Xianghua Fang

Body-mass index and cancer mortality in the Asia-Pacific Cohort Studies Collaboration: pooled analyses of 424 519 participants

BACKGROUND Excess bodyweight is an established risk factor for several types of cancer, but there are sparse data from Asian populations, where the proportion of overweight and obese individuals is increasing rapidly and adiposity can be substantially greater for the same body-mass index (BMI) compared with people from Western populations. METHODS We examined associations of adult BMI with cancer mortality (overall and for 20 cancer sites) in geographic populations from Asia and from Australia and New Zealand (ANZ), within the Asia-Pacific Cohort Studies Collaboration, by use of Cox regression analysis. Pooled data from 39 cohorts (recruitment 1961-99, median follow-up 4 years) were analysed for 424,519 participants (77% Asian; 41% female; mean recruitment age 48 years) with individual data on BMI. FINDINGS After excluding those with follow-up of less than 3 years, 4872 cancer deaths occurred in 401,215 participants. Hazard ratios for cancer sites with increased mortality risk in obese (BMI > or = 30 kg/m(2)) compared with normal weight participants (BMI 18.5-24.9 kg/m(2)) were: 1.21 (95% CI 1.09-1.36) for all-cause cancer (excluding lung and upper aerodigestive tract), 1.50 (1.13-1.99) for colon, 1.68 (1.06-2.67) for rectum, 1.63 (1.13-2.35) for breast in women 60 years or older, 2.62 (1.57-4.37) for ovary, 4.21 (1.89-9.39) for cervix, 1.45 (0.97-2.19) for prostate, and 1.66 (1.03-2.68) for leukaemia (all after left censoring at 3 years). The increased risk associated with a 5-unit increase in BMI for those with BMI of 18.5 kg/m(2) or higher was 1.09 (95% CI 1.04-1.14) for all cancers (excluding lung and upper aerodigestive tract). There was little evidence of regional differences in relative risk of cancer with higher BMI, apart from cancers of the oropharynx and larynx, where the association was inverse in ANZ and absent in Asia. INTERPRETATION Overweight and obese individuals in populations across the Asia-Pacific region have a significantly increased risk of mortality from cancer. Strategies to prevent individuals from becoming overweight and obese in Asia are needed to reduce the burden of cancer that is expected if the obesity epidemic continues. FUNDING National Health and Medical Research Council of Australia, Health Research Council of New Zealand, and Pfizer Inc.

Isolated Low Levels of High-Density Lipoprotein Cholesterol Are Associated With an Increased Risk of Coronary Heart Disease An Individual Participant Data Meta-Analysis of 23 Studies in the Asia-Pacific Region

