High Sodium Intake in Women with Metabolic Syndrome

BACKGROUND AND OBJECTIVES: Metabolic syndrome and high sodium intake are associated with frequent cardiovascular events. Few studies have estimated sodium intake in subjects with metabolic syndrome by 24-hour urine sodium excretion. We evaluated sodium intake in individuals with metabolic syndrome. SUBJECTS AND METHODS: Participants were recruited by random selection and through advertisement. Twenty four-hour urine collection, ambulatory blood pressure measurements, and blood test were performed. Sodium intake was estimated by 24-hour urine sodium excretion. Participants receiving antihypertensive medications were excluded from analysis. RESULTS: Among the 463 participants recruited, subjects with metabolic syndrome had higher levels of 24-hour urine sodium excretion than subjects without metabolic syndrome (p=0.0001). There was a significant relationship between the number of metabolic syndrome factors and 24-hour urine sodium excretion (p=0.001). The proportion of subjects with metabolic syndrome was increased across the tertile groups of 24-hour urine sodium excretion (p<0.0001). The association of high sodium intake and metabolic syndrome was significant only among women. Among the factors related to metabolic syndrome, body mass index had an independent association with 24-hour urine sodium excretion (p<0.0001). CONCLUSION: Women with metabolic syndrome exhibited significantly higher sodium intake, suggesting that dietary education to reduce sodium consumption should be emphasized for women with metabolic syndrome.

Subclinical Renal Insufficiency Range of Estimated Glomerular Filtration Rate and Microalbuminuria Are Independently Associated with Increased Arterial Stiffness in Never Treated Hypertensives

BACKGROUND AND OBJECTIVES: Microalbuminuria (MAU) and decreased estimated glomerular filtration rate (eGFR) are risk factors for cardiovascular disease (CVD) in patients with hypertension. However, in hypertensive patients with normal or minimally reduced eGFR (> or =60 mL/min/1.73 m2) and with normo- or MAU, the value of combined estimation of eGFR and urine microalbumin for the risk assessment has not been widely reported. We evaluated the association between arterial stiffness and the combined estimation of eGFR and urine microalbumin. SUBJECTS AND METHODS: Subjects with never treated hypertension and normal or minimally reduced eGFR were evaluated (n=491, 50.1+/-10.4 years). eGFR was calculated by the simplified Modification of Diet in Renal Disease formula. Urinary albumin-to-creatinine ratio (UACR) was assessed with spot urine. Arterial stiffness was assessed with heart-femoral pulse wave velocity (hfPWV). All subjects were divided into four groups; group 1, eGFR > or =90 mL/min/1.73 m2 (normal eGFR) and normo-albuminuria (NAU); group 2, eGFR 89.9-60 mL/min/1.73 m2 (minimally reduced eGFR) and NAU; group 3, normal eGFR and MAU; group 4, minimally reduced eGFR and MAU. RESULTS: Group 1 had the lowest hfPWV (964.6+/-145.4; group 2, 1013.5+/-168.9; group 3, 1058.2+/-238.0; group 4, 1065.8+/-162.9 cm/sec). Analysis adjusting age, sex, body mass index, heart rate and mean arterial pressure showed significantly lower hfPWV of group 1 compared to group 2 (p=0.032) and 3 (p=0.007). Multiple regression analysis showed a significant association of hfPWV with logUACR {beta=0.096, 95% confidence interval (CI) 8.974-60.610, p=0.008} and eGFR (beta=-0.069, 95% CI -1.194 - -0.005, p=0.048). CONCLUSION: Minimally reduced eGFR or MAU is independently associated with increased arterial stiffness, indicating greater CVD risk.

Relationship Between Serum Uric Acid Levels, Metabolic Syndrome, and Arterial Stiffness in Korean

BACKGROUND AND OBJECTIVES: Associations have been reported between the serum uric acid (SUA) level, metabolic syndrome (MS), and atherosclerosis. We have determined the relationship between the SUA level, MS, and arterial stiffness in Korean. SUBJECTS AND METHODS: Cross-sectional data from 1,276 adults who underwent routine laboratory tests and pulse wave velocity (PWV) measurements during a health check-up were analyzed in a gender-specific manner. None of the participants had atherosclerotic cardiovascular disease, diabetes, renal disease, or systemic disease, or were under treatment which would affect SUA levels, or taking medications for hypertension or dyslipidemia. RESULTS: After adjustment for age, smoking status, total cholesterol (TC), and creatinine, the odds ratios (ORs, 95% confidence interval) of gender-specific quartiles of SUA for MS were 1.0, 1.28 (0.66-2.47), 1.46 (0.76-2.82), and 2.21 (1.15-4.26) in females, and 1.0, 1.33 (0.82-2.17), 1.60 (0.96-2.66), and 2.03 (1.21-3.40) in males. However, after adjustment for waist circumference, there were no significant differences in the ORs among the SUA quartile groups in females and males (both, p=NS). The Pearson's correlation coefficients for the relationship between SUA levels and heart-femoral (hf) PWVs or brachial-ankle (ba) PWVs were not significant in females and males (r=0.054 and r=0.015, respectively, in females; r=-0.036 and r=-0.015, respectively, in males; all, p=NS). CONCLUSION: An elevated SUA level is associated with abdominal obesity among the MS components, but the SUA level is not associated with PWV in females or males.

Effects of Physical Activity and Aerobic Exercise Capacity on Aortic Stiffness in Patients With Untreated Hypertension

BACKGROUND AND OBJECTIVES: High aerobic exercise capacity and sport-related physical activity are reported to be inversely associated with arterial stiffness in healthy young adults. However, it is unknown whether increased physical activity and/or high aerobic exercise capacity attenuate arterial stiffness in patients with untreated hypertension. SUBJECTS AND METHODS: We studied subjects with never-treated hypertension {n=84 (55 males); mean age+/-SD, 49+/-7 years; age range, 36-65 years}. We excluded subjects with a history of diabetes, angina, myocardial infarction, major arrhythmia, or cerebrovascular diseases and those who were taking any cardiovascular medications, including lipid-lowering agents. Carotid intima-media thickness (IMT) and heart-femoral pulse wave velocity (hfPWV) were measured before exercise testing was performed. Physical activity was estimated using a modified Baecke questionnaire. Aerobic exercise capacity was measured with maximal cardiopulmonary exercise testing (maximum oxygen uptake, Vo2max). RESULTS: Linear regression analysis showed a significant inverse correlation between sport-index and hfPWV (r=-0.404; p0.05). Carotid IMT was not associated with physical activity indices or Vo2max. CONCLUSION: In patients with untreated hypertension, increased sport activity was associated with lower aortic stiffness, but high aerobic exercise capacity was not. These results suggest that regular daily exercise, but not exercise capacity, is an important determinant of aortic stiffness in patients with untreated hypertension.

Increased Arterial Stiffness in Behcet's Disease Patients

BACKGROUND AND OBJECTIVES : Pulse wave velocity (PWV) is an ideal indicator of arterial stiffness. This study investigated arterial stiffness of different vascular regions in patients suffering with Behcet's disease (BD), and we assessed whether arterial stiffness was affected by the clinical parameters of BD. Subjects and METHODS : This study included 53 BD patients (mean age: 38+/-8 years) and 65 healthy controls (mean age: 38+/-8 years) who were without any known cardiovascular diseases. After recording the clinical parameters of the BD patients, pulse wave velocity was measured with an automated device in the heart-femoral, heart-carotid, heart-brachial and femoral-ankle segments. RESULTS : Patients with BD had significantly higher PWV values than did the controls in all the regional arterial segments. The PWV values were not correlated with the duration of the disease, corticosteroid use or the presence of active disease at the time of examination. The clinical variables related to severe BD manifestations, which included severe disease, male gender, vascular lesions or immunosuppressant use, were partly associated with increased PWV on the univariate analysis, but any statistical significance for these clinical variables was lost in all the regional arterial segments on multivariate analysis. In addition, multivariate regression analysis revealed that age and the mean arterial pressure were independently associated with increased PWV in most regional arterial segments for BD patients. CONCLUSION : The patients with BD had significantly increased arterial stiffness in all the regional arterial segments when compared with the healthy controls. Longitudinal studies that employ a large population are required to determine the pathophysiologic and prognostic implications of increased arterial stiffness in BD.

Late Late Stent Thrombosis after Intracoronary Brachytherapy: Learning from Brachytherapy Experiences in the Drug-Eluting Stent Era

Stent thrombosis is generally a fatal complication after percutaneous coronary intervention. Combined antiplatelet therapy is recommended to prevent stent thrombosis in those patients who have undergone stenting. However, there are conflicting opinions on the appropriate duration of instituting antiplatelet treatment, especially after intracoronary radiation therapy or drug-eluting stent implantation, which are two situations closely associated with an increased risk of stent thrombosis. We report here on 2 cases of late stent thrombosis that occurred despite giving combined antiplatelet therapy, and these maladies developed more than 4 years after intracoronary brachytherapy.

Morphologic Follow-Up of the Anastomotic Sites Using One-year and Five-year Angiography after Coronary Artery Bypass Grafting / 대한흉부외과학회지

BACKGROUND: We analysed the characteristics of anastomotic sites after coronary artery bypass grafting (CABG) using coronary angiographies (CAGs) performed at one and five years postoperatively in the same patient population. MATERIAL AND METHOD: Among the 219 patients who underwent isolated CABGs between January 1995 and December 1997, follow-up coronary angiograms were performed in 149 (75.3%) patients at one year and in 115 (58.1%) patients at five years postoperatively. FitzGibbon grading system was used to evaluate the anastomotic sites. RESULT: The patency rates of arterial grafts at one- and five-year were 96.5% (192/199) and 93.1% (134/144), which were higher than those of saphenous vein grafts (SVGs) (82.9% (224/270) and 77.5% (141/182), respectively) (p=0.01). Although there were significant decreases in the patency rates between one- and five-year CAGs of both arterial and venous grafts, the proportion of FitzGibbon grade B among the SVGs was increased from 5.2% (one-year) to 8.2% (five-year), suggesting the progression of vein graft disease (p<0.01). CONCLUSION: The patency rate of the arterial graft was higher than that of SVG in both one- and five-year CAGs. The attrition rate of saphenous vein graft was higher than arterial grafts.

Association of the Invasively Measured Aortic Stiffness and Coronary Artery Disease

BACKGROUND AND OBJECTIVES: Aortic stiffness is believed to be an important risk factor of coronary artery atherosclerosis (CAA), as it directly affects coronary perfusion. The following aspects of the invasively measured aortic pulse wave velocity (PWV) were assessed in relation to CAA: The effect of cardiovascular risk factors on PWV, the effect of PWV on the severity of CAA and on the development of the restenosis after drug-eluting stent (DES) implantation. SUBJECTS AND METHODS: 371 subjects who had undergone coronary angiography were enrolled, with all undergoing an invasive aortic PWV measurement also. 112 patients, who had undergone a DES implantation, were prospectively investigated for the effect of PWV in relation to the subsequent risk of major adverse cardiac events (MACE). RESULTS: Among the conventional cardiovascular risk factors, an age >60 (10.79+/-4.92 vs. 8.35+/-4.02, p=0.0006), diabetes (10.97+/-4.66 vs. 9.26+/-4.70 m/sec, p=0.0118) and dyslipidemia (10.38+/-4.97 vs. 9.47+/-4.55m/sec, p=0.0421) were significantly associated with an increased PWV, but sex, smoking and hypertension were not associated with an increased PWV. The PWV was shown to be significantly associated with the severity of CAD. The odds ratio (OR) of 1m/sec increment in the PWV for an increased vessel score was 1.08 (95% confidence interval (CI): 1.03-1.13, p=0.0017). There were no differences in the incidence of MACE and the changes in the angiographic parameters between the high (>10 m/sec) and low PWV groups. CONCLUSION: The invasively measured aortic PWV was affected by age (>60), diabetes and dyslipidemia, and also showed a strong association with the severity of CAD. The aortic PWV was not a significant risk factor for restenosis following a DES implantation.

NF-kappa B decoy potentiates the effects of radiation on vascular smooth muscle cells by enhancing apoptosis

NF-kappa B promotes cell survival against external stress such as radiation. We examined whether NF-kappa B decoy transfection enhances the antiproliferative effects of radiation on vascular smooth muscle cells (VSMCs) in vitro. The irradiation induced activation or nuclear translocation of NF-kappa B p65 in VSMCs was confirmed by immunofluorescence. NF-kB decoy transfection resulted in inhibition of the radiation-induced NF-kB activation in VSMCs and the subsequent reduction of transcription and translocation of ICAM, iNOS, and TNF-alpha, downstream molecules under the control of NF-kappa B. By using MTT assay, NF-kappa B decoy augmented the antiproliferative effects of radiation, where the effect of low dose radiation (2 and 8-Gy) of the cells transfected with NF-kappa B decoy was equivalent to the high dose (16-Gy) irradiated non-transfected cells at 48 h after irradiation: 1.06+/-0.16, 1.11+/-0.22, 1.20+/-0.25, respectively. The decrease in proliferation and survival of the radiation treated cells by flow cytometry analysis showed that NF-kappa B inhibition did not show any additive effects on the cell cycle of the irradiated VSMCs, while apoptosis was significantly increased after NF-kappa B decoy transfection in the irradiated VSMCs (apoptosis fraction: 13.33+/-2.08% vs. 26.29+/-7.43%, for radiation only vs. radiation+NF-kappa B decoy transfection, P < 0.05). In addition, at 48 h, NF-kappa B decoy transfection dose dependently (10 mM vs. 20 mM) inhibited proliferation of 16Gy-irradiated VSMCs, and showed greater antiproliferative efficacy than 100 mM sulfasalazine, a specific NF-kappa B inhibitor. These results indicate that NF-kappa B inhibition reduces proliferation and survival of irradiated VSMCs, likely by increased apoptosis rather than additive cell cycle arrest and suggest the possibility of adjunctive gene therapy using NF-kappa B decoy to improve efficacy and to decrease the adverse effects of intracoronary radiation therapy.

Long-Term Effect of Repeated Brachytherapy in Intracoronary Brachytherapy Failed Lesions

BACKGROUND AND OBJECTIVES: An intracoronary brachytherapy is the only approved treatment for in-stent restenosis. However, a considerable rate of restenosis occurs after a brachytherapy. Up to now, there was no long term outcome for repeated brachytherapy for these lesions. SUBJECTS AND METHODS: Eleven patients were admitted due to angina, with significant ischemic evidence in the stress test after the intracoronary brachytherapy. These patients were re-treated with a beta-emitting 188 rhenium-DTPA (diethylene triamine penta-acetic acid) filled balloon catheter system, using an identical method and radiation dose (17.6 Gy) to the initial radiation treatment. The long term angiographic and clinical outcomes of repeated brachytherapy in these patients were evaluated. RESULTS: The angiographic and clinical data of ten patients were evaluated, as 1 was lost. The follow-up period was 37.4+/-16.2 months (range, 8 to 53 months). There was no angiographic restenosis or target lesion revascularization (TLR) during the short term follow-up period (mean 6 months). but 2 restenosis (25%) occurred in the 2 year follow-up period and one other was added during the long term clinical follow-up period. All these restenosis lesions needed revascularization. These three TLRs occurred at 15, 24 and 43 months after the repeated brachytherapy. There was no death or nonfatal MI. No vascular perforation, aneurysm or late thrombosis was observed. CONCLUSION: A repeated brachytherapy for the treatment of a failed intracoronary brachytherapy lesion is safe and acceptably effective during the long term follow-up period. This modality might be considered as a therapeutic option for failed intracoronary brachytherapy lesions.

Long-term clinical outcomes of newly implanted stents during intracoronary radiation / 대한내과학회지

BACKGROUND: New stent implantation during intracoronary brachytherapy is discouraged due to the high risk of late thrombosis. However, new stent implantation is inevitable in some cases due to the inadequate ballooning or major dissections. Long-term follow-up results of newly implanted stents during brachytherapy are not well-known. We performed this study to evaluate the long-term clinical outcomes of newly implanted stents during intracoronary brachytherapy. METHODS: In the Seoul national university Post-Angioplasty RhEnium irradiation (SPARE) trial, patients were treated with conventional catheter-based technique and then randomized to either beta- radiation (RG) or control group (CG). Radiation was performed with 188 -rhenium-filled conventional balloon catheter system. From 1999 to 2001, new stent implantation was performed in 58 and 56 patients in RG and CG, respectively. Clinical and angiographic follow up data were analyzed. RESULTS: In RG, short-term angiographic restenosis rate was lower than CG (28.6% vs 53%, p=0.03). In RG, late thrombosis was found in 3 patients. However, there was no late thrombosis in CG. Two year major cardiac event rates were not different between the 2 groups (RG: 25.9% vs CG: 28.3%). Independent predictors for major cardiac event in RG were major dissections (>or=type C) after stent implantation (beta=70, p=0.01) and longer administration of dual antiplatelets (aspirin+clopidogrel/ ticlopidine, >6 months, beta=0.07, p=0.04). CONCLUSION: Stenting during intracoronary brachytherapy seems to be ineffective in reducing long-term event rates. When new stent implantation is inevitable during brachytherapy, extreme attention is required not to make a dissection and long-term dual antiplatelet treatment should be followed after stent implantation.

Incidence, Risk factors, and Clinical Outcomes of Contrast Induced Nephropathy After Percutaneous Coronary Intervention in Elderly Patients

BACKGROUND: Contrast induced nephropathy(CIN) has been known to be a risk factor of significant in-hospital and long-term adverse outcomes. In old aged patients undergoing percutaneous coronary intervention(PCI) in the modern era, the incidence and prognostic implications of nephropathy are unknown. METHODS: With a retrospective analysis of the clinical and angiographic data, we determined the incidence of, risk factors for, and prognostic implications of CIN(defined as an increase in serum creatinine[Cr] >0.5 mg/dL from baseline) after PCI. RESULTS: Of 360 patients, 16(4.4%) patients experienced CIN and 5(1.4%) patients required temporary renal replacement therapy (hemodialysis or hemofiltration). Patients with baseline Cr 1.4 mg/dL and diabetic patients had a significant risk of CIN. In multivariate analysis, CIN was significantly associated with baseline renal dysfunction and diabetes showed marginal significance in developing CIN. Twenty-five percent of patients with CINdied during the index hospitalization compared with only 1.2% of patients without CIN (p<0.001). In patients with CIN, events of CIN impair renal function at six-month follow up. CONCLUSIONS: In old aged patients who are undergoing PCI, diabetic patients with baseline renal impairment are at higher risk for CIN. Furthermore, CIN was highly correlated with death during the index hospitalization.

Cellular Cardiomyoplasty Using Bone Marrow Derived Mesenchymal Stem Cells Transplantation in Post Myocardial Infarction Heart Failure

BACKGROUND AND OBJECTIVES: Cellular cardiomyoplasty (CCM) is considered to be a novel therapeutic approach for post-myocardial infarction (MI) heart failure. In this study, the functional effects of cultured mesenchymal stem cells (MSCs) transplantation and the associated histopathologic changes were evaluated in a rat model of MI. MATERIALS AND METHODS: Rats were subjected to 5 hours of coronary ligation followed by reperfusion, and 10 days after MI, animals were randomized into either the MSCs transplantation (MI-MSC, n=8) group or the control (n=8) group. Allogeneic MSCs (3x10(6) cells) or media were epicardially injected into the center and the border area of the infarct scar. RESULTS: Four weeks after the MSCs transplantation, the echocardiogram showed preserved anterior regional wall motion and increases in fractional shortening in the MI-MSC heart relative to the control heart. Left ventricular (LV) end diastolic pressure was smaller in the MI-MSC than in the control group. Implanted MSCs formed islands of cell clusters on the border of the infarct scar, and the cells were positively immunostained by sarcomeric alpha-actinin and cardiac troponin T. In addition, the number of microvessels on the border area of the infarct scar was greater in the MI-MSC than in the control group. CONCLUSION: Allogeneic MSCs transplanted into the MI scar formed clusters of cell grafts on the border of the infarct, expressed cardiac muscle proteins, increased microvessel formation, and improved regional and global LV function. Our data indicate that CCM using MSCs may have a significant role in the treatment of post-MI heart failure.

Risk Factors of No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention with Stent Implantation

BACKGROUND AND OBJECTIVES: No-reflow is an important phenomenon for limiting the prognosis of patients following primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Coronary stenting is the current standard procedure for primary PCI in AMI. However, stenting is suspected to cause more microembolization, and no-reflow phenomenon. This study was performed to elucidate the risk factors for the no-reflow phenomenon following primary PCI with stenting, in patients with AMI. SUBJCETS AND METHODS: The clinical, angiographic and procedure related parameters were reviewed in patients with AMI that had undergone primary PCI, with stent implantation, within 12 h of the onset of chest pain, at Seoul National University Hospital, Yonsei University Hospital Cardiovascular Center and Chungbuk National University Hospital (n=183). RESULTS: 29 patients (16%) showed no-reflow phenomenon (final TIMI flow grade less than 3). Conventional risk factors for coronary artery disease were not significant risk factors for the no-reflow phenomenon. In a univariate analysis, a high initial CK-MB level (>50 IU) (8.45% vs. 21.9%, p=0.04), low left ventricular ejection fraction (LV EF) (30 sec) (31% vs. 15%, p=0.04) were significant risk factors of the no-reflow phenomenon. A low LV EF and long pre-dilatation balloon inflation time were significant risk factors in a multivariate analysis. CONCLUSION: LV dysfunction at presentation and a long pre-dilatation balloon inflation time were independent risk factors for the no-reflow phenomenon following primary PCI with stenting for AMI. Preventive measures against the no-reflow phenomenon should be considered in patients with these risk factors.

Risk Factors of No-Reflow Phenomenon after Primary Percutaneous Coronary Intervention with Stent Implantation

BACKGROUND AND OBJECTIVES: No-reflow is an important phenomenon for limiting the prognosis of patients following primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Coronary stenting is the current standard procedure for primary PCI in AMI. However, stenting is suspected to cause more microembolization, and no-reflow phenomenon. This study was performed to elucidate the risk factors for the no-reflow phenomenon following primary PCI with stenting, in patients with AMI. SUBJCETS AND METHODS: The clinical, angiographic and procedure related parameters were reviewed in patients with AMI that had undergone primary PCI, with stent implantation, within 12 h of the onset of chest pain, at Seoul National University Hospital, Yonsei University Hospital Cardiovascular Center and Chungbuk National University Hospital (n=183). RESULTS: 29 patients (16%) showed no-reflow phenomenon (final TIMI flow grade less than 3). Conventional risk factors for coronary artery disease were not significant risk factors for the no-reflow phenomenon. In a univariate analysis, a high initial CK-MB level (>50 IU) (8.45% vs. 21.9%, p=0.04), low left ventricular ejection fraction (LV EF) (30 sec) (31% vs. 15%, p=0.04) were significant risk factors of the no-reflow phenomenon. A low LV EF and long pre-dilatation balloon inflation time were significant risk factors in a multivariate analysis. CONCLUSION: LV dysfunction at presentation and a long pre-dilatation balloon inflation time were independent risk factors for the no-reflow phenomenon following primary PCI with stenting for AMI. Preventive measures against the no-reflow phenomenon should be considered in patients with these risk factors.

Multicenter Analysis of Clinical Characteristics of the Patients with Congestive Heart Failure in Korea

