Abstract
Objective: Excessive salt intake is the leading dietary risk factor for cardiovascular disease (CVD). This increased risk may be attributed to alterations in the human metabolome. Salt sensitivity is associated with ethnicity, and ethnic differences in the interaction between sodium intake and the metabolome may play an integral part in CVD development. We therefore investigated 1) the urinary metabolomic profiles of Black and White adults according to low, moderate and high dietary salt intake; and 2) explored the relationships of identified metabolites with blood pressure. Design and Methods: This study included data of White (N = 447) and Black (N = 380) adults aged 20 to 30 years from the African-PREDICT study. Estimated salt intake was determined from 24hr urinary sodium. Urinary amino acids and acylcarnitines were measured using liquid chromatography tandem mass spectrometry. Clinic, 24hr and central systolic blood pressure (SBP) were measured. Results: Whites with a high salt intake (> 10 g/day) had higher SBP (clinic, 24hr and central) compared to those with low (< 5 g/day) or moderate (5 to 10 g/day) salt intakes (all p < 0.05). The metabolites GABA (q = 0.020), citrulline (q = 0.020), glutamic acid (q = 0.046), serine (q = 0.054) and proline (q = 0.054) were lower in those with higher salt intake. In stepwise multivariable adjusted regression analyses, we found that clinic SBP of white adults were inversely associated with GABA (Adj. R2 = 0.35; Std. β=-0.123; p = 0.005), serine (Adj. R2 = 0.35; Std. β=-0.099; p = 0.022) and proline (Adj. R2 = 0.35; Std. β=-0.099; p = 0.021), and central SBP with GABA (Adj. R2 = 0.34; Std. β=-0.094; p = 0.036), glutamic acid (Adj. R2 = 0.34; Std. β=-0.090; p = 0.035) and proline (Adj. R2 = 0.034; Std. β=-0.106; p = 0.015). In Black adults, there were no differences in SBP or metabolites between low, moderate or high salt intake groups, with no relationships between SBP and GABA, glutamic acid, citrulline, serine or proline. Conclusion: In White adults, high salt intake was associated with low levels of GABA, glutamic acid, serine and proline, which in turn were related to high SBP. We hypothesise that metabolomic changes are related to salt intake and may contribute to pathophysiological mechanisms associated with increased blood pressure.
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