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Purpose The role of estrogen in cardiovascular health remains contested with discrepancies between findings from randomized controlled trials and observational studies. Mendelian randomization, which assesses the effect of lifelong endogenous exposure, may help elucidate these discrepancies. Methods We used separate sample instrumental variable analysis to estimate the association of log 17β-estradiol with factors related to cardiovascular disease risk (systolic and diastolic blood pressure, lipids, fasting glucose, body mass index, waist hip ratio, and waist circumference) and Framingham score, a predictor of 10-year risk of ischemic heart disease events, in older Chinese women from the Guangzhou Biobank Cohort Study (GBCS, n = 3092). The estimate was derived using the Wald estimator, that is, the ratio of the association of genetic determinants (rs1008805 and rs2175898) of log 17β-estradiol with cardiovascular disease risk factors and Framingham score in GBCS and the association of these genetic determinants with log 17β-estradiol in a sample of young women from Hong Kong (n = 236). Results Genetically, higher 17β-estradiol was not associated with any cardiovascular disease-related risk factor or with Framingham score (−0.01, 95% confidence interval = −1.34 to 1.31). Conclusions Lifetime exposure to estrogen does not appear to be cardioprotective via the cardiovascular disease-related risk factors examined.

Purpose In Asia, moderate alcohol users have better lung function. Never users have more inactive aldehyde dehydrogenase 2 (ALDH2) alleles (A) potentially generating confounding because inactive alleles may increase acetaldehyde exposure and reduce lung function. Methods We examined the association of ALDH2 genotypes with percentage predicted lung function (forced expiratory volume in 1 second; forced vital capacity) for age, sex, and height among 5641 older Chinese using multivariable linear regression. Results ALDH2 genotypes were associated with alcohol use and height but not other attributes. Inactive alleles were inversely associated with lung function (percentage predicted forced expiratory volume in 1 second −1.52%, 95% confidence interval [CI], −2.52% to −0.51% for one inactive allele and −2.05%, 95% CI, −3.85% to −0.26% for two inactive alleles compared with two active alleles; and for percentage predicted forced vital capacity −1.25%, 95% CI −2.15% to −0.35% and −1.65%, 95% CI, −3.25% to −0.04%). The association of moderate use with lung function was attenuated after adjusting for ALDH2, in addition to other potential confounders. Conclusions Previous findings in Chinese may be confounded by ALDH2. High frequency of inactive ALDH2 alleles in East Asia may exacerbate the effect of environmental acetaldehyde exposure on lung function and potentially on chronic obstructive pulmonary disease.

Adult height is the sum of growth during fetal, infancy, childhood, and puberty, controlled by different biological factors. In long-term developed Western populations, height is positively associated with socioeconomic position, but less clearly so in recently developing populations. We aimed to elucidate socioeconomic influences on height at different growth phases.We examined the associations of parents' education and grandparents' education with birth weight and height gain z-scores during infancy (birth to2 years), childhood (2 to8 years), and puberty (8 to14 years) adjusted for parents' height using generalized estimating equations in Hong Kong's "Children of 1997" birth cohort (n = 8264).Parents' education, but not grandparents', was positively associated with birth weight (z-score, 0.07; 95% confidence interval [CI] 0.01-0.12 for grade ≥12 compared with grade ≤9) and height gain during infancy (0.11; 95% CI, 0.05-0.18), adjusted for gender, gestational age, initial size, parity, parents' age, parents' birthplace, and parents' height. Conversely, similarly adjusted, grandparents' education, but not parents', was associated with height gain during childhood (0.11; 95% CI, 0.04-0.18).Parental education was associated with fetal and infant, but not childhood, linear growth, suggesting the mechanism underlying socioeconomic influences on height at different growth phases may be contextually specific.

