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Background: Real-world utilization data for evolocumab, the first proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to be introduced in Japan in 2016, to date are limited. This study aimed to clarify the current real-world patient user profiles of evolocumab based on large-scale health claims data.Methods and Results: This retrospective database study examined patients from a health administrative database (MDV database) who initiated evolocumab between April 2016 (baseline) and November 2021. Characteristics and clinical profiles of this patient population are described. In all, 4,022 patients were included in the final analysis. Most evolocumab prescriptions occurred in the outpatient setting (3,170; 78.82%), and 940 patients (23.37%) had a recent diagnosis of familial hypercholesterolemia. Common recent atherosclerotic cardiovascular disease events at baseline included myocardial infarction (1,633; 40.60%), unstable angina (561; 13.95%), and ischemic stroke (408; 10.14%). Comorbidity diseases included hypertension (2,504; 62.26%), heart failure (1,750; 43.51%), diabetes (1,199; 29.81%), and chronic kidney disease (297; 7.38%). Among the lipid-lowering regimens concomitant with evolocumab, ezetimibe+statin was used most frequently (1,281; 31.85%), followed by no concomitant lipid-lowering regimen (1,190; 29.59%), statin (950; 23.62%), and ezetimibe (601; 14.94%). The median evolocumab treatment duration for all patients was 260 days (interquartile range 57-575 days)., Conclusions: This study provides real-world insights into evolocumab utilization in Japan for optimizing patient care and adherence to guideline-based therapies to better address hypercholesterolemia in Japan.

Background: The aim of the current study was to determine if the slowed exercise oxygen uptake (VO(2)) kinetics, which is developed by myocardial ischemia, would be accompanied by delayed recovery VO(2) kinetics in patients with coronary artery disease (CAD)., Methods and Results: Thirty-seven patients with significant ST depression during treadmill exercise underwent cardiopulmonary exercise testing with cycle ergometer. Measurements performed are the ratios of change in increase in oxygen (O(2)) uptake relative to increase in work rate (DeltaVO(2)/DeltaWR) across anaerobic threshold (AT) and 1 mm ST depression point (ST-dep), the time constants of VO(2) during recovery (T(1/2) VO(2)), stress radio-isotope scintigraphy and coronary angiography. Patients were divided into CAD positive (CAD+) and CAD negative (CAD-) groups, based on coronary angiography. In CAD+, DeltaVO(2)/DeltaWR decreased above AT and ST-dep, in contrast to CAD- patients. The T(1/2) VO(2) in CAD+ (103.1 +/-13.0 s) was greater than that of CAD- (76.5 +/-8.7 s) and showed negative correlations to the ratios of DeltaVO(2)/DeltaWR across AT and ST-dep. These parameters improved in the patients who underwent coronary bypass surgery., Conclusions: Exercise and recovery VO(2) kinetics were slowed when myocardial ischemia was provoked by exercise. Measurement of exercise and recovery VO(2) kinetics improve the accuracy of the exercise electrocardiogram diagnosis of CAD.

Background: The aim of this study was to clarify the influence of sympathetic and parasympathetic nerve (SN and PN) dysfunction on the heart rate (HR) response to exercise and the exercise capacity of patients with acute myocardial infarction (AMI) and diabetes mellitus (DM)., Methods and Results: Fifty-two male patients who underwent cardiopulmonary exercise testing (CPX) 1 month after onset of AMI were divided into 2 groups: (DM (+) group, n=20; DM (-) group, n=32). HR, peak oxygen uptake (VO2peak), and plasma norepinephrine (NE) levels were measured during CPX. The high-frequency power (HF) was analyzed by HR variability. The DeltaHR/logDeltaNE obtained from changes of HR and NE from rest to peak exercise and HR change from baseline to the minimum HF (DeltaHRHF) were calculated as parameters of HR response derived from SN and PN activities, respectively. DeltaHR, VO2peak, DeltaHR/logDeltaNE, and DeltaHRHF were significantly lower in the DM (+) group than in the DM (-) group, and both of them showed positive correlations with VO2peak., Conclusion: An inadequate HR response to exercise is a major factor causing a decline of exercise capacity, which is derived from both of SN and PN dysfunction, in AMI patients with DM.

Heart rate (HR) response during exercise in patients with ischemic heart disease was evaluated, and the appropriateness of Karvonen's method for determining rehabilitation exercise target HR was investigated. The study group comprised 24 patients with acute myocardial infarction (AMI) and 37 patients who had undergone coronary artery bypass grafting (CABG). Cardiopulmonary exercise testing (CPX) was performed with a cycle ergometer and changes in HR (deltaHR)/changes in work rate (deltaWR) and interval changes of the coefficient of Karvonen's formula were evaluated. In the AMI group and the CABG group, deltaHR/deltaWR were significantly lower than those of age-matched control subjects (p<0.01). Karvonen's coefficients ranged from 0.37 to 0.54 when calculated from actual peak HR and 0.21 to 0.32 calculated from the predicted peak HR. An impaired HR response was found in patients with AMI and those who had had CABG up to 6 months previously. Because the Karvonen's coefficient values, which ranged from 0.6 to 0.8, were elevated for these patients, and considering the data from the CPX, increased exercise is recommended for such cases.

The present study investigated the serial changes in serum magnesium (Mg) and erythrocyte concentration of Mg in patients with acute myocardial infarction (AMI) and the relationship between these changes and left ventricular ejection fraction (LVEF) at 1 month after the onset of infarction. The study group comprised 26 patients with AMI (mean age, 57.9+/-8.9 years). Serum Mg and erythrocyte Mg were measured on hospital days 1, 2, 4, 7 and 21. The change in erythrocyte Mg during the acute phase was calculated as a ratio: [(erythrocyte Mg at day 2)-(erythrocyte Mg at day 1)]/(erythrocyte Mg at day 1). The change in serum Mg was calculated similarly. The following results were obtained. (1) Serum Mg tended to increase from the onset of myocardial infarction (day 1: 1.86+/-0.19, day 2: 1.93+/-0.22, day 4: 2.17+/-0.23; day 7: 2.25+/-0.20; day 21: 2.12+/-0.15 mg/dl). (2) Erythrocyte Mg on day 2 and day 4 showed a significant decrease compared with day 1 (day 1: 2.45+/-0.40, day 2: 2.09+/-0.41, day 4: 2.07+/-0.37, day 7: 2.22+/-0.33, day 7: 2.34+/-0.28 mg/dl per 400x10(4)/mm3 cells). (3) A significant positive correlation was observed between the change in serum Mg and LVEF (r=0.55, p<0.05), and a significant negative correlation was observed between the change in erythrocyte Mg and LVEF (r=-0.57, p<0.05). Thus, it was concluded that an extracellular shift in intracellular Mg occurred during the first 2 days after the onset of myocardial infarction. This responsive increase in the extracellular Mg level may be an important factor for maintaining left ventricular function in patients 1 month after the onset of AMI.

A 61-year-old female, with a history of uterine and cervical cancer treated with radical hysterectomy and 2 years of postoperative chemotherapy, presented to the emergency department with dyspnea on exertion. Computed tomography of the chest revealed a large pericardial effusion and a sacciform aneurysm of the ascending aorta. The patient subsequently underwent emergency pericardiocentesis with drainage of approximately 330 ml of a bloody and turbid effusion. Cultures from the effusion yielded group B streptococcus. Multiple organ failure and disseminated intravascular coagulation syndrome occurred in the acute phase, but gradually improved with continuous antibiotic therapy. On the 194th hospital day, in situ reconstruction of the ascending aorta was successfully performed using a synthetic graft. Although rarely reported, both purulent bacterial pericarditis and mycotic aneurysm can be life-threatening.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide produced by vascular endothelial cells. However, the role of ET-1 in exercise-induced physiological responses is still to be investigated. The purpose of the present study was to investigate in healthy volunteers whether the ET-1 plasma concentration in nonworking muscles is changed by exercise and to investigate the physiological role of ET-1 during exercise. Bicycle ergometer cardiopulmonary exercise tests were performed in 36 healthy men (mean age, 22.5 years). Blood samples for measuring ET-1 were drawn from the cubital vein during rest and immediately after the exercise test. The ET-1 change ratio was calculated as ET-1 immediately following exercise/ET-1 during the resting state. Cardiac output (CO) was measured during the exercise test by the impedance method. Arterial venous oxygen difference (AVO2D) when CO reached 10L/min or 15L/min was calculated as AVO2D = VO2/CO. Results were as follows: (1) the ET-1 change ratio correlated inversely with exercise time at the anaerobic threshold (r = -0.37, p = 0.03) and peak exercise time (r = -0.35, p = 0.04); (2) the ET-1 change ratio tended toward an inverse correlation with deltaVO2/deltawork rate (r = -0.29, p = 0.09); (3) the ET-1 change ratio correlated positively with AVO2D when CO reached 10L/min (r = 0.42, p = 0.02) and tended toward a positive correlation with AVO2D when CO reached 15 L/min (r = 0.32, p = 0.08). These results indicate that an increase in ET-1 in nonworking muscles may participate in the exercise-induced redistribution of blood flow and in increasing the blood flow to working muscles.

Recent observations have shown that plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) correlate with cardiac function or prognosis in heart failure patients. However, relatively little is known about changes in their plasma concentration during commonly occurring physiological states such as fatigue. Therefore, this study was designed to examine the physiological changes of plasma ANP and BNP concentrations using a chronic sleep-deprivation model. Bicycle ergometer cardiopulmonary exercise tests were performed in 10 healthy volunteers (mean age: 22.7 years). Blood samples for measuring ANP and BNP were drawn during the resting state and immediately after each exercise test. Cardiac output (CO) was measured during the exercise test by the impedance method. The study conditions were designed as follows: (A) a day following a period of normal sleep (control state) and (B) a day preceded by 1 month during which sleep lasted <60% of normal (chronic sleep-deprived state). Results were as follows. (1) Peak oxygen uptake and peak CO decreased during the sleep-deprived state compared with the control state. (2) There was no difference between peak heart rates measured during exercise under the 2 conditions. (3) Plasma ANP concentration during exercise increased significantly during the control state, whereas only a tendency toward increase was observed during the sleep-deprived state. (4) Plasma BNP concentration during exercise tended to increase in the control state compared with the resting state, whereas there was no difference in plasma BNP between after exercise and resting state in the sleep-deprived state. These results indicate that changes of ANP or BNP induced by exercise tended to be decreased by chronic sleep deprivation.

We have previously reported that chronic sleep deprivation causes a deficiency of intracellular magnesium (Mg) and decreased exercise tolerance. The aim of this study was to clarify whether oral administration of Mg could be effective in restoring the exercise tolerance that is decreased by chronic sleep deprivation. A bicycle ergometer cardiopulmonary exercise test was performed by 16 healthy volunteers (mean age 21.9 years). They were divided into 2 groups: 8 received doses of 100 mg of Mg orally per day for 1 month (Mg group) and the remaining 8 received no Mg and served as the control group. The study conditions were designed as follows: (1) the usual state (good sleep); and (2) the sleep-deprived state (sleeping time up to 60% less than the usual state for 1 month). The ratio of intracellular Mg content of the sleep-deprived state to the usual sleep state was significantly higher in the Mg group (p<0.05) than the untreated control group. There was no difference between the sleep-deprived state and the usual state with regard to anaerobic threshold and peak oxygen uptake in the Mg group, whereas both of these decreased in the sleep-deprived state in the control group. These results indicate that decreased exercise tolerance observed in the sleep-deprived state could be improved by oral Mg administration.

The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the reninangiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI.

To predict exercise tolerance in the chronic phase of myocardial infarction (MI), cardiopulmonary exercise testing was performed using a ramp treadmill protocol in 25 patients at 1 and 3 months after the onset of MI. Oxygen uptake, heart rate and O2 pulse were estimated at rest, during a warm-up period, and at the levels of anaerobic threshold (AT), respiratory compensation (RC) and peak exercise. Results were as follows: 1) AT and peak oxygen uptake at 3 months after the onset of MI were 14.1 +/- 2.8 and 21.8 +/- 5.2 ml/min/Kg, respectively. 2) The subjects were divided into 2 groups according to peak oxygen uptake at 3 months: one showing peak oxygen uptake > 22 ml/min/Kg and the other < 22 ml/min/Kg. The former group (n = 13) was referred to as the good tolerance group, and the latter group (n = 12) was referred to as the poor tolerance group. Oxygen uptake at AT, RC and peak exercise was lower in the poor tolerance group than in the good tolerance group (11.2 vs 14.7, 15.1 vs 20.4, 17.1 vs 23.4 ml/min/Kg, respectively). 3) The increases in oxygen uptake from AT to RC and from AT to peak exercise were less in the poor tolerance group than in the good tolerance group. 4) O2 pulse at rest, warm-up, AT, RC and peak exercise were also lower in the poor tolerance group.2+ tolerance in the chronic phase of MI.