Abstract
Prehypertension is a risk factor for atherosclerosis. We investigated alterations in plasma metabolites that are associated with prehypertension. A group of 53 individuals was identified who remained within the range of prehypertension during repeated measurements in a 3-year period. This group was compared with the control group of 53 normotensive subjects who were matched for age and gender. Metabolomic profiles were analyzed with UPLC-LTQ-Orbitrap mass spectrometry. The prehypertensive group showed higher levels of lysophosphatidylcholines (lysoPCs) containing C14:0, C16:1, C16:0, C18:2, C18:1, C18:0, C20:5, C20:4, C20:3, and C22:6, higher circulating Lp-PLA2 activity, oxidized LDL (ox-LDL), interleukin 6 (IL-6), urinary 8-epi-PGF2α, and higher brachial-ankle pulse wave velocity (ba-PWV), before and after adjusting for BMI, WHR, smoking, alcohol consumption, serum lipid profiles, glucose, and insulin. LysoPC (16:0) was the most important plasma metabolite for evaluating the difference between control and prehypertensive groups, with a variable important in the projection (VIP) value of 17.173, and it showed a positive and independent association with DBP and SBP. In the prehypertensive group, the levels of lysoPC (16:0) positively and significantly correlated with ox-LDL, Lp-PLA2 activity, 8-epi-PGF2α, ba-PWV, and IL-6 before and after adjusting for confounding variables. Prehypertension-associated elevations in lysoPCs, Lp-PLA2 activity, ox-LDL, urinary 8-epi-PGF2α, IL-6, and ba-PWV could indicate increased oxidative stress from Lp-PLA2-catalyzed PC hydrolysis during increased LDL oxidation, thereby enhancing proinflammation and arterial stiffness.
Highlights
Hypertension is a risk factor for atherosclerosis and cardiovascular disease (CVD) [1,2,3,4], the mechanisms by which hypertension is related to atherosclerosis are not clearly established
It is necessary to determine the role of prehypertensionassociated alterations in circulating metabolic profiles
We performed metabolic profiling in a group of 53 individuals who remained within the range of prehypertension during repeated measurements in a 3-year period, and compared these with the metabolic profiles of age- and sex-matched normotensive controls in the same cohort
Summary
Hypertension is a risk factor for atherosclerosis and cardiovascular disease (CVD) [1,2,3,4], the mechanisms by which hypertension is related to atherosclerosis are not clearly established. Several metabolomic studies have been published that investigate the metabolic effects of hypertension [5,6,7]. These studies reported abnormalities in gender-linked steroid patterns [5] or lipid metabolism [6,7]. Prehypertension can precede hypertension and atherosclerosis for decades, and it is a condition that represents early CVD. We performed metabolic profiling in a group of 53 individuals who remained within the range of prehypertension during repeated measurements in a 3-year period, and compared these with the metabolic profiles of age- and sex-matched normotensive controls in the same cohort. We determined lipoprotein-associated phospholipase A2 (Lp-PLA2) activity, oxidized LDL (ox-LDL), lipid peroxides, and brachial-ankle pulse wave velocities (baPWV)
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