Determinants and associations of homocysteine and prothrombotic risk factors in Kuwaiti patients with cerebrovascular accident.

OBJECTIVE: The objective of this study was to evaluate the determinants and associations of some prothrombotic risk factors in patients with cerebrovascular accidents (CVAs). SUBJECTS AND METHODS: In this case-control study, plasma total homocysteine (tHcy), lupus anticoagulant, protein C, protein S, activated protein C resistance (APC-R) and antithrombin were measured in 102 patients (60 males and 42 females) and 167 controls (87 males, 80 females). Serum vitamin B(12), folate, red cell folate, creatinine, lipid profile and glucose were also determined. Glomerular filtration rate (GFR) was calculated. RESULTS: 13 (22%) of the 60 male patients, and 16 (39%) of the 42 female patients had hyperhomocysteinemia. Median (interquartile range) tHcy was higher in male patients [11.22 micromol/l (9.60-15.40)] than female patients [10.05 micromol/l (8.72-17.54)]. On binary logistic regression analysis, the significant (p < 0.05) determinants of tHcy were urea, creatinine and GFR. Comparing patients with control subjects showed that tHcy, age, fasting glucose, urea, serum creatinine, white blood cell count, protein S, APC-R and factor VIII were significantly higher, while protein C, factor II, total cholesterol, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were significantly lower in patients. Lupus anticoagulant was not associated with tHcy and not detected in patients and controls. Low concentrations of vitamins B(12) and folate were not associated with tHcy. Logistic regression analysis showed a significant association of tHcy with CVA (OR = 9.55; p = 0.047) in males in the presence of other traditional CVA risk factors but tHcy is not independently associated with CVA in females. CONCLUSION: Hyperhomocysteinemia is common in Kuwaiti patients with CVA and tHcy probably interacts with prothrombotic factors (protein C, APC-R and factor VIII) to increase CVA risk. The main determinants, age and GFR markers, should be kept in mind when determining the risk associated with tHcy.

Plasma homocysteine and hematological factors in patients with venous thromboembolic diseases in Kuwait.

BACKGROUND: Venous thromboembolic disease (VTE) is a common cause of morbidity in Kuwait, but the risk factors have not been studied. Hyperhomocysteinemia has been suggested as one of the risk factors. We postulate that hyperhomocysteinemia acts synergistically with hematological variables to increase VTE risk. This study evaluates the roles of hyperhomocysteinemia and hematological variables in patients with VTE. METHODS: We measured fasting plasma total homocysteine (tHcy), activated protein C resistance, protein C (PC), protein S (PS) and antithrombin (AT) in 201 patients with VTE and 166 healthy controls. We also measured factor VIII, factor II, lupus anticoagulant, anticardiolipin, serum vitamin B12, folate, creatinine, lipid profile, glucose, full blood count and red cell folate. The glomerular filtration rate (GFR) was calculated from creatinine. RESULTS: When patients on warfarin were excluded, 13.1% of patients (18 out of 137) had a deficiency in PC, 16.8% (23 out of 137) had a deficiency in PS, and when patients on heparin were excluded, 8.3% of patients (14 out of 168) had low AT. Spearman's rank correlation analysis showed that tHcy had significant correlations with age, creatinine and PS, and significant inverse correlations with GFR, high-density lipoprotein cholesterol and serum folate. Partial correlation analysis after correcting for age and sex showed that tHcy retained a significant correlation with creatinine, GFR and serum folate. Binary logistic regression analyses of the determinants of hyperhomocysteinemia included age, creatinine, GFR and serum folate. Multivariate logistic regression analysis showed significant association of tHcy with VTE (OR = 5.6; p < 0.0001) in the presence of known risk factors for VTE. CONCLUSION: We conclude that elevated tHcy is a significant risk factor for the development of VTE, and therefore, it should be included in the workup for patients at risk of VTE, but the determinants of tHcy should be kept in mind.

Determinants of plasma homocysteine in relation to hematological and biochemical variables in patients with acute myocardial infarction.

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 oftHcy 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.