Plasma homocysteine level and the angiographic extent of coronary artery disease

Recent epidemiologic studies have shown that moderately elevated plasma homocysteine concentrations are associated with an increased risk for the development of atherosclerotic cardiovascular diseases. But, it is not known whether moderate hyperhomocysteinemia is associated with the angiographic extent of atherosclerotic cardiovascular disease in patients with coronary artery disease (CAD). A possible relationship was investigated between admission plasma homocysteine level and the angiographic extent of coronary artery disease in patients with CAD. In this study, 156 consecutive patients presenting with coronary artery disease (group 1) and control group (group 2) of 35 age-matched persons with normal coronary angiography were enrolled. Blood samples for homocysteine were obtained on admission. Plasma homocysteine concentration was measured with high-performance liquid chromatography with fluorescence detection. Radiographs from coronary angiography were viewed and scored using Sullivan's method to assess the atherosclerotic involvement of coronary artery disease. There were significant elevations in homocysteine level in group 1 compared to group 2 (15.59 +/-5.7 micromol/L, 9.24 +/-1.50 micromol/L; respectively, p < 0.001). All scores (demonstrated angiographic extension of CAD) correlated significantly with plasma homocysteine levels; however, the Sullivan's extent score correlated more closely (r = 0.68, p < 0.001) than both the stenosis score (r = 0.44, p < 0.01) and vessel score (r = 0.35, p < 0.05). Elevated homocysteine levels in patients with coronary artery disease correlated with the angiographic extent of atherosclerotic disease.     

Plasma homocysteine levels in acute coronary syndromes

Hyperhomocysteinemia is currently regarded as an independent and modifiable risk factor for ischemic vascular diseases and thrombosis. We measured fasting plasma total homocysteine levels by HPLC with fluorescence detection in 30 patients presenting with acute coronary syndromes and 30 age and sex-matched control subjects. Demographic data, classical risk factors (systolic blood pressure, diabetes mellitus, smoking, ethanol intake, family history of ischaemic heart disease) and life-style habits were recorded. Lipid fractions including total cholesterol, triglycerides, HDL-cholesterol, total cholesterol/HDL-cholesterol ratio, serum creatinine, LDL-cholesterol and vitamins involved in the metabolism of homocysteine, folic acid and vitamin B12 were also assessed. Total fasting homocysteine concentrations were significantly higher in the patient group (12.2 +/- 1.01 micromol/l) than in the control subjects (7.05 +/- 0.36 micromol/l; p < 0.0001). Homocysteine correlated positively with age (r = 0.617; p < 0.01) and serum creatinine (r = 0.457; p < 0.01) in the patient group. Hyperhomocysteinemia was not associated with vitamin B12 or folate deficiency states. Vitamin B12 concentration was 273 +/- 16.4 ng/l in the control group and 284.3 +/- 32.2 ng/l in the patient group (p = NS). Serum folate concentration also was not significantly different between controls and patients; 7.57 +/- 0.58 microg/l and 8.05 +/- 0.72 microg/l, respectively. Since no significant difference was observed in the lipid parameters between patients and controls, the hyperhomocysteinemia in the patient group supports the view that homocysteine is an independent risk factor for cardiovascular diseases. Our results strongly suggest that elevated homocysteine levels are among the interacting factors in the complex, multifactorial pathophysiology of ischemic heart disease.     

Plasma homocysteine levels in obstructive sleep apnea: association with cardiovascular morbidity

