Each year, heart and blood vessel diseases (commonly known as cardiovascular disease [CVD]) such as heart attack and stroke result in millions of deaths around the world. Many individuals have raised cholesterol levels in their blood that causes fatty deposits to narrow their blood vessels.
Previous tools used to assess an individual’s likelihood of having a disease of the heart and blood vessels have been based on a single/one-time measurement of cholesterol and other factors known to increase one’s risk of cardiovascular disease. Two recent studies from the US have shown that cholesterol build-up over early adulthood increases one’s risk of some cardiovascular diseases in the future.
Using electronic patient records from general practices across the UK, this study aims to revisit how diseases of the heart and blood vessels are assessed. Repeated cholesterol measurements during childhood and adulthood together with other factors known to increase one’s risk (such as high blood pressure, smoking, obesity) will be described and then used to assess an individual’s risk of cardiovascular disease later in life.
The findings of this study will provide evidence that could influence the decision to start managing cholesterol levels at a much younger age. Additionally, the study will look at the risk of cardiovascular disease in difference groups of people, based on ethnicity and social deprivation. That way, we will be able to define characteristics of people who might be at a greater risk than the general population, to ensure they are given the necessary attention.
Background: Previous observational studies have demonstrated long-term exposure to elevated cholesterol levels in young adults allow cholesterol to accumulate and increase the risk of cardiovascular disease, similar to pack-years in smoking.
Aim: To investigate trajectories of cholesterol and associations between cumulative exposure to atherogenic risk factors (blood lipid, glycated haemoglobin, smoking habits, body mass index, blood pressure) and incidence of cardiovascular morbidity and mortality outcomes in the UK general population.
Study Design: Open cohort using prospectively recorded primary and secondary care data
Setting: UK General Practices
Participants: Patients with cholesterol measurements recorded from the study start date of 1st January 1997
Primary outcome: Major adverse cardiovascular event (defined as the first occurrence of a composite of either coronary heart disease, stroke, peripheral vascular disease, heart failure, or cardiovascular-related mortality).
Methods: An age-based analysis will be used to quantify the cardiovascular risk associated with cumulative exposure to atherogenic risk factors over time. A non-parametric cubic spline based on a mixed-effects model will be used to estimate the subject-specific exposure for all patients. The relationship between the atherogenic risk exposure measures and outcome events after age 40 years will be assessed using Fine and Gray competing risk models. The models will be adjusted for relevant confounders including sex, ethnicity, alcohol status, comorbid conditions, and prescribed medications.
Outputs: Evidence on the relationship between cumulative exposure of atherogenic risk factors and cardiovascular morbidity and mortality outcomes in a real-world setting.
The primary outcome of interest is the first occurrence of major adverse cardiovascular event (defined as the composite of either coronary heart disease, stroke, peripheral vascular disease, heart failure, or cardiovascular-related mortality).
• Morbidity outcomes:
o Coronary heart disease (defined as a diagnosis of either myocardial infarction, angina (stable or unstable), CHD not otherwise specified, or a record for coronary revascularisation [coronary bypass surgery or coronary angioplasty]). [1]
o Stroke (including haemorrhagic stroke, ischaemic stroke, stroke not-otherwise defined).
o Peripheral vascular disease
o Heart failure
• Mortality outcomes:
o Cardiovascular-related mortality (defined as death attributable to myocardial ischemia and infarction, heart failure, cardiac arrest because of other or unknown cause, or cerebrovascular accident).
o All-cause mortality
Ralph Kwame Akyea - Chief Investigator - University of Nottingham
Ralph Kwame Akyea - Corresponding Applicant - University of Nottingham
Folkert Asselbergs - Collaborator - University College London ( UCL )
George Ntaios - Collaborator - University of Thessaly
Joe Kai - Collaborator - University of Nottingham
Laila Tata - Collaborator - University of Nottingham
Nadeem Qureshi - Collaborator - University of Nottingham
Yana Vinogradova - Collaborator - University of Nottingham
Yiyi Zhang - Collaborator - Columbia University
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation