Depression and Outcomes in Japanese Outpatients With Cardiovascular Disease　- A Prospective Observational Study.

BACKGROUND: The aim of this study was to determine the prevalence of depression assessed by the 9-item test from the Patient Health Questionnaire (PHQ-9) and the effect of depression on adverse cardiovascular outcomes in Japanese outpatients with cardiovascular disease (CVD).Methods and Results:This prospective observational study enrolled 1,453 outpatients with CVD (mean age 67±13 years; 31.3% female; 32.6% ischemic heart disease). Depression was defined as a PHQ-9 score ≥10. The main composite outcome was the time to death from any cause or a cardiovascular event. 81 patients (5.6%) were diagnosed with depression (PHQ-9 ≥10). NYHA class III, living alone, and unemployment were independently associated with depression. During an average follow-up of 584±80 days, the main outcome occurred in 85 patients (5.8%). There was a higher incidence of the main outcome in patients with depression than in those without depression (P<0.001). Depression was an independent predictor of the primary outcome (hazard ratio 4.64, 95% confidence interval 2.24-9.09, P<0.001). CONCLUSIONS: Depression assessed by the PHQ-9 was found in 5.6% of Japanese outpatients with CVD and was an important risk factor for adverse outcomes. (UMIN-CTR No. UMIN 000023514) (Circ J 2016; 80: 2482-2488).

Depression and outcomes in hospitalized Japanese patients with cardiovascular disease. - Prospective single-center observational study-.

BACKGROUND: Several studies have suggested that depression poses a risk in cardiovascular patients. The aim of the present study was to evaluate the prevalence of depression and its effect on cardiovascular events and mortality in Japanese inpatients with cardiovascular disease. METHODS AND RESULTS: A total of 505 patients hospitalized with cardiovascular disease (28% female; mean age, 61 ± 14 years; 31% ischemic heart disease; 47% New York Heart Association [NYHA] class II-IV; 25% implantation of pacing devices) were enrolled in the present prospective observational study. The Zung Self-Rating Depression Scale (SDS) was used to screen for depression. The primary outcome was the time to death or cardiovascular event, and the secondary outcome was death. In total, 109 patients (22%) were diagnosed with depression (Zung SDS index score ≥ 60). NYHA class III/IV, defibrillator implantation, and being unmarried were independently associated with depression. During an average follow-up period of 38 ± 15 months, 92 patients (18%) reached the primary outcome. There was a higher incidence of the primary outcome in patients with depression than in those who were not depressed (P<0.01). Depressed patients had a significantly higher rate of mortality than non-depressed patients (P<0.01). Depression was an independent predictor of the primary outcome (hazard ratio, 2.25; 95% confidence interval: 1.30-3.92, P<0.01). CONCLUSIONS: Depression was not uncommon in Japanese inpatients with cardiovascular disease and was associated with cardiovascular outcomes.

Patient Health Questionnaire-2 Screening for Depressive Symptoms in Japanese Outpatients with Heart Failure.

Objective Depression is common in patients with heart failure (HF) and is a possible risk factor for adverse outcomes. The aim of this study was to determine the prevalence of depression assessed by the 2-item Patient Health Questionnaire (PHQ-2) and the effect of depression on outcomes in Japanese outpatients with HF. Methods This sub-analysis of a prospective observational study assessed 976 patients with HF (mean age 66±13 years; 26.7% female; 42.7% with an ischemic etiology). Depression was defined as a PHQ-2 score ≥3. The main composite outcome was death from any cause or hospitalization due to worsening HF. PHQ-2 items were extracted from the PHQ-9 results. To evaluate the association of PHQ-2 scores with outcomes, Cox proportional hazards models were evaluated. Results Fifty-seven (5.8%) patients were diagnosed with depression. During a median follow-up of 21 months, the incidence rates for death from any cause and hospitalization due to worsening HF in patients with and without depression were 2.2 vs. 0.9 per 100 person-years and 6.7 vs. 1.6, p<0.001, respectively. There was a higher incidence of the main outcome in patients with depression than in those without depression (p<0.001). After adjustment for conventional risk factors, depression (PHQ-2 ≥3) was an independent predictor of the main outcome (hazard ratio 2.41, 95% confidence interval 1.14-4.67, p=0.022), and a score for item 1 of the PHQ-2 (loss of interest or pleasure) ≥2 was also an independent risk factor (hazard ratio 3.57, 95% confidence interval 1.85-6.46, p<0.001). Conclusion Depression as assessed by the PHQ-2 was identified in 5.8% of Japanese outpatients with HF and was associated with outcomes.

Self-Reported Non-adherence to Medication in Japanese Patients with Cardiovascular Diseases.

OBJECTIVE: Non-adherence to medication is an important problem in cardiovascular treatment. The aim of this study was to assess self-reported non-adherence in Japanese patients with cardiovascular disease. METHODS: A total of 1372 outpatients at three university hospitals who completed self-reported questionnaires were analyzed in this prospective study (mean age 67 ± 12 years; 31% female). Self-reported adherence to cardiovascular drugs was measured with a modified Siegal scale. Depressive symptoms were defined as a Patient Health Questionnaire-9 score of ≥ 10. RESULTS: A total of 227 patients (17%) were defined as non-adherent. Multiple logistic regression analysis showed that ≥ 2 times daily dosing frequency, age < 65 years and active employment were significantly associated with non-adherence, with odds ratios of 4.42 [95% confidence interval (CI) 3.02-6.48], 1.70 (95% CI 1.23-2.35) and 1.43 (95% CI 1.03-1.99), respectively. However, depression was not a significant factor in non-adherence. CONCLUSIONS: Our study showed that self-reported non-adherence to medications was 17% in Japanese patients with cardiovascular disease in the university hospital setting. Daily dosing frequency, younger age and employment were significantly associated with non-adherence. TRIAL REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN-CTR) no. UMIN 000023514.

Compositional Analysis of Coronary Artery Calcification in Dialysis Patients in vivo by Dual-Energy Computed Tomography Angiography.

While vascular calcification is an important factor regulating prognosis in dialysis patients, its components have not been adequately studied. We analyzed in vivo components of calcification in the coronary arteries of dialysis patients using the effective atomic number from dual-energy computed tomography. In dialysis patients (hemodialysis, N = 10; peritoneal dialysis, N = 12), average of median effective atomic number was 13.8 in the hemodialysis group, and 13.7 in the peritoneal dialysis group. No significant differences were seen between groups, with calcium oxalate monohydrate identified as the most common component in each. To confirm the accuracy of this method, we investigated the composition of surgically removed calcified tissues using already established methods. Comparison with the effective atomic number from dual-energy computed tomography showed that the results of calcification analysis were the same. We concluded that calcium oxalate monohydrate might be one of the major components of coronary artery calcification in dialysis patients.

Adherence to medication and characteristics of Japanese patients with non-valvular atrial fibrillation.

BACKGROUND: Adherence to medication plays an important role in the prevention of morbidity and mortality in non-valvular atrial fibrillation (NVAF) patients. The aim of this study is to assess adherence to medication and risk factors for non-adherence in Japanese NVAF patients who are prescribed anticoagulants. METHODS: A total of 378 outpatients with NVAF who completed self-reported questionnaires were analyzed in this prospective study (mean age 69±12 years; 26% female). Self-reported adherence to cardiovascular drugs including anticoagulants was measured with a modified Siegal scale. Depression was defined as a Patient Health Questionnaire-9 score of ≥10. Univariate and multivariate analyses were performed on several variables to analyze factors affecting non-adherence. RESULTS: In total, 291 (77%) of our patients received warfarin, and the remainder received direct oral anticoagulants. Fifty-two (14%) patients were defined as non-adherent. Univariate analyses showed that age <65 years, ≥2 times daily dosing of cardiovascular drugs and employment, but not depression, were significantly associated with non-adherence, 1.87 (95% CI: 1.01-3.42, p=0.04), 2.97 (95% CI: 1.64-5.49, p<0.01), 2.11 (95% CI: 1.16-3.93, p=0.01), and 0.74 (95% CI: 0.26-2.64), respectively. Multivariate analysis showed that only ≥2 times daily dosing was a significant independent risk factor (HR 3.06, 95% CI: 1.67-5.69, p<0.01). CONCLUSIONS: Our study showed that the prevalence of non-adherence to medications was 14% in NVAF patients. Frequent daily dosing was an independent risk factor for non-adherence to medication (UMIN-CTR No. UMIN 000023514).

Clinical application of effective atomic number for classifying non-calcified coronary plaques by dual-energy computed tomography.

BACKGROUND AND AIMS: Coronary computed tomography (CT) angiography allows non-invasive classification of non-calcified coronary plaques (NCCPs) based on Hounsfield unit (HU) values. This methodology, however, is somewhat limited for reliable classification of NCCPs. Therefore, we evaluated the effective atomic number (EAN) for classifying NCCPs by single-source dual-energy CT with fast tube voltage switching (SSDECT). METHODS: We prospectively enrolled 18 patients undergoing both SSDECT and intravascular ultrasonography (IVUS). Monochromatic images at 70 keV and EAN images were reconstructed from SSDECT data sets. Regions of interest (ROIs) within NCCPs were placed on IVUS-matched SSDECT images, and mean HU values and EANs for soft and fibrous plaques, classified using IVUS, were compared with an unpaired t-test. RESULTS: We placed 96 ROIs in 29 soft plaques and 37 ROIs in 15 fibrous plaques in 12 coronary arteries of 11 patients. The mean HU value in soft plaques (58.2 ± 32.8 HU) was significantly lower than that in fibrous plaques (103.9 ± 48.3 HU) (p < 0.001). The mean EAN in soft plaques (8.7 ± 0.5) was also significantly lower than that in fibrous plaques (9.6 ± 0.5) (p < 0.0001). Area under the curve for EAN (0.91) was significantly higher than that for HU value (0.79) in receiver operating characteristic curve analysis (p = 0.046). With a cutoff EAN of 9.3, sensitivity was 90% and specificity, 87%; whereas with a cutoff HU value of 55.0 HU, sensitivity was 62% and specificity, 93%. CONCLUSIONS: EAN measurement by SSDECT can be clinically useful for accurately classifying soft and fibrous coronary plaques.

