Risk Factors for Hyperuricemia or Gout in Men and Women: The Circulatory Risk in Communities Study (CIRCS).

AIM: We aimed to examine sex-specific risk factors for hyperuricemia or gout in Japanese cohorts. METHODS: We followed up 3,188 men (mean age, 55.6 years) and 6,346 women (mean age, 54.1 years) without hyperuricemia, gout, or elevated liver enzymes at baseline from 1986 to 1990 for a median of 14.6 years. The participants were considered as having hyperuricemia or gout if their serum uric acid levels were ≥ 7.0 mg/dL or they were receiving treatment for hyperuricemia or gout during annual health checkups. The sex-specific multivariable hazard ratios (HRs) of hyperuricemia or gout incidence were calculated after adjustment for smoking and drinking status, body mass index, hypertension, diabetes, hypercholesterolemia, and hypertriglyceridemia using the Cox proportional-hazard model. RESULTS: During follow-up, 733 men and 355 women had hyperuricemia or gout. Among men, the multivariable HRs (95% confidence intervals) of hyperuricemia or gout were 1.23 (1.00-1.52) and 1.41 (1.13-1.75) for drinkers of ＜46 and ≥ 46 g ethanol/day, respectively, compared with non-drinkers; 1.00 (0.81-1.24) and 1.18 (0.93-1.50) for smokers of 1-19 and ≥ 20 cigarettes/day, respectively, compared with never smokers; and 1.41 (1.20-1.65) for hypertensive compared with non-hypertensive participants. The HRs for women were 1.02 (0.70-1.48), 1.66 (1.05-2.63), and 1.12 (0.88-1.42) for current drinkers, current smokers, and hypertensive participants, respectively. For both men and women, body mass index, diabetes, hypercholesterolemia, and hypertriglyceridemia were not associated with hyperuricemia or gout incidence. CONCLUSIONS: Hypertension and alcohol drinking are risk factors for hyperuricemia or gout among men and smoking among women.

Relationships between Age at Menarche and Risk of Cardiovascular Disease Mortality among Japanese Women: The Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC) Study.

AIM: In this study, we aimed to evaluate the association between age at menarche and risk of cardiovascular disease mortality. METHODS: In total, 54,937 women aged 40-79 years old between 1988 and 1990 without a history of cardiovascular disease were eligible for analysis and were followed through December 2009. We used the Cox proportional hazards models to examine the association between age at menarche and risk of cardiovascular disease. RESULTS: Compared with women with age at menarche of 15 years, the hazard ratios (95% confidence intervals) of stroke were 1.22 (0.85-1.75) for women with age at menarche of 9-12 years, 1.08 (0.85-1.36) for those of 13 years, 1.23 (1.02-1.47) for those of 14 years, 1.27 (1.07-1.50) for those of 16 years, 1.16 (0.95-1.41) for those of 17 years, and 1.39(1.16-1.68) for those of 18-20 years (P for trend=0.045). A similar pattern was observed for hemorrhagic stroke, ischemic stroke, and total cardiovascular disease. No such association was found for coronary heart disease. When stratified by age, for women aged 40-59 at baseline, the similar U-shaped association was observed. In contrast, for women aged 60-79 years at baseline, a significantly high hazard ratio was noted in the group of late age at menarche, but not in the group of early age at menarche. CONCLUSIONS: Both women with early and late age at menarche were determined to have higher risk of death from stroke and cardiovascular disease.

Smoking Cessation and Mortality from Aortic Dissection and Aneurysm: Findings from the Japan Collaborative Cohort (JACC) Study.

AIMS: Active cigarette smoking was intensively reported to increase the risk of aortic mortality while research on the association between smoking cessation and aortic mortality remains scarce. This study aimed to reconfirm the associations of exposure to cigarettes and smoking cessation associated with aortic mortality in a large Japanese population. METHODS: In the Japan Collaborative Cohort (JACC) Study, 91,141 residents (57±10 years; men, 43%) who were free of stroke, coronary heart disease, and cancer were followed up from 1989-90 until 2009 during which 110 deaths from aortic dissection and 112 deaths from aneurysm were identified. Cox proportional hazard model was used to estimate multivariable hazard ratios (95%CI) for total and specific aortic mortality. RESULTS: Compared to never smoking, HRs for total aortic mortality were 2.39 (1.40-4.08) for ＜20, 3.57 (2.19-5.83) for 20-39, and 3.92 (2.37-6.48) for ≥ 40 pack-years exposure. Compared to current smoking, HRs for total aortic mortality were 0.42 (0.18-0.97) for 10-15 years, 0.27 (0.11-0.66) for ＞15 years of cessation, and 0.24 (0.13-0.44) for never smoking. Similar inverse dose-response pattern was observed between smoking cessation duration and risk of mortality from aortic aneurysm (p for trend=0.001), but the association with aortic dissection mortality did not reach statistical significance. CONCLUSIONS: Cigarette smoking was associated with an increased risk of aortic mortality while smoking cessation was so with a reduced risk among the Japanese population.

