Relationship Between RR Intervals and Early Diastolic Mitral Annulus Velocities in Atrial Fibrillation Patients Who do not Have Significant Valvular Diseases

BACKGROUND AND OBJECTIVES: Irregular RR intervals in atrial fibrillation (AF) results in beat to beat changes in hemodynamical parameters. Early diastolic mitral annulus velocity (E') is one of the parameters that represent diastolic function of the left ventricle (LV). In this study, we have investigated the effects of continuous changes of systolic functions in AF on the diastolic functions of the LV. SUBJECTS AND METHODS: E' (35-40 beats) was recorded in 31 AF patients that did not have significant valvular heart diseases. The relationships between preceding RR intervals (RR-1) or pre-preceding RR intervals (RR-2) and E's were obtained using a logarithmic function. RESULTS: Slopes between RR-1 and E' varied from -1.62 to 1.04 in total coordinates. In the logistic regression analysis patients with negative slopes were found to have a larger left atrial size than patients with positive slopes (5.5+/-0.67 cm vs. 4.9+/-0.56 cm, p=0.02). Slopes were negatively related with mean RR intervals in the Pearson correlation analysis (r=-0.40, p=0.028). Slopes between RR-2 and E' were also variable and were not associated with other parameters. CONCLUSION: Beat to beat changes in systolic functions derived from irregular RR intervals in AF had variable effects on diastolic functions among patients. The relationship between RR-1 and E' was associated with LA sizes and mean RR intervals.

Association of New Parameters Derived from Relation between RR intervals and Left Ventricular Performances with Heart Failure in Patients with Atrial Fibrillation and Normal Systolic Function

BACKGROUND AND OBJECTIVES: Heart failure (HF) may occur in atrial fibrillation (AF) patients with a normal left ventricular (LV) systolic function if the diastolic function is impaired. The association of new parameters from the relationship between the preceding RR interval (RR-1) and LV outflow peak ejection velocity (Vpe) with systolic function has been reported. The aim of this study was to observe whether these parameters were associated with HF in AF patients with a normal systolic function. SUBJECTS AND METHODS: AF patients with a normal systolic function were divided into two groups according to the presence (n=16) or absence (n=30) of a history of HF. From the logarithmic equation between RR-1 and Vpe, the slope, Vpe at RR-1 second (Vpe-1), and Slope/Vpe-1 were calculated. RESULTS: Patients with a history of HF were older (p=0.037) and tended to more frequently have hypertension (p=0.063) than those with no history of HF. The ejection fractions were similar between the two groups. In the coordinates with RR-1 from 0.6 to 1 second, the slope tended to be steeper (p=0.074) and slope/Vpe-1 was higher in patients with a history of HF (p=0.011). The Vpe-1 was similar between the two groups (p=0.66). A multiple forward logistic regression analysis showed that slope/Vpe-1 was the only independent variable associated with the occurrence of HF. Slope/Vpe-1 was related with aortic regurgitation, HF history, and the interventricular septal thickness in a multiple stepwise regression analysis. CONCLUSION: New parameters from the relationship between the RR intervals and LV performances were associated with the occurrence of HF in AF patients with a normal systolic function. This finding suggests that these parameters may be related with the LV diastolic function.

Effect of fenofibrate on C-reactive protein levels in hypertriglyceridemic patients / 대한내과학회지

BACKGROUND: High levels of C-reactive protein (CRP) are associated with an increased risk for cardiovascular diseases. Most reports on the effect of fibrate on CRP level have inadequate study designs and the results are inconsistent. This study was designed to evaluate the effect of fenofibrate on CRP levels in hypertriglyceridemic patients. METHODS: Patients with triglyceride (TG) level over 200 mg/dL were treated with 200 mg of fenofibrate (Fenofibrate group, n=30) or with general measures (Control group, n=30). Patients with CRP levels >10 mg/L were excluded. Patients with hypercholesterolemia were treated with HMG CoA reductase inhibitor (Statin group, n=30). Lipid and lipoprotein levels were measured before and 2 months after medication. RESULTS: Baseline characteristics were similar in Fenofibrate and Control groups. Baseline CRP levels were independently associated with the presence of diabetes mellitus. Fenofibrate therapy did not change CRP levels (1.67+/-1.60 vs 1.76+/-1.88 mg/L, p=0.79) as did Control group (p=0.46). When both Fenofibrate and Control groups were divided into three subgroups in terms of baseline CRP levels, CRP levels were increased in the lowest group (p=0.019), did not change in the middle and the highest groups (p=0.89 and p=0.47 respectively). In patients with baseline CRP level > or =3 mg/L, CRP levels were decreased (p=0.041). Changes of CRP levels were independently associated with baseline CRP levels. Statin therapy decreased CRP levels (p=0.046). CONCLUSIONS: Fenofibrate did not change CRP levels in hypertriglyceridemic patients. Cardioprotective effects of fibrates may not be associated with anti-inflammatory mechanisms in contrast to those of statins.

