Circulating oxidized low-density lipoproteins and arterial elasticity: comparison between men with metabolic syndrome and physically active counterparts

Hanna Pohjantähti-Maaroos, Ari Palomäki, Päivi Kankkunen, Ruth Laitinen, Sari Husgafvel, Kalevi Oksanen, Hanna Pohjantähti-Maaroos, Ari Palomäki, Päivi Kankkunen, Ruth Laitinen, Sari Husgafvel, Kalevi Oksanen

Abstract

Background: Accumulation of oxidized low-density lipoproteins in the intimae of arteries and endothelial dysfunction are key events in the development of atherosclerosis. Patients with metabolic syndrome are at high risk for cardiovascular diseases but the linkage between metabolic syndrome and atherosclerosis is incompletely understood. We studied whether the levels of oxidized LDL and arterial elasticity differ between metabolic syndrome patients and physically active controls.

Methods: 40 men with metabolic syndrome and 40 physically active controls participated in this cross-sectional study. None of the study subjects had been diagnosed with cardiovascular disease. Levels of oxidized LDL were assessed by a two-site ELISA immunoassay. Arterial elasticity was assessed non-invasively by the HDI/PulseWave CR-2000 arterial tonometer.

Results: Levels of oxidized LDL were 89.6 +/- 33.1 U/L for metabolic syndrome subjects and 68.5 +/- 23.6 U/L for controls (p = 0.007). The difference remained significant after adjustment for LDL cholesterol. Large artery elasticity index (C1) was 16.2 +/- 4.1 mL/mmHgx10 for metabolic syndrome subjects and 19.4 +/- 3.7 mL/mmHgx10 for controls (p = 0.001), small artery indices (C2) were 7.0 +/- 3.2 mL/mmHgx100 and 6.5 +/- 2.9 mL/mmHgx100 (NS), respectively.

Conclusions: Subjects with metabolic syndrome had elevated levels of oxidized LDL and reduced large arterial elasticity compared to controls. This finding may partly explain the increased risk for cardiovascular diseases among metabolic syndrome patients.

Trial registration: ClinicalTrials.gov NCT01114763.

Figures

Figure 1
Figure 1
Oxidized LDL. Levels of oxidized LDL (U/L) among metabolic syndrome subjects and controls.
Figure 2
Figure 2
Arterial elasticity. Large (C1, mL/mmHgx10) and small (C2, mL/mmHgx100) arterial elasticity among metabolic syndrome subjects and controls.

References

    1. Sattar N, Gaw A, Scherbakova O, Ford I, O'Reilly D, Haffner S, Isles C, Macfarlane P, Packard C, Shepherd J. Metabolic syndrome with and without C-reactive protein as a predictor of coronary heart disease and diabetes in the West of Scotland coronary prevention study. Circulation. 2003;108:414–419. doi: 10.1161/01.CIR.0000080897.52664.94.
    1. Lakka H-M, Laaksonen D, Lakka T, Niskanen L, Kumpusalo E, Tuomilehto J, Salonen J. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA. 2002;288:2709–2716. doi: 10.1001/jama.288.21.2709.
    1. Steinberg D, Parthasarathy S, Carew T, Khoo J, Witztum J. Beyond cholesterol. Modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915–924. doi: 10.1056/NEJM198901053200122.
    1. Hulthe J, Fagerberg B. Circulating oxidized LDL is associated with subclinical atherosclerosis development and inflammatory cytokines (Air Study) Arterioscler Thromb Vasc Biol. 2002;22:1162–1167. doi: 10.1161/.
    1. Meisinger C, Baumert J, Khuseyinova N, Loewel H, Koenig W. Plasma oxidized low- density lipoprotein, a strong predictor for acute coronary heart disease events in apparently healthy, middle-aged men from the general population. Circulation. 2005;112:651–657. doi: 10.1161/CIRCULATIONAHA.104.529297.
    1. Cohn J. Vascular wall function as a risk marker for cardiovascular disease. J Hypertens. 1999;17:41–44. doi: 10.1097/00004872-199917080-00026.
    1. Boutouyrie P, Tropeano I, Asmar R, Gautier I, Benetos A, Lacolley P, Laurent S. Aortic stiffness is an independent predictor of primary coronary events in hypertensive patients. A longitudinal study. Hypertension. 2002;39:10–15. doi: 10.1161/hy0102.099031.
    1. Meaume S, Benetos A, Henry OF, Rudnichi A, Safar ME. Aortic pulse wave velocity predicts cardiovascular mortality in subjects > 70 years of age. Arterioscler Thromb Vasc Biol. 2001;21:2046–2050. doi: 10.1161/hq1201.100226.
    1. Cohn J, Finkelstein S, McVeigh G, Morgan D, LeMay L, Robinson J, Mock J. Non-invasive pulse wave analysis for the early detection of vascular disease. Hypertension. 1995;26:503–508.
    1. Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III) Final report. Circulation. 2002;106:3143–3421.
    1. Aittasalo M, Miilunpalo S, Suni J. The effectiveness of physical activity counselling in a work-site setting. A randomized controlled trial. Patient Educ Couns. 2004;55:193–202. doi: 10.1016/j.pec.2003.09.003.
    1. Ainsworth B, Haskell W, Whitt M, Irwin M, Swartz A, Strath S, O'Brien W, Basset D, Schmitz K, Emplaincourt P, Jacobs D, Leon A. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc. 2000;32:498–516. doi: 10.1097/00005768-200009001-00009.
    1. Nathan DM, Kuenen J, Borg R, Zheng H, Schoenfeld D, Heine RJ. A1c-Derived Average Glucose Study Group. Translating the A1C assay into estimated average glucose values. Diabetes Care. 2008;31:1473–1478. doi: 10.2337/dc08-0545.
    1. Pai J, Curhan C, Cannuscio C, Rifai N, Ridker P, Rimm E. Stability of novel plasma markers associated with cardiovascular disease: processing within 36 hours of specimen collection. Clin Chem. 2002;48:1781–1784.
    1. Holvoet P, Mertens A, Verhamme P, Bogaerts K, Beyens G, Verhaeghe R, Collen D, Muls E, Van de Werf F. Circulating oxidized LDL is a useful marker for identifying patients with coronary artery disease. Arterioscler Thromb Vasc Biol. 2001;21:844–848. doi: 10.1161/hq1201.100221.
    1. Valle Gottlieb M, da Gruz I, Duarte M, Moresco R, Wiehe M, Schwanke C, Bodanese L. Associations among metabolic syndrome, ischemia, inflammatory, oxidatives, and lipids biomarkers. J Clin Endocrinol Metab. 2010;95:586–591. doi: 10.1210/jc.2009-1592.
    1. Ueba T, Nomura S, Nishikawa T, Kajiwara M, Yamashita K. Circulating oxidized LDL, measured with FOH1a/DLH3 antibody, is associated with metabolic syndrome and the coronary heart disease risk score in healthy Japanese. Atherosclerosis. 2009;203:243–248. doi: 10.1016/j.atherosclerosis.2008.05.048.
    1. Lapointe A, Couillard C, Piche M-E, Weisnagel S, Bergeron J, Nadeau Andre, Lemieux S. Circulating oxidized LDL is associated with parameters of the metabolic syndrome in postmenopausal women. Atherosclerosis. 2007;191:362–368. doi: 10.1016/j.atherosclerosis.2006.03.036.
    1. Holvoet P, Kritchevsky S, Tracy R, Mertens A, Rubin S, Butler J, Goodpaster B, Harris T. The metabolic syndrome, circulating oxidized LDL, and risk of myocardial infarction in well-functioning elderly people in the health, aging, and body composition cohort. Diabetes. 2004;53:1068–1073. doi: 10.2337/diabetes.53.4.1068.
    1. Sigurdardottir V, Fagerberg B, Hulthe J. Circulating oxidized low-density lipoprotein (LDL) is associated with risk factors of the metabolic syndrome and LDL size in clinically healthy 58-year-old men (AIR study) J Intern Med. 2002;252:440–447. doi: 10.1046/j.1365-2796.2002.01054.x.
    1. Sjogren P, Basu S, Rosell M, Silveira A, de Faire U, Vessby B, Hamsten A, Hellenius M-L, Fisher R. Measures of oxidized low-density lipoprotein and oxidative stress are not related and not elevated in otherwise healthy men with the metabolic syndrome. Arterioscler Thromb Vasc Biol. 2005;25:2580–2586. doi: 10.1161/01.ATV.0000190675.08857.3d.
    1. Talmud PJ, Stphens JW, Hawe E, Demissie S, Cupples LA, Hurel SJ, Humphries SE, Ordovas JM. The significant increase in cardiovascular disease risk in APOEepsilon4 carriers is evident only in men who smoke: potential relationship between reduced antioxidant status and ApoE4. Ann Hum Genet. 2005;69:613–622. doi: 10.1111/j.1529-8817.2005.00205.x.
    1. Schroder H, Marrugat J, Fito M, Weinbrenner T, Covas MI. Alcohol consumption is directly associated with circulating oxidized low-density lipoprotein. Free Radic Biol Med. 2006;40:1474–1481. doi: 10.1016/j.freeradbiomed.2005.12.014.
    1. Ziegler S, Schaller G, Mittermayer F, Pleiner J, Mihaly J, Niessner A, Richter B, Steiner- Boeker S, Penak M, Strasser B, Wolz M. Exercise training improves low-density lipoprotein oxidability in untrained subjects with coronary artery disease. Arch Phys Med Rehabil. 2006;87:265–269. doi: 10.1016/j.apmr.2005.09.025.
    1. Hansel B, Giral P, Nobecourt E, Chantepie S, Bruckert E, Chapman M, Kontush A. Metabolic syndrome is associated with elevated oxidative stress and dysfunctional dense high-density lipoprotein particles displaying impaired antioxidative activity. J Clin Endocrinol Metab. 2004;89:4963–4971. doi: 10.1210/jc.2004-0305.
    1. Madamanchi N, Vendrov A, Runge M. Oxidative stress and vascular disease. Arterioscler Thromb Vasc Biol. 2005;25:29–38. doi: 10.1161/01.ATV.0000161050.77646.68.
    1. Sarigianni M, Bekiari E, Tsapas A, Topouridou K, Kaloyianni M, Koliakos G, Paletas K. Effect of glucose and insulin on oxidized low-density lipoprotein phagocytosis by human monocytes: a pilot study. Angiology. 2010. in press .
    1. Lamarche B. Abdominal obesity and its metabolic complications: implications for the risk of ischaemic heart disease. Coron Artery Dis. 1998;9:473–481. doi: 10.1097/00019501-199809080-00002.
    1. Tentolouris N, Papazafiropoulou A, Moyssakis I, Liatis S, Perrea D, Kostakis M, Katsilambros N. Metabolic syndrome is not associated with reduction in aortic distensibility in subjects with type 2 diabetes mellitus. Cardiovasc Diabetol. 2008;7:1. doi: 10.1186/1475-2840-7-1.
    1. Woodman R, Kingwell B, Beilin L, Hamilton S, Dart A, Watts G. Assessment of central and peripheral arterial stiffness. Studies indicating the need to use a combination of techniques. Am J Hypertens. 2005;18:249–260. doi: 10.1016/j.amjhyper.2004.08.038.
    1. Van Bortel L, Duprez D, Starmans-Kool M, Safar M, Giannattasio C, Cockroft J, Kaiser D, Thuillez C. Applications of arterial stiffness, Task Force III: recommendations for user procedures. Am J Hypertens. 2002;15:445–452. doi: 10.1016/S0895-7061(01)02326-3.
    1. Ge JY, Li XL, Zhang HF, Xu Q, Tong M, Wang JG. Elasticity indices of large and small arteries in relation to the metabolic syndrome in Chinese. Am J Hypertens. 2008;21:143–147. doi: 10.1038/ajh.2007.26.
    1. Fjeldstad A, Fjeldstad C, Acree L, Nickel K, Montgomery P, Comp P, Whitsett T, Gardner A. The relationship between arterial elasticity and metabolic syndrome features. Angiology. 2007;58:5–10. doi: 10.1177/0003319706297911.