OBJECTIVES: Obstructive sleep apnea (OSA) is associated with cardiovascular morbidity and mortality. Plasma levels of homocysteine are also associated with cardiovascular morbidity and mortality. We therefore investigated homocysteine and conventional cardiovascular risk factors in OSA patients with and without cardiovascular morbidity in comparison with normal control subjects and ischemic heart disease (IHD) patients without OSA. SETTING: Technion Sleep Medicine Center, Haifa, Israel. METHODS AND PARTICIPANTS: Levels of homocysteine, cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides, creatinine, vitamins B(12) and B(6), and folic acid were determined in 345 participants after overnight fasting. These included OSA patients with IHD (n = 49), with hypertension (n = 61), or without any cardiovascular disease (n = 127). Two control groups were employed: IHD patients without or with low likelihood for sleep apnea (n = 35), and healthy control subjects (n = 73). RESULTS: After adjustment for age, body mass index, creatinine, and existence of diabetes mellitus, OSA patients with IHD had significantly higher homocysteine levels (14.6 +/- 6.77 micromol/L) than all other groups including the IHD-only patients. Hypertensive OSA patients had comparable homocysteine levels to IHD patients (11.80 +/- 5.28 micromol/L and 11.92 +/- 5.7 micromol/L, respectively), while patients with OSA only had comparable levels to normal control subjects (9.85 +/- 2.99 micromol/L and 9.78 +/- 3.49 micromol/L, respectively). No differences in conventional cardiovascular risk factors or in vitamin levels were found between groups. CONCLUSIONS: Patients with the combination of IHD and OSA have elevated homocysteine levels. We hypothesize that these results may be explained by endothelial dysfunction combined with excess free-radical formation in OSA patients.     

Homocysteinemia and coronary artery disease: a case-control study in a Tunisian population

We have determined the prevalence of hyperhomocysteinemia and tested its relationship with coronary heart disease in Tunisian patients. The study included 70 angiogrphically proven coronary patients and 140 age- and sex-matched healthy subjects. Plasma homocysteine folate and vitamin B12 were analyzed by immunoenzymatic methods. Hyperhomocysteinemia was considered for plasma homocysteine concentration >17 micromol/L. Mean plasma homocysteine concentration and hyperhomocysteinemia prevalence were significantly (p<0.001) higher in patients (16.3 +/- 7.9 micromol/L and 29%) than controls (12.6 +/- 4.0 micromol/L and 10%). The association between hyperhomocysteinemia and coronary heart disease persisted after adjusting on main cardiovascular risk factors (multi adjusted odds ratio, 2.99; 95% CI, 1.18-7.59; p=0.02). No association was observed between hyperhomocysteinemia and coronary disease severity and extent. This study showed an independent association between hyperhomocysteinemia and coronary heart disease, suggesting a role of hyperhomocysteinemia in atherothrombogenesis. However, causal relationship is not yet established. Until results of homocysteine-lowering therapy trials become available, hyperhomocysteinemia should be researched and treated in coronary heart disease patients.     

血浆同型半胱氨酸与冠状动脉病变支数的关系

目的 探讨冠心病新的危险因素同型关胶氨酸（Ｈｃｙ）与冠状动脉（冠脉）病变支数的关系。方法 采用高效液相色谱法对１１７例行选择性冠脉造影的口才进行了血浆Ｈｃｙ水平的测定。冠脉造影显示３支冠脉中至少单支血管病变狭窄≥５０％者为冠心病患者（１０１例）。３支血管中任一血管狭窄程度均为０％者归入下沉对照组（１６例）。冠心病患者分为单支病变组（２９例）、双支病变组（３５例）及３支病变组（３７例）。结果 冠心病     

Fractions of total plasma homocysteine in patients with ischemic stroke before the age of 55 years

The mechanism responsible for the association between elevated circulating homocysteine levels and ischemic stroke remains unclear. Therefore, the authors assessed total plasma homocysteine (tHcy) and its fractions (free [fHcy] and protein-bound [bHcy] homocysteine) in patients with ischemic stroke before the age of 55 years. Fifty patients (23 men, mean age 46.8+/-7.6 years) with ischemic stroke or transient ischemic attacks, with symptoms lasting < 72 hours were enrolled. In this group: 32 (64%) patients had hypertension; 12 (24%), ischemic heart disease (IHD); and 20 (40%), type 2 diabetes mellitus (DM). The control group consisted of 30 matched healthy individuals (17 men, mean age 44.6+/-6.2 years). The tHcy, fHcy, and bHcy levels were determined by high-performance liquid chromatography. tHcy and its fractions did not differ significantly between patients and controls. However, stroke patients with hypertension had significantly higher concentrations of tHcy and bHcy compared to stroke patients without hypertension (tHcy 13.0+/-3.3 vs 10.7 +/-3.2 micromol/L, p < 0.05; bHcy 9.7+/-2.6 vs 7.8+/-2.3 micromol/L, p < 0.01, respectively); fHcy was borderline significant: 3.1 (1.5-6.5) vs 2.5 (1.8-5.3) micromol/L, p = 0.05. The presence of IHD, DM, hyperlipoproteinemia, clinical subtypes of stroke, smoking, and family history of stroke did not influence these parameters. In the group of 50 patients, tHcy correlated with mean systolic blood pressure (BP) (r = 0.3, p < 0.05) and bHcy correlated with mean systolic and mean diastolic BP (r = 0.3, p < 0.05). These findings suggest an association between hypertension and redox status of Hcy in patients with ischemic stroke before the age of 55 years. This observation supports the hypothesis that elevated BP may contribute to Hcy-related vascular injury.     

Absence of association between serum homocysteine levels and coronary artery disease in south Indian males.

BACKGROUND: Asian Indians are reported to have a very high prevalence of premature coronary artery disease. However, traditional risk factors do not explain this excess of coronary artery disease. Elevated levels of homocysteine are reported to be associated with coronary artery disease among Europeans. This study looked at the association of serum homocysteine levels with coronary artery disease in South Indians. METHODS AND RESULTS: Four groups of patients were studied: Group 1 consisted of healthy nondiabetic subjects without coronary artery disease (n=18): Group 2 consisted of nondiabetic subjects with coronary artery disease (n=21); Group 3 consisted of type 2 diabetic patients without coronary artery disease (n=18) and Group 4 consisted of type 2 diabetic patients with coronary artery disease (n=20). The mean homocysteine value was 12.4+/-3.4 micromol/L in Group 1; 12.6+/-4.6 micromol/L in Group 2; 10.1+/-4.4 micromol/L in Group 3; and 10.4+/-3.9 micromol/ L in Group 4. There was no significant difference in the homocysteine levels between the groups studied. The prevalence of hyperhomocysteinemia, defined as a level of 17.1 micromol/L (the 95th percentile for serum homocysteine in the control group) was not significantly different among the groups. CONCLUSIONS: Elevated serum homocysteine levels are not associated with coronary artery disease in South Indian male subjects with or without diabetes. However, the results must be interpreted with caution because of the small numbers studied.     

Elevated levels of homocysteine in plasma as a risk factor for coronary artery disease

This study was performed to assess the significance of association between coronary artery disease (CAD) and circulating homocysteine concentrations. 100 consecutive CAD patients (78 men and 22 women, aged 31 to 79 years) qualified for PTCA were investigated. At the time of PTCA, the risk factors for CAD and plasma for homocysteine and vitamins were obtained. The controls were without clinical evidence of coronary artery disease and hypertension (90 men and 30 women aged 32 to 81 years). Homocysteine was assayed using ELISA test. Red cell folate and plasma vitamin B12 were assayed by immunofluoroscency (Delphia test). Homocysteine concentrations were higher in patients than in controls (13.61 +/- 4.5 vs 10.99 +/- 4.49 mumol/L, p < 0.001, adjusted for age). Male patients had nonsignificantly higher homocysteine levels than females (13.94 +/- 5.21 vs 11.46 +/- 5.16 mumol/L, p = 0.05, adjusted for age). Elevated homocysteine level--defined as one in the top fifth of the control distribution > or = 12.83 mumol/L--was seen in 46% of the patients compared with 20% of the control group (p = 0.001). The odds ratio (OR) for CAD in persons with elevated homocysteine level was 3.1 (95% Cl 1.6-5.8, p < 0.001, adjusted for age). The OR for CAD of 5 mumol/L increment in homocysteine level was 2.1 (95% Cl 1.4-3.1 p < 0.001, adjusted for age). After adjustment for conventional risk factors (age, smoking, hypertension, family history of CAD, hyperlipidemia), elevated homocysteine level remained independent risk factor for CAD (OR 2.88, 95% Cl 1.1-7.8, p < 0.05). We observed inverse correlation between homocysteine and folate level (r = -0.32, p = 0.005) and between homocysteine and vitamin B12 concentrations (r = -0.24, p = 0.03), especially in men. Patients with elevated homocysteine level had lower levels of folate (629.6 +/- 241.2 nmol/L vs 735.1 +/- 252.4 nmol/L, p < 0.05), and vitamin B12 (213.6 +/- 64.4 pmol/L vs 246.6 +/- 62.3 pmol/L, p < 0.05) than patients with normal level of homocysteine. Elevated plasma homocysteine level is a strong risk factor for coronary artery disease. A 5 mumol/L increment in total homocysteine level may be associated with twofold increase of risk for the disease.     

