Endothelial dysfunction: The contribution of diabetes mellitus to the risk factor burden in a high risk population

Muluemebet Ketete, Rabia Cherqaoui, Abid R. Maqbool, John Kwagyan, Shichen Xu, Otelio S. Randall

Department of Medicine, Division of Cardiovascular Medicine, Howard University, Washington DC, USA.
Department of Medicine, Division of Endocrinology and Metabolism, Howard University, Washington DC, USA.

DOI: 10.4236/jbise.2013.66075                

Abstract

Background: Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in Western societies and are rapidly becoming a worldwide health problem. African-Americans have increased morbidity and mortality rates from CVD. Our study aimed to assess the effects of the CVD risk factors burden alone versus with diabetes mellitus in a high riskCVDpopulation. Methods: The two study groups consisted of thirty seven diabetics and thirty seven non-diabetic African-Americans aged ≥55 years without clinical atherosclerosis having similar cardiovascular risk factors (age, hypertension, hypercholesterolemia, smoking, and body mass index) except for diabetes mellitus. Brachial artery flow-mediated dilation (FMD), Nitroglycerin-mediated dilatation (NMD) and carotid intima-media thickness (IMT) were recorded in all subjects. Results: Endothelial function as assessed by the brachial artery FMD was significantly impaired in the diabetic group compared to the non-diabetic group (7.8 ± 5 vs 3.3 ± 4; p = 0.0001). There were no differences in neither Nitroglycerin-mediated dilatation (NMD) nor carotid intima-media thickness (IMT) in the diabetic and non-diabetic groups. Conclusion: The contribution of diabetes to the development of endothelial dysfunction in subjects with clustering of CVD risk factors may be early as indicated by significant functional changes preceeding structural vascular changes..

Keywords

Diabetes; Endothelial Dysfunction; Cardiovascular Risk Factors

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Roger, V.L., Go, A.S., Lloyd-Jones, D.M., Benjamin, E.J., Berry, J.D., Borden, W.B., et al. (2012) Heart disease and stroke statistics—2012 update: A report from the American Heart Association. Circulation, 125, e2-e220. doi:10.1161/CIR.0b013e31823ac046
[2]	Van Dieren, S., Beulens, J.W., van der Schouw, Y.T., Grobbee, D.E. and Neal, B. (2010) The global burden of diabetes and its complications: An emerging pandemic. European Journal of Cardiovascular Prevention & Rehabilitation, 17, S3-S8. doi:10.1097/01.hjr.0000368191.86614.5a
[3]	Takase, B., Matsushima, Y., Uehata, A., Ishihara, M. and Kurita, A. (2008) Endothelial dysfunction, carotid artery plaque burden, and conventional exercise-induced myocardial ischemia as predictors of coronary artery disease prognosis. Cardiovascular Ultrasound, 6, 61. doi:10.1186/1476-7120-6-61
[4]	Yeboah, J., Folsom, A.R., Burke, G.L., Johnson, C., Polak, J.F., Post, W. and Lima, J.A. (2009) Predictive value of brachial flow mediated dilation for incident cardiovascular events in a population-based study: The multiethnic study of atherosclerosis. Circulation, 120, 502-509. doi:10.1161/CIRCULATIONAHA.109.864801
[5]	Kwagyan, J., Hussein, S., Xu, S., Ketete, M., Maqbool, A.R., Schneider, R.H. and Randall, O.S. (2009) The relationship between flow-mediated dilatation of the brachial artery and intima-media thickness of the carotid artery to Framingham risk scores in older African Americans. The Journal of Clinical Hypertension, 11, 713-719. doi:10.1111/j.1751-7176.2009.00175.x
[6]	Liu, J., Sempos, C., Donahue, R.P., Dorn, J., Trevisan, M. and Grundy, S.M. (2005) Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes. Diabetes Care, 28, 1916-1921. doi:10.2337/diacare.28.8.1916
[7]	Fox, C.S., Coady, S., Sorlie, P.D., D’Agostino Sr., R.B., Pencina, M.J., Vasan, R.S., Meigs, J.B., Levy, D. and Savage, P.J. (2007) Increasing cardiovascular disease burden due to diabetes mellitus: The Framingham heart study. Circulation, 115, 1544-1550. doi:10.1161/CIRCULATIONAHA.106.658948
[8]	Lloyd-Jones, D.M., Leip, E.P., Larson, M.G., D’Agostino, R.B., Beiser, A., Wilson, P.W., Wolf, P.A. and Levy, D. (2006) Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation, 113, 791-798. doi:10.1161/CIRCULATIONAHA.105.548206
[9]	Yokoyama, H., Sone, H., Saito, K., Yamada, D., Honjo, J. and Haneda, M. (2011) Flow-mediated dilation is associated with microalbuminuria independent of cardiovascular risk factors in type 2 diabetes-interrelations with arterial thickness and stiffness. Journal of Atherosclerosis and Thrombosis, 18, 744-752. doi:10.5551/jat.7526
[10]	Wagenknecht, L.E., D’Agostino Jr., R., Savage, P.J., O’Leary, D.H., Saad, M.F. and Haffner, S.M. (1997) Duration of diabetes and carotid wall thickness. The Insulin Resistance Atherosclerosis Study (IRAS). Stroke, 28, 999-1005. doi:10.1161/01.STR.28.5.999
[11]	Ishibashi, Y., Takahashi, N., Shimada, T., Sugamori, T., Sakane, T., Umeno, T., Hirano, Y., Oyake, N. and Murakami, Y. (2006) Short duration of reactive hyperemia in the forearm of subjects with multiple cardiovascular risk factors. Circulation Journal, 70, 115-123. doi:10.1253/circj.70.115
[12]	Hashimoto, M., Kozaki, K., Eto, M., Akishita, M., Ako, J., Iijima, K., Kim, S., Toba, K., Yoshizumi, M. and Ouchi, Y. (2000) Association of coronary risk factors and endothelium-dependent flow-mediated dilatation of the brachial artery. Hypertension Research, 23, 233-238. doi:10.1291/hypres.23.233
[13]	Tsuchiya, K., Nakayama, C., Iwashima, F., Sakai, H., Izumiyama, H., Doi, M. and Hirata, Y. (2007) Advanced endothelial dysfunction in diabetic patients with multiple risk factors; importance of insulin resistance. Journal of Atherosclerosis and Thrombosis, 14, 303-309. doi:10.5551/jat.E525
[14]	Corrado, E., Rizzo, M., Coppola, G., Muratori, I., Carella, M. and Novo, S. (2008) Endothelial dysfunction and carotid lesions are strong predictors of clinical events in patients with early stages of atherosclerosis: A 24-month follow-up study. Coronary Artery Disease, 19, 139-144. doi:10.1097/MCA.0b013e3282f3fbde
[15]	Yeboah, J., Crouse, J.R., Hsu, F.C., Burke, G.L. and Herrington, D.M. (2007) Brachial flow-mediated dilation predicts incident cardiovascular events in older adults: The Cardiovascular Health Study. Circulation, 115, 23902397. doi:10.1161/CIRCULATIONAHA.106.678276
[16]	Brevetti, G., Silvestro, A., Schiano, V. and Chiariello, M. (2003) Endothelial dysfunction and cardiovascular risk prediction in peripheral arterial disease: Additive value of flow-mediated dilation to ankle-brachial pressure index. Circulation, 108, 2093-2098. doi:10.1161/01.CIR.0000095273.92468.D9
[17]	Chan, S.Y., Mancini, G.B., Kuramoto, L., Schulzer, M., Frohlich, J. and Ignaszewski, A. (2003) The prognostic importance of endothelial dysfunction and carotid atheroma burden in patients with coronary artery disease. Journal of the American College of Cardiology, 42, 10371043. doi:10.1016/S0735-1097(03)00927-6
[18]	Shechter, M., Issachar, A., Marai, I., Koren-Morag, N., Freinark, D., Shahar Y., Shechter A. and Feinberg M.S. (2009) Long-term association of brachial artery flow-mediated vasodilation and cardiovascular events in middleaged subjects with no apparent heart disease. International Journal of Cardiology, 134, 52-58. doi:10.1016/j.ijcard.2008.01.021
[19]	Woodman, R.J., Playford, D.A. and Watts, G.F. (2006) Basal production of nitric oxide (NO) and non-NO vasodilators in the forearm microcirculation in Type 2 diabetes: Associations with blood pressure and HDL cholesterol. Diabetes Research and Clinical Practice, 71, 59-67. doi:10.1016/j.diabres.2005.05.008
[20]	Jawa, A., Nachimuthu, S., Pendergrass, M., Asnani, S. and Fonseca, V. (2006) Impaired vascular reactivity in African-American patients with type 2 diabetes mellitus and microalbuminuria or proteinuria despite angiotensinconverting enzyme inhibitor therapy. The Journal of Clinical Endocrinology & Metabolism, 91, 31-35. doi:10.1210/jc.2005-1632
[21]	Watts, G.F., O’Brien, S.F., Silvester, W. and Millar, J.A. (1996) Impaired endothelium-dependent and independent dilatation of forearm resistance arteries in men with diettreated non-insulin-dependent diabetes: Role of dyslipidaemia. Clinical Science, 91, 567-573.
[22]	Lockhart, C.J., Agnew, C.E., McCann, A., Hamilton, P.K., Quinn, C.E., McCall, D.O., Plumb, R.D., McClenaghan, V.C., McGivern, R.C., Harbinson, M.T. and McVeigh, G.E. (2001) Impaired flow-mediated dilatation response in uncomplicated type 1 diabetes mellitus: Influence of shear stress and microvascular reactivity. Clinical Science, 121, 129-139. doi:10.1042/CS20100448
[23]	Meyer, M.F., Lieps, D., Schatz, H. and Pfohl, M. (2008) Impaired flow-mediated vasodilation in type 2 diabetes: Lack of relation to microvascular dysfunction. Microvascular Research, 76, 61-65. doi:10.1016/j.mvr.2008.03.001
[24]	Celermajer, D.S., Sorensen, K.E., Bull, C., Robinson, J. and Deanfield, J.E. (1994) Endothelium-dependent dilation in the systemic arteries of asymptomatic subjects relates to coronary risk factors and their interaction. Journal of the American College of Cardiology, 24, 14681474. doi:10.1016/0735-1097(94)90141-4
[25]	Naka, K.K., Papathanassiou, K., Bechlioulis, A., Kazakos, N., Pappas, K., Tigas, S., Makriyiannis, D., Tsatsoulis, A. and Michalis, L.K. (2012) Determinants of vascular function in patients with type 2 diabetes. Cardiovascular Diabetology, 11, 127. doi:10.1186/1475-2840-11-127
[26]	Ferguson 3rd, J.J. and Randall, O.S. (1986) Systolic, diastolic, and combined hypertension. Differences between groups. Archives of Internal Medicine, 146, 1090-1093. doi:10.1001/archinte.1986.00360180072012
[27]	Osher, E. and Stern, N. (2008) Diastolic pressure in type 2 diabetes: Can target systolic pressure be reached without “diastolic hypotension?” Diabetes Care, 31, 249-254. doi:10.2337/dc08-s262