Endothelial dysfunction in patients with metabolic syndrome: a prospective study in a rural institute in India

Khwaja Saifullah Zafar, P. S. Singh, Vijay Kumar Verma, N. A. Wafai


Background: The objective was to evaluate endothelial dysfunction in patients with metabolic syndrome.

Methods: This prospective, cross-sectional, hospital based observational study included 45 patients with metabolic syndrome and 20 age and sex matched controls who attended hypertension clinic, diabetes clinic, general medicine OPD and patients admitted in wards department of medicine, UPRIMS&R, Saifai, Etawah, UP, India. All patients who fulfilled inclusion criteria were subjected to the color Doppler of the brachial artery in the department of radio-diagnosis of the same institute.

Results: Of the 45 patients with metabolic syndrome included in the study, 22 patients (48.9%) were males and 23 patients (51.1%) were females. Ten males (45.5%) had a waist circumference of >90 cm whereas 20 females (87%) had waist circumference of >80 cm. 9 males (40.9%) had abnormal waist hip ratio whereas 22 females (95.7%) had abnormal waist hip ratio. 43 patients (95.6%) had a SBP >130 mm of Hg whereas 39 patients (86.7%) had a DBP >85 mm of Hg. 24 patients (53.3%) had impaired fasting blood sugar i.e. >100 mg/dl ,25 patients (55.6%) had a TGL level >150 mg/dl, and 9 males (40.0%) had HDL < 40 mg/dl whereas 18 females (78.3%) had HDL value < 50 mg/dl respectively. The mean brachial artery baseline diameter were 3.50 ± 0.39 mm in males and 3.25 ± 0.29 mm in females respectively, FMD percentage was 14.91 ± 3.56 in females and 14.53 ± 4.02 in males, and GTN mediated dilatation were 27.67 ± 9.83% in females and 27.62 ± 6.85% in males respectively.

Conclusion: Estimation of Endothelial Dysfunction in patients at risk of developing full blown Metabolic Syndrome may predict the cardiovascular morbidity and mortality in these individuals even before fulfilling the 3/5 criteria of NCEP/ATP III Guidelines for the diagnosis of metabolic syndrome.



Cardiovascular disease, Endothelial function, Flow-mediated vasodilation, Finger plethysmography, Metabolic syndrome, Pulse wave velocity

Full Text:



Després JP, Brewer HB. Metabolic syndrome: the dysmetabolic state of dysfunctional adipose tissue and insulin resistance. Eur Heart J 2008;10(Suppl. B):B1-3.

Gonzalez AS, Guerrero DB, Soto MB, et al. Metabolic syndrome, insulin resistance and the inflammation markers C-reactive protein and ferritin. Eur J Clin Nutr 2006;60:802-9.

Deanfield JE, Halcox JP, Rabelink TJ. Endothelial function and dysfunction: testing and clinical relevance. Circulation. 2007;115:1285–95.

Flammer AJ, Lu scher TF. Three decades of endothelium research: from the detection of nitric oxide to the everyday implementation of endothelial function measurements in cardiovascular diseases. Swiss Med Wkly. 2010;140:w13122.

Rubinshtein R, Kuvin JT, Soffler M, Lennon RJ, Lavi S, Nelson RE, et al. Assessment of endothelial function by non-invasive peripheral arterial tonometry predicts late cardiovascular adverse events. Eur Heart J. 2010;31:1142–8.

Ludmer PL, Selwyn AP, Shook TL, Wayne RR, Mudge GH, Alexander RW, et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Engl J Med. 1986;315:1046–51.

Schachinger V, BrittenMB, Zeiber, AM. Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 2000;101:1899-1906.

Leung DY, Leung M. Non-invasive/invasive imaging: significance and assessment of coronary microvascular dysfunction. Heart. 2011;97:587–95.

Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet. 1992;340:1111–5.

Anderson EA, Mark AL. Flow-mediated and reflex changes in large peripheral artery tone in humans. Circulation. 1989;79:93–100.

Laclaustra M, Frangi AF, Garcia D, Boisrobert L, Frangi AG, Pascual I. Detailed exploration of the endothelium: parameterization of flow-mediated dilation through principal component analysis. Physiol Meas. 2007;28:301–20.

Charakida M, Masi S, Lu¨ scher TF, Kastelein JJP, Deanfield JE. Assessment of atherosclerosis: the role of flow-mediated dilatation. Eur Heart J. 2010;31:2854–61.

Al-Qaisi M, Kharbanda RK, Mittal TK, Donald AE. Measurement of endothelial function and its clinical utility for cardiovascular risk. Vasc Health Risk Manag.2008;4:647–52.

Bots ML, Westerink J, Rabelink TJ, De Koning EJP. Assessment of flow-mediated vasodilatation (FMD) of the brachial artery: effects of technical aspects of the FMD measurement on the FMD response. Eur Heart J. 2005;26:363–8.

