N-terminal prohormone of brain natriuretic peptide (NT-proBNP) is an established biomarker for diagnosis of heart failure. The study aims to explore whether known cardiovascular risk factors, including education and income as indicators of socioeconomic position (SEP), may interact with the genetic effect of NT-proBNP-related single nucleotide polymorphisms (SNP) to influence plasma levels of NT-proBNP in a population-based study sample. Information on effect alleles of three SNPs previously reported to be related to NT-proBNP was combined individually for 4,520 participants of the Heinz Nixdorf Recall Study to calculate a genetic risk allele sum score (GRS_NT-proBNP). Linear Regression models were used to examine the association of cardiovascular risk factors and GRS_NT-proBNP with log-transformed NT-proBNP levels, as well as cardiovascular risk factor by GRS_NT-proBNP interactions. The GRS_NT-proBNP was associated with NT-proBNP showing 1.13-fold (95% CI 1.10–1.16) higher plasma levels per additional effect allele. Interaction terms included in the regression models gave some indication for interaction of the GRS_NT-proBNP with the SEP indicator income as well as with C-reactive protein. In regression models stratified by income quartiles the strongest genetic effect was observed in the third income quartile showing 1.18-fold (95% CI 1.12–1.25) higher average NT-proBNP levels per additional allele compared to the lowest income quartile with 1.08-fold (95% CI 1.01–1.15) higher NT-proBNP levels. The results of the present study indicate that genetic effects of NT-proBNP increasing alleles are stronger in higher SEP groups. This may be due to a stronger influence of non-genetic cardiovascular risk on NT-proBNP in low SEP groups.