BACKGROUND AND OBJECTIVES: Congestive heart failure is one of the most frequent problems in cardiovascular patients. However, very little data concerning this syndrome in Korea was available. The objectives of this study were to evaluate the demographic and clinical characteristics of hospitalized Korean patients with congestive heart failure. SUBJECTS AND METHODS: Six university hospitals that fulfilled the protocol for clinical information of the patients with heart failure, were prospectively engaged in this study. Six hundred and ninety patients, admitted between Jan. 1. 1998 and Dec. 31. 1999, were enrolled. RESULTS: Ischemic heart disease was the most frequent underlying disease (33.2%), with the other causes of heart failure being cardiomyopathy (23%), hypertensive heart disease (22%) and valvular heart disease (12.7%). Compared with ischemic cardiomyopathy, the patients with idiopathic dilated cardiomyopathy were younger (61.1+/-16.6 vs. 66.9+/-10.3, p<0.05), had less incidence of diabetes (16.8% vs. 32.2%) and smoked less (13.5+/-21.5 vs. 20.4+/-26.0 pack-year). The common aggravating factors were arrhythmia (22%), myocardial ischemia (21.7%) and infection (18.7%). Thirty nine (5.7%) patients died during the one year follow up period. Ischemic heart disease was the main underlying disease in the fatal cases (46.2%). CONCLUSION: Ischemic heart disease was the major cause of heart failure, and the leading cause of death in Korean patients with congestive heart failure.

Long-Term Follow-Up Results of Intracoronary Beta-Radiation Therapy with a Rhenium-188 Diethylene Triamine Penta-Acetic Acid-Filled Balloon

BACKGROUND AND OBJECTIVES: Intracoronary irradiation has emerged as a successful intervention for the treatment of restenosis. However, the radiation process is complex, difficult and hard to perform. On the contrary, intracoronary radiation therapy using a 188Re-DTPA-filled balloon system is simple and inexpensive. The short-term follow-up results of this system have been reported, but the long-term results remain to be elucidated. The object of this study is to evaluate the short and long-term follow-up results of intracoronary radiation using a 188ReDTPA-filled balloon system in restenotic lesions. SUBJECTS AND METHODS: Thirty-eight patients, with restenotic lesion after previous percutaneous coronary intervention, were selected from the SPARE trial (Seoul National University Post-Angioplasty RhEnium irradiation trial). There were 27 cases in the irradiation group, with 11 in the control group. Irradiation was performed in the restenotic lesions after successful interventions. The results of 6-month angiographic and 6-month and 3-year clinical follow-up data were compared between the two groups. RESULTS: A 6-month angiographic follow-up was performed in 33 patients (87%), 25 in the radiation group and 8 in control. Binary restenosis developed in 1 of 25 (4%) and 4 of 8 (50%) in the radiation and control groups, respectively (p=0.008). At the 6-month clinical follow-up, there were no significant differences in the event rates between the two groups. At the 3-year clinical follow-up, there was a significant difference in the target vessel revascularization: 2 of 27 (7.4%) and 5 of 11 (45.4%) in the radiation and control groups, respectively (p=0.017). There were no deaths or myocardial infarctions. CONCLUSION: Radiation therapy using a 188ReDTPA-filled balloon system is feasible, and may be effective in improving the long-term outcomes in restenotic lesions.

Role of 5-HT2A Receptor Gene T102C Polymorphism in Coronary Artery Disease and Serum Lipid Level

BACKGROUND AND OBJECTIVES: The 5-HT2A receptor is one of the main mediators of a serotonin-evoked coronary artery contraction. This is because vasoconstriction is selectively blocked by the 5-HT2 receptor antagonist, with the 5-HT2A receptor gene mRNA being detected in spastic coronary arteries. The relationship between the T102C polymorphism of the 5-HT2A receptor gene and the response to the 5-HT2A antagonist (clozapine) has recently been established, suggestive of a functional implication. Previous studies have observed an association between low cholesterol levels and mental disorders, but the underlying cause has not been determined. It has been established that the T102C polymorphism of the 5-HT2A serotonin receptor gene and a variety of psychological problems are related, but the relationship between the serum lipid level and this genetic polymorphism has not been reported. We investigated the influence of this polymorphism on coronary artery disease, including vasospastic angina and the clinical parameters, such as the lipid profile. SUBJECTS AND METHODS: After a diagnostic angiography was performed, the genotype was identified from the genomic DNA extracted from the peripheral blood of 646 patients without specific psychiatric diseases. RESULTS: There were no differences in the genotype frequencies between coronary artery disease, coronary artery disease with vasospasm, and the normal control groups, even from a subgroup analysis of the clinical parameters. Contrary to previous reports, the genotype distribution was not related to a myocardial infarction or hypertension. The lipid profile analysis showed significantly lower total cholesterol (193.5 vs. 202.1mg/dL, p=0.016) and HDL-cholesterol (42.7 vs. 46.2mg/dL, p=0.003) levels in the CC genotype than the other genotypes, and the frequencies of CC genotype showed a significantly decreasing trend between the HDL-cholesterol (p=0.003) and total cholesterol (p=0.003) quartiles. From a multivariate analysis, only the HDL-cholesterol level was significantly associated with a lower frequency of the CC genotype (p=0.006). CONCLUSION: The T102C polymorphism is not related to coronary artery disease, including vasospasm of the coronary artery, but the CC genotype of this polymorphism is related to low HDL-cholesterol. We identified a novel genetic polymorphism of the serotonin receptor, which affects the HDL-cholesterol level. Because previous observational studies have shown an association between low cholesterol levels and mental disorders, our data should be considered when analyzing the serum lipid levels and serotonin receptor function in humans.

Clinical Presentation of Adverse Drug Reaction of Dalteparin in Acute Coronary Syndrome

BACKGROUND AND OBJECTIVES: Heparin is crucial in the treatment of acute coronary syndrome. However, unfractionated heparin has pharmacokinetic, biophysical and biological limitations, but its low molecular weight has been used to overcome these limitations. The aim of this study was to find the optimal dose of dalteparin in Koreans. Instead, significant rises in the levels of aminotransferase were found in the liver during the study. SUBJECTS AND METHODS: A clinical investigation was conducted, at Seoul National University Hospital, between December 2000 and February 2001. The anti-Xa activity was checked just before the first, and 4 hours after, the second and ninth doses of dalteparin. Liver function tests were obtained on the first and follow-up day (day 6 or 7). RESULTS: Of the 17 patients who completed 10 doses of dalteparin, 13 showed significant rises in the levels of liver aminotransferase. In 5 cases, the levels of aminotransferase rose to 3 times, and in one case, to over 10 times the upper normal limit. All of the patients were asymptomatic, and the levels showed a decline one or two days later. The follow-up aminotransferase level was normalized in 8 out of 11 patients whose liver function tests were followed up. CONCLUSION: Previous studies have shown that 120 IU/kg of dalteparin was the optimal dose in Western countries. Whether this is the optimal dose for Koreans has not been proven, and there have been no studies to elucidate its adverse effects (e.g. hepatotoxicity) in Koreans. Therefore, large scale, randomized trials may be warranted to determine the pharmacodynamics and kinetics of dalteparin in Koreans.

Usefulness of Mitral Inflow Velocity and Mitral Annulus Velocity for Predicting Long-term Prognosis in Heart Failure with Restrictive Filling Pattern

BACKGROUND AND OBJECTIVES: The restrictive filling pattern (RFP) is accepted as a poor prognostic marker in congestive heart failure (CHF) patients. But, recently the RFP has been categorized into various prognosis subgroups by their clinical signs or echocardiographic markers with loading manipulation. But, in critically ill or severe dyspneic patients these loading manipulations are not practical to apply. Therefore, we tried to establish simple, reliable prognostic echocardiographic variables in CHF patients with the RFP. MATERIALS AND METHOD: 40 patients with the RFP were observed for 35+/-19 months after echocardiographic examination. We obtained baseline peak early (E), late (A) mitral inflow velocities, E/A ratio, deceleration time of E velocity (DT), peak early (E'), late (A') diastolic mitral annulus velocities, E'/A' ratio, reversibility of the RFP. The reversibility of RFP was defined as E/A ratio reverse (<1) during the Valsalva's maneuver. With the clinical and survival data during follow up period, we established significant prognostic variables in these patients. RESULTS: In univariate analysis, low systolic blood pressure (p=0.013), low A velocity (p=0.044), low A' velocity (p=0.028) and the irreversibility of RFP (p=0.024) were significant drastic prognosis variables. Especially, patients with A velocity <0.32 m/sec or A' velocity <0.04 m/sec showed significantly higher mortality. CONCLUSION: In CHF patients with the RFP, A velocity and A' velocity are very practical prognostic echocardiographic variables and patients with the low A velocity (<0.32 m/sec) or the low A' velocity (<0.04 m/sec) showed higher mortality rate.