Homocysteine and restenosis after percutaneous coronary intervention.

Numerous clinical studies in Western and Asian countries suggest that individuals with elevated blood levels of homocysteine have an increased risk of atherosclerosis, myocardial infarction, cerebral infarction, and deep vein thrombosis. Homocysteine is also known to induce both atherogenic and thrombogenic mediators in cultured vascular cells so that homocysteine may influence the damage of endothelial cells, promote smooth muscle cell growth, induce atherogenic mediators and thrombus formation after coronary angioplasty. The association between homocysteine and restenosis after percutaneous coronary intervention (PCI) has been discussed. In this study, the relationship between plasma homocysteine levels and restenosis after PCI to investigate whether plasma homocysteine levels may be a predictor of restenosis after PCI was examined. One hundred consecutive patients who underwent successful PCI were enrolled and plasma homocysteine level was measured in all patients prior to PCI. Plasma for homocysteine level was obtained in 99 of 100 patients who had angioplasty. The mean plasma homocysteine concentration in the enrolled patients was 13.61 +/- 6.04 micromol/L. The minimum and maximum of plasma homocysteine were 4.40 micromol/L and 50.00 micromol/L, respectively. In healthy subjects, the normal reference range of homocysteine level is 5-15 micromol/L However, recent data suggest that some patients may be at increased cardiovascular and cerebrovascular risk at levels as low as 12 micromol/L. For this reason, both cut off points of homocysteine level > or = 15 micromol/L or > or = 12 micromol/L to identify the high homocysteine level group were used. Of 99 patients, high homocysteine level (> or = 15 micromol/L) was established in 9 patients with restenosis versus 20 patients without restenosis. If the cut off point of homocysteine level > or = 12 micromol/L was used, high homocysteine level was established in 14 patients with restenosis versus 39 patients without restenosis. From both cut off points of homocysteine level, there was no correlation between plasma homocysteine level and the restenosis group. (p>0.05).

Serum lipoprotein (a) level and restenosis after percutaneous coronary intervention.

Restenosis is regarded as the result of a combination of various pathological events. The mechanisms are complex and not completely understood. In this study, the authors focused on the lipoprotein (a) (Lp (a)). It is one of the novel risk factors in atherosclerotic vascular disease. Numerous clinical studies suggest that individuals with elevated blood levels of Lp (a) have been shown to be associated with atherosclerotic vascular disease. However, whether a high serum concentration of Lp (a) affects restenosis after PCI remains controversial. In this study, the relationship between serum Lp (a) levels and restenosis after PCI was examined to investigate whether serum Lp (a) levels may be a predictor of restenosis after PCI. Of the 100 patients studied, 31 patients (31%) were classified as the restenosis group and 69 patients (69%) the non-restenosis group. Both groups did not significantly differ in serum concentration of total cholesterol, triglyceride, HDL-C, and LDL-C. The mean serum Lp (a) concentration in patients with restenosis was 41.50 +/- 34.99 mg/dL compared with a mean serum Lp (a) concentration of 29.87 +/- 25.47 mg/dL in those without restenosis. There was no statistical significance of Lp (a) level between the restenosis and non-restenosis groups (p=0.06). In healthy subjects, the normal reference range of serum Lp (a) concentration is below 30 mg/dL. From this reference, if a cut off point of serum Lp (a) concentration equal to 30 mg/dL or above to identify high Lp (a) level group was used. High serum Lp (a) level was established in 15 patients with restenosis versus 21 patients without restenosis. From this cut off point of serum Lp (a) level, the authors did not find a correlation between serum Lp (a) level and the restenosis group. (p=0.08).

Serum magnesium in Thai coronary artery disease patients.

