Association of Selected Risk Factors with the Severity of Atherosclerotic Disease at the Carotid Bifurcation

Czech version

Authors: D. Václavík ¹; D. Školoudík ²; O. Škoda ³; P. Praks ⁴; K. Axmanová ¹; I. Vlachová ⁵
Authors‘ workplace: Neurologické oddělení, Vítkovická nemocnice a. s., Ostrava ¹; Neurologická klinika FNsP Ostrava-Poruba ²; Neurologické oddělení, Nemocnice Pelhřimov ³; Katedra matematiky VŠB-TU Ostrava ⁴; Neurologická klinika LF UP a FN Olomouc ⁵
Published in: Cesk Slov Neurol N 2008; 71/104(3): 285-292
Category: Original Paper

Overview

In addition to standard risk factors of atherosclerosis such as cholesterol, arterial hypertension, smoking and diabetes mellitus, also the role of other risk factors in the development of atherosclerosis has been studied in recent years. The goal of the study was to find the differences between the levels of apolipoprotein B, homocysteine, hypersensitive CRP and lipoprotein(a) in patients with initial atherosclerotic affection of the carotid arteries in the presence of atherosclerotic plaques only, and in patients with significant carotid artery disease, with internal carotid stenosis exceeding 50 %.

Study material:
Group 1 consisted of 92 patients with atherosclerotic plaque in carotid arteries without the presence of arterial stenosis. Group 2 consisted of 77 patients with carotid artery stenosis exceeding 50 %. Ultrasound examination was used to ascertain the degree of affection of the carotid arteries.

Method:
Samples for the above factors were taken in both groups and compared between each other with linear regressive analysis being performed at the next stage in order to assess the dependence on standard risk factors.

Results:
The groups were compared using the Mann-Whitney (Wilcoxon) W test. Significantly higher levels of hypersensitive GRP (p = 0.026) and apolipoprotein B (p = 0.00063) were found in Group 2. Subsequent linear regressive analysis performed with the use of the general linear model and evaluation using the ANOVA test showed the independence of both apolipoprotein B and hypersensitive CRP from standard risk factors (arterial hypertension, age, smoking, and diabetes mellitus).

Conclusion:
In our study, apolipoprotein B and hypersensitive CRP was significantly higher in patients with carotid artery stenosis as compared with patients who had atherosclerotic plaques only in their carotid arteries, without the presence of stenosis.

Key words:
carotid arteries – atherosclerotic plaque – homocysteine – hypersensitive CRP – apolipoprotein B – lipoprotein(a)

Sources

1. Fruchart JCH, Melchior CN, Stroes ESG, Kastelein JJP, Duriez P. New Risk Factors for Atherosclerosis and Patient Risk Assessment. in Atherosclerosis. Evolving Vascular Biology and Clinical Implications. Circulation 2004; 109(23): 15–19.

2. Inzitari D, Eliasziw M, Gates P, Sharpe BL, Chan RK, Meldrum HE et al. The causes and risk of stroke in patients whith asymptomatic internal-carotid-artery stenosis. North American Symptomatic Caroditd Endarterectomy Trial Collaborators. N Engl J Med 2000; 342(23): 1693–1700.

3. Bock RW, Gray-Weale AC, Mock PA, App Stats M, Robinson DA, Irwing L et al. The natural history of asymptomatic carotid artery disease. J Vasc Surg 1993; 17(1): 160–171.

4. Risk of stroke in the distribution of an asymptomatic carotid artery. The European Carotid Surgery Trialist Collaborative group. Lancet 1995; 345: 209–212.

5. Endarerectomy for Asymptomatic carotid stenosis. Interim results from the MRC European Carotid Surgery Trial. Lancet 1996; 347: 1591–1593.

6. Barnett HJM, Taylor DW, Eliasziw M, Fox AJ, Fergusson GG, Haynes RB et al. Benefit of carotid endarerectomy in patients whit symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarerectomy Trial Collaborators. N Engl J Med 1998; 339(20): 1415–1425.

7. Selhub J. Homocysteine metabolismus. Annu Rev Nutr 1999; 19: 217–246

8. Guilland LC, Favier A, Potier de Courcy G, Galan P, Hercberg S. Hyperhomocysteinemia: an independent risk factor or a simple marker of vascular disease? 1. Basic data. Pathol Biol 2003; 51: 101–110.

9. Selhub J, Jacques FP, Bostom AG, Ralph B, D'Agostino, Wilson PWF et al. Association between Plasma Homocysteine Concentrations and Extracranial Carotid-Artery Stenosis. N Engl J Med 1995; 332(5): 286–291.

10. Lupattelli G, Rufini S, Locati EH, Lombardini R, Ciuffetti G, Siepi D et al. Hyperhomocyst(e)inemia is associated with carotid atherosclerosis. Angiology 1999; 50(10): 823-830.

11. Robertson J, Iemolo F, Stabler SP, Allen RH, Spence JD. Vitamin B12, homocysteine and carotid plaque in the era of folic acid fortification of enriched cereal grain products. CMAJ 2005; 172(12): 1569–1573.

12. Sasaki T, Watanabe M, Nagai Z, Hoshi T, Takasawa M, Nukata M et al. Association of Plasma Homocysteine Concentration With Atherosclerotic Carotid Plaques and Lacunar Infarction. Stroke 2002; 33(6): 1493–1496.

13. Wang HL, Fan DS, Shen Y, Sun AP, Zhang J, Yang YJ. The relationship between carotid artery atherosclerosis and hyperhomocysteinaemia. Zhonghua Nei Ke Za Zhi 2005; 44(4): 258–261.

14. Mueller T, Furtmueller B, Aigelsdorfer J, Luft C, Poelz W, Haltmayer M. Total serum homocysteine--a predictor of extracranial carotid artery stenosis in male patients with symptomatic peripheral arterial disease. Vasc Med 2001; 6(3): 163–167.

15. Toole TJF, Malinow MR, Chambless LE, Spence JD, Pettigrew LC, Howard WJ et al. Lowering Homocysteine in Patients With Ischemic Stroke to Prevent Recurrent Stroke, Myocardial Infarction, and Death The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled. JAMA 2004; 291(5): 565–575.

16. Dusitanond P, Eikelboom JW, Hankey GJ, Thom J, Gilmore G, Loh K et al. Homocysteine-lowering treatment with folic acid, cobalamin, and pyridoxine does not reduce blood markers of inflammation, endothelial dysfunction, or hypercoagulability in patients with previous transient ischemic attack or stroke: a randomized substudy of the VITATOPS trial. Stroke. 2005; 36(1): 144–146.

17. Vaverková H, Soska V, Rosolová H, Ceska R, Cífková R, Freiberger T et al. Czech Atherosclerosis Society Guidelines for the diagnosis and treatment of dyslipidemias in adults.Vnitr Lek 2007; 53(2): 181–193.

18. Meer IM, Moniek PM, Hak AE, Kiliaan AJ, Sol AI, Van Der Kuip DA et al. C-reactive Protein Predicts Progression of Atherosclerosis Measured at Various Sites in the Arterial Tree. The Rotterdam Study. Stroke 2002; 33(12): 2750–2757.

19. Magyar MT, Szikszai Z, Balla J, Valikovics A, Kappelmayer J, Imre S et al. Early-Onset Carotid Atherosclerosis Is Associated With Increased Intima-Media Thickness and Elevated Serum Levels of Inflammatory Markers. Stroke 2003; 34(1): 58–63.

20. Napoli MD, Schwaninger M, Cappelli R, Ceccarelli E, Gianfilippo GD, Donati C et al. Evaluation of C-Reactive Protein Measurement for Assessing the Risk and Prognosis in Ischemic Stroke. Stroke 2005; 36(6): 1316–1329.

21. Dvořáková A, Poledne R. Ultrasenzitivně měřený C-reaktivní protein – nový parametr kardiovaskulárního rizika. Vnitř lék 2004; 50(11): 852–857.

22. Kazmierski R, Podsiadly E, Tylewska-Wierzbanowska S, Kozubski W. Association between carotid atherosclerosis, inflammatory markers and Chlamydia pneumoniae infection. Neurol Neurochir Pol 2005; 39(4): 277–286.

23. Benbir G, Bozluolcay M, Ince B. Is the level of C-reactive protein correlated with the extent of carotid atherosclerosis? Acta Neurol Belg 2005; 105(2): 73–80.

24. Del Rincón I, Williams K, Stern MP, Freeman GL, O'Leary DH, Escalante A. Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects. Arthritis Rheum 2003; 48(7): 1833–1840.

25. Blackburn R, Giral P, Bruckert E, André JM, Gonbert S, Bernard M et al. Elevated C – reactive protein constitutes an independent predictor of advanced karotid plaques in dyslipidemic subjects. Arterioscler Tromb Vasc Biol 2001; 21(12): 1962–1968.

26. Schillinger M, Exner M, Mlekusch W, Sabeti S, Amighi J, Nikowitsch R et al. Inflammation and Carotid Artery-Risk for Atherosclerosis Study (ICARAS). Circulation 2005; 111(17): 2203–2209.

27. Vlachová I, Herzig R, Vaverková H, Novotný D, Krcová V, Bártková A et al. Prediktivní hodnota ultrasenzitivního C-reaktivního proteinu u cévní mozkové příhody a jeho vztah k ateroskleróze karotid. Cesk Slov Neurol N 2007; 70/103(1): 49–55.

28. Sniderman AD, Scantlebury T, Cianflone K. Hypertriglyceridemic HyperapoB: The Unappreciated Atherogenic Dyslipoproteinemia in Type 2 Diabetes Mellitus. Ann Intern Med 2001; 135(6): 447–459.

29. Williams K, Sniderman AD, Sattar, D’Agostino, Wagenknecht LE, Haffner SM. Comparison of the Associations of Apolipoprotein B and Low-Density Lipoprotein Cholesterol With Other Cardiovascular Risk Factors in the Insulin Resistance Atherosclerosis Study (IRAS). Circulation 2003; 108(19): 2312–2316.

30. Wallenfeldt K, Bokemark L, Wikstrand J, Hulthe J, Fagerberg B. Apolipoprotein B/apolipoprotein A-I in relation to the metabolic syndrome and change in carotid artery intima-media thickness during 3 years in middle-aged men. Stroke 2004; 35(10): 2248–2255.

31. Stewart BF, Brown BG, Zhao XQ, Hillger LA, Sniderman AD, Dowdy A et al. Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol. J Am Coll Cardiol 1994; 23: 899–906.

32. Pedersen TR, Olsson AG, Faergeman O, Kjekshus J, Wedel H, Berg K et al. Lipoprotein changes and reduction in the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 1998; 97(15): 1453–1460.

33. Gotto AM Jr, Whitney E, Stein EA, Shapiro DR, Clearfield M, Weis S et al. Relation between baseline and on-treatment lipid parameters and first acute major coronary events in the Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS). Circulation 2000; 101(5): 477–484.

34. Sramek A, Reiber JH, Baak-Pablo R, Sturk A, Rosendaal FR. Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery. J Thromb Haemost 2003; 1(2): 374–379.

35. Wissen S, Smilde T J, Boo TT, Kastelein JJP, Stalenhoef AFH. Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia. Heart 2003; 89(8): 893–896.