Abstract
Increased heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in the general population and in some clinical conditions. Endothelial dysfunction is an adverse prognostic factor for cardiovascular events. The aim of the study was to evaluate the effect of HR on central hemodynamic parameters and endothelial function in hypertension. We evaluated forearm blood flow (FBF) response to intra-arterial infusion of acetylcholine (ACh) and sodium nitroprusside (SNP) in 30 patients with HR ≤60 min−1 and 30 with HR ≥80 min−1. The FBF was measured by strain-gauge plethysmography. Transesophageal atrial pacing was used to increase the HR. Radial artery applanation tonometry and pulse wave analysis were used to derive central aortic pressures and correlate hemodynamic indices. The FBF response to ACh is lower in hypertensives with HR ≤60 min−1 than in those with HR ≥80 min−1 (10.6 ± 4.2 vs. 13.6 ± 5.1 ml × 100 ml−1 of tissue × min−1, P < 0.001). Vascular resistance decreases to 9.3 ± 2.8 U in patients with lower HR versus 7.2 ± 2.1 U in those with higher HR (P = 0.002). The FBF response to SNP is similar in both groups. Central systolic and pulse pressure are higher in bradycardic patients than in those with HR ≥80 min−1 (140 ± 8 vs. 131 ± 8 mmHg, P = 0.0001 and 49 ± 10 vs. 39 ± 11 mmHg, P = 0.0001). All central hemodynamic parameters decrease during incremental atrial pacing. Augmentation index is the strongest predictor of endothelial dysfunction at multivariate analysis. These findings demonstrate that low HR affects endothelium-dependent vasodilation in hypertension. Increased central aortic pressure and hemodynamic correlates seem to be the underlying mechanisms by which bradycardia interferes with endothelium-dependent reactivity.
Similar content being viewed by others
References
Palatini P, Thijs L, Staessen JA et al (2002) Systolic Hypertension in Europe (Syst-Eur) Trial Investigators. Predictive value of clinic and ambulatory heart rate for mortality in elderly subjects with systolic hypertension. Arch Intern Med 162:2313–2321
Jouven X, Empana JP, Schwartz PJ, Desnos M, Courbon D, Ducimetière P (2005) Heart-rate profile during exercise is a predictor of sudden death. N Engl J Med 352:1951–1958
Custodis F, Schirmer SH, Baumhäkel M, Hensch G, Böhm M, Laufs U (2010) Vascular pathophysiology in response to increased heart rate. J Am Coll Cardiol 56:1973–1983
Bangalore S, Sawhney S, Messerli FH (2008) Relation of beta-blocker-induced heart rate lowering and cardioprotection in hypertension. J Am Coll Cardiol 52:1482–1489
Fox K, Ford I, Steg PG, Tendera M, Ferrari R, BEAUTIFUL Investigators (2008) Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet 372:807–816
Wilkinson IB, MacCallum H, Flint L, Cockcroft JR, Newby DE, Webb DJ (2000) The influence of heart rate on augmentation index and central arterial pressure in humans. J Physiol 525:263–270
Papaioannou TG, Vlachopoulos CV, Alexopoulos NA et al (2008) The effect of heart rate on wave reflections may be determined by the level of aortic stiffness: clinical and technical implications. Am J Hypertens 21:334–340
Wilkinson IB, Mohammad NH, Tyrrell S et al (2002) Heart rate dependency of pulse pressure amplification and arterial stiffness. Am J Hypertens 15:24–30
Roman MJ, Devereux RB, Kizer JR, Lee ET, Galloway JM, Ali T, Umans JG, Howard BV (2007) Central pressure more strongly relates to vascular disease and outcome than does brachial pressure: the Strong Heart Study. Hypertension 50:197–203
Laurent S, Boutouyrie P (2007) Recent advances in arterial stiffness and wave reflection in human hypertension. Hypertension 49:1202–1206
Ceravolo R, Maio R, Pujia A, Sciacqua A, Ventura G, Costa MC, Sesti G, Perticone F (2003) Pulse pressure and endothelial dysfunction in never-treated hypertensive patients. J Am Coll Cardiol 41:1753–1758
Vane JR, Anggard EE, Botting RM (1990) Regulatory functions of the vascular endothelium. N Engl J Med 323:27–36
Lüscher TF, Vanhoutte PM (1990) The endothelium: modulator of cardiovascular function. CRC Press, Boca Raton
Ross R (1998) Atherosclerosis—an inflammatory disease. N Engl J Med 334:1349–1357
Suwaidi JA, Hamasaki S, Higano ST, Nishimura RA, Olmes DR Jr, Lerman A (2000) Long-term follow-up of patients with mild coronary artery disease and endothelial dysfunction. Circulation 101:948–954
Schächinger V, Britten MB, Zeiher AM (2000) Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease. Circulation 101:1899–1906
Perticone F, Ceravolo R, Pujia A et al (2001) Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 104:191–196
Panza JA, Quyyumi AA, Brush JE, Epstein SE (1990) Abnormal endothelium-dependent vascular relaxation in patients with essential hypertension. N Engl J Med 323:22–27
Creager MA, Cooke JP, Mendelsohn ME et al (1990) Impaired vasodilation of forearm resistance vessel in hypercholesterolemic humans. J Clin Invest 86:228–234
Johnstone MT, Creager SJ, Scales KM, Cusco JA, Lee BK, Creager MA (1993) Impaired endothelium-dependent coronary arterial vasodilation in patients with insulin-dependent diabetes mellitus. Circulation 88:2510–2516
Zeiher AM, Schächinger V, Minners J (1995) Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilation function. Circulation 92:1094–1100
Quyyumj AA (1998) Endothelial function in health and disease: new insights into the genesis of cardiovascular disease. Am J Med 105:32S–39S
Chambers JC, Ueland PM, Wright M, Doré CJ, Refsum H, Kooner JS (2001) Investigation of relationship between reduced, oxidized, and protein-bound homocysteine and vascular endothelial function in healthy human subjects. Circ Res 89:187–192
Lewis TV, Dart AM, Chin-Dusting JPF (1999) Endothelium-dependent relaxation by acetylcholine is impaired in hypertriglyceridemic humans with normal levels of plasma LDL-cholesterol. J Am Coll Cardiol 33:805–812
Guidelines for the Management of Arterial Hypertension (2007) The Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens 25:1105–1187
Millasseau SC, Patel SJ, Redwood SR, Ritter JM, Chowienczyk PJ (2003) Pressure wave reflection assessed from the peripheral pulse: is a transfer function necessary? Hypertension 41:1016–1020
Chen CH, Ting CT, Nussbacher A et al (1996) Validation of carotid artery tonometry as a means of estimating augmentation index of ascending aortic pressure. Hypertension 27:168–175
Kelly RP, Hayward CS, Ganis J, Daley J, Avolio A, O’Rourke M (1989) Non-invasive registration of the arterial pressure pulse waveform using high-fidelity applanation tonometry. J Vasc Med Biol 1:142–149
Williams B, Lacy PS, Thom SM et al (2006) CAFE Investigators; Anglo-Scandinavian Cardiac Outcomes Trial Investigators; CAFE Steering Committee and Writing Committee. Differential impact of blood pressure–lowering drugs on central aortic pressure and clinical outcomes: principal results of the conduit artery function evaluation (CAFE) Study. Circulation 113:1213–1225
Avolio AP, Van Bortel LM, Boutouyrie P et al (2009) Role of pulse pressure amplification in arterial hypertension. Hypertension 54:375–383
Green D, Cheetham C, Henderson C, Weerasooriya R, O’Driscoll G (2002) Effect of cardiac pacing on forearm vascular responses and nitric oxide function. Am J Physiol Heart Circ Physiol 283:H1354–H1360
McEniery CM, Wallace S, Mackenzie IS, Mc Donnell B, Yasmin Newby DE, Cockcroft JR, Wilkinson IB (2006) Endothelial function is associated with pulse pressure, pulse wave velocity, and augmentation index in healthy humans. Hypertension 48:602–608
Wallace SML, Yasmin McEniery CM et al (2007) Isolated systolic hypertension is characterized by increased aortic stiffness and endothelial dysfunction. Hypertension 50:228–233
Ziegler T, Bouzourene K, Harrison VJ, Brunner HR, Hayoz D (1998) Influence of oscillatory and unidirectional flow environments on the expression of endothelin and nitric oxide synthase in cultured endothelial cells. Arterioscler Thromb Vasc Biol 18:686–692
Drexler H, Zeiher AM, Wollschlanger H, Meinertz T, Just H, Bonzel T (1989) Flow-dependent coronary artery dilation in humans. Circulation 80:466–474
Sorensen KE, Celermajer DS, Gooch VM et al (1992) Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 340:1111–1115
De Keulenaer GW, Chappell DC, Ishizaka N et al (1998) Oscillatory and steady laminar shear stress differentially affect human endothelial redox state: role of a superoxide producing NADH oxidase. Circ Res 82:1094–1101
Fyhrquist F, Dahlof B, Devereux RB et al (2005) LIFE Study Group. Pulse pressure and effects of losartan or atenolol in patients with hypertension and left ventricular hypertrophy. Hypertension 45:580–585
Roman MJ, Pickering TG, Pini R, Schwartz JE, Devereux RB (1995) Prevalence and determinants of cardiac and vascular hypertrophy in hypertension. Hypertension 26:369–373
Perticone F, Maio R, Ceravolo R, Cosco C, Cloro C, Mattioli PL (1999) Relationship between left ventricular mass and endothelium-dependent vasodilation in never-treated hypertensive patients. Circulation 99:1991–1996
Conflict of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Maio, R., Miceli, S., Sciacqua, A. et al. Heart rate affects endothelial function in essential hypertension. Intern Emerg Med 8, 211–219 (2013). https://doi.org/10.1007/s11739-011-0618-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11739-011-0618-3