Background— Previous studies have suggested that there is a novel dyslipidemic profile consisting of isolated low high-density lipoprotein cholesterol (HDL-C) level that is associated with increased risk of coronary heart disease, and that this trait may be especially prevalent in Asian populations. Methods and Results— Individual participant data from 220 060 participants (87% Asian) in 37 studies from the Asia-Pacific region were included. Low HDL-C (HDL <1.03 mmol/L in men and <1.30 mmol/L in women) was seen among 33.1% (95% confidence interval [CI], 32.9–33.3) of Asians versus 27.0% (95% CI, 26.5–27.5) of non-Asians ( P <0.001). The prevalence of low HDL-C in the absence of other lipid abnormalities (isolated low HDL-C) was higher in Asians compared with non-Asians: 22.4% (95% CI, 22.2–22.5) versus 14.5% (95% CI, 14.1–14.9), respectively ( P <0.001). During 6.8 years of follow-up, there were 574 coronary heart disease and 739 stroke events. There was an inverse relationship between low HDL-C with coronary heart disease in all individuals (hazard ratio, 1.57; 95% CI, 1.31–1.87). In Asians, isolated low levels of HDL-C were as strongly associated with coronary heart disease risk as low levels of HDL-C combined with other lipid abnormalities (hazard ratio, 1.67 [95% CI, 1.27–2.19] versus 1.63 [95% CI, 1.24–2.15], respectively). There was no association between low HDL-C and stroke risk in this population (hazard ratio, 0.95 [95% CI, 0.78 to 1.17] with nonisolated low HDL-C and 0.81 [95% CI, 0.67–1.00] with isolated low HDL-C). Conclusion— Isolated low HDL-C is a novel lipid phenotype that appears to be more prevalent among Asian populations, in whom it is associated with increased coronary risk. Further investigation into this type of dyslipidemia is warranted. # Clinical Perspective {#article-title-36}Background— Previous studies have suggested that there is a novel dyslipidemic profile consisting of isolated low high-density lipoprotein cholesterol (HDL-C) level that is associated with increased risk of coronary heart disease, and that this trait may be especially prevalent in Asian populations. Methods and Results— Individual participant data from 220 060 participants (87% Asian) in 37 studies from the Asia-Pacific region were included. Low HDL-C (HDL <1.03 mmol/L in men and <1.30 mmol/L in women) was seen among 33.1% (95% confidence interval [CI], 32.9–33.3) of Asians versus 27.0% (95% CI, 26.5–27.5) of non-Asians (P<0.001). The prevalence of low HDL-C in the absence of other lipid abnormalities (isolated low HDL-C) was higher in Asians compared with non-Asians: 22.4% (95% CI, 22.2–22.5) versus 14.5% (95% CI, 14.1–14.9), respectively (P<0.001). During 6.8 years of follow-up, there were 574 coronary heart disease and 739 stroke events. There was an inverse relationship between low HDL-C with coronary heart disease in all individuals (hazard ratio, 1.57; 95% CI, 1.31–1.87). In Asians, isolated low levels of HDL-C were as strongly associated with coronary heart disease risk as low levels of HDL-C combined with other lipid abnormalities (hazard ratio, 1.67 [95% CI, 1.27–2.19] versus 1.63 [95% CI, 1.24–2.15], respectively). There was no association between low HDL-C and stroke risk in this population (hazard ratio, 0.95 [95% CI, 0.78 to 1.17] with nonisolated low HDL-C and 0.81 [95% CI, 0.67–1.00] with isolated low HDL-C). Conclusion— Isolated low HDL-C is a novel lipid phenotype that appears to be more prevalent among Asian populations, in whom it is associated with increased coronary risk. Further investigation into this type of dyslipidemia is warranted.

Effects of prehypertension and hypertension subtype on cardiovascular disease in the Asia-Pacific Region

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure defined blood pressure (BP) levels of 120 to 139/80 to 89 mm Hg as prehypertension and those of ≥140/90 mm Hg as hypertension. Hypertension can be divided into 3 categories, isolated diastolic (IDH; systolic BP <140 mm Hg and diastolic BP ≥90 mmHg), isolated systolic (systolic BP ≥140 mm Hg and diastolic BP <90 mmHg), and systolic-diastolic hypertension (systolic BP ≥140 mm Hg and diastolic BP ≥90 mmHg). Although there is clear evidence that isolated systolic hypertension and systolic-diastolic hypertension increase the risks of future vascular events, there remains uncertainty about the effects of IDH. The objective was to determine the effects of prehypertension and hypertension subtypes (IDH, isolated systolic hypertension, and systolic-diastolic hypertension) on the risks of cardiovascular disease (CVD) in the Asia-Pacific Region. The Asia Pacific Cohort Studies Collaboration is an individual participant data overview of cohort studies in the region. This analysis included a total of 346570 participants from 36 cohort studies. Outcomes were fatal and nonfatal CVD. The relationship between BP categories and CVD was explored using a Cox proportional hazards model adjusted for age, cholesterol, and smoking and stratified by sex and study. Compared with normal BP (<120/80 mmHg), hazard ratios (95% CIs) for CVD were 1.41 (1.31–1.53) for prehypertension, 1.81 (1.61–2.04) for IDH, 2.18 (2.00–2.37) for isolated systolic hypertension, and 3.42 (3.17–3.70) for systolic-diastolic hypertension. Separately significant effects of prehypertension and hypertension subtypes were also observed for coronary heart disease, ischemic stroke, and hemorrhagic stroke. In the Asia-Pacific region, prehypertension and all hypertension subtypes, including IDH, thus clearly predicted increased risks of CVD.

