Determinants of plasma homocysteine in relation to hematological and biochemical variables in patients with acute myocardial infarction.Background: Elevated plasma total homocysteine Homocysteine Definition Homocysteine is a naturally occurring amino acid found in blood plasma. High levels of homocysteine in the blood are believed to increase the chance of heart disease, stroke, Alzheimer's disease, and osteoporosis. (tHcy) is a risk factor for coronary artery disease coronary artery disease, condition that results when the coronary arteries are narrowed or occluded, most commonly by atherosclerotic deposits of fibrous and fatty tissue. (CAD), but the mechanism is not known. This study evaluates the determinants and associations of tHcy in patients presenting with acute myocardial infarction acute myocardial infarction (  ·kyōōtˑ mī·ō·karˑ·dē· (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 [B.sub.12], folate folate /fo·late/ (fo´lat) 1. the anionic form of folic acid. 2. more generally, any of a group of substances containing a form of pteroic acid conjugated with l-glutamic acid and having a variety of substitutions. , creatinine, lipid profile lipid profile, n a series of tests used to gauge a person's risk for coro-nary heart conditions. Blood levels examined in a lipid profile include those for total cholesterol, LDL- and HDL-cholesterol, and triglycerides. , fasting glucose fasting glucose Fasting blood sugar, fasting plasma glucose Endocrinology Glucose obtained from a Pt who has had nothing–except water by mouth for 8+ hrs; FG is used in evaluating Pts for possible DM Ref range 65-115 mg/dL non-diabetic; 110-140 mg/dL, , full blood count and red cell folate were determined. Creatinine clearance creatinine clearance n. The volume of serum or plasma that would be cleared of creatinine by one minute's excretion of urine. creatinine clearance was calculated using the modification of diet in renal disease Renal disease Kidney disease. Mentioned in: Glycogen Storage Diseases hypertension High blood pressure Cardiovascular disease An abnormal ↑ systemic arterial pressure, corresponding to a systolic BP of > 160 mm Hg 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 [B.sub.12] 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 HDL cholesterol n. See high-density lipoprotein. HDL Cholesterol About one-third or one-fourth of all cholesterol is high-density lipoprotein 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 glomerular filtration rate n. Abbr. GFR The volume of water filtered out of the plasma through glomerular capillary walls into Bowman's capsules per unit of time. and the status of vitamins [B.sub.12] and folate. The above determinants should be kept in mind when using tHcy as a risk factor for CAD. Key Words: homocysteine, myocardial infarction myocardial infarction: see under infarction. , coronary disease, risk factors ********** Coronary artery disease (CAD) is a common cause of morbidity and mortality Morbidity and Mortality can refer to:
In a previous study, it was shown that the glomerular filtration rate (GFR GFR - Grim File Reaper ) was the main determinant of tHcy in Kuwaiti patients with type 2 diabetes type 2 diabetes n. See diabetes mellitus. . (2) However, other known determinants of hyperhomocystinemia, such as vitamins [B.sub.12] and folate, have been identified in other populations. (3) A number of hematological hematological, hematologic pertaining to or emanating from blood cells. hematological tests total and differential white cell counts, hematocrit estimation, erythrocyte count. factors have also been shown to increase the risk of CAD. These include protein C (PC), protein S (PS), antithrombin (AT), factor VII factor VII n. A factor in the clotting of blood that forms a complex with tissue thromboplastin and calcium to activate the prothrombinase, thus acting to accelerate the conversion of prothrombin to thrombin. , factor II, lupus anticoagulant lupus anticoagulant Lupus inhibitor Lab Medicine Any IgG or IgM class antibody that arise spontaneously in Pts with SLE; while LAs produce in vitro interference with phospholipid-dependent coagulation–eg, activated partial thromboplastin time–aPTT and (LA) and anticardiolipin (ACL See access control list. 1. ACL - Access Control List. 2. ACL - Association for Computational Linguistics. 3. ACL - A Coroutine Language. A Pascal-based implementation of coroutines. ["Coroutines", C.D. ) antibodies. (4-6) We hypothesize hy·poth·e·size v. hy·poth·e·sized, hy·poth·e·siz·ing, hy·poth·e·siz·es v.tr. To assert as a hypothesis. v.intr. To form a hypothesis. that there is interplay between hyperhomocystinemia and hematological factors that contribute to the increased risk of CAD in the Kuwaiti population. Therefore, the main aim of this study is to evaluate the determinants of tHcy in relation to hematological and biochemical variables in Kuwaiti patients presenting with acute myocardial infarction (AMI) for the first time. Patients, Materials, and Methods Patients Two hundred and ten (177 males and 33 females) patients with a mean (95% confidence interval [CI]) age of 54.05 (52.3 - 55.8) years presenting at Mubarak Al-Kabeer Hospital Mubarak Al-Kabeer Hospital is a general hospital built in Jabriya, Kuwait in 1982. The hospital was named after Shiekh Mubarak Al-Kabeer Al-Sabah. It serves the Hawalli governorate and covers about 700,000 people in the area. were studied. Inclusion criteria consisted of first AMI, admitted within 12 hours of symptom onset. The diagnosis of AMI was based on the presence of chest pain of at least 30 minutes' duration and elevation of cardiac enzymes (creatine kinase [CK] and CK-MB CK-MB Creatine phosphokinase MB isoenzyme Cardiology A CK isoenzyme usually ↑ in acute MI; CK-MB may be ↑ in muscular dystrophy, polymyositis, myoglobinuria, malignancy–eg, lung CA. Cf Troponin I, Troponin T. isoenzyme isoenzyme /iso·en·zyme/ (-en´zim) isozyme. i·so·en·zyme n. See isozyme. i ), accompanied by characteristic electrocardiographic electrocardiographic emanating from or pertaining to electrocardiography. electrocardiographic monitoring maintenance of a more or less continuous surveillance of a patient's cardiac status by means of electrocardiography. changes. The control subjects consisted of 167 (87 males and 80 females) apparently healthy subjects with a mean (95% CI) age of 40.93 (39.6 - 42.3) years. Exclusion criteria consisted of a refusal to participate in the study. All patients and control subjects gave informed voluntary consent to participate in the study according to the protocol approved by the local ethics committee and in accordance with the ethical standards laid down in the Helsinki declaration. The following data were collected from patients and control subjects: age, sex, weight, blood pressure and/or history of hypertension, diabetes mellitus, smoking status, past medical history, family history of myocardial infarction and diabetes mellitus. A medication history was also obtained. Methods Venous blood samples were collected without tourniquet tourniquet (t  r`nĭkĕt, –kā, tûr`–), compression device used to cut off the flow of blood to a part of the body, most often an arm or leg. on admission
(before commencement of specific therapy for AMI) within 12 hours of
symptom onset. Samples for homocysteine estimation were collected in
EDTA EDTA: see chelating agents. tubes and immediately chilled on ice. They were then centrifuged at
2 to 4[degrees]C and the plasma stored at -20[degrees]C until analyzed.
(7)
For coagulation coagulation (kōăg'y  lā`shən), the collecting into a mass of minute particles of a solid dispersed throughout a liquid (a sol), usually followed by the precipitation or studies, blood samples were collected in trisodium
citrate. Samples were centrifuged at 2,500 rpm for 15 minutes at
4[degrees]C; platelet-poor plasma was separated and kept frozen at
-70[degrees]C until analyzed. (8)
Assays Estimation of tHcy was carried out on the IMX IMX In My eXperience IMX Interactive Music Exchange (TV show) IMX Integrated Multimedia Exchange IMX Industrywide Mortgage Exchange IMX Intermodal Marketing Extension IMX Inverse Multiplexor analyser (Abbott Diagnostics, Chicago, USA), which measured the total concentration of homocysteine. Hyperhomocystinemia was defined as fasting plasma homocysteine level > 15.0[micro]mol/L. (2,9) Vitamin status Radioassay (dual count) was used to estimate vitamin [B.sub.12] and folate (Diagnostic Products Corp., Los Angeles, CA). Red cell folate was calculated from folate and hematocrit Hematocrit Definition The hematocrit measures how much space in the blood is occupied by red blood cells. It is useful when evaluating a person for anemia. Purpose Blood is made up of red and white blood cells, and plasma. according to the kit manufacturer's instructions (Diagnostic Products Corp.). Hematological parameters Full blood count was determined by Gen S Coulter counter (Beckman-Coulter, Brea, CA). PC and PS, factors II and VII were measured with functional assays, (Instrumentation Laboratory, Milano, Italy). AT was measured by a chromogenic chro·mo·gen·ic adj. Of or relating to a chromogen or to chromogenesis. chromogenic (krō´mōjen´ik), adj pertaining to color production. assay; activated protein C-resistance (APC-R) was tested by activated partial thromboplastin thromboplastin: see blood clotting. time-based method (both by Instrumentation Laboratory). LA was detected using two methods--Russell viper venom time (American Diagnostica, Greenwich, CT) followed by automated confirmatory test on the ACL 9000 (Tectron, International Laboratory Co., Milano, Italy; IL Test LA Screen and IL Test LA Confirm tests). ACL antibody assay was performed by immunometric enzyme immunoassay Immunoassay An assay that quantifies antigen or antibody by immunochemical means. The antigen can be a relatively simple substance such as a drug, or a complex one such as a protein or a virus. (Orgentec GmbH, Mainz, Germany). Coagulation studies were performed on automated coagulation analyzer ACL 9,000. Other assays Serum creatinine was determined on the Beckman LX20 automated analyzer (Beckman Corp., Brea, CA) and creatinine clearance was calculated with the modified modification of diet in renal disease (MDRD MDRD Modification of Diet in Renal Disease MDRD Mobilization, Deployment, Redeployment and Demobilization MdRD Median Round Delay MDRD Maximum Deflection Ratio Detector ) formula (10) to assess renal function in patients and controls. Fasting glucose and full lipid profile (total cholesterol, triglycerides Triglycerides Fatty compounds synthesized from carbohydrates during the process of digestion and stored in the body's adipose (fat) tissues. High levels of triglycerides in the blood are associated with insulin resistance. , HDL cholesterol) were determined for each subject and LDL cholesterol was calculated with the Friedewald formula. (11) Statistical methods Statistical analyses were performed using the Statistical Package for Social Sciences (SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. Inc., Chicago, IL) version 12.0. Distributions of continuous variables were tested for normality with the Kolmogorov-Smirnov test and the natural log transformations of skewed skewed curve of a usually unimodal distribution with one tail drawn out more than the other and the median will lie above or below the mean. skewed Epidemiology adjective Referring to an asymmetrical distribution of a population or of data variables were used to improve normality to use parametric methods. Data are presented as mean (95% CI). Spearman spear·man n. A man, especially a soldier, armed with a spear. rank correlation coefficient was used to assess the extent of association between tHcy and other measured variables. In view of the well-known relationship between tHcy and GFR and since there was a significant gender difference in tHcy, partial correlation was used to assess the extent of