Approved research

Lipoprotein(a) Distribution and Relation to Long-Term Cardiovascular Outcomes According to Sex, Ethnicity, LDL-C Levels, Prevalent Cardiovascular Disease and Diabetes Status, and Cholesterol-Lowering

Lay summary

Cardiovascular disease is the leading cause of morbidity and mortality in developed and many developing countries. While the relation of low density lipoprotein (LDL) cholesterol with risk for cardiovascular disease is well-documented, 'residual risk' of cardiovascular disease often remains despite well-controlled LDL-C levels. Such residual risk is due to a variety of factors including abnormalities in other lipoproteins. Elevated lipoprotein(a), a lipid biomarker, is largely genetically determined and an important independent risk factor for cardiovascular disease, and very high levels are associated with premature cardiovascular disease and aortic stenosis, even if LDL-C levels are not elevated. Up to 25% of different populations have increased levels of lipoprotein(a) that are associated with greater cardiovascular disease risk. Certain subpopulations, notably those of Asian Indian descent, may be at greater risk at lower thresholds of lipoprotein(a) and this study will have the ability to examine this. Moreover, prior studies have focused on smaller observational cohorts or clinical trials that can be subject to selection biases and other limitations. The UK Biobank offers a unique opportunity to examine the relation of lipoprotein(a) with a wide range of cardiovascular outcomes over approximately 10 years of follow-up in among the largest real word cohorts available. Information obtained from the proposed study will provide important answers on whether the relation of lipoprotein(a) depends on sex, ethnicity, levels of 'bad' LDL-cholesterol, the presence of known diabetes or cardiovascular disease, or use of cholesterol-lowering medication. Such information will be of value for better understanding the potential impact newer therapies aimed to reduce lipoprotein(a) levels may have on different cardiovascular endpoints.