Purpose With economic development, there is an emerging epidemic of diabetes in China despite relatively low levels of obesity. Muscle mass, for which adolescence is a key developmental window, may reduce vulnerability to diabetes. We examined the association of recalled adolescent build with diabetes in a large sample from the developing country setting of southern China. Methods We used multivariable regression in cross-sectional data (2005–2008), from the Guangzhou Biobank Cohort Study (phases 2 and 3) for 19,524 older (≥50 years) Chinese to examine the adjusted associations of recalled adolescent relative weight (light [ n = 6843], average [ n = 9529], and heavy [ n = 3152]) with clinically measured diabetes. Results As older adults, heavy adolescents had a lower risk of diabetes (odds ratio = 0.86, 95% confidence interval: 0.75–0.99) than light adolescents adjusted for age, sex, education, smoking, leg length, and seated height. This association was stronger after additional adjustment for waist/hip ratio and body mass index. Conclusions Poor living conditions during adolescence, resulting in low muscle mass, could contribute to vulnerability to diabetes, which, if confirmed, could be relevant to the emerging epidemic of diabetes in the developing world, as well as to minorities and migrants elsewhere.

Purpose Women usually report attributes of masculinity as attractive. These are attributes are metabolically expensive. We examined the trade off of a key attribute of masculinity, muscularity, proxied by recalled adolescence build, with lifetime reproductive success in the developing country setting of Southern China. Methods We used poisson multivariable regression in 19,168 older (≥50 years) Chinese from the Guangzhou Biobank Cohort Study (phases 2 and 3) to examine the sex-stratified, adjusted associations of recalled adolescent relative weight (light ( n = 6730), average ( n = 9344), and heavy ( n = 3094)) with number of offspring. Results Among men, recalled heavy adolescent weight compared with light was associated with an incident rate ratio for offspring of 1.08 (95% confidence interval [CI] 1.04–1.13) adjusted for age. This estimate was unchanged by adjustment for life course socio-economic position. There was no such association in women. Conclusions Male physical attractiveness, possibly representing levels of testosterone, was rewarded by lifetime reproductive success, despite potential costs. Socio-economic development may facilitate an inevitable move toward environmentally driven higher levels of testosterone with corresponding public health implications for any conditions or societal attributes driven by testosterone. Further investigation is warranted.

Purpose Earlier pubertal maturation in women may be associated with better cognition. It is unclear whether or not this also occurs in men. We tested the hypothesis that earlier pubertal development in men was associated with better cognition in later adulthood in a developing Chinese population. Methods Multivariable linear regression was used in cross-sectional study of 2463 older, Chinese men from the Guangzhou Biobank Cohort Study. Mean pubertal age was calculated as the mean of recalled ages of first nocturnal emission, voice breaking and pubarche. We assessed the association of mean pubertal age with delayed 10-word recall and mini-mental state examination (MMSE) scores. Results Adjusted for age and education, 1 year earlier mean pubertal age was associated with higher delayed 10-word recall (0.06 [95% confidence interval = 0.02–0.10]) and higher MMSE (0.08 [0.03–0.13]) scores. Additional adjustment for childhood and adulthood socio-economic position, sitting height, and leg length did not change the results. Conclusions These preliminary findings suggest earlier maturation in men is associated with better cognitive function in later adulthood. Whether pubertal timing is a marker of earlier life exposures or reflects a biological relation between somatrophic and/or gonadotrophic hormones and cognitive development is unclear.

Purpose A high rate of infant growth may be associated with adult cardiovascular disease. We investigated factors associated with infant weight growth in a large sample from the recently transitioned population of Hong Kong. Methods We used a nonlinear shape invariant model with random effects among 5949 term, singletons (77% follow-up) from a population-representative Hong Kong Chinese birth cohort “Children of 1997” to investigate factors associated with weight growth in the first year of life. Results Overall birth weight was lower but infant growth was more rapid than the 2006 WHO standards. Shorter gestation and lower birth order were associated with lower birth weight and faster infant growth. Female sex, maternal smoking in pregnancy, and a mother born in Hong Kong were associated with lower birth weight, but not with faster growth. Higher maternal education was associated with faster infant growth, grades 10–11 (1.03, 95% confidence interval [CI] = 1.03–1.05), greater than or equal to grade12 (1.07, CI = 1.04–1.09) compared with less than or equal to grade 9. Conclusions Infant growth may respond more rapidly to socio-economic development than birth weight. Whether mother’s education is associated with rapid infant growth via current conditions or her own “constitution” is unclear, nevertheless we believe this study illustrates the importance of contextually specific research for understanding the determinants of population health.

Purpose A U-shaped relation between alcohol use and mortality may be due to biological hormesis, differential response (i.e., effect modification) by health status or changes in alcohol use with ill-health and aging (i.e., reverse causality).We examined whether alcohol had the same association with mortality in healthy and unhealthy older people. Methods We used Cox regression analysis to examine the association of alcohol with mortality by health status in a population-based cohort of 56,167 people (65+ years), enrolled during July 1998 to December 2000 in Hong Kong. Results After a mean follow-up of 4.1 years, there were 3,819 deaths in 54,087 subjects. Adjusted for age, socioeconomic position and lifestyle, both occasional and moderate types of alcohol use were associated with lower mortality compared to never-drinkers, relative risk (RR) 0.72 (95% confidence interval [CI] 0.63–0.83) and 0.73 (95% CI 0.59–0.90) in men and 0.77 (95% CI 0.64–0.94) and 0.54 (95% CI 0.29–1.01) in women. However, these associations were not maintained in those with good health status: RR 1.02 (95% CI 0.74–1.39) and 1.09 (95% CI 0.71–1.68) in men and 0.63 (95% CI 0.36–1.12) and 1.27 (95% CI 0.40–4.01) in women. Conclusions Moderate alcohol use may only be beneficial for older adults in poor health.

Physical activity is associated with longevity; however, whether these beneficial effects extend to Chinese populations is unclear. We examined the relationship between leisure time physical activity (LTPA) and mortality in Hong Kong.Using a case-control study, past (10 years prior) levels of LTPA were ascertained via proxy informants for 24,079 dead cases (81% of all registered deaths) and 13,054 live controls aged #10878;35 years and were analyzed by unmatched logistic regression to determine their association with all-cause and cause-specific mortality.Compared with an exercise frequency of1 episode per month,or = 1 episode of LTPA per month was inversely associated with all-cause mortality [multivariable odds ratio (OR)=0.63, 95% confidence interval (CI), 0.59, 0.68 for males; OR=0.75, 95% CI, 0.70, 0.80 for females; adjusted for age, education, smoking status, alcohol consumption, and physical demand at work]. Each activity level above the reference level of1 episode per month (i.e., 1 episode per month to 1-3 episodes per week,or = 4 episodes per week) had approximately the same level of risk reduction and no dose-response gradient was observed. The inverse association was stronger for cardiovascular than cancer deaths, particularly in males and was strongest for respiratory mortality. One-fifth of all 31,349 registered deaths in those aged 35 years and over in Hong Kong in 1998 were attributable to physical inactivity.The present data confirm and extend previous findings in Caucasian populations on the association between leisure time physical activity and longevity. The population attributable risk from physical inactivity exceeds that due to tobacco smoking in this Hong Kong Chinese population. We predict mainland China will witness a similarly large mortality burden as it undergoes further socioeconomic development in the next few decades.

Purpose To evaluate the credibility of twin status as an instrumental variable for birth weight and infant growth and to obtain less-confounded estimates of the associations of birth weight or infant growth with adolescent blood pressure (BP). Methods Prospective population-based “Children of 1997” birth cohort of all surviving infants born in Hong Kong, China, from April to May 1997 with sex-, age-, and height-specific BP z-score at approximately 11 years (n = 6276) and approximately 13 years (n = 5305). Results In instrumental variable analyses, birth weight-for-gestational age z-score was not associated with z-score for systolic BP (0.01; 95% confidence interval [CI], −0.22 to 0.25) or diastolic BP (0.04; 95% CI, −0.09 to 0.18) at approximately 11 years adjusted for maternal age and migrant status (F = 38.6). Change in weight z-score at 0 to 12 months was not associated with z-score for systolic BP (−0.003; 95% CI, −0.15 to 0.15) or diastolic BP (−0.02; 95% CI, −0.10 to 0.07) at approximately 11 years (F = 54.4). Estimates were similar for BP at approximately 13 years, although the F-statistic was lower. Conclusions Birth weight and infant growth may make little contribution to adolescent BP. Extending consideration of the effects of early life to other growth periods, such as puberty, on BP might yield public health benefits.

Purpose To examine whether mode of delivery was associated with childhood adiposity in a developed non-Western context. Methods We used generalized estimating equations to estimate the association of mode of delivery (vaginal or cesarean) with body mass index (BMI) z-score and overweight (including obesity) from 3 months to 13 years, in 7809 term birth (94% follow-up) from a population-representative Chinese birth cohort, “Children of 1997.” We used multiple imputation for missing data. Results The cesarean section rate (26%) was higher for children born in private hospitals, with lower gestational age, lower birth order, higher maternal age, higher maternal BMI, and higher family socioeconomic position. Cesarean section was not associated with BMI z-score from 3 months to 13 years (mean difference, 0.03; 95% confidence interval, −0.02 to 0.09) or overweight from 3 years to 13 years (odds ratio, 0.98; 95% confidence interval, 0.77 to 1.25) after adjusting for infant and maternal characteristics and family socioeconomic position. Conclusions In a non-Western developed setting, mode of delivery was not clearly associated with BMI or overweight (including obesity) into late childhood. From a public health perspective, the role of mode of delivery and its mechanistic pathway in the current burgeoning epidemic of obesity needs to be clarified.

Purpose In randomized controlled trials reducing high hematocrit (Hct) in patients with polycythemia vera protects against cardiovascular disease (CVD) events, whereas increasing Hct in anemia patients causes CVD events. Hct is influenced by environmental and lifestyle factors. Given limited knowledge concerning the drivers of Hct, we took an agnostic approach to identify drivers of Hct. Methods We used an environment-wide association study to identify environmental and lifestyle factors associated with Hct in 20443 older Chinese adults (mean age = 62.7 years) from the Guangzhou Biobank Cohort Study. We evaluated the role of 25 nutrients, 40 environmental contaminants, two metals (only available for 10405 participants), and six lifestyle factors in relation to Hct, adjusted for sex, age, recruitment phase, and socioeconomic position. Results In a mutually adjusted model vitamin A, serum calcium, serum magnesium, and alcohol use were associated with higher Hct, whereas physical activity was associated with lower Hct. Conclusions Despite the difficulty of ascertaining causality, finding both expected (vitamin A and physical inactivity) and novel factors (serum calcium, serum magnesium and alcohol use) strongly associated with Hct illustrates the utility of environment-wide association study to generate hypotheses regarding the potential contribution of modifiable exposures to CVD.

Purpose Observationally in Western settings, breastfeeding is associated with less childhood wheezing disorders but may be confounded by socioeconomic position. We examined the association of breastfeeding with asthma and other wheezing disorders in a developed non-Western setting with unique social patterning of breastfeeding. Methods Using Cox regression, we examined the adjusted associations of breastfeeding with public hospital admissions for asthma, bronchitis, and bronchiolitis (International Classification of Diseases, Ninth Version. Clinical Modification: 466, 490, and 493) from 3 months to 12 years in a population-representative birth cohort of 8327 Hong Kong Chinese children. Results We did not find an association of exclusive breastfeeding for 3 months or more, compared with never breastfeeding, with hospitalization for asthma, bronchitis, and bronchiolitis to 12 years (hazard ratio [HR], 0.89; 95% confidence interval [CI], 0.63–1.25) nor for partial breastfeeding for any length of time or exclusive breastfeeding for less than 3 months (HR, 1.02; 95% CI, 0.86–1.21), adjusted for infant and parental characteristics and socioeconomic position. We also did not find an association of exclusive breastfeeding for 3 months or more with hospitalization for asthma only (International Classification of Diseases, Ninth Version. Clinical Modification: 493) (HR, 1.27; 95% CI, 0.82–1.98). Conclusions In a large population-representative Chinese birth cohort, we did not find an association of breastfeeding with childhood hospitalizations for asthma and other wheezing disorders.

Life expectancy is strongly related to national income, whether there is an additional contribution of income inequality is unclear.We used negative binomial regression to examine the association of neighborhood-level Gini, adjusted for age, sex, and income, with mortality rates in Hong Kong from 1976 to 2006.The association of neighborhood Gini with all-cause mortality varied over time (p-value for interaction.01). Neighborhood Gini was positively associated with nonmedical mortality in 1976 to 1986; incident rate ratio (IRR) 1.09, 95% confidence interval (95% CI) 1.02-1.16 per 0.1 change and in 1991 to 2006, IRR 1.24, 95% CI 1.13-1.36, adjusted for age, sex and absolute income. Similarly adjusted, Gini was not associated with all-cause mortality in 1976 to 1986 (IRR 0.96, 95% CI 0.93-1.00) but was in 1991 to 2006 (IRR 1.25, 95% CI 1.20-1.29), when Gini was also positively associated with death from cardiovascular diseases, respiratory diseases and some cancers.Independent of income, income inequality was positively associated with nonmedical mortality rates at a low level of spatial aggregation, indicating the consistent harms of social disharmony. However, the impact on medical mortality was less consistent, suggesting the relevance of contextual factors.

Purpose Infant growth and early puberty are associated with the risk of cardiovascular disease. It is unclear whether pubertal timing has an independent etiologic role or is a marker of preceding growth. We examined whether infant growth was associated with age at pubertal onset and whether any associations were mediated by childhood height or body mass index. Methods We used multivariable interval–censored proportional hazards regression in 6873 term births (87% follow-up, 53% male) from a population–representative Hong Kong Chinese birth cohort, “Children of 1997.” We examined the adjusted associations of sex–specific infant growth trajectories, derived from latent class analyses by the use of, on average, 4.2 measurements per child, with clinically assessed age at pubertal onset (Tanner stage II). We used Sobel tests to assess mediation. Results Compared with children of average birth weight whose weight followed the same centile curve, a faster weight growth trajectory from birth to 12 months was associated with earlier pubertal onset (time ratio, 0.979; 95% confidence interval, 0.965–0.993) among boys, whereas girls born light with slow infant growth had later puberty (time ratio 1.020, 95% confidence interval 1.006–1.034). These associations were mediated by both height and body mass index among girls but only by height in boys. Conclusions Infant weight growth may be associated with earlier pubertal onset, particularly in boys, at least in part because it is associated with more linear growth in childhood. Earlier pubertal onset may be an indicator of up-regulation of growth axes related to the risk of cardiovascular disease.

Purpose Observational studies in Western settings show moderate alcohol use associated with better cognitive function, but they are vulnerable to contextual bias. Evidence from non-Western settings may be useful to verify causality. We examined such association in southern China where alcohol use is low. Methods We used multivariable linear regression in cross-sectional data from the Guangzhou Biobank Cohort Study to assess sex-stratified associations of alcohol use (never, occasional, moderate, heavy and former drinker) with delayed 10-word recall score for all 3 phases (N = 28,537) and Mini-Mental State Examination (MMSE) score in phase 3 (N = 9,571). Results Delayed 10-word recall scores were higher in moderate drinkers compared with never drinkers among men (0.30 words, 95% confidence interval [CI]: 0.18 to 0.42) but not women (0.02; 95% CI: –0.12 to 0.17), adjusted for sociodemographic factors. Occasional alcohol users also had higher 10-word recall scores among men (0.27; 95% CI: 0.18 to 0.37) and women (0.30; 95% CI: 0.23 to 0.37). These estimates were little altered by further adjustment for cardiovascular risk factors. Results for MMSE scores were similar. Conclusions Alcohol may not drive the association between moderate use and better cognitive function, which instead may be due to confounding by general moderation in lifestyle.