Plasma homocysteine, methylenetetrahydrofolate reductase genotypes, and age at onset of symptoms of myocardial ischemia

Elevated fasting plasma homocysteine is a graded risk factor of coronary artery disease (CAD) and may accelerate onset of CAD. Homozygosity for the C677T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene is commonly but inconsistently associated with hyperhomocysteinemia. In the present study we examined the possible relation between levels of fasting plasma homocysteine and age at CAD onset in different MTHFR genotypes. We studied 182 patients with CAD, 74 patients with early onset CAD (aged < or = 45 years), and 108 patients with later onset CAD (aged 46 to 65 years). Plasma homocysteine levels in 90 subjects without CAD were used for control. Fasting plasma homocysteine levels in T/T homozygotes with early onset CAD (20.2 +/-12.5 micromol/L) was markedly higher than in T/T homozygotes with later onset CAD (13.4 +/- 6.8 micromol/L) and in patients with early onset CAD who were not T/T homozygotes (11.9 +/- 3.7 micromol/L; p = 0.034 and p = 0.0001, respectively). CAD developed earlier in T/T homozygotes who were hyperhomocysteinemic (>15 micromol/L) than in the T/T homozygotes who were not (p = 0.036). Plasma homocysteine levels had no effect on age at onset of CAD in patients who were non-T/T genotypes. Homocysteine levels in control subjects and in patients who were non-T/T genotypes were comparable and were not influenced by age. The results reveal an inverse relation between the level of fasting plasma homocysteine and age at onset of CAD in T/T homozygotes as opposed to no association in patients who were non-T/T genotypes. Additionally, these results show that hyperhomocysteinemia and the T/T genotype have a stronger effect on the pathogenesis of CAD when they are combined, and that a marked increase (>15 micromol/L) in fasting plasma homocysteine in T/T homozygotes is a risk factor for early onset of CAD.     

Hyperhomocysteinaemia and coronary artery disease in the Turkish population

OBJECTIVE: Many studies have demonstrated a strong association between elevated plasma total homocysteine (Hcy) levels and vascular disease. The objective of this study was to examine the relation between homocysteine levels and coronary artery disease in Turkish patients. METHODS AND RESULTS: In this study plasma homocysteine levels were measured in control and patient groups. A significant coronary artery lesion was defined as a stenosis of > or = 70% as shown by coronary angiography and determined by on-line quantitative measurements; treatment was by coronary angioplasty. Total plasma Hcy level was measured before the coronary intervention. Plasma homocysteine levels were measured by an HPLC method in patients with a definite diagnosis of coronary artery disease and compared with age- and sex-matched controls. Patients with coronary artery disease had significantly higher mean homocysteine concentrations than control subjects (geometric mean +/- 95% CI: 12.5 +/- 1.1 micromol/l vs. 8.60 +/- 1.07 micromol/l, p<0.001). Eighty-three (59%) members of the patient group and 14 (21%) members of the control group had plasma homocysteine concentrations above the 11.3 micromol/l, which represents the concentration which includes the uppermost quintile of the control group distribution (odds ratio 4.35, 95% CI; 2.1-8.94). CONCLUSION: Results of this study indicate that high plasma levels of homocysteine in Turkish subjects are associated with coronary artery disease. Our data suggest that focusing public health initiatives on this issue may reduce the high prevalence of cardiovascular disease in the Turkish population.     

