Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: The Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

INTRODUCTION: Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome, and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD. METHODS: We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 and/or proteinuria) at baseline. Breakfast skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the estimated glomerular filtration rate (eGFR) from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors. RESULTS: During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p = 0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI: 1.29-5.26) for the breakfast-skipping group (p = 0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR, and baseline proteinuria. CONCLUSION: Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.

Association between serum uric acid and new onset and progression of chronic kidney disease in a Japanese general population: Iki epidemiological study of atherosclerosis and chronic kidney disease.

BACKGROUND: Although several risk factors for chronic kidney disease (CKD) have been proposed, it remains unclear whether elevated serum uric acid (SUA) is negatively association with kidney function. The aim of this study was to elucidate the association between SUA and new onset and progression of CKD in a Japanese general population. METHODS: This was a population-based retrospective cohort study using annual health checkup data of residents of Iki Island. A total of 5,507 adults (979 with CKD and 4,528 without) were included. The outcomes were new onset of CKD among participants without CKD at baseline, and progression of CKD among those with CKD. A Cox proportional hazards model was used to evaluate the association between SUA and new onset and progression of CKD. RESULTS: During mean follow-up of 4.6 years, 757 cases of new onset of CKD and 193 with progression of CKD were observed. SUA was significantly associated with new onset of CKD (adjusted hazard ratio 1.13, [95% confidence interval 1.03-1.24] per standard deviation [SD] increase in SUA). In contrast, SUA was not significantly associated with progression of CKD (hazard ratio 1.08, [0.92-1.27] per SD increase). Similar results were obtained when classifying uric acid as categorical. CONCLUSION: SUA was significantly associated with increased risk for new onset of CKD, but not with progression of CKD among a Japanese general population.

Risk of Stroke in Atrial Fibrillation According to Sex in Patients Aged Younger Than 75 Years: A Large-Scale, Observational Study Using Real-World Data.

BACKGROUND: It is unclear whether women have a higher risk of stroke than men. This study aimed to clarify the effects of a sex difference on the risk of ischaemic stroke in patients with atrial fibrillation (AF). METHODS: Health check and insurance claims data were used of people who were aged <75 years from 2005 to 2017 in Japan. Patients with AF who were not on anticoagulation therapy were identified. After excluding patients with artificial valves (n=28), haematological disease (n=1,124), aged ≤20 years (n=207), and taking anticoagulant therapy (n=11,848), 9,733 remained for inclusion into the study. The primary outcome was hospital admission due to ischaemic stroke. RESULTS: Of the 9,733 participants, 7,079 (72.7%) were men. The mean age of women (54.4 years) was significantly higher than that of men (53.2 years). During a mean 2.5-year follow-up period, 143 ischaemic stroke events occurred. Female sex was not associated with ischaemic stroke (adjusted hazard ratio [95% confidence interval]: 1.13 [0.78-1.66]). When stratified using the CHA2DS2-VASc score, the annual incidence of ischaemic stroke was similarly low among women with a CHA2DS2-VASc score of 1 (0.8%) and men with a score of 0 (0.7%). The incidence of ischaemic stroke increased with a CHA2DS2-VASc score of 2 in women and 1 in men. CONCLUSIONS: In this large-scale, real-world study of patients with AF, the risk of ischaemic stroke among those aged <75 years was comparable between women and men. These findings are consistent with the current guidelines, which do not recommend anticoagulant therapy for women with no other risk factors (CHA2DS2-VASc score of 1).

Increased Incident Ischemic Stroke Risk in Advanced Kidney Disease: A Large-Scale Real-World Data Study.

