Approved Research

The association of metabolic trajectory with cardiovascular events, cancers events and all-cause death based on cohort study and Mendelian randomization study

Lay summary

Accelerated urbanization caused by rapid economic development has brought about a series of unhealthy lifestyle changes, such as lack of physical activities, unhealthy diet and stress, which may increase the risk of metabolic syndrome. The metabolic syndrome is closely related to the occurrence of cardiovascular events, and increases the risk of all-cause death, seriously endangering human life and health. Therefore, this study intends to investigate the influence of various trajectories of metabolic status on the incidence of cardiovascular diseases and all-cause mortality conducted by prospective cohort study design with trajectory model method and used the Mendelian randomized (MR) study method to infer the causal association between metabolic status and cardiovascular events, cancer or all-cause death. Based on the cohort study design, the study will be performed using the trajectory model method, which is used to assess the relationships between long-term exposure and outcome. A promising approach known as Mendelian randomization (MR), which uses inherited genetic variants as instrumental variables, provides stronger evidence for the causal effect of exposure on the diseases largely overcoming the traditional limitations due to confounding and reverse causality. In addition, a novel analytical framework was applied to evaluate the causal association between gene expression or DNA methylation levels and diseases that could minimize confounding and reverse causation through an MR approach integrating quantitative trait loci (QTL) and genome wide association study (GWAS) data. We plan to complete the project in 24 months. Early detection of individual metabolic status can provide new ideas for early prevention of chronic noncommunicable diseases and help to reduce the risk and burden of disease.

Scope extension:

Accelerated urbanization caused by rapid economic development has brought about a series of unhealthy lifestyle changes, such as lack of physical activities, unhealthy diet and stress, which may increase the risk of metabolic syndrome. The metabolic syndrome is closely related to the occurrence of cardiovascular events, cancer, and increases the risk of all-cause death, seriously endangering human life and health. Therefore, this study intends to investigate the influence of various trajectories of metabolic status on the incidence of cardiovascular diseases, cancer, and all-cause mortality conducted by prospective cohort study design with trajectory model method, so as to provide new ideas for disease prevention.

In addition, we intend to use the Mendelian randomized (MR) study method to infer the causal association between metabolic status and cardiovascular events, cancer or all-cause death. In this MR study based on a cohort study design, we aimed to explore: 1) whether there exists causal association between metabolic status and cardiovascular events, cancer or all-cause death; 2) whether this causal association according to metabolic components, i.e. high-density lipoprotein or blood pressure, which have a different underlying pathogenesis.

Globally, it is estimated that 17.9 million (32%) people died from cardiovascular diseases (CVDs) in 2019, and 85% of those deaths were due to heart attack and stroke. In 2010, the American Heart Association developed a new concept, cardiovascular health (CVH), which is defined by health behaviors (smoking, body mass index, physical activity and diet) and health factors (total cholesterol, blood pressure, and fasting blood glucose), focusing on prevention and reducing the burden of CVDs. Previous studies showed that ideal CVH metrics or higher CVH scores were associated with a decreased risk of CVDs, stroke, heart failure (HF) and mortality, which presented an inverse gradient curve. Data from the Kuopio Ischemic Heart Disease study indicate that ideal CVH metrics were inversely associated with acute myocardial infarction, sudden cardiac death, and all-cause mortality among Finnish men during a follow-up period of 25 years. The CVH components included modified lifestyle factors and biological factors. Therefore, this study intends to investigate the joint and independent effect of metabolic status and CVH on the incidence of cardiovascular diseases and all-cause mortality conducted by prospective cohort study design, so as to provide new ideas for disease prevention.

Based on a cohort study design, we aimed to further explore the joint association of CVH and metabolic health with cardiovascular disease, death, and life expectancy.