association between tHcy and other variables after controlling for sex and creatinine. Comparison between groups was done by the Student t test. To assess the effect of variables on the risk (expressed as odds ratio [OR]) of AMI, logistic regression analyses was used to ascertain the association between AMI (which was recoded as a binary outcome) and the variables. Logistic regression analyses were also used to ascertain the association between hyperhomocystinemia (tHcy recoded into binary variable (0 = normal homocysteine, 1 = homocysteine > 15 [micro]mol/L) and other variables. Values of P [less than or equal to] 0.05 were considered to be statistically significant. Results General results Table 1 summarizes the clinical characteristics of patients and control subjects grouped according to gender. Table 2 summarizes the biochemical and hematological variables. Biochemical variables When patients with AMI were compared with controls, the proportion of patients with hyperhomocystinemia was significantly higher, 16.1%, compared with controls at 5.4% (P < 0.0001) (Table 2). Comparison of patients in first and fourth quartiles of tHcy When male and female patients in the first quartile Quartile A statistical term describing a division of observations into four defined intervals based upon the values of the data and how they compare to the entire set of observations. Notes: Each quartile contains 25% of the total observations. of homocysteine were compared with patients in the fourth quartile, hemoglobin (P = 0.012), GFR (P < 0.0001), PC (P = 0.005), vitamin [B.sub.12] (P = 0.001), serum folate (P < 0.0001) and red cell folate (P < 0.0001) were significantly lower in patients with tHcy in the fourth quartile. Correlations of homocysteine Table 3 shows the correlations of tHcy with other variables in the patients. In the study patients, tHcy showed significant correlations with age (P = 0.002) and creatinine (P < 0.0001), and significant negative correlations with hemoglobin (P < 0.0001), GFR (P < 0.0001), PC (P = 0.015), vitamin [B.sub.12] (P < 0.0001), serum folate (P < 0.0001) and red cell folate (P = 0.007). The Figure shows the relationship between GFR and tHcy in patients and controls. In view of the significant gender difference in tHcy and correlation with creatinine, we performed partial correlation analyses correcting for sex and then for sex and creatinine. After correction for sex, tHcy showed significant correlations with age (rs = 0.30; P < 0.0001), hemoglobin (rs = -0.23; P = 0.002), creatinine (rs = 0.21; P < 0.0001), GFR (rs = -0.37; P < 0.0001), serum vitamin [B.sub.12] (rs = -0.25; P < 0.0001), serum folate (rs = -0.24; P = 0.001) and red cell folate (rs = -0.25; P = 0.001). These suggest that the correlations of tHcy with these variables are independent of sex. After correction for sex and creatinine, tHcy retained significant correlations with age (rs = 0.20; P = 0.006), hemoglobin (rs = -0.18; P = 0.012), vitamin [B.sub.12] (rs = -0.26; P < 0.0001), serum folate (rs = -0.19; P = 0.009), red cell folate (rs = -0.25; P = 0.001) as well as APC-R (rs = -0.16; P = 0.032), suggesting that the correlations of tHcy with these variables are independent of gender and renal function. Association of hyperhomocystinemia with myocardial infarction Binary logistic regression analyses with CAD as the dependent variable showed that tHcy is significantly associated with CAD; OR (95% CI) = 1.11 (1.00-1.23); P = 0.05. When the confounding effects of other traditional risk factors (age, sex, weight, blood pressure, lipid profile) were included in the model, tHcy retained significant association with CAD; OR (95% CI) = 1.39 (1.01-1.91); P = 0.047. Determinants of hyperhomocystinemia To determine factors that were significantly associated with hyperhomocystinemia, we performed binary logistic regression analysis and found that in male patients, the most significant determinants were age (OR [95% CI] = 1.07 [1.03-1.12]; P = 0.001), creatinine (OR [95% CI] = 13.17 [2.44-71.00] P = 0.003), GFR (OR [95% CI] = 0.97 [0.94-0.99] P = 0.001); vitamin [B.sub.12] (OR [95% CI] = 0.39 [0.21-0.73] P = 0.003), red cell folate (OR [95% CI] = 0.35 [0.12-0.98] P = 0.046). However, these determinants were not found to be significant in female patients, possibly because of the relatively smaller number of female patients. Discussion In agreement with the findings from other populations (12) we have found that tHcy is significantly associated with CAD in Kuwaiti patients presenting with AMI. In this population, we have also found that the most significant determinants of tHcy are age, creatinine, GFR, vitamin [B.sub.12] and folate status. Plasma total homocysteine has been shown to act synergistically syn·er·gis·tic adj. 1. Of or relating to synergy: a synergistic effect. 