The Norwegian Stroke in the Young Study (NOR-SYS): rationale and design

Annette Fromm, Lars Thomassen, Halvor Naess, Rudy Meijer, Geir Egil Eide, Jostein Kråkenes, Christian A Vedeler, Eva Gerdts, Terje H Larsen, Karel K-J Kuiper, Elin Laxdal, David Russell, Turgut Tatlisumak, Ulrike Waje-Andreassen, Annette Fromm, Lars Thomassen, Halvor Naess, Rudy Meijer, Geir Egil Eide, Jostein Kråkenes, Christian A Vedeler, Eva Gerdts, Terje H Larsen, Karel K-J Kuiper, Elin Laxdal, David Russell, Turgut Tatlisumak, Ulrike Waje-Andreassen

Abstract

Background: Ischemic stroke in young adults is a major health problem being associated with a higher vascular morbidity and mortality compared to controls, and a stroke recurrence rate of 25% during the first decade. The assumed cause of infarction and the detected risk factors determine the early- and long-term treatment. However, for many patients the cause of stroke remains unknown. Risk factor profile and etiology differ in young and elderly ischemic stroke patients, and atherosclerosis is the determined underlying condition in 10 to 15%. However, subclinical atherosclerosis is probably more prevalent and may go unrecognized.

Methods/design: NOR-SYS is a prospective long-term research program. Standardized methods are used for anamnestic, clinical, laboratory, imaging, and ultrasound data collection in ischemic stroke patients aged ≤60 years, their partners and joint adult offspring. The ultrasound protocol includes the assessment of intracranial, carotid and femoral arteries, abdominal aorta, and the estimation of VAT. To date, the study is a single centre study with approximately 400 patients, 250 partners and 350 adult offspring expected to be recruited at our site.

Discussion: NOR-SYS aims to increase our knowledge about heredity and the development of arterial vascular disease in young patients with ischemic stroke and their families. Moreover, optimization of diagnostics, prophylaxis and early intervention are major targets with the intention to reduce stroke recurrence and other clinical arterial events, physical disability, cognitive impairment and death.

Trial registration: ClinicalTrials.gov NCT01597453.

Figures

Figure 1
Figure 1
NOR-SYS Assessment chart. RF = Risk factors; CT = Computed tomography; MRI = Magnetic resonance imaging; TCCS = Transcranial color-coded sonography; ABI = Ankle-Brachial Index; ECG = Electrocardiogram; TTE = Transthoracic echocardiography, TEE = Transesophageal echocardiography; 24 h BP = 24 hour blood pressure monitoring; BMI = Body Mass Index.
Figure 2
Figure 2
Ultrasonographic IMT measurement in the proximal ICA (left), the bifurcation (middle) and the distal CCA segment (right) by QLAB software.
Figure 3
Figure 3
Meijer’s Carotid Arc® (publication with written informed consent by the patient).
Figure 4
Figure 4
Ultrasonographic epicardial (left), intraabominal visceral (middle) and abdominal subcutaneous adipose tissue (right) in B-mode ultrasonography.
Figure 5
Figure 5
B-mode ultrasonography and IMT measurement in the distal CFA (left) and the proximal SFA segment (right) performed by QLAB software.

References

    1. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367(9524):1747–1757. doi: 10.1016/S0140-6736(06)68770-9.
    1. Kolominsky-Rabas PL, Weber M, Gefeller O, Neundoerfer B, Heuschmann PU. Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence, recurrence, and long-term survival in ischemic stroke subtypes: a population-based study. Stroke. 2001;32(12):2735–2740. doi: 10.1161/hs1201.100209.
    1. Fromm A, Waje-Andreassen U, Thomassen L, Naess H. Comparison between ischemic stroke patients <50 years and >/=50 years admitted to a single centre: the bergen stroke study. Stroke Res Treat. 2011;2011:183256.
    1. Naess H, Nyland HI, Thomassen L, Aarseth J, Myhr KM. Etiology of and risk factors for cerebral infarction in young adults in western Norway: a population-based case–control study. Eur J Neurol. 2004;11(1):25–30. doi: 10.1046/j.1351-5101.2003.00700.x.
    1. Adams HP Jr, Kappelle LJ, Biller J, Gordon DL, Love BB, Gomez F, Heffner M. Ischemic stroke in young adults. Experience in 329 patients enrolled in the Iowa Registry of stroke in young adults. Arch Neurol. 1995;52(5):491–495. doi: 10.1001/archneur.1995.00540290081021.
    1. Waje-Andreassen U, Naess H, Thomassen L, Eide GE, Vedeler CA. Long-term mortality among young ischemic stroke patients in western Norway. Acta Neurol Scand. 2007;116(3):150–156. doi: 10.1111/j.1600-0404.2007.00822.x.
    1. Waje-Andreassen U, Naess H, Thomassen L, Eide GE, Vedeler CA. Arterial events after ischemic stroke at a young age: a cross-sectional long-term follow-up of patients and controls in western Norway. Cerebrovasc Dis. 2007;24(2–3):277–282.
    1. Naess H, Nyland HI, Thomassen L, Aarseth J, Nyland G, Myhr KM. Incidence and short-term outcome of cerebral infarction in young adults in western Norway. Stroke. 2002;33(8):2105–2108. doi: 10.1161/01.STR.0000023888.43488.10.
    1. Naess H, Nyland HI, Thomassen L, Aarseth J, Myhr KM. Long-term outcome of cerebral infarction in young adults. Acta Neurol Scand. 2004;110(2):107–112. doi: 10.1111/j.1600-0404.2004.00273.x.
    1. Putaala J, Haapaniemi E, Metso AJ, Metso TM, Artto V, Kaste M, Tatlisumak T. Recurrent ischemic events in young adults after first-ever ischemic stroke. Ann Neurol. 2010;68(5):661–671. doi: 10.1002/ana.22091.
    1. Hankey GJ, Jamrozik K, Broadhurst RJ, Forbes S, Anderson CS. Long-term disability after first-ever stroke and related prognostic factors in the Perth community stroke study, 1989–1990. Stroke. 2002;33(4):1034–1040. doi: 10.1161/01.STR.0000012515.66889.24.
    1. Mazighi M, Labreuche J, Gongora-Rivera F, Duyckaerts C, Hauw JJ, Amarenco P. Autopsy prevalence of intracranial atherosclerosis in patients with fatal stroke. Stroke. 2008;39(4):1142–1147. doi: 10.1161/STROKEAHA.107.496513.
    1. Gongora-Rivera F, Labreuche J, Jaramillo A, Steg PG, Hauw JJ, Amarenco P. Autopsy prevalence of coronary atherosclerosis in patients with fatal stroke. Stroke. 2007;38(4):1203–1210. doi: 10.1161/01.STR.0000260091.13729.96.
    1. Macleod MR, Amarenco P, Davis SM, Donnan GA. Atheroma of the aortic arch: an important and poorly recognised factor in the aetiology of stroke. Lancet Neurol. 2004;3(7):408–414. doi: 10.1016/S1474-4422(04)00806-3.
    1. Schiano V, Sirico G, Giugliano G, Laurenzano E, Brevetti L, Perrino C, Brevetti G, Esposito G. Femoral plaque echogenicity and cardiovascular risk in claudicants. JACC Cardiovasc Imaging. 2012;5(4):348–357. doi: 10.1016/j.jcmg.2012.01.011.
    1. Ricotta JJ, Bryan FA, Bond MG, Kurtz A, O’Leary DH, Raines JK, Berson AS, Clouse ME, Calderon-Ortiz M, Toole JF. et al.Multicenter validation study of real-time (B-mode) ultrasound, arteriography, and pathologic examination. J Vasc Surg. 1987;6(5):512–520.
    1. Lorenz MW, Markus HS, Bots ML, Rosvall M, Sitzer M. Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis. Circulation. 2007;115(4):459–467. doi: 10.1161/CIRCULATIONAHA.106.628875.
    1. Salonen JT, Salonen R. Ultrasound B-mode imaging in observational studies of atherosclerotic progression. Circulation. 1993;87(3 Suppl):II56–65.
    1. Bots ML, Hoes AW, Koudstaal PJ, Hofman A, Grobbee DE. Common carotid intima-media thickness and risk of stroke and myocardial infarction: the Rotterdam Study. Circulation. 1997;96(5):1432–1437. doi: 10.1161/01.CIR.96.5.1432.
    1. del Sol AI, Moons KG, Hollander M, Hofman A, Koudstaal PJ, Grobbee DE, Breteler MM, Witteman JC, Bots ML. Is carotid intima-media thickness useful in cardiovascular disease risk assessment? The Rotterdam Study. Stroke. 2001;32(7):1532–1538. doi: 10.1161/01.STR.32.7.1532.
    1. Chambless LE, Folsom AR, Sharrett AR, Sorlie P, Couper D, Szklo M, Nieto FJ. Coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC) study. J Clin Epidemiol. 2003;56(9):880–890. doi: 10.1016/S0895-4356(03)00055-6.
    1. Ebrahim S, Papacosta O, Whincup P, Wannamethee G, Walker M, Nicolaides AN, Dhanjil S, Griffin M, Belcaro G, Rumley A. et al.Carotid plaque, intima media thickness, cardiovascular risk factors, and prevalent cardiovascular disease in men and women: the British Regional Heart Study. Stroke. 1999;30(4):841–850. doi: 10.1161/01.STR.30.4.841.
    1. Joakimsen O, Bonaa KH, Mathiesen EB, Stensland-Bugge E, Arnesen E. Prediction of mortality by ultrasound screening of a general population for carotid stenosis: the Tromso Study. Stroke. 2000;31(8):1871–1876. doi: 10.1161/01.STR.31.8.1871.
    1. Lorenz MW, von Kegler S, Steinmetz H, Markus HS, Sitzer M. Carotid intima-media thickening indicates a higher vascular risk across a wide age range: prospective data from the Carotid Atherosclerosis Progression Study (CAPS) Stroke. 2006;37(1):87–92.
    1. Waje-Andreassen U, Naess H, Thomassen L, Eide GE, Meijer R, Vedeler CA. Ultrasound, atherosclerosis and stroke at a young age: a cross-sectional long-term follow-up in western Norway. Eur J Neurol. 2008;15(5):512–519. doi: 10.1111/j.1468-1331.2008.02118.x.
    1. O’Leary DH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK Jr. Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular health study collaborative research group. N Engl J Med. 1999;340(1):14–22. doi: 10.1056/NEJM199901073400103.
    1. Amarenco P, Lavallee PC, Labreuche J, Ducrocq G, Juliard JM, Feldman L, Cabrejo L, Meseguer E, Guidoux C, Adrai V. et al.Prevalence of coronary atherosclerosis in patients with cerebral infarction. Stroke. 2011;42(1):22–29. doi: 10.1161/STROKEAHA.110.584086.
    1. Polak JF, Person SD, Wei GS, Godreau A, Jacobs DR Jr, Harrington A, Sidney S, O’Leary DH. Segment-specific associations of carotid intima-media thickness with cardiovascular risk factors: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Stroke. 2010;41(1):9–15. doi: 10.1161/STROKEAHA.109.566596.
    1. Den Ruijter HM, Peters SA, Anderson TJ, Britton AR, Dekker JM, Eijkemans MJ, Engstrom G, Evans GW, de Graaf J, Grobbee DE. et al.Common carotid intima-media thickness measurements in cardiovascular risk prediction: a meta-analysis. JAMA. 2012;308(8):796–803. doi: 10.1001/jama.2012.9630.
    1. Dichgans M. Genetics of ischaemic stroke. Lancet Neurol. 2007;6(2):149–161. doi: 10.1016/S1474-4422(07)70028-5.
    1. Logallo N, Lind J, Naess H, Idicula T, Brogger J, Waje-Andreassen U, Thomassen L. Middle cerebral artery stenosis: transcranial color-coded sonography based on continuity equation versus CT-angiography. Germany: Ultraschall in der Medizin; 2012.
    1. de Bray JM, Glatt B. Quantification of atheromatous stenosis in the extracranial internal carotid artery. Cerebrovasc Dis. 1995;5(6):414–426. doi: 10.1159/000107895.
    1. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, Csiba L, Desvarieux M, Ebrahim S, Fatar M. et al.Mannheim carotid intima-media thickness consensus (2004–2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis. 2007;23(1):75–80. doi: 10.1159/000097034.
    1. Mookadam F, Goel R, Alharthi MS, Jiamsripong P, Cha S. Epicardial fat and its association with cardiovascular risk: a cross-sectional observational study. Heart Views. 2010;11(3):103–108. doi: 10.4103/1995-705X.76801.
    1. Iacobellis G, Willens HJ. Echocardiographic epicardial fat: a review of research and clinical applications. J Am Soc Echocardiogr. 2009;22(12):1311–1319. doi: 10.1016/j.echo.2009.10.013. quiz 1417–1318.
    1. Stolk RP, Meijer R, Mali WP, Grobbee DE, van der Graaf Y. Ultrasound measurements of intraabdominal fat estimate the metabolic syndrome better than do measurements of waist circumference. Am J Clin Nutr. 2003;77(4):857–860.
    1. Paivansalo MJ, Merikanto J, Jerkkola T, Savolainen MJ, Rantala AO, Kauma H, Lilja M, Reunanen YA, Kesaniemi A, Suramo I. Effect of hypertension and risk factors on diameters of abdominal aorta and common iliac and femoral arteries in middle-aged hypertensive and control subjects: a cross-sectional systematic study with duplex ultrasound. Atherosclerosis. 2000;153(1):99–106. doi: 10.1016/S0021-9150(00)00374-9.
    1. Norgren L, Hiatt WR, Dormandy JA, Nehler MR, Harris KA, Fowkes FG, Group TIW, Bell K, Caporusso J, Durand-Zaleski I. et al.Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) Eur J Vasc Endovasc Surg. 2007;33(Suppl 1):S1–75.
    1. Weimar C, Diener HC, Alberts MJ, Steg PG, Bhatt DL, Wilson PW, Mas JL, Rother J. Investigators REoAfCHR. The Essen stroke risk score predicts recurrent cardiovascular events: a validation within the REduction of Atherothrombosis for Continued Health (REACH) registry. Stroke. 2009;40(2):350–354. doi: 10.1161/STROKEAHA.108.521419.
    1. Kappelle LJ, Adams HP Jr, Heffner ML, Torner JC, Gomez F, Biller J. Prognosis of young adults with ischemic stroke. A long-term follow-up study assessing recurrent vascular events and functional outcome in the Iowa registry of stroke in young adults. Stroke. 1994;25(7):1360–1365. doi: 10.1161/01.STR.25.7.1360.
    1. Guldiken S, Tuncbilek N, Okten OO, Arikan E, Tugrul A. Visceral fat thickness determined using ultrasonography is associated with anthropometric and clinical parameters of metabolic syndrome. Int J Clin Pract. 2006;60(12):1576–1581. doi: 10.1111/j.1742-1241.2005.00803.x.
    1. De Groot E, Hovingh GK, Zwinderman AH, Wiegman A, Smit AJ, Kastelein JJ. Data density curves of B-mode ultrasound arterial wall thickness measurements in unaffected control and at-risk populations. International angiology : a journal of the International Union of Angiology. 2005;24(4):359–365.
    1. Chambless LE, Heiss G, Folsom AR, Rosamond W, Szklo M, Sharrett AR, Clegg LX. Association of coronary heart disease incidence with carotid arterial wall thickness and major risk factors: the Atherosclerosis Risk in Communities (ARIC) Study, 1987–1993. Am J Epidemiol. 1997;146(6):483–494. doi: 10.1093/oxfordjournals.aje.a009302.
    1. Bots ML, Grobbee DE. Intima media thickness as a surrogate marker for generalised atherosclerosis. Cardiovascular drugs and therapy/sponsored by the International Society of Cardiovascular Pharmacotherapy. 2002;16(4):341–351. doi: 10.1023/A:1021738111273.
    1. Iwakiri T, Yano Y, Sato Y, Hatakeyama K, Marutsuka K, Fujimoto S, Kitamura K, Kario K, Asada Y. Usefulness of carotid intima-media thickness measurement as an indicator of generalized atherosclerosis: findings from autopsy analysis. Atherosclerosis. 2012;225(2):359–362. doi: 10.1016/j.atherosclerosis.2012.10.033.
    1. Chaubey S, Nitsch D, Altmann D, Ebrahim S. Differing effect of modifiable cardiovascular risk factors on intima-media thickening and plaque formation at different sites of the arterial vasculature. Heart. 2010;96(19):1579–1585. doi: 10.1136/hrt.2009.188219.
    1. Tajik P, Meijer R, Duivenvoorden R, Peters SA, Kastelein JJ, Visseren FJ, Crouse JR 3rd, Palmer MK, Raichlen JS, Grobbee DE. et al.Asymmetrical distribution of atherosclerosis in the carotid artery: identical patterns across age, race, and gender. European journal of preventive cardiology. 2012;19(4):687–697. doi: 10.1177/1741826711410821.
    1. Stein JH, Korcarz CE, Hurst RT, Lonn E, Kendall CB, Mohler ER, Najjar SS, Rembold CM, Post WS. American Society of Echocardiography Carotid Intima-Media Thickness Task F. Use of carotid ultrasound to identify subclinical vascular disease and evaluate cardiovascular disease risk: a consensus statement from the american society of echocardiography carotid intima-media thickness task force. Endorsed by the society for vascular medicine. J Am Soc Echocardiogr. 2008;21(2):93–111. doi: 10.1016/j.echo.2007.11.011. quiz 189–190.
    1. Ziegelbauer K, Schaefer C, Steinmetz H, Sitzer M, Lorenz MW. Clinical usefulness of carotid ultrasound to improve stroke risk assessment: ten-year results from the Carotid Atherosclerosis Progression Study (CAPS) European journal of preventive cardiology. 2012. Epub ahead of print.
    1. Inaba Y, Chen JA, Bergmann SR. Carotid plaque, compared with carotid intima-media thickness, more accurately predicts coronary artery disease events: a meta-analysis. Atherosclerosis. 2012;220(1):128–133. doi: 10.1016/j.atherosclerosis.2011.06.044.
    1. Jensen SA, Vatten LJ, Romundstad PR, Myhre HO. The prevalence of intermittent claudication. Sex-related differences have been eliminated. Eur J Vasc Endovasc Surg. 2003;25(3):209–212. doi: 10.1053/ejvs.2002.1836.
    1. Fowkes FG, Housley E, Cawood EH, Macintyre CC, Ruckley CV, Prescott RJ. Edinburgh Artery Study: prevalence of asymptomatic and symptomatic peripheral arterial disease in the general population. Int J Epidemiol. 1991;20(2):384–392. doi: 10.1093/ije/20.2.384.
    1. Pedersen G, Laxdal E, Hagala M, Aune S. The impact of comorbidity on long-term results of above-knee prosthetic femoropopliteal bypass for intermittent claudication. International angiology : a journal of the International Union of Angiology. 2005;24(3):245–249.
    1. Smith GD, Shipley MJ, Rose G. Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study. Circulation. 1990;82(6):1925–1931. doi: 10.1161/01.CIR.82.6.1925.
    1. Rothwell PM, Coull AJ, Silver LE, Fairhead JF, Giles MF, Lovelock CE, Redgrave JN, Bull LM, Welch SJ, Cuthbertson FC. et al.Population-based study of event-rate, incidence, case fatality, and mortality for all acute vascular events in all arterial territories (Oxford Vascular Study) Lancet. 2005;366(9499):1773–1783. doi: 10.1016/S0140-6736(05)67702-1.
    1. De Groot E, Jukema JW, van Swijndregt AD M, Zwinderman AH, Ackerstaff RG, van der Steen AF, Bom N, Lie KI, Bruschke AV. B-mode ultrasound assessment of pravastatin treatment effect on carotid and femoral artery walls and its correlations with coronary arteriographic findings: a report of the Regression Growth Evaluation Statin Study (REGRESS) J Am Coll Cardiol. 1998;31(7):1561–1567. doi: 10.1016/S0735-1097(98)00170-3.
    1. van Boven AJ, Jukema JW, Zwinderman AH, Crijns HJ, Lie KI, Bruschke AV. Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. REGRESS Study Group. Circulation. 1996;94(7):1503–1505. doi: 10.1161/01.CIR.94.7.1503.
    1. Steinmetz EF, Buckley C, Thompson RW. Prospects for the medical management of abdominal aortic aneurysms. Vasc Endovascular Surg. 2003;37(3):151–163. doi: 10.1177/153857440303700301.
    1. Kurvers HA, van der Graaf Y, Blankensteijn JD, Visseren FL, Eikelboom B. SS Group. Screening for asymptomatic internal carotid artery stenosis and aneurysm of the abdominal aorta: comparing the yield between patients with manifest atherosclerosis and patients with risk factors for atherosclerosis only. J Vasc Surg. 2003;37(6):1226–1233. doi: 10.1016/S0741-5214(02)75140-9.
    1. Newman AB, Siscovick DS, Manolio TA, Polak J, Fried LP, Borhani NO, Wolfson SK. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. Circulation. 1993;88(3):837–845. doi: 10.1161/01.CIR.88.3.837.
    1. Banerjee A, Fowkes FG, Rothwell PM. Associations between peripheral artery disease and ischemic stroke: implications for primary and secondary prevention. Stroke. 2010;41(9):2102–2107. doi: 10.1161/STROKEAHA.110.582627.
    1. Gerdts E, Cramariuc D, de Simone G, Wachtell K, Dahlof B, Devereux RB. Impact of left ventricular geometry on prognosis in hypertensive patients with left ventricular hypertrophy (the LIFE study) European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology. 2008;9(6):809–815. doi: 10.1093/ejechocard/jen155.
    1. Devereux RB, Pickering TG. Relationship between ambulatory or exercise blood pressure and left ventricular structure: prognostic implications. Journal of hypertension Supplement : official journal of the International Society of Hypertension. 1990;8(6):S125–134.
    1. Van Bortel LM, Laurent S, Boutouyrie P, Chowienczyk P, Cruickshank JK, De Backer T, Filipovsky J, Huybrechts S, Mattace-Raso FU, Protogerou AD. et al.Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity. J Hypertens. 2012;30(3):445–448. doi: 10.1097/HJH.0b013e32834fa8b0.
    1. Dormandy J, Heeck L, Vig S. Lower-extremity arteriosclerosis as a reflection of a systemic process: implications for concomitant coronary and carotid disease. Semin Vasc Surg. 1999;12(2):118–122.
    1. Sen S, Hinderliter A, Sen PK, Simmons J, Beck J, Offenbacher S, Ohman EM, Oppenheimer SM. Aortic arch atheroma progression and recurrent vascular events in patients with stroke or transient ischemic attack. Circulation. 2007;116(8):928–935. doi: 10.1161/CIRCULATIONAHA.106.671727.
    1. Vasan RS, Pencina MJ, Cobain M, Freiberg MS, D’Agostino RB. Estimated risks for developing obesity in the Framingham Heart Study. Ann Intern Med. 2005;143(7):473–480. doi: 10.7326/0003-4819-143-7-200510040-00005.
    1. Dulloo AG, Montani JP. Body composition, inflammation and thermogenesis in pathways to obesity and the metabolic syndrome: an overview. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2012;13(Suppl 2):1–5.
    1. Lakka TA, Lakka HM, Salonen R, Kaplan GA, Salonen JT. Abdominal obesity is associated with accelerated progression of carotid atherosclerosis in men. Atherosclerosis. 2001;154(2):497–504. doi: 10.1016/S0021-9150(00)00514-1.
    1. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss. Arterioscler Thromb Vasc Biol. 2006;26(5):968–976. doi: 10.1161/01.ATV.0000216787.85457.f3.
    1. Ho E, Shimada Y. Formation of the epicardium studied with the scanning electron microscope. Dev Biol. 1978;66(2):579–585. doi: 10.1016/0012-1606(78)90263-4.
