Endothelial dysfunction and cardiovascular outcome in asymptomatic patients with type 2 diabetes: A pilot study.
Biomarkers
/ analysis
Blood Glucose
/ analysis
Cardiovascular Diseases
/ epidemiology
Diabetes Mellitus, Type 2
/ physiopathology
Endothelium, Vascular
/ pathology
Female
Follow-Up Studies
Humans
Incidence
Italy
/ epidemiology
Male
Middle Aged
Pilot Projects
Prognosis
Prospective Studies
Risk Factors
clinical outcome
endothelial function
type 2 diabetes mellitus
Journal
Diabetes/metabolism research and reviews
ISSN: 1520-7560
Titre abrégé: Diabetes Metab Res Rev
Pays: England
ID NLM: 100883450
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
25
03
2019
revised:
02
09
2019
accepted:
04
09
2019
pubmed:
12
9
2019
medline:
2
12
2020
entrez:
12
9
2019
Statut:
ppublish
Résumé
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events, but risk stratification of asymptomatic T2DM patients remains a challenging issue. We conducted a pilot study to assess whether endothelial dysfunction might help identify, among asymptomatic T2DM patients, those at increased risk of cardiovascular events. We studied 61 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy. Endothelial function was assessed by flow-mediated dilation (FMD) of the right brachial artery. The primary endpoint was a combination of major cardiovascular events (MACE: cardiovascular death, acute coronary events, coronary interventions, and acute cerebrovascular accidents). FMD was repeated at follow-up in 48 patients (79%). A total of 10 MACE (16.4%) occurred during a mean follow-up of 48 months, including three acute myocardial infarctions, five coronary revascularizations for stable angina, and two acute ischaemic strokes. FMD at enrolment was lower in patients with compared with patients without MACE (3.78 ± 0.97% vs 4.70 ± 1.33%, respectively; P = .04). No other clinical or laboratory variables (age, diabetes duration, glycated haemoglobin, cardiovascular risk factors, drug therapy, and nitrate-mediated dilation) were associated with MACE. FMD at follow-up was also lower in patients with (n = 10) compared with those without (n = 38) MACE (3.66 ± 1.29 vs 4.85 ± 1.92; P = .006). Our data suggest that assessment of FMD might be helpful to identify patients at increased risk of MACE among individuals with asymptomatic T2DM; accordingly, a large study is warranted to adequately define the clinical utility of FMD assessment in the management of T2DM patients.
Sections du résumé
BACKGROUND
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events, but risk stratification of asymptomatic T2DM patients remains a challenging issue. We conducted a pilot study to assess whether endothelial dysfunction might help identify, among asymptomatic T2DM patients, those at increased risk of cardiovascular events.
METHODS
We studied 61 consecutive T2DM patients with no evidence of cardiovascular disease and no insulin therapy. Endothelial function was assessed by flow-mediated dilation (FMD) of the right brachial artery. The primary endpoint was a combination of major cardiovascular events (MACE: cardiovascular death, acute coronary events, coronary interventions, and acute cerebrovascular accidents). FMD was repeated at follow-up in 48 patients (79%).
RESULTS
A total of 10 MACE (16.4%) occurred during a mean follow-up of 48 months, including three acute myocardial infarctions, five coronary revascularizations for stable angina, and two acute ischaemic strokes. FMD at enrolment was lower in patients with compared with patients without MACE (3.78 ± 0.97% vs 4.70 ± 1.33%, respectively; P = .04). No other clinical or laboratory variables (age, diabetes duration, glycated haemoglobin, cardiovascular risk factors, drug therapy, and nitrate-mediated dilation) were associated with MACE. FMD at follow-up was also lower in patients with (n = 10) compared with those without (n = 38) MACE (3.66 ± 1.29 vs 4.85 ± 1.92; P = .006).
CONCLUSIONS
Our data suggest that assessment of FMD might be helpful to identify patients at increased risk of MACE among individuals with asymptomatic T2DM; accordingly, a large study is warranted to adequately define the clinical utility of FMD assessment in the management of T2DM patients.
Substances chimiques
Biomarkers
0
Blood Glucose
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e3215Informations de copyright
© 2019 John Wiley & Sons, Ltd.
Références
American Diabetes Association. Standards of Medical Care in Diabetes 2018. Diabetes Care 208;41(Suppl 1):S1-S159.
Authors/Task Force Members, Rydén L, Grant PJ, et al. ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases. Eur Heart J. 2018;34:3035-3087.
Miller FJ Jr, Gutterman DD, Rios CD, Heistad DD, Davidson BL. Superoxide production in vascular smooth muscle contributes to oxidative stress and impaired relaxation in atherosclerosis. Circ Res. 1998;82(12):1298-1305.
Sitia S, Tomasoni L, Atzeni F, et al. From endothelial dysfunction to atherosclerosis. Autoimmun Rev. 2010;9(12):830-834.
Munzel T, Daiber A, Ullrich V, Mulsch A. Vascular consequences of endothelial nitric oxide synthase uncoupling for the activity and expression of the soluble guanylyl cyclase and the cGMP-dependent protein kinase. Arterioscler Thromb Vasc Biol. 2005;25(8):1551-1557.
Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980;288(5789):373-376.
Cosentino F, Lüscher TF. Endothelial dysfunction in diabetes mellitus. J Cardiovasc Pharmacol. 1998;32(Suppl 3):S54-S61.
Cersosimo E, DeFronzo RA. Insulin resistance and endothelial dysfunction: the road map to cardiovascular diseases. Diabetes Metab Res Rev. 2006;22(6):423-436.
Hink U, Li H, Mollnau H, et al. Mechanisms underlying endothelial dysfunction in diabetes mellitus. Circ Res. 2001;88(2):E14-E22.
Ho HCH, Maddaloni E, Buzzetti R. Risk factors and predictive biomarkers of early cardiovascular disease in obese youth. Diabetes Metab Res Rev. 2019;35(4):e3134. https://doi.org/10.1002/dmrr.3134. Epub 2019 Feb 21
Shechter M, Issachar A, Marai I, et al. Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol. 2009;134(1):52-58.
Ras RT, Streppel MT, Draijer R, Zock PL. Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis. Int J Cardiol. 2013;168(1):344-351.
Matsuzawa Y, Kwon TG, Lennon RJ, Lerman LO, Lerman A. Prognostic value of flow-mediated vasodilation in brachial artery and fingertip artery for cardiovascular events: a systematic review and meta-analysis. J Am Heart Assoc. 2015;4. pii: e002270(11). https://doi.org/10.1161/JAHA.115.002270
van Sloten TT, Henry RMA, Dekker JM, et al. Endothelial dysfunction plays a key role in increasing cardiovascular risk in type 2 diabetes; the Hoorn Study. Hypertension. 2014;64(6):1299-1305.
Levey AS, Coresh J, Greene T, et al. Chronic Kidney Disease Epidemiology Collaboration. Using standardized serum creatinine values in the Modification of Diet in Renal Disease study equation for estimating glomerular filtration rate. Ann Intern Med. 2006;145(4):247-254.
Ghiadoni L, Faita F, Salvetti M, et al. Assessment of flow-mediated dilation reproducibility: a nationwide multicenter study. J Hypertens. 2012;30(7):1399-1405.
Nerla R, Tarzia P, Sestito A, et al. Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function. Nutr Metab Cardiovasc Dis. 2012;22(8):626-634.
Faulx MD, Wright AT, Hoit BD. Detection of endothelial dysfunction with brachial artery ultrasound scanning. Am Heart J. 2003;145(6):943-951.
Thijssen DHJ, Black MA, Pyke KE, et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300(1):H2-H12.
Padilla J, Johnson BD, Newcomer SC, et al. Normalization of flow-mediated dilation to shear stress area under the curve eliminates the impact of variable hyperemic stimulus. Cardiovasc Ultrasound. 2008;6(1):44.
Pyke KE, Tschakovsky ME. Peak vs. total reactive hyperemia: which determines the magnitude of flow-mediated dilation? J Appl Physiol. 2007;102(4):1510-1519.
Lanza GA, Spera FR, Villano A, et al. Effect of smoking on endothelium-independent vasodilatation. Atherosclerosis. 2015;240(2):330-332.
Gaiz A, Mosawy S, Colson N, Singh I. Thrombotic and cardiovascular risks in type two diabetes; Role of platelet hyperactivity. Biomed Pharmacother. 2017;94:679-686.
Fiorentino TV, Succurro E, Andreozzi F, Sciacqua A, Perticone F, Sesti G. One-hour post-load hyperglycemia combined with HbA1c identifies individuals with higher risk of cardiovascular diseases: cross-sectional data from the CATAMERI study. Diabetes Metab Res Rev. 2019;35(2):e3096. https://doi.org/10.1002/dmrr.3096. Epub 2018 Nov 20
Gong W, Lu B, Yang Z, et al. Early-stage atherosclerosis in newly diagnosed, untreated type 2 diabetes mellitus and impaired glucose tolerance. Diabetes Metab. 2009;35(6):458-462.
Berenson GS, Srinivasan SR, Bao W, Newman WP 3rd, Tracy RE, Wattigney WA. Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study. N Engl J Med. 1998;338(23):1650-1656.
Knoflach M, Kiechl S, Kind M, et al. Cardiovascular risk factors and atherosclerosis in young males: ARMY study (Atherosclerosis Risk-Factors in Male Youngsters). Circulation. 2003;108(9):1064-1069.
Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004;109(Suppl 1):III27-III32.
Yu B, Shahid M, Egorina EM, et al. Endothelial dysfunction enhances vasoconstriction due to scavenging of nitric oxide by a hemoglobin-based oxygen carrier. Anesthesiology. 2010;12:586-594.
M1 S, Issachar A, Marai I, et al. Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middle-aged subjects with no apparent heart disease. Int J Cardiol. 2009;134:52-58.
Shechter M, Shechter A, Koren-Morag N, Feinberg MS, Hiersch L. Usefulness of brachial artery flow-mediated dilation to predict long-term cardiovascular events in subjects without heart disease. Am J Cardiol. 2014;113(1):162-167.
Kimura Y, Matsumoto M, Den YB, et al. Impaired endothelial function in hypertensive elderly patients evaluated by high resolution ultrasonography. Can J Cardiol. 1999;15(5):563-568.
Li J, Zhao SP, Li XP, Zhuo QC, Gao M, Lu SK. Non-invasive detection of endothelial dysfunction in patients with essential hypertension. Int J Cardiol. 1997;61(2):165-169.
Shivalkar B, Dhondt D, Goovaerts I, et al. Flow mediated dilatation and cardiac function in type 1 diabetes mellitus. Am J Cardiol. 2006;97(1):77-82.