Application of plasma lipidomics in studying the response of patients with essential hypertension to antihypertensive drug therapy

Hypertension is a key risk factor in the progression of cardiovascular disease (CVD). Dyslipidemia, a strong predictor of CVD, frequently coexists with hypertension. Therefore, the control of hypertension and dyslipidemia may help reduce CVD morbidity and mortality. In the present study, the therapeutic effects of antihypertensive agents on blood pressure control and plasma lipid metabolism were evaluated. The plasma lipid profiles of patients with treated (n = 25) or untreated (n = 30) essential hypertension as well as of subjects with normotension (n = 28) were analyzed using liquid chromatography mass spectrometry. Principal component analysis of the lipidomics data revealed distinct clusters