Hypomagnesemia or magnesium (Mg) deficiency has been hypothesized to play a role in coronary artery disease (CAD). The authors aimed to evaluate serum Mg concentration in 100 CAD patients compared with 100 healthy controls. Mean values of serum Mg level in CAD and the control group were 2.14 +/- 0.39, 2.24 +/- 0.3 mg/dL respectively (P=0.052). The prevalence of Mg deficiency was 12 per cent in the CAD patients, and 5 per cent in the control group (odds ratio=2.59, 95% confident interval = 0.88-7.65, P=0.063). There was no significant difference in the serum Mg level between the 2 groups, although it tended to be lower in CAD patients. The prevalence of Mg deficiency did not differ significantly between the study group, however, it tended to be higher in CAD patients. These findings demonstrated that CAD patients may be associated with Mg deficiency, and contribute to the pathogenesis of CAD or acute thrombosis. Following this evidence, Mg treatment may be necessary in CAD patients with Mg deficiency or acute myocardial infarction (AMI).

Rapid detection of Chlamydia pneumoniae DNA in peripheral blood mononuclear cells of coronary artery disease patients by real-time fluorescence PCR.

Several recent reports including serological, pathological and animal studies have associated Chlamydia pneumoniae with coronary artery disease (CAD). In order to establish whether chronic C. pneumoniae infection is linked to coronary artery disease, clinical intervention trials may be needed. However, to detect eligible patients with persistent infection, a reliable diagnostic marker must be developed for identifying cases and assessing efficacy of antichlamydial therapy. Moreover, the prevalence of circulating C. pneumoniae DNA in CAD patients varied widely from previous reports. A real-time PCR has been established by using HL-1 and HR-1 primer to amplify 437 base pairs product. Confirmation of the product was performed on LightCycler by melting curve analysis of detection probes labeled with LC-Red705. Ninety-five angiographically confirmed CAD patients and 104 normal, healthy volunteers were recruited. The mononuclear cell layer was separated from collected blood and rapid, single step real-time PCR was used to detect C. pneumoniae DNA. C. pneumoniae DNA in peripheral blood mononuclear cells (PBMC) was found in 17 per cent of 95 CAD patients and 1 per cent of 104 normal healthy volunteers (odds ratio 20.86, 95% confidence interval 2.71 - 160.67, p < 0.0001). There was no association between C. pneumoniae DNA in PBMC and serological status. The rapid, real-time PCR showed a clear-cut result between positive and negative cases. PBMC-based real-time PCR may be a useful tool for identifying subjects carrying C. pneumoniae in the circulation or in the vascular wall as well. It will be a specific indicator of current infection and will be used as a marker for assessing the microbiological efficacy of antichlamydial therapy in clinical intervention trials.

Roxithromycin in prevention of acute coronary syndrome associated with Chlamydia pneumoniae infection: a randomized placebo controlled trial.

The role of Chlamydia pneumoniae infection in precipitating acute coronary syndrome (ACS) is unclear. Some studies have indicated that intervention with macrolide antibiotics might reduce coronary events in patients with ACS. A double blind, randomized, placebo-control trial was conducted on 84 ACS patients. Patients were randomized to 30 days of treatment with roxithromycin (150 mg, twice daily) or matching placebo. The follow-up period was 90 days, and the primary clinical end point included cardiovascular death, unplanned revascularization and recurrent angina/MI. Anti-C. pneumoniae IgG positive in 24 of 43 (55.8%) patients in the roxithromycin group and 23 of 41 (56.1%) patients in the placebo group. Anti-C. pneumoniae IgA positive in 20 of 43 (46.5%) patients in the roxithromycin group and 13 of 41 (31.7%) patients in the placebo group. Thirty-three cardiac events occurred (2 cardiovascular deaths, 9 CABG, 12 PTCA and 10 recurrent angina/MI) with 17 events in the roxithromycin group and 16 events in the placebo group. There was no significant difference of cardiac events between the roxithromycin and placebo groups. The present study suggests that antibiotic therapy with roxithromycin is not associated with reduction of cardiac events as reported by other investigators. However, therapeutic interventions may need to be specifically targeted to a group of patients who are confirmed with chronic C. pneumoniae infection.

Serum concentrations of lipids and apolipoprotein E in angiographically defined coronary artery disease patients.