Binding of Annexin V to Oxidized Lipid on Oxidatively Damaged Erythrocyte

BACKGROUND AND OBJECTIVES: Annexin V is known to bind to the phosphatidylserine (PS) of damaged cell membranes. We recently demonstrated that annexin V binds to oxidized red blood cells (oxRBC). The aim of this study was to find whether annexin V binds to oxidized lipids or to the PS of oxRBC. MATERIALS AND METHODS: Red blood cells (RBC) were oxidized by the addition of CuSO4, and the degree of oxidation evaluated using the semiquantitative measurement of thiobarbituric acid reactive substance (TBARS). The binding of annexin V to oxRBC was evaluated by flow cytometry. RESULTS: Annexin V was found to bind to oxRBC, but not to native RBC. The percentage of RBC binding to annexin V was closely correlated with the degree of oxidation, as measured using TBARS (r=0.99, p=0.000) in relation to the concentration of CuSO4. The binding of annexin V to oxRBC was attenuated in the presence of oxidized low density lipoprotein (oxLDL), with these phenomena also being dosedependent. The binding was reduced by 71.0+/-3.0% in the presence of 100 microgram/mL oxLDL. LDL had no influence on the binding of annexin V to oxRBC. CONCLUSION: These findings suggest that annexin V may bind to the oxidized lipids of cell membranes. Further studies will be required to evaluate the relative importance between oxidized lipids and PS, and to find the characteristics of oxidized lipids in the binding of annexin V to damaged cell membranes.

New Parameters for Left Ventricular Function in Atrial Fibrillation: Based on the Relationship between RR Interval and Performance

This study was designed to obtain new parameters representing left ventricular (LV) function independent of irregular RR intervals in atrial fibrillation (AF). AF patients were divided into Normal (n=9) and LV Dysfunction (n=9) groups. The relations between LV outflow peak ejection velocity (Vpe) and preceding (RR-1) or prepreceding RR intervals (RR-2) were obtained using logarithmic equations, from which the squared correlation coefficient (r2), slope, Vpe at RR-1 or RR-2=1 sec (Vpe-1), and the ratio of slope to Vpe-1 (Slope/Vpe-1) were calculated. Among the parameters between RR-1 and Vpe, Slope/Vpe-1 was higher in LV Dysfunction group than in Normal group (p=0.05). When only coordinates with RR-1 from 0.6 to 1 sec were included, Slope/Vpe-1 (p=0.001) was higher in LV Dysfunction group than in Normal group. Among the parameters between RR-2 and Vpe, Slope/Vpe-1, slope, and r2 were different between the two groups. In multivariate analysis, Slope/Vpe-1 between RR-2 and Vpe was only independent parameter. However, Slope/Vpe-1 between RR-1 and Vpe in the coordinates with RR-1 from 0.6 to 1 sec had the highest discriminating power. New parameters derived from the relations between RR intervals and LV performance might be useful to evaluate LV function quantitatively in AF.

Effect of Fibrate on Lipoprotein(a) Level in Hypertriglyceridemic Patients

BACKGROUND AND OBJECTIVES: The responses of lipoprotein (a) [Lp(a)] to lipid-lowering drugs are different from those of other lipids and lipoproteins. Most reports on the effect of fibrate on the Lp (a) level have only a few cases, with inconsistent results. This study was designed to evaluate the effect of fibrate on the Lp (a) level in hypertriglyceridemic patients. SUBJECTS AND METHODS: Patients with either a triglyceride (TG) level over 300mg/dL or TG level over 200mg/dL and a high density lipoprotein cholesterol level below 40mg/dL, were enrolled. They were treated with either fibrate (Fibrate group, n=29) or general measures (Control group, n=29). Gender and age matched patients with hypercholeste-rolemia were adopted and treated with statin (Statin group, n=29). The lipid and lipoprotein levels were measured before and after the medication for 2 months. RESULTS: The baseline Lp (a) levels were similar between the Fibrate and Control groups (p=0.19). Fibrate therapy increased the Lp (a) level from 10.3+/-16.4 to 15.1+/-15.2 mg/dL (p=0.003), but there were no changes in the Lp (a) levels in the Statin and Control groups. Before the treatment, the Lp (a) levels were negatively associated with the TG levels (r=-0.36, p=0.001). The relationship became weaker and insignificant after the medication. The more the TG level was decreased, the more the Lp (a) level was increased in all of the cases (r=-0.35, p=0.001 ) as well as in the Fibrate group (r=-0.46, p=0.013). CONCLUSION: Fibrate increased the Lp (a) level, and this elevation was associated with the reduction in the TG level. This finding might be related with a lesser cardioprotective effect of fibrate than that of statin in addition to the effect on the cholesterol level.

Overweight and Effect of Hormone Replacement Therapy on Lipid Profiles in Postmenopausal Women

BACKGROUND: Many experimental and observational studies have suggested that hormone replacement therapy (HRT) in postmenopausal women is cardioprotective. However, the results of randomized controlled trials have been discouraging. We attempted to evaluate the influence of overweight, a frequent risk factor for coronary artery disease, on the lipid-modifying effects of HRT. METHODS: A total of 345 postmenopausal women were divided into 2 groups according to body mass index (BMI) : the control group; BMI or=25 Kg/m2 (n=97). All women received either 0.625 mg conjugated equine estrogen (CEE) (n=139), CEE plus 5 mg medroxyprogesterone acetate (MPA) (n=97) or CEE plus 10 mg MPA (n=109). Lipid profiles were measured before and 12 months after HRT. RESULTS: In both the control and overweight groups, HRT reduced low density lipoprotein cholesterol (LDL-C) (p=0.000 and p=0.000 respectively) and lipoprotein (a) [Lp (a) ] levels (p=0.000 and p=0.000 respectively) and raised high density lipoprotein cholesterol (HDL-C) levels (p=0.000 and p=0.002 respectively). However, the elevation of the HDL-C level was higher in the control group than in overweight group (17.5% vs. 10.4%, p=0.015), and this was significant after adjusting for changes in body weights (p=0.016). There were no differences in the reduction of LDL-C (p=0.20) and Lp (a) (p=0.09) levels between the two groups. CONCLUSION: HRT had less favorable effects on HDL-C levels in overweight postmenopausal women than in women with normal body weight. This finding may be partially associated with no cardioprotective effect of HRT in postmenopausal patients at a high risk due to multiple risk factors including obesity.

Effect of Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitor on High Sensitivity C-Reactive Protein Levels in Hypercholesterolemic Patients without Atherosclerotic Diseases

BACKGROUND AND OBJECTIVES: High C-reactive protein (CRP) levels are associated with an increased risk of cardiovascular diseases. The hydroxymethyl glutaryl Coenzyme A reductase inhibitors (statin) lowers the CRP level in the population of developed countries. The aim of the study was to evaluate the effect of statin on the CRP levels in Korean hypercholesterolemic patients without atherosclerotic diseases. SUBJCETS AND METHODS: A total of 32 patients with hypercholesterolemia, administered 20 mg lovastatin or 10 mg atorvastatin, and the same number of similar aged, sex-matched, hypercholesterolemic patients, as a control group, were enrolled. Non-drug measures were recommended for those without the medication. The patients with atherosclerotic cardiovascular diseases were excluded. The lipid profiles and high sensitive CRP levels were measured before and after 2 months of the medication. RESULTS: The baseline CRP levels were not related to the levels of lipids. Statin therapy reduced the CRP levels from 2.17+/-2.40 (median value 1.11) mg/L to 1.24+/-1.79 (0.68) mg/L (p=0.003). In all the cases, the magnitude of change in the CRP was related to the statin therapy allocation and the magnitude of changes in the total and low density lipoprotein cholesterols in a univariate analysis. Multiple stepwise regression analysis showed that only the statin therapy allocation was an independent variable. For each group, no significant relationship between the changes of CRP and lipids was observed. CONCLUSION: Short term statin therapy reduced the CRP levels in Korean hypercholesterolemic patients without atherosclerotic diseases, and the phenomenon was independent of the changes in lipids.