    1. Iacobellis G, Leonetti F, Di Mario U. Images in cardiology: Massive epicardial adipose tissue indicating severe visceral obesity. Clin Cardiol. 2003;26(5):237. doi: 10.1002/clc.4960260508.
    1. Liu KH, Chan YL, Chan JC, Chan WB. Association of carotid intima-media thickness with mesenteric, preperitoneal and subcutaneous fat thickness. Atherosclerosis. 2005;179(2):299–304. doi: 10.1016/j.atherosclerosis.2004.10.038.
    1. Iacobellis G, Ribaudo MC, Assael F, Vecci E, Tiberti C, Zappaterreno A, Di Mario U, Leonetti F. Echocardiographic epicardial adipose tissue is related to anthropometric and clinical parameters of metabolic syndrome: a new indicator of cardiovascular risk. J Clin Endocrinol Metab. 2003;88(11):5163–5168. doi: 10.1210/jc.2003-030698.
    1. Rexrode KM, Buring JE, Manson JE. Abdominal and total adiposity and risk of coronary heart disease in men. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 2001;25(7):1047–1056. doi: 10.1038/sj.ijo.0801615.
    1. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P, Lang CC, Rumboldt Z, Onen CL, Lisheng L. et al.Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case–control study. Lancet. 2005;366(9497):1640–1649. doi: 10.1016/S0140-6736(05)67663-5.
    1. Fox CS, Massaro JM, Hoffmann U, Pou KM, Maurovich-Horvat P, Liu CY, Vasan RS, Murabito JM, Meigs JB, Cupples LA. et al.Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation. 2007;116(1):39–48. doi: 10.1161/CIRCULATIONAHA.106.675355.
    1. Schaffer JE. Lipotoxicity: when tissues overeat. Curr Opin Lipidol. 2003;14(3):281–287. doi: 10.1097/00041433-200306000-00008.
    1. Montague CT, O’Rahilly S. The perils of portliness: causes and consequences of visceral adiposity. Diabetes. 2000;49(6):883–888. doi: 10.2337/diabetes.49.6.883.
    1. Bastard JP, Maachi M, Lagathu C, Kim MJ, Caron M, Vidal H, Capeau J, Feve B. Recent advances in the relationship between obesity, inflammation, and insulin resistance. Eur Cytokine Netw. 2006;17(1):4–12.
    1. Arcaro G, Zamboni M, Rossi L, Turcato E, Covi G, Armellini F, Bosello O, Lechi A. Body fat distribution predicts the degree of endothelial dysfunction in uncomplicated obesity. International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity. 1999;23(9):936–942. doi: 10.1038/sj.ijo.0801022.
    1. DHHS N-N, NIH NIH, editor. Health NIo. Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults: Evidence Report. Bethesda MD: Publication. No. 98–4083; 1998.
    1. Sacks HS, Fain JN. Human epicardial adipose tissue: a review. Am Heart J. 2007;153(6):907–917. doi: 10.1016/j.ahj.2007.03.019.
    1. Corradi D, Maestri R, Callegari S, Pastori P, Goldoni M, Luong TV, Bordi C. The ventricular epicardial fat is related to the myocardial mass in normal, ischemic and hypertrophic hearts. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. 2004;13(6):313–316. doi: 10.1016/j.carpath.2004.08.005.
    1. Iacobellis G, Bianco AC. Epicardial adipose tissue: emerging physiological, pathophysiological and clinical features. Trends in endocrinology and metabolism: TEM. 2011;22(11):450–457. doi: 10.1016/j.tem.2011.07.003.
    1. Gabriely I, Ma XH, Yang XM, Atzmon G, Rajala MW, Berg AH, Scherer P, Rossetti L, Barzilai N. Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: an adipokine-mediated process? Diabetes. 2002;51(10):2951–2958. doi: 10.2337/diabetes.51.10.2951.
    1. Roopakala MS, Suresh A, Ashtalakshmi, Srinath, Ashok, Giridhar, Anand, Silvia WD. Anthropometric measurements as predictors of intraabdominal fat thickness. Indian J Physiol Pharmacol. 2009;53(3):259–264.

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel