Background:Temporal trends in clinical characteristics, management and prognosis of patients with symptomatic heart failure (HF) remain to be elucidated in Japan.Methods and Results:From the Chronic ...Heart Failure Analysis and Registry in the Tohoku District-1 (CHART-1; 2000–2005, n=1,278) and CHART-2 (2006-present, n=10,219) Studies, we enrolled 1,006 and 3,676 consecutive symptomatic stage C/D HF patients, respectively. As compared with the patients in the CHART-1 Study, those in the CHART-2 Study had similar age and sex prevalence, and were characterized by lower brain natriuretic peptide, higher prevalence of preserved left ventricular ejection fraction (LVEF) and higher prevalence of hypertension, diabetes mellitus and ischemic heart disease (IHD), particularly IHD with LVEF ≥50%. From CHART-1 to CHART-2, use of renin-angiotensin system inhibitors, β-blockers and aldosterone antagonists was significantly increased, while that of loop diuretics and digitalis was decreased. Three-year incidences of all-cause death (24 vs. 15%; adjusted hazard ratio adjHR, 0.73; P<0.001), cardiovascular death (17 vs. 7%; adjHR, 0.38; P<0.001) and hospitalization for HF (30 vs. 17%; adjHR, 0.51; P<0.001) were all significantly decreased from CHART-1 to CHART-2. In the CHART-2 Study, use of β-blockers was associated with improved prognosis in patients with LVEF <50%, while that of statins was associated with improved prognosis in those with LVEF ≥50%.Conclusions:Along with implementation of evidence-based medications, the prognosis of HF patients has been improved in Japan. (Trial registration: clinicaltrials.gov identifier: NCT00418041) (Circ J 2015; 79: 2396–2407)
Aim: Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor (PPAR)-α, a key regulator of lipid and glucose metabolism. We compared the efficacy and safety of ...pemafibrate with those of bezafibrate, a nonselective PPAR-α agonist.Methods: In this randomized crossover study, 60 patients with hypertriglyceridemia (fasting triglyceride TG ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks. The primary endpoint was percent change (%Change) from baseline in TG levels, while the secondary endpoints were %Change in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) levels.Results: The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (−46.1% vs. −34.7%, p＜0.001; 9.2% vs. 5.7%, p =0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate. Creatinine levels significantly increased in both treatments; however, its %Change was significantly lower with pemafibrate than with bezafibrate (5.72% vs. 15.5%, p＜0.001). The incidence of adverse events (AEs) or serious AEs did not differ between the two treatments; however, the number of patients with elevated creatinine levels (≥ 0.5 mg/dL and/or 25% from baseline) was significantly lower in the bezafibrate group than in the pemafibrate group (16/60 vs. 3/60, p =0.004).Conclusion: Compared with bezafibrate, pemafibrate is more effective in decreasing TG levels and increasing Apo A-I levels and is safer regarding liver and renal function.
The association between insulin resistance and lipid dysmetabolism after consuming a meal is unclear. We aimed at assessing the effects of ezetimibe on postprandial hyperlipidemia and ...hyperinsulinemia and to find out whether the medication improves endothelial function in obese metabolic syndrome (MetS) patients with coronary artery disease (CAD). We obtained oral fat loading test results (4 and 6 h after load) and brachial flow-mediated vasodilation (FMD) measurements before and 24 weeks after ezetimibe treatment initiation from 27 MetS patients with CAD and from 68 control patients with CAD alone. Serum triglyceride (TG) and insulin levels (2 h after the loading dose) were significantly higher in MetS patients than in control patients. The incremental areas under the curve (
i
AUCs) for these levels decreased significantly after ezetimibe treatment in MetS patients but not in control patients. Treatment with ezetimibe resulted in significant FMD changes in MetS patients (from 3.4 to 4.9%,
P
= 0.002), but not in control patients (from 5.1 to 5.4%,
P
= 0.216). When MetS patients were divided into two groups based on the median insulin
i
AUC reduction rate (higher group ≥ 34%,
n
= 14; lower group < 34%,
n
= 13), those in the higher group showed a significantly higher rate of change in the
i
AUCs of TG and FMD than those in the lower group (TG, 31.0% vs. 10.8%;
P
= 0.033; FMD, 39.2% vs. 9.8%;
P
= 0.037). These results suggest that ezetimibe may reverse insulin resistance, reducing lipid dysmetabolism after a meal and endothelial dysfunction in MetS patients with CAD.
Positioning a patient on the catheterization table is important for proper cardiac or respiratory function during peripheral vascular interventions. Fowler's position, where the patient's head is a ...45° angle, is more effective in reducing venous blood volume returning to the heart from the periphery compared with the supine position. The Terumo R2P system has been developed for transradial peripheral vascular interventions.
Two patients with heart failure (a 75-year-old Japanese female and a 74-year-old Japanese male) underwent lower-extremity peripheral vascular interventions in Fowler's position to prevent worsening heart failure. Because their head position was opposite the C-arm of the X-ray machine, the left radial artery was selected as the access site. The Terumo R2P system was used for transradial peripheral vascular intervention. We successfully treated superficial artery diseases with long shaft balloons and rapid-exchange Terumo R2P Misago stents.
Although lower-extremity peripheral vascular intervention using Fowler's position and the Terumo R2P system has several limitations, including device availability and technical complexity, it may be effective for particular patients who have higher risk of worsening heart failure in the supine position.
This study examined the effects of pemafibrate, a selective peroxisome proliferator-activated receptor α agonist, on the serum biochemical parameters of male patients with coronary artery disease and ...metabolic syndrome (MetS). This was a post hoc analysis of a randomized, crossover study that treated hypertriglyceridemia with pemafibrate or bezafibrate for 24 weeks, followed by a crossover of another 24 weeks. Of the 60 patients enrolled in the study, 55 were male. Forty-one of 55 male patients were found to have MetS. In this sub-analysis, male patients with MetS (MetS group,
n
= 41) and those without MetS (non-MetS group,
n
= 14) were compared. The primary endpoint was a change in fasting serum triglyceride (TG) levels during pemafibrate therapy, and the secondary endpoints were changes in insulin resistance-related markers and liver function parameters.
S
erum TG levels significantly decreased (MetS group, from 266.6 to 148.0 mg/dL,
p
< 0.001; non-MetS group, from 203.9 to 97.6 mg/dL,
p
< 0.001); however, a percent change (%Change) was not significantly different between the groups (− 44.1% vs. − 51.6%,
p
= 0.084). Serum insulin levels and homeostasis model assessment of insulin resistance significantly decreased in the MetS group but not in the non-MetS group. %Change in liver enzyme levels was markedly decreased in the MetS group compared with that in the non-MetS group (alanine aminotransferase, − 25.1% vs. − 11.3%,
p
= 0.027; gamma-glutamyl transferase, − 45.8% vs. − 36.2%,
p
= 0.020). In conclusion, pemafibrate can effectively decrease TG levels in patients with MetS, and it may be a more efficient drug for improving insulin resistance and liver function in such patients.
Pulmonary artery pseudoaneurysms (PAPs) are uncommon, yet they frequently result in hemoptysis and are associated with a poor prognosis. We report a case of an 87-year-old male patient. Initially, he ...was admitted to a previous hospital, and diagnosed with a lung abscess in the left lower lobe. On the second hospital day, he developed hemoptysis. A contrast-enhanced chest computed tomography (CT) identified an infectious pulmonary artery pseudoaneurysm. On the ninth hospital day, pulmonary artery coil embolization was successfully performed, significantly improving the patient's condition.
A 79-year-old woman was admitted to our hospital for ischemic necrosis of the right first toe. During having normal lipid profiles, such as low-density lipoprotein cholesterol and triglyceride, ...plasma levels of lipoprotein(a) (Lp(a) were abnormally high (141 mg/dL). She had a history of heart failure (HF) due to aortic valve stenosis (AS) and drug-eluting coronary stenting due to angina pectoris. To avoid worsening of HF and limb ischemia during minor amputation, she underwent balloon aortic valvuloplasty and endovascular therapy. She was also placed on proprotein convertase subtilisin/kexin type 9 inhibitors (140 mg of evolocumab) every 2 weeks, which decreased her plasma Lp(a) levels to 105 mg/dL (26% decrease) at discharge. Elevated plasma Lp(a) levels could strongly affect the development of AS and progression of systemic atherosclerosis. The screening and treatment of increased plasma Lp(a) are imperative for patients with AS having peripheral arterial disease.
Matrix metalloproteinase-13 (MMP-13) has been implicated to play a key role in the pathology of osteoarthritis. On the basis of X-ray crystallography, we designed a series of potent MMP-13 selective ...inhibitors optimized to occupy the distinct deep S1′ pocket including an adjacent branch. Among them, carboxylic acid inhibitor 21k exhibited excellent potency and selectivity for MMP-13 over other MMPs. An effort to convert compound 21k to the mono sodium salt 38 was promising in all animal species studied. Moreover, no overt toxicity was observed in a preliminary repeat dose oral toxicity study of compound 21k in rats. A single oral dose of compound 38 significantly reduced degradation products (CTX-II) released from articular cartilage into the joint cavity in a rat MIA model in vivo. In this article, we report the discovery of highly potent, selective, and orally bioavailable MMP-13 inhibitors as well as their detailed structure–activity data.
•Transient upregulation of mature and furin-cleaved circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) in acute myocardial infarction (MI).•Persistent, significant increase of plasma ...mature PCSK9 levels by PCSK9 inhibitor.•Decrease in plasma furin-cleaved PCSK9 levels by PCSK9 inhibitor.•Increased plasma lipoprotein(a) levels and significant inhibition in acute MI.
There are two types of circulating proprotein convertase subtilisin/kexin type 9 (PCSK9), mature and furin-cleaved. Most types of lipoprotein(a) Lp(a), an independent risk factor of cardiovascular events, bind to mature PCSK9.
This study examined the effects of monoclonal anti-PCSK9 antibody on plasma PCSK9 and Lp(a) levels in acute myocardial infarction (MI).
Acute MI patients (n=36) were randomly divided into evolocumab (140mg; n=17) and non-evolocumab (n=19) groups. Changes in plasma PCSK9 and Lp(a) levels were monitored before and 1, 3, 5, 10, and 20 days after evolocumab administration.
In the non-evolocumab group, plasma levels of mature PCSK9, furin-cleaved PCSK9, and Lp(a) (236.4±57.3ng/mL, 22.4±5.8ng/mL, and 19.2.±16.5mg/dL, respectively) significantly increased by day 3 (408.8±77.1ng/mL, p<0.001; 47.2±15.7ng/mL, p<0.001; and 39.7±21.3mg/dL, p<0.005, respectively) and returned to the baseline by day 10 or 20. In the evolocumab group, mature PCSK9 significantly increased by >1000ng/mL with a simultaneous decline of furin-cleaved PCSK9 below the measurement sensitivity level after day 3. The incremental area under the curve for plasma Lp(a) levels was significantly smaller in the evolocumab group compared with the non-evolocumab group (p=0.038).
Mature and furin-cleaved PCSK9 are transiently upregulated after MI onset. Evolocumab significantly increases mature PCSK9 and decreases furin-cleaved PCSK9 and might inhibit transient increase of plasma Lp(a) in acute MI.
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