Effect of Hydroxymethyl Glutaryl Coenzyme A Reductase Inhibitor on High Sensitivity C-Reactive Protein Levels in Hypercholesterolemic Patients without Atherosclerotic Diseases

BACKGROUND AND OBJECTIVES: High C-reactive protein (CRP) levels are associated with an increased risk of cardiovascular diseases. The hydroxymethyl glutaryl Coenzyme A reductase inhibitors (statin) lowers the CRP level in the population of developed countries. The aim of the study was to evaluate the effect of statin on the CRP levels in Korean hypercholesterolemic patients without atherosclerotic diseases. SUBJCETS AND METHODS: A total of 32 patients with hypercholesterolemia, administered 20 mg lovastatin or 10 mg atorvastatin, and the same number of similar aged, sex-matched, hypercholesterolemic patients, as a control group, were enrolled. Non-drug measures were recommended for those without the medication. The patients with atherosclerotic cardiovascular diseases were excluded. The lipid profiles and high sensitive CRP levels were measured before and after 2 months of the medication. RESULTS: The baseline CRP levels were not related to the levels of lipids. Statin therapy reduced the CRP levels from 2.17+/-2.40 (median value 1.11) mg/L to 1.24+/-1.79 (0.68) mg/L (p=0.003). In all the cases, the magnitude of change in the CRP was related to the statin therapy allocation and the magnitude of changes in the total and low density lipoprotein cholesterols in a univariate analysis. Multiple stepwise regression analysis showed that only the statin therapy allocation was an independent variable. For each group, no significant relationship between the changes of CRP and lipids was observed. CONCLUSION: Short term statin therapy reduced the CRP levels in Korean hypercholesterolemic patients without atherosclerotic diseases, and the phenomenon was independent of the changes in lipids.

The Relationship between Preceding RR Intervals and Peak Ejection Velocity of Left Ventricular Outflow in Atrial Fibrillation without Organic Heart Diseases

BACKGROUND AND OBJECTIVES: Cardiac performance is dependent on both the preceding RR interval (RR-1) and the prepreceding RR interval (RR-2) in atrial fibrillation (AF). We reported a new method for improving the relation between the two RR intervals and cardiac performance in AF of various causes. The aim of this study was to re-evaluate the method and its relationship in AF without organic heart disease. SUBJECTS AND METHODS: The beat to beat variation in the left ventricular outflow peak ejection velocity (Vpe) was measured by pulsed Doppler ultrasound in 28 consecutive patients with lone AF. The relations between the RR-2 and the Vpe were obtained before and after the exclusion of coordinates with the RR-1<0.5 second. The association of the Vpe with the RR-1 was adjusted by the RR-2 using an equation obtained from the relation between the RR-2 and the Vpe. RESULTS: The RR-2 was found to have a weak, negative, association with the Vpe. The mean squared correlation coefficient (r2) between the RR-2 and the Vpe was 0.14+/-0.13, which was improved to 0.23+/-0.21 (p=0.007) following the exclusion of coordinates with a RR-1<0.5 second. The RR-1 was positively associated with the Vpe. The mean r2 between the RR-1 and the Vpe was 0.55+/-0.15, which became stronger, at 0.68+/-0.12 (p<0.001), following adjustment with the RR-2. A multiple stepwise regression analysis revealed that the mean and standard deviation of the RR interval, and the duration of AF were independently associated with the modified r2 between the RR-2 and the Vpe. CONCLUSION: Simple modification could improve the relationship of both the RR-1 and the RR-2 with the cardiac performance in AF without organic heart disease, as with AF of various causes.

