Evaluation of novel cardiovascular risk prediction approaches for UK adults
Conventional strategies for prevention of cardiovascular diseases (CVD) have focused on global CVD risk assessment using cigarette smoking, elevated levels of blood pressure or LDL-cholesterol and diabetes and targeting individuals above a certain threshold for risk factor modification. Clinical guidelines advocate estimation of absolute risk (10-year risk or life-time risk) of CVD using one of several global CVD risk assessment tools (Framingham, European SCORE or Ideal Cardiovascular Health), but the reliability of such approaches are uncertain. Additional clinical measurements such as “grip strength” or BMI have been advocated to supplement global CVD risk assessment. Appreciation of the magnitude of residual risk despite optimum control of conventional risk factors has prompted interest in more personalised approaches using novel genetic scores or novel plasma biomarkers (apolipoproteins, triglycerides, Lp(a) or C-reactive protein). We aim to use data from the UK Biobank study (UKB) to evaluate conventional and novel risk factors for CVD.
The UKB is a prospective cohort study of 0.5M adults recruited during 2008-2010 from the United Kingdom, with extensive data collection of lifestyle information (e.g. smoking, physical activity), and physical measurements (e.g. blood pressure, BMI and grip strength). Currently the UKB has ~ 40K CVD events recorded. Genotyping is available on all participants and blood biochemistry on all in 2018.
RESEARCH EXPERIENCE, RESEARCH METHODS AND TRAINING
This project aims to evaluate cardiovascular risk prediction approaches that can be used in contemporary UK and other Western populations.
The aims of this DPhil project are to:
- Review the literature on conventional global CVD risk prediction, utility of the addition of grip strength or BMI, or addition of polygenic risk scores or plasma measures of CRP or Lp(a) for prediction of overall and sub-types of CVD.
- Compare performance (calibration, discrimination, internal and external validity) of conventional global CVD risk assessment tools for prediction of CVD and sub-types of CVD in age and sex-specific groups in UKB.
- Evaluate the addition of other clinical measures (BMI, grip strength) or polygenic risk scores, CRP or Lp(a) to conventional global CVD risk assessment tools.
- Evaluate diagnostic performance and cost effectiveness of novel paradigms to screen for elevated levels of Lp(a) or CRP for CVD risk prediction and impact if any on non-CVD outcomes compared with conventional global risk assessment.
This project will involve working within a multi-disciplinary team and the candidate will gain research experience in systematic reviews, study design and planning, epidemiological and modern statistical methods.
FIELD WORK, SECONDMENTS, INDUSTRY PLACEMENTS AND TRAINING
By the end of their DPhil, it is expected that the candidate will be able to plan, undertake, interpret, and report their findings in a clear and concise manner. The student will have acquired transferable skills such as the writing of project proposals and presenting the research findings at local, national, and international meetings. The student will be expected to publish several peer-reviewed papers as the lead author by the end of their DPhil.
The candidate should have a 2.1 or higher degree in a quantitative subject and an MSc in Epidemiology or Medical Statistics. The candidate should also have a strong interest in cardiovascular disease epidemiology.