The change in low-density lipoprotein cholesterol concentration is positively related to plasma docosahexaenoic acid but not eicosapentaenoic acid.

AIM: The Japan EPA Lipid Intervention Study (JELIS) reported a 19% reduction of the risk for coronary artery disease after long-term use of pure eicosapentaenoic acid (EPA) in Japanese patients with hypercholesterolemia. The variation in plasma fatty acid composition influenced the risk of coronary events. The aim of this study was to examine in JELIS participants the possible correlation of changes in plasma fatty acids with those of serum lipids. METHODS: The coefficient for the correlation between the absolute change in plasma fatty acid concentrations and the changes in serum lipids was calculated in 13,901 JELIS participants. RESULTS: Low-density lipoprotein (LDL) cholesterol exhibited a positive correlation with docosahexaenoic acid (DHA; r=0.117 in control group, r=0.155 in EPA group) and linoleic acid (r=0.139 in control group, r=0.177 in EPA group), but the correlation coefficients with EPA (r=0.097 in control group, r=-0.032 in EPA group) were less than 0.1. We distributed the patients into 9 groups according to tertiles of the change in EPA and DHA. The average absolute decrease of LDL cholesterol and L/H ratio in each group was significantly smaller (p<0.001) in the DHA-high tertile, but not in any EPA tertile. CONCLUSION: The changes in DHA, but not in EPA, showed a positive correlation with the changes in LDL-cholesterol.

Role of ¹²³I-BMIPP and serum B-type natriuretic peptide for the evaluation of patients with heart failure.

INTRODUCTION: Myocardial scintigraphy with ¹²³I-15-(p-iodophenyl)-3-methyl pentadecanoic acid (¹²³I-BMIPP) is used to evaluate impaired fatty acid metabolism. B-type natriuretic peptide (BNP), which is secreted by the ventricular myocardium on stretching and/or pressure overload, is a useful cardiac biomarker. This study aimed to evaluate the usefulness of ¹²³I-BMIPP imaging and serum BNP levels in patients with heart failure (HF). METHODS: 113 patients with HF were enrolled. There were 68 patients with ischaemic heart disease (IHD) and 22 with overt HF. Cardiac scintigraphy was performed 7 ± 3 days after admission, and heart-to-mediastinum (H/M) count ratios on early and delayed images and washout rates (WR) of ¹²³I-BMIPP were recorded. Serum BNP levels were recorded on the day of ¹²³I-BMIPP imaging. The ejection fraction (EF) was calculated just before cardiac scintigraphy using conventional echocardiography. RESULTS: The mean BNP level and EF were 282 pg/mL and 47%, respectively, with significant correlation between them. The mean H/M count ratios on early and delayed images were 2.29 and 1.93, respectively, showing significant positive correlations with EF (r = 0.31, p = 0.0006). The WR was significantly correlated with EF (r = -0.36, p < 0.0001) and BNP levels (r = 0.33, p = 0.003), and mean WR was significantly higher in patients with overt HF compared to those without (p < 0.001). Patients with IHD had significantly higher EFs than those with non-IHD (p = 0.03). CONCLUSION: The evaluation of impaired myocardial metabolism using ¹²³I-BMIPP scintigraphy and serum BNP levels appears to be useful for the evaluation of severity of HF.

Discrepancy between myocardial perfusion and fatty acid metabolism following acute myocardial infarction for evaluating the dysfunctional viable myocardium.

