The Southern Medical Journal (SMJ) is the official, peer-reviewed journal of the Southern Medical Association. It has a multidisciplinary and inter-professional focus that covers a broad range of topics relevant to physicians and other healthcare specialists.

SMJ // Article

Original Article

Determinants of Plasma Homocysteine in Relation to Hematological and Biochemical Variables in Patients with Acute Myocardial Infarction

Authors: Rajaa Marouf, FRCPath, Mohammad Zubaid, FRCPC, Olusegun A. Mojiminiyi, FRCPath, Mohammad Qurtom, FRCPI, Nabila A. Abdella, FRCP, Hanan Al Wazzan, MRCPath, Salah Al Humood, FRCPC

Abstract

Background: Elevated plasma total homocysteine (tHcy) is a risk factor for coronary artery disease (CAD), but the mechanism is not known. This study evaluates the determinants and associations of tHcy in patients presenting with acute myocardial infarction (AMI).


Methods: Plasma concentration of tHcy, protein C, protein S, and antithrombin were measured in 210 (177 males and 33 females) patients with first AMI and 167 (87 males and 80 females) controls. Serum vitamin B12, folate, creatinine, lipid profile, fasting glucose, full blood count and red cell folate were determined. Creatinine clearance was calculated using the modification of diet in renal disease formula. Univariate and multivariate analyses were used to determine the associations of tHcy.


Results: Mean tHcy was higher in male than female patients. On logistic regression analysis, the most important determinants of tHcy in the patients were age, creatinine, creatinine clearance, vitamin B12 and red cell folate. When study patients were compared with the controls, tHcy, fasting glucose and serum creatinine were significantly higher, while creatinine clearance and HDL cholesterol were significantly lower in the study patients. Logistic regression analysis showed significant association of tHcy with AMI, odds ratio = 1.39, in the presence of other confounding factors.


Conclusions: Our results show that tHcy is a significant risk factor for CAD in our patient population. The determinants in the patients are age, glomerular filtration rate and the status of vitamins B12 and folate. The above determinants should be kept in mind when using tHcy as a risk factor for CAD.


Key Points


* The most significant determinants of plasma homocysteine were gender, age, markers of glomerular filtration rate and vitamins B12 and folate.


* Plasma total homocysteine is a significant risk factor for coronary artery disease in the presence of other traditional and nontraditional risk factors.


* The determinants of plasma total homocysteine should be considered when evaluating cardiovascular disease risk.

This content is limited to qualifying members.

Existing members, please login first

If you have an existing account please login now to access this article or view purchase options.

Purchase only this article ($25)

Create a free account, then purchase this article to download or access it online for 24 hours.

Purchase an SMJ online subscription ($75)

Create a free account, then purchase a subscription to get complete access to all articles for a full year.

Purchase a membership plan (fees vary)

Premium members can access all articles plus recieve many more benefits. View all membership plans and benefit packages.

References

1. Fox KA, Birkhead J, Wilcox R, et al. British Cardiac Society Working Group on the definition of myocardial infarction. Heart 2004;90:603–609.
 
2. Abdella NA, Mojiminiyi OA, Akanji AO, et al. Associations of plasma homocysteine concentration in subjects with type 2 diabetes mellitus. Acta Diabetol 2002;39:183–190.
 
3. Booth GL, Wang EE. Preventive health care, 2000 update: screening and management of hyperhomocystinemia for the prevention of coronary artery disease events: the Canadian Task Force on Preventive Health Care. CMAJ 2000;163:21–29.
 
4. Dahlback B, Carlsson M, Svensson PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Nat Acad Sci U S A 1993;90:1004–1008.
 
5. Bertina RM, Koeleman BP, Koster T, et al. Mutation in the blood coagulation factor V associated with resistance to activated protein C. Nature 1994;369:64–67.
 
6. Cumming AM, Shiach CR. The investigation and management of inherited thrombophilia. Clin Lab Haematol 1999;21:77–92.
 
7. Marangon K, O’Byrne D, Devaraj S, et al. Validation of an immunoassay for measurement of plasma total homocysteine. Am J Clin Pathol 1999;112:757–762.
 
8. Collection, Transport and Preparation of Blood Specimens for Coagulation Testing and Performance of Coagulation Assays. NCCLS Document H21-A2 1991; Vol 11, No. 23.
 
9. Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997;337:230–236.
 
10. Levey AS, Bosch JP, Lewis JB, et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation: Modification of Diet in Renal Disease Study Group.Ann Intern Med 1999;130:461–470.
 
11. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972;18:499–502.
 
12. Graham IM, Daly LE, Refsum HM, et al. Plasma homocysteine as a risk factor for vascular disease: the European Concerted Action Project. JAMA 1997;277:1775–1781.
 
13. Hacker SM, Williamson BD, Lisco S, et al. Protein C deficiency and acute myocardial infarction in the third decade. Am J Cardiol 1991;68:137–138.
 
14. Kario K, Matsuo T, Tai S, et al. Congenital protein C deficiency and myocardial infarction: concomitant factor VII hyperactivity may play a role in the onset of arterial thrombosis. Thromb Res1992;67:95–103.
 
15. Rodgers GM, Conn MT. Homocysteine, an atherogenic stimulus, reduces protein C activation by arterial and venous endothelial cells. Blood 1990;75:895–901.
 
16. Bick RL, Baker WF. Antiphospholipid syndrome and thrombosis. Semin Thromb Hemost1999;25:333–350.
 
17. Lowe GD, Rumley A, Woodward M, et al. Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA Survey: I, illustrative reference ranges by age, sex and hormone use. Br J Haematol 1997;97:775–784.
 
18. Refsum H, Smith AD, Ueland PM, et al. Facts and recommendations about total homocysteine determinations: an expert opinion. Clin Chem 2004;50:3–32.
 
19. Galli M, Luciani D, Bertolini G, et al. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature.Blood 2003;101:1827–1832.
 
20. Vaarala O, Manttari M, Manninen V, et al. Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. Circulation 1995;91:23–27.
 
21. Tuhrim S, Rand JH, Wu XX, et al. Elevated anticardiolipin antibody titer is a stroke risk factor in a multiethnic population independent of isotype or degree of positivity. Stroke 1999;30:1561–1565.
 
22. Sutton-Tyrrell K, Bostom A, Selhub J, et al. High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation 1997;96:1745–1749.
 
23. Welch GN, Loscalzo J. Homocysteine and atherosclerosis. N Engl J Med 1998;338:1042–1050.
 
24. Lesniak W, Kolasinska-Kloch W, Kiec B. Vascular endothelium: function, disorders and clinical modification probes. Folia Med Cracov 2001;42:5–14.
 
25. Woo KS, Chook P, Lolin YI, et al. Hyperhomocyst (e)inemia is a risk factor for arterial endothelial dysfunction in humans. Circulation 1997;96:2542–2544.
 
26. Hayashi T, Honda G, Suzuki K. An atherogenic stimulus homocysteine inhibits cofactor activity of thrombomodulin and enhances thrombomodulin expression in human umbilical vein endothelial cells.Blood 1992;79:2930–2936.
 
27. Ridker PM, Hennekens CH, Selhub J, et al. Interrelation of hyperhomocyst (e)inemia, factor V Leiden, and risk of future venous thromboembolism. Circulation 1997;95:1777–1782.
 
28. Durand P, Lussier-Cacan S, Blache D. Acute methionine load-induced hyperhomocystinemia enhances platelet aggregation, thromboxane biosynthesis, and macrophage-derived tissue factor activity in rats. FASEB J 1997;11:1157–1168.
 
29. Khare A, Ghosh K, Shetty S, et al. Combination of thrombophilia markers in acute myocardial infarction of the young. Indian J Med Sci 2004;58:381–388.
 
30. Kark JD, Sinnreich R, Rosenberg IH, et al. Plasma homocysteine and parental myocardial infarction in young adults in Jerusalem. Circulation 2002;105:2725–2729.
 
31. Selhub J, Jacques PF, Wilson PWF, et al. Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. JAMA 1993;270:2693–2697.
 
32. Joosten E, van den Berg A, Riezler R, et al. Metabolic evidence that deficiencies of vitamin B-12 (cobalamin), folate, and vitamin B-6 occur commonly in elderly people. Am J Clin Nutr 1993;58:468–476.
 
33. Graham I, Meleady R. Heart attacks and homocysteine. BMJ 1996;313:1419–1420.