Polygenic Risk Scores in Cardiovascular Risk Prediction
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Addition of polygenic risk scores (PRSs) to conventional risk factors can modestly enhance prediction of first-onset cardiovascular disease (CVD) and could translate into population health benefits if used at scale, according a recent finding.

Using data from UK Biobank, researchers calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol).

Participants were 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age: 56.0 years; females: 57%; median follow-up: 8.1 years), They then modelled the population health implications of initiating statin therapy as recommended by current guidelines using data from 2.1 million individuals from the Clinical Practice Research Datalink.

The C-index, a measure of risk discrimination, was 0.710 for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012, and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively.

They estimated that targeted assessment of PRSs among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened, which would be almost 15 times more efficient than blanket assessment of PRS.

“Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone,” the researchers commented.

They further added, “Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein.”

The researchers mentioned that the study had limitations, since they studied only middle-aged European ancestry participants in the UK, which limits the generalisability of their results.

Future studies (including health economic evaluations) are needed to evaluate a range of different CVD screening strategies, including a ‘genome first’ approach that inverts the current ‘conventional risk factors first’ approach to CVDs, the researchers stated.

Source:
https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003498
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