Lack of correlation between the optimal glycaemic control and coronary micro vascular dysfunction in patients with diabetes mellitus: a cross sectional study

Cardiovascular Diabetology

Amir Lerman¹  Rafael J Ruiz-Salmeron²  Lilach O Lerman³  Ryan J Lennon⁴  Taek-Geun Kwon¹  Jaskanwal D S Sara¹  Yasushi Matsuzawa¹  Luis Felipe Valenzuela-Garcia² 

[1] Division of Cardiovascular Diseases and Department of Internal Medicine, Mayo College of Medicine, 200 First Street SW, Rochester 55905, MN, USA;Heart Center, Virgen Macarena Hospital, Avenida Doctor Fedriani, nº 3, Seville, 41007, Spain;Division of Nephrology and Hypertension, Mayo Clinic, 200 First Street SW, Rochester, MN, USA;Division of Biomedical Statistics and Informatics, Mayo College of Medicine, 200 First Street SW, Rochester, MN, USA

关键词: Coronary microcirculation;    Diabetes mellitus;    Endothelial dysfunction;   

Others  :  1222732
DOI  :  10.1186/s12933-015-0269-1

 received in 2015-06-04, accepted in 2015-07-31,  发布年份 2015

【 摘 要 】

Background

Coronary microvascular dysfunction (CMD) is associated with cardiovascular events in type 2 diabetes mellitus (T2DM). Optimal glycaemic control does not always preclude future events. We sought to assess the effect of the current target of HBA1c level on the coronary microcirculatory function and identify predictive factors for CMD in T2DM patients.

Methods

We studied 100 patients with T2DM and 214 patients without T2DM. All of them with a history of chest pain, non-obstructive angiograms and a direct assessment of coronary blood flow increase in response to adenosine and acetylcholine coronary infusion, for evaluation of endothelial independent and dependent CMD. Patients with T2DM were categorized as having optimal (HbA1c < 7 %) vs. suboptimal (HbA1c ≥ 7 %) glycaemic control at the time of catheterization.

Results

Baseline characteristics and coronary endothelial function parameters differed significantly between T2DM patients and control group. The prevalence of endothelial independent CMD (29.8 vs. 39.6 %, p = 0.40) and dependent CMD (61.7 vs. 62.2 %, p = 1.00) were similar in patients with optimal vs. suboptimal glycaemic control. Age (OR 1.10; CI 95 % 1.04–1.18; p < 0.001) and female gender (OR 3.87; CI 95 % 1.45–11.4; p < 0.01) were significantly associated with endothelial independent CMD whereas glomerular filtrate (OR 0.97; CI 95 % 0.95–0.99; p < 0.05) was significantly associated with endothelial dependent CMD. The optimal glycaemic control was not associated with endothelial independent (OR 0.60, CI 95 % 0.23–1.46; p 0.26) or dependent CMD (OR 0.99, CI 95 % 0.43–2.24; p = 0.98).

Conclusions

The current target of HBA1c level does not predict a better coronary microcirculatory function in T2DM patients. The appropriate strategy for prevention of CMD in T2DM patients remains to be addressed.

【 授权许可】

   
2015 Valenzuela-Garcia et al.

【 图 表 】

Fig.1.

【 参考文献 】

• [1]Gerstein HC, Bosch J, Dagenais GR, Diaz R, Jung H, Maggioni AP et al.. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012; 367(4):319-328.
• [2]Hayward RA, Reaven PD, Wiitala WL, Bahn GD, Reda DJ, Ge L et al.. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015; 372(23):2197-2206.
• [3]Giorgino F, Leonardini A, Laviola L. Cardiovascular disease and glycemic control in type 2 diabetes: now that the dust is settling from large clinical trials. Ann N Y Acad Sci. 2013; 1281:36-50.
• [4]Picchi A, Capobianco S, Qiu T, Focardi M, Zou X, Cao JM et al.. Coronary microvascular dysfunction in diabetes mellitus: a review. World J Cardiol. 2010; 2(11):377-390.
• [5]Hamilton SJ, Watts GF. Endothelial dysfunction in diabetes: pathogenesis, significance, and treatment. Rev Diabet Stud: RDS. 2013; 10(2–3):133-156.
• [6]Standards of medical care in diabetes—2010. Diabetes Care. 2010; 33 Suppl 1:S11-S61.
• [7]Erdogan D, Akcay S, Yucel H, Ersoy IH, Icli A, Kutlucan A et al.. The effects of good glycaemic control on left ventricular and coronary endothelial functions in patients with poorly controlled Type 2 diabetes mellitus. Clin Endocrinol. 2015; 82(3):388-396.
• [8]Li YJ, Hyun MH, Rha SW, Chen KY, Jin Z, Dang Q et al.. Diabetes mellitus is not a risk factor for coronary artery spasm as assessed by an intracoronary acetylcholine provocation test: angiographic and clinical characteristics of 986 patients. J Invasive Cardiol. 2014; 26(6):234-239.
• [9]Layland J, Judkins C, Palmer S, Whitbourn R, Wilson-O’Brien A, MacIsaac A et al.. The resting status of the coronary microcirculation is a predictor of microcirculatory function following elective PCI for stable angina. Int J Cardiol. 2013; 169(2):121-125.
• [10]Cassar A, Chareonthaitawee P, Rihal CS, Prasad A, Lennon RJ, Lerman LO et al.. Lack of correlation between noninvasive stress tests and invasive coronary vasomotor dysfunction in patients with nonobstructive coronary artery disease. Circ Cardiovasc Interv. 2009; 2(3):237-244.
• [11]Ryden L, Grant PJ, Anker SD, Berne C, Cosentino F, Danchin N et al.. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013; 34(39):3035-3087.
• [12]Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA et al.. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009; 120(16):1640-1645.
• [13]Goldenberg R, Punthakee Z. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes. 2013; 37 Suppl 1:S8-11.
• [14]Mourmoura E, Vial G, Laillet B, Rigaudiere JP, Hininger-Favier I, Dubouchaud H et al.. Preserved endothelium-dependent dilatation of the coronary microvasculature at the early phase of diabetes mellitus despite the increased oxidative stress and depressed cardiac mechanical function ex vivo. Cardiovasc Diabetol. 2013; 12:49. BioMed Central Full Text
• [15]Hasdai D, Cannan CR, Mathew V, Holmes DR, Lerman A. Evaluation of patients with minimally obstructive coronary artery disease and angina. Int J Cardiol. 1996; 53(3):203-208.
• [16]Maiorana A, O’Driscoll G, Cheetham C, Dembo L, Stanton K, Goodman C et al.. The effect of combined aerobic and resistance exercise training on vascular function in type 2 diabetes. J Am Coll Cardiol. 2001; 38(3):860-866.
• [17]Reboussin DM, Goff DC, Lipkin EW, Herrington DM, Summerson J, Steffes M et al.. The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results. Diabet Med: J Br Diabet Assoc. 2004; 21(10):1082-1089.
• [18]Cortigiani L, Rigo F, Gherardi S, Sicari R, Galderisi M, Bovenzi F et al.. Additional prognostic value of coronary flow reserve in diabetic and nondiabetic patients with negative dipyridamole stress echocardiography by wall motion criteria. J Am Coll Cardiol. 2007; 50(14):1354-1361.
• [19]Pristipino C, Beltrame JF, Finocchiaro ML, Hattori R, Fujita M, Mongiardo R et al.. Major racial differences in coronary constrictor response between japanese and caucasians with recent myocardial infarction. Circulation. 2000; 101(10):1102-1108.
• [20]Halcox JP, Schenke WH, Zalos G, Mincemoyer R, Prasad A, Waclawiw MA et al.. Prognostic value of coronary vascular endothelial dysfunction. Circulation. 2002; 106(6):653-658.
• [21]Targonski PV, Bonetti PO, Pumper GM, Higano ST, Holmes DR, Lerman A. Coronary endothelial dysfunction is associated with an increased risk of cerebrovascular events. Circulation. 2003; 107(22):2805-2809.
• [22]Hamasaki S, Al Suwaidi J, Higano ST, Miyauchi K, Holmes DR, Lerman A. Attenuated coronary flow reserve and vascular remodeling in patients with hypertension and left ventricular hypertrophy. J Am Coll Cardiol. 2000; 35(6):1654-1660.
• [23]Treasure CB, Manoukian SV, Klein JL, Vita JA, Nabel EG, Renwick GH et al.. Epicardial coronary artery responses to acetylcholine are impaired in hypertensive patients. Circ Res. 1992; 71(4):776-781.
• [24]Zeiher AM, Drexler H, Saurbier B, Just H. Endothelium-mediated coronary blood flow modulation in humans. Effects of age, atherosclerosis, hypercholesterolemia, and hypertension. J Clin Investig. 1993; 92(2):652-662.
• [25]Sucato V, Evola S, Quagliana A, Novo G, Andolina G, Assennato P et al.. Comparison of coronary artery flow impairment in diabetic and hypertensive patients with stable microvascular angina. Eur Rev Med Pharmacol Sci. 2014; 18(23):3687-3689.
• [26]Reriani MK, Dunlay SM, Gupta B, West CP, Rihal CS, Lerman LO et al.. Effects of statins on coronary and peripheral endothelial function in humans: a systematic review and meta-analysis of randomized controlled trials. Eur J Cardiovasc Prev Rehabil: Off J Eur Soc Cardiol Work Groups Epidemiol Prev Card Rehabil Exerc Physiol. 2011; 18(5):704-716.
• [27]Li S, Wu Y, Yu G, Xia Q, Xu Y. Angiotensin II receptor blockers improve peripheral endothelial function: a meta-analysis of randomized controlled trials. PLoS One. 2014; 9(3):e90217.
• [28]Bank AJ, Kelly AS, Thelen AM, Kaiser DR, Gonzalez-Campoy JM. Effects of carvedilol versus metoprolol on endothelial function and oxidative stress in patients with type 2 diabetes mellitus. Am J Hypertens. 2007; 20(7):777-783.
• [29]Colette C, Monnier L. Acute glucose fluctuations and chronic sustained hyperglycemia as risk factors for cardiovascular diseases in patients with type 2 diabetes. Horm Metab Res. 2007; 39(9):683-686.
• [30]Rohlfing CL, Wiedmeyer HM, Little RR, England JD, Tennill A, Goldstein DE. Defining the relationship between plasma glucose and HbA(1c): analysis of glucose profiles and HbA(1c) in the Diabetes Control and Complications Trial. Diabetes Care. 2002; 25(2):275-278.
• [31]Penno G, Solini A, Zoppini G, Orsi E, Fondelli C, Zerbini G et al.. Hemoglobin A1c variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study. Cardiovasc Diabetol. 2013; 12:98. BioMed Central Full Text
• [32]Ceriello A, Esposito K, Piconi L, Ihnat MA, Thorpe JE, Testa R et al.. Oscillating glucose is more deleterious to endothelial function and oxidative stress than mean glucose in normal and type 2 diabetic patients. Diabetes. 2008; 57(5):1349-1354.
• [33]Torimoto K, Okada Y, Mori H, Tanaka Y. Relationship between fluctuations in glucose levels measured by continuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetes mellitus. Cardiovasc Diabetol. 2013; 12:1. BioMed Central Full Text
• [34]Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabetic complications. JAMA J Am Med Assoc. 2006; 295(14):1707-1708.
• [35]Advani A, Bugyei-Twum A, Connelly KA. Cardiovascular effects of incretins in diabetes. Can J Diabetes. 2013; 37(5):309-314.
• [36]Tesauro M, Schinzari F, Adamo A, Rovella V, Martini F, Mores N et al.. Effects of GLP-1 on forearm vasodilator function and glucose disposal during hyperinsulinemia in the metabolic syndrome. Diabetes Care. 2013; 36(3):683-689.
• [37]Matsubara J, Sugiyama S, Akiyama E, Iwashita S, Kurokawa H, Ohba K et al.. Dipeptidyl peptidase-4 inhibitor, sitagliptin, improves endothelial dysfunction in association with its anti-inflammatory effects in patients with coronary artery disease and uncontrolled diabetes. Circ J: Off J Jpn Circ Soc. 2013; 77(5):1337-1344.