Usefulness of plasma vitamin B(6), B(12), folate, homocysteine, and creatinine in predicting outcomes in heart transplant recipients

Atherothrombotic complications are frequently seen in patients undergoing heart transplantation. These patients have high plasma total homocysteine concentrations associated with lower folate and vitamin B(6) levels. The relation between these metabolic abnormalities and the development of vascular complications, however, remains unclear. Fasting plasma total homocysteine, folate, vitamin B(12), vitamin B(6), and creatinine were measured in 160 cardiac transplant recipients who were followed for a mean duration of 28 +/- 9 months after blood draw (mean 59 +/- 28 months after transplant). Cardiovascular events and causes of mortality were determined and Cox proportional-hazards regression analysis was used to identify the independent predictors for cardiovascular events and mortality. Twenty-five patients developed cardiovascular events and 17 died (11 cardiovascular deaths). Mean +/- SD total homocysteine value was 18.4 +/- 8.5 (range 4.3 to 63.5 micromol/L). Hyperhomocysteinemia (> or =15 micromol/L) was seen in 99 patients (62%). Levels were no different in patients with or without cardiovascular complications/death (16.8 +/- 6.2 vs 18.9 +/- 9 micromol/L, p = 0.4). However, vitamin B(6) deficiency was seen in 21% of recipients with and in 9% without cardiovascular complications/death (p = 0.05). The relative risk for cardiovascular events, including cardiovascular death, increased 2.7 times (confidence interval 1.2 to 5.9) for B(6) levels < or =20 nmol/L compared with those with normal B(6) levels (p = 0.02). Thus, hyperhomocysteinemia is common in transplant recipients but may have no causal role in the atherothrombotic vascular complications of transplantation. Deficiency of vitamin B(6), however, may predict adverse outcomes, suggesting a possible role for supplementation with this vitamin.     

Hyperhomocysteinemia: an additional risk factor in white coat hypertension

The association between homocysteine and sustained hypertension (HT) has been studied. The aim of this study was to assess homocysteine levels in white coat hypertension (WCH) as an indicator of increased risk in the development of cardiovascular diseases. WCH was defined as clinical hypertension and a daytime ambulatory blood pressure of < 135/85 mmHg. Plasma levels of homocysteine were determined in patients with WCH, hypertension, and normotension (NT). The study group included 100 subjects, 33 with WCH (16 males, 17 females) aged 49.1 +/- 1.9; 35 sustained hypertensives (17 males,18 females) aged 48.5 +/- 1.7 and 32 normotensive control subjects (15 males, 17 females) aged 48.8 +/- 2.2. The subjects were matched for age, gender, and body mass index. Patients with a smoking habit, dyslipidemia, or diabetes mellitus were not included in the study. Homocysteine levels were analyzed by ELISA. Plasma homocysteine levels were significantly higher in the WCH group compared to the controls (12.32 +/- 1.07 versus 5.35 +/- 1.38 micromol/L; P < 0.001) and the WCH group had significantly lower homocysteine values than the hypertensives (19.03 +/- 0.76 micromol/L P < 0.001). Total cholesterol and tri-glycerides were not different among the groups. There were no statistically significant differences in urinary albumin excretion (UAE) or creatinine clearance between the three groups. Hypertensive retinopathy was observed in the WCH group, but was less severe and less frequent compared to HTs. LVMI was greater in the WCH group compared to the NTs, but significantly less than HTs. The data demonstrate that WCH is associated with high levels of homocysteine. The increase in homocysteine level in WCH is not as high as in SHT. Since an elevated plasma homocysteine level is a strong risk factor for coronary artery disease and there was target organ damage in our WCH group, we conclude that WCH should not be considered to be an innocent trait.     

Hyperhomocysteinemia in patients with heart failure referred for cardiac transplantation: preliminary observations

BACKGROUND: Hyperhomocysteinemia is becoming recognized as a risk factor for cardiovascular disease, yet there are limited data on the prevalence of hyperhomocysteinemia in patients with heart failure. HYPOTHESIS: The purpose of this study was to examine the prevalence of hyperhomocysteinemia in patients with severe heart failure and to correlate serum homocysteine levels with factors that may affect homocysteine metabolism. METHODS: Serum homocysteine levels were measured at the time of cardiac transplant evaluation in 89 consecutive patients with severe heart failure. Homocysteine levels for patients with ischemic cardiomyopathy (ICM) were compared with levels obtained in patients with nonischemic cardiomyopathy (NICM), and homocysteine levels were correlated with demographic and hemodynamic parameters as well as functional status. RESULTS: The mean plasma homocysteine level was increased (14.3 +/- 5.3 micromol/l, normal <9.0 micromol/l) and was equivalent between patients with ICM versus NICM (14.7 +/- 5.8 micromol/l vs. 13.8 +/- 4.5 micromol/l, p = 0.44). Elevated homocysteine levels were seen in a large proportion (89%) of patients and were equally common to patients with NICM (94%) and ICM (85%). Serum homocysteine levels correlated with serum creatinine (r = 0.51, p < 0.001), with a history of diabetes (p = 0.028), and with a history of peripheral vascular disease (p = 0.045). Only 6% of patients were receiving folic acid therapy at the time of transplant referral. CONCLUSION: Hyperhomocysteinemia is common in patients with severe heart failure, and plasma homocysteine levels are uniformly elevated regardless of the etiology of heart failure. Elevated plasma homocysteine levels are likely a consequence of heart failure-related renal insufficiency.     

Increased serum leptin concentrations in patients with chronic stable angina pectoris and ST-elevated myocardial infarction

Leptin is an adipocytokine that is produced mainly by adipose tissue; it is also identified in atherosclerotic lesions in human coronary atherosclerosis. However, the relation of serum leptin concentrations to ischemic heart disease (IHD) is still obscure. The aims of the present study were to investigate serum leptin concentrations in patients with ST-elevated myocardial infarction (STEMI) and with chronic stable angina pectoris (CSAP) and to evaluate the possible correlations of leptin to other atherosclerotic risk factors; including serum high sensitive C-reactive protein (Hs-CRP), serum homocysteine, and fibrinogen concentrations. For this purpose, 35 patients with CSAP, 40 with acute STEMI, and 30 control subjects with normal findings from coronary angiography were taken into the study prospectively. Serum leptin concentrations were significantly higher in patients with CSAP and STEMI compared to the control group (7.74 +/-1.34 vs 6.37 +/-1.85 ng/mL, p=0.021 and 8.22 +/-3.13 vs 6.37 +/-1.85 ng/mL, p=0.023, respectively). In addition, serum homocysteine concentrations were significantly increased in patients with CSAP (15.23 +/-5.96 vs 11.40 +/-2.11 micromol/L, p=0.025) and patients with STEMI (15.90 +/-5.02 vs 11.40 +/-2.11 micromol/L, p=0.012) compared to the control group. Serum fibrinogen concentrations were significantly increased only in the CSAP group as compared to controls (4.15 +/-1.39 vs 3.45 +/-1.19 g/L, p=0.025). No significant correlation was found between leptin levels and selected risk factors. In conclusion, serum leptin concentrations were significantly higher in both the CSAP and STEMI groups. However, owing to the lack of correlation between the leptin levels and selected classical coronary risk factors, it may be considered that leptin can be evaluated as one of the independent risk factors for IHD. Further randomized and controlled studies will be required to determine the pathophysiological meaning of the increased leptin levels and the central role between adipocyte function and atherosclerosis.     

Low-grade urinary albumin excretion in normotensive/non-diabetic obstructive sleep apnea patients

Previous studies have indicated that high levels of urinary albumin excretion (UAE) are associated with an increased incidence of cardiovascular morbidity and mortality. This study examined the association between UAE and obstructive sleep apnea syndrome (OSAS). The study included 35 newly diagnosed OSAS patients and 11 nonapneic controls. Subjects with diabetes mellitus, hypertension, a history of renal failure, cardiac failure, coronary heart disease, collagen tissue disease, high serum creatinine, and urinary infection, and who use angiotensin-converting enzyme inhibitors and were women were excluded from the study. A single void morning urine sample at the baseline examination was used to measure UAE. There were no significant differences in the age, body mass index (BMI), and smoking habits of the OSAS patients and controls. UAE of the OSAS group was significantly higher than that of the control group (23.3 +/- 6.1 microg/min vs. 6.5 +/- 2.1 microg/min, respectively; P = 0.002). UAE was positively correlated to length of time spent at an oxygen saturation of <90% (r = 0.503, P = 0.002) and BMI (r = 0.361, P = 0.033). Regression analyses (r (2) = 0.504, P < 0.0001) showed that the length of time spent at an oxygen saturation of <90% (P < 0.0001) was risk factor for UAE, independent of age and BMI. Our study supports the notion that low-grade UAE is associated with non-hypertensive/non-diabetic OSAS, independent of age and BMI. Low-grade UAE may be a marker for subclinical vascular damage that predisposes OSAS patients to future cardiovascular disease.     

Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B6 and B12

An increased plasma homocysteine concentration is a risk factor for atherosclerosis. Folic acid lowers homocysteine but the optimal dose in patients with coronary artery disease (CAD) is unclear. This placebo-controlled, single-blind, dose-ranging study evaluates the effect of low-dose folic acid on homocysteine levels in 95 patients aged 61 +/- 11 years (mean +/- SD) with documented CAD. Patients in each group were given either placebo or 1 of 3 daily supplements of folic acid (400 microg, 1 mg, or 5 mg) for 3 months. Each active treatment arm also received 500 microg vitamin B12 and 12.5 mg vitamin B6. Total plasma homocysteine levels were measured after 30 and 90 days. Folic acid 400 microg reduced homocysteine levels from 13.8 +/- 8.8 to 9.6 +/- 2.0 micromol/L at 90 days (p = 0.001). On 1- and 5-mg folic acid, levels decreased from 13.0 +/- 6.4 to 9.8 +/- 4.0 micromol/L (p = 0.001) and from 14.8 +/- 6.9 to 9.7 +/- 3.3 micromol/L (p < 0.001), respectively. The decrease was similar in all treatment groups. There was no significant change with placebo. Although the sample size is small, these findings suggest that daily administration of 400 microg/day folic acid combined with vitamin B12 and vitamin B6 may be equivalent to higher doses in reducing homocysteine levels in patients with CAD.     

Relationship between plasma homocysteine levels and saphenous vein graft disease after coronary artery bypass grafts.

The long-term efficacy of coronary artery bypass graft (CABG) surgery is limited by saphenous vein graft (SVG) disease. Elevated levels of plasma homocysteine are a known independent risk factor for cardiovascular disease. However, its influence on the patency of SVG is unknown. To determine whether plasma homocysteine levels are related to SVG disease after CABG we measured homocysteine levels in 80 patients who underwent CABG (age: 64+/-8, interval after bypass surgery: 6.4+/-3.1, range: 1-13 years). The patients were divided into a vein graft disease group (more than 50% angiographical stenosis in any vein graft, n=40) and a no-vein graft disease group (<50% stenosis in any vein graft, n=40). The presence of a mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene was also determined by polymerase chain reaction. Homocysteine levels in the vein graft disease group were significantly higher than in the no-vein graft disease group (11.2 vs. 9.1 micromol/l, p=0.01). Multiple regression analysis showed that the interval after CABG was an independent factor for SVG disease (odds ratio: 1.014, 95% confidence intervals: 1.003-1.025, p=0.013) and elevated levels of homocysteine tended to be an independent factor for SVG disease (odds ratio: 1.098, 95% confidence intervals: 0.994-1.213, p=0.067). There was no significant difference in MTHFR genotypes between the two groups. These findings indicate that elevated levels of plasma homocysteine are related to SVG disease after CABG.     

Homocysteine and coronary events in coronary disease patients

The objective of this study was to determine the prognostic value of serum homocysteine levels in patients with coronary heart disease. Homocysteine was assayed in 76 coronary patients with a mean age of 59.2 years hospitalized for myocardial ischaemia or myocardial infarction. Percutaneous transluminal angioplasty was performed in 47 (70%) of these patients during this hospitalization. The mean follow-up for these patients was 22 months (range: 11 to 67 months). In these patients, serum homocysteine levels were not correlated with the usual risk factors of coronary heart disease (age, sex, treated hypercholesterolaemia, smoking, diabetes) except for hypertension. It was strongly correlated with serum creatinine (R = 0.61; p = 0.0001). Eleven patients presented a major event during follow-up (8 deaths, 1 nonfatal myocardial infarction, 1 cardiac transplantation) and 16 underwent a revascularization procedure. The blood homocysteine level does not have any prognostic value for any coronary events. However, it is higher in patients who develop a major event than in those which do not (15.8 +/- 4 mumol/l versus 11.5 +/- 6.6 mumol/l, p = 0.05). Using multivariate analysis, taking into account age, serum creatinine and serum homocysteine, only serum homocysteine was predictive of major event-free survival (p = 0.02).     

The relation between homocysteine and calcific aortic valve stenosis

BACKGROUND: In patients diagnosed with calcific aortic valve stenosis, cardiac risk factors are similar to those of coronary artery disease; homocysteine concentration is an independent risk factor for coronary artery disease. The aim of this study was to investigate the correlation between plasma homocysteine levels and aortic valve stenosis and the influence of homocysteine levels on the coexistence of coronary artery disease in patients with moderate to severe aortic valve stenosis. METHODS: Fifty-eight patients who had been diagnosed with moderate to severe aortic stenosis formed the test group of this study, and 47 healthy subjects without coronary artery disease or aortic valve stenosis formed the control group. The patients with aortic stenosis were divided into two groups according to the presence or absence of coronary artery disease in their coronary angiograms. After 12 h fasting venous blood samples were collected and total cholesterol, low-density lipoprotein, high-density lipoprotein, triglycerides and homocysteine levels were measured and compared between the two groups. MEASUREMENTS AND RESULTS: The mean blood homocysteine level was 10.8 +/- 3.3 micromol/l in patients with aortic valve stenosis and 8.1 +/- 4.7 micromol/l in the control group; the difference between these levels was statistically insignificant. The patients with aortic valve stenosis had significantly higher levels of total cholesterol and hypertension and were more likely to have a positive family history for coronary artery disease. When the two subgroups of patients with aortic valve stenosis were compared, mean blood homocysteine levels were 13.2 +/- 3.1 and 8.3 +/- 2.2 micromol/l, respectively, showing significantly higher levels in the group with coronary artery disease. In this comparison patients with coronary artery disease were also found to have significantly higher levels of total cholesterol and LDL and they were more likely to be smokers. CONCLUSIONS: Although there was no relation between blood homocysteine levels and the existence of aortic valve stenosis, in cases with both coronary heart disease and aortic stenosis homocysteine levels were significantly higher than in the patients with pure aortic valve stenosis.     

Plasma total homocysteine levels in a healthy Turkish population sample

OBJECTIVE: The objective of this study is to determine the reference values of homocysteine levels from a sample of healthy native Turks, and the relationship of these levels with gender, age and other risk factors. METHODS AND RESULTS: Plasma homocysteine level was measured in 159 healthy Turkish individuals. Homocysteine levels were determined by the HPLC method and differences between sex and age groupings (20-40 years, 41-60 years, and 61 and older) were compared. Mean homocysteine levels were 8.91 +/- 1.41 micromol/l. The median homocysteine level was 8.35 micromol/l (men 8.80, women 7.0). Homocysteine levels significantly increased with age (r = 0.49) and higher in men than in women in each age group (p < 0.05) (men: 9.51 +/- 1.40; women 7.38 +/- 1.36; p < 0.001). The cut-off point for high homocysteine level is selected to be the value that marks the upper 20% of the control population distribution (12.26 micromol/l). Postmenopausal > 60-year-old women manifested significantly higher increases in total homocysteine concentrations than 20 to 40-year-old premenopausal women. There were no significant correlations between homocysteine and body mass index, glucose, total and lipoprotein lipids, C-reactive protein, creatinine, smoking and alcohol consumption except blood pressure and uric acid. CONCLUSIONS: These data indicate the significance of sex- and age-associated differences of homocysteine levels in native Turkish subjects. Upper reference limits for the plasma total homocysteine concentration increased with age and were higher for men than for women at all ages. Focusing public health initiatives on this issue may reduce the high prevalence of cardiovascular disease in the Turkish population.