D. Gu

Cardiovascular risk prediction tools for populations in Asia

Background: Cardiovascular risk equations are traditionally derived from the Framingham Study. The accuracy of this approach in Asian populations, where resources for risk factor measurement may be limited, is unclear. Objective: To compare “low-information” equations (derived using only age, systolic blood pressure, total cholesterol and smoking status) derived from the Framingham Study with those derived from the Asian cohorts, on the accuracy of cardiovascular risk prediction. Design: Separate equations to predict the 8-year risk of a cardiovascular event were derived from Asian and Framingham cohorts. The performance of these equations, and a subsequently “recalibrated” Framingham equation, were evaluated among participants from independent Chinese cohorts. Setting: Six cohort studies from Japan, Korea and Singapore (Asian cohorts); six cohort studies from China; the Framingham Study from the US. Participants: 172 077 participants from the Asian cohorts; 25 682 participants from Chinese cohorts and 6053 participants from the Framingham Study. Main results: In the Chinese cohorts, 542 cardiovascular events occurred during 8 years of follow-up. Both the Asian cohorts and the Framingham equations discriminated cardiovascular risk well in the Chinese cohorts; the area under the receiver–operator characteristic curve was at least 0.75 for men and women. However, the Framingham risk equation systematically overestimated risk in the Chinese cohorts by an average of 276% among men and 102% among women. The corresponding average overestimation using the Asian cohorts equation was 11% and 10%, respectively. Recalibrating the Framingham risk equation using cardiovascular disease incidence from the non-Chinese Asian cohorts led to an overestimation of risk by an average of 4% in women and underestimation of risk by an average of 2% in men. Interpretation: A low-information Framingham cardiovascular risk prediction tool, which, when recalibrated with contemporary data, is likely to estimate future cardiovascular risk with similar accuracy in Asian populations as tools developed from data on local cohorts.

Adult height and the risks of cardiovascular disease and major causes of death in the Asia-Pacific region: 21 000 deaths in 510 000 men and women

BACKGROUNDnIn Caucasian populations, adult height is inversely associated with cardiovascular disease (CVD) risk and positively related to some cancers. However, there are few data from Asian populations and from women. We sought to determine the sex- and region-specific associations between height and cardiovascular outcomes, and deaths due to cancer, respiratory and injury in populations from the Asia-Pacific region.nnnMETHODSnThirty-nine studies from the Asia Pacific Cohort Studies Collaboration database were included. We used Cox proportional hazard regression models to estimate the associations between height and pre-specified outcomes.nnnRESULTSnA total of 510,800 participants with 21,623 deaths were included. Amongst men, inverse linear associations were observed between height and coronary heart disease (CHD), stroke, CVD, injury and total mortality. The hazard ratios [95% confidence intervals, (CI)] for a 1-SD (= 6 cm) increment in height ranged from 0.85 (0.80-0.91) for injury to 0.97 (0.95-0.98) for total mortality. Similar trends were found between height and CHD, haemorrhagic stroke and CVD in women. A positive linear association was observed between height and cancer mortality. For each standard deviation greater height, the risk of cancer was increased by 5% (2-8%) and 9% (5-14%) in men and women, respectively. No regional difference was observed between Asian and Australasian cohorts. Adjusting for markers of education did not alter the results.nnnCONCLUSIONSnThe opposing relationships of height with CVD and cancer suggest that care is required in setting national policies on childhood nutrition lest they have unintended consequences on the incidence of major non-communicable diseases.

Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region

Objective To assess the association between systolic blood pressure (SBP) and cardiovascular diseases (CVD) among participants with and without diabetes from cohorts in the Asia–Pacific region. Research design and methods Hazards ratios and 95% confidence intervals (CI) for CVD were calculated from Cox models, stratified by sex and region and adjusted for age using individual participant data from 36 cohort studies. Repeat measurements of SBP were used to adjust for regression dilution bias. Results During follow-up, 7387 fatal or non-fatal cardiovascular endpoints were recorded among 368 307 participants (6.4% with diabetes). SBP was associated with coronary heart disease (CHD), ischaemic stroke and haemorrhagic stroke in a continuous log-linear fashion among individuals with diabetes, as well as those without diabetes. Overall, each 10 mmHg higher usual SBP was associated with 18% (95% CI: 9–27%) and 23% (19–26%) greater risk for CHD among those with and without diabetes, respectively. The corresponding values for ischaemic stroke were 29% (14–45%) and 43% (37–50%), and for haemorrhagic stroke, 56% (32–83%) and 74% (66–82%). The test for heterogeneity by diabetes status in each of these associations was not significant (P ≥ 0.10). Conclusions Systolic blood pressure is an important marker of risk of CVD in people with and without diabetes. A given reduction in systolic blood pressure is likely to have a similar relative effect on reducing the risk of a cardiovascular event, regardless of diabetes status.

The fraction of ischaemic heart disease and stroke attributable to smoking in the WHO Western Pacific and South-East Asian regions

Background: Tobacco will soon be the biggest cause of death worldwide, with the greatest burden being borne by low and middle-income countries where 8/10 smokers now live. Objective: This study aimed to quantify the direct burden of smoking for cardiovascular diseases (CVD) by calculating the population attributable fractions (PAF) for fatal ischaemic heart disease (IHD) and stroke (haemorrhagic and ischaemic) for all 38 countries in the World Health Organization Western Pacific and South East Asian regions. Design and subjects: Sex-specific prevalence of smoking was obtained from existing data. Estimates of the hazard ratio (HR) for IHD and stroke with smoking as an independent risk factor were obtained from the ∼600 000 adult subjects in the Asia Pacific Cohort Studies Collaboration (APCSC). HR estimates and prevalence were then used to calculate sex-specific PAF for IHD and stroke by country. Results: The prevalence of smoking in the 33 countries, for which relevant data could be obtained, ranged from 28–82% in males and from 1–65% in females. The fraction of IHD attributable to smoking ranged from 13–33% in males and from <1–28% in females. The percentage of haemorrhagic stroke attributable to smoking ranged from 4–12% in males and from <1–9% in females. Corresponding figures for ischaemic stroke were 11–27% in males and <1–22% in females. Conclusions: Up to 30% of some cardiovascular fatalities can be attributed to smoking. This is likely an underestimate of the current burden of smoking on CVD, given that the smoking epidemic has developed further since many of the studies were conducted.

Blood Pressure Is a Major Risk Factor for Renal Death: An Analysis of 560 352 Participants From the Asia-Pacific Region

Chronic kidney disease is a major worldwide public health problem that causes substantial morbidity and mortality. Studies from the Asia-Pacific region have reported some of the highest chronic kidney disease prevalence rates in the world, but access to dialysis is limited in many countries, making it imperative to identify high-risk individuals. We performed a participant-level data overview of prospective studies conducted in the Asia-Pacific region to quantify the magnitude and direction of the associations between putative risk factors and renal death. Age- and sex-adjusted Cox proportional hazards models were applied to pooled data from 35 studies to calculate hazard ratios (95% CIs) for renal death associated with a standardized change in risk factors. Among 560 352 participants followed for a median of 6.8 years, a total of 420 renal deaths were observed. Continuous and positive associations among systolic blood pressure, diastolic blood pressure, fasting blood glucose, and total cholesterol levels with renal death were observed, as well as a continuous but inverse association with high-density lipoprotein cholesterol. Systolic blood pressure was the strongest risk factor for renal death with each SD increase in systolic blood pressure (19 mm Hg) associated with >80% higher risk (hazard ratio: 1.84; 95% CI: 1.60 to 2.12). Neither cigarette smoking nor excess weight was related to the risk of renal death (P>0.10). The results were similar for cohorts in Asia and Australia. These results suggest that primary prevention strategies for renal disease should focus on individuals with elevated blood pressure, diabetes mellitus, and dyslipidemia.

Association of smoking and smoking cessation with major causes of mortality in the Asia Pacific Region: the Asia Pacific Cohort Studies Collaboration

Background: Although the dangers of smoking, and the benefits of quitting, are well established and understood in the West, smoking remains popular among Asian men. We investigated the associations between smoking (including ex-smoking) and major causes of mortality in Asian men and women, and compared with Australians and New Zealanders (ANZ). Methods: An overview of 34 cohort studies in the Asia Pacific region involving 512 676 individuals (81 from Asia), followed up for a median of 6.7 years (20 804 deaths). Results: Mortality rates for cause-specific and all causes of mortality were systematically higher for current compared with never smokers. Hazard ratios (HR) for overall and cause-specific mortality comparing current-smokers with never smokers, ex- smokers with current-smokers and comparing numbers of cigarettes smoked per day, were higher for ANZ than Asia (p<0.001). For overall mortality, the HR (95 CI) comparing current-smoking with not was 1.37 (1.23 to 1.53) and 1.33 (1.26 to 1.40) in Asian men and women respectively. The corresponding figures in ANZ were 1.95 (1.81 to 2.09) and 1.85 (1.69 to 2.02). The HR for quitting in ANZ was 0.67 (0.63 to 0.71) and 0.66 (0.58 to 0.74) in men and women respectively. Quitting smoking had a significant benefit among Asian men, the HR was 0.88 (0.81 to 0.97) after ignoring the first 3 years of follow-up. There was no evidence of benefit for Asian women, for whom ex-smoking is rare. Conclusions: Allowing for the recent uptake of smoking in Asia, its effects are comparable to those observed in ANZ. Stringent tobacco control measures and smoking cessation strategies are urgently required in Asia.

Impact of cigarette smoking on the relationship between body mass index and coronary heart disease: a pooled analysis of 3264 stroke and 2706 CHD events in 378579 individuals in the Asia Pacific region

Background Elevated levels of body mass index (BMI) and smoking are well established lifestyle risk factors for coronary heart disease (CHD) and stroke. If these two risk factors have a synergistic relationship, rigorous lifestyle modification may contribute to greater reduction in cardiovascular burden than previously expected. Methods A pooled analysis of individual participant data from 38 cohorts, involving 378,579 participants. Hazards ratios (HRs) and 95% confidence intervals (CIs) for BMI by cigarette smoking status were estimated using Cox proportional hazard models. Results During a mean follow-up of 3.8 years, 2706 CHD and 3264 strokes were recorded. There was a log-linear, positive relationship of BMI with CHD and stroke in both smokers and non-smokers with evidence of a synergistic effect of smoking on the association between BMI and CHD only: HRs (95% CIs) associated with a 2 kg/m2 higher BMI were 1.13 (1.10 – 1.17) in current smokers and 1.09 (1.06 – 1.11) in non-smokers (p-value for interaction = 0.04). Conclusion Smoking amplifies the positive association between BMI and CHD but not stroke. If confirmed, these results suggest that effective strategies that target smoking cessation and weight loss are likely to have a greater impact than anticipated on reducing the burden of CHD.BackgroundElevated levels of body mass index (BMI) and smoking are well established lifestyle risk factors for coronary heart disease (CHD) and stroke. If these two risk factors have a synergistic relationship, rigorous lifestyle modification may contribute to greater reduction in cardiovascular burden than previously expected.MethodsA pooled analysis of individual participant data from 38 cohorts, involving 378,579 participants. Hazards ratios (HRs) and 95% confidence intervals (CIs) for BMI by cigarette smoking status were estimated using Cox proportional hazard models.ResultsDuring a mean follow-up of 3.8 years, 2706 CHD and 3264 strokes were recorded. There was a log-linear, positive relationship of BMI with CHD and stroke in both smokers and non-smokers with evidence of a synergistic effect of smoking on the association between BMI and CHD only: HRs (95% CIs) associated with a 2 kg/m2 higher BMI were 1.13 (1.10 – 1.17) in current smokers and 1.09 (1.06 – 1.11) in non-smokers (p-value for interaction = 0.04).ConclusionSmoking amplifies the positive association between BMI and CHD but not stroke. If confirmed, these results suggest that effective strategies that target smoking cessation and weight loss are likely to have a greater impact than anticipated on reducing the burden of CHD.