Risk of Atherosclerotic Cardiovascular Disease in Early Type 2 Diabetes: A Retrospective Study Using CPRD Aurum Data

Study type
Protocol
Date of Approval
Study reference ID
24_003716
Lay Summary

Atherosclerotic cardiovascular disease (ASCVD) is a condition where fat deposits build up in the body's blood vessels, leading to heart attacks and blood clots in the brain, a condition called a stroke. ASCVD is more common in people with type 2 diabetes (T2D), a condition that leads to difficulties in managing blood sugar levels, leading to an increased life-time risk of heart attacks and strokes compared to the general population.

Website-based computer programs exist that include several factors such as age, sex, blood pressure, and smoking status to calculate the chances that the person will experience a heart attack or stroke over the next 10 years. These programs can support healthcare professionals (HCPs) and patients in making further treatment decisions, including changes in lifestyle factors and use of medications.

Our research will investigate how great a risk of heart attack and stroke people with T2D have when they just start or are early in their treatment to lower their blood sugar levels. We will also investigate the risk associated with specific groups of patients, such as those with a high body weight. This can identify people who are at especially high risk and may benefit from earlier, more intensive treatment of their T2D.

Early intervention in people with T2D is essential to prevent the development of ASCVD. Our findings will provide important insights into the cardiovascular risks in subgroups of people with T2D, enabling improved treatment management and may ultimately reduce their burden of ASCVD.

Technical Summary

This retrospective study will use CPRD Aurum data to estimate the 10-year ASCVD risk in type 2 diabetes patients at the time of prescription of 1st and 2nd line therapy for hyperglycaemia. The purpose of this study is to understand the unmet needs of these individuals in terms of cardiovascular disease prevention. The primary exposures will be predictors in the ASCVD Risk Estimator Plus and QRISK3 engines, including age, sex, race, cholesterol levels, blood pressure, diabetes, and smoking status. Both engines are based on Cox proportional hazards models where parameters and source code are publicly available. From the models and the covariate information, cumulative hazard can be calculated and translated into probability of ASCVD occurring during the 10 year timeframe. The risks will be calculated in all patients, and investigated in specific subgroups such as those with high BMI, specific age and deprivation groups, or comorbidities such as chronic kidney disease. The statistical methods will involve descriptive statistics of the distributions of probabilities in the various groups. In the event of missing data, multiple imputation will be applied to find a median imputed value for each covariate for each patient, in order to obtain a complete case dataset. The intended public health benefit of this research is to increase understanding of the unmet need for this patient group in terms of intervening early to prevent cardiovascular disease, which is a major cause of morbidity and mortality in these patients.

Health Outcomes to be Measured

Outcomes to be Measured

Primary Outcome:
10-year ASCVD Risk Estimator Plus and QRISK®3 engine risk in the entire patient population

ASCVD Risk Estimator Plus Key Variables:
- Age
- Sex (Male/Female)
- Race (White / African-American / Other)
- Smoking status (Current / Former / Never)
- Diabetes status (Yes / No) (is a variable in the ASCVD Risk Estimator Plus. All patients included will be diagnosed with type 2 diabetes)
- Total Cholesterol (mmol/L)
- HDL (mg/dL)
- LDL (mg/dL)
- Systolic blood pressure (mmHg)
- Diastolic blood pressure (mmHg)
- Hypertension treatment (Yes/No)
- Statin treatment (Yes/No)
- Aspirin treatment (Yes/No)

QRISK®3 Key Variables:
- Age
- Sex (Male/Female)
- Ethnicity
- Smoking status
- Diabetes 1 or 2 (included verbatim per QRISK®3 definition, while study population is solely T2D)
- Family history angina or heart attack
- Chronic Kidney Disease Stages 3, 4, or 5
- Atrial fibrillation
- Hypertension treatment (Yes/No)
- Migraines
- Rheumatoid arthritis
- Systemic lupus erythematosus
- Schizophrenia, bipolar disorder or moderate/severe depression
- Atypical antipsychotic medication
- Steroid tablets
- Diagnosis of or treatment for erectile disfunction
- Cholesterol/HDL ratio
- Systolic blood pressure (mmHg)
- Standard deviation of at least two most recent systolic blood pressure readings (mmHg)
- Height (cm)
- Weight (kg/lbs)

Collaborators

Esther Zimmermann - Chief Investigator - Novo Nordisk A/S
Christian Kruse - Corresponding Applicant - Novo Nordisk A/S
Anders Boeck Jensen - Collaborator - Novo Nordisk A/S
John Wilding - Collaborator - University of Liverpool
Kamlesh Khunti - Collaborator - University of Leicester
Manjunatha Revanna - Collaborator - Novo Nordisk A/S
Stephen Bain - Collaborator - Swansea University

Linkages

HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation