BP Polygenic Risk Scores May Complement Measured BP for CVD Prevention
Key findings
- This analysis of the prospective UK Biobank study examined whether blood pressure polygenic risk score (BP PRS) is associated with new-onset cardiovascular disease independent of measured BP and use of antihypertensive medication in middle-aged adults
- Genetic predisposition to elevated BP was associated with independent and generally greater CVD risk compared with single in-office BP measures
- BP PRS identified one in 10 individuals with normal BP who had the same level of CVD risk as those with untreated hypertension, otherwise overlooked based on measured BP
- Similarly, BP PRS showed one in four individuals with untreated hypertension had a CVD risk compared to those who had been prescribed antihypertensives
- BP PRS may be an important complement to measured BP in guiding hypertension screening, supporting earlier use of antihypertensives, and determining more aggressive BP targets
Sustained elevation in blood pressure (BP) is strongly associated with a higher risk of cardiovascular disease (CVD), but the substantial intraindividual variability complicates clinical management. Now, researchers at Massachusetts General Hospital have determined that BP polygenic risk scores (PRS) predict new-onset CVD in middle-aged adults independent of measured BP.
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So Mi Jemma Cho, PhD, a fellow at the Cardiovascular Research Center, Pradeep Natarajan, MD, MMSc, director of the Cardiovascular Disease Prevention Center and the Paul and Phyllis Fireman Endowed Chair in Vascular Medicine, and colleagues report the details in JAMA Cardiology.
Methods
The researchers drew data from the UK Biobank, a prospective cohort study of the general U.K. population aged 40 to 69 years between March 2006 and August 2010. They had BP measured as part of the baseline physical examination.
The current analysis included 331,078 participants without a prior diagnosis of CVD. The mean age was 57, and 54% were female. At baseline, 25% had normal BP (<130/80 mm Hg without antihypertensives), 60% had untreated hypertension (systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg), and 15% were being treated with antihypertensives.
BP PRSs were derived based on a genome-wide association study in the Million Veteran Program published in Nature Genetics. The primary outcome was the first CVD event, defined as myocardial infarction, stroke, heart failure, or CVD-related death.
Results
After adjustment for sociodemographics, clinical risk factors, the number of antihypertensive medications prescribed and measured BP, the hazard ratios for CVD per each standard deviation of increase in BP PRS were:
Systolic BP PRS
- Overall—1.07
- Normal BP—1.13
- Untreated hypertension—1.04
- Treated hypertension—1.06
Diastolic BP PRS
- Overall—1.04
- Normal BP—1.05
- Untreated hypertension—1.04
- Treated hypertension—1.04
BP genetic risk identified one in 10 normotensive individuals who had comparable CVD risk as those with untreated hypertension even after accounting for measured BPs. Similarly, BP PRS showed that one in four individuals with untreated hypertension had the same CVD risk as those treated with antihypertensives.
Clinical Applications
The study results imply knowledge of BP PRS could be used to:
- Aid primary prevention of CVD in individuals with normal BP by supporting public health surveillance for hypertension and favorable lifestyle
- Help identify individuals for whom early treatment with antihypertensives should be considered
- Suggest when individuals with treated hypertension are at residual risk of CVD and need treatment intensification and more aggressive BP targets
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