Heart attacks, strokes and blood circulation problems are the main cause of death in the United Kingdom. Health care professionals usually measure amount of fat in the blood because they are linked to these problems. There are different types of fat in the blood. The main blood fat that is measured and treated is cholesterol. Despite reducing cholesterol to very low levels, there remains a risk of heart attacks and strokes. It is important to understand if reducing other types of blood fats will reduce a person’s risk of having heart attacks or strokes. In addition, previous studies have suggested that abnormal amounts of fat in blood is linked to damage to back of eyes, kidneys, and nerves (which are cable like structures to carry signals between brain and rest of body and help to feel sensations and pain).
We are planning to use information collected in patients’ electronic health records and death registers to understand:
i) How common raised levels of fats are in the general population.
ii) The link between levels of different types of fat and risk of heart attack and strokes.
iii) To confirm the relationship between elevated fat levels and damage to eyes, kidneys, and nerves by examining this in a much larger number of people compared to other studies.
The findings of this study may help us to find another treatment target to prevent complications of raised fat in blood.
Hypertriglyceridemia is a residual cardiovascular risk factor, independently associated with atherosclerotic cardiovascular disease (ASCVD) and diabetic microvascular complications. Establishing the role of hypertriglyceridaemia in cardiovascular and microvascular complications is crucial with new drug developments.
This study aims to explore association of hypertriglyceridemia with cardiovascular disease and diabetes-related microvascular complications.
Data will be obtained from CPRD Aurum with linkage to hospital (Hospital Episodes Statistics), mortality (Office for National Statistics) and deprivation (Index of Multiple Deprivation) data.
The study populations will comprise of 3 cohorts.
1. Adults with prior ASCVD (Secondary prevention cohort)
2. Adults with no prior ASCVD but have diabetes mellitus and one or more other established CV risk factors (Primary prevention cohort)
3. All adults with diagnosis of diabetes mellitus (Diabetes cohort)
Cohorts will be defined using SNOMED CT (UK edition), Read Version 2, and local EMIS Web® software-specific codes between 1 January 2010 and 31 December 2022 (or latest available data) for cohort 1 and 2, and 1 January 2000 to 31st December 2022 (or latest available data) for cohort 3.
The primary outcomes will be a composite of fatal and non-fatal cardiovascular events in Cohort 1 and 2, and a composite of end-stage retinopathy, nephropathy and neuropathy in Cohort 3. The secondary outcomes will comprise several cardiovascular endpoints, cerebrovascular endpoints, peripheral vascular endpoints, cardiovascular, and all-cause mortality in cohort 1 and 2, indivisual end-stage microvascular endpoints (retinopathy, nephropathy, neuropathy) in cohort 3 and effect of triglyceride lowering drugs (statins, fibrates, omega 3 fatty acids) on composite of fatal and non fatal cardiovascular and composite of end-stage microvascular end points.
Kaplan-Meier plots will be used to estimate the observed cumulative incidence of each outcome. Cox Proportional Hazard models will be used to estimate hazard ratios for the risk of outcomes across triglyceride groups.
Primary outcomes:
1. Composite of fatal and non-fatal cardiovascular events (Angina, Myocardial Infarction (MI), coronary revascularisation, stroke, Transient Ischemic Attack (TIA), Peripheral Artery Disease (PAD), Peripheral artery revascularisation, cardiovascular death) in cohort 1 and 2.
2. Composite of end-stage microvascular complications (retinopathy, nephropathy, neuropathy) in cohort 3.
Blindness, Laser treatment, proliferative retinopathy will be surrogate markers for end-stage retinopathy
End stage renal failure, Dialysis, creation of AV fistula and renal transplant will be surrogate markers for end-stage nephropathy
Non-traumatic lower extremity amputation will be surrogate marker for end-stage neuropathy.
Secondary Outcomes:
1. In cohort 1 and 2:
a) Cardiovascular endpoint: A composite of angina, myocardial infarction and coronary revascularisation.
b) Cerebrovascular endpoint: A composite of Stroke and transient ischemic attack.
c) Peripheral vascular endpoing: A composite of peripheral artery disease and peripheral artery revascularisation.
d) cardiovascular death
e) All cause death
In Cohort 3:
a) End-stage retinopathy
b) End-stage nephropathy
c) End-stage neuropathy
3. In Cohort 1 and 2 – Comparison of composite of fatal and non-fatal cardiovascular events in patients with and without triglyceride lowering medication (fibrates, statins, omega 3 fatty acids)
4. In cohort 3 – Comparison of composite of end-stage microvascular complications (neuropathy, nephropathy and retinopathy) with and without triglyceride lowering medication (fibrates, statins, omega 3 fatty acids)
Handrean Soran - Chief Investigator - University of Manchester
Bilal Bashir - Corresponding Applicant - University of Manchester
Alison Wright - Collaborator - University of Manchester
Darren Ashcroft - Collaborator - University of Manchester
Maryam Ferdousi - Collaborator - University of Manchester
Safwaan Adam - Collaborator - University of Manchester
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation