Approved Research

Causal pathways of lipoproteins in atherosclerotic cardiovascular diseases and cause-specific mortality: observational, metabolomic, and genetic studies

Lay summary

Atherosclerotic disease, leading to clogged blood vessels in the heart, brain, and legs, is the main cause of mortality world-wide. Atherosclerotic disease is becoming more common, partly because more people reach higher ages, but also because more people smoke, are exposed to environmental pollution, eat more processed food, and exercise less. Elevated low-density lipoproteins carry cholesterol in the bloodstream and can accumulate in the blood vessel walls, thereby causing atherosclerotic disease. There are also other lipoproteins, called remnant lipoproteins, that cause atherosclerosis and increase inflammation in the body. However, the mechanism behind this is not known, nor is it known if different lipoproteins affect blood vessels in the heart, brain, and legs the same. Furthermore, it is not known if individuals with elevated remnant lipoproteins are at higher risk of dying from causes not related to atherosclerosis.

Aims:

The aims of this study are to:

- Determine if different lipoproteins may similarly cause atherosclerotic disease in the heart, brain, and legs.

- Determine if different lipoproteins may cause cardiovascular, cancer and other mortality.

- Determine if different lipoproteins may similarly cause atherosclerotic disease in the heart, brain, and legs and cardiovascular, cancer and other mortality in individuals with diabetes.

Scientific rationale:

Drugs that can lower remnant lipoproteins, in addition to low-density lipoproteins, are likely to soon become clinically available. This opens the possibility to identify groups that may especially benefit from lowering of remnant lipoproteins in relation to low-density lipoproteins.

This can be done using a method called Mendelian Randomization, which and can be used to determine causality of risk factors such as low-density lipoproteins and remnant lipoproteins. It is best when done in large population studies like the UK biobank, in which is possible to compare the people that develop different atherosclerotic diseases and die from different causes.

Project duration:

For a start 36 months, may thereafter be extended.

Public health impact:

We expect to provide knowledge for improved prevention of atherosclerotic diseases and death from different causes. Our results may help scientists develop new preventive treatments, clinicians identify which lipoprotein to treat, individuals change lifestyle, and policymakers design public health interventions. Ultimately, we hope our research will contribute to fewer people suffering from disease and more people living longer healthier lives.