2. Producing or capable of producing synergy: synergistic drugs. 3. with other risk factors. In this regard, table 2 shows that PC, AT, APC-R and factor VII were found to be lower in patients with CAD. Of all the hematological variables, tHcy showed significant correlation with only PC in male patients when patients in the highest quartile of homocysteine were compared with patients in the lowest quartile. This is in agreement with other studies that have shown that PC is a strong risk factor for thrombotic diseases. (13,14) Furthermore, the inverse correlation between tHcy and PC (Table 3) suggests that the two risk factors may be acting synergistically, as tHcy is known to cause inactivation inactivation /in·ac·ti·va·tion/ (in-ak?ti-va´shun) the destruction of biological activity, as of a virus, by the action of heat or other agent. of PC, thereby increasing the risk of arterial thrombosis. (15) AT was significantly lower in male patients compared with controls, as it is known to decrease in patients with AMI. (16) Age is a known risk factor for CAD, and in this study, we have found a significant association between tHcy and age independent of the renal function. We have also found lower AT in male patients, although this could be due to the age-related decrease in AT. (17) Therefore, increased tHcy and low AT could act synergistically to increase thrombotic risk in the elderly population. This is supported by the reported strong association between hyperhomocystinemia and CAD in the elderly population. (18) The exact mechanisms underlying the apparent adverse effect of hyperhomocystinemia on the risk of CAD are not clear at present, but several possibilities have been proposed. Hyperhomocystinemia has been shown to cause increased arterial blood pressure, (19) thereby increasing the risk of CAD. Elevated plasma tHcy has also been shown to induce oxidative injury to vascular endothelial cells and cause impairment of the endothelial endothelial /en·do·the·li·al/ (-the´le-al) pertaining to or made up of endothelium. Endothelial A layer of cells that lines the inside of certain body cavities, for example, blood vessels. production of nitric oxide, a strong vascular relaxing factor. (20) Other proposed mechanisms include enhancement of platelet adhesion to endothelial cells, (21) promotion of the growth of vascular smooth muscle Vascular smooth muscle refers to the particular type of smooth muscle found within, and composing the majority of the wall of blood vessels. Vascular smooth muscle contracts or relaxes to both change the volume of blood vessels and the local blood pressure, a mechanism that cells (22) and association of increased tHcy with higher levels of prothrombotic factors such as [beta]-thromboglobulin, tissue plasminogen activator tissue plasminogen activator n. Abbr. TPA 1. An enzyme that catalyzes the conversion of plasminogen to plasmin, used to dissolve blood clots rapidly and selectively, especially in the treatment of heart attacks. 2. and factor VIIc, (23) toxicity of homocysteine on the vascular endothelium endothelium /en·do·the·li·um/ (-the´le-um) pl. endothe´lia the layer of epithelial cells that lines the cavities of the heart, the serous cavities, and the lumina of the blood and lymph vessels. , (24) impaired endothelium-dependent relaxation, (25) induction of hypercoagulable state due to downregulation of thrombomodulin expression, (26) activation of factor V, (27) inhibition of PC activation (15) and increased platelet aggregation. (28) [FIGURE OMITTED] Regardless of the exact mechanisms, a critical question is whether the relation of homocysteine and AMI is confounded by an association of tHcy levels with other strong predictors of AMI, such as age, sex, smoking and association with other known predictors of hyperhomocystinemia, such as GFR, sex and age. After adjustment for the confounding effect of these factors, hyperhomocystinemia was still significantly associated with AMI. This is in agreement with studies in other populations. (29,30) Although none of our patients had deficiencies of vitamin [B.sub.12] and folate, we found inverse correlations with tHcy. This is in agreement with other studies which suggest that increased tHcy is a sensitive marker of low intake of vitamin [B.sub.12] and folate. (31,32) This has led to the suggestion that the recommended daily intakes of these vitamins be revised as a primary prevention mechanism to prevent mild hyperhomocystinemia and resultant increased risk of CAD. (33) In conclusion, the determinants of tHcy in Kuwaiti patients with AMI are age, GFR and the status of vitamins [B.sub.12] and folate. Our results show that tHcy is a significant risk factor in Kuwaiti patients, but the above determinants should be kept in mind when using tHcy as a risk factor for CAD. Acknowledgments This project was supported by Kuwait University Research grant number MG02/00. We thank Mehrez Jadaon, Hadeel Muzaini, Rasha Abdullah, Sicy Easow, Dr. Sunila George and Reema Matthews for technical assistance. 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. 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Epidemiology of coagulation factors, inhibitors and activation markers: the Third Glasgow MONICA MONICA Cardiology A WHO initiative–Multinational Monitoring of Trends & Determinants of Cardiovascular Disease–which evaluated the effects of various factors on mortality in Pts MIs 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 i·so·type n. An antigenic marker that occurs in all members of a subclass of an immunoglobulin class. i 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 fo·li·a n. Plural of folium. Med Cracov 2001;42:5-14. 25. Woo KS, Chook chook chicken. 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 atherogenie 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 factor V Leiden Hematology A variant of factor V present in 3%-8% of Caucasians associated with a ↑ risk of DVT. See LETS, Hereditary thrombophilia. , and risk of future venous thromboembolism thromboembolism /throm·bo·em·bo·lism/ (-em´bo-lizm) obstruction of a blood vessel with thrombotic material carried by the blood from the site of origin to plug another vessel. throm·bo·em·bo·lism n. . Circulation 1997;95:1777-1782. 28. Durand P, Lussier-Cacan S, Blache D. Acute methionine methionine (mĕthī`ənēn), organic compound, one of the 20 amino acids commonly found in animal proteins. Only the L-stereoisomer appears in mammalian protein. load-induced hyperhomocystinemia enhances platelet aggregation, thromboxane thromboxane /throm·box·ane/ (-bok´san) either of two compounds, one designated A2 and the other B2. Thromboxane A2 is synthesized by platelets and is an inducer of platelet aggregation and platelet release functions and is a biosynthesis Biosynthesis The synthesis of more complex molecules from simpler ones in cells by a series of reactions mediated by enzymes. The overall economy and survival of the cell is governed by the interplay between the energy gained from the breakdown of compounds , and macrophage-derived tissue factor activity in rats. FASEB FASEB Federation of American Societies for Experimental Biology 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 PWF Pacific Whale Foundation (Maui, Hawaii) PWF Public Workstation Facility PWF Polarimetric Whitening Filter PWF Pro Wrestling Fan PWF Preserved Wood Foundation PWF Peter Westbrook Foundation PWF Personnel Working File PWF Power Weight Filter , 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 Van den Berg is the surname of:
33. Graham I, Meleady R. Heart attacks and homocysteine. BMJ BMJ n abbr (= British Medical Journal) → vom BMA herausgegebene Zeitschrift 1996;313:1419-1420. Rajaa Marouf, FRCPath, Mohammad Zubaid, FRCPC FRCPC Fellow of the Royal College of Physicians and Surgeons of Canada , Olusegun A. Mojiminiyi, FRCPath, Mohammad Qurtom, FRCPI FRCPI Fellow of the Royal College of Physicians of Ireland , Nabila A. Abdella FRCP FRCP Fellow of the Royal College of Physicians. FRCP abbr. Fellow of the Royal College of Physicians , Hanan Al Wazzan, MRCPath, and Salah Al Humood, FRCPC From the Departments of Pathology and Medicine, Kuwait University, Faculty of Medicine and the Ministry of Health, Kuwait. Reprint requests to Dr. Rajaa Marouf, Kuwait University, PO Box 24923, Safat Kuwait code 13110. Email: r-marouf@hsc.edu.kw Funding agency: Kuwait University Research grant number MG02/00. Accepted April 19, 2006. RELATED ARTICLE: 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.
