What is the clinical evidence from this study?

Study design: Cohort. Population: Hypertension (n=17000). Intervention: Genetic risk score (GRS) vs. Traditional risk factors. Primary outcome: Hypertension incidence (OR 1.110, 95% CI 1.065-1.156, p=6.7 E-07).

What does this research mean for the field?

A 29-SNP genetic risk score is independently associated with long-term blood pressure increases and incident hypertension, but it does not improve risk prediction beyond traditional clinical risk factors. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

December 12, 2012Open Access

Prediction of Blood Pressure Changes Over Time and Incidence of Hypertension by a Genetic Risk Score in Swedes

Key Result

A 29-SNP genetic risk score was independently associated with incident hypertension (OR 1.110; 95% CI 1.065-1.156; P=6.7E-07) over 23 years, but did not improve prediction over traditional risk factors.

Study Design

Type

Cohort (n=17,000)

Structured PICO

Does a 29-SNP genetic risk score predict blood pressure changes and incident hypertension in middle-aged adults?

Population

>17,000 middle-aged Swedes participating in the prospective Malmö Preventive Project

Intervention

Genetic risk score (GRS) based on 29 independent single nucleotide polymorphisms

Outcome

Blood pressure change over time and hypertension incidencesurrogate

A 29-SNP genetic risk score is independently associated with long-term blood pressure increases and incident hypertension, but does not improve predictive accuracy over traditional clinical risk factors.

Main Result

Effect estimate: OR 1.110 (95% CI 1.065-1.156)

p-value: p=6.7 E-07

Limitations

A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors.

Abstract

Recent Genome-Wide Association Studies (GWAS) have pinpointed different single nucleotide polymorphisms consistently associated with blood pressure (BP) and hypertension prevalence. However, little data exist regarding single nucleotide polymorphisms predicting BP variation over time and hypertension incidence. The aim of this study was to confirm the association of a genetic risk score (GRS), based on 29 independent single nucleotide polymorphisms, with cross-sectional BP and hypertension prevalence and to challenge its prediction of BP change over time and hypertension incidence in >17 000 middle-aged Swedes participating in a prospective study, the Malmö Preventive Project, investigated at baseline and over a 23-year average period of follow-up. The GRS was associated with higher systolic and diastolic BP values both at baseline (β ± SEM, 0.968 ± 0.102 mm Hg and 0.585 ± 0.064 mm Hg; P<1E-19 for both) and at reinvestigation (β ± SEM, 1.333 ± 0.161 mm Hg and 0.724 ± 0.086 mm Hg; P<1E-15 for both) and with increased hypertension prevalence (odds ratio 95% CI, 1.192 1.140-1.245 and 1.144 1.107-1.183; P<1E-15 for both). The GRS was positively associated with change (Δ) in BP (β ± SEM, 0.033 ± 0.008 mm Hg/y and 0.023 ± 0.004 mm Hg/y; P<1E-04 for both) and hypertension incidence (odds ratio 95% CI, 1.110 1.065-1.156; P=6.7 E-07), independently from traditional risk factors. The relative weight of the GRS was lower in magnitude than obesity or prehypertension, but comparable with diabetes mellitus or a positive family history of hypertension. A C-statistics analysis does not show any improvement in the prediction of incident hypertension on top of traditional risk factors. Our data from a large cohort study show that a GRS is independently associated with BP increase and incidence of hypertension.