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.

Impact of hospital volume on clinical outcomes of hospitalized heart failure patients: analysis of a nationwide database including 447,818 patients with heart failure.

BACKGROUND: Hospital volume is known to be associated with outcomes of patients requiring complicated medical care. However, the relationship between hospital volume and prognosis of hospitalized patients with heart failure (HF) remains not fully understood. We aimed to clarify the impact of hospital volume on clinical outcomes of hospitalized HF patients using a nationwide inpatient database. METHODS AND RESULTS: We studied 447,818 hospitalized HF patients who were admitted from January 2010 and discharged until March 2018 included in the Japanese Diagnosis Procedure Combination database. According to the number of patients, patients were categorized into three groups; those treated in low-, medium-, and high-volume centers. The median age was 81 years and 238,192 patients (53%) were men. Patients who had New York Heart Association class IV symptom and requiring inotropic agent within two days were more common in high volume centers than in low volume centers. Respiratory support, hemodialysis, and intra-aortic balloon pumping were more frequently performed in high volume centers. As a result, length of hospital stay was shorter, and in-hospital mortality was lower in high volume centers. Lower in-hospital mortality was associated with higher hospital volume. Multivariable logistic regression analysis fitted with generalized estimating equation indicated that medium-volume group (Odds ratio 0.91, p = 0.035) and high-volume group (Odds ratio 0.86, p = 0.004) had lower in-hospital mortality compared to the low-volume group. Subgroup analysis showed that this association between hospital volume and in-hospital mortality among overall population was seen in all subgroups according to age, presence of chronic renal failure, and New York Heart Association class. CONCLUSION: Hospital volume was independently associated with ameliorated clinical outcomes of hospitalized patients with HF.

Cardiovascular Health Metrics of 87,160 Couples: Analysis of a Nationwide Epidemiological Database.

AIM: Clinical evidence on cardiovascular health metrics of couples, as defined by the American Heart Association (AHA), remains to be scarce. This study aims to explore the correlation of the AHA-defined cardiovascular health metrics within couples using a nationwide epidemiological database. METHODS: We examined the modified cardiovascular health metrics among 87,160 heterosexual couples using the health claims database from the Japan Medical Data Center. The ideal cardiovascular health metrics is comprised of (1) nonsmoking, (2) body mass index ＜25 kg/m2, (3) physical activity at goal, (4) untreated blood pressure ＜120/80 mm Hg, (5) untreated fasting glucose ＜100 mg/dL, and (6) untreated total cholesterol ＜200 mg/dL. RESULTS: A correlation was noted on the ideal modified cardiovascular health metrics between couples. The prevalence of meeting ≥ 5 ideal components in the female partners increased from 32 % in the male partners meeting 0-1 ideal component to 56 % in those meeting 6 ideal components. The same trend has been observed in all generations (20-39 years, 40-49 years, 50-59 years, ≥ 60 years). The association between couples is found to be better in terms of smoking status, blood pressure, and fasting glucose level. CONCLUSION: There was an intracouple correlation of the ideal modified cardiovascular health metrics, suggesting the importance of couple-based intervention to improve cardiovascular health status.

Reverse J-shaped relationship between body mass index and in-hospital mortality of patients hospitalized for heart failure in Japan.

Several lines of evidence demonstrated body mass index (BMI) to be inversely associated with outcomes of patients with HF, so-called obesity paradox. However, the relationship between BMI and outcomes of patients with HF in Japan has been poorly understood. This study sought to explore the relationship between BMI and in-hospital mortality of patients hospitalized for heart failure (HF) in Japan and whether BMI at hospital admission could be used for the risk stratification of hospitalized HF patients. We studied 407,722 patients hospitalized for HF between January 2010 and March 2018, using the Diagnosis Procedure Combination database, a national inpatient database in Japan. Patients were categorized into four groups: underweight (BMI < 18.5 kg/m2), 66,342 patients (16.3%); normal (18.5-24.9 kg/m2), 240,801 patients (59.1%); pre-obesity (25.0-29.9 kg/m2), 76,954 patients (18.9%); and obesity (≥ 30.0 kg/m2), 23,625 patients (5.8%). Pre-obese and obese patients were younger and more likely to be male. Advanced HF symptoms were more common among underweight patients. Multivariable logistic regression analysis fitted with generalized estimating equation showed that, compared with normal weight patients underweight patients had higher in-hospital mortality (odds ratio 1.50, 95% confidence interval 1.45-1.55), whereas pre-obese patients (odds ratio 0.80, 95% confidence interval 0.77-0.83) and obese patients (odds ratio 0.90, 95% confidence interval 0.84-0.97) had lower in-hospital mortality. Restricted cubic spline showed a reverse J-shaped relationship between BMI and in-hospital mortality with the bottoms of splines around BMI 26 kg/m2. In conclusion, underweight patients had higher, and pre-obese and obese patients had lower in-hospital mortality compared to patients with normal weight patients. Furthermore, restricted cubic spline indicated a reverse J-shaped relationship between BMI and in-hospital mortality. Our findings are informative for the risk stratification of patients hospitalized for HF according to BMI.

Serial Changes in Clinical Presentations and Outcomes of 5,740 Patients Requiring Repeated Hospital Admissions (Four or More Times) due to Worsened Heart Failure.

Heart failure (HF) is a major cause of death and hospitalization worldwide. In particular, hospital readmission due to worsened HF occurs frequently after the onset of HF. However, the association of repeated hospital admission with clinical manifestations and outcomes is unclear. The aim of this study was to clarify the serial changes in presentation and clinical course of patients requiring repeated hospital admission due to worsened HF. Among 466,921 patients who were admitted and discharged between January 2010 and March 2018, with the main discharge diagnosis of HF, we studied 5,740 patients who were hospitalized 4 times or more, using the Diagnosis Procedure Combination database. We evaluated serial changes in continuous data using the Jonckheere trend test, and categorical data using the Cochran-Armitage trend test. The median age of the patients was 78 years, and 3,326 patients (58%) were male. Body mass index and Barthel Index decreased with increased numbers of admissions. Patients requiring respiratory support and hemodialysis increased, whereas patients undergoing intra-aortic balloon pumping decreased with increased numbers of admissions. The length of hospital stay was prolonged and the interval between hospitalizations was shortened with increased numbers of hospital admissions. The in-hospital mortality rate was 8.8% at the fourth admission. In conclusion, this is the first large-scale real-world study on the serial changes in characteristics and outcomes of HF patients requiring repeated hospitalization, suggesting that repeated hospitalization might adversely affect the general status of patients with HF and result in a vicious clinical cycle.

Association of Isolated Diastolic Hypertension Based on the Cutoff Value in the 2017 American College of Cardiology/American Heart Association Blood Pressure Guidelines With Subsequent Cardiovascular Events in the General Population.

Background The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines lowered the threshold of blood pressure (BP) for hypertension to 130/80 mm Hg. However, the clinical significance of isolated diastolic hypertension (IDH) according to the cutoff value of the 2017 ACC/AHA guidelines was uncertain. Methods and Results We analyzed the claims database of Japan Medical Data Center (a nationwide epidemiological database). We excluded individuals who were aged <20 years, had systolic hypertension, were taking antihypertensive medication, or had prevalent cardiovascular disease, and studied 1 746 493 individuals (mean age, 42.9±10.7 years; 961 097 men [55.0%]). The average observational period was 1107±855 days. Stage 1 IDH, defined as diastolic BP 80 to 89 mm Hg, and stage 2 IDH, defined as diastolic BP ≥90 mm Hg, were found in 230 513 (13.2%) and 16 159 (0.9%) individuals, respectively. Compared with individuals with normal diastolic BP, individuals with stage 1 and stage 2 IDH were older and more likely to be men. Prevalence of classic risk factors was higher in patients with IDH. Kaplan-Meier curves showed that stage 1 and stage 2 IDH were associated with a higher incidence of cardiovascular events, defined as myocardial infarction, angina pectoris, and stroke. Multivariable analysis showed that stage 1 (hazard ratio [HR], 1.17) and stage 2 (HR, 1.28) IDH were independently associated with a higher incidence of cardiovascular events. Subgroup analyses showed that the association of IDH with cardiovascular events was seen irrespective of age and sex. Conclusions The analysis of a nationwide epidemiological database showed that IDH based on the cutoff value in the 2017 ACC/AHA BP guidelines was associated with an elevated risk of subsequent cardiovascular events.

Association of Cancer With Outcomes in Patients Hospitalized for Heart Failure.

BACKGROUND: The complex clinical status of heart failure (HF) patients with concomitant cancer is gaining clinical interest. This study sought to explore the prevalence of cancer in patients with HF and its effect on outcomes using a nationwide inpatient database.Methods and Results:In total, 447,818 HF patients who were admitted and discharged between January 2010 and March 2018 were studied and included in the Diagnosis Procedure Combination (DPC) database. The median age was 81 years; 238,192 patients (53.2%) were men and 25,951 (5.8%) had concomitant cancer. The prevalence of cancer peaked in patients aged in their 70 s and 80 s and increased with time. Patients with cancer were older and more likely to be male. Cigarette smoking was more common in patients with cancer. Patients with cancer more frequently had infectious complications during hospitalization. Advanced medical procedures were less frequently performed for patients with cancer. In-hospital mortality was higher in patients with cancer than those without (10.0% vs. 6.7%, P<0.001). Among patients with cancer, in-hospital mortality was higher in patients with metastasis than those without (18.9% vs. 9.4%, P<0.001). Multivariable logistic regression analysis, fitted with a generalized estimating equation, indicated cancer is associated with higher in-hospital mortality (odds ratio 1.51, 95% confidential interval 1.43-1.59, P<0.001). CONCLUSIONS: Cancer was frequently observed in patients hospitalized for worsened HF, and its prevalence increased with time. The presence of cancer increased the risk of in-hospital death. Further studies are warranted to establish the optimal management strategy for HF patients with cancer in the field of cardio-oncology.

Association of body weight gain with subsequent cardiovascular event in non-obese general population without overt cardiovascular disease.

BACKGROUND: Body weight (BW) gain in adulthood frequently leads to the development of obesity and is associated with subsequent cardiovascular disease (CVD). However, the pathological significance of BW gain in non-obese individuals is not fully understood. METHODS AND RESULTS: Using data from a nationwide epidemiological database, we studied 1,558,774 non-obese subjects aged ≥20 years and without prior history of CVD. The subjects' mean age was 44.7 ±â€¯11.2 years, and 853,391 subjects (54.7%) were male. BW gain, which was defined as BW gain of ≥10 kg from the age of 20 years, was seen in 302,997 subjects (19.4%). Subjects with BW gain were older and more likely to be male than those without BW gain. Body mass index and waist circumference were higher in subjects with BW gain. The prevalence of classical CVD risk factors was higher in subjects with BW gain. Kaplan-Meier curves and log-rank tests showed that subjects with BW gain had higher incidences of composite endpoints, including myocardial infarction, angina pectoris, and stroke. Multivariable Cox regression analysis including other covariates presented that BW gain was independently associated with the incidence of composite endpoint (Hazard ratio 1.10, 95% confidence interval 1.07-1.13, p < 0.001). Subgroup analyses showed that the association of BW gain with the development of CVD was observed regardless of age, sex, and body mass index. CONCLUSION: Subjects with BW gain of ≥10 kg from the age of 20 years had high incidence of cardiovascular events even if they did not yet develop obesity. The results suggest the significance of substantial BW gain in adulthood in the development of subsequent CVDs.

Association between the number of hospital admissions and in-hospital outcomes in patients with heart failure.

Readmission to the hospital is a major issue in clinical care for patients with heart failure (HF). However, the impact of the number of hospital admissions due to worsened HF is not fully understood. We sought to clarify the association between the number of hospital admissions due to worsened HF and patient outcomes. We studied 331,259 patients (median age was 81 years, and 175,286 patients (52.9%) were men) hospitalized for HF between January 2010 and March 2018 using the Japanese Diagnosis Procedure Combination Database, a national inpatient database. Patients were categorized into five groups based on the number of times they were admitted: once (n = 264,583), twice (n = 42,385), three times (n = 13,205), four times (n = 5347), and five or more times (n = 5739). The patients with larger numbers of admissions were more likely to have comorbidities and to use inotropic agents. The interval period between hospitalizations was shortened with an increasing number of hospital admissions, whereas the length of hospital stay was prolonged with an increasing number of hospital admissions. Multivariable logistic regression analysis fitted with a generalized estimating equation showed that an increased number of hospital admissions was independently associated with higher in-hospital mortality. In conclusion, readmission to the hospital due to worsened HF was still common, and in-hospital mortality was higher in those with larger numbers of readmissions, suggesting a clinical significance of the number of readmissions in patients with HF.

Characteristics and Outcomes of Super-Elderly Patients (Aged ≥90 Years) Hospitalized for Heart Failure　- Analysis of a Nationwide Inpatient Database.

Background: Although the aged population is increasing in developed countries, clinical evidence on super-elderly heart failure (HF) patients is scarce. This study determined the characteristics and outcomes of Japanese hospitalized super-elderly HF patients (aged ≥90 years) using a nationwide inpatient database. Methods and Results: A comprehensive analysis was performed of 447,818 HF patients in the Diagnosis Procedure Combination database who were hospitalized and discharged between January 2010 and March 2018. Among the study population, 243,028 patients (54.3%) were aged ≥80 years and 64,628 patients (14.4%) were aged ≥90 years. The percentage of elderly patients increased over time. Elderly patients were more likely to be female and had a higher New York Heart Association functional class at admission. Invasive and advanced procedures were rarely performed, whereas infectious complications were more common in patients with older age. Length of hospital stay and in-hospital mortality increased with age. Multivariable logistic regression analysis fitted with a generalized estimating equation showed higher in-hospital mortality in patients aged ≥80 and ≥90 years (odds ratios 1.99 and 3.23, respectively) compared with those aged <80 years. Conclusions: The number of hospitalized super-elderly HF patients has increased, and these patients are associated with worse clinical outcomes. The results of this study may be useful in establishing an optimal management strategy for super-elderly HF patients in the era of HF pandemic.