Higher Serum Concentrations of N-Terminal Pro-B-Type Natriuretic Peptide Associate with Prevalent Hypertension whereas Lower Associate with Incident Hypertension

Abstract

BackgroundThe role of the natriuretic peptides (NPs) in hypertension is complex. Thus, a higher blood NP concentration is a robust marker of pressure-induced cardiac damage in patients with hypertension, whereas genetically elevated NP concentrations are associated with a reduced risk of hypertension and overweight individuals presumably at high risk of hypertension have lower NP concentrations.ObjectiveTo investigate the associations between serum N-terminal pro-B-type natriuretic peptide (NT-proBNP), used as a surrogate marker for active BNP, and prevalent as well as 5-year incident hypertension in a Danish general population sample.MethodsCross-sectional and prospective population-based study.ResultsAt baseline, among 5,307 participants (51.3% women, mean age 46.0±7.9 years) with a complete set of data, we recorded 1,979 cases with prevalent hypertension (PHT). Among 2,389 normotensive participants at baseline with a complete set of data, we recorded 324 cases with incident hypertension (IHT) on follow-up 5 years later. In models adjusted for age, sex, lifestyle, social, dietary, anthropometric, pulmonic, lipid, metabolic and renal risk factors, as well as heart rate and baseline blood pressure (only incident model), one standard deviation increase in baseline log-transformed NT-proBNP concentrations was on one side associated with a 21% higher risk of PHT (odds ratio [OR]: 1.21 [95% confidence interval (CI): 1.13-1.30], P<0.001), and on the other side with a 14% lower risk of IHT (OR: 0.86 [95%CI:0.76-0.98], P = 0.020).ConclusionsHigher serum concentrations of NT-proBNP associate with PHT whereas lower concentrations associate with IHT. This suggests that a lower amount of circulating BNP, resulting in diminished vasodilation and natriuresis, could be involved in the pathogenesis of hypertension in its early stages.

Abdominal Adiposity Distribution Quantified by Ultrasound Imaging and Incident Hypertension in a General Population

“…On the basis of these findings, it is reasonable to suggest that the lower amount of circulating B-type natriuretic peptide associated with increased VAT, resulting in diminished vasodilation and natriuresis, 40 could be involved in the pathogenesis of increased VAT-related hypertension in early stages of this disease. 41 Finally, although increased visceral fat has been related to the increased activation of the components in the reninangiotensin-aldosterone system (RAAS), 42 O'Seaghdha et al found no association between VAT and circulating measures of RAAS activity in the Framingham Heart Study, 43 and therefore, it was concluded that further studies are required to determine whether adipocyte-derived RAAS components contribute to systemic RAAS activity in humans. 43 In this study, we did not attempt to adjust for adipocytokines or measures of insulin resistance because previous studies from the Region of Copenhagen, conducted by our research group, have not found strong evidence to support that these substances are predictors of overweight-related incident hypertension or overweight-related incident CVD in Danish cohort studies.…”

NT-proBNP and the risk of incident hypertension

“…The many modifications of cardiac, arterial, as well as kidney function that are associated with hypertension may therefore affect BNP serum concentration, being concomitantly possible targets of BNP-mediated effects. A possible role of diminished vasodilation and natriuresis in the pathogenesis of hypertension has been very recently suggested by Seven et al [26], showing that lower 'baseline' NT-proBNP concentrations were associated with a higher risk of developing hypertension during the 5-year follow-up of a cohort of 5307 participants. However, they did not report 'changes' of serum levels of natriuretic peptides over time in patients who did develop hypertension as compared with patients whose blood pressure remained in the normotensive range.…”

Serum proatrial natriuretic peptide does not increase with higher systolic blood pressure in obese men

“…Common genetic variant s of NPPA and NPPB (encoding NP precursors A and B), which are associated with lower circulating NP concentrations, are correlated with higher systolic and diastolic BP along with an increased risk of hypertension, whereas common genetic variants in these loci, which are associated with higher circulating NP concentrations, are correlated with lower systolic and diastolic BP along with a decreased risk of hypertension 26 27. Overall, the data suggest that high to normal circulating amounts of NPs could protect against the development of hypertension through increased vasodilation and natriuresis,1 low to normal circulating amounts of NP concentrations could lead to higher BP through diminished vasodilation and natriuresis1 and could thus be causally related to the development of hypertension 19. In contrast, abnormally high circulating amounts of NPs may be the consequence of increased left atrial size, LVH and myocardial stretch caused by already developed hypertension with target organ damage than the primary cause of hypertension.…”

“…Nevertheless, based on the normal physiological response of the heart to increases in pressure load,1 14–17 we had expected the opposite: that circulating NP concentrations would have been robustly positively associated with mean 24-hour systolic ABP. Because proANP is not cleared by the NP clearance receptor,18 our findings suggest that mechanisms involved in normal NP secretion are somehow malfunctioning in obese patients with higher BP, resulting in low circulating amounts of NPs, which eventually could contribute to the development of hypertension in these patients 19…”