Table 1. Clinical characteristics of patients and controls
Males
Patients Controls P
Number 177 87
Age (years) 53.38 (29.38-77.00) 40.94 (38.90-42.95) 0.0001
Weight (kg) 83.84 (60.00-120.27) 87.03 (83.69-90.36) 0.131
Hypertension 30.1% (49/177) 0%
Diabetes mellitus 33.7% (56/177) 0%
Smoking status:
Nonsmoker 36.1% (60/177) 67.9% (57/87) 0.782
Current smoker 62.7% (104/177) 29.8% (25/87) 0.0001
Ex-smoker 1.2% (2/177) 2.4% (2/87) 1.000
Previous MI 19.1% (30/177) 0%
Family history of 36.9% (58/177)
MI
Family history of 35.5% (55/177)
DM
Family history of 13.5% (21/177)
stroke
Aspirin intake 78.3% (123/177) 2.5% (2/87) 0.0001
Females
Patients Controls P
Number 33 80
Age (years) 57.84 (51.79-63.89) 40.94 (39.14-42.73) 0.0001
Weight (kg) 73.16 (63.91-82.41) 74.66 (71.47-77.85) 0.700
Hypertension 56.0% (14/33) 0%
Diabetes mellitus 64.0% (16/33) 0%
Smoking status:
Nonsmoker 79.2% (19/33) 98.7% (77/80) 0.0001
Current smoker 20.8% (5/33) 1.3% (1/80) 0.102
Ex-smoker 0% 0%
Previous MI 13.0% (3/33) 0%
Family history of 20.8% (5/33)
MI
Family history of 37.5% (9/33)
DM
Family history of 25.0% (6/33)
stroke
Aspirin intake 76.2% (16/33) 0%
Continuous variables are expressed as means (95% confidence interval).
Nominal variables are expressed as percentages (number/total). MI,
myocardial infarmation; DM, diabetes mellitus.
Table 2. Biochemical and hematological variables in patients and
controls.
Males
Patients Controls P
Fasting glucose 8.16 5.53 0.0001
(mmol/L) (7.61-8.71) (5.37-5.70)
Serum creatinine 95.90 86.20 0.002
([micro]mol/L) (91.83-99.98) (82.80-89.60)
GFR by MDRD formula 81.94 94.37 0.0001
(mL/min/1.73[m.sup.2]) (78.48-85.39) (89.99-98.75)
Total cholesterol 5.18 5.10 0.609
(mmol/L) (4.98-5.39) (4.86-5.34)
HDL cholesterol 1.19 1.01 0.011
(mmol/L) (1.05-1.33) (0.95-1.07)
LDL cholesterol 3.52 3.37 0.633
(mmol/L) (3.06-3.98) (3.14-3.60)
Triglycerides 2.06 1.63 0.107
(mmol/L) (1.73-2.40) (1.27-1.99)
Vitamin [B.sub.12] 304.41 252.92 0.087
(pmol/L) (268.67-340.15) (210.18-295.65)
Serum folate (nmol/L) 24.62 24.29 0.818
(22.95-26.30) (22.01-26.56)
Red cell folate 1114.47 1120.11 0.913
(nmol/L) (1054.41-1174.53) (1039.89-1200.32)
Homocysteine 11.68 9.15 0.0001
([micro]mol/L) (10.95-12.40) (8.40-9.90)
White blood cells 10.65 6.98 0.0001
(count* 10^9/L) (10.09-11.21) (6.54-7.42)
Hemoglobin (g/L) 145.72 147.66 0.323
(143.38-148.06) (144.84-150.47)
Platelets 270.65 260.29 0.271
(count* 10^9/L) (259.69-281.62) (245.89-274.68)
Protein C (%) 102.83 115.66 0.0001
(98.88-106.77) (110.95-120.36)
Protein S (%) 85.20 85.20 1.000
(81.55-88.85) (81.13-89.26)
Antithrombin (%) 92.33 103.35 0.0001
(89.85-94.81) (100.13-106.56)
APC-R ratio 2.11 2.27 0.0001
(2.07-2.16) (2.21-2.32)
Factor II (%) 90.84 87.48 0.103
(88.30-93.38) (84.82-90.15)
Factor VII (%) 100.20 118.30 0.0001
(94.59-105.81) (109.51-127.09)
Positive LA 0.6% (1/177) 0%
Presence of 11.4% (16/177) 8.0% (7/87) 0.061
ACL antibodies
Females
Patients Controls P
Fasting glucose 10.50 5.94 0.0001
(mmol/L) (8.34-12.67) (5.39-5.69)
Serum creatinine 82.46 64.87 0.0001
([micro]mol/L) (69.25-95.67) (62.72-67.02)
GFR by MDRD formula 75.76 95.62 0.0001
(mL/min/1.73[m.sup.2]) (64.56-86.95) (91.99-99.58)
Total cholesterol 5.66 5.17 0.058
(mmol/L) (5.02-6.29) (4.96-5.38)
HDL cholesterol 1.10 1.25 0.260
(mmol/L) (0.80-1.40) (1.18-1.31)
LDL cholesterol 3.24 3.41 0.745
(mmol/L) (2.73-3.75) (3.24-3.59)
Triglyceride4s 2.00 1.17 0.0001
(mmol/L) (1.53-2.47) (1.01-1.32)
Vitamin [B.sub.12] 360.72 209.03 0.0001
(pmol/L) (287.88-433.55) (174.87-243.18)
Serum folate (nmol/L) 28.48 25.16 0.217
(23.14-33.82) (22.53-27.80)
Red cell folate 1309.57 1161.22 0.144
(nmol/L) (1087.26-1531.88) (1068.50-1253.93)
Homocysteine 10.62 8.50 0.040
([micro]mol/L) (9.15-12.09) (7.08-9.93)
White blood cells 9.17 6.72 0.0001
(count* 10^9/L) (7.90-10.44) (6.30-7.14)
Hemoglobin (g/L) 126.84 123.19 0.265
(119.06-134.62) (120.41-125.97)
Platelets 295.08 309.22 0.393
(count* 10^9/L) (263.71-326.45) (293.43-325.01)
Protein C (%) 121.64 118.68 0.584
(111.98-131.30) (112.99-124.36)
Protein S (%) 90.15 71.39 0.001
(78.73-101.57) (66.17-76.60)
Antithrombin (%) 99.88 99.84 0.989
(94.87-104.89) (96.40-103.28)
APC-R ratio 2.20 2.25 0.216
(2.11-2.29) (2.21-2.30)
Factor II (%) 99.48 92.63 0.005
(94.98-103.99) (90.11-95.14)
Factor VII (%) 108.79 123.05 0.043
(98.41-119.17) (115.20-130.90)
Positive LA 3.0% (1/33) 0%
Presence of 0.0% (0/33) 11.3% (9/80) 0.0001
ACL antibodies
GFR, glomerular filtration rate; MDRD, modification of diet in renal
disease; APC-R, activated protein C-resistance; LA, lupus anticoagulant;
ACL, anticardiolipin.
Table 3. Spearman rank correlations (rs) of plasma total homocysteine in
patient group
Correlation
coefficient P
Age (years) 0.263 0.000
Weight (kg) -0.115 0.155
White blood cells (count x 10^9/L) -0.050 0.496
Hemoglobin (g/L) -0.190 0.009
Platelets (count x 10^9/L) -0.038 0.604
Fasting glucose (mmol/L) -0.089 0.226
Urea (mmol/L) 0.212 0.003
Creatinine ([micro]mol/L) 0.371 0.000
GFR by MDRD formula (mL/min/1.73[m.sup.2]) -0.356 0.000
Cholesterol (mmol/L) -0.018 0.809
HDL- cholesterol (mmol/L) -0.162 0.460
LDL- cholesterol (mmol/L) -0.336 0.240
Triglycerides (mmol/L) -0.085 0.259
Protein C (%) -0.183 0.009
Protein S (%) -0.040 0.567
Antithrombin (%) 0.050 0.474
APC-R ratio -0.141 0.044
Factor II (%) -0.091 0.197
Factor VII (%) -0.051 0.463
Serum vitamin [B.sub.12] (pmol/L) -0.308 0.000
Serum folate (nmol/L) -0.297 0.000
Red cell folate (nmol/L) -0.265 0.000
GFR, glomerular filtration rate; MDRD, modification of diet in renal
disease; APC-R, activated protein C-resistance
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