Adiposity, major plasma biomarkers and the risk of cardiovascular diseases and mortality in Chinese adults

As a result of rapid social and lifestyle changes a growing proportion of the world population, especially those in low- and middle-income countries such as China, is becoming overweight or obese. Excess weight can lead to high blood pressure, diabetes, cardiovascular diseases (CVD), certain cancers, and is now responsible for causing, directly or indirectly, about 3.5 million annual deaths worldwide. However, the prevalence of overweight/obese varies greatly between different populations. In Western populations a high proportion of those with low body mass index (BMI) (e.g. <22.5 kg/m2) may have pre-existing diseases, while this is not the case in China where the population mean BMI is much lower than in the West. A few large studies in China have assessed the association of BMI with mortality, but most were conducted during the previous decades and the results were somewhat inconsistent, perhaps due to different methodological approaches used. Furthermore, both in the West and China, there is generally a lack of genetic data to help assess causality between adiposity and specific disease risks.

Numerous studies have investigated the association of BMI, with overall and cause-specific mortality. In general, they have shown a J-shaped association, with high BMI (>25 kg/m2) associated with increased mortality from vascular, certain cancer, diabetic and hepatic diseases and low BMI (<22.5 kg/m2) generally associated with increased mortality from chronic respiratory diseases and lung cancer. Some of the inverse associations observed may be due to incomplete control for reverse causation (i.e. pre-existing diseases causing low BMI) and/or inappropriate control for confounding factors (e.g. smoking). Among people with certain conditions such as diabetes, there is also a so-called adiposity paradox, in which individuals with high BMI tend to have better survival prognosis than those with low BMI, for reasons that are not fully explained.

China Kadoorie Biobank is a prospective cohort study of 0.5 million people contacted in 2004-08 from 10 diverse areas of China, with extensive data collection and with long-term storage of blood samples. All the participants are being followed up for cause-specific mortality and hospitalised episodes using ICD-10. CKB is well placed to provide large-scale new evidence about the impact and the implications of underweight and excess weight, measured in various ways (e.g. BMI, waist circumference (WC), %body fat), on overall and cause-specific mortality in Chinese adults.

The overall aim of this project is to assess the associations of different measures of adiposity with cardio-metabolic diseases among participants without prior diseases and those with certain specific pre-existing chronic diseases, especially diabetes. There are a few specific objectives, including a) Examine the association of general and central adiposity measures with stroke subtypes; b) Investigate the associations of adiposity measures with plasma biomarkers and the potential mediating roles of these, and additional (e.g., blood pressure), biomarkers in the association of adiposity with stroke subtypes; c) Use genetic data to assess the potential causality of the observed associations between adiposity and stroke subtypes; d) Examine the association of various adiposity measures with all-cause and cause-specific mortality among people with and without pre-existing diseases e.g., diabetes.