INTRODUCTION: Evidence using real-world data is sparse regarding the effects of oral anticoagulants (OACs) among patients with kidney disease. The aim of this study was to investigate the effects of kidney disease on ischemic stroke (IS) or systemic embolism (SE) among patients taking OAC, using large-scale real-world data in Japan. METHODS: This was a retrospective cohort study using claims data and health checkup data from health insurance associations in Japan, from January 2005 to June 2017. We enrolled 21,581 patients diagnosed with atrial fibrillation (AF). Of the total population, 11,848 (54.9%) patients were taking OAC. A Cox proportional hazards model was used to examine the effect of kidney disease on IS/SE with or without OAC. RESULTS: During follow-up, 208 participants who were not taking OAC (mean follow-up 2.6 years) and 200 who were taking OAC (mean follow-up 3.0 years) experienced IS/SE. The % IS/SE incidence rates with and without kidney disease were 2.42/person-year and 0.63/person-year in the total population, 3.66/person-year and 0.76/person-year in the group without OAC use, and 1.52/person-year and 0.55/person-year in patients with OAC use, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) of kidney disease for IS/SE were high, irrespective of OAC, even after adjustment: adjusted HR 2.62 (95% CI: 1.72-3.99) without OAC and adjusted HR 2.03 (95% CI: 1.20-3.44) with OAC; p = 0.193 for interaction between no OAC and OAC. Although bleeding risk was also high for kidney disease irrespective of OAC use (HR 2.93 [95% CI: 2.27-3.77] in the total population, HR 3.08 [95% CI: 2.15-4.43] in the group without OAC, and HR 2.73 [95% CI: 1.90-3.91] in the group with OAC use), net clinical benefit indicated that the benefit of OAC use exceeded the risk of bleeding: HR 4.50 (95% CI: 0.76-8.23) among those with kidney disease and HR 0.35 (95% CI: 0.04-0.66) among those without kidney disease. CONCLUSION: Although we found that OAC use was effective and recommended for patients with AF, advanced kidney disease is still an independent risk factor for IS/SE, even in patients taking OAC. Physicians should be aware of this risk and strictly control modifiable risk factors, regardless of OAC use.

Association of Work Situation With Cardiovascular Disease Mortality Risk Among Working-Age Japanese Men　- A 20-Year Follow-up of NIPPON DATA90.

BACKGROUND: Several cohort studies have demonstrated an association between socioeconomic status (SES) and health outcomes in Japan. As long-term employment is common in Japan, the size of the company may be related to cardiovascular disease (CVD) mortality risk. We examined the association of employment conditions with CVD mortality risk among working-age Japanese men (30-59 years, n=2,091).Methods and Results:We used 20-year follow-up data from NIPPON DATA90, for which baseline data were obtained from the 4th National Survey on Circulatory Disorders in 1990. Participants were classified into 4 groups: 3 strata for indefinite-term employees according to company size (large company/public office, moderate-sized, or small), and the self-employed/administrator group. Multivariable-adjusted hazard ratios (HRs) were adjusted for age, lifestyle, and CVD risk factors. Smokers were more common, habitual exercise was less common, and the average systolic blood pressure was higher among indefinite-term employees of small companies compared with employees at large companies/public offices. There was no significant difference in the total CVD mortality risk between indefinite-term employees and self-employed/administrator participants. The age-adjusted HR (95% confidence interval) for total CVD using indefinite-term employees of large companies/public office as a reference was 2.53 (1.12, 5.69) for employees of small companies. CONCLUSIONS: Working as an indefinite-term employee at a small company in Japan was significantly associated with elevated risk of CVD mortality among Japanese men.

Association Between Body Mass Index and All-Cause Death in Japanese Population: Pooled Individual Participant Data Analysis of 13 Cohort Studies.

BACKGROUND: We sought to investigate the optimal values of BMI for the lowest risk of all-cause death and whether the optimal BMI differs according to smoking status in large-scale pooled analysis of 13 Japanese cohorts. METHODS: Data from 179,987 participants of 13 well-qualified cohort studies conducted throughout Japan were used for our analysis. A cohort-stratified Cox proportional hazard model was used. P values for interactions were calculated based on the cross product of BMI and age, sex, or smoking status. RESULTS: In the entire study population, all-cause mortality risk was lowest when the BMI was 22.0-24.9 kg/m2. This was also the case for selected healthy participants (never smoked, baseline total cholesterol level ≥4.1 mmol/L; the first 5 years of follow-up data were excluded). No effect modification of age, sex, or smoking status was observed. Regardless of their BMI, never smokers always had a lower all-cause mortality risk than did current smokers even with an ideal BMI in terms of mortality risk. CONCLUSION: A BMI of 22-24.9 kg/m2 correlated with the lowest risk of mortality, regardless of whether all participants or selected healthy participants were analyzed. The fact that smoking was more strongly associated with mortality than obesity emphasizes the urgency for effective anti-smoking programs.

Socioeconomic and lifestyle factors associated with depressive tendencies in general Japanese men and women: NIPPON DATA2010.

BACKGROUND: The gender-specific characteristics of individuals at an increased risk of developing depression currently remain unclear despite a higher prevalence of depression in women than in men. This study clarified socioeconomic and lifestyle factors associated with an increased risk of subclinical depression in general Japanese men and women. METHODS: Study participants were residents not receiving psychiatric treatments in 300 sites throughout Japan in 2010 (1152 men, 1529 women). Multivariable-adjusted odds ratios (OR) and 95% confidence intervals (95%CIs) for socioeconomic factors and lifestyle factors were calculated using a logistic regression analysis. RESULTS: Risk of depressive tendencies was significantly higher in men who were single and living alone (OR, 3.27; 95% CI, 1.56-6.88) than those married. The risk was significantly lower in women who were not working and aged ≥ 60 years (OR, 0.39; 95% CI, 0.22-0.68) and higher in men who were not working and aged < 60 years (OR, 3.57; 95%CI, 1.31-9.72) compared with those who were working. Current smoking was also associated with a significantly increased risk of depressive tendencies in women (OR, 2.96; 95% CI, 1.68-5.22) but not in men. CONCLUSIONS: Socioeconomic and lifestyle factors were associated with an increased risk of depressive tendencies in general Japanese. Related factors were different by sex.

Does clinical practice supported by artificial intelligence improve hypertension care management? A pilot systematic review.

Although artificial intelligence (AI) is considered to be a promising tool, evidence for the effectiveness of AI-supported clinical practice for lowering blood pressure (BP) in the real world is scarce. We conducted a systematic review to elucidate whether AI-supported clinical care improves BP control. We identified two randomized control trials (RCTs) in a literature search. The results revealed no significant difference between AI-supported care and usual care in a random-effects model meta-analysis of RCTs (AI vs. usual care: systolic/diastolic BP difference: -2.13 [95% confidence interval: -4.72 to 0.46] / -1.03 [-2.52 to 0.46]). In this review, we were unable to clarify whether AI-supported clinical practice improved BP control compared with usual care. Further studies will be needed to provide robust evidence for the effectiveness of AI-supported care in clinical settings.

Current use of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors for hypertension in patients with chronic kidney disease with proteinuria: a cross-sectional study based on real-world data.

Japanese guidelines recommend angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) as first-line therapy in hypertensive patients with chronic kidney disease (CKD) and proteinuria, but calcium channel blockers in patients with stage G4-5 CKD aged ≥75 years; however, the implementation of these guidelines in clinical practice is unclear. We investigated the actual use of these agents in this patient population. We conducted a cross-sectional study using the DeSC database, which includes anonymous information from various health insurance systems in Japan. A total of 34,362 hypertensive patients aged <75 years with CKD stage G1-G5 with urinary protein ≥1+ or aged ≥75 years with CKD stage G1-G3 with urinary protein ≥1+, for whom Japanese guidelines recommend first-line ARBs/ACEIs, were included in the analysis. Prescription rates of ARBs and ACEIs were calculated overall and separately for each age group and glomerular filtration rate category. The mean participant age was 65.8 ± 14.8 years, including 24,585 patients (72%) <75 years and 9777 (28%) ≥75 years. Of these, 9529 were prescribed ARBs/ACEIs (prescription rate 28%). The prescription rate was lower in patients aged <75 years with CKD stage G1-G5 (prescription rate 23%) compared with patients aged ≥75 years old with CKD stage G1-G3 (prescription rate 41%) (p < 0.001). Patients with CKD stage G1 had the lowest prescription rates for ARBs/ACEIs in both age categories. These results indicate that, despite guideline recommendations, ARBs/ACEIs are insufficiently prescribed for patients with hypertension associated with CKD with proteinuria. ARBs and ACEIs were only used in 28% of hypertensive patients aged<75 years (CKD stage G1-G5) or aged ⩾75 years (CKD stage G1-G3), with urinary protein ⩾1+, for whom Japanese guidelines recommend ARBs/ACEIs. The prescription rate was lower in the younger compared with the older patients.

Relationship between abdominal circumference and the incidence of hyperuricemia in the general Japanese population.

In this study, we aimed to separately evaluate the relationship between waist circumference and the incidence of hyperuricemia in men and women in the general Japanese population. We performed a population-based longitudinal study using data from the annual health examination of residents of Iki City, Japan. A total of 5567 participants without hyperuricemia at baseline were included in the analysis. The men and women were placed into groups according to the tertile of waist circumference. The outcome was incident hyperuricemia (uric acid > 416 µmol/L [7.0 mg/dL]). The relationship between waist circumference and the incidence of hyperuricemia was investigated using Cox proportional hazards models. During the follow-up period, hyperuricemia developed in 697 people (551 men and 146 women). The incidence (per 1000 person-years) of hyperuricemia increased with increasing waist circumference in the men (34.9 for tertile 1, 49.9 for tertile 2 and 63.3 for tertile 3; Ptrend < 0.001) and women (5.5 for tertile 1, 6.3 for tertile 2 and 11.9 for tertile 3; Ptrend < 0.001). Significant associations were identified after adjustment for potential confounders (men: Ptrend < 0.001; women: Ptrend = 0.014). In conclusion, both men and women with larger waist circumferences were at higher risks of subsequent hyperuricemia.

Differences in the effects of exercise on blood pressure depending on the physical condition of the subject and the type of exercise: a systematic review and meta-analysis.

Although hypertension is a major cause of cardiovascular disease, the control of blood pressure (BP) is insufficient worldwide. Exercise is an effective treatment for reducing BP, but the differences in the blood pressure lowering effects of exercise according to the underlying pathophysiological condition, the type of exercise, and the geographic region are not fully understood. An umbrella review with a meta-analysis of 435 randomized controlled trials that investigated the BP-lowering effects of exercise was performed using Ovid MEDLINE and the Cochrane Library, covering the period from inception to August 1, 2023. A random effects model meta-analysis was performed to estimate the effect size across multiple studies. Exercise significantly reduced systolic BP in healthy subjects (-3.51 mmHg, 95% confidence interval: -3.90, -3.11; p < 0.001) and in those with lifestyle-related diseases including hypertension (-5.48 mmHg, -6.51, -4.45; p < 0.001), but not in those with cardiovascular diseases (-1.16 mmHg, -4.08, 1.76; p = 0.44). According to the type of exercise, all types significantly reduced systolic BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases. According to the region, in Oceania, there were no reductions in systolic BP. In Asia, systolic BP was reduced in patients with cardiovascular diseases. In conclusion, any type of exercise reduced BP in healthy subjects and in those with lifestyle-related diseases, but not in those with cardiovascular diseases, and the region affected the effect of exercise. When using exercise to reduce hypertension, it is important to consider the patient's pathophysiological condition and the region.

Marital status, household size, and lifestyle changes during the first COVID-19 pandemic: NIPPON DATA2010.

Stay-at-home strategies taken during the COVID-19 pandemic changed our lifestyle drastically. Although marital status and household size are important social determinants of health that affect lifestyle, their impacts on lifestyle during the pandemic are still unclear. We aimed to evaluate the association between marital status, household size, and lifestyle changes during the first pandemic in Japan. Questionnaire surveys on lifestyle changes from before to during the first COVID-19 pandemic were conducted on October 2020 in Japan. Classified into age groups, multivariable logistic regression analysis was performed to examine the combined association of marital status and household size on lifestyle, adjusted for potential confounders including socioeconomic factors. In our prospective cohort study, 1928 participants were included. Among older participants, the singles living alone were likely to perceive more unhealthy lifestyle changes (45.8%), compared with the married (33.2%), and significantly associated with at least one unhealthy change [adjusted odds ratio (OR): 1.81, 95% confidence interval (CI): 1,18-2.78], mainly due to decreased physical activity and increased alcohol consumption. Meanwhile, the younger participants showed no significant association between marital status, household size, and unhealthy changes, while those living alone had 2.87 times higher odds of weight gain (≥ 3 kg) than the married (adjusted OR: 2.87, 95% CI: 0.96-8.54) during the pandemic. Our findings suggest that older singles living alone are potentially vulnerable subgroups to drastic social changes which warrant special attention to prevent adverse health outcomes and additional burden on health systems in the following future.

Urate-lowering drugs for chronic kidney disease with asymptomatic hyperuricemia and hypertension: a randomized trial.