The Effect of Modifiable Risk Factors on Pancreatic Cancer Mortality in Populations of the Asia-Pacific Region

Background: Pancreatic cancer accounts for about 220,000 deaths each year. Known risk factors are smoking and type 2 diabetes. It remains to be seen whether these risk factors are equally important in Asia and whether other modifiable risk factors have important associations with pancreatic cancer. Methods: An individual participant data analysis of 30 cohort studies was carried out, involving 420,310 Asian participants (33% female) and 99,333 from Australia/New Zealand (45% female). Cox proportional hazard models, stratified by study and sex and adjusted for age, were used to quantify risk factors for death from pancreatic cancer. Results: During 3,558,733 person-years of follow-up, there were 324 deaths from pancreatic cancer (54% Asia and 33% female). Mortality rates (per 100,000 person-years) from pancreatic cancer were 10 for men and 8 for women. The following are age-adjusted hazard ratios (95% confidence interval) for death from pancreatic cancer: for current smoking, 1.61 (1.12-2.32); for diabetes, 1.76 (1.15-2.69); for a 2-cm increase in waist circumference, 1.08 (1.02-1.14). All three relationships remained significant (P < 0.05) after adjustment for other risk factors. There was no evidence of heterogeneity in the strength of these associations between either cohorts from Asia and Australia/New Zealand or between the sexes. In men, the combination of cigarette smoking and diabetes more than doubled the likelihood of pancreatic cancer (2.47; 95% confidence interval, 1.17-5.21) in both regions. Conclusions: Smoking, obesity, and diabetes are important and are potentially modifiable risk factors for pancreatic cancer in populations of the Asia-Pacific region. Activities to prevent them can be expected to lead to a major reduction in the number of deaths from this cancer, particularly in Asia with its enormous population. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2435–40)

Subtype Hypertension and Risk of Stroke in Middle-Aged and Older Chinese: A 10-Year Follow-Up Study

Background and Purpose— Hypertension is the most important indicator of stroke. We aim to compare the long-term effects of the subtypes of hypertension on the risk of stroke in a Chinese cohort. Methods— A total of 26 587 subjects ≥35 years of age and free of stroke were recruited in 5 cities in 1987. The subtypes of hypertension were defined as isolated systolic hypertension (ISH), isolated diastolic hypertension (IDH), systolic and diastolic hypertension (SDH), as well as managed hypertension (MHT), according to the criteria of systolic blood pressure ≥140 or diastolic blood pressure >90 mm Hg or under antihypertensive treatment. The relative risks of stroke with the subtypes of hypertension, compared with normotensives, were estimated using the Cox model after adjustments for age, sex, and other confounders. Results— The prevalence of hypertension was: ISH 7.1%, SDH 18.4%, IDH 6.7%, and MHT 3.9%. During a total of 233 437 person years of follow-up, 1107 subjects developed stroke (614 ischemic and 451 hemorrhagic events and 42 unclassified). SDH patients were at the highest risk of stroke among all the hypertensives. The hazard ratio and 95% CI was 2.96 (2.49 to 3.52) for all stroke, 4.05 (3.10 to 5.30) for hemorrhagic, and 2.33 (1.84 to 2.95) for ischemic stroke. Although the incidence of stroke was higher in the older population, the effect of hypertension, especially SDH, on hemorrhagic stroke is stronger in the middle-aged population. Conclusion— ISH and IDH are similarly prevalent in the population; both are independent predictors of stroke. Patients with SDH are at the highest risk of stroke and should be treated more aggressively.

The association between resting heart rate, cardiovascular disease and mortality: evidence from 112,680 men and women in 12 cohorts

Background: Multiple studies have examined the relationship between heart rate and mortality; however, there are discrepancies in results. Our aim was to describe the relationship between resting heart rate (RHR) and both major cardiovascular (CV) outcomes, as well as all-cause mortality in the Asia-Pacific region. Design and methods: Individual data from 112,680 subjects in 12 cohort studies were pooled and analysed using Cox models, stratified by study and sex, and adjusted for age and systolic blood pressure. Results: During a mean 7.4 years follow-up, 6086 deaths and 2726 fatal or nonfatal CV events were recorded. There was a continuous, increasing association between having a RHR above approximately 65 beats/min and the risk of both CV and all-cause mortality, yet there was no evidence of associations below this threshold. The hazard ratio (95% CI) comparing the extreme quarters of RHR (80+ v <65 beats/min) was 1.44 (1.29–1.60) for CV and 1.54 (1.43–1.66) for total mortality. These associations were not materially changed by adjustment for other risk factors and exclusion of the first 2 years of follow-up. Hazard ratios of a similar magnitude were found for ischemic and hemorrhagic stroke, but the hazard ratio for heart failure was higher (2.08, 95% CI 1.07–4.06) and for Coronary Heart Disease (CHD) was lower (1.11, 95% CI 0.93–1.31) than for stroke. Conclusions: RHR of above 65 beats/min has a strong independent effect on premature mortality and stroke, but a lesser effect on CHD. Lifestyle and pharmaceutical regimens to reduce RHR may be beneficial for people with moderate to high levels of RHR.

Behavioural and metabolic risk factors for mortality from colon and rectum cancer: analysis of data from the Asia-Pacific Cohort Studies Collaboration.

BACKGROUND Colorectal cancer has several modifiable behavioural risk factors but their relationship to the risk of colon and rectum cancer separately and between countries with high and low incidence is not clear. METHODS Data from participants in the Asia Pacific Cohort Studies Collaboration (APCSC) were used to estimate mortality from colon (International Classification of Diseases, revision 9 (ICD-9) 153, ICD-10 C18) and rectum (ICD-9 154, ICD-10 C19-20) cancers. Data on age, body mass index (BMI), serum cholesterol, height, smoking, physical activity, alcohol and diabetes mellitus were entered into Cox proportional hazards models. RESULTS 600,427 adults contributed 4,281,239 person-years follow-up. The mean ages (SD) for Asian and Australia/New Zealand cohorts were 44.0 (9.5) and 53.4 (14.5) years, respectively. 455 colon and 158 rectum cancer deaths were observed. Increasing age, BMI and attained adult height were associated with increased hazards of death from colorectal cancer, and physical activity was associated with a reduced hazard. After multiple adjustment, any physical activity was associated with a 28% lower hazard of colon cancer mortality (HR 0.72, 95%CI 0.53-0.96) and lower rectum cancer mortality (HR 0.75, 95%CI 0.45-1.27). A 2cm increase in height increased colon and all colorectal cancer mortality by 7% and 6% respectively. CONCLUSIONS Physical inactivity and greater BMI are modifiable risk factors for colon cancer in both Western and Asian populations. Further efforts are needed to promote physical activity and reduce obesity while biological research is needed to understand the mechanisms by which they act to cause cancer mortality.

Socioeconomic status in relation to cardiovascular disease and cause-specific mortality: a comparison of Asian and Australasian populations in a pooled analysis

Objectives In Western countries, lower socioeconomic status is associated with a higher risk of cardiovascular disease (CVD) and premature mortality. These associations may plausibly differ in Asian populations, but data are scarce and direct comparisons between the two regions are lacking. We, thus, aimed to compare such associations between Asian and Western populations in a large collaborative study, using the highest level of education attained as our measure of social status. Setting Cohort studies in general populations conducted in Asia or Australasia. Participants 303 036 people (71% from Asia) from 24 studies in the Asia Pacific Cohort Studies Collaboration. Studies had to have a prospective cohort study design, have accumulated at least 5000 person-years of follow-up, recorded date of birth (or age), sex and blood pressure at baseline and date of, or age at, death during follow-up. Outcome measures We used Cox regression models to estimate relationships between educational attainment and CVD (fatal or non-fatal), as well as all-cause, cardiovascular and cancer mortality. Results During more than two million person-years of follow-up, 11 065 deaths (3655 from CVD and 4313 from cancer) and 1809 CVD non-fatal events were recorded. Adjusting for classical CVD risk factors and alcohol drinking, hazard ratios (95% CIs) for primary relative to tertiary education in Asia (Australasia) were 1.81 (1.38, 2.36) (1.10 (0.99, 1.22)) for all-cause mortality, 2.47(1.47, 4.17) (1.24 (1.02, 1.51)) for CVD mortality, 1.66 (1.00, 2.78) (1.01 (0.87, 1.17)) for cancer mortality and 2.09 (1.34, 3.26) (1.23 (1.04, 1.46)) for all CVD. Conclusions Lower educational attainment is associated with a higher risk of CVD or premature mortality in Asia, to a degree exceeding that in the Western populations of Australasia.