    1. Kals J, Kampus P, Kals M, Zilmer K, Kullisaar T, Teesalu R, Pulges A, Zilmer M. Impact of oxidative stress on arterial elasticity in patients with atherosclerosis. Am J Hypertens. 2006;19:902–908. doi: 10.1016/j.amjhyper.2006.02.003.
    1. Morishita R, Ishii J, Kusumi Y, Yamada S, Komai N, Ohishi M, Nomura M, Hishida H, Niihashi M, Mitsumata M. Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: potential role of oxidized lipoprotein(a) in the vascular wall. J Atheroscler Thromb. 2009;16:410–418.
    1. Moreau K, Gavin K, Plum A, Seals D. Oxidative stress explains differences in large artery elastic compliance between sedentary and habitually exercising postmenopausal women. Menopause. 2006;13:951–958. doi: 10.1097/01.gme.0000243575.09065.48.
    1. Toikka J, Niemi P, Ahotupa M, Niinikoski H, Viikari J, Rönnemaa T, Hartiala J, Raitakari O. Large-artery elastic properties in young men. Relationships to serum lipoproteins and oxidized low-density lipoproteins. Arterioscler Thromb Vasc Biol. 1999;19:436–441.
    1. Escobedo J, Schargrodsky H, Champagne B, Silva H, Boissonnet C, Vinueza R, Torres M, Hernandez R, Wilson E. Prevalence of the metabolic syndrome in Latin America and its association with sub-clinical carotid atherosclerosis: the CARMELA cross sectional study. Cardiovasc Diabetol. 2009;8:52. doi: 10.1186/1475-2840-8-52.
    1. Glasser S, Arnett D, McVeigh G, Finkelstein S, Bank A, Morgan D, Cohn J. Vascular compliance and cardiovascular disease. A risk factor or a marker? Am J Hypertens. 1997;10:1175–1189. doi: 10.1016/S0895-7061(97)00311-7.
    1. Van Popele N, Grobbee D, Bots M, Asmar R, Topouchian J, Reneman R, Hoeks A, Van der Kuip D, Hofman A, Witteman J. Association between arterial stiffness and atherosclerosis. The Rotterdam study. Stroke. 2001;32:454–460.
    1. Sugawara J, Inoue H, Haysashi K, Yokoi T, Kono I. Effect of low-intensity aerobic exercise training on arterial compliance in postmenopausal women. Hypertens Res. 2004;27:897–901. doi: 10.1291/hypres.27.897.
    1. Miyachi M, Donato A, Yamamoto K, Takahashi K, Gates P, Moreau K, Tanaka H. Greater age-related reductions in central arterial compliance in resistance trained men. Hypertension. 2003;41:130–135. doi: 10.1161/01.HYP.0000047649.62181.88.
    1. Miyachi M, Kawano H, Sugawara J, Takahashi K, Hayashi K, Yamazaki K, Tabata I, Tanaka H. Unfavorable effects of resistance training on central arterial compliance. A randomized intervention study. Circulation. 2004;110:2858–2863. doi: 10.1161/01.CIR.0000146380.08401.99.
    1. Perkins G, Owen A, Swaine L, Wiles J. Relationships between pulse wave velocity and heart rate variability in healthy men with a range of moderate to vigorous physical activity levels. Eur J Appl Physiol. 2006;98:516–523. doi: 10.1007/s00421-006-0303-9.
    1. Plantinga Y, Ghiadoni L, Magagna A, Giannarelli C, Penno G, Pucci L, Taddei S, Del Prato S, Salvetti A. Peripheral wave reflection and endothelial function in untreated essential hypertensive patients with and without metabolic syndrome. J Hypertens. 2008;26:1216–1222. doi: 10.1097/HJH.0b013e3282fa7158.
    1. McVeigh G, Brennan G, Hayes R, Cohn J, Finkelstein S, Johnston D. Vascular abnormalities in non-insulin dependent diabetes mellitus identified by arterial waveform analysis. Am J Med. 1993;95:424–430. doi: 10.1016/0002-9343(93)90313-E.
    1. McVeigh G, Burns D, Finkelstein S, McDonald K, Mock J, Feske W, Carlyle P, Flack J, Grimm R, Cohn J. Reduced vascular compliance as a marker for essential hypertension. Am J Hypertens. 1991;4:245–251.
    1. Leibovitz E, Hazanov N, Zimlichman R, Shargorodsky M, Gavish D. Treatment with atorvastatin improves small artery compliance in patients with severe hypercholesterolemia. Am J Hypertens. 2001;14:1096–1098. doi: 10.1016/S0895-7061(01)02210-5.
    1. Cohn J. ACE inhibition and vascular remodeling of resistance vessels. Vascular compliance and cardiovascular implications. Heart Dis. 2000;2:52–56.
    1. Nashar K, Nguyen J, Jesri A, Morrow J, Egan B. Angiotensin receptor blockade improves arterial distensibility and reduces exercise-induced pressor responses in obese hypertensive patients with the metabolic syndrome. Am J Hypertens. 2004;17:477–482. doi: 10.1016/j.amjhyper.2004.02.015.

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