Risk factors for pre-heart failure or symptomatic heart failure based on NT-proBNP.

AIMS: Evidence on the risk factors for incident heart failure in Asia has been limited. We sought to identify the risk factors for pre-heart failure or symptomatic heart failure, based on N-terminal pro-B-type natriuretic peptide (NT-proBNP), in the Japanese general population. METHODS: We performed a retrospective cohort study based on the Circulatory Risk in Communities Study involving 5335 Japanese individuals whose NT-proBNP levels were measured between 2010 and 2015. Of these, 2768 people aged between 30 and 69 years who undertook annual cardiovascular risk surveys at least once between 1990 and 2000 were retrospectively eligible to be participants in this study. We performed multivariable logistic regression analyses to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) of pre-heart failure or symptomatic heart failure defined as NT-proBNP >400 pg/mL or as having a diagnosis of heart failure and taking medication for heart failure for several cardiovascular risk factors (body mass index, blood pressure, diabetes mellitus, total cholesterol, triglyceride, smoking status, drinking status). RESULTS: We identified 85 cases of heart failure. The multivariable ORs (95% CIs) were 5.70 (2.70-12.0) for body mass index of 27-29.9 kg/m2 and 5.91 (2.19-16.0) for ≥30 kg/m2 compared with 21-22.9 kg/m2 ; 2.49(1.01-6.13) for systolic blood pressure of ≥160 mmHg vs. <130 mmHg; 2.87(1.23-6.68) for diastolic blood pressure of ≥100 mmHg vs. <80 mmHg; 5.16(2.14-12.4) for diabetes vs. non-diabetes; and 2.24 (0.92-5.49) for current smokers of ≥20 cigarettes/day vs. never smokers. The multivariable ORs (95% CIs) of the number of risk factors, defined as the sum of four risk factors (obesity, hypertension, diabetes, and current smoker) was 6.80 (3.69-12.5) for ≥2 risk factors vs. no risk factors. CONCLUSIONS: The accumulation of these risk factors was associated with a graded higher risk of pre-heart failure or symptomatic heart failure.

The association of smoking cessation with mortality from pneumonia among middle-aged and elderly community residents: The Japan Collaborative Cohort (JACC) study.

Several studies have shown that smoking is a significant risk factor for pneumonia, but it is uncertain to what extent smoking cessation reduces the risk. This study aimed to investigate whether and to what extent smoking cessation is associated with reduced risk of mortality from pneumonia in a Japanese, prospective, community-based cohort. We examined 94,972 individuals (mean age, 57 years; women, 57%) who provided valid responses to a lifestyle questionnaire including questions about smoking. We used years of smoking cessation at baseline to divide former smokers into 5 groups: 0-1 year, 2-4 years, 5-9 years, 10-14 years, and 15 years or more. The endpoint was the underlying cause of death from pneumonia. During the median 19-year follow-up of 94,972 study participants, 1806 died from pneumonia. Multivariable hazard ratios (95% confidence intervals) compared with the current smokers were 1.02 (0.72-1.45) for 0-1 year of smoking cessation at baseline, 0.92 (0.70-1.22) for 2-4 years, 0.95 (0.74-1.21) for 5-9 years, 0.71 (0.53-0.96) for 10-14 years, 0.63 (0.48-0.83) for 15 years or more, and 0.50 (0.36-0.70) for never-smokers. Although smoking increases the risk of pneumonia mortality, the present study showed that the risk of pneumonia mortality decreased with years of smoking cessation, eventually improving to levels similar to those of non-smokers for 10 years or more. Continued smoking cessation may be effective in preventing pneumonia deaths.

Apolipoprotein A2 Isoforms in Relation to the Risk of Myocardial Infarction: A Nested Case-Control Analysis in the JPHC Study.

AIM: The fact that low concentrations of high-density lipoprotein cholesterol are associated with the risk of cardiovascular disease is well known, but high-density lipoprotein metabolism has not been fully understood. Apolipoprotein A2 (ApoA2) is the second-most dominant apolipoprotein of high-density lipoprotein. We tested the hypothesis that ApoA2 isoforms are inversely associated with myocardial infarction. METHODS: We measured the plasma levels of three ApoA2 isoforms (ApoA2-ATQ/ATQ, ApoA2-ATQ/AT, ApoA2-AT/AT) in nested case-control study samples of 1:2 from the Japan Public Health-Center-based Study (JPHC Study): 106 myocardial infarction incidence cases and 212 controls. RESULTS: ApoA2-AT/AT was inversely associated with risk of myocardial infarction, in a matched model (OR, 2.78; 95% CI, 1.26-6.09 for lowest compared with the highest quartile), but its association was attenuated after adjustment for smoking only (OR=2.13; 95% CI, 0.91-4.97) or drinking only (OR=2.11; 0.91-4.89), and the multivariable OR was 1.20 (95% CI, 0.41-3.57). Neither ApoA2-ATQ/ATQ nor ApoA2-ATQ/AT was associated with the risk of myocardial infarction. CONCLUSIONS: Our nested case-control study did not show a significant association of ApoA2 isoforms with a risk of myocardial infarction.

Epidemiology of antibiotic treatment for uncomplicated cystitis in adults in Japan.

INTRODUCTION: A large number of antibiotics are used for the treatment of uncomplicated cystitis owing to its high morbidity. As the administration of antibiotics for uncomplicated cystitis may be considered an example of inappropriate use, outpatient antimicrobial stewardship for this condition is important. We evaluated the current pharmacoepidemiology trends for the treatment of uncomplicated cystitis in Japan to predict stewardship strategies. METHODS: This descriptive observational study analyzed data from an anonymized claims database of employees and their family members covered by the employer's health insurance. We identified female outpatients diagnosed with acute cystitis (ICD-10 code N300) aged ≥15 years and extracted oral antibiotic prescription records between 2013 and 2016. We excluded prescriptions for >7 days. RESULTS: The most prescribed antibiotic category was fluoroquinolones (52.67%), followed by cephalosporins and penems (40.63%). Third-generation cephalosporins accounted for 90.91% of cephalosporin and penem prescriptions. The most common duration of antibiotic prescription was 5 days, except for first-generation cephalosporins, penem (7 days) and sulfamethoxazole and trimethoprim (3 days). CONCLUSION: Fluoroquinolones and third-generation cephalosporins were prescribed to most uncomplicated cystitis cases in Japan. Although the lack of alternatives to quinolones and beta-lactams in Japan is an obstacle for antimicrobial stewardship for uncomplicated cystitis, promoting accurate diagnoses and establishing alternatives available in the Japanese market are important. Shortening the treatment duration is also an important strategy. Further research is needed on local antimicrobial resistance patterns to determine a fixed treatment strategy for uncomplicated cystitis.

Passive smoking and mortality from aortic dissection or aneurysm.

BACKGROUND AND AIMS: Evidence on the association between passive smoking and risk of aortic dissection or aneurysm is limited. This study aimed to investigate whether passive smoking increases risk of mortality from aortic dissection or aneurysm. METHODS: The Japan Collaborative Cohort (JACC) Study is a prospective community-based cohort study begun in 1988-90 and followed up to the end of 2009. We examined 48,677 individuals (mean age, 56 years; women, 46%) without history of stroke, coronary heart disease, or cancer, who provided valid responses to a lifestyle questionnaire including questions on active and passive smoking. We used 3 categories (passive smoking out of home, passive smoking at home, and passive smoking out of or at home combined) to divide never-smokers into 3 exposure groups: low, intermediate, and high exposures, respectively. The endpoint was underlying cause of death from aortic dissection or aneurysm. RESULTS: During the median 19-year follow-up of 48,677 study participants, 66 died of aortic dissection, and 75 of aortic aneurysm. Multivariable hazard ratios (95% confidence intervals) for the high passive-smoking group as compared with the low passive-smoking group were 2.45 (1.02-5.88) out of home, 1.82 (0.84-3.96) at home, and 2.35 (1.09-5.09) out of or at home combined. The corresponding hazard ratios for current smokers as compared with the low passive-smoking group were 3.97 (2.14-7.39), 3.41 (1.84-6.32) and 4.09 (1.99-8.39), respectively. CONCLUSIONS: Out-of-home passive smoking and out-of- or at-home combined passive smoking were associated with increased mortality from aortic dissection or aneurysm.