The relationships between the plasma metabolome and orthostatic blood pressure responses

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: Foundation. Main funding source(s): the Swedish Heart-Lung Foundation OBJECTIVE: Impaired orthostatic blood pressure responses may be an indicator of cardiovascular autonomic dysfunction, which can be seen in the metabolic syndrome. Whereas autonomic dysfunction and the metabolic syndrome are clinically associated, the relationships with the plasma metabolome is unknown. We explored the association between orthostatic blood pressure responses and over 800 plasma metabolites in middle-aged subjects from the general population. METHODS: We included 3,803 subjects (mean age, 57 years; 52 % women) with information on smoking habits, diabetes, antihypertensive drug treatment, anthropometrics, hemodynamic measurements and 818 plasma metabolites (mass-spectrometry). The associations between each metabolite and orthostatic systolic blood pressure responses as well as orthostatic hypotension were determined using multivariable linear regression analysis. The Bonferroni corrected p-value was used in this study (p value < 6.11×10-5 (0.05/818) and 2.273×10-3 (0.05/22) respectively). RESULTS: We identified five amino acids, five vitamins, co-factors and carbohydrates, nine lipids and two xenobiotics that were associated with orthostatic blood pressure responses. After additional adjustments for BMI, diabetes, smoking and antihypertensive treatment, the association remained significant for six lipids, four amino acids and one xenobiotic, with the most significant relationships for lipids in the dihydrosphingomyelin and sphingosine pathways. CONCLUSIONS: In this exploratory study, we found that 22 out of 818 plasma metabolites were associated with orthostatic blood pressure responses. Eleven metabolites, including lipids in the dihydrosphingomyelin and sphingosine pathways, were independently associated with orthostatic systolic blood pressure responses after additional adjustment for markers of cardio-metabolic disease. [Figure: see text]