INTRODUCTION: Xanthine oxidase (XO) inhibitors may slow down chronic kidney disease (CKD) progression. The comparative effectiveness of the different urate-lowering drugs is unknown. The aim of this study was to determine whether urate-lowering therapy with an XO inhibitor (febuxostat) and that with a uricosuric drug (benzbromarone) are comparable in slowing renal function decline in patients with CKD complicated with hypertension and hyperuricemia. METHODS: This study was an open-label randomized parallel-group clinical trial of 95 patients with stage G3 CKD in Japan. The patients had hypertension and hyperuricemia without a history of gout. They were randomized to receive febuxostat ( n  = 47; febuxostat group) or benzbromarone ( n  = 48; benzbromarone group) and titrated to reduce their serum urate level to <6.0 mg/dl. The primary end-point was change in estimated glomerular filtration rate (eGFR) from baseline to 52 weeks. The secondary end-points included changes in uric acid level, blood pressure, urinary albumin-to-creatinine ratio, and XO activity. RESULTS: Of the 95 patients, 88 (92.6%) completed the trial. There were no significant differences in change in eGFR (in ml/min/1.73 m 2 ) between the febuxostat [-0.23, 95% confidence interval (CI), -2.00 to 1.55] and benzbromarone (-2.18, 95% CI, -3.84 to -0.52) groups (difference, 1.95; 95% CI, -0.48 to 4.38; P  = 0.115) nor in the secondary end-points, except for XO activity. Febuxostat significantly reduced XO activity ( P  = 0.010). There were no significant differences in primary and secondary outcomes between the groups. A decrease in eGFR was significantly less in the febuxostat group than that of the benzbromarone group in the CKDG3a, but not in CKDG3b, in the subgroup analysis. There were no adverse effects specific to either drug. CONCLUSIONS: No significant differences were found in the effects of febuxostat and benzbromarone in renal function decline in stage G3 CKD complicated with hyperuricemia and hypertension.

Serum triglyceride levels and incidence of hypertension in a general Japanese population: ISSA-CKD study.

The aim of this study was to clarify the relationship between fasting and nonfasting serum triglyceride (TG) levels and the incidence of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data of residents of Iki City, Nagasaki Prefecture, Japan. A total of 3202 participants without hypertension at baseline were included in the present analysis. TG levels were classified as quartile 1 (<0.82 mmol/L), quartile 2 (0.83-1.13 mmol/L), quartile 3 (1.14-1.70 mmol/L) and quartile 4 (≥1.71 mmol/L) for men, and as quartile 1 (<0.70 mmol/L), quartile 2 (0.71-0.96 mmol/L), quartile 3 (0.97-1.34 mmol/L) and quartile 4 (≥1.35 mmol/L) for women. The outcome was incident hypertension. During an average follow-up of 4.4 years, 983 participants developed hypertension, according to the Cox proportional hazards model. The annual incidence of hypertension increased with an elevation in TG levels for men (5.88% in quartile 1, 8.30% in quartile 2, 7.62% in quartile 3, and 9.82% in quartile 4). This association was significant, even after adjustment for other risk factors: hazard ratio 1.41 [95% CI 1.07-1.85] for quartile 2, 1.30 [0.99-1.71] for quartile 3, and 1.59 [1.22-2.08] for quartile 4 compared with quartile 1 (p = 0.041 for trend). In contrast, there was no clear association between serum TG levels and the incidence of hypertension after adjustment for confounding factors among women (p = 0.240 for trend). High levels of serum TG were associated with the future incidence of hypertension in a general population of Japanese men but were not associated with that in women. Casual serum triglyceride levels and incidence of hypertension in a general Japanese population: ISSA-CKD study.

Elevation in white blood cell count and development of hyper LDL cholesterolemia.

To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03-1.62) for 3rd quartile group and 1.39 (1.10-1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population.

Association between serum ALT levels and incidence of new-onset diabetes in general population of Japanese: a longitudinal observational study (ISSA-CKD).

