Published online before print May 24, 2004, doi: 10.1161/01.CIR.0000129304.98566.D8
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2004;109:2885-2889.)
© 2004 American Heart Association, Inc.
Clinical Investigation and Reports |
Determinants of Arterial Nitrate-Mediated Dilatation in Children
Role of Oxidized Low-Density Lipoprotein, Endothelial Function, and Carotid Intima-Media Thickness
From the Department of Clinical Physiology and Turku PET Centre (M.J.J., O.T.R.), Turku University Hospital, and the Research Centre of Applied and Preventive Cardiovascular Medicine (M.J.J.), University of Turku, and the Laboratory of Atherosclerosis Genetics (T.L.), Department of Clinical Chemistry, Centre for Laboratory Medicine, Tampere University Hospital and University of Tampere, Finland.
Correspondence to Mikko J Järvisalo, Turku PET Centre, Turku University Hospital, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland. E-mail mikko.jarvisalo{at}utu.fi
Received December 8, 2003; revision received February 27, 2004; accepted March 4, 2004.
Background— Impaired arterial dilatation response to nitroglycerin has been observed in adults with risk factors for atherosclerosis and in patients with established atherosclerotic disease. This defect parallels changes in vascular endothelial function and may be attributed to increased oxidative stress. Because atherosclerosis begins in childhood, we examined the correlates of nitrate-mediated dilatation (NMD) in children, including brachial artery endothelial function, oxidized LDL, and carotid artery intima-media thickness (IMT).
Methods and Results— Brachial artery flow-mediated endothelium-dependent dilatation (FMD) and nitrate-mediated smooth muscle function, IMT of the carotid bulb, and brachial artery and oxidized LDL were measured in 142 children (mean age, 11 years; range, 8 to 17 years), including 87 healthy children, 41 diabetic children, and 14 children with familial hypercholesterolemia. NMD correlated directly with FMD (r=0.46, P<0.001) and inversely with brachial artery baseline diameter (r=–0.36, P<0.001), age (r=–0.25, P=0.003), body mass index (r=–0.31, P<0.001), diabetes (r=–0.22, P=0.008), oxidized LDL (r=–0.18, P=0.045), and IMT (r=–0.33, P<0.001). In a multivariate regression model, the significant correlates for NMD were FMD response (ß=0.003, P<0.001), brachial artery diameter (ß=–0.03, P=0.01), oxidized LDL (ß=–0.07, P=0.02), and IMT (ß=–0.15, P=0.03).
Conclusions— Reduced endothelial function, increased oxidative stress, and preclinical carotid atherosclerosis are independent determinants of impaired NMD in children. These data thus suggest that primary nitrate tolerance occurs in children at risk for atherosclerosis.
Key Words: arteries • diabetes mellitus • endothelium • nitroglycerin • pediatrics
This article has been cited by other articles:
 |
|
 |
|
  E. M. Urbina, R. V. Williams, B. S. Alpert, R. T. Collins, S. R. Daniels, L. Hayman, M. Jacobson, L. Mahoney, M. Mietus-Snyder, A. Rocchini, et al. Noninvasive Assessment of Subclinical Atherosclerosis in Children and Adolescents: Recommendations for Standard Assessment for Clinical Research: A Scientific Statement From the American Heart Association Hypertension, November 1, 2009; 54(5): 919 - 950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Violi, V. Sanguigni, R. Carnevale, A. Plebani, P. Rossi, A. Finocchi, C. Pignata, D. De Mattia, B. Martire, M. C. Pietrogrande, et al. Hereditary Deficiency of gp91phox Is Associated With Enhanced Arterial Dilatation: Results of a Multicenter Study Circulation, October 20, 2009; 120(16): 1616 - 1622. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. P. van der Zwan, T. Teerlink, J. M. Dekker, R. M. A. Henry, C. D. A. Stehouwer, C. Jakobs, R. J. Heine, and P. G. Scheffer Circulating oxidized LDL: determinants and association with brachial flow-mediated dilation J. Lipid Res., February 1, 2009; 50(2): 342 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Bjarnegard, H. J Arnqvist, T.;r. Lindstro;m, L. Jonasson, and T. Lanne Long-term hyperglycaemia impairs vascular smooth muscle cell function in women with type 1 diabetes mellitus Diabetes and Vascular Disease Research, January 1, 2009; 6(1): 25 - 31. [Abstract] [PDF]
|
|
|
|
 |
|
 F. Martino, L. Loffredo, R. Carnevale, V. Sanguigni, E. Martino, E. Catasca, C. Zanoni, P. Pignatelli, and F. Violi Oxidative Stress Is Associated With Arterial Dysfunction and Enhanced Intima-Media Thickness in Children With Hypercholesterolemia: The Potential Role of Nicotinamide-Adenine Dinucleotide Phosphate Oxidase Pediatrics, September 1, 2008; 122(3): e648 - e655. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Juonala, M. Kahonen, T. Laitinen, N. Hutri-Kahonen, E. Jokinen, L. Taittonen, M. Pietikainen, H. Helenius, J. S.A. Viikari, and O. T. Raitakari Effect of age and sex on carotid intima-media thickness, elasticity and brachial endothelial function in healthy adults: The Cardiovascular Risk in Young Finns Study Eur. Heart J., May 1, 2008; 29(9): 1198 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Fulop, E. Jebelovszki, N. Erdei, T. Szerafin, T. Forster, I. Edes, A. Koller, and Z. Bagi Adaptation of Vasomotor Function of Human Coronary Arterioles to the Simultaneous Presence of Obesity and Hypertension Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2348 - 2354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Haney, L. H. Huffman, C. Bougatsos, M. Freeman, R. D. Steiner, and H. D. Nelson Screening and Treatment for Lipid Disorders in Children and Adolescents: Systematic Evidence Review for the US Preventive Services Task Force Pediatrics, July 1, 2007; 120(1): e189 - e214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kallio, E. Jokinen, O. T. Raitakari, M. Hamalainen, M. Siltala, I. Volanen, T. Kaitosaari, J. Viikari, T. Ronnemaa, and O. Simell Tobacco Smoke Exposure Is Associated With Attenuated Endothelial Function in 11-Year-Old Healthy Children Circulation, June 26, 2007; 115(25): 3205 - 3212. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dalla Pozza, S. Bechtold, W. Bonfig, S. Putzker, R. Kozlik-Feldmann, H. Netz, and H.-P. Schwarz Age of Onset of Type 1 Diabetes in Children and Carotid Intima Medial Thickness J. Clin. Endocrinol. Metab., June 1, 2007; 92(6): 2053 - 2057. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. S. Pena, E. Wiltshire, K. MacKenzie, R. Gent, L. Piotto, C. Hirte, and J. Couper Vascular Endothelial and Smooth Muscle Function Relates to Body Mass Index and Glucose in Obese and Nonobese Children J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4467 - 4471. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Juonala, J. S.A. Viikari, T. Ronnemaa, H. Helenius, L. Taittonen, and O. T. Raitakari Elevated Blood Pressure in Adolescent Boys Predicts Endothelial Dysfunction: The Cardiovascular Risk in Young Finns Study Hypertension, September 1, 2006; 48(3): 424 - 430. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Tsimikas, J. T. Willerson, and P. M. Ridker C-reactive protein and other emerging blood biomarkers to optimize risk stratification of vulnerable patients. J. Am. Coll. Cardiol., April 18, 2006; 47(8 Suppl): C19 - C31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kravariti, K. K. Naka, S. N. Kalantaridou, N. Kazakos, C. S. Katsouras, A. Makrigiannakis, E. A. Paraskevaidis, G. P. Chrousos, A. Tsatsoulis, and L. K. Michalis Predictors of Endothelial Dysfunction in Young Women with Polycystic Ovary Syndrome J. Clin. Endocrinol. Metab., September 1, 2005; 90(9): 5088 - 5095. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Juonala, J. S.A. Viikari, M. Kahonen, L. Taittonen, T. Ronnemaa, T. Laitinen, N. Maki-Torkko, V. Mikkila, L. Rasanen, H. K. Akerblom, et al. Geographic Origin as a Determinant of Carotid Artery Intima-Media Thickness and Brachial Artery Flow-Mediated Dilation: The Cardiovascular Risk in Young Finns Study Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 392 - 398. [Abstract] [Full Text] [PDF]
|
|