Apolipoprotein (apo) E is an important component of plasma lipoproteins and influences lipoprotein metabolism through its action as a receptor ligand. The association of serum apo E concentrations and coronary artery diseases (CAD) was investigated in 100 CAD patients (71 men, 29 women, mean age 62.0 years) and 155 healthy volunteers (87 men, 68 women, mean age 50.6 years). Patients with CAD had lower serum apo E concentrations (5.1+1.3 mg/dL) than the healthy volunteers (5.9+1.8 mg/dL, p <0.001). There were no significant differences between the number of disease vessels and the concentration of serum apo E. Serum apo E concentrations may have an anti-atherosclerotic effect and the serum apo E levels could be a useful parameter for defining cardiovascular risk factor.

Prevalence of hyperhomocysteinemia in normal healthy Thai subjects.

The concentration of circulating total homocysteine is a sensitive marker of inadequate folate and vitamin B12 status. The elevations of plasma homocysteine concentration are associated with an increased risk of vascular disease. The primary goals of this study were to identify plasma homocysteine concentrations in Thai residents and to test for differences in homocysteine levels among sex and age categories. The authors measured plasma total homocysteine concentrations in 3,345 Shinawatra employees (1,133 males, 2,212 females aged between 20-65 years) by using fluorescence polarization immunoassay (FPIA) method. The mean plasma homocysteine concentrations of males and females were 11.495 and 8.547 micromol/L respectively. Plasma homocysteine concentrations were significantly lower in females than in males (p < 0.0001). The age-specific plasma homocysteine levels were lower in females than in males for each group, but the levels of each group was not significantly different both in males and females. When more than 12 micromol/L was used as the cut-off value, it was found that 33.6 per cent of males and 6.69 per cent of females were classified as hyperhomocysteinemia subjects. The authors concluded that the prevalence of hyperhomocysteinemia in Thai males is more common than in females. Further investigation should be done to clarify the association between serum folate, vitamin B12, vitamin B6 concentrations and plasma homocysteine concentration.

Chlamydia pneumoniae antibodies and angiographically demonstrated coronary artery disease in Thailand.

Recent reports have suggested an association between Chlamydia pneumoniae and coronary artery disease. This study investigated the relationship between the presence of immunoglobulin G (IgG), immunoglobulin A (IgA) of C. pneumoniae in angiographically diagnosed coronary disease. Patients enrolled were 243 (178 male, 65 female, mean age 61 +/- 10 years) with angiographically proven at least one significant coronary artery stenosis. Fifty-eight patients (33 male, 25 female, mean age 57 +/- 11 years) with no angiographic evidence of coronary lesions were used as the normal coronary angiogram group. Control subjects (95 male, 92 female, mean age 58 +/- 17 years) were used as normal healthy persons who had no history of coronary artery disease. C. pneumoniae IgG and IgA antibodies were measured by ELISA method. We found that 179 out of 243 (73.7%) coronary artery disease (CAD) patients were positive for IgG and 132 out of 243 (54.3%) were positive for IgA. In 58 normal coronary angiogram patients, 23 (39.7%) cases were positive for IgG and 6 (10.3%) cases were positive for IgA. Among 187 healthy controls, 111 (59.4%) cases were positive for IgG and 83 (44.4%) were positive for IgA. When C. pneumoniae IgG antibodies were considered, there was significant difference between CAD patients and healthy controls (OR = 1.91, 95% CI = 1.27 - 2.88, p = 0.0018). In cases of positive IgA antibodies, significant difference was also found between CAD patients and healthy controls (OR = 1.49, 95% CI = 1.02 - 2.19, p = 0.0257). These findings were also found with higher odds ratio when we compared between CAD patients and normal coronary angiogram patients. The result suggested that C. pneumoniae infection is common in Thai people and chronic C. pneumoniae infection is more common in CAD patients. Chronic C. pneumoniae infection may be associated with the development of atherosclerotic coronary disease and treatment with antibiotics should be considered in ischemic heart disease.

Comparison of the Thai version of the Rose questionnaire for angina pectoris with the exercise treadmill test.

Prior to exercise treadmill testing (ETT), 157 patients (92 males and 65 females) were interviewed twice separately, using a Thai version of the Rose questionnaire for angina pectoris. One interview was conducted by a physician and the other by a nurse. The questionnaire responses were compared with ETT results. Based on physician-conducted interview, the Rose questionnaire had a sensitivity of 30.3 per cent, a specificity of 83.9 per cent, a positive predictive value of 35.3 per cent, a negative predictive value of 81.9 per cent, and the total accuracy of 72.6 per cent. There were gender differences in the validity of the questionnaire, with higher specificity, higher positive predictive value, and lower negative predictive value in males than in females. The sensitivity and accuracy were not different between the two sexes. In 87.9 per cent of cases, responses to physician-conducted and nurse-conducted interview were the same. There were no significant differences between responses to the questionnaires by the physicians and by the nurses.

Association between serum homocysteine, vitamin B12, folate and Thai coronary artery disease patients.

BACKGROUND: Homocysteine is an intermediate compound formed during metabolism of methionine. The plasma level of homocysteine is dependent on the genetically regulated level of essential enzymes and the intake of folic acid, vitamin B6 (pyridoxine), and vitamin B12 (cobalamine). Elevated serum homocysteine levels are a known risk factor for coronary artery disease (CAD). To establish the magnitude of the CAD that is associated with an increased serum homocysteine level, we compared CAD patients with normal healthy Thai controls. METHOD: In a cross-sectional study design we investigated the association between serum homocysteine, vitamin B12 and folate levels and the coronary heart disease in 178 CAD patients and 178 normal healthy controls by age and sex matching. These comprised 266 men and 90 women, mean age 58 +/- 10 years for normal controls and 60 +/- 10 years for CAD patients. Serum homocysteine, vitamin B12 and folate were measured by ELISA method and electrochemiluminescense method respectively. RESULTS: Paired t-test analysis showed that serum homocysteine concentrations were significantly higher in CAD patients (23.83 +/- 11.29 mumol/L) than in control subjects (19.69 +/- 8.51 mumol/L; p < 0.001). Homocysteine levels were also higher in males than in females. These findings were similar in healthy controls (male: 20.37 +/- 8.5 mumol/L, female: 17.77 +/- 8.2 mumol/L, p < 0.05) and in CAD patients (male: 24.91 +/- 11.8 mumol/L, female: 20.73 +/- 8.9 mumol/L, p < 0.05). Homocysteine above 17 mumol/L occurred more common in CAD patients than in control groups (OR = 1.65, 95% CI = 1.09-2.52, p = 0.0249). Low levels of vitamin B12 and folate did not reaching statistical significance when comparing controls and CAD patients. CONCLUSIONS: Serum homocysteine concentrations were significantly higher in CAD patients than in controls. Serum vitamin B12 and serum folate levels were not statistically significantly different between CAD patients and control groups. The data also demonstrated that the serum homocysteine level is almost always higher in men than in women as previously reported. Although serum vitamin B12 and serum folate levels were not below the upper limit of normal, vitamin B12 and folic acid treatment may reduce serum homocysteine concentrations in CAD patients. We hope that the reversible risk factors will be concern to clinicians for the reduction in the risk of myocardial infarction.

Hyperhomocysteinemia in patients with coronary artery disease.

Hyperhomocysteinemia has been recognized as a risk factor of atherosclerosis. This study was aimed to measure the risk of coronary artery disease in patients with hyperhomocysteinemia. Age, HDL level, tHcy level and history of DM were independent risk factors for coronary artery disease. The level of tHcy of 11.0 mmol/L provides the best sensitivity and specificity of predicting coronary artery disease.

Seroprevalence of Chlamydia pneumoniae infection in Thailand.

Chlamydia pneumoniae (C. pneumoniae) is an emerging infectious agent, with a spectrum of clinical manifestations, and it has recently been tentatively linked to atherosclerosis. In order to describe the seroprevalence of C. pneumoniae in Thailand, we evaluated 1,798 normal healthy subjects (aged 20-93 years) for anti-C. pneumoniae IgG and IgA. Specific antibodies were measured by the fully automated ELISA method using elementary bodies of C. pneumoniae as an antigen. IgG antibodies against C. pneumoniae were presented in 55.16 per cent of men and 41.63 per cent of women. Anti-C. pneumoniae IgA were presented in 31.50 per cent of men and 27.49 per cent of women. The prevalence of IgG antibody increased with age and reached 78 per cent in subjects between 51-93 years. The pattern of IgA antibody was a saddle shape, which indicated 2 peaks of chronic infection. Our results suggested that C. pneumoniae infection was common in Thailand. The high prevalence of evidence of exposure to C. pneumoniae may have implications for the prevention of cardiovascular disease if further study concludes that infection with this organism is a risk for cardiovascular disease.

Comparison of parathyroid hormone in angiographically-demonstrated coronary artery disease patients and healthy Thais.

Parathyroid hormone (PTH) influences the calcium metabolism. The idea of cardiovascular effects of PTH is not new. Target cells for PTH are cardiomyocytes and smooth muscle cells. Evidence from previous studies suggest that many patients with heart disease have elevated PTH concentrations. Our objective was to determine PTH status in patients with coronary artery disease (CAD). We compared intact PTH levels in 109 CAD patients with 103 healthy people by electrochemiluminescence immunoassay. Mean values of PTH in healthy Thais and CAD patients were 37.4 +/- 17.9 and 40.2 +/- 21.8 respectively. No statistical difference was shown. In addition, we compared PTH levels among various numbers of coronary occlusion and also found no differences. We propose that intact PTH concentrations in CAD patients are not higher than in the healthy population.

Biochemical markers of bone turnover in angiographically-demonstrated coronary artery disease patients and healthy Thais.

The patients with coronary artery disease (CAD) were suffering from dyspnea. Physical activity of these patients was limited. Their lifestyle may be contributory factors for osteoporosis. Recent research has shown that biochemical markers may be used to predict future bone loss and identify individuals at risk for osteoporosis. Our objectives were to estimate reference ranges of bone markers in healthy Thais and to compare bone turnover between 105 healthy people and 118 CAD patients by using biochemical markers of bone formation and resorption. Mean values of bone markers in controls and patients were 22.9 +/- 12.9, 21.6 +/- 16.2 respectively for N-Mid osteocalcin and 0.45 +/- 0.30, 0.47 +/- 0.37 respectively for beta-Crosslaps. There was no statistical difference of N-Mid osteocalcin (p=0.50) and beta-Crosslaps (p=0.64) values between groups. Our data from this study suggested that that CAD patients have no higher risk for osteoporosis than healthy people.

Impaired fasting glucose, diabetes mellitus and coronary risk factors.

The authors conducted a prevalence survey of impaired fasting glucose and diabetes mellitus in 3,615 Shinawatra employees, and we also determined various risk factors of coronary artery disease such as blood pressure level, body mass index and serum lipids. The prevalence of impaired fasting glucose and diabetes mellitus were 1.7 per cent and 0.8 per cent respectively. The prevalences were more common in males and increased with increasing age. Coronary risk factors were higher in impaired fasting glucose (IFG) and diabetes mellitus (DM) when compared with normal glucose levels. There were also significant differences between impaired fasting glucose and diabetes mellitus, except for pulse pressure, serum cholesterol level, LDL-cholesterol level and HDL-cholesterol level.

Regular exercise and cardiovascular risk factors.

Physical inactivity has been counted as a risk factor for coronary artery disease. Regular exercise has also been reported to reduce risk of cardiovascular disease and its risk factors. We surveyed 3615 subjects for their conventional risk factors of coronary disease and for the frequency of their exercise. We found that subjects who had regular exercise were more likely to have lower triglyceride and resting heart rate. HDL cholesterol was higher in the group of subjects who had regular exercise. There was no difference in fasting plasma glucose, total cholesterol or blood pressure levels between those who had and those who did not have regular exercise.

Are routine checkups necessary?: The Shinawatra's employee study.

