Woon-Puay Koh

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

BACKGROUNDnMost 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.nnnMETHODSnWe 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnUnderweight 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.

Association between body mass index and cardiovascular disease mortality in east Asians and south Asians: pooled analysis of prospective data from the Asia Cohort Consortium

Objective To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design Pooled analyses of 20 prospective cohorts in Asia, including data from 835u2009082 east Asians and 289u2009815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants 1u2009124u2009897 men and women (mean age 53.4 years at baseline). Main outcome measures Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results 49u2009184 cardiovascular deaths (40u2009791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and <15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Conclusions Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Western-Style Fast Food Intake and Cardiometabolic Risk in an Eastern Country

Background— Western-style fast food contributes to a dietary pattern portending poor cardiometabolic health in the United States. With globalization, this way of eating is becoming more common in developing and recently developed populations. Methods and Results— We examined the association of Western-style fast food intake with risk of incident type 2 diabetes mellitus and coronary heart disease mortality in Chinese Singaporeans. This analysis included men and women 45 to 74 years of age who enrolled in the Singapore Chinese Health Study from 1993 to 1998. For CHD mortality, 52 584 participants were included and 1397 deaths were identified through December 31, 2009, via registry linkage. For type 2 diabetes mellitus, 43 176 participants were included and 2252 cases were identified during the follow-up interview (1999–2004) and validated. Hazard ratios for incident type 2 diabetes mellitus and coronary heart disease mortality were estimated with thorough adjustment for demographic, lifestyle, and dietary factors. Chinese Singaporeans with relatively frequent intake of Western-style fast food items (≥2 times per week) had an increased risk of developing type 2 diabetes mellitus (hazard ratio, 1.27; 95% confidence interval, 1.03–1.54) and dying of coronary heart disease (hazard ratio, 1.56; 95% confidence interval, 1.18–2.06) relative to their peers with little or no reported intake. These associations were not materially altered by adjustments for overall dietary pattern, energy intake, and body mass index. Conclusions— Western-style fast food intake is associated with increased risk of developing type 2 diabetes mellitus and of coronary heart disease mortality in an Eastern population. These findings suggest the need for further attention to global dietary acculturation in the context of ongoing epidemiological and nutrition transitions.

A vegetable-fruit-soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women

BACKGROUNDnProspective epidemiologic studies in Asian populations consistently show that soy is protective against breast cancer.nnnOBJECTIVEnThe objective was to prospectively evaluate whether the protective effect of soy is due to soy isoflavones alone or to their combination with other beneficial dietary factors in an Asian population.nnnDESIGNnUsing principal components analysis, we previously identified a meat-dim sum pattern characterized by meat, starch, and dim sum items and a vegetable-fruit-soy pattern characterized by cruciferous vegetables, fruit, and tofu items in a population-based cohort of Singapore Chinese initiated between 1993 and 1998. Component scores representing intakes of each pattern were used in multivariable Cox regression models to analyze the relation between diet at baseline and breast cancer incidence.nnnRESULTSnAs of 31 December 2005, 629 incident breast cancer cases had been diagnosed among the 34,028 women. With greater intake of the vegetable-fruit-soy dietary pattern, we observed a dose-dependent trend (P < 0.01) for decreasing breast cancer risk among postmenopausal women [hazard ratio (HR): 0.70; 95% CI: 0.51, 0.95 for the fourth compared with first quartile]. A stronger association for the vegetable-fruit-soy pattern was observed among postmenopausal women with > or =5 y of follow-up (HR: 0.57; 95% CI: 0.36, 0.88; P for trend <0.01). No trend was observed for a greater intake of the meat-dim sum dietary pattern and increased breast cancer risk.nnnCONCLUSIONnOur findings support the hypothesis that a diet characterized by vegetables, fruit, and soy has an early-acting protective effect on breast carcinogenesis.

Smoking as an independent risk factor for hepatocellular carcinoma: the Singapore Chinese Health Study

Background:Given the close correlation between smoking and alcohol intake in most epidemiologic studies, it is difficult to exclude the residual confounding effect of alcohol in the association between smoking and hepatocellular carcinoma (HCC).Method:We evaluated the association between smoking and risk of HCC in the Singapore Chinese Health Study, a prospective cohort with a low prevalence of alcohol intake. Information on cigarette smoking and alcohol consumption was obtained through in-person interviews conducted at enrolment.Results:After a mean of 11.5 years of follow-up, there were 394 incident cases of HCC. Participants who consumed more than two alcoholic drinks per day showed an increased risk for HCC (hazard ratio (HR)=2.24; 95% confidence interval (CI)=1.46–3.41). After adjusting for alcohol consumption and other potential confounders, current vs never smokers had a statistically significant, increased risk of HCC (HR=1.63; 95% CI=1.27–2.10) that was dose-dependent (number of cigarettes per day, P for trend<0.001). The observed tobacco–HCC association also was duration-dependent (years of smoking in ever smokers, P for trend=0.002). When we excluded daily drinkers from the analysis, all risk estimates remained essentially the same and statistically significant.Conclusion:Our findings strongly implicate tobacco smoke as a causal factor of HCC development.

A prospective study of tobacco and alcohol use as risk factors for pharyngeal carcinomas in Singapore Chinese

Nasopharyngeal carcinoma (NPC) is a rare disease in most populations; however, in areas of Southeast Asia and North Africa and in the Arctic, undifferentiated NPC is the most frequent pharyngeal malignancy. Although smoking and alcohol have been established firmly as synergistic risk factors for other pharyngeal carcinomas, previous studies on the association between these risk factors and NPC have not been consistent. Therefore, the authors analyzed this relation in a cohort of Singapore Chinese, which is a population with a high incidence of NPC.

Genetic and environmental predictors of serum 25-hydroxyvitamin D concentrations among middle-aged and elderly Chinese in Singapore

Vitamin D is known for maintaining Ca homeostasis and bone structure, and may also decrease susceptibility to chronic and infectious diseases. However, data on vitamin D status and its predictors among Southeast Asian populations are limited. We evaluated the distribution and determinants (genetic and environmental) of serum 25-hydroxyvitamin D (25(OH)D) concentrations among 504 middle-aged and elderly participants (aged 45-74 years) in the Singapore Chinese Health Study. Data on dietary and other lifestyle factors were collected by trained interviewers. Serum 25(OH)D concentrations and genetic polymorphisms in vitamin D metabolism pathway enzymes (cytochrome P450 (CYP) 2R1, 3A4, 27B1, 24A1; vitamin D binding protein (also known as group-specific component, GC); and vitamin D receptor) were measured using stored biospecimens. Mean 25(OH)D concentration was 68·8 nmol/l. Serum 25(OH)D concentrations were positively associated with dietary vitamin D intake, and inversely associated with hours spent sitting at work. BMI was not associated with 25(OH)D concentrations. CYP2R1 rs10741657, rs12794714, rs1993116; CYP3A4 rs2242480; and GC rs4588, rs7041, rs16847015, rs2298849 were statistically significantly associated with 25(OH)D concentrations. Individuals with the Gc2-2 haplotype (rs4588AA/rs7041TT) had statistically significantly lower 25(OH)D concentrations compared to all other Gc haplotypes (P-trend < 0·001). The majority of participants (86 %) had 25(OH)D concentrations ≥ 50 nmol/l, which is consistent with the 2011 Institute of Medicine (US) recommendation for bone health, and 32 % had concentrations of ≥ 75 nmol/l that are thought to be required for broader health effects. Dietary vitamin D intake, hours spent indoors at work and genetic variation in CYP2R1, CYP3A4 and GC are significant predictors of 25(OH)D concentrations among Singapore Chinese.

Age at Menarche and Cardiovascular Disease Mortality in Singaporean Chinese Women: The Singapore Chinese Health Study

PURPOSEnTo examine whether age at menarche was inversely associated with cardiovascular disease (CVD) mortality in Singaporean Chinese women.nnnMETHODSnWe followed prospectively 34,022 Chinese women aged 45 to 74 at enrollment (1993-1998), with complete data on study variables, through 2009 for primary cause of death from CVD, including coronary heart disease (CHD) and cerebrovascular disease (CERE). Hazard ratios (HRs) for CVD mortality were computed across menarcheal age categories and adjusted for potential confounders and body mass index.nnnRESULTSnOver 460,374 person-years of follow-up, 1852 women died from CVD, 998 from CHD and 557 from CERE. There was a significant interaction between age at menarche and smoking (P < .05). In nonsmokers, age at menarche was inversely associated with risk for CVD and CHD mortality. HRs (and 95% confidence interval) for CVD mortality across menarcheal age categories (≤ 12, 13-14, 15-16, ≥ 17) were 1.06 (0.87-1.29), 1 (referent), 0.89 (0.79-1.00), and 0.80 (0.69-0.93), respectively (P(trend) < .001); HRs for CHD mortality were 1.06 (0.80-1.34), 1 (referent), 0.76 (0.65-0.90), and 0.72 (0.58-0.88), respectively (P(trend) < .001). Among nonsmokers, there was no association between age at menarche and CERE mortality. Among smokers, menarcheal age was not associated with CVD, CHD or CERE mortality.nnnCONCLUSIONSnMenarcheal age was inversely associated with risk of CVD mortality in nonsmoking Chinese women.

Mortality due to coronary heart disease and kidney disease among middle-aged and elderly men and women with gout in the Singapore Chinese Health Study

Objectives Whether the link between gout and mortality is causal or confounded by lifestyle factors or comorbidities remains unclear. Studies in Asia are warranted due to the rapid modernisation of the locale and ageing of the population. Methods The association between gout and mortality was examined in a prospective cohort, the Singapore Chinese Health Study, comprising 63 257 Singapore Chinese individuals, aged 45–74 years during the enrolment period of 1993–8. All enrollees were interviewed in person on lifestyle factors, current diet and medical histories. All surviving cohort members were contacted by telephone during 1999–2004 to update selected exposure and medical histories (follow-up I interview), including the history of physician-diagnosed gout. Cause-specific mortality in the cohort was identified via record linkage with the nationwide death registry, up to 31 December 2009. Results Out of 52 322 participants in the follow-up I interview, 2117 (4.1%) self-reported a history of physician-diagnosed gout, with a mean age at diagnosis of 54.7 years. After a mean follow-up period of 8.1 years, there were 6660 deaths. Relative to non-gout subjects, subjects with gout had a higher risk of death (HR 1.18; 95% CI 1.06 to 1.32), and specifically from death due to coronary heart disease (CHD) (HR 1.38, 95% CI 1.10 to 1.73) and kidney disease (HR 5.81, 95% CI 3.61 to 9.37). All gout–mortality risk associations were present in both genders but the risk estimates appeared higher for women. Conclusion Gout is an independent risk factor for mortality, and specifically for death due to CHD and kidney disease.

Associations Between Soy, Diet, Reproductive Factors, and Mammographic Density in Singapore Chinese Women

Abstract: Although the evidence is not completely consistent, soy intake has been inversely associated with breast cancer risk, and the strongest results have been observed in certain Asian populations. To address this issue and to examine the association between mammographic density and reproductive factors in this population, we conducted a crosssectional analysis of mammograms and validated food-frequency questionnaires from 380 Chinese women living in Singapore. Percent mammographic density, a biomarker for breast cancer risk, was assessed using a validated computer-assisted method. We used generalized linear models to estimate mean mammographic density by quartiles of soy intake and intake of other dietary factors while adjusting for potential confounders. Percent mammographic density was inversely associated with age, body mass index, parity, breastfeeding, and soy intake. The difference in mammographic density between the highest and lowest quartiles of soy intake was 4–5%; this difference was statistically significant for soy protein and soy isoflavone intake and is similar in magnitude to what has been reported in Western populations when women undergo menopause or commence hormone therapy. We found no evidence that high fiber, fruit, or vegetable intake has protective effects on mammographic density. Our results suggest that the effect of soy intake on percent mammographic density is moderate but possibly of clinical relevance.