Background:
Obese individuals have disturbed blood pressure (BP) rhythmicity and relative natriuretic peptide (NP) deficiency. The relationship of diurnal variation in NP levels and 24h BP rhythm is not known. Furthermore, mechanisms behind difference in circulating NPs in healthy obese and lean individuals has not been explored. We conducted a prospective clinical trial to evaluate 1) the diurnal rhythmicity of NPs and its relationship with 24-hour BP rhythm between healthy lean and obese individuals, and 2) elucidate mechanism behind NP deficiency in obese.
Methods:
Healthy, normotensive, lean (BMI:18.5-25 kg/m
2
) and obese (BMI:30-45 kg/m
2
) individuals aged 18-40 years, underwent 24-hour standardized inpatient protocol involving ambulatory BP monitoring (ABPM), controlled light intensity, and 10 blood draws, following 5-days of standardized diet. NP gene expression was evaluated in a cohort of 37 healthy donor heart tissues obtained from the MAGNet repository.
Results:
Among 52 participants screened, a total of 40 participants (18 lean; 22 obese) were enrolled. Diurnal variation in MRproANP levels was seen in both lean and obese individuals (p for rhythmicity=0.001). The mesor of the NP rhythm was 15% (8.5-21.6%) lower in obese. The diurnal variation in MRproANP was in antiphase with diurnal variation of systolic BP (p<0.001) (
Figure
). Obese participants had lower 24h renin levels (p=0.06) and higher nocturnal sodium excretion (p=0.08). Among obese, there was lower expression of NP production genes (
NPPA, NPPB)
(p<0.05)
,
and higher expression of clearance gene (
NPR3
) (p<0.001) in heart tissue.
Conclusions:
In a mechanistic human trial, we elucidate key neurohormonal differences in rhythm and evidence of poor salt handling in obese. Decreased production and increased clearance may contribute to the NP deficiency in obese. Targeting the diurnal NP-BP rhythm axis may reduce the cardiovascular risk burden, specifically in obese individuals.
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