Paroxysmal atrial fibrillation recurrences and quality of life in symptomatic patients: A crossover study of flecainide and pilsicainide.

BACKGROUND: The therapeutic goals of atrial fibrillation (AF) patients are to reduce symptoms and prevent severe complications associated with AF. This study compared the efficacy of flecainide versus pilsicainide in reducing the frequency of AF and improving quality of life (QOL) in symptomatic paroxysmal AF patients without structural heart disease. METHODS: The Atrial Fibrillation and Quality Of Life (AF-QOL) study was a prospective, multicenter, randomized, open-label crossover study that compared flecainide and pilsicainide as antiarrhythmic drug therapy. Patients were randomized to receive 3 months of treatment with flecainide twice daily or pilsicainide 3 times daily. Each treatment consisted of a dose-finding phase (weeks 1-4) and an efficacy phase (weeks 5-12). Forty-three patients completed the trial. The main outcome was the number of days with documented AF episodes using a patient-operated electrocardiogram. QOL questionnaires (SF-36 and AF-specific QOL scores) were also completed. RESULTS: The median (range) AF frequencies (days/8 weeks) were 2 (0-50) in the flecainide treatment group and 1 (0-54) in the pilsicainide treatment group (no significant between-group difference). No significant difference in the first recurrence of AF during the efficacy phase was noted between flecainide and pilsicainide treatments. The frequency and severity scores of AF-related symptoms improved from baseline to the end of the treatment periods. No significant differences in SF-36 or AF-related QOL scores were noted between the treatment groups. CONCLUSIONS: This study found no difference in AF frequency or QOL between symptomatic paroxysmal AF patients who received flecainide or pilsicainide.

Analysis of coronary arterial calcification components with coronary CT angiography using single-source dual-energy CT with fast tube voltage switching.

Clinical cardiac applications of single-source dual-energy computed tomography (DECT) have recently been introduced. This study aimed to analyze the components of coronary arterial calcification (CAC) in vivo by material decomposition achieved with DECT. We reconstructed computed tomography (CT) angiography images for 51 consecutive patients with CACs who had undergone electrocardiography-gated coronary CT angiography by single-source DECT with fast tube voltage switching. We placed regions of interest (ROIs) within the CAC with margins of at least 0.5 mm to minimize partial volume averaging. We compared histograms for the effective atomic number (EAN) and the median, mean, and maximum EANs for each CAC with the theoretical EANs for possible CAC components, including hydroxyapatite (HA), calcium oxalate monohydrate (COM), and dicalcium phosphate dehydrate. We also investigated the in vivo EAN for COM and in vitro EAN for HA by our phantom experiment. Analysis of the CAC components was feasible in 177 ROIs from 28 patients. The median EAN was 13.8 ± 0.8 (95% confidence interval 13.7-13.9), which is similar to the theoretical EAN for COM (13.8). The EAN for HA in vitro was 16.5 ± 0.1, which was slightly higher than the theoretical EAN value for HA (16.1). Notably, the median EAN in 144 ROIs (81.4%) was between 11.2 and 14.4, which is the reported range of the in vivo EAN for COM. Our results suggest that COM might be a more frequent CAC component than previously reported.

Single administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve: a transthoracic Doppler echocardiography study.

HMG-CoA reductase inhibitors (statins) have been shown to improve the endothelial function by lowering lipids. Recent studies also suggest a direct impact of statins on the vascular wall. We assessed the rapid effect of cerivastatin on the coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography (TTDE). The coronary flow velocity from the distal left anterior descending artery was measured in 16 healthy subjects (all male, age 24-38 years) using a 5-MHz transducer, on the day before, just before, and 3 h after administering 0.3 mg of cerivastatin. Hyperemia was achieved by the intravenous administration of adenosine, and the CFVR was calculated as the radio of the mean diastolic hyperemic coronary flow velocity to the basal flow velocity. The serum lipid profile and high-sensitivity C-reactive protein (hsCRP) were measured. The CFVR following the single administration of cerivastatin increased from 2.93+/-0.58 to 3.91+/-0.86, P=0.003, and was significantly higher than the CFVR measured at the same time on the previous day (3.91+/-0.86 vs 3.37+/-0.48, P=0.009). Neither the serum lipid profile nor hsCRP exhibited a remarkable change after cerivastatin administration. We concluded that a single-dose administration of cerivastatin, an HMG-CoA reductase inhibitor, improves the coronary flow velocity reserve without modifying the serum lipid profile.

Direct in vivo evidence of a vascular statin: a single dose of cerivastatin rapidly increases vascular endothelial responsiveness in healthy normocholesterolaemic subjects.

AIMS: HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. METHODS: We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group (n = 15) or cerivastatin group (n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. RESULTS: There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h (P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endothelium--independent dilatation of brachial artery was not altered. CONCLUSIONS: A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.