Abstract
Polymorphisms within individual natriuretic peptide genes have been associated with risk factors for cardiovascular disease, but their association with clinical outcomes was previously unknown. This study aimed to investigate the association between genetic variants in key genes of the natriuretic peptide system with cardiovascular outcomes in patients with coronary artery disease. Coronary disease patients (n
=
1810) were genotyped for polymorphisms within
NPPA,
NPPB,
NPPC,
NPR1 and
NPR2. Clinical history, natriuretic peptide concentrations, echocardiography, all-cause mortality and cardiovascular hospital readmissions were recorded over a median 2.8
years. Minor alleles of
NPPA rs5068, rs5065 and rs198358 were associated with less history of hypertension; minor alleles of
NPPA rs5068 and rs198358 was also associated with higher circulating natriuretic peptide levels (p
=
0.003 to p
=
0.04). Minor alleles of
NPPB rs198388, rs198389, and rs632793 were associated with higher circulating BNP and NT-proBNP (p
=
0.001 to p
=
0.03), and reduced E/E
1 (p
=
0.011), or LVESVI (p
=
0.001) and LVEDVI (p
=
0.004). Within
NPPC, both rs11079028 and rs479651 were associated with higher NT-proBNP and CNP (p
=
0.01 to p
=
0.03), and rs479651 was associated with lower LVESVI (p
=
0.008) and LVEDVI (p
=
0.018).
NPR2 rs10758325 was associated with smaller LVMI (p
<
0.02). A reduced rate of cardiovascular readmission was observed for minor alleles of
NPPA rs5065 (p
<
0.0001),
NPPB rs632793 (p
<
0.0001), rs198388 (p
<
0.0001), rs198389 (p
<
0.0001), and
NPR2 rs10758325 (p
<
0.0001). There were no associations with all-cause mortality. In established cardiovascular disease, natriuretic peptide system polymorphisms were associated with natriuretic peptide levels, hypertension, echocardiographic indices and the incidence of hospital readmission for cardiovascular events.
►
NPPA,
NPPB and
NPPC polymorphisms are associated with plasma natriuretic peptides. ►
NPPA polymorphisms were associated with less hypertension. ►
NPPB, NPPC, NPR1 and
NPR2 polymorphisms were related to indices of cardiac function. ►
NPPA, NPPB and
NPR2 polymorphisms were associated with cardiovascular outcomes. ► This gives further evidence for a protective role of the natriuretic peptide system.