Yi-Ting Lin1,2,3, Samira Salihovic1,4,5, Tove Fall1, Ulf Hammar1, Erik Ingelsson1,6,7,8, Johan Ärnlöv9,10, Lars Lind1, Johan Sundström1,11. 1. From the Department of Medical Sciences, Uppsala University, Sweden (Y.-T.L., S.S., T.F., U.H., E.I., L.L., J.S.). 2. Department of Family Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Taiwan (Y.-T.L.). 3. Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Taiwan (Y.-T.L.). 4. School of Medical Sciences, Örebro University, Sweden (S.S.). 5. School of Science and Technology, Örebro University, Sweden (S.S.). 6. Division of Cardiovascular Medicine, Department of Medicine, Stanford University School of Medicine, CA (E.I.). 7. Stanford Cardiovascular Institute, Stanford University School of Medicine, CA (E.I.). 8. Stanford Diabetes Research Center, Stanford University School of Medicine, CA (E.I.). 9. Division of Family Medicine and Primary Care, Department of Neurobiology, Care Science and Society, Karolinska Institutet, Huddinge, Sweden (J.Ä.). 10. School of Health and Social Studies, Dalarna University, Falun, Sweden (J.Ä.). 11. The George Institute for Global Health, University of New South Wales, Sydney, NSW, Australia (J.S.).
Abstract
OBJECTIVE: The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approach and Results: Circulating metabolite levels were assessed with liquid- and gas-chromatography coupled to mass spectrometry among persons without BP-lowering medication at baseline. We studied associations of baseline levels of metabolites with changes in BP levels and the clinical BP stage between baseline and a follow-up examination 5 years later. In the discovery cohort, we investigated 504 individuals that contributed with 757 observations of paired BP measurements. The mean baseline systolic and diastolic BPs were 144 (19.7)/76 (9.7) mm Hg, and change in systolic and diastolic BPs were 3.7 (15.8)/-0.5 (8.6) mm Hg over 5 years. The metabolites associated with diastolic BP change were ceramide, triacylglycerol, total glycerolipids, oleic acid, and cholesterylester. No associations with longitudinal changes in systolic BP or BP stage were observed. Metabolites with similar structures to the 5 top findings in the discovery cohort were investigated in the validation cohort. Diacylglycerol (36:2) and monoacylglycerol (18:0), 2 glycerolipids, were associated with diastolic BP change in the validation cohort. CONCLUSIONS: Circulating baseline levels of ceramide, triacylglycerol, total glycerolipids, and oleic acid were positively associated with longitudinal diastolic BP change, whereas cholesterylester levels were inversely associated with longitudinal diastolic BP change. Two glycerolipids were validated in an independent cohort. These metabolites may point towards pathophysiological pathways of hypertension.
OBJECTIVE: The pathophysiology of hypertension remains incompletely understood. We investigated associations of circulating metabolites with longitudinal blood pressure (BP) changes in the Prospective Investigation of the Vasculature in Uppsala Seniors cohort and validated the findings in the Uppsala Longitudinal Study of Adult Men cohort. Approach and Results: Circulating metabolite levels were assessed with liquid- and gas-chromatography coupled to mass spectrometry among persons without BP-lowering medication at baseline. We studied associations of baseline levels of metabolites with changes in BP levels and the clinical BP stage between baseline and a follow-up examination 5 years later. In the discovery cohort, we investigated 504 individuals that contributed with 757 observations of paired BP measurements. The mean baseline systolic and diastolic BPs were 144 (19.7)/76 (9.7) mm Hg, and change in systolic and diastolic BPs were 3.7 (15.8)/-0.5 (8.6) mm Hg over 5 years. The metabolites associated with diastolic BP change were ceramide, triacylglycerol, total glycerolipids, oleic acid, and cholesterylester. No associations with longitudinal changes in systolic BP or BP stage were observed. Metabolites with similar structures to the 5 top findings in the discovery cohort were investigated in the validation cohort. Diacylglycerol (36:2) and monoacylglycerol (18:0), 2 glycerolipids, were associated with diastolic BP change in the validation cohort. CONCLUSIONS: Circulating baseline levels of ceramide, triacylglycerol, total glycerolipids, and oleic acid were positively associated with longitudinal diastolic BP change, whereas cholesterylester levels were inversely associated with longitudinal diastolic BP change. Two glycerolipids were validated in an independent cohort. These metabolites may point towards pathophysiological pathways of hypertension.
Entities:
Keywords:
blood pressure; body mass index; glomerular filtration rate; hypertension; oleic acid
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