Toshimi Sairenchi

Association between Body-Mass Index and Risk of Death in More Than 1 Million Asians

BACKGROUND Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin. METHODS We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors. RESULTS In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI. CONCLUSIONS Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.

Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes : a meta-analysis

BACKGROUND Chronic kidney disease is characterised by low estimated glomerular filtration rate (eGFR) and high albuminuria, and is associated with adverse outcomes. Whether these risks are modified by diabetes is unknown. METHODS We did a meta-analysis of studies selected according to Chronic Kidney Disease Prognosis Consortium criteria. Data transfer and analyses were done between March, 2011, and June, 2012. We used Cox proportional hazards models to estimate the hazard ratios (HR) of mortality and end-stage renal disease (ESRD) associated with eGFR and albuminuria in individuals with and without diabetes. FINDINGS We analysed data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts. In the combined general population and high-risk cohorts with data for all-cause mortality, 75,306 deaths occurred during a mean follow-up of 8·5 years (SD 5·0). In the 23 studies with data for cardiovascular mortality, 21,237 deaths occurred from cardiovascular disease during a mean follow-up of 9·2 years (SD 4·9). In the general and high-risk cohorts, mortality risks were 1·2-1·9 times higher for participants with diabetes than for those without diabetes across the ranges of eGFR and albumin-to-creatinine ratio (ACR). With fixed eGFR and ACR reference points in the diabetes and no diabetes groups, HR of mortality outcomes according to lower eGFR and higher ACR were much the same in participants with and without diabetes (eg, for all-cause mortality at eGFR 45 mL/min per 1·73 m(2) [vs 95 mL/min per 1·73 m(2)], HR 1·35; 95% CI 1·18-1·55; vs 1·33; 1·19-1·48 and at ACR 30 mg/g [vs 5 mg/g], 1·50; 1·35-1·65 vs 1·52; 1·38-1·67). The overall interactions were not significant. We identified much the same findings for ESRD in the chronic kidney disease cohorts. INTERPRETATION Despite higher risks for mortality and ESRD in diabetes, the relative risks of these outcomes by eGFR and ACR are much the same irrespective of the presence or absence of diabetes, emphasising the importance of kidney disease as a predictor of clinical outcomes. FUNDING US National Kidney Foundation.

Estimated glomerular filtration rate and albuminuria for prediction of cardiovascular outcomes: a collaborative meta-analysis of individual participant data

Background The utility of estimated glomerular filtration rate (eGFR) and albuminuria for cardiovascular prediction is controversial. Methods We meta-analyzed individual-level data from 24 cohorts (with a median follow-up time longer than 4 years, varying from 4.2 to 19.0 years) in the Chronic Kidney Disease Prognosis Consortium (637,315 participants without a history of cardiovascular disease) and assessed C-statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in 5-year timeframe, contrasting prediction models consisting of traditional risk factors with and without creatinine-based eGFR and/or albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria). Findings The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR and more evident for cardiovascular mortality (c-statistic difference 0.0139 [95%CI 0.0105–0.0174] and 0.0065 [0.0042–0.0088], respectively) and heart failure (0.0196 [0.0108–0.0284] and 0.0109 [0.0059–0.0159]) than for coronary disease (0.0048 [0.0029–0.0067] and 0.0036 [0.0019–0.0054]) and stroke (0.0105 [0.0058–0.0151] and 0.0036 [0.0004–0.0069]). Dipstick proteinuria demonstrated smaller improvement than ACR. The discrimination improvement with kidney measures was especially evident in individuals with diabetes or hypertension but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these conditions. In participants with chronic kidney disease (CKD), the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the c-statistic for cardiovascular mortality declined by 0.023 [0.016–0.030] vs. <0.007 when omitting eGFR and ACR vs. any single modifiable traditional predictors, respectively. Interpretation Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when they are already assessed for clinical purpose and/or cardiovascular mortality and heart failure are the outcomes of interest (e.g., the European guidelines on cardiovascular prevention). ACR may have particularly broad implications for cardiovascular prediction. In CKD populations, the simultaneous assessment of eGFR and ACR will facilitate improved cardiovascular risk classification, supporting current CKD guidelines. Funding US National Kidney Foundation and NIDDKBACKGROUND The usefulness of estimated glomerular filtration rate (eGFR) and albuminuria for prediction of cardiovascular outcomes is controversial. We aimed to assess the addition of creatinine-based eGFR and albuminuria to traditional risk factors for prediction of cardiovascular risk with a meta-analytic approach. METHODS We meta-analysed individual-level data for 637 315 individuals without a history of cardiovascular disease from 24 cohorts (median follow-up 4·2-19·0 years) included in the Chronic Kidney Disease Prognosis Consortium. We assessed C statistic difference and reclassification improvement for cardiovascular mortality and fatal and non-fatal cases of coronary heart disease, stroke, and heart failure in a 5 year timeframe, contrasting prediction models for traditional risk factors with and without creatinine-based eGFR, albuminuria (either albumin-to-creatinine ratio [ACR] or semi-quantitative dipstick proteinuria), or both. FINDINGS The addition of eGFR and ACR significantly improved the discrimination of cardiovascular outcomes beyond traditional risk factors in general populations, but the improvement was greater with ACR than with eGFR, and more evident for cardiovascular mortality (C statistic difference 0·0139 [95% CI 0·0105-0·0174] for ACR and 0·0065 [0·0042-0·0088] for eGFR) and heart failure (0·0196 [0·0108-0·0284] and 0·0109 [0·0059-0·0159]) than for coronary disease (0·0048 [0·0029-0·0067] and 0·0036 [0·0019-0·0054]) and stroke (0·0105 [0·0058-0·0151] and 0·0036 [0·0004-0·0069]). Dipstick proteinuria showed smaller improvement than ACR. The discrimination improvement with eGFR or ACR was especially evident in individuals with diabetes or hypertension, but remained significant with ACR for cardiovascular mortality and heart failure in those without either of these disorders. In individuals with chronic kidney disease, the combination of eGFR and ACR for risk discrimination outperformed most single traditional predictors; the C statistic for cardiovascular mortality fell by 0·0227 (0·0158-0·0296) after omission of eGFR and ACR compared with less than 0·007 for any single modifiable traditional predictor. INTERPRETATION Creatinine-based eGFR and albuminuria should be taken into account for cardiovascular prediction, especially when these measures are already assessed for clinical purpose or if cardiovascular mortality and heart failure are outcomes of interest. ACR could have particularly broad implications for cardiovascular prediction. In populations with chronic kidney disease, the simultaneous assessment of eGFR and ACR could facilitate improved classification of cardiovascular risk, supporting current guidelines for chronic kidney disease. Our results lend some support to also incorporating eGFR and ACR into assessments of cardiovascular risk in the general population. FUNDING US National Kidney Foundation, National Institute of Diabetes and Digestive and Kidney Diseases.

Body Mass Index and Diabetes in Asia: A Cross-Sectional Pooled Analysis of 900,000 Individuals in the Asia Cohort Consortium

Background The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia. Methods and Findings A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5–24.9 Kg/m2 as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m2 to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m2. The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction<0.001), in cohorts from India and Bangladesh (p<0.001), in individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no differences were observed by gender, urban residence, or alcohol drinking. Conclusions This study estimated the shape and the strength of the association between BMI and prevalence of diabetes in Asian populations and identified patterns of the association by age, country, and other risk factors for diabetes.

Low-density lipoprotein cholesterol concentrations and death due to intraparenchymal hemorrhage: the Ibaraki Prefectural Health Study.

Background— Few studies have examined the association between low levels of low-density lipoprotein (LDL) cholesterol and risk of intraparenchymal hemorrhage. Methods and Results— A total of 30 802 men and 60 417 women, 40 to 79 years of age with no history of stroke or coronary heart disease, completed a baseline risk factor survey in 1993 under the auspices of the Ibaraki Prefectural Health Study. Systematic mortality surveillance was performed through 2003, and 264 intraparenchymal hemorrhage deaths were identified. LDL cholesterol levels were calculated with the Friedewald formula. Persons with LDL cholesterol ≥140 mg/dL had half the sex- and age-adjusted risk of death due to intraparenchymal hemorrhage of those with LDL cholesterol <80 mg/dL. After adjustment for cardiovascular risk factors, the multivariable hazard ratio compared with persons with LDL cholesterol <80 mg/dL was 0.65 (95% CI 0.44 to 0.96) for those with LDL cholesterol 80 to 99 mg/dL, 0.48 (0.32 to 0.71) for 100 to 119 mg/dL, 0.50 (0.33 to 0.75) for 120 to 139 mg/dL, and 0.45 (0.30 to 0.69) for ≥140 mg/dL. These inverse associations were not altered substantially after the exclusion of persons with hypertriglyceridemia, after analysis with a Cox proportional hazard model with time-dependent covariates, or in sensitivity analysis for the potential effect of competing risks. Conclusions— Low LDL cholesterol levels are associated with elevated risk of death due to intraparenchymal hemorrhage.

Underweight as a Predictor of Diabetes in Older Adults: A large cohort study

A total of 39,201 men and 88,012 women aged 40–79 years who underwent health checkups in 1993 and who were free of diabetes were followed until the end of 2004 to examine an association between underweight and risk of diabetes. Incident diabetes was defined by a fasting blood glucose concentration ≥7.0 mmol/l or nonfasting glucose ≥11.1 mmol/l and/or diabetes treatment. The multivariable hazard ratio of diabetes adjusted for age, baseline blood glucose level, fasting status, and other confounding variables among subjects who had a BMI <18.5 kg/m2 compared with those with a BMI 18.5–24.9 kg/m2 was 1.32 (95% CI 1.12–1.56) in men aged 60–79 years and 1.31 (1.07–1.60) in women aged 60–79 years. Underweight may be associated with risk of diabetes among older adults. In the present study, we enrolled 181,863 nondiabetic Japanese subjects (58,402 men and 123,461 women) from community residents aged 40–79 years who underwent health checkups in 1993 conducted by the local governments under the Japan Health Laws. We excluded 19,201 men and 35,449 women who did not participate in the 1994 survey, thereby ensuring that the subjects were followed up for at least 1 year. A total of 39,201 men and …

Adiposity Rebound and the Development of Metabolic Syndrome

OBJECTIVE: The age of adiposity rebound (AR) is defined as the time at which BMI starts to rise after infancy and is thought to be a marker of later obesity. To determine whether this age is related to future occurrence of metabolic syndrome, we investigated the relationship of the timing of AR with metabolic consequences at 12 years of age. METHODS: A total of 271 children (147 boys and 124 girls) born in 1995 and 1996 were enrolled in the study. Serial measurements of BMI were conducted at the ages of 4 and 8 months and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 years, based on which age of AR was calculated. Plasma lipids and blood pressure were measured at 12 years of age. RESULTS: An earlier AR (<4 years of age) was associated with a higher BMI (≥20) and a lipoprotein phenotype representative of insulin resistance. This phenotype consists of elevated triglycerides, apolipoprotein B, and atherogenic index and decreased high-density lipoprotein cholesterol in boys and elevated apolipoprotein B in girls at 12 years of age. The earlier AR was also related to elevated blood pressure in boys. CONCLUSIONS: This longitudinal population-based study indicates that children who exhibit AR at a younger age are predisposed to future development of metabolic syndrome. Therefore, monitoring of AR may be an effective method for the early identification of children at risk for metabolic syndrome.

Underweight as a predictor of diabetes mellitus in older adults: A large cohort study

A total of 39,201 men and 88,012 women aged 40–79 years who underwent health checkups in 1993 and who were free of diabetes were followed until the end of 2004 to examine an association between underweight and risk of diabetes. Incident diabetes was defined by a fasting blood glucose concentration ≥7.0 mmol/l or nonfasting glucose ≥11.1 mmol/l and/or diabetes treatment. The multivariable hazard ratio of diabetes adjusted for age, baseline blood glucose level, fasting status, and other confounding variables among subjects who had a BMI <18.5 kg/m2 compared with those with a BMI 18.5–24.9 kg/m2 was 1.32 (95% CI 1.12–1.56) in men aged 60–79 years and 1.31 (1.07–1.60) in women aged 60–79 years. Underweight may be associated with risk of diabetes among older adults. In the present study, we enrolled 181,863 nondiabetic Japanese subjects (58,402 men and 123,461 women) from community residents aged 40–79 years who underwent health checkups in 1993 conducted by the local governments under the Japan Health Laws. We excluded 19,201 men and 35,449 women who did not participate in the 1994 survey, thereby ensuring that the subjects were followed up for at least 1 year. A total of 39,201 men and …

Age-Specific Relationship between Blood Pressure and the Risk of Total and Cardiovascular Mortality in Japanese Men and Women

To examine the impact of age on the relationship between blood pressure (BP) levels and each of cardiovascular disease mortality and all-cause mortality, a total of 30,226 men and 58,798 women aged 40–79 years who had no history of stroke or heart disease underwent health checkups in Ibaraki-ken, Japan, in 1993 and were followed through 2002. Risk ratios for mortality by BP category based on the 1999 WHO-ISH guidelines were calculated by age subgroups (40–59 years, 60–79 years) using a Cox proportional hazards model. Compared with optimal BP levels, the multivariate risk ratios of cardiovascular mortality for stage 2 or 3 hypertension were 5.99 (95% confidence interval: 2.13–16.8) in middle-aged men and 4.09 (1.70–9.85) in middle-aged women. These excess cardiovascular mortality risks were larger in the 40–59 years age group than in the 60–79 years age group for both genders (p for interaction=0.01 for both). In men, the population attributable risk percents of cardiovascular mortality were 60% for younger men and 28% for older men, while for women they were 15% for younger women and 7% for older women. Weaker but significant excess risks of total mortality were observed for stage 2 or 3 hypertension in men of both age groups and in the older age group for women. The impact of BP on the risk of cardiovascular mortality was larger among middle-aged persons than among the elderly in both men and women. Our findings indicate the importance of BP control to prevent cardiovascular disease among middle-aged individuals.

Age-and Gender-specific BMI in Terms of the Lowest Mortality in Japanese General Population

Objective: The primary purposes of our study were to establish age‐ and gender‐specific BMIs in terms of lowest mortality (risk nadir BMIs) for the Japanese population, and to then compare those to (i) BMIs for whites as determined by similar studies and to (ii) the official BMI guidelines.