Multimodality Risk Assessment of Patients with Ischemic Heart Disease Using Deep Learning Models Applied to Electrocardiograms and Chest X-rays.

Comprehensive management approaches for patients with ischemic heart disease (IHD) are important aids for prognostication and treatment planning. While single-modality deep neural networks (DNNs) have shown promising performance for detecting cardiac abnormalities, the potential benefits of using DNNs for multimodality risk assessment in patients with IHD have not been reported. The purpose of this study was to investigate the effectiveness of multimodality risk assessment in patients with IHD using a DNN that utilizes 12-lead electrocardiograms (ECGs) and chest X-rays (CXRs), with the prediction of major adverse cardiovascular events (MACEs) being of particular concern.DNN models were applied to detection of left ventricular systolic dysfunction (LVSD) on ECGs and identification of cardiomegaly findings on CXRs. A total of 2107 patients who underwent elective percutaneous coronary intervention were categorized into 4 groups according to the models' outputs: Dual-modality high-risk (n = 105), ECG high-risk (n = 181), CXR high-risk (n = 392), and No-risk (n = 1,429).A total of 342 MACEs were observed. The incidence of a MACE was the highest in the Dual-modality high-risk group (P < 0.001). Multivariate Cox hazards analysis for predicting MACE revealed that the Dual-modality high-risk group had a significantly higher risk of MACE than the No-risk group (hazard ratio (HR): 2.370, P < 0.001), the ECG high-risk group (HR: 1.906, P = 0.010), and the CXR high-risk group (HR: 1.624, P = 0.018), after controlling for confounding factors.The results suggest the usefulness of multimodality risk assessment using DNN models applied to 12-lead ECG and CXR data from patients with IHD.

Age prediction from coronary angiography using a deep neural network: Age as a potential label to extract prognosis-related imaging features.

Coronary angiography (CAG) is still considered the reference standard for coronary artery assessment, especially in the treatment of acute coronary syndrome (ACS). Although aging causes changes in coronary arteries, the age-related imaging features on CAG and their prognostic relevance have not been fully characterized. We hypothesized that a deep neural network (DNN) model could be trained to estimate vascular age only using CAG and that this age prediction from CAG could show significant associations with clinical outcomes of ACS. A DNN was trained to estimate vascular age using ten separate frames from each of 5,923 CAG videos from 572 patients. It was then tested on 1,437 CAG videos from 144 patients. Subsequently, 298 ACS patients who underwent percutaneous coronary intervention (PCI) were analysed to assess whether predicted age by DNN was associated with clinical outcomes. Age predicted as a continuous variable showed mean absolute error of 4 years with R squared of 0.72 (r = 0.856). Among the ACS patients stratified by predicted age from CAG images before PCI, major adverse cardiovascular events (MACE) were more frequently observed in the older vascular age group than in the younger vascular age group (p = 0.017). Furthermore, after controlling for actual age, gender, peak creatine kinase, and history of heart failure, the older vascular age group independently suffered from more MACE (hazard ratio 2.14, 95% CI 1.07 to 4.29, p = 0.032). The vascular age estimated based on CAG imaging by DNN showed high predictive value. The age predicted from CAG images by DNN could have significant associations with clinical outcomes in patients with ACS.

Sex Difference in the Association between Lipid Profile and Incident Cardiovascular Disease among Young Adults.

AIM: Using a nationwide epidemiological database, we sought to examine whether there was a sex difference in the association between lipid profiles and subsequent cardiovascular disease (CVD) in young adults. METHODS: Medical records of 1,909,362 young adults (20-49 years old) without a prior history of CVD and not taking lipid-lowering medications were extracted. We conducted multivariable Cox regression analyses to identify the association between the number of abnormal lipid profiles and incident CVD. RESULTS: After a mean follow-up of 3.4±2.6 years, myocardial infarction (MI), angina pectoris (AP), stroke, and heart failure (HF) developed in 2,575 (0.1%), 26,006 (1.4%), 10,748 (0.6%), and 24,875 (1.3%) subjects, respectively. The incidence of MI, AP, and HF increased with the number of abnormal lipid profiles in both men and women, whereas the incidence of stroke increased with the number of abnormal lipid profiles only in men but not in women. Multivariable adjusted hazard ratios (HRs) for MI per 1-point higher abnormal lipid profile were 1.57 (95% confidence interval [CI] 1.49-1.65) in men and 1.25 (95% CI 1.07-1.47) in women. HRs for AP, stroke, and HF per 1-point higher abnormal lipid profile were 1.14 (95% CI 1.12-1.16), 1.06 (95% CI 1.02-1.09), and 1.10 (95% CI 1.08-1.12) in men and 1.18 (95% CI 1.13-1.23), 1.09 (95% CI 1.03-1.16), and 1.10 (95% CI 1.05-1.14) in women. CONCLUSION: Our analysis demonstrated an association between the number of abnormal lipid profiles and incident CVD in both men and women. The association between the number of abnormal lipid profiles and incident MI was pronounced in men.

Semiquantitative assessed proteinuria and risk of heart failure: analysis of a nationwide epidemiological database.

BACKGROUND: Heart failure (HF) is increasing in prevalence worldwide. We explored whether adults with trace and positive proteinuria were at a high risk for incident HF compared with those with negative proteinuria using a nationwide epidemiological database. METHODS: This is an observational cohort study using the JMDC Claims Database collected between 2005 and 2020. This is a population-based sample [n = 1 021 943; median age 44 years (interquartile range 37-52); 54.8% men]. No participants had a known history of cardiovascular disease (CVD). Each participant was categorized into three groups according to the urine dipstick test results: negative proteinuria (n = 902 273), trace proteinuria (n = 89 599) and positive proteinuria (≥1+; n = 30 071). The primary outcome was HF. The secondary outcomes were myocardial infarction (MI), stroke and atrial fibrillation (AF). We performed multivariable Cox regression analyses to identify the association between the proteinuria category and incident HF and other CVD events. RESULTS: Over a mean follow-up of 1150 ± 920 days, 17 182 incident HF events occurred. After multivariable adjustment, hazard ratios for HF events were 1.09 [95% confidence interval (CI) 1.03-1.15] and 1.59 (95% CI 1.49-1.70) for trace proteinuria and positive proteinuria versus negative proteinuria, respectively. This association was present irrespective of clinical characteristics. A stepwise increase in the risk of MI, stroke and AF with proteinuria category was also observed. Our primary results were confirmed in participants after multiple imputations for missing values and in those having no medications for hypertension, diabetes mellitus and dyslipidemia. The discriminative predictive value for HF events improved by adding the results of urine dipstick tests to traditional risk factors [net reclassification improvement 0.0497 (95% CI 0.0346-0.0648); P < 0.001]. CONCLUSIONS: Not only positive proteinuria, but also trace proteinuria was associated with a greater incidence of HF in the general population. Semiquantitative assessment of proteinuria would be informative for the risk stratification of HF.

Incorporation of Retinal Arteriolosclerosis into Risk Stratification of Blood Pressure Category According to the 2017 ACC/AHA Blood Pressure Guideline.

AIM: We investigated whether retinal arteriolosclerosis (RA) could be used for cardiovascular disease (CVD) risk stratification of individuals categorized according to the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) Blood Pressure (BP) guideline. METHODS: We studied 291,522 participants without a history of CVD and not taking any BP-lowering medications from the JMDC Claims Database. RA was defined as Keith-Wagener-Barker system grade ≥ 1. Each participant was classified into one of the six groups: (1) normal or elevated BP without RA, (2) normal or elevated BP with RA, (3) stage 1 hypertension without RA, (4) stage 1 hypertension with RA, (5) stage 2 hypertension without RA, and (6) stage 2 hypertension with RA. RESULTS: Median (interquartile range) age was 46 (40-53) years, and 141,397 (48.5%) of the participants were men. During a mean follow-up of 1,223±830 days, 527 myocardial infarction (MI), 5,718 angina pectoris, 2,890 stroke, and 5,375 heart failure (HF) events occurred. Multivariable Cox regression analyses revealed that the risk of CVD increased with BP category, and this association was pronounced by the presence of RA. Compared with normal or elevated BP without RA, the hazard ratios (HRs) for MI (HR 1.17, 95% CI 0.93-1.47) were higher in stage 1 hypertension without RA. The HRs for MI further increased in stage 1 hypertension with RA (1.86 [1.17-2.95]). This association was present in stroke and HF. CONCLUSION: Incorporation of the assessment for RA may facilitate the CVD risk stratification of people classified based on the 2017 ACC/AHA BP guideline, particularly for those categorized in stage 1 hypertension.

Potential value of saline-induced Pd/Pa ratio in patients with coronary artery stenosis.

Background: Fractional flow reserve (FFR) is the current gold standard for identifying myocardial ischemia in individuals with coronary artery stenosis. However, FFR is not penetrated as much worldwide due to time consumption, costs associated with adenosine, FFR-related discomfort, and complications. Resting physiological indexes may be widely accepted alternatives to FFR, while the discrepancies with FFR were found in up to 20% of lesions. The saline-induced Pd/Pa ratio (SPR) is a new simplified option for evaluating coronary stenosis. However, the clinical implication of SPR remains unclear. Objectives: In the present study, we aimed to compare the accuracies of SPR and resting full-cycle ratio (RFR) and to investigate the incremental value of SPR in clinical practice. Methods: In this multicenter prospective study, 112 coronary lesions (105 patients) were evaluated by SPR, RFR, and FFR. Results: The overall median age was 71 years, and 84.8% were men. SPR was correlated more strongly with FFR than with RFR (r = 0.874 vs. 0.713, respectively; p < 0.001). Using FFR < 0.80 as the reference standard variable, the area under the receiver-operating characteristic (ROC) curve for SPR was superior to that of RFR (0.932 vs. 0.840, respectively; p = 0.009). Conclusion: Saline-induced Pd/Pa ratio predicted FFR more accurately than RFR. SPR could be an alternative method for evaluating coronary artery stenosis and further investigation including elucidation of the mechanism of SPR is needed (225 words).

Untreated Hypertension and Subsequent Incidence of Colorectal Cancer: Analysis of a Nationwide Epidemiological Database.

Background Studies of the association of hypertension with incident colorectal cancer (CRC) may have been confounded by including individuals taking antihypertensive medication, at high risk for CRC (ie, colorectal polyps and inflammatory bowel disease), or with shared risk factors (eg, obesity and diabetes). We assessed whether adults with untreated hypertension are at higher risk for incident CRC compared with those with normal blood pressure (BP), and whether any association is evident among individuals without obesity or metabolic abnormalities. Methods and Results Analyses were conducted using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2 220 112; mean age, 44.1±11.0 years; 58.4% men). Participants who were taking antihypertensive medications or had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Each participant was categorized as having normal BP (systolic BP [SBP]<120 mm Hg and diastolic BP [DBP] <80 mm Hg, n=1 164 807), elevated BP (SBP 120-129 mm Hg and DBP <80 mm Hg, n=341 273), stage 1 hypertension (SBP 130-139 mm Hg or DBP 80-89 mm Hg, n=466 298), or stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg, n=247 734). Over a mean follow-up of 1112±854 days, 6899 incident CRC diagnoses occurred. After multivariable adjustment, compared with normal BP, hazard ratios for incident CRC were 0.93 (95% CI, 0.85-1.01) for elevated BP, 1.07 (95% CI, 0.99-1.15) for stage 1 hypertension, and 1.17 (95% CI, 1.08-1.28) for stage 2 hypertension. The hazard ratios for incident CRC for each 10-mm Hg-higher SBP or DBP were 1.04 (95% CI, 1.02-1.06) and 1.06 (95% CI, 1.03-1.09), respectively. These associations were present among adults who did not have obesity, high waist circumference, diabetes, or dyslipidemia. Conclusions Higher SBP and DBP, and stage 2 hypertension are associated with a higher risk for incident CRC, even among those without shared risk factors for CRC. BP measurement could identify individuals at increased risk for subsequent CRC.

Relation of the Metabolic Syndrome to Incident Colorectal Cancer in Young Adults Aged 20 to 49 Years.

Onco-cardiology is the emerging field, and the concept of shared risk factor holds an important position in this field. The increasing prevalence of colorectal cancer (CRC) in young adults is a critical epidemiological issue. Although metabolic syndrome, which is a major risk factor for cardiovascular disease, is known to be associated with CRC incidence in middle-aged and elderly individuals, it is unclear whether this association is present in young adults. We assessed whether metabolic syndrome was associated with CRC events in young adults (aged <50 years), and whether the association differed by the definition of metabolic syndrome. We retrospectively analyzed 902,599 adults (20 to 49 years of age) enrolled in the JMDC Claims Database which is a nationwide epidemiological database in Japan between January 2005 and August 2018. Participants who had a history of CRC, colorectal polyps, or inflammatory bowel disease were excluded. Study participants were categorized into 2 groups according to the presence of metabolic syndrome, defined using the Japanese criteria (waist circumference ≥85 cm for men and ≥90 cm for women, and ≥2 metabolic parameters including elevated blood pressure, elevated triglycerides, reduced high-density lipoprotein cholesterol, or elevated fasting plasma glucose). Clinical outcomes were collected between January 2005 and August 2018. The primary outcome was CRC of any stage. Median (interquartile range) age was 41 (37 to 45), and 55.4% were men. Over a median follow-up of 1,008 (429 to 1,833) days, there were 1,884 incidences of CRC. After multivariable adjustment, the hazard ratio (HR) of metabolic syndrome for CRC events was 1.26 (95% confidence interval [CI] = 1.07 to 1.49). Cox regression analysis after multiple imputation for missing values showed that metabolic syndrome was associated with CRC incidence (HR = 1.35, 95% CI = 1.17 to 1.56). Metabolic syndrome was also associated with a higher incidence of CRC in individuals with a follow-up period of ≥365 days (HR = 1.33, 95% CI = 1.10 to 1.60). This association was observed when metabolic syndrome was defined according to the International Diabetes Federation criteria (HR = 1.30, 95% CI = 1.09 to 1.55) and the National Cholesterol Education Program Adult Treatment Panel III criteria (HR = 1.39, 95% CI = 1.12 to 1.72). In conclusion, metabolic syndrome was associated with a higher incidence of CRC among individuals aged <50 years. These results could be informative for risk stratification of subsequent CRC among young adults.

Promoting analysis of real-world data: Prospects for preventive cardiology in Japan.

According to the statistics for 2018 in Japan, cardiovascular disease and cerebrovascular disease were the most common causes of death (cardiovascular disease with 208,210, cerebrovascular disease with 108,165), and these two diseases account for 23.2% of all deaths. Stroke, especially cerebral hemorrhage, was the main cause of death in Japan after World War II. Along with improved management of hypertension, the mortality rate from cerebral hemorrhage reached a high of 266.7 per 100,000 men in 1960 and 213.9 per 100,000 women in 1951, then decreased to 15.9 per 100,000 men and 6.9 per 100,000 women in 2013. However, mortality from lifestyle-related diseases such as metabolic syndrome and ischemic heart disease has been on the rise since 1990 due to the westernization of diet, urban lifestyles, and lack of exercise habits. Moreover, since aging is the greatest risk factor for heart failure, the number of patients with heart failure in Japan will inevitably increase in the future. A large amount of evidence has demonstrated that prevention and proper management of risk factors can reduce the future incidence of cardiovascular disease. Specific health checkups (metabolic syndrome checkups) have been carried out in Japan since 2008. Big data on physical examinations are valuable real-world data that can be utilized for clinical research. As the importance of preventive cardiology increases in the future, we should analyze the real-world data from health checkups in Japan in detail and disseminate these results to clinical practice, which will contribute to development of preventive cardiology and the promotion of public health.

Possible Gender Difference in the Association Between Abdominal Obesity, Chronic Inflammation, and Preclinical Atherosclerosis in the General Population.

Chronic inflammation due to abdominal obesity plays a major role in the development of cardiovascular disease (CVD). Gender differences are well characterized in the development of CVD; however, in the association among abdominal obesity, chronic inflammation, and preclinical atherosclerosis, gender differences in the general population remain to be clarified. We retrospectively analyzed 1,163 subjects who underwent voluntary health checkups at our institute. We defined carotid artery plaque formation as carotid intima-media thickness ≥ 1.1 mm. Multiple regression analysis showed that waist circumference was a major independent predictor of increase in serum C-reactive protein (CRP) level in both men and women. Serum CRP level was significantly increased in men with carotid artery plaque formation, but not in women. Multivariable logistic regression analysis demonstrated that serum CRP level, as well as age and hypertension, was independently associated with carotid artery plaque formation only in men. This result may suggest a potential of gender-specific difference in the association between serum CRP level and the prevalence of carotid artery plaque formation. Further investigations are required to confirm our results and to clarify the underlying mechanism.

Association of Body Mass Index with Ischemic and Hemorrhagic Stroke.

Data on the association between body mass index (BMI) and stroke are scarce. We aimed to examine the association between BMI and incident stroke (ischemic or hemorrhagic) and to clarify the relationship between underweight, overweight, and obesity and stroke risk stratified by sex. We analyzed the JMDC Claims Database between January 2005 and April 2020 including 2,740,778 healthy individuals (Median (interquartile) age, 45 (38-53) years; 56.2% men; median (interquartile) BMI, 22.3 (20.2-24.8) kg/m2). None of the participants had a history of cardiovascular disease. Each participant was categorized as underweight (BMI <18.5 kg/m2), normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), or obese (BMI ≥ 30 kg/m2). We investigated the association of BMI with incidence stroke in men and women using the Cox regression model. We used restricted cubic spline (RCS) functions to identify the association of BMI as a continuous parameter with incident stroke. The incidence (95% confidence interval) of total stroke, ischemic stroke, and hemorrhagic stroke was 32.5 (32.0-32.9), 28.1 (27.6-28.5), and 5.5 (5.3-5.7) per 10,000 person-years in men, whereas 25.7 (25.1-26.2), 22.5 (22.0-23.0), and 4.0 (3.8-4.2) per 10,000 person-years in women, respectively. Multivariable Cox regression analysis showed that overweight and obesity were associated with a higher incidence of total and ischemic stroke in both men and women. Underweight, overweight, and obesity were associated with a higher hemorrhagic stroke incidence in men, but not in women. Restricted cubic spline showed that the risk of ischemic stroke increased in a BMI dose-dependent manner in both men and women, whereas there was a U-shaped relationship between BMI and the hemorrhagic stroke risk in men. In conclusion, overweight and obesity were associated with a greater incidence of stroke and ischemic stroke in both men and women. Furthermore, underweight, overweight, and obesity were associated with a higher hemorrhagic stroke risk in men. Our results would help in the risk stratification of future stroke based on BMI.

Acute-phase initiation of cardiac rehabilitation and clinical outcomes in hospitalized patients for acute heart failure.

BACKGROUND: Extensive data support the clinical benefit of cardiac rehabilitation (CR) for patients with chronic heart failure (HF). However, whether CR could be beneficial for patients hospitalized for acute heart failure remains unclear. METHODS: We retrospectively analyzed data from the Diagnosis Procedure Combination database, a nationwide inpatient database. We included patients hospitalized for HF, who were aged ≥20 years and with New York Heart Association class ≥II, between January 2010 and March 2018. We excluded patients with length of hospital stay ≤2 days, those undergoing major procedures under general anesthesia, those requiring advanced mechanical supports within 2 days after admission, and those with disturbance of consciousness. Propensity score matching and instrumental variable analyses were conducted to compare clinical outcomes between the patients with and without acute-phase initiation of CR defined as initiation of CR within two days after hospital admission. RESULTS: Among 430,216 eligible patients, 63,470 patients (14.8%) received the acute-phase initiation of CR. Propensity score matching created 63,470 pairs and found that the acute-phase initiation of CR was associated with lower in-hospital mortality (odds ratio [OR] 0.76, 95% confidence interval [CI] 0.73-0.80), shorter hospital stay and lower incidence of 30-day readmission due to HF. The instrumental variable analysis also showed patients with acute-phase initiation of CR was associated with lower in-hospital mortality than those without (OR, 0.73; 95% CI, 0.68-0.79). CONCLUSION: Our analysis suggested a potential benefit of acute-phase initiation of CR for short-term clinical outcomes in hospitalized patients with acute HF.

Fasting Plasma Glucose and Incident Colorectal Cancer: Analysis of a Nationwide Epidemiological Database.

CONTEXT: Although diabetes mellitus (DM) was reported to be associated with incident colorectal cancer (CRC), the detailed association between fasting plasma glucose (FPG) and incident CRC has not been fully understood. OBJECTIVE: We assessed whether hyperglycemia is associated with a higher risk for CRC. DESIGN: Analyses were conducted using the JMDC Claims Database [n = 1 441 311; median age (interquartile range), 46 (40-54) years; 56.6% men). None of the participants were taking antidiabetic medication or had a history of CRC, colorectal polyps, or inflammatory bowel disease. Participants were categorized as normal FPG (FPG level < 100 mg/dL; 1 125 647 individuals), normal-high FPG (FPG level = 100-109 mg/dL; 210 365 individuals), impaired fasting glucose (IFG; FPG level = 110-125 mg/dL; 74 836 individuals), and DM (FPG level ≥ 126 mg/dL; 30 463 individuals). RESULTS: Over a mean follow-up of 1137 ± 824 days, 5566 CRC events occurred. After multivariable adjustment, the hazard ratios for CRC events were 1.10 (95% CI 1.03-1.18) for normal-high FPG, 1.24 (95% CI 1.13-1.37) for IFG, and 1.36 (95% CI 1.19-1.55) for DM vs normal FPG. We confirmed this association in sensitivity analyses excluding those with a follow-up of< 365 days and obese participants. CONCLUSION: The risk of CRC increased with elevated FPG category. FPG measurements would help to identify people at high-risk for future CRC.

Risk Factors and Lifestyles in the Development of Atrial Fibrillation Among Individuals Aged 20-39 Years.

Epidemiological evidence on the relationship of modifiable risk factors and lifestyles with incident atrial fibrillation (AF) in young adults remains insufficient. We aimed to identify the determinants of AF among young adults using a nationwide epidemiological database. Medical records of 286,876 individuals (20-39 years) without prior history of cardiovascular disease were extracted from the JMDC Claims Database. We analyzed the association of modifiable risk factors with the incidence of AF. The median (interquartile range) age was 34 (29-37) years, and 54.4% were men. After a mean follow-up of 1,017 ± 836 days, 267 individuals (0.1%) developed AF. Multivariable Cox regression analysis demonstrated that high waist circumference, hypertension, cigarette smoking, and poor sleep quality as well as age and sex were associated with increased incidence of AF. Kaplan-Meier curves showed that number of modifiable components including high waist circumference, hypertension, cigarette smoking, and poor sleep quality clearly stratified the risk of AF development (Log rank test, p < 0.001). Age- and sex-adjusted Cox regression analyses showed individuals with one (hazard ratio [HR] 1.56, 95% confidence interval [CI] 1.13-2.18), two (HR 2.03, 95% CI 1.40-2.95), three (HR 3.48, 95% CI 2.19-5.54), and four (HR 10.78, 95% CI 5.26-22.11) components were associated with an increased incidence of AF compared with individuals with no components. In conclusion, high waist circumference, hypertension, cigarette smoking, and poor sleep quality were associated with the development of AF among young adults, suggesting the importance of maintaining these modifiable factors for the primordial prevention of AF in young adults.

Relation of Serum Uric Acid and Cardiovascular Events in Young Adults Aged 20-49 Years.

Serum uric acid (SUA) was reported to be associated with incident cardiovascular disease (CVD). However, the relationship between SUA and CVD among young adults has not been clarified yet. In this study, we aimed to identify the association of medication naïve SUA with incident CVD including myocardial infarction (MI), stroke, heart failure (HF) and atrial fibrillation (AF) using a nationwide epidemiological database. We analyzed 353,613 participants aged 20-49 years, who were not taking UA lowering medications, and had no prevalent history of cardiovascular disease (CVD) using a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018. Median [interquartile range] age was 40 [34-44] years, and 46.9% were men. Over a mean follow-up of 1,176±876 days, 391 (0.1%) incident MI, 1,308 (0.4%) incident stroke, 3,374 (1.0%) incident HF, and 684 (0.2%) incident AF events occurred. Kaplan-Meier curves and the log-rank test showed that there was a significant difference in incident MI, stroke, HF, and AF among the groups based on SUA tertile (all log-rank p< 0.001). Multivariable Cox regression analysis showed that the upper tertile of SUA (SUA ≥ 5.7 mg/dL) was associated with higher incidence of MI (HR 1.45, 95% CI 1.00-2.10), HF (HR 1.13, 95% CI 1.01-1.28), and AF (HR 1.35, 95% CI 1.02-1.78) compared with the first tertile of SUA (SUA < 4.4 mg/dL). SUA as continuous variable was independently associated with incident MI (HR 1.10, 95% CI 1.00-1.20), stroke (HR 1.06, 95% CI 1.00-1.11), HF (HR 1.07, 95% CI 1.03-1.10), and AF (HR 1.11, 95% CI 1.04-1.19). SUA ≥ 7.0 mg/dL was independently associated with incident HF (HR 1.24, 95% CI 1.12-1.38). In conclusion, higher SUA was associated with increased incidence of CVD events in individuals aged< 50 years, suggesting the potential significance of the optimal UA control for the primary CVD prevention even in young adults.

Association Between Blood Pressure Classification Using the 2017 ACC/AHA Blood Pressure Guideline and Retinal Atherosclerosis.

BACKGROUND: We aimed to explore the association between the blood pressure (BP) classification defined by the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guideline and the prevalence of retinal atherosclerosis. METHODS: This study was a retrospective observational cross-sectional analysis using the JMDC Claims Database. We analyzed 280,599 subjects not taking any antihypertensive medications. According to the 2017 ACC/AHA guideline, each subject was categorized as having normal BP (n = 159,524), elevated BP (n = 35,603), stage 1 hypertension (n = 54,795), or stage 2 hypertension (n = 30,677) using the BP value at the initial health checkup. Retinal photographs were assessed according to the Keith-Wagener-Barker system. RESULTS: The median age was 46 years, and 50.4% subjects were men. Retinal atherosclerosis, defined as Keith-Wagener-Barker system grade ≥1, was observed in 3.2% in normal BP, 5.2% in elevated BP, 7.7% in stage 1 hypertension, and 18.7% in stage 2 hypertension. Compared with normal BP, elevated BP (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.23-1.38), stage 1 hypertension (OR, 1.71; 95% CI, 1.64-1.79), and stage 2 hypertension (OR, 4.10; 95% CI, 3.93-4.28) were associated with a higher prevalence of retinal atherosclerosis. Among 92,121 subjects without obesity, high waist circumference, diabetes mellitus, dyslipidemia, cigarette smoking, and alcohol consumption, elevated BP (OR, 1.34; 95% CI, 1.19-1.51), stage 1 hypertension (OR, 1.79; 95% CI, 1.61-1.98), and stage 2 hypertension (OR, 4.42; 95% CI, 4.00-4.92) were associated with a higher prevalence of retinal atherosclerosis. This association was observed in all subgroups stratified by age or sex. CONCLUSIONS: Our investigation suggests that retinal atherosclerosis could start even in individuals with elevated BP and stage 1 hypertension.

Association of Blood Pressure Classification Using the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline With Risk of Heart Failure and Atrial Fibrillation.

BACKGROUND: Heart failure (HF) and atrial fibrillation (AF) are growing in prevalence worldwide. Few studies have assessed to what extent stage 1 hypertension in the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines is associated with incident HF and AF. METHODS: Analyses were conducted with a nationwide health claims database collected in the JMDC Claims Database between 2005 and 2018 (n=2 196 437; mean age, 44.0±10.9 years; 58.4% men). No participants were taking antihypertensive medication or had a known history of cardiovascular disease. Each participant was categorized as having normal BP (systolic BP <120 mm Hg and diastolic BP <80 mm Hg; n=1 155 885), elevated BP (systolic BP 120-129 mm Hg and diastolic BP <80 mm Hg; n=337 390), stage 1 hypertension (systolic BP 130-139 mm Hg or diastolic BP 80-89 mm Hg; n=459 820), or stage 2 hypertension (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg; n=243 342). Using Cox proportional hazards models, we identified associations between BP groups and HF/AF events. We also calculated the population attributable fractions to estimate the proportion of HF and AF events that would be preventable if participants with stage 1 and stage 2 hypertension were to have normal BP. RESULTS: Over a mean follow-up of 1112±854 days, 28 056 incident HF and 7774 incident AF events occurred. After multivariable adjustment, hazard ratios for HF and AF events were 1.10 (95% CI, 1.05-1.15) and 1.07 (95% CI, 0.99-1.17), respectively, for elevated BP; 1.30 (95% CI, 1.26-1.35) and 1.21 (95% CI, 1.13-1.29), respectively, for stage 1 hypertension; and 2.05 (95% CI, 1.97-2.13) and 1.52 (95% CI, 1.41-1.64), respectively, for stage 2 hypertension versus normal BP. Population attributable fractions for HF associated with stage 1 and stage 2 hypertension were 23.2% (95% CI, 20.3%-26.0%) and 51.2% (95% CI, 49.2%-53.1%), respectively. The population attributable fractions for AF associated with stage 1 and stage 2 hypertension were 17.4% (95% CI, 11.5%-22.9%) and 34.3% (95% CI, 29.1%-39.2%), respectively. CONCLUSIONS: Both stage 1 hypertension and stage 2 hypertension were associated with a greater incidence of HF and AF in the general population. The American College of Cardiology/American Heart Association BP classification system may help identify adults at higher risk for HF and AF events.

Surgical treatment for infective endocarditis in the ageing society: a nationwide retrospective study in Japan.

OBJECTIVE: The current status of surgical treatment for infective endocarditis (IE) among very elderly people is unclear. METHODS: We extracted data on patients in Japan with community-acquired IE who were admitted and discharged between April 2010 and February 2018 using a nationwide inpatient, the Diagnosis Procedure Combination database. We divided patients into three groups: non-elderly (<65 years), elderly (65-79 years) and very elderly (≥80 years). A 1:1 propensity score matching was performed to compare proportions of surgical treatment and in-hospital mortality among the groups. RESULTS: We identified 20 667 eligible patients (median age 70 years, 61.0% men). The proportion of very elderly patients significantly increased (19.1% in 2010 to 29.7% in 2018). The proportion of surgical treatment was significantly lower, and in-hospital mortality was significantly higher in very elderly patients. This tendency was more pronounced among patients with in-hospital complications such as heart failure, stroke or embolism. Surgical treatment was significantly associated with lower in-hospital mortality even in very elderly patients, both in an unmatched (OR 0.61; 95% CI 0.47 to 0.78) and a propensity score matched cohort (OR 0.61; 95% CI 0.43 to 0.85). CONCLUSIONS: The proportion of very elderly patients with IE was increasing, and very elderly patients had higher in-hospital mortality. The proportion of surgical treatment for IE among very elderly patients was low, but it was associated with lower in-hospital mortality. Further studies are needed to establish the optimal strategy for IE among very elderly patients.

Metabolically Healthy Obesity and the Risk of Cardiovascular Disease in the General Population　- Analysis of a Nationwide Epidemiological Database.

BACKGROUND: Obesity and metabolic disorders frequently coexist, and both are established risk factors for cardiovascular disease (CVD). Although the phenotype of obesity without metabolic disorders, referred to as metabolically healthy obesity (MHO), is attracting clinical interest, the pathophysiological impact of MHO remains unclear.Methods and Results:Using the Japan Medical Data Center database, we studied 802,288 subjects aged ≥20 years without any metabolic disorders or a prior history of CVD. MHO, defined as obesity (body mass index ≥25 kg/m2) with no metabolic disorders, was observed in 9.8% of the study population. The subjects' mean (±SD) age was 42.8±9.4 years and 44.7% were men. The mean follow-up period was 1,126±849 days. Multivariable Cox regression analysis showed that MHO alone did not significantly increase the risk of any CVD. However, abdominal obesity alone increased the risk of heart failure and atrial fibrillation. Moreover, the coexistence of MHO and abdominal obesity increased the risk of myocardial infarction, angina pectoris, heart failure, and atrial fibrillation. The incidence of stroke was not associated with the presence of MHO and abdominal obesity. CONCLUSIONS: Among individuals with no metabolic disorders, MHO alone did not significantly increase the subsequent CVD risk. However, individuals with comorbid MHO and abdominal obesity had a higher risk of myocardial infarction, angina pectoris, heart failure, and atrial fibrillation, suggesting the prognostic importance of abdominal obesity in subjects with MHO.