The authors performed a survey in 3,615 Shinawatra employees aged 18-60 years to determine the abnormalities found with routine checkup. The annual checkup included: history taking. anthropometric measurement, physical examination, complete blood count, urine analysis, chest roentgenography, blood chemistry (fasting blood glucose, BUN, creatinine, uric acid, AST/ALT, cholesterol, triglyceride and HDL-cholesterol). The prevalence of abnormalities with management change detected by complete blood count, urine analysis was low and we did not recommend the routine use of complete blood count and urine analysis. The prevalence of hypertension was more common in males and the prevalence increased sharply after the age of 25 years in males and 40 years in females. The prevalence of abnormalities of BUN, creatinine (both males and females) and uric acid (in females) was very low. There was high prevalence of high AST/ALT which suggested hepatitis in our population, and the prevalence was more common in males beginning at a young age. Diabetes mellitus was more common in males especially after the age of 45 years. Chest roentgenography abnormalities were found in 9.4 per cent and the prevalence of abnormalities increased with age and was common after the age of 44 years. Most of the abnormalities found by chest roentgenography were pulmonary infiltration and cardiomegaly. The authors' findings did not recommend the routine use of complete blood count, urine analysis, fasting BUN and creatinine. We recommend routine blood pressure measurement in males aged 25 years or more and in females aged 40 years or more. We suggest routine blood cholesterol measurement in both sexes, blood triglyceride measurement in males aged 25 years or more and fasting blood sugar tests in males aged more than 44 years, chest roentgenography in males and females after the age of 45 years.

Prevalence of new coronary risk factors in Thai population.

Many new cardiovascular biomarkers of atherosclerosis have recently been emerging. However, there is a paucity of these data in the Thai population. This study aims to determine the prevalence of these biomarkers of atherosclerosis and the relationship between these new risk factors and other conventional risk factors for atherosclerosis in the healthy Thai population. As a yearly check-up program, we surveyed 3,615 normal healthy populations for their conventional risk factors and some new cardiovascular biomarkers for atherosclerosis. The authors found hyperhomocysteinemia and high level of Lp(a) in 27 per cent and 32 per cent of the cases respectively. Prevalence of recent and past chlamydial infection was found in 30 per cent and 51 per cent respectively.

Acute and follow-up results of laser angioplasty: single center experience.

Excimer laser angioplasty was used to treat total occluded coronary arteries and instent restenosis lesions with high success rate. To assess immediate and long-term results of patients treated with excimer laser, we analyzed demographic information and the immediate results of 44 patients who underwent ELCA. The patients were followed up and assessed for clinical restenosis. The initial success rate of ELCA was 86.4 per cent which is comparable to plain balloon angioplasty performed during the same period. Clinical restenosis was 29 per cent. In conclusion, ELCA for patients with coronary artery disease can be performed with initial high success rate and reasonable long-term restenosis.

Correlation of serum lipoprotein(a) with the clinical presentation of Thai coronary artery disease patients.

Elevated serum levels of lipoprotein(a) [Lp(a)] confer an increased risk of coronary artery disease (CAD) and have been confirmed as a strong and independent risk factor for this disease. This case-control study was to determine the significance of elevated Lp(a) levels for the existence of CAD by systematically recording cardiovascular risk factors in diagnostic coronary angiography in a group of patients. Two hundred thirty seven consecutive patients (175 men, 62 women, aged 61+/-10 years) which comprised 24 acute myocardial infarction (AMI), 76 unstable angina (UA) and 137 stable angina (SA) who underwent coronary angiography, were used as cases. One hundred seventy normal healthy volunteers (95 men, 75 women, and aged 58+/-15 years) were used as controls. Lp(a) concentration were measured by an immunoturbidimetric method (Roche Diagnostics, Switzerland). There was a significant difference between Lp(a) levels in UA compared with the control subjects (44.2+/-49.0 vs. 27.6+/-25.3 mg/dL, p = 0.0006). When we compared SA and the control group (35.6+/-31.3 vs. 27.6+/-25.3 mg/dL, p = 0.0139) there was a significant difference between these two groups. UA patients also had a significantly higher prevalence of abnormal Lp(a) (>30 mg/dL) compared with the normal healthy control group (43.2% UA vs. 28.8% control, OR = 1.90, 95%CI = 1.08-3.32, p = 0.0248). SA patients also had the same finding as UA patients in a higher prevalence of abnormal Lp(a) when compared with the control group (45.2% SA vs. 28.8% control, OR = 2.04, 95%CI = 1.27-3.27, p = 0.0028). These data further support the role of Lp(a) in atherosclerotic coronary disease and the pathogenesis of acute coronary syndromes.