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/1.73m2 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 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.

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.

Validation Study of the MDS Criteria for the Diagnosis of Multiple System Atrophy in the Mayo Clinic Brain Bank.

BACKGROUND AND OBJECTIVE: The second consensus criteria in 2008 have been used in diagnosing multiple system atrophy (MSA). The International Parkinson and Movement Disorder Society (MDS) proposed new diagnostic criteria for MSA in 2022. This study aimed to compare the diagnostic accuracy between these 2 criteria and validate the clinical utility of the newly proposed criteria for MSA. METHODS: We conducted a retrospective autopsy cohort study of consecutive patients with a clinical or pathologic diagnosis of MSA from the Mayo Clinic brain bank between 1998 and 2021. We studied 352 patients (250 pathologically diagnosed MSA and 102 non-MSA); MDS criteria and the second consensus criteria were applied. The sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic curves were compared between these criteria. Comparison was conducted between clinical subtypes and among clinically challenging cases (those with different clinical diagnoses or those with suspected but undiagnosed MSA before death). We also used machine learning algorithm, eXtreme Gradient Boosting, to identify clinical features contributing diagnostic performance. RESULTS: The sensitivity and specificity of clinically established and probable MSA by the MDS criteria were 16% and 99% and 64% and 74%, respectively. The sensitivity and specificity of probable MSA and possible MSA by the second consensus criteria were 72% and 52% and 93% and 21%, respectively. The AUC of MDS clinically probable MSA was the highest (0.69). The diagnostic performance did not differ between clinical subtypes. In clinically challenging cases, MDS clinically established MSA maintained high specificity and MDS clinically probable MSA demonstrated the highest AUC (0.62). MRI findings contributed to high specificity. In addition, combining core clinical features with 2 or more from any of the 13 supporting features and the absence of exclusion criteria also yielded high specificity. Among supporting features, rapid progression was most important for predicting MSA pathology. DISCUSSION: The MDS criteria showed high specificity with clinically established MSA and moderate sensitivity and specificity with clinically probable MSA. The observation that high specificity could be achieved with clinical features alone suggests that MSA diagnosis with high specificity is possible even in areas where MRI is not readily available.

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.

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.

Impact of non-motor fluctuations on QOL in patients with Parkinson's disease.

Introduction: Long-term levodopa treatment in patients with Parkinson's disease (PwPD) often causes motor fluctuations, which are known to affect their quality of life (QOL). These motor fluctuations may be accompanied by fluctuations in non-motor symptoms. There is no consensus on how non-motor fluctuations affect QOL. Methods: This was a single-center, retrospective study and included 375 patients with Parkinson's disease (PwPD) who visited the neurology outpatient department of Fukuoka University Hospital between July 2015 and June 2018. All patients were evaluated for age, sex, disease duration, body weight, and motor symptoms by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III, depression scale by the Zung self-rating depression scale, apathy scale, and cognitive function by the Japanese version of The Montreal Cognitive Assessment. A nine-item wearing-off questionnaire (WOQ-9) was used to assess the motor and non-motor fluctuations. QOL in PwPD was investigated using the eight-item Parkinson's Disease Questionnaire (PDQ-8). Results: In total, 375 PwPD were enrolled and classified into three groups according to the presence or absence of motor and non-motor fluctuations. The first group included 98 (26.1%) patients with non-motor fluctuations (NFL group), the second group included 128 (34.1%) patients who presented with only motor fluctuations (MFL group), and the third group included 149 (39.7%) patients without fluctuations in motor or non-motor symptoms (NoFL group). Among them, the PDQ-8 SUM and SI were significantly higher in the NFL group than in the other groups (p < 0.005), implying that the NFL group had the poorest QOL among groups. Next, multivariable analysis showed that even one non-motor fluctuation was an independent factor that worsened QOL (p < 0.001). Conclusion: This study showed that PwPD with non-motor fluctuation had a lower QOL than those with no or only motor fluctuation. Moreover, the data showed that PDQ-8 scores were significantly reduced even with only one non-motor fluctuation.

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.

Constipation Symptoms in Multiple System Atrophy Using Rome Criteria and Their Impact on Personalized Medicine.

Constipation is one of the most common non-motor symptoms in multiple system atrophy (MSA); however, it has not been evaluated according to the standard diagnostic criteria for constipation in patients with MSA. We evaluated the characteristics of constipation in patients with MSA by using Rome criteria (Rome III), which has been validated and the widely used for gastrointestinal disorders. Fifty-one patients with MSA (29 female) were enrolled in the study. Based on the Rome III criteria, constipation was diagnosed in 29 patients (56.9%); irritable bowel syndrome was not detected. Thirty-seven patients (72.5%) were aware of their constipation. The most common constipation symptom was the sensation of anorectal obstruction (68.6%). Patients' self-awareness of constipation was most strongly correlated to the sensation of incomplete evacuation (odds ratio: 7.377, 95% confidence interval: 1.402−38.817). The number of constipation-related symptoms was correlated with the total levodopa equivalent dose (p < 0.05). Rome criteria, which can detect various constipation symptoms, are useful for evaluating constipation in MSA, and these findings may greatly impact personalized medicine.

Association between pulse pressure and progression of chronic kidney disease.

The aim of this study was to investigate the association between pulse pressure (PP) and chronic kidney disease (CKD) progression among the general population in Japan. We conducted a population-based cohort study of the residents of Iki Island, Nagasaki, Japan, from 2008 to 2018. We identified 1042 participants who had CKD (estimated glomerular filtration rate(eGFR) < 60 mL/min/1.73 m2 or the presence of proteinuria) at baseline. Cox's proportional hazard model was used to evaluate the association between PP and progression of CKD. During a 4.66-year mean follow-up, there were 241 cases of CKD progression (incident rate: 49.8 per 1000 person-years). A significant increase existed in CKD progression per 10 mmHg of PP elevation, even when adjusted for confounding factors [adjusted hazard ratio 1.17 (1.06-1.29) p < 0.001]. Similar results were obtained even after dividing PP into quartiles [Q2: 1.14 (0.74-1.76), Q3: 1.35 (0.88-2.06), Q4: 1.87 (1.23-2.83) p = 0.003 for trend]. This trend did not change significantly irrespective of baseline systolic or diastolic blood pressures. PP remained a potential predictive marker, especially for eGFR decline. In conclusion, we found a significant association between PP and CKD progression. PP might be a potential predictive marker for CKD progression.

Effect of chronic kidney disease on the association between hyperuricemia and new-onset hypertension in the general Japanese population: ISSA-CKD study.

We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA-CKD study, a population-based retrospective cohort study that used annual health check-up data of residents from Iki Island, Japan. After the exclusion of 1881 with l < 1-year follow-up, 2812 with hypertension at baseline, and 165 with missing information on SUA, a total of 3037 participants were enrolled in this analysis. Participants were divided into four groups according to the quartiles of SUA level at baseline, and multivariable-adjusted hazard ratios for new-onset hypertension were calculated. Stratified analyses were performed for each subgroup (defined by sex, age, alcohol intake, and CKD) to assess the interaction effects. During a mean follow-up period of 4.4 years, 943 participants developed hypertension. The first quartile group was set as the reference group, and the multivariable-adjusted hazard ratios (95% confidence interval) for new-onset hypertension were 1.11 (0.90-1.36) in the second quartile, 1.25 (1.02-1.54) in the third quartile, and 1.35 (1.07-1.70) in the fourth quartile compared with those in the reference group (p = .007 for trend). The stratified analyses showed that the association between SUA and hypertension was significantly stronger in participants with CKD than in those without CKD (p = .035 for interaction). SUA level is an independent risk factor for new-onset hypertension. This tendency was significantly stronger in participants with CKD.

Fluctuating pain in Parkinson's disease: Its prevalence and impact on quality of life.

Pain is a common non-motor symptom in Parkinson's disease (PD) patients, and the incidence of fluctuating pain may be improved by taking levodopa. There are only a few detailed reports regarding fluctuating pain. In this study, 331 PD patients were classified into three groups: no-pain group (67.4%), non-fluctuating pain group (22.1%), and fluctuating pain group (10.6%). We evaluated patients' background and its impact on the quality of life (QOL) of each group. The pain group exhibited higher levels of depression (p < 0.0001), had a higher frequency of visual hallucinations (p = 0.007), and lower QOL (p < 0.0001) compared with the no-pain group. The fluctuating pain group had a younger onset (p = 0.006), higher Hoehn & Yahr stage (p = 0.018), and higher frequency of wearing-off (p < 0.001) and dyskinesia (p = 0.007) than the other groups. We compared the Parkinson's Disease Questionnaire-8 summary index (PDQ-8 SI) in each pain group to the no-pain group using analysis of variance. As a result, PDQ-8 SI was significantly higher in both the non-fluctuating and fluctuating pain groups (p < 0.0001). Pain is regarded as a non-negligible symptom that affects the QOL of PD patients, and given the unique characteristics, fluctuating pain might be considered as an independent clinical subtype of PD.

Eating before bed and new-onset hypertension in a Japanese population: the Iki city epidemiological study of atherosclerosis and chronic kidney disease.

The aim of this study was to determine the relationship between eating before bed and the development of hypertension in a general Japanese population. We conducted a population-based retrospective cohort study using annual health check-up data collected from the residents of Iki City, Nagasaki Prefecture, Japan. In total, 2930 participants without hypertension at baseline (mean age 57.0 years, male 42.8%) were included in the present analysis. Eating before bed was defined as eating within 2 h of bedtime. The outcome of this study was incident hypertension (blood pressure ≥140/90 mmHg or initiation of blood pressure-lowering medications). Multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During an average follow-up of 4.5 years, 909 participants developed hypertension. The incidence (per 1000 person-years) of hypertension in the group of individuals who ate before bed was 82.8, whereas that in the group of individuals who did not eat before bed was 65.8. The association was significant even after adjusting for other risk factors, including age, sex, current smoking status, current alcohol intake, regular exercise, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia, with a hazard ratio of 1.23 (95% CI: 1.05-1.44) for the group of individuals who ate before bed compared with the group of individuals who did not eat before bed (P = 0.01 for trend). Eating before bed was correlated with a future risk of developing hypertension in the general Japanese population.

Comparison of Body Mass Index and Waist Circumference in the Prediction of Diabetes: A Retrospective Longitudinal Study.

INTRODUCTION: Both body mass index (BMI) and waist circumference (WC) are associated with diabetes risk, and the difference between them in predictive ability for diabetes is still contentious. We conducted a population-based study to investigate and compare the association of them with diabetes by sex. METHODS: This study included a total of 4754 subjects aged 40-80 years with no diabetes at baseline between 2008 and 2017. Using multivariate Cox proportional hazards models, we calculated hazard ratios for diabetes according to tertiles of BMI or WC. Harrell's C statistics was applied to assess and compare the predictive ability of the models using BMI and WC. RESULTS: Both BMI and WC showed the significant positive trends with diabetes risk. In men, the extreme tertiles (BMI > 25.1 kg/m2 and WC > 88.0 cm) provided 1.58-fold or 2.04-fold higher risk compared with the first tertiles (< 22.6 kg/m2 and < 81.2 cm). In women, BMI > 24.4 kg/m2 showed 3.28-fold higher risk than the first tertile (< 21.6 kg/m2), whereas WC ≥ 78.2 cm was more than twice as likely to suffer from diabetes as WC < 78.2 cm. BMI and WC showed a comparative performance in predicting diabetes in both sexes (P value 0.447 in men, and 0.337 in women). CONCLUSION: Both BMI and WC showed a positive association with diabetes and offered a comparative predictive performance for diabetes in both sexes. The cut-off points, BMI 25.1 kg/m2 and WC 88.0 cm in men and BMI 24.4 kg/m2 and WC 78.2 cm in women, might contribute to the effective prevention strategies for diabetes.

Effects of Weight Gain after 20 Years of Age and Incidence of Hyper-Low-Density Lipoprotein Cholesterolemia: The Iki Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. METHODS: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. RESULTS: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08-1.58, p = 0.006). CONCLUSION: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese.

Eating Speed and Incidence of Diabetes in a Japanese General Population: ISSA-CKD.

BACKGROUND: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. METHODS: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. RESULTS: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p < 0.001 for trend). The HRs were 1.69 (95%CI 0.94-3.06) for the medium eating speed and 2.08 (95%CI 1.13-3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. CONCLUSION: Faster eating speed increased a risk for the incidence of diabetes in a 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.

White blood cell count and incidence of hypertension in the general Japanese population: ISSA-CKD study.

OBJECTIVES: This study aimed to clarify the relationship between the white blood cell (WBC) count and hypertension in the general Japanese population. METHODS: 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 2935 participants without hypertension at baseline were included in the present analysis. WBC counts were classified as tertile 1 (<4700/µL), tertile 2 (4700-5999/µL), and tertile 3 (≥6000/µL). The outcome was incident hypertension (blood pressure ≥140 mmHg). Multivariable-adjusted hazard ratios and 95% confidence intervals (95% CIs) were estimated using the Cox proportional hazards model. RESULT: During an average follow-up of 4.5 years, 908 participants developed hypertension. The incidence (per 100 person-years) of hypertension increased with an elevation in the WBC count (6.3 in tertile 1, 7.0 in tertile 2, and 7.4 in tertile 3). This association was significant, even after adjustment for other risk factors, including age, sex, current smoking habits, current alcohol intake, exercise habits, obesity, elevated blood pressure, diabetes mellitus, and dyslipidemia. The hazard ratios were 1.07 for tertile 2 (95% CI 0.90-1.26) and 1.27 for tertile 3 (95% CI 1.06-1.51) compared with the reference group of tertile 1 (p = 0.009). CONCLUSION: The WBC count was associated with future development of hypertension in the general Japanese 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).

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.