OBJECTIVE: We aimed to clarify the relationship between serum alanine transaminase (ALT) levels and incidence of new-onset diabetes in a Japanese general population. SETTING: Population-based retrospective cohort study using annual health check-up data for residents of Iki City, Nagasaki Prefecture, Japan. PARTICIPANTS: A total of 5330 Japanese individuals (≥30 years old) without diabetes at baseline were analysed. PRIMARY AND SECONDARY OUTCOME MEASURES: Serum ALT levels were determined using an enzymatic method and were classified into gender-specific quartile groups as follows: group 1 (3-16 U/L in men and 3-13 U/L in women), group 2 (17-21 U/L in men and 14-16 U/L in women), group 3 (22-29 U/L in men and 17-22 U/L in women) and group 4 (30-428 U/L in men and 23-268 U/L in women). The study outcome was the incidence of diabetes (fasting glucose ≥7.0 mmol/L, non-fasting glucose ≥11.1 mmol/L, glycated haemoglobin ≥6.5% or use of glucose-lowering therapies). RESULTS: After an average follow-up period of 5.0 years, 279 individuals developed diabetes. The incidence rate of diabetes increased with elevation of serum ALT levels (0.7% per 100 person-years in group 1, 0.9% in group 2, 0.9% in group 3 and 1.7% in group 4) (p<0.001 for trend). This association was significant after adjustment for other risk factors including age, sex, obesity, hypertension, dyslipidaemia, smoking, current daily alcohol intake and regular exercise (p<0.001 for trend). Comparable associations were observed between men and women (p=0.459 for interaction). CONCLUSION: Serum ALT levels were associated with future development of diabetes in the general Japanese population.

Efficacy of trastuzumab in Japanese patients with HER2-positive advanced gastric or gastroesophageal junction cancer: a subgroup analysis of the Trastuzumab for Gastric Cancer (ToGA) study.

BACKGROUND: The Trastuzumab for Gastric Cancer (ToGA) study is the first international trial to include Japanese patients with human epidermal growth factor 2 (HER2) positive advanced/metastatic gastric or gastroesophageal junction cancer. ToGA showed that trastuzumab plus chemotherapy (capecitabine/cisplatin or 5-fluorouracil/cisplatin) improved overall survival in the overall population (hazard ratio 0.74). Regional differences in outcome in favor of Japanese populations were observed in other studies; therefore, subgroup analyses of ToGA may contribute to the evaluation of the potential benefits of this regimen in Japanese patients. METHODS: We performed subgroup analyses on 101 Japanese patients enrolled into ToGA (trastuzumab plus chemotherapy, n = 51; chemotherapy, n = 50). RESULTS: Median overall survival in the Japanese subgroup was 15.9 months (95% confidence interval 12-25) for trastuzumab plus chemotherapy and 17.7 months (95% confidence interval 12-24) for chemotherapy (hazard ratio 1.00; 95% confidence interval 0.59-1.69). After adjusting for prespecified covariates, the estimated hazard ratio for overall survival was 0.68 (95% confidence interval 0.36-1.27). Further post hoc and exploratory examinations supported the robustness of the adjusted hazard ratios. CONCLUSIONS: After adjusting for imbalanced patient backgrounds between arms, overall survival of Japanese patients with human epidermal growth factor 2 positive advanced/metastatic gastric or gastroesophageal junction cancer who received trastuzumab plus chemotherapy was improved compared with patients who received chemotherapy alone.

A Comparison of Segment-Specific and Composite Measures of Carotid Intima-Media Thickness and their Relationships with Coronary Calcium.

AIMS: The utility of carotid intima-media thickness (cIMT) as a marker for coronary heart disease is under heavy debate. This is predominantly due to the lack of a standard definition of cIMT, leading to inconsistent results. We investigated and compared the relationships of five different measures of cIMT with coronary calcium. METHODS: Japanese men aged 40-79y ( n=869) from Shiga Epidemiological Study of Subclinical Atherosclerosis were examined. Mean cIMT was measured in three segments of the carotid arteries: common carotid artery (CCAmean), internal carotid artery (ICAmean) and bifurcation (Bifmean). Mean cIMT of average values (Mean cIMT) and mean cIMT of maximum values (Mean-Max cIMT) of all segments combined were assessed. Coronary calcium was assessed as coronary artery calcification (CAC). Ordinal logistic regression was used to determine the odds ratio (OR) of higher CAC per 1 standard deviation higher cIMT measure. Analyses were adjusted for cardiovascular covariates and stratified by age quartiles. RESULTS: All cIMT measures had positive associations with CAC (p＜0.001): [OR, 95% Confidence Interval]: ICAmean [1.23, 1.07-1.42], CCAmean [1.27, 1.08-1.49], Bifmean [1.33, 1.15-1.53], Mean cIMT [1.42, 1.22-1.66], and Mean-Max [1.50, 1.28-1.75]. In age-stratified analyses, only Mean-Max cIMT maintained a significant relationship with CAC in every age quartile (p＜0.05), while CCAmean had some of the weakest associations among age quartiles. CONCLUSIONS: Mean-Max cIMT had consistently stronger associations with coronary calcium, independent of important confounders, such as age. The most oft-used measure, CCAmean, was no longer associated with coronary calcium after age-adjustment and stratification.

Body weight and lifestyle changes under the COVID-19 pandemic in Japan: a cross-sectional study from NIPPON DATA2010.

OBJECTIVES: The COVID-19 pandemic has had an impact on people's lifestyles such as causing body weight changes. This study examined associations among lifestyle changes and body weight during the COVID-19 pandemic among the Japanese population. DESIGN: A cross-sectional study. SETTING: A nationwide survey of the general Japanese population. PARTICIPANTS: Total participants were 2244 men and women, of which 911 young/middle-aged (30-69 years old) and 899 older adults (70 years and older) were analysed separately. OUTCOME: Changes in lifestyle (physical activity, dietary habits and alcohol intake) and body weight during the first wave of COVID-19 in spring 2020. RESULTS: Under the COVID-19 pandemic, 24.1% and 10.1% of Japanese respondents reported weight gain and reduction, respectively. Multivariable-adjusted stepwise logistic regression analyses revealed that the young/middle-aged respondents in the group increased body weight, weight gain was significantly associated with decrease in physical activity (OR 4.01, 95% CI 2.83 to 5.69) and both increase (OR 5.82, 95% CI 3.85 to 8.80) and decrease (OR 2.73, 95% CI 1.52 to 4.93) in eating between meals. In the group that decreased body weight, body weight reduction was significantly associated with increase in physical activity (OR 3.66, 95% CI 1.94 to 6.90), decrease in eating between meals (OR 5.97, 95% CI 3.11 to 11.48) and both increase and decrease in alcohol intake in the young/middle age. For the older adults, body weight gain was higher in women than in men, and significantly associated with higher quartile of regional COVID-19 infection, decrease in physical activity (OR 2.98, 95% CI 1.98 to 4.49), increase in home-cooked meals and increase in eating between meals (OR 4.22, 95% CI 2.55 to 6.99). On the other hand, body weight reduction was significantly associated with decreases in physical activity (OR 2.63, 95% CI 1.62 to 4.27), home-cooked meals and eating between meals (OR 1.95, 95% CI 1.05 to 3.61) in the older adults. CONCLUSION: Changes in physical activity and eating between meals were associated with body weight change under the COVID-19 pandemic among Japanese.

Residual risks of ischaemic stroke and systemic embolism among atrial fibrillation patients with anticoagulation: large-scale real-world data (F-CREATE project).

OBJECTIVE: Among patients with atrial fibrillation, the risks of ischaemic stroke and systemic embolism (IS/SE) are high even with effective anticoagulation. Using large-scale, real-world data from Japan, this study aims to clarify residual risks of IS/SE attributable to modifiable risk factors among patients with atrial fibrillation who are taking oral anticoagulants. METHODS: The study design we employed was a retrospective cohort. Health check-ups and insurance claims data of Japanese health insurance companies were accumulated from January 2005 to June 2017. We identified 11 848 participants with atrial fibrillation who were on oral anticoagulants during the study period. We set the modifiable risk factors as hypertension, diabetes and dyslipidaemia. A Cox proportional hazards model was used to obtain the effects of the risk factors for IS/SE. RESULTS: During an average of 3 years' follow-up, 200 cases of IS/SE occurred (incidence rate 0.57 per 100 person-years). In multivariable analyses, older age (65-74 vs <65 years; adjusted HR 2.02 (95% CI 1.49 to 2.73)), hypertension (adjusted HR 1.41 (1.04 to 1.92)) and dyslipidaemia (adjusted HR 1.46 (1.07 to 1.98)) were significantly associated with increased risk of IS/SE. Percentage of IS/SE risk attributable to modifiable risk factors (hypertension, diabetes and dyslipidaemia) was 30.0% (16.1% to 41.6%). CONCLUSION: Among patients with atrial fibrillation on anticoagulant therapy, approximately one-third of the residual risks were estimated to be attributable to modifiable risk factors such as hypertension, diabetes and dyslipidaemia.