Efficacy and safety of the combination therapy of HMG CoA reductase inhibitor and fibrate in combined dyslipidemia / 대한내과학회지

BACKGROUND: The combination therapy of HMG CoA reductase inhibitor (statin) and fibrate is more effective than each ones in managing combined dyslipidemia. However, this therapy tends to be avoided due to potential risk of rhabdomyolysis. The aim of the study was to reevaluate the efficacy and safety of combination therapy. METHODS: A total 61 patients were divided into three groups according to lipid levels and medications; statin+fibrate group (n=10), statin group (n=31) and fibrate group (n=18). Patients with active hepatitis or renal dysfunction who were at high risk for complications were excluded. Lipid profiles were measured before and 2 months after medications. RESULTS: Combination therapy markedly decreased total cholesterol, low density lipoproteincholesterol (LDL-C) and triglyceride concentrations (p=0.008, p=0.028 and p=0.018 respectively), and increased high density lipoprotein-cholesterol (HDL-C)(p=0.028). The effects of this therapy on HDL-C and triglyceride were more potent than those of statin. Combination therapy was more effective in lowering LDL-C than fibrate. Serious complications such as myopathy and marked elevation of transaminase level were not observed in all groups. In statin+fibrate group, transaminase level was elevated slightly above the normal range in two cases. Creatine kinase level showed the trend to increase with borderline significance. However the levels were within normal range in 9 cases and elevated twofold in one patient. CONCLUSION: Combination therapy of statin and fibrate was effective in combined dyslipidemia and well tolerated in patients without high risk for the complications although the number of cases was small to get a conclusion.

The Oxidation Process of Red Blood Cells and the Molecules Involved in their Binding to Macrophage

BACKGROUND AND OBJECTIVES: Controversy exists about the characteristics of the lipid-oxidizing process, and the molecules in oxidized lipids that are involved in the binding and uptake to macrophages, in atherosclerosis. The aim of this study was to find answers to these questions using oxidized red blood cells (ox-RBCs). MATERIALS AND METHODS: The RBCs were oxidized in the presence of various concentrations of CuSO4, and the degree of oxidation evaluated by the semiquantitative measurement of the thiobarbituric acid reactive substance (TBARS). The ox-RBC was characterized using annexin-V and flow cytometry. The relationships between the CuSO4 concentration, the degree of oxidation, characteristics of the ox-RBC and it's binding to macrophages transformed from THP-1 cells, were evaluated. RESULTS: The RBCs were oxidized, not by their gradual changes, but by the sudden transformation of a proportion of the RBCs in relation to the CuSO4 concentration. There were few RBCs between oxidized and non-oxidized groups. The annexin-V bound only to the ox-RBC, with a similar degree of binding in all ox-RBCs. The binding of ox-RBC to macrophages was completely inhibited by oxidized low density lipoprotein, which was directly related to the CuSO4 concentration, the TBARS and the proportion of ox-RBC. CONCLUSION: These results suggest that the oxidation of lipids might be an on-off phenomenon process. Molecules that have the ability to bind annexin-V, presumptively phosphatidyl serine, may be involved in the process of binding the ox-lipids to macrophages. Further study will be needed to clarify these molecules.

Characterization of Binding and Phagocytosis of Oxidatively Damaged Erythrocyte to Macrophage

BACKGROUND: Scavenger receptors are thought to be involved in the recognition of oxidized low-density lipoprotein (oxLDL) and oxidized erythrocyte (oxRBC). However, there are controversies about the kind of receptors and ligands related to the binding. Macrophages lacking class A scavenger receptor show identical binding of oxRBC with wild-type ones. METHODS: RBCs were oxidized with ascorbic acid and CuSO4. Lipid oxidation was measured indirectly by measuring TBARS semiquantitatively. The binding and phagocytosis were measured by counting the number of oxRBC bound or taken up after incubation at 4 degrees C or 37 degrees C for 60 minutes to 100 macrophages differentiated from human monocytic leukemia cell line. RESULTS: The degree of oxidation and the binding of oxRBCs were dependent on the concentration of CuSO4. The binding and phagocytosis of oxRBC were inhibited by 99% with oxLDL. Fucoidan, competing class A scavenger receptor, inhibited the binding by more than 90%. The binding of oxRBC was higher at 37 degrees C than at 4 degrees C by 3 times. The binding of oxRBCs was maximal at pH 6.5 and higher than at physiologic pH by 2.8 times. At pH 8.5 and 9.5, binding decreased by 67 and 88%, respectively. CONCLUSION: OxRBCs might bind and be taken up to macrophages not mainly through class A nor B scavenger receptors, but through other scavenger receptors and/or pathways. These processes are dynamic and ionic strength might be involved.

Prediction of Left Ventricular Peak Ejection Velocity by Preceding and Prepreceding RR Intervals in Atrial fibrillation:A New Method to Adjust the Influence between Two Intervals

In atrial fibrillation, cardiac performance is dependent on both preceding RR (RR-1) and prepreceding RR (RR-2) intervals. However, relative contributions were not well defined. Left ventricular outflow peak ejection velocity (Vpe) was measured by echocardiography from 21 patients. The relation between RR-1 and Vpe could be divided into two zones; steep slope in short RR-1 intervals ( 0.5 sec). RR-2 had a weak negative association with Vpe. The mean squared correlation coefficient (r2 ) between RR-2 and Vpe was 0.15 +/-0.13 and improved to 0.29 +/-0.21 (p<0.001), when coordinates with RR-1

Effect of long-term 3-hydroxy 3-methyl glutaryl CoA reductase inhibitor therapy on lipoprotein (a) concentration / 대한내과학회지

BACKGROUND: The effect of 3-hydroxy 3-methyl glutaryl CoA reductase inhibitor (statin) on the concentration of lipoprotein (a) [Lp(a)] is controversial. Most studies evaluated the effect of statin administered for less than 2 years. We were to analyze the effect of long-term treatment of statin on the concentration of Lp(a) retrospectively. METHODS: A total 93 cases were enrolled and divided into two groups; statin group (20 mg of lovastatin, n=33) and control group (n=60). Lp(a) and lipid profiles were measured before and after the medication for at least 2 years. RESULTS: Between two groups, there were no differences in baseline clinical variables and in biochemical parameters except total cholesterol and low density lipoprotein-cholesterol (LDL-C) levels. Mean duration of follow-up was similar between control and statin groups (58.7+/-15.0 vs. 54.7+/-16.4 months, p=0.24). Lp(a) levels did not change in both statin group (30.1+/-29.6 mg/dL vs. 28.2+/-23.1 mg/dL, p=0.89) and control group (p=0.49). The change of Lp(a) was not different between two groups (p=0.43). Statin was also ineffective in cases with Lp(a) level over 10 mg/dL. Total cholesterol and LDL-C levels decreased in statin group by 26.4% (p=0.000) and 40.5% (p=0.000) respectively. The elevation of HDL-C was similar between two groups. CONCLUSION: Long-term treatment of lovastatin did not modify Lp(a) level in retrospective study. To clarify the effect of statin precisely, prospective study might be needed.

Effect of long-term 3-hydroxy 3-methyl glutaryl CoA reductase inhibitor therapy on lipoprotein (a) concentration / 대한내과학회지

BACKGROUND: The effect of 3-hydroxy 3-methyl glutaryl CoA reductase inhibitor (statin) on the concentration of lipoprotein (a) [Lp(a)] is controversial. Most studies evaluated the effect of statin administered for less than 2 years. We were to analyze the effect of long-term treatment of statin on the concentration of Lp(a) retrospectively. METHODS: A total 93 cases were enrolled and divided into two groups; statin group (20 mg of lovastatin, n=33) and control group (n=60). Lp(a) and lipid profiles were measured before and after the medication for at least 2 years. RESULTS: Between two groups, there were no differences in baseline clinical variables and in biochemical parameters except total cholesterol and low density lipoprotein-cholesterol (LDL-C) levels. Mean duration of follow-up was similar between control and statin groups (58.7+/-15.0 vs. 54.7+/-16.4 months, p=0.24). Lp(a) levels did not change in both statin group (30.1+/-29.6 mg/dL vs. 28.2+/-23.1 mg/dL, p=0.89) and control group (p=0.49). The change of Lp(a) was not different between two groups (p=0.43). Statin was also ineffective in cases with Lp(a) level over 10 mg/dL. Total cholesterol and LDL-C levels decreased in statin group by 26.4% (p=0.000) and 40.5% (p=0.000) respectively. The elevation of HDL-C was similar between two groups. CONCLUSION: Long-term treatment of lovastatin did not modify Lp(a) level in retrospective study. To clarify the effect of statin precisely, prospective study might be needed.