Hiroshi Yatsuya

Association of coffee consumption with serum adiponectin, leptin, inflammation and metabolic markers in Japanese workers: a cross-sectional study

Background:Mechanisms underlying coffees beneficial actions against cardiovascular disease and glucose metabolism are not well understood. Little information is available regarding association between coffee consumption and adipocytokines.Objective:We investigated potential associations between coffee consumption and adiponectin, leptin, markers for subclinical inflammation, glucose metabolism, lipids and liver enzymes. We then investigated whether adipocytokines played a role in the association between coffee consumption and these markers.Design and subjects:This is a cross-sectional study comprising 2554 male and 763 female Japanese workers. Potential relations between coffee consumption and adipocytokines or other markers were evaluated using a multiple linear regression model adjusted for confounding factors. We evaluated whether adiponectin and leptin partly explain the associations between coffee consumption and each marker by multiple mediation analysis.Results:Coffee consumption showed significant positive associations with adiponectin and total and low-density lipoprotein cholesterol, and inverse associations with leptin, high sensitivity C-reactive protein (hs-CRP), triglycerides and liver enzymes (all P<0.05). An adjustment for adiponectin and leptin significantly attenuated the associations between coffee consumption and hs-CRP or triglycerides, but not for liver enzymes. No associations were observed between coffee consumption and glucose metabolism-related markers.Conclusion:Coffee consumption was associated with high adiponectin and low leptin levels. We speculated that adipocytokines mainly explain the associations of coffee consumption with lipids and hs-CRP. Factors other than adipocytokines may explain the association between coffee consumption and liver function.

Neoadjuvant Oxaliplatin and Capecitabine and Bevacizumab without Radiotherapy for Poor-risk Rectal Cancer: N-SOG 03 Phase II Trial

OBJECTIVEnThis Phase II trial was designed to evaluate the safety and efficacy of neoadjuvant oxaliplatin and capecitabine and bevacizumab without radiotherapy in patients with poor-risk rectal cancer.nnnMETHODSnPatients with magnetic resonance imaging-defined poor-risk rectal cancer received neoadjuvant oxaliplatin and capecitabine and bevacizumab followed by total mesorectal excision or more extensive surgery.nnnRESULTSnBetween February 2010 and December 2011, 32 patients were enrolled in this study. The completion rate of the scheduled chemotherapy was 91%. Reasons for withdrawal were refusal to continue therapy in two patients and disease progression in one, with two of these three patients not undergoing surgery. Among the 29 patients who completed the scheduled chemotherapy, one refused surgery within 8 weeks after the completion of chemotherapy, which was the period stipulated by the protocol, and another had rectal perforation, requiring urgent laparotomy. As a result, the completion rate of this experimental treatment was 84%. Of the 30 patients who underwent surgery, the R0 resection rate was 90% and a postoperative complication occurred in 43%. A pathological complete response was observed in 13% and good tumor regression was exhibited in 37%.nnnCONCLUSIONSnNeoadjuvant oxaliplatin and capecitabine plus bevacizumab for poor-risk rectal cancer caused a high rate of anastomotic leakage and experienced a case with perforation during chemotherapy, both of which were bevacizumab-related toxicity. Although the short-term results with the completion rate of 84.4% and the pathological complete response rate of 13.3% were satisfactory, we have to reconsider the necessity of bevacizumab in neoadjuvant chemotherapy (UMIN number, 000003507).

Differences by sex in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa: a systematic review and meta-analysis

OBJECTIVEnTo assess differences between men and women in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa.nnnMETHODSnIn September 2011, the PubMed and Web of Science databases were searched for community-based, cross-sectional studies providing sex-specific prevalences of any of the three study conditions among adults living in parts of sub-Saharan Africa (i.e. in Eastern, Middle and Southern Africa according to the United Nations subregional classification for African countries). A random-effects model was then used to calculate and compare the odds of men and women having each condition.nnnFINDINGSnIn a meta-analysis of the 36 relevant, cross-sectional data sets that were identified, impaired fasting glycaemia was found to be more common in men than in women (OR: 1.56; 95% confidence interval, CI: 1.20-2.03), whereas impaired glucose tolerance was found to be less common in men than in women (OR: 0.84; 95% CI: 0.72-0.98). The prevalence of diabetes mellitus - which was generally similar in both sexes (OR: 1.01; 95% CI: 0.91-1.11) - was higher among the women in Southern Africa than among the men from the same subregion and lower among the women from Eastern and Middle Africa and from low-income countries of sub-Saharan Africa than among the corresponding men.nnnCONCLUSIONnCompared with women in the same subregions, men in Eastern, Middle and Southern Africa were found to have a similar overall prevalence of diabetes mellitus but were more likely to have impaired fasting glycaemia and less likely to have impaired glucose tolerance.

Dietary intake of saturated fatty acids and incident stroke and coronary heart disease in Japanese communities: the JPHC Study

Aims Although dietary saturated fatty acids (SFA) are considered atherogenic, associations between SFAs intake and stroke and coronary heart disease are still debated. We sought to test the hypothesis that SFA intake is associated inversely with risk of stroke and its subtypes and positively with coronary heart disease among Japanese, whose average SFA intake is lower than that of Westerners. Methods and results The Japan Public Health Center-based prospective Study involves two subcohorts: Cohort I, aged 45-64 in 1995 and followed-up through 2009, and Cohort II, aged 45-74 in 1998 and followed-up through 2007. A total of 38 084 men and 43 847 women were included in this report. Hazards ratios for incident total stroke, ischaemic stroke, intraparhenchymal haemorrhage, subarachnoid haemorrhage, myocardial infarction, and sudden cardiac death across quintiles of dietary SFAs were examined. We found inverse associations between SFA intake and total stroke [multivariable hazard ratio (95% confidence interval) for the highest vs. lowest quintiles = 0.77 (0.65-0.93), trend P = 0.002], intraparenchymal haemorrhage [0.61 (0.43-0.86), P for trend = 0.005], and ischaemic stroke [0.84 (0.67-1.06), trend P = 0.08], primarily for deep intraparenchymal haemorrhage [0.67 (0.45-0.99), P for trend = 0.04] and lacunar infarction [0.75 (0.53, 1.07), trend P = 0.02]. We also observed a positive association between SFAs intake and myocardial infarction [1.39 (0.93-2.08), trend P = 0.046] primarily among men. No associations were observed between SFAs intake and incidence of subarachnoid haemorrhage or sudden cardiac death. Conclusions In this Japanese population, SFAs intake was inversely associated with deep intraparenchymal haemorrhage and lacunar infarction and positively associated with myocardial infarction.

Association of Kidney Disease Measures With Ischemic Versus Hemorrhagic Strokes Pooled Analyses of 4 Prospective Community-Based Cohorts

Background and purpose— Although low glomerular filtration rate (GFR) and albuminuria are associated with increased risk of stroke, few studies compared their contribution to risk of ischemic versus hemorrhagic stroke separately. We contrasted the association of these kidney measures with ischemic versus hemorrhagic stroke. Methods— We pooled individual participant data from 4 community-based cohorts: 3 from the United States and 1 from The Netherlands. GFR was estimated using both creatinine and cystatin C, and albuminuria was quantified by urinary albumin-to-creatinine ratio (ACR). Associations of estimated GFR and ACR were compared for each stroke type (ischemic versus intraparenchymal hemorrhagic) using study-stratified Cox regression. Results— Among 29 595 participants (mean age, 61 [SD 12.5] years; 46% men; 17% black), 1261 developed stroke (12% hemorrhagic) during 280 549 person-years. Low estimated GFR was significantly associated with increased risk of ischemic stroke, but not hemorrhagic stroke, whereas high ACR was associated with both stroke types. Adjusted hazard ratios for ischemic and hemorrhagic stroke at estimated GFR of 45 (versus 95) mL/min per 1.73 m2 were 1.30 (95% confidence interval, 1.01–1.68) and 0.92 (0.47–1.81), respectively. In contrast, the corresponding hazard ratios for ACR of 300 (versus 5) mg/g were 1.62 (1.27–2.07) for ischemic and 2.57 (1.37–4.83) for hemorrhagic stroke, with significantly stronger association with hemorrhagic stroke (P=0.04). For hemorrhagic stroke, the association of elevated ACR was of similar magnitude as that of elevated systolic blood pressure. Conclusions— Whereas albuminuria showed significant association with both stroke types, the association of decreased estimated GFR was only significant for ischemic stroke. The strong association of albuminuria with both stroke types warrants clinical attention and further investigations.

Association between Physical Activity and Risk of Stroke Subtypes: The Atherosclerosis Risk in Communities Study

Background: The relationship between stroke subtypes and physical activity is unclear. Methods: Using data from 13,069 men and women aged 45–64 years who participated in the Atherosclerosis Risk in Communities Study, physical activity was assessed by self-report using the Baecke questionnaire at baseline (1987–1989). The American Heart Association’s ideal cardiovascular health guidelines served as a basis for the calculation of three physical activity categories: poor, intermediate, and ideal. Stroke and its subtypes were ascertained from physician review of medical records. Multivariable adjusted hazard ratios (HR) and 95% confidence intervals (CI) were calculated using Cox regression models. Results: During a median follow-up of 18.8 years, a total of 648 incident ischemic strokes occurred. Significant inverse associations were found between physical activity categories and total, total ischemic, and nonlacunar stroke in adjusted models (age, sex, race-center, education, cigarette-years). Compared with poor physical activity, the adjusted HR (95% CI) for ideal physical activity were 0.78 (0.62–0.97) for total, 0.76 (0.59–0.96) for total ischemic, 0.85 (0.51–1.40) for lacunar, 0.77 (0.47–1.27) for cardioembolic, and 0.71 (0.51–0.99) for nonlacunar stroke. Additional adjustments for waist-to-hip ratio, systolic blood pressure, antihypertensive medication, diabetes, left ventricular hypertrophy and laboratory parameters attenuated the HR. Further sex- and race-specific analyses revealed that the association was predominantly observed among males and among African-Americans. Conclusion: These data suggest a tendency toward a reduced risk of total, total ischemic, and nonlacunar stroke with higher levels of physical activity.

Alcohol consumption and risk of stroke and coronary heart disease among Japanese women: the Japan Public Health Center-based prospective study.

OBJECTIVEnThe study aims to examine the association between a wide range of alcohol consumption and risk of stroke and coronary heart disease.nnnMETHODSnThe Japan Public Health Center-based prospective study was initiated in 1990 in Cohort I and in 1993 in Cohort II, with follow-up until 2009. The sample consisted of 47,100 women aged 40-69 years.nnnRESULTSnDuring an average of 16.7-years, the incidence of 1846 strokes and 292 coronary heart diseases was observed. Heavy drinking (≥ 300 gethanol/week) was associated with increased risk of total stroke. The multivariable hazard ratios for heavy versus occasional drinkers were 2.19 (95% confidence interval: 1.45-3.30) for total stroke, 2.25 (1.29-3.91) for hemorrhagic stroke, 2.24 (1.05-4.76) for intraparenchymal hemorrhage, 2.26 (1.01-5.09) for subarachnoid hemorrhage and 2.04 (1.09-3.82) for ischemic stroke. In the exposure-updated analysis, the positive association between heavy drinking and risks of total stroke, hemorrhagic stroke and intraparenchymal hemorrhage became more evident. Light drinking (<150 gethanol/week) was not associated with risk of ischemic stroke. There was also no association between alcohol consumption and risk of coronary heart disease.nnnCONCLUSIONnHeavy drinking was associated with increased risk of hemorrhagic and ischemic strokes among Japanese women.

Risk of cardiovascular disease from cumulative cigarette use and the impact of smoking intensity

Background: Relative risks (RRs) for cardiovascular disease (CVD) by smoking rate exhibit a concave pattern, with RRs in low rate smokers exceeding a linear extrapolation from higher rate smokers. However, cigarettes/day does not by itself fully characterize smoking-related risks. A reexamination of the concave pattern using a comprehensive representation of smoking may enhance insights. Methods: Data were from the Atherosclerosis Risk in Communities (ARIC) Study, a prospective cohort enrolled in four areas of the US in 1987–1989. Follow-up was through 2008. Analyses included 14,233 participants, 245,915 person-years, and 3,411 CVD events. Results: The concave RRs with cigarettes/day were consistent with cigarettes/day modifying a linear RR association of pack-years with CVD (i.e., strength of the pack-years association depended on cigarettes/day, indicating that the manner of pack-years accrual impacted risk). Smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration (P < 0.01). For 50 pack-years (365,000 cigarettes), estimated RRs of CVD were 2.1 for accrual at 20 cigarettes/day and 1.6 for accrual at 50 cigarettes/day. Years since smoking cessation did not alter the diminishing strength of association with increasing cigarettes/day. Analyses that accounted for competing risks did not affect findings. Conclusion: Pack-years remained the primary determinant of smoking-related CVD risk; however, accrual influenced RRs. For equal pack-years, smoking fewer cigarettes/day for longer duration was more deleterious than smoking more cigarettes/day for shorter duration. This observation provides clues to better understanding the biological mechanisms, and reinforces the importance of cessation rather than smoking less to reduce CVD risk.

Breakfast Skipping is Positively Associated With Incidence of Type 2 Diabetes Mellitus: Evidence From the Aichi Workers’ Cohort Study

BACKGROUNDnSkipping breakfast has been suspected as a risk factor for type 2 diabetes (T2DM), but the associations are not entirely consistent across ethnicities or sexes, and the issue has not been adequately addressed in the Japanese population.nnnMETHODSnWe followed 4631 participants (3600 men and 1031 women) in a work-site cohort of participants aged 35-66 years in 2002 through 2011 for T2DM development. Frequency of eating breakfast was self-reported and was subsequently dichotomized to breakfast skippers, who eat breakfast 3-5 times/week or less, and to eaters. Cox proportional hazards models were used to adjust for potential confounding factors, including dietary factors, smoking and other lifestyles, body mass index (BMI), and fasting blood glucose (FBG) at baseline.nnnRESULTSnDuring 8.9 years of follow-up, 285 T2DM cases (231 men and 54 women) developed. Compared to participants who reported eating breakfast every day, maximally-adjusted hazard ratios and 95% confidence intervals (CI) of those with the frequency of almost every day and 3-5, 1-2, and 0 days/week were: 1.06 (95% CI, 0.73-1.53), 2.07 (95% CI, 1.20-3.56), 1.37 (95% CI, 0.82-2.29), and 2.12 (95% CI, 1.19-3.76), respectively. In a dichotomized analysis, breakfast skipping was positively associated with T2DM incidence (maximally-adjusted hazard ratio 1.73; 95% CI, 1.24-2.42). The positive associations were found in both men and women, current and non-current smokers, normal weight and overweight (BMI ≥ 25 kg/m(2)), and normal glycemic status and impaired fasting glycemic status (FBG 110 to <126 mg/dL) individuals at baseline (Ps for interaction all >0.05).nnnCONCLUSIONSnThe present study in middle-aged Japanese men and women suggests that skipping breakfast may increase the risk of T2DM independent of lifestyles and baseline levels of BMI and FBG.Background Skipping breakfast has been suspected as a risk factor for type 2 diabetes (T2DM), but the associations are not entirely consistent across ethnicities or sexes, and the issue has not been adequately addressed in the Japanese population. Methods We followed 4631 participants (3600 men and 1031 women) in a work-site cohort of participants aged 35–66 years in 2002 through 2011 for T2DM development. Frequency of eating breakfast was self-reported and was subsequently dichotomized to breakfast skippers, who eat breakfast 3–5 times/week or less, and to eaters. Cox proportional hazards models were used to adjust for potential confounding factors, including dietary factors, smoking and other lifestyles, body mass index (BMI), and fasting blood glucose (FBG) at baseline. Results During 8.9 years of follow-up, 285 T2DM cases (231 men and 54 women) developed. Compared to participants who reported eating breakfast every day, maximally-adjusted hazard ratios and 95% confidence intervals (CI) of those with the frequency of almost every day and 3–5, 1–2, and 0 days/week were: 1.06 (95% CI, 0.73–1.53), 2.07 (95% CI, 1.20–3.56), 1.37 (95% CI, 0.82–2.29), and 2.12 (95% CI, 1.19–3.76), respectively. In a dichotomized analysis, breakfast skipping was positively associated with T2DM incidence (maximally-adjusted hazard ratio 1.73; 95% CI, 1.24–2.42). The positive associations were found in both men and women, current and non-current smokers, normal weight and overweight (BMI ≥25 kg/m2), and normal glycemic status and impaired fasting glycemic status (FBG 110 to <126 mg/dL) individuals at baseline (Ps for interaction all >0.05). Conclusions The present study in middle-aged Japanese men and women suggests that skipping breakfast may increase the risk of T2DM independent of lifestyles and baseline levels of BMI and FBG.

Adiposity and risk of cardiovascular diseases in Japan: secular trend, individual level associations and causal pathway - implications for the prevention of cardiovascular diseases in societies with rapid economic development.

In Japan, overweight/obesity in adults defined as a body mass index of 25xa0kg/m2 or over has roughly doubled among middle-aged men over the past few decades. In parallel with a population rightward shift in the degree of obesity, the proportion of hypertension attributed to overweight has increased. There is an indication that the incidence of ischemic stroke and coronary heart disease remains stable or has been increasing among men. These facts indicate that the relative importance of cardiovascular diseases (CVD) risk factors may have changed. Although it was confirmed at an individual level that the degree of obesity was positively associated with CVD incidence, there is a sizeable proportion of individuals who are at an increased CVD risk state without being overweight/obese in today’s Japan. Thus, further implementation and promotion of activities are needed to bring about meaningful changes in the obesity trend in communities that are harmonized with other domains of CVD prevention activities.