OBJECTIVE: Following acute myocardial infarction (AMI) the area of myocardial perfusion and metabolism mismatch is designated as dysfunctional viable myocardium. (123)I-beta-methyl iodophenyl pentadecanoic acid (BMIPP) is clinically very useful for evaluating myocardial fatty acid metabolism, and (99)mTc-Tetrofosmin (TF) is a widely used tracer for myocardial perfusion. This study was designed to evaluate the degree of discrepancy between BMIPP and TF at the subacute state of AMI. METHODS: Fifty-two patients (aged 59 ± 10 years; mean 46 years) with AMI were enrolled, and all of them underwent percutaneous coronary intervention (PCI). Patients were classified according to ST-T change and PCI timing. (123)I-beta-methyl iodophenyl pentadecanoic acid and TF cardiac scintigraphy were performed on 7 ± 3.5 days of admission using a dual headed gamma camera. Perfusion and fatty acid metabolism defect were scored on a 17 segments model. RESULTS: The mean BMIPP defect score on early and delayed images were 16.67 ± 10.19 and 16.25 ± 10.40, respectively. The mean TF defect score was 10 ± 7.69. Defect score of BMIPP was significantly higher than that of the TF (P < 0.0001; 95% CI 4.32-7.02), and there was a strong correlation between perfusion and metabolism defect score (r = 0.89, P < 0.00001). Forty-seven (90%) patients showed mismatched defect (BMIPP > TF), and 5 (10%) patients showed matched defect (BMIPP = TF). Mismatched defect score (MMDS) was significantly higher in patients with ST-segment elevation myocardial infarction (STEMI) than that of non-ST-segment elevation myocardial infarction (NSTEMI) (P < 0.041; 95% CI 0.11-5.19). CONCLUSION: At the subacute state of AMI, most of the patients showed perfusion-metabolism mismatch, which represents the dysfunctional viable myocardium, and patients with STEMI showed higher mismatch.

Relationship between coronary artery disease and non-HDL-C, and effect of highly purified EPA on the risk of coronary artery disease in hypercholesterolemic patients treated with statins: sub-analysis of the Japan EPA Lipid Intervention Study (JELIS).

AIM: The present study examined the importance of reducing non-high-density lipoprotein cholesterol (non-HDL-C) for the primary prevention of the occurrence of coronary artery disease (CAD) in the JELIS, and the effects of EPA. METHODS: The patients were distributed into 4 subgroups using the lipid management goal for LDL-C recommended by the Japan Atherosclerosis Society guideline (2007) and the goal for non-HDL-C defined as 30 mg/dL higher than LDL-C: A) achieved both goals; B) achieved the LDL-C but not non-HDL-C goal; C) achieved the non-HDL-C but not LDL-C goal; and D) did not attain either goal. The incidences of CAD in the 4 subgroups were compared, and the effects of eicosapentaenoic acid (EPA) on the risk of CAD in these subgroups were examined. RESULTS: In the non-EPA group, the incidence of CAD in patients who did not achieve the goals for LDL-C or non-HDL-C was higher than in patients who achieved those goals. Patients in subgroups B, C, and D were at higher risk for CAD than those in subgroup A (B, HR 2.31; C, HR 1.90; D, HR 2.47). EPA reduced the risk of CAD by 38% in subgroups B, C, and D (p= 0.007). CONCLUSION: We reconfirmed non-HDL-C as a predictor of the risk for CAD and a residual risk marker of CAD after LDL-C-lowering therapy. EPA was useful to reduce the occurrence of CAD in patients who did not achieve the goals for LDL-C and/or non-HDL-C.

Prediction of the no-reflow phenomenon during percutaneous coronary intervention using coronary computed tomography angiography.

Coronary computed tomography angiography (CTA) can assess plaque characteristics and plaque size noninvasively. The purpose of this study was to investigate whether coronary CTA before percutaneous coronary intervention (PCI) can predict the no-reflow phenomenon during PCI. Seventy-eight patients [acute coronary syndrome (ACS) = 43, stable angina pectoris (SAP) = 35, male/female = 72/6, age: 65 ± 10 years] who underwent 16- or 64-slice CTA in the 4 weeks before PCI were enrolled. The low attenuation plaque size on CTA was compared between patients with (NR+) and without the no-reflow phenomenon (NR-). No-reflow phenomenon was observed in 11 patients, including 10 patients with ACS and 1 patient with SAP. Low attenuation plaque was detected in 9 (82%) NR(+) lesions and 35 (52%) NR(-) lesions. The length of low attenuation plaque was significantly longer in NR(+) than in NR(-) patients (9.0 ± 6.5 vs. 1.6 ± 2.7 mm, p < 0.0001). On step-wise regression analysis, ACS (p = 0.036, 95% CI = 0.009-0.258) and the presence of low attenuation plaque with a length >4.7 mm (p < 0.001, 95% CI = 0.447-0.778) were significant independent predictors of NR(-) no-reflow phenomenon. Low attenuation plaque with lesion length of >4.7 mm on coronary CTA and ACS were the significant predictors for the no-reflow phenomenon during PCI. Coronary CTA assessment before PCI would be useful to predict coronary events during PCI in advance.

Relationships between plasma fatty acid composition and coronary artery disease.

AIM: The Japan EPA Lipid Intervention Study (JELIS) was the first prospective randomized clinical trial to demonstrate prevention of coronary events by pure eicosapentaenoic acid (EPA). The aim of this study was to examine the relationships between various plasma fatty acid concentrations and the risk of coronary events in JELIS participants. METHODS: In 15,534 participants, we calculated the hazard ratio for major coronary events (sudden cardiac death, fatal or nonfatal myocardial infarction, unstable angina pectoris, and angioplasty/stenting or coronary artery bypass grafting) relative to the on-treatment average level of plasma fatty acids with the Cox proportional hazard model. RESULTS: As a result of EPA intervention, the plasma EPA concentration increased, but the docosahexaenoic acid (DHA) concentration did not. The other fatty acids measured decreased slightly. The higher plasma level of EPA (hazard ratio=0.83, p=0.049, in all participants and hazard ratio=0.71, p=0.018, in the EPA intervention group), but not of DHA, was inversely associated with the risk of major coronary events. The associations between other fatty acids and the risk of major coronary events were not significant. In all JELIS participants, the risk of major coronary events was significantly decreased (20%) in the group with high (150 µg/mL or more) on-treatment plasma EPA concentration compared with that in the low (less than 87 µg/mL) group. CONCLUSION: The risk of coronary artery disease is influenced by variations in plasma fatty acid composition. Among n-3 polyunsaturated fatty acids, EPA and DHA exhibited differences in the correlation with the risk of major coronary events.

Cardio-renal interaction: impact of renal function and anemia on the outcome of chronic heart failure.

The purpose of this study is to investigate the effects of renal function and anemia on the outcome of chronic heart failure (CHF). We targeted 711 consecutive patients who were hospitalized at the Division of Cardiology of Fujita Health University Hospital during a 5-year period. The subjects were divided into four groups according to their estimated glomerular filtration rate (e-GFR) calculated using the Modification of Diet in Renal Disease (MDRD) formula. Intergroup comparisons were conducted for underlying heart diseases, clinical findings at the time of hospitalization, treatment, and outcome. Moreover, the patients were divided into two groups according to their serum hemoglobin concentration at the time of hospitalization, using 12.0 g/dl as the dividing point, to study the effects of anemia on the outcome. In the group with decreased renal function, the average age was higher, and ischemic heart disease and associated conditions such as hypertension and diabetes mellitus were observed in most of the patients. In addition, the rate of anemia development and the plasma B-type natriuretic peptide concentration were also high. The greater the deterioration in renal function, the poorer the outcome became (P < 0.0001). Chronic heart failure complicated by anemia showed an especially poor outcome (P < 0.0001). As this study showed that renal function and anemia significantly affected the outcome of CHF, it is clear that the preservation of renal function and the management of anemia are important in addition to the conventional treatments for CHF.

Do drug elution components increase the risk of fracture of sirolimus-eluting stents?

OBJECTIVES: Stent fracture (SF) of sirolimus-eluting stents (SES) has emerged recently in the literature and shown to be associated with an increased risk of restenosis; however, little is known regarding SF after bare-metal stent implantation. We sought to assess whether the use of SES was associated with an increased risk of SF compared with its bare-metal platform, the Bx-velocity stent (BX-BMS). METHODS: A total of 478 lesions in 416 patients undergoing SES implantation and subsequent angiography 6-9 months after the index procedure were compared with 152 lesions in 142 consecutive patients treated with BX-BMS. Stented lesions with total stent-length greater than 40 mm were excluded. RESULTS: There were no significant differences in overall baseline clinical and anatomic features between the SES and BX-BMS groups, or in SF frequencies at 6-9 month follow-up (4.4% for SES and 1.3% for BX-BMS, P= 0.078). In-stent restenosis was observed more often in SF lesions versus non-SF lesions (34.8 vs. 7.7%, P< 0.001) in association with a higher 3-year adverse events rate (27.3 vs. 13.6%, P = 0.076). The risk of SF at 6-9 months was independently associated with total stent length [odds ratio (OR), 2.13; 95% confidence interval (CI), 1.18-3.83; P = 0.012], angulated lesions (OR, 4.25; 95% CI, 1.80-10.00; P = 0.001), and right coronary artery lesions (OR, 3.55; 95% CI, 1.46-8.62; P = 0.005) but not with SES use. CONCLUSION: Stent implantation in right coronary artery lesions, tortuous lesions, and/or longer lesions covered with longer stents, and not SES versus BX-BMS use, may be associated with increased likelihood of SF.

Preventive effects of eicosapentaenoic acid on coronary artery disease in patients with peripheral artery disease.

BACKGROUND: The JELIS trial examined the preventive effects of eicosapentaenoic acid (EPA) on coronary artery disease (CAD) in hypercholesterolemia. Previous investigators have reported that patients with peripheral artery disease (PAD) have a poor prognosis due to the potential risk for CAD. We conducted a subanalysis to examine whether the incidence of CAD was high in patients with PAD and whether EPA prevented the occurrence of CAD. METHODS AND RESULTS: Of 18,645 the Japan EPA lipid intervention study (JELIS) patients, 223 had PAD (control group; complicated (n=77), newly diagnosed (n=29), EPA group; complicated (n=96), newly diagnosed (n=21)). We analyzed the incidence of major coronary events (MCE) in the 2 groups. Cox proportional hazard ratio adjusted for baseline risk factor levels was used to test differences between the 2 groups. The incidence of MCE in the control group was significantly higher in patients complicated with PAD and in those newly diagnosed with PAD than in patients without PAD (complicated: hazard ratio 1.97, P=0.039; newly diagnosed: hazard ratio 2.88, P=0.030). As for patients with PAD, the EPA group had a significantly lower MCE hazard ratio than the control group (hazard ratio 0.44, 95% confidence interval 0.19-0.97, P=0.041). CONCLUSIONS: Subanalysis of the JELIS trial demonstrated that in patients with PAD the incidence of CAD was higher than in controls, and that EPA markedly reduced the occurrence of CAD in those patients.

The washout rate of (123)I-BMIPP and the evolution of left ventricular function in patients with successfully reperfused ST-segment elevation myocardial infarction: comparisons with the echocardiography.

The evolution of the oxidative metabolism of (11)C acetate parallels the recovery of left ventricular(LV) contraction following acute myocardial infarction(AMI). This study was designed to unravel, for the first time, the impact of the global washout rate(WR) of (123)I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) on the recovery of LV function followingAMI, as evidenced from conventional echocardiography.Twenty consecutive patients (age: 58 +/- 13 years; 16 males and 4 females) with ST-segment elevation myocardial infarction (STEMI) were enrolled and all of them underwent successful percutaneous coronary intervention (PCI). (123)I-BMIPP cardiac scintigraphy was performed at 7 +/- 3 days after admission. The WR was calculated from the polar map and the regional BMIPP defect score was calculated using a 17 segment model. Echocardiography was performed within 24 h of admission and at 3 months to record the ejection fraction (EF), the wall motion score index (WMSI), the ratio of the mitralinflow velocity to the early diastolic velocity (E/E0)and the myocardial performance index (MPI). The mean global WR of the BMIPP was 22.12 +/- 7.22%, and it was significantly correlated with the improvement of the WMSI (r = 0.61, P\0.004). However,the relative changes of the EF, E/E0 and MPI were not correlated with the WR. The BMIPP defect score (18 +/- 10) was significantly correlated with the WMSI on admission (r = 0.74, P = 0.0002), but the defect score was not correlated with the relative changes of any of the echocardiographic parameters. We proved that the WR of the BMIPP is a promising indicator of improvement of the LV wall motion (WMSI) following ST-segment elevation myocardial infarction and successful reperfusion.

Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure.

It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of ACE, has direct effects on cardiac function. However, the role of ACE2 in the development of human heart failure is not fully understood. We evaluated the expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14 patients with end-stage heart failure. The amount of ACE2 mRNA positively correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01) but did not significantly correlate with LV ejection fraction or plasma brain natriuretic peptide levels. In conclusion, our data show that the up-regulation of the ACE2 gene in the LV myocardium of patients with severe heart failure was associated with the degree of LV dilatation and may thereby constitute an important adaptive mechanism to retard the progression of adverse LV remodeling.

The effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis in Japanese patients with dyslipidemia.

AIM: To demonstrate the clinical benefit of inhibiting intestinal cholesterol absorption, we evaluated the effects of ezetimibe on surrogate markers of cholesterol absorption and synthesis, lipid and glucose metabolism, and markers of obesity and inflammation. METHODS: A total of 120 patients with dyslipidemia (46 men; mean age 66.5 years), who had not achieved the low density lipoprotein cholesterol (LDL-C) goal recommended by the Japan Atherosclerosis Society Guideline despite diet and exercise or any statin therapy, were enrolled and additionally treated with ezetimibe (10 mg/day) for 12 weeks. RESULTS: Compared to the baseline, LDL-C was reduced by 19.2% (p<0.001) after ezetimibe monotherapy and by 24.7% (p<0.001) after co-administration with ezetimibe and any statin. Ezetimibe therapy decreased cholesterol absorption markers and increased a cholesterol synthesis marker. Treatment with ezetimibe reduced the fasting serum insulin level (p<0.05) and HbA1c (p<0.05), increased serum adiponectin (p<0.01), and showed a significant decrease of high-sensitive C-reactive protein (hsCRP, p<0.01). No adverse events occurred during the study. CONCLUSION: Thus, cholesterol absorption inhibition by ezetimibe is an important therapeutic strategy since LDL-C and cholesterol absorption markers had a positive correlation. Ezetimibe not only reduced the serum LDL-C level but also improved glucose metabolism as well as obesity and inflammation markers. These findings support the benefit of ezetimibe as a new option for the treatment of dyslipidemia.

Fatty acid metabolism and myocardial perfusion imaging for the evaluation of global left ventricular dysfunction following acute myocardial infarction: comparisons with echocardiography.

BACKGROUND: Myocardial fatty acid metabolic imaging with beta-methyl iodophenyl pentadecanoic acid (BMIPP) and perfusion imaging with tetrofosmin (TF) combined can predict post ischemic salvageable myocardium and persistent left ventricular (LV) dysfunction. This study was designed for the first time to assess systolic, diastolic and global LV dysfunction considering BMIPP and TF mismatched defect score (MMDS), and comparing this approach with the conventional Doppler echocardiography. METHODS: Thirty four patients with first acute myocardial infarction (AMI) were enrolled, and all of them underwent percutaneous coronary intervention (PCI). BMIPP and Tetrofosmin (TF) scans were performed at 7+/-3.5 days of admission. Echocardiography was performed within 24 h of admission, at an interval of 1 and 3 months. MMDS was compared with systolic: ejection fraction (EF), wall motion score index (WMSI), fractional shortening (FS); diastolic: mitral valve deceleration time (MVDT), E/E', left atrial volume index (LAVI); combined systolic and diastolic parameter: left ventricular myocardial performance index (LVMPI). RESULTS: A good correlation was observed between BMIPP and TF defect score (p<0.00001), and in 31 (91%) patients BMIPP defect score was higher than that of TF. The MMDS showed significant correlation with EF (r=-0.64, p=<0.00001), WMSI (r=0.61, p<0.0001), and FS(r=-0.65, p<0.00001), LAVI (r=-0.32, p<0.05), and LVMPI (r=0.37, p<0.02) during follow up echocardiography at 1 month. MVDT and E/E' did not correlate with MMDS. CONCLUSION: Perfusion-metabolism mismatched defect score was well correlated with the evolution of global left ventricular dysfunction following AMI evidenced from conventional Doppler echocardiography.

Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction.

PURPOSE: We prospectively investigated the prognostic value of pentraxin 3 (PTX3) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND: PTX3 may be a useful marker for localized vascular inflammation and damage to the cardiovascular system. Recent studies have shown that plasma PTX3 is elevated in patients with UA/NSTEMI; however, its prognostic value in UA/NSTEMI remains unclear. METHODS: PTX3, high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I were measured on admission in 204 consecutive patients (mean age of 69 years; 144 males) hospitalized for UA/NSTEMI within 24h (mean of 7.5h) after the onset of chest symptoms. A cardiac event, which was defined as cardiac death, rehospitalization for acute coronary syndrome (ACS), or rehospitalization for worsening heart failure, was monitored for 6 months after admission. RESULTS: A total of 26 (13%) cardiac events occurred during the 6-month follow-up period. In a stepwise Cox regression analysis including 18 well-known clinical and biochemical predictors of ACS outcome, both PTX3 (relative risk 3.86 per 10-fold increment, P=0.01) and NT-proBNP (relative risk 2.16 per 10-fold increment, P=0.02), but not hsCRP, were independently associated with the 6-month cardiac event. The cardiac event rate was higher in patients with increased PTX3 (> or = 3.1ng/mL of median value) than those without (20% vs. 5.8%, P=0.003). A Kaplan-Meier analysis revealed that patients with increased PTX3 had a higher risk for cardiac events than those without (P=0.002). CONCLUSION: PTX3 and NT-proBNP may be potent and independent predictors for 6-month cardiac events in patients hospitalized for UA/NSTEMI within 24h after the onset. Measurement of plasma PTX3 may substantially improve the early risk stratification of patients with UA/NSTEMI.

(123)I-BMIPP and (99m)Tc-TF discordance on myocardial scintigraphy and it's correlation with functional recovery following acute myocardial infarction: role of conventional echocardiography.

(123)I-beta-methyl-iodophenyl pentadecanoic acid (BMIPP) and (99m)Tc-Tetrofosmin (TF) mismatch designated as stunned myocardium having both systolic and diastolic components. The degree of mismatch might reflect subsequent functional improvement, and this study was designed to unravel the impact of mismatched defect score (MMDS) on recovery of both systolic and diastolic function following acute myocardial infarction (AMI). Forty patients with recent AMI were recruited, and all of them underwent emergency percutaneous coronary intervention. Echocardiography and BMIPP and TF cardiac scintigraphy were performed on 7 +/- 3 days of admission. Follow up echocardiography was performed after 3 months. MMDS were compared with the systolic [ejection fraction (EF) and wall motion score index (WMSI)] and diastolic [peak velocity of early diastolic filling of mitral inflow/peak early diastolic velocity of the mitral annulus(E/E') and left atrial volume index(LAVI)] parameters. BMIPP defect score was significantly higher than the TF defect score and there was a strong positive correlation between them (r = 0.90, P < 0.00001). Thirty-two (80%) patients showed mismatched defect and rest 8(20%) showed matched defect. Of 32 patients 24(75%), 22(69%), 19(59%), and 20(62.5%) showed improved EF, WMSI, E/E' and LAVI respectively. Conversely out of 8 only 2(25%), 1(12.5%), and 2(25%) patients showed improvement of EF, WMSI and LAVI, respectively. E/E' was not improved in patients with matched defect. MMDS were significantly correlated with the improvement of EF (r = -0.46, P = 0.002), WMSI (r = 0.41, P = 0.007), E/E' (r = 0.56, P < 0.0002), and LAVI (r = 0.44, P = 0.004). Mismatched defect score could predict the approximate amount of viable dysfunctional myocardium, and the degree of mismatch showed a significant correlation with the improvement of both systolic and diastolic function.

Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: potential role of oxidized lipoprotein(a) in the vasucular wall.

AIM: A new antibody reacted with an epitope in Lp(a) that has undergone oxidation treatment, but is not present in native Lp(a), was developed. Thus, we determined serum oxidized Lp(a) concentration in healthy volunteers, and coronary artery disease (CAD), diabetes mellitus (DM), and hypertensive patients. METHODS: We measured serum levels of oxidized Lp(a), Lp(a), LDL-cholesterol and HDL-cholesterol in 122 consecutive patients who underwent routine coronary angiography and had significant coronary artery stenosis (>75%), and 164 age-matched healthy volunteers. Moreover, serum native Lp(a), oxidized Lp(a) concentration, and pulse wave velocity (PWV) were determined in 181 hypertensive patients. RESULTS: Oxidized Lp(a) level in CAD patients with DM was significantly higher than in healthy volunteers (p<0.01). Moreover, serum oxidized Lp(a) concentration showed a significant positive correlation with pulse wave velocity, an index of arteriosclerosis (r=0.431, p<0.01). Of importance, the deposition of oxidized Lp(a) was readily detected in calcified areas of coronary arteries in patients with myocardial infarction. CONCLUSION: The present study demonstrated that oxidized Lp(a) may be a new risk factor for coronary artery disease. As the deposition of oxidized Lp(a) was detected in calcified areas of coronary arteries, oxidized Lp(a) might be implicated in endothelial dysfunction.

Effects of long-acting beraprost sodium (TRK-100STP) in Japanese patients with pulmonary arterial hypertension.

The long-acting beraprost preparation TRK-100STP is formulated to provide sustained release of an orally active prostacyclin derivative to maintain the optimal plasma concentration for a longer period of time compared with the currently used conventional beraprost sodium. In the present study, we evaluated the efficacy of this newly developed formulation for pulmonary arterial hypertension (PAH).An open-label, 12-week multicenter clinical trial was performed in 46 patients with PAH. They were initially treated with 120 microg of TRK-100STP divided into 60 microg twice daily, followed by a stepwise increase to 360 microg given as 180 microg twice daily. The 6-minute walking distance showed a significant increase by 33.4+/-66.0 m (95% confidence interval [CI], 13.4 to 53.5) from the baseline measurement. Mean pulmonary artery pressure, total pulmonary vascular resistance, and pulmonary vascular resistance decreased by -2.8+/-5.5 mmHg (95% CI, -4.6 to -1.0), by -0.92+/-2.63 mmHg*L(-1)*min (95% CI, -1.78 to -0.05), and by -0.89+/-2.81 mmHg*L(-1)*min (95% CI, -1.84 to 0.06), respectively, from the baseline measurements. A higher efficacy was observed in patients with a maximum tolerated dose of 360 microg daily than those of 240 microg daily or less.Treatment with TRK-100STP for a 12-week period improved the exercise capacity, mean pulmonary artery pressure, and total pulmonary vascular resistance. TRK-100STP was effective for Japanese patients with PAH.

Computed tomographic angiography characteristics of atherosclerotic plaques subsequently resulting in acute coronary syndrome.

OBJECTIVES: In a computed tomographic (CT) angiography study, we identified the characteristics of atherosclerotic lesions that were associated with subsequent development of acute coronary syndrome (ACS). BACKGROUND: The CT characteristics of culprit lesions in ACS include positive vessel remodeling (PR) and low-attenuation plaques (LAP). These 2 features have been observed in the lesions that have already resulted in ACS, but their prospective relation to ACS has not been previously described. METHODS: In 1,059 patients who underwent CT angiography, atherosclerotic lesions were analyzed for the presence of 2 features: PR and LAP. The remodeling index, and plaque and LAP areas and volumes were calculated. The plaque characteristics of lesions resulting in ACS during the follow-up of 27 +/- 10 months were evaluated. RESULTS: Of the 45 patients showing plaques with both PR and LAP (2-feature positive plaques), ACS developed in 10 (22.2%), compared with 1 (3.7%) of the 27 patients with plaques displaying either feature (1-feature positive plaques). In only 4 (0.5%) of the 820 patients with neither PR nor LAP (2-feature negative plaques) did ACS develop. None of the 167 patients with normal angiograms had acute coronary events (p < 0.001). ACS was independently predicted by PR and/or LAP (hazard ratio: 22.8, 95% confidence interval: 6.9 to 75.2, p < 0.001). Among 2- or 1-feature positive segments, those resulting in ACS demonstrated significantly larger remodeling index (126.7 +/- 3.9% vs. 113.4 +/- 1.6%, p = 0.003), plaque volume (134.9 +/- 14.1 mm(3) vs. 57.8 +/- 5.7 mm(3), p < 0.001), LAP volume (20.4 +/- 3.4 mm(3) vs. 1.1 +/- 1.4 mm(3), p < 0.001), and percent LAP/total plaque area (21.4 +/- 3.7 mm(2) vs. 7.7 +/- 1.5 mm(2), p = 0.001) compared with segments not resulting in ACS. CONCLUSIONS: The patients demonstrating positively remodeled coronary segments with low-attenuation plaques on CT angiography were at a higher risk of ACS developing over time when compared with patients having lesions without these characteristics.

Incremental effects of eicosapentaenoic acid on cardiovascular events in statin-treated patients with coronary artery disease.

BACKGROUND: Results from JELIS (Japan EPA Lipid Intervention Study) demonstrated the efficacy of pure eicosapentaenoic acid (EPA) in preventing coronary artery disease (CAD) in hypercholesterolemic patients under statin treatment. The present study examined in detail whether EPA is effective for the secondary prevention of CAD. METHODS AND RESULTS: Patients with established CAD and a total cholesterol level > or =250 mg/dl were observed with a mean follow-up of 4.6 years. They were randomly assigned to receive either 1,800 mg of EPA + statin (EPA group) or statin alone (control group). The incidence of major coronary events (MCE) were compared in the 2 groups. The incidence of MCE was significantly lower in the EPA group (8.7% vs 10.7%, adjusted hazard ratio =0.77, 95% confidence interval (CI) 0.63-0.96, P=0.017, number needed to treat (NNT) =49). Among 1,050 patients with prior myocardial infarction (MI), the incidence of MCE in the EPA group (15.0%) was significantly lower than that in the control group (20.1%, adjusted hazard ratio =0.73, 95%CI 0.54-0.98, P=0.033, NNT =19). CONCLUSIONS: EPA is effective for secondary prevention of CAD, especially in individuals with prior MI, and should be added to conventional treatment.

Management of severe heart failure.

Patients admitted to the hospital with heart failure (HF) include those with new-onset of acute HF and those with acute exacerbation of chronic HF (CHF). In therapy for new-onset acute HF associated with acute myocardial infarction, therapy to inhibit left ventricular (LV) remodeling in the convalescent phase is required in addition to that needed to overcome the acute phase. Hitherto, CHF therapy was aimed at improving LV contractability, whereas more recently the aim has shifted to resting the heart. Most patients with HF should be routinely managed with a combination of 3 types of drugs: a diuretic; an angiotensin converting enzyme inhibitor and/or an angiotensin II receptor blocker; and a beta-blocker. The administration of beta-blockers is of particular importance. For HF unresponsive to medical therapy, non-pharmacological therapies are considered. When a HF patient fails to respond to all available therapies, heart transplantation becomes necessary. Of the 1,000 HF patients admitted to our hospital, two cases received heart transplants. 11 cases were indicated for heart transplantation but died before registration. It should be remembered that although in Japan the possibility of receiving a heart transplant is very low, it is by no means entirely impossible.