. Eur Heart J 2006, 27:2982-2988.
- [21]Tajika K, Okamatsu K, Takano M, Inami S, Yamamoto M, Murakami D, Kobayashi N, Ohba T, Hata N, Seino Y, Mizuno K: Malondialdehyde-modified low-density lipoprotein is a useful marker to identify patients with vulnerable plaque. Circ J 2012, 76:2211-2217.
- [22]Kondo A, Manabe M, Saito K, Maekawa M, Kanno T: Insulin treatment prevents LDL from accelerated oxidization in patients with diabetes. J Atheroscler Thromb 2002, 9:280-287.
- [23]Abdel-Wahab MH, Abd- Allah AR: Possible protective effect of melatonin and/or desferrioxamine against streptozotocin-induced hyperglycaemia in mice. Pharmacol Res 2000, 41:533-537.
- [24]Sandhu S, Wiebe N, Fried LF, Tonelli M: Statins for improving renal outcomes: a meta-analysis. J Am Soc Nephrol 2006, 17:2006-2016.
- [25]Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Charlton-Menys V, Demicco DA, Fuller JH: CARDS Investigators: Effects of atorvastatin on kidney outcomes and cardiovascular disease in patients with diabetes: an analysis from the Collaborative Atorvastatin Diabetes Study (CARDS). Am J Kidney Dis 2009, 54:810-819.
- [26]Shepherd J, Kastelein JJ, Bittner V, Deedwania P, Breazna A, Dobson S, Wilson DJ, Zuckerman A, Wenger NK: Treating to New Target investigators: Effect of intensive lipid lowering with atorvastatin on renal function in patients with coronary heart disease: the Treating to New Targets (TNT) study. Clin J Am Soc Nephrol 2007, 2:1131-1139.
- [27]Athyros VG, Mikhailidis DP, Papageorgiou AA, Symeonidis AN, Pehlivanidis A, Bouloukos VI, Elisaf M: The effect of statins versus untreated dyslipidaemia on renal function in patients with coronary heart disease. A subgroup analysis of the Greek atorvastatin and coronary heart disease evaluation (GREACE) study. J Clin Pathol 2004, 57:728-734.
- [28]Takemoto M, Ishikawa T, Onishi S, Okabe E, Ishibashi R, He P, Kobayashi K, Fujimoto M, Kawamura H, Yokote K: Atorvastatin ameliorates podocyte injury in patients with type 2 diabetes complicates with dyslipidemia. Diabetes Res Clin Pract 2013, 100:e26-29.
- [29]Khush KK, Waters DD, Bittner V, Deedwania PC, Kastelein JJ, Lewis SJ, Wenger NK: Effect of high-dose atorvastatin on hospitalizations for heart failure: subgroup analysis of the Treating to New Targets (TNT) study. Circulation 2007, 115:576-583.
- [30]Li M, Xu A, Lam KS, Cheung BM, Tse HF: Impact of combination therapy with amlodipine and atorvastatin on plasma adiponectin levels in hypertensive patients with coronary artery disease: combination therapy and adiponectin. Postgrad Med 2011, 123:66-71.
- [31]Schroeder K, Fahey T, Ebrahim S: How can we improve adherence to blood pressure-lowering medication in ambulatory care? Systematic review of randomized controlled traials. Arch Intern Med 2004, 164:722-732.
- [32]Bangalore S, Kamalakkannan G, Parker S, Messerli FH: Fixed-dose combinations improve medication compliance: a meta-analysis. Am J Med 2007, 120:713-719.
- [33]Bell KJ, Kirby A, Hayen A, Irwig L, Glasziou P: Monitoring adherence to drug treatment by using change in cholesterol concentration: secondary analysis of trial data. BMJ 2011, 342:d12.