Low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride and diverse non-cardiovascular diseases: a large population-based cohort study using CALIBER dataset

Date of ISAC Approval: 
Lay Summary: 
It is generally agreed that high levels of low-density lipoprotein cholesterol (LDL, which is regarded as a bad blood lipid), but low levels of high-density lipoprotein cholesterol (HDL, which is regarded as a good blood lipid), can lead to cardiovascular disease. However, some studies suggested that low LDL, and perhaps high HDL, might increase the risks of other diseases, such as, some eye diseases, Alzheimer's disease, Parkinson's disease, diabetes, cirrhosis, and some autoimmune diseases. However, limitations of existing evidence make it difficult to draw any conclusion. This study aims to investigate whether or not low LDL, and high HDL, levels increase risks of these diseases. Use of the data from a very large number of people in England will provide comprehensive information with a wide range of cholesterol levels and variety of clinical outcomes during over 13 years of follow-up. Our study will include those who have a baseline cholesterol measurement while free of these specified diseases. We will employ statistical methods to examine whether LDL and HDL levels are related to the first diagnosis of these diseases. The finding of the study will provide new insight into the role of LDL- and HDL-cholesterol across the whole range of values.
Technical Summary: 
Observational studies have shown that LDL, and HDL, cholesterol levels might be associated with some autoimmune disorders and some idiosyncratic adverse events. Due to limitations of existing evidence, however, the role of LDL, and HDL, cholesterol in non-cardiovascular diseases is still questioned. This observational study aims to examine the associations between LDL, HDL and the incidence of diverse non-cardiovascular diseases, including cataract, age-related macular degeneration, Alzheimer's disease, Parkinson's disease, type 2 diabetes, cirrhosis, psoriasis, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis. Use of CALIBER data will allow us to investigate the full spectrum of LDL and HDL levels. We will include the population without pre-existing disease of interest whose LDL and HDL measurement was available during 1996 to 2000, and we will follow them up until the disease of interest occurred until 2010. Hazard ratios of the incidence of disease for each unit change in LDL and HDL will be calculated using time-dependent Cox proportional hazard models adjusted for potential confounders. We will also examine the role of age, gender as effect modifiers. The findings of this study will allow the investigator to conduct further research to understand more about the role of LDL and HDL cholesterol in non-cardiovascular diseases.
Health Outcomes to be Measured: 
Incidence of diverse non-cardiovascular diseases (non-CVDs), including cataract, aged-related macular degeneration, Alzheimer's disease, Parkinson's disease, site-specific cancer, type 2 diabetes, liver cirrhosis, psoriasis, rheumatoid arthritis, multiple sclerosis, and systemic sclerosis in a large unselected population without pre-existing diseases of interest. Time to first diagnosis of diseases listed above.

Professor Harry Hemingway - Chief Investigator - University College London (UCL)
Dr Alireza Moayyeri - Collaborator - UCB Pharma SA - UK
Dr Amitava Banerjee - Collaborator - University College London (UCL)
Nat Na-Ek - Corresponding Applicant - Farr Institute of Health Informatics Research