Body mass index and risk of total and type-specific stroke in Chinese adults: results from a longitudinal study in China

Background The prevalence rate of overweight and obese has been escalating over the past two decades in China. Even so, the association between obesity and stroke still remains unclear to some extent. Aims The aim of this study was to elucidate the association between body mass index and stroke in a large Chinese population cohort. Methods A cohort of 26 607 Chinese people, aged over 35 years, was investigated in 1987. Baseline information of body weight and height was used to calculate BMI (weight in kilograms divided by height in meters squared, kg/m2). Cox proportional hazards model was fitted to estimate hazard ratios of stroke adjusted for age, educational level, smoking and alcohol consumption. Results The 11-year follow-up revealed (241 149 person-years) a total of 1108 stroke events (614 ischemic, 451 hemorrhagic, and 44 undefined stroke). Body mass index ≥ 30·0 was an independent risk factor for stroke both in men and women. Compared with normal weight, hazard ratios for total stroke were 0·74 in men underweight (95% confidence interval: 0·53∼1·03), 1·63 overweight (95% confidence interval: 1·35∼1·96), and 2·20 with obesity (95% confidence interval: 1·47∼3·30); and with ischemic stroke, hazard ratios were 0·52 in those underweight (95% confidence interval: 0·30∼0·89), 208 overweight (95% confidence interval: 1·65∼2·62), and 3·80 with obesity (95% confidence interval: 2·47∼5·86). In women, the corresponding hazard ratios for total stroke were 0·79 underweight (95% confidence interval: 0·58∼1·07), 1·42 overweight (95% confidence interval: 1·16∼1·73), and 1·57 with obesity (95% confidence interval: 1·06∼2·31); and for those with ischemic stroke, 0·92 underweight (95% confidence interval: 0·59∼1·43), 1·90 overweight (95% confidence interval: 1·44∼2·50), and 2·42 with obesity (95% confidence interval: 1·50∼3·93). There appeared an evident dose-response relationship between body mass index and the risk of developing stroke, which still appeared, however, adjusted low for hypertension, diabetes, and heart disease. Decreased risk for stroke in the leanest group was confined to men only. No association was found between body mass index and hemorrhagic stroke in both genders. Conclusions Our data suggest that body mass index was an independent risk factor for total and ischemic stroke but not for hemorrhagic stroke in both genders. Association between body mass index and stroke was extremely mediated by hypertension, diabetes, and heart disease. Decreased risk for the leanest group was confined to men.

Does Body Mass Index Impact on the Relationship Between Systolic Blood Pressure and Cardiovascular Disease? Meta-Analysis of 419 488 Individuals From the Asia Pacific Cohort Studies Collaboration

Background and Purpose— Elevated blood pressure and excess body mass index (BMI) are established risk factors for cardiovascular disease (CVD) but controversy exists as to whether, and how, they interact. Methods— The interactions between systolic blood pressure and BMI on coronary heart disease, ischemic and hemorrhagic stroke and CVD were examined using data from 419 448 participants (≥30 years) in the Asia-Pacific region. BMI was categorized into 5 groups, using standard criteria, and systolic blood pressure was analyzed both as a categorical and continuous variable. Cox proportional hazard models, stratified by sex and study, were used to estimate hazard ratios, adjusting for age and smoking and the interaction was assessed by likelihood ratio tests. Results— During 2.6 million person-years of follow-up, there were 10 877 CVD events. Risks of CVD and subtypes increased monotonically with increasing systolic blood pressure in all BMI subgroups. There was some evidence of a decreasing hazard ratio, per additional 10 mm Hg systolic blood pressure, with increasing BMI, but the differences, although significant, are unlikely to be of clinical relevance. The hazard ratio for CVD was 1.34 (95% CI, 1.32–1.36) overall with individual hazard ratios ranging between 1.28 and 1.36 across all BMI groups. For coronary heart disease, ischemic stroke, and hemorrhagic stroke, the overall hazard ratios per 10 mm Hg systolic blood pressure were 1.24, 1.46, and 1.65, respectively. Conclusions— Increased blood pressure is an important determinant of CVD risk irrespective of BMI. Although its effect tends to be weaker in people with relatively high BMI, the difference is not sufficiently great to warrant alterations to existing guidelines.