Corretti MC, Anderson TJ, Benjamin EJ, Celermajer D, Charbonneau F, Creager MA, et al. Guidelines for the ultrasound assessment of endothelialdependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. J Am Coll Cardiol.2002;39:257–65.

Thijssen DHJ, Black MA, Pyke KE, Padilla J, Atkinson G, Harris RA, et al. Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2011;300:H2–12.

Pa´ linka´ s A, To´ th E, Venneri L, Rigo F, Csana´dy M, Picano E. Temporal heterogeneity of endothelium-dependent and -independent dilatation of brachial artery in patients with coronary artery disease. Int J Cardiovasc Imaging.2002;18:337–42.

Frangi AF, Laclaustra M, Lamata P. A registration-based approach to quantify flow-mediated dilation (FMD) of the brachial artery in ultrasound image sequences. IEEE Trans Med Imaging. 2003;22: 1458–69.

Sonka M, Liang W, Lauer RM. Automated analysis of brachial ultrasound image sequences: early detection of cardiovascular disease via surrogates of endothelial function. IEEE Trans Med Imaging. 2002;21:1271–9.

Gori T, Parker JD, Mu¨ nzel T. Flow-mediated constriction: further insight into a new measure of vascular function. Eur Heart J. 2011;32:784–7.

Laclaustra M, Frangi AF, Frangi AG, Casasnovas JA, Cia P. Association of endothelial function and vascular data with LDL-c and HDL-c in a homogeneous population of middle-aged, healthy military men: Evidence for a critical role of optimal lipid levels. Int J Cardiol. 2008;125:376–82

Halcox JPJ, Donald AE, Ellins E, Witte DR, Shipley MJ, Brunner EJ, et al. Endothelial function predicts progression of carotid intima-media thickness. Circulation.2009;119:1005–12.

Gokce N, Keaney Jr JF, Hunter LM, Watkins MT, Nedeljkovic ZS, Menzoian JO, et al. Predictive value of noninvasively determined endothelial dysfunction for long-term cardiovascular events in patients with peripheral vascular disease. J Am Coll Cardiol. 2003;41:1769–75.

Karatzis EN, Ikonomidis I, Vamvakou GD, Papaioannou TG, Protogerou AD, Andreadou I, et al. Long-term prognostic role of flow-mediated dilatation of the brachial artery after acute coronary syndromes without ST elevation. Am J Cardiol. 2006;98:1424–8.

Gokce N, Keaney Jr JF, Hunter LM, Watkins MT, Menzoian JO, Vita JA. Risk stratification for postoperative cardiovascular events via noninvasive assessment of endothelial function: a prospective study. Circulation. 2002;105:1567–72.

Zambanini A, Cunningham SL, Parker KH, Khir AW, McG Thom SA, Hughes AD. Wave-energy patterns in carotid, brachial, and radial arteries: a noninvasive approach using wave-intensity analysis. Am J Physiol Heart Circ Physiol.2005;289:H270–6.

Nelson MR, Stepanek J, Cevette M, Covalciuc M, Hurst RT, Tajik AJ. Noninvasive measurement of central vascular pressures with arterial tonometry: clinical revival of the pulse pressure waveform? Mayo Clin Proc. 2010;85:460–72.

Hayward CS, Kraidly M, Webb CM, Collins P. Assessment of endothelial function using peripheral waveform analysis: a clinical application. J Am Coll Cardiol.2002;40:521–8.

Rietzschel ER, Boeykens E, De Buyzere ML, Duprez DA, Clement DL. A comparison between systolic and diastolic pulse contour analysis in the evaluation of arterial stiffness. Hypertension. 2001;37:E15–22.

Cavalcante JL, Lima JAC, Redheuil A, Al-Mallah MH. Aortic stiffness: current understanding and future directions. J Am Coll Cardiol. 2011;57:1511–22.

Adji A, Hirata K, O’Rourke MF. Clinical use of indices determined non-invasively from the radial and carotid pressure waveforms. Blood Press Monit. 2006;11:215–21.

Horva´ th IG, Ne´meth A, Lenkey Z, Alessandri N, Tufano F, Kis P, et al. Invasive validation of a new oscillometric device (Arteriograph) for measuring augmentation index, central blood pressure and aortic pulse wave velocity. J Hypertens.2010;28: 2068–75.

Wassertheurer S, Kropf J, Weber T, Van der Giet M, Baulmann J, Ammer M, et al. A new oscillometric method for pulse wave analysis: comparison with a common tonometric method. J Hum Hypertens. 2010;24:498–504.

Sigrist MK, Chiarelli G, Levin A, Romann A, Weber C. Pulse wave velocity measurements are reproducible in multiple trained observers: a short report. Nephron Clin Pract. 2010;116:c60–4.

Van Leeuwen-Segarceanu EM, Tromp WF, Bos W-JW, Vogels OJ, Groothoff JW, Van der Lee JH. Comparison of two instruments measuring carotid-femoralpulse wave velocity: Vicorder versus SphygmoCor. J Hypertens. 2010;28:1687–91.