Presentation: Patient with commercial ‘polygenic score’ results and a family history of cardiovascular disease
A patient buys a direct-to-consumer polygenic score test to better understand their risk of cardiovascular disease. Polygenic scores cannot yet be used clinically to predict disease risk and cannot be used to diagnose an underlying inherited cardiac condition.
At a glance:
- Polygenic scores (PGSs) are calculated by aggregating many genetic variants (single nucleotide polymorphisms (SNPs)) to indicate an individual’s predisposition to common diseases like cardiovascular disease. There are >250 PGSs for cardiovascular disease and there is wide variation in their performance according to the choice and number of SNPs used in their calculation.
- PGSs for cardiovascular disease show potential in research settings to improve cardiovascular risk assessment and a large NHS study is investigating if they can be integrated with QRISK3, known as integrated risk scores, to improve performance. However, as PGSs have predominantly been derived from European ancestry groups, their application to other ancestry groups restricts their current clinical utility.
- For most diseases, a PGS contributes to a minority of an individual’s total risk; when used in isolation, it does not take into account environmental risk factors or inherited cardiac conditions.
- Alert! PGSs cannot yet be recommended for cardiovascular risk assessment in clinical settings.
Example clinical scenario
A 37-year-old man presents with the results of a direct-to-consumer genomic test that calculates his lifetime risk of developing cardiovascular disease based on a PGS of 12 SNPs. He is worried about his risk of cardiovascular disease as his father had a myocardial infarction at 55 years of age and a paternal uncle has angina.
Identifying those at risk of a genomic condition
- Identify individuals who may be at risk of an inherited cardiac condition, such as inherited cardiomyopathy or familial hypercholesterolaemia.
- Flags for an underlying genetic diagnosis include:
- very high cholesterol levels:
- age <30 years old, with either total cholesterol >7.5mmol/L , LDL-cholesterol >4.9mmol/L or non-HDL cholesterol >6.0mmol/L;
- age >30 years old, with either total cholesterol >9.0mmol/L , LDL-cholesterol >6.4mmol/L or non-HDL cholesterol >7.5mmol/L ;
- a clinical diagnosis of familial hypercholesterolaemia according to the Simon Broome criteria or Dutch Lipid Network tools.
- a family history of sudden cardiac death: sudden cardiac death at a young age can be caused by inherited cardiovascular diseases, such as cardiomyopathies and inherited arrhythmia syndromes (see Presentation: Patient with a family history of sudden cardiac death); and
- a family history of cardiomyopathy: 40%–60% cases of cardiomyopathies are familial (see Presentation: Patient with a family history of cardiomyopathy).
- very high cholesterol levels:
What should you do next?
- Establish if there is an increased risk of cardiovascular disease based on traditional risk factors using a validated clinical tool in routine practice, such as QRISK.
- Do not use the commercial PGS to make a personalised risk prediction for cardiovascular disease.
- Flags for cardiovascular disease include:
- hypertension;
- hypercholesterolaemia;
- diabetes;
- chronic kidney disease;
- atrial fibrillation;
- rheumatoid arthritis, systemic lupus erythematosus and other inflammatory autoimmune disorders;
- serious mental health disorders, such as schizophrenia, post-traumatic stress disorder and anxiety;
- influenza;
- periodontitis;
- ancestry, with an increased risk in those of South East Asian or Sub-Saharan African ancestry;
- a family history of cardiovascular disease;
- smoking;
- physical inactivity; and
- obesity.
- Arrange a cardiovascular disease risk assessment:
- body mass index, blood pressure, urea and electrolytes, liver function testing, lipid profile and including (if appropriate) haemoglobin A1c (HbA1c).
- Calculate QRISK3 score and manage according to NICE/CKS guidelines.
- Address any lifestyle factors, including smoking, obesity and diet.
- If the patient has a raised cholesterol, consider familial hypercholesterolaemia as a possible diagnosis. See Presentation: Patient with raised cholesterol.
- Research is ongoing into PGSs to understand causes of disease and to explore their role in stratification of populations into low and high risk of disease.
- In the future, integrated risk scores may be used in clinical practice to assess cardiovascular risk. For this reason it may be advisable to review the patient’s PGS results in 3–5 years.
- If you are discussing genomics concepts with your patients, you may find it helpful to use the visual communication aids for genomics conversations.
Resources
For clinicians
- Heart UK: Find your nearest lipid clinic today
- NICE: CVD risk assessment and management: What are the risk factors?
- NICE: Hypercholesterolaemia – familial
- NHS England’s Genomics Education Programme: NHS launches new polygenic scores trial for heart disease
- NHS England’s Genomics Education Programme: Polygenic risk scores and DTC testing: a problematic pairing?
For patients
- British Heart Foundation: Inherited heart conditions
- British Heart Foundation: Familial hypercholesterolaemia
- Heart UK: Eating for lower cholesterol