Associations of Acetic Acid Intake with Protein and Vitamin Intake Estimated via a Food Recording Application.

A conventional questionnaire-based assessment of acetic acid intake is based on the intake of seasonings such as mayonnaise, which could thereby lead to an underestimation. We here determine the relationships of acetic acid intake with nutrient intake estimated using a food recording app (Asken) based on meal recipes. A total of 141 individuals (48 men and 93 women) used the app for at least 7 days per month. The mean daily intake of acetic acid was 0.16 ± 0.19 g and the mean frequency of acetic acid intake was 2.77 ± 1.66 days per week. A multivariate regression analysis adjusted for age, sex, BMI, and energy intake revealed that the amount of acetic acid consumed was significantly and positively associated with the intake of protein (11.9 (5.1, 18.6), p < 0.001), cholesterol (80.7 (4.5, 156.9), p = 0.04), and all vitamins except vitamin K. The frequency of acetic acid intake was significantly and positively associated with protein (1.04 (0.20, 1.87), p = 0.015), vitamin B1 (0.3 (0.02,0.5), p = 0.031), niacin (0.5 (0.04,1.0), p = 0.032), and vitamin B12 (0.4 (0.1,0.7), p = 0.002) intake, suggesting that individuals who frequently consume acetic acid tend to consume more protein and some vitamins. Thus, the amount and frequency of acetic acid may reflect protein and vitamin intake.

Sex and Age Differences in the Effects of Food Frequency on Metabolic Parameters in Japanese Adults.

Owing to differences in dietary preferences between men and women, the associations between dietary intake frequency and metabolic parameters may differ between the sexes. A retrospective observational study of the checkup findings of 3147 Japanese individuals (968 men, 2179 women) aged 20-59 years was conducted to examine differences in dietary habits and associations between food frequency and blood parameters (eGFR, HbA1c, uric acid, and lipids) by sex and age. Males were more likely to consume meat, fish, soft drinks, and alcohol, whereas women were more likely to consume soybeans, dairy products, vegetables, fruits, and snacks. Multivariate linear regression models adjusted for age and BMI revealed that meat intake frequency was positively associated with HbA1c (ß = 0.007, p = 0.03) and negatively associated with eGFR (ß = -0.3, p = 0.01) only in males, whereas fish intake frequency was positively associated with eGFR (ß = 0.4, p = 0.005) only in females. Egg and soy intake frequencies were positively and negatively associated with non-HDL-C (egg: ß = 0.6, p = 0.02; soy: ß = -0.3, p = 0.03) only in females. Alcohol consumption frequency was associated with uric acid (M: ß = 0.06, p < 0.001; F: ß = 0.06, p < 0.001) and HDL-C (M: ß = 1.0, p < 0.001; F: ß = 1.3, p < 0.001) in both sexes. Future research is needed to determine whether varying the emphasis of dietary guidance by sex and age group is effective, since the effects of dietary preferences on metabolic parameters vary by age and sex.

Humoral and Cellular Response Induced by Primary Series and Booster Doses of mRNA Coronavirus Disease 2019 Vaccine in Patients with Cardiovascular Disease: A Longitudinal Study.

Preexisting cardiovascular disease (CVD) is a pivotal risk factor for severe coronavirus disease 2019 (COVID-19). We investigated the longitudinal (over 1 year and 9 months) humoral and cellular responses to primary series and booster doses of mRNA COVID-19 vaccines in patients with CVD. Twenty-six patients with CVD who received monovalent mRNA COVID-19 vaccines were enrolled in this study. Peripheral blood samples were serially drawn nine times from each patient. IgG against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike receptor-binding domain (RBD) was measured using an enzyme-linked immunosorbent assay. The numbers of interferon-γ-releasing cells in response to SARS-CoV-2 peptides were measured using an enzyme-linked immunospot assay. The RBD-IgG titers increased 2 weeks after the primary series and booster vaccination and waned 6 months after vaccination. The S1-specific T cell responses in patients aged < 75 years were favorable before and after booster doses; however, the Omicron BA.1-specific T cell responses were poor. These results suggest that regular vaccination is useful to maintain long-term antibody levels and has implications for booster dose strategies in patients with CVD. Additional booster doses, including Omicron variant-adapted mRNA vaccines, may be recommended for patients with CVD, regardless of age.

Efficacy of CHA2DS2-VASc scores in predicting chronic kidney disease risk in patients treated in cardiac intensive care units.

The CHA2DS2 -VASc score is a vital clinical tool for evaluating thromboembolic risk in patients with atrial fibrillation (AF). This study investigated the efficacy of the CHA2DS2 -VASc score in a cohort of 737 heterogeneous patients (mean age: 63 years) receiving care in cardiac intensive care units (CICUs), with a creatinine-based estimated glomerular filtration rate (eGFR) of ≥60 mL/min/1.73 m2 upon admission and discharge. Incident chronic kidney disease (CKD) was defined as the emergence of a new-onset eGFR<60 mL/min/1.73 m2, accompanied by a decline of >5 mL/min/1.73 m2 compared to that at discharge. The primary endpoint was the incidence of CKD, and the secondary endpoints included all-cause mortality, cardiovascular events, and progression to end-stage kidney disease. In this cohort, 210 (28 %) patients developed CKD. Multivariate analyses revealed that CHA2DS2 -VASc score was a significant independent predictor of incident CKD, regardless of the presence of AF. Integration of CHA2DS2 -VASc scores with eGFR enhanced the predictive accuracy of incident CKD, as evidenced by the improved C-index, net reclassification improvement, and integrated discrimination improvement values (all p < 0.05). Over the 12-month follow-up period, a composite endpoint was observed in 61 patients (8.3 %), with elevated CHA2DS2 -VASc scores being independently associated with this endpoint. In conclusion, CHA2DS2-VASc scores have emerged as robust predictors of both CKD incidence and adverse outcomes. Their inclusion substantially refined the 12-month risk stratification of patients with preserved renal function hospitalized in the CICUs.

A Study on the Compatibility of a Food-Recording Application with Questionnaire-Based Methods in Healthy Japanese Individuals.

In Japan, nutritional guidance based on food-recording apps and food frequency questionnaires (FFQs) is becoming popular. However, it is not always recognized that different dietary assessment methods have different nutritional values. Here, we compared the compatibility of dietary intake data obtained from an app with those obtained from FFQs in 59 healthy individuals who recorded information regarding their diet for at least 7 days per month using an app developed by Asken (Tokyo, Japan). The diurnal coefficient of variation in total energy and protein intake was 20%, but those for vitamins B12 and D were >80%, reflecting the importance of 7 days of recording rather than a single day of recording for dietary intake analyses. Then, we compared the results of two FFQs-one based on food groups and one based on a brief self-administered diet history questionnaire-for 7 days, as recorded by the app. There was a correlation coefficient of >0.4 for all the items except salt. Regarding the compatibility between the app and FFQs, the percentage errors for total energy and nutrients were >40-50%, suggesting no agreement between the app and the two FFQs. In conclusion, careful attention should be paid to the impact of different dietary assessment methods on nutrient assessment.

Differing Effects of Body Size on Circulating Lipid Concentrations and Hemoglobin A1c Levels in Young and Middle-Aged Japanese Women.

The condition of being underweight is a social problem in Japan among women. However, there is a lack of evidence for dietary guidance for underweight women because there has been no comparison of lipids or HbA1c among underweight, normal weight, and overweight women in different age groups. We analyzed the effect of body size and age on the serum lipid and hemoglobin A1c levels in Japanese women in a cross-sectional study. A total of 26,118 women aged >20-65 years underwent physical examinations between 2012 and 2022. Seventeen percent of women aged >20-29 years were underweight, and 8% of those aged 50-65 years were underweight. Total cholesterol and non-HDL-C concentrations increased with age, but the difference between underweight and overweight individuals was lowest among women aged 50-65 years. On the other hand, the differences in HDL-C, TG, and HbA1c levels between underweight and overweight subjects were greatest in the 50-65 age group, but the differences between underweight and normal weight subjects were much smaller. Considering that, unlike HDL-C, TG, and HbA1c, TC and non-HDL-C increase to levels comparable to overweight levels in underweight women in aged 50-65 years, educating people about a diet that lowers non-HDL-C is necessary even in young underweight women.

Assessment of the renal angina index in patients hospitalized in a cardiac intensive care unit.

The renal angina index (RAI) is a validated scoring tool for predicting acute kidney injury (AKI). We investigated the efficacy of the RAI in 2436 heterogeneous patients (mean age, 70 years) treated in cardiac intensive care units (CICUs). The RAI was calculated from creatinine and patient condition scores. AKI was diagnosed by the Kidney Disease: Improving Global Outcome criteria. The primary and secondary endpoints were the development of severe AKI and all-cause mortality, respectively. Four hundred thirty-three patients developed AKI, 87 of them severe. In multivariate analyses, the RAI was a significant independent predictor of severe AKI. During the 12-month follow-up period, 210 patients suffered all-cause death. Elevated RAI was independently associated with all-cause mortality, as was NT-proBNP (p < 0.001). The RAI is a potent predictor not only of severe AKI but also of adverse outcomes and substantially improved the 12-month risk stratification of patients hospitalized in CICUs.

Clinical Outcomes Based on Coronary Computed Tomography-Derived Fractional Flow Reserve and Plaque Characterization.

BACKGROUND: Coronary computed tomography angiography (CTA) followed by computed tomography angiography-derived fractional flow reserve (FFRCT) is now commonly used for the management of chronic coronary syndrome (CCS). CTA-verified high-risk plaque (HRP) characteristics have also been reported to be associated with a greater likelihood of adverse cardiac events but have not been used for management decisions. OBJECTIVES: The aim of this study was to evaluate clinical outcomes based on a combination of point-of-care computed tomography angiography-derived fractional flow reserve (POC-FFRCT) and the presence of HRP in CCS patients initially treated medically or with revascularization based on invasive coronary angiography findings. METHODS: CTA was performed as the initial test in 5,483 patients presenting with CCS between September 2015 and December 2020 followed by invasive coronary angiography and revascularization as necessary. POC-FFRCT assessment and HRP characterization were obtained subsequently in 745 consecutive patients. We investigated how HRP and POC-FFRCT, which were not available during the original clinical decision making, correlated with the endpoint defined as a composite of cardiac death, acute coronary syndrome, and a need for unplanned revascularization. RESULTS: Cardiac events occurred in 20 patients (2.7%) during a median follow-up of 744 days. The event rate was significantly higher in patients with POC-FFRCT <0.80 compared with POC-FFRCT ≥0.8 (5.4 vs 0.5 per 100 vessel years; log-rank P < 0.0001) and in patients with HRP compared to those without HRP (3.6 vs 0.8 per 100 vessel years; log-rank P = 0.0001). POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events (HR: 16.67; 95% CI: 2.63-105.39; P = 0.002) compared with POC-FFRCT ≥0.8 and absent HRP. For the vessels with POC-FFRCT <0.80 and HRP, a significantly higher rate of adverse events was observed in patients who did not undergo revascularization compared with those revascularized (16.4 vs 1.4 per 100 vessel years; log-rank P = 0.006). CONCLUSIONS: POC-FFRCT <0.80 and the presence of HRP were the independent predictors of cardiac events, and revascularization of HRP lesions with abnormal POC-FFRCT was associated with a lower event rate.

Young Japanese Underweight Women with "Cinderella Weight" Are Prone to Malnutrition, including Vitamin Deficiencies.

Undernutrition among young women at "Cinderella weight" is socially important in Japan. To determine the nutritional status of Cinderella-weight women, we conducted an exploratory cross-sectional study on the health examination results of employees aged 20 to 39 (n = 1457 and 643 for women and men, respectively). The percentage of underweight women was found to be much higher than that of men (16.8% vs. 4.5%, respectively). In underweight women (n = 245), handgrip strength (22.82 ± 5.55 vs. 25.73 ± 5.81 kg, p < 0.001), cholesterol level (177.8 ± 25.2 vs. 194.7 ± 31.2 mg/dL, p < 0.05), and lymphocyte count (1883 ± 503 vs. 2148 ± 765/µL, p < 0.001) were significantly lower than in overweight women (n = 116). Then, the BMI < 17.5 group (n = 44) was referred to the outpatient nutrition evaluation clinic. Lower prealbumin, cholesterol, and lymphocyte levels were also observed in 34%, 59%, and 32% of the patients, respectively. Regarding dietary characteristics, 32% of the underweight women in this study skipped breakfast, and 50% had low dietary diversity scores. Lower total energy intake, carbohydrate and fiber intake, and Ca and Fe intake were also observed in 90% of the patients. Deficiencies in vitamin B1, B12, D, and folate were diagnosed in 4.6%, 25%, 14%, and 98% of the patients, respectively. Thus, young underweight women may be prone to malnutrition.

Predictors of in-hospital mortality in elderly patients with heart failure treated with tolvaptan.

Objectives: We conducted an analysis of first-time tolvaptan users (≥80 years old) to determine the factors associated with the prognosis of elderly patients with heart failure. Methods: We retrospectively analyzed 66 consecutive patients with worsening heart failure (aged ≥80 years) who were admitted to Fujita Health University Bantane Hospital from 2011 to 2016 and treated with tolvaptan. Differences between the in-hospital death and survival groups were evaluated. Multivariate logistic regression analysis was also performed to identify the risk factors for mortality. Results: Sixty-six patients were included, and 26 patients died during the index hospitalization. The patients who died had a significantly higher prevalence of ischemic heart disease; a higher heart rate; higher levels of plasma C-reactive protein, blood urea nitrogen (BUN), and creatinine; a lower serum albumin level; and a lower estimated glomerular filtration rate than surviving patients. The proportion of patients requiring early initiation of tolvaptan treatment (within 3 days of admission) was significantly higher in surviving patients. On the basis of multivariate logistic regression analysis, although a high heart rate and high BUN levels were independent factors for in-hospital prognosis, they were not significantly associated with the early use of tolvaptan (≤3 days vs. ≥4 days; odds ratio=0.39; 95% confidence interval=0.07-2.21; p=0.29). Conclusions: This study revealed that a higher heart rate and higher BUN levels were independent factors for in-hospital prognosis in elderly patients who received tolvaptan and that early tolvaptan use may not always be effective in elderly patients.

Serum angiotensin-converting enzyme levels indicating early sarcoidosis diagnosis and immunosuppressive therapy efficacy.

AIMS: This study aimed to determine the new cut-off value of serum angiotensin-converting enzyme (ACE) levels for detecting patients with sarcoidosis and to examine the change in ACE levels after the initiation of immunosuppressive therapy. METHODS AND RESULTS: We retrospectively examined patients in whom serum ACE levels were measured for suspected sarcoidosis between 2009 and 2020 in our institution. For patients diagnosed with sarcoidosis, changes in ACE levels were also observed. Of the 3781 patients (51.1% men, 60.1 ± 17.0 years old), 477 were excluded for taking ACE inhibitors and/or immunosuppression agents or those with any diseases affecting serum ACE levels. In 3304 patients including 215 with sarcoidosis, serum ACE levels were 19.6 IU/L [interquartile range, 15.1-31.5] in patients with sarcoidosis and 10.7 [8.4-16.5] in those without sarcoidosis (P < 0.01), and the best cut-off value was 14.7 IU/L with 0.865 of the area under the curves. Compared with the current ACE cut-off of 21.4, the sensitivity improved from 42.3 to 78.1 at the new cut-off, although specificity slightly decreased from 98.6 to 81.7. The ACE level significantly decreased more in those with immunosuppression therapy than in those without it (P for interaction <0.01), although it decreased in both groups (P < 0.01). CONCLUSIONS: Because the sensitivity for detecting sarcoidosis is comparatively low at the current standard value, further examinations are needed for patients suspected of sarcoidosis with relatively high ACE levels in the normal range. In patients with sarcoidosis, ACE levels decreased after the initiation of immunosuppression therapy.

Long-term prognostic value of changes in left ventricular global longitudinal strain in patients with heart failure with preserved ejection fraction.

BACKGROUND: Left ventricular (LV) global longitudinal strain (GLS) has emerged as a more sensitive index than LV ejection fraction (LVEF) for detecting subclinical LV dysfunction. We examined whether changes in GLS values are associated with the long-term prognosis of patients with a preserved LVEF and acute decompensated heart failure (HF). METHODS: We studied 100 consecutive patients (mean age: 71 years) who were hospitalized for HF with preserved ejection fraction (HFpEF) and had a preserved LVEF (≥ 50%) in both the acute and stable phases. We performed two-dimensional speckle-tracking echocardiography in the acute (GLS-acute) and stable (GLS-stable) phases at a median of 2 and 347 days after admission, respectively, and calculated the rate of change of the absolute value of GLS-stable with respect to that of GLS-acute. An improved GLS was defined as a rate of change in GLS ≥ 16%, and a non-improved GLS was a rate of change < 16%. The primary endpoint was the occurrence of major cardiovascular events (MACE). RESULTS: During a mean follow-up period of 1218 days, MACE occurred in 26 patients, including 8 all-cause deaths and 18 readmissions for HF. The rate of change in GLS for patients with MACE was lower than compared to those without MACE (10.6% vs 26.0%, p < 0.001). Multivariate Cox regression analyses indicated the rate of change in GLS was an independent predictor of MACE (p < 0.001). A non-improved GLS was correlated with a high risk of MACE. CONCLUSION: Changes in GLS values could be useful for the long-term risk stratification of patients hospitalized for HFpEF and persistently preserved LVEF.

An early return-to-work program for COVID-19 close contacts in healthcare during the Omicron wave in Japan.

During the coronavirus disease 2019 (COVID-19) pandemic, maintaining adequate staffing in healthcare facilities is important to provide a safe work environment for healthcare workers (HCWs). Japan's early return-to-work (RTW) program may be a rational strategy at a time when there is an increased demand for the services of HCWs. We assessed whether the early RTW program for HCWs who have been in close contact with a COVID-19 case in our hospital was justified. Close contacts were identified according to the guidance document of the World Health Organization. HCWs who met all of the following conditions were eligible to apply to an early RTW program: (1) difficult to replace with another HCW, (2) received the third dose of a COVID-19 mRNA vaccine, (3) a negative COVID-19 antigen test before each work shift, and (4) consent from relevant HCWs and their managers to participate in the program. Between January and March 2022, 256 HCWs were identified as close contacts (median age, 35 years; 192 female). Thirty-seven (14%) secondary attack cases of COVID-19 were detected. Among 141 HCWs (55%) who applied to the early RTW program, nurses and physicians comprised about three-quarters of participants, with a higher participation rate by physicians (78%) than nurses (59%). Eighteen HCWs tested positive for COVID-19 by the sixth day after starting the early RTW program. No COVID-19 infection clusters were reported during the observation period. These findings suggest that the early RTW program for COVID-19 close contacts was a reasonable strategy for HCWs during the Omicron wave.

A simple proteinuria-based risk score predicts contrast-associated acute kidney injury after percutaneous coronary intervention.

Contrast-associated acute kidney injury (CA-AKI) is a complication of percutaneous coronary intervention (PCI). Because proteinuria is a sentinel marker of renal dysfunction, we assessed its role in predicting CA-AKI in patients undergoing PCI. A total of 1,254 patients undergoing PCI were randomly assigned to a derivation (n = 840) and validation (n = 414) dataset. We identified the independent predictors of CA-AKI where CA-AKI was defined by the new criteria issued in 2020, by a multivariate logistic regression in the derivation dataset. We created a risk score from the remaining predictors. The discrimination and calibration of the risk score in the validation dataset were assessed by the area under the receiver-operating characteristic curves (AUC) and Hosmer-Lemeshow test, respectively. A total of 64 (5.1%) patients developed CA-AKI. The 3 variables of the risk score were emergency procedures, serum creatinine, and proteinuria, which were assigned 1 point each based on the correlation coefficient. The risk score demonstrated a good discriminative power (AUC 0.789, 95% CI 0.766-0.912) and significant calibration. It was strongly associated with the onset of CA-AKI (Cochran-Armitage test, p < 0.0001). Our risk score that included proteinuria was simple to obtain and calculate, and may be useful in assessing the CA-AKI risk before PCI.

Antibody Responses to BNT162b2 Vaccination in Japan: Monitoring Vaccine Efficacy by Measuring IgG Antibodies against the Receptor-Binding Domain of SARS-CoV-2.

To fight severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), mass vaccination has begun in many countries. To investigate the usefulness of a serological assay to predict vaccine efficacy, we analyzed the levels of IgG, IgM, and IgA against the receptor-binding domain (RBD) of SARS-CoV-2 in the sera from BNT162b2 vaccinated individuals in Japan. This study included 219 individuals who received two doses of BNT162b2. The levels of IgG, IgM, and IgA against RBD were measured by enzyme-linked immunosorbent assay before and after the first and second vaccination, respectively. The relationship between antibody levels and several factors, including age, gender, and hypertension were analyzed. Virus-neutralizing activity in sera was measured to determine the correlation with the levels of antibodies. A chemiluminescent enzyme immunoassay (CLEIA) method to measure IgG against RBD was developed and validated for the clinical setting. The levels of all antibody isotypes were increased after vaccination. Among them, RBD-IgG was dramatically increased after the second vaccination. The IgG levels in females were significantly higher than in males. There was a negative correlation between age and IgG levels in males. The IgG levels significantly correlated with the neutralizing activity. The CLEIA assay measuring IgG against RBD showed a reliable performance and a high correlation with neutralizing activity. Monitoring of IgG against RBD is a powerful tool to predict the efficacy of SARS-CoV-2 vaccination and provides useful information in considering a personalized vaccination strategy for COVID-19. IMPORTANCE Mass vaccination campaigns using mRNA vaccines against SARS-CoV-2 have begun in many countries. Serological assays to detect antibody production may be a useful tool to monitor the efficacy of SARS-CoV-2 vaccination in individuals. Here, we reported the induction of antibody isotype responses after the first and second dose of the BNT162b2 vaccine in a well-defined cohort of employees in Japan. We also reported that age, gender, and hypertension are associated with differences in antibody response after vaccination. This study not only provides valuable information with respect to antibody responses after BNT162b2 vaccination in the Japanese population but also the usefulness of serological assays for monitoring vaccine efficacy in clinical laboratories to determine a personalized vaccination strategy for COVID-19.

Relationship between epicardial adipose tissue and coronary artery stenoses on computed tomography in patients scheduled for carotid artery revascularization.

BACKGROUND: We aimed to clarify the relationship between epicardial adipose tissue (EAT) volume and the presence of severe stenoses (SS) on coronary computed tomography angiography (CTA) for risk stratification of the patients with carotid artery stenoses. METHODS: We prospectively performed CTA for 125 consecutive patients (72.4 ± 8.1 years, 85% men) without a history of coronary artery disease (CAD), who were scheduled for carotid artery revascularization from 2014 to 2020. SS was defined as ≥70% luminal stenosis on CTA. EAT was quantified automatically as the total volume of tissue with -190 to -30 HU. RESULTS: Of 125 patients, 76 had SS. Between the patients with and without SS, there were significant differences in coronary artery calcium score (CACS), left ventricular ejection fraction (LVEF), dyslipidemia, and EAT, despite no differences in carotid echocardiography findings. After adjustment for age, gender, and dyslipidemia, EAT was an independent factor associated with SS (p=0.011), as well as CACS and LVEF. The addition of EAT to a baseline model including age, gender, dyslipidemia, LVEF, and CACS achieved both net reclassification improvement (0.505, p=0.003) and integrated discrimination improvement (0.059, p=0.003). CONCLUSIONS: In patients with carotid stenoses, EAT is associated with CAD and is useful for additional risk stratification. Epicardial fat may have a specific role in the development of CAD in patients with suspected systemic atherosclerosis.

Small Dense Low-Density Lipoprotein Cholesterol and Cardiovascular Risk in Statin-Treated Patients with Coronary Artery Disease.

AIM: We investigated the relationship between small dense low-density cholesterol (sdLDL-C) and risk of major adverse cardiovascular events (MACE) in patients treated with high- or low-dose statin therapy. METHODS: This was a prospective case-cohort study within the Randomized Evaluation of Aggressive or Moderate Lipid-Lowering Therapy with Pitavastatin in Coronary Artery Disease (REAL-CAD) study, a randomized trial of high- or low-dose (4 or 1 mg/d pitavastatin, respectively) statin therapy, in patients with stable coronary artery disease (CAD). Serum sdLDL-C was determined using an automated homogenous assay at baseline (randomization after a rule-in period, ＞1 month with 1 mg/d pitavastatin) and 6 months after randomization, in 497 MACE cases, and 1543 participants randomly selected from the REAL-CAD study population. RESULTS: High-dose pitavastatin reduced sdLDL-C by 20% than low-dose pitavastatin (p for interaction ＜0.001). Among patients receiving low-dose pitavastatin, baseline sdLDL-C demonstrated higher MACE risk independent of LDL-C (hazard ratio [95% confidence interval], 4th versus 1st quartile, 1.67 [1.04-2.68]; p for trend=0.034). High-dose (versus low-dose) pitavastatin reduced MACE risk by 46% in patients in the highest baseline sdLDL-C quartile (＞34.3 mg/dL; 0.54 [0.36-0.81]; p=0.003), but increased relative risk by 40% in patients with 1st quartile (≤ 19.5 mg/dL; 1.40 [0.94-2.09]; p=0.099) and did not alter risk in those in 2nd and 3rd quartiles (p for interaction=0.002). CONCLUSIONS: These findings associate sdLDL-C and cardiovascular risk, independent of LDL-C, in statin-treated CAD patients. Notably, high-dose statin therapy reduces this risk in those with the highest baseline sdLDL-C.

Effect of Omega-3 Fatty Acids on Coronary Plaque Morphology　- A Serial Computed Tomography Angiography Study.

BACKGROUND: Omega-3 fatty acids have been proposed to be useful in the prevention of cardiac events. High-risk plaque (HRP) and plaque progression on serial coronary computed tomography angiography (CTA) have been suggested to be the predecessor of acute coronary syndrome (ACS). The purpose of this study was to investigate whether addition of omega-3 fatty acids to statin therapy for secondary prevention would lead to change in plaque characteristics detected by using serial CTA.Methods and Results: This study enrolled 210 patients with ACS: no eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA; EPA/DHA), low-dose EPA+DHA, high-dose EPA+DHA, and high-dose EPA alone. HRP was significantly more frequent in patients with plaque progression (P=0.0001). There was a significant interaction between plaque progression and EPA dose regardless of the DHA dose; 20.3% in EPA-none (no EPA/DHA), 15.7% in EPA-low (low-dose EPA+DHA), and 5.6% in EPA-high (high-dose EPA+DHA and high-dose EPA alone). On multivariate logistic regression analysis, HRP (OR 6.44, P<0.0001), EPA-high (OR 0.13, P=0.0004), and Rosvastatin (OR 0.24, P=0.0079) were the independent predictors for plaque progression. In quantitative analyses (n=563 plaques), the interval change of low attenuation plaque (LAP) volume was significantly different based on EPA dose; LAP was significantly increased in the EPA-none group and significantly decreased in the EPA-high group. CONCLUSIONS: In patients with ACS, addition of high-dose EPA (EPA-high) to statin therapy, compared to statin therapy without EPA, was associated with a lower rate of plaque progression.

Immunogenicity of BNT162b2 mRNA COVID-19 Vaccine in Patients with Cardiovascular Disease.

Concern has been raised about the effectiveness of the coronavirus disease 2019 (COVID-19) vaccine in the population of patients with various comorbidities such as heart disease. We investigated the humoral response to the BNT162b2 mRNA COVID-19 vaccine in patients with cardiovascular disease (CVD). We measured IgG against severe acute respiratory syndrome coronavirus 2 spike receptor-binding domain (RBD-IgG) in 85 CVD patients and 179 healthcare workers (HCWs). Blood samples were collected from patients and HCWs three times: (1) before the first dose of vaccination, (2) two weeks after the first dose of vaccination, and (3) two weeks after the second dose of vaccination. Patients with CVD showed a significantly inferior serological response to the BNT162b2 mRNA COVID-19 vaccine at 14 days after the prime dose compared to HCWs (21% vs. 95%, p < 0.001). Median RBD-IgG titers of patients with CVD at 14 days after the second dose were significantly lower than those of HCWs (137.2 U/mL (80.6-200.4 U/mL) vs. 176.2 U/mL (123.9-260.0 U/mL), p < 0.001). In multivariable analyses, CVD is significantly associated with seropositivity after first vaccination and RBD-IgG titers after second vaccination. CVD patients may have a poor humoral response to the BNT162b2 mRNA COVID-19 vaccine, need to be closely monitored, and require earlier revaccination to ensure stronger immunity and protection against infection.

Combined Assessment of D-Dimer with the Get with the Guidelines-Heart Failure Risk Score and N-Terminal Pro-B-Type Natriuretic Peptide in Patients with Acute Decompensated Heart Failure with Preserved and Reduced Ejection Fraction.

The prognostic role of D-dimer in different types of heart failure (HF) is poorly understood. We investigated the prognostic value of D-dimer on admission, both independently and in combination with the Get With The Guidelines-Heart Failure (GWTG-HF) risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients with preserved left ventricular ejection fraction (LVEF) and acute decompensated HF (HFpEF) or reduced LVEF (HFrEF). Baseline D-dimer levels were measured on admission in 1670 patients (mean age: 75 years) who were hospitalized for worsening HF. Of those patients, 586 (35%) were categorized as HFpEF (LVEF ≥ 50%) and 1084 as HFrEF (LVEF < 50%). During the 12-month follow-up period after admission, 360 patients died. Elevated levels (at least the highest tertile value) of D-dimer, GWTG-HF risk score, and NT-proBNP were all independently associated with mortality in all HFpEF and HFrEF patients (all p < 0.05). Adding D-dimer to a baseline model with a GWTG-HF risk score and NT-proBNP improved the net reclassification and integrated discrimination improvement for mortality greater than the baseline model alone in all populations (all p < 0.001). The number of elevations in D-dimer, GWTG-HF risk score, and NT-proBNP were independently associated with a higher risk of mortality in all study populations (HFpEF and HFrEF patients; all p < 0.001). The combination of D-dimer, which is independently predictive of mortality, with the GWTG-HF risk score and NT-proBNP could improve early prediction of 12-month mortality in patients with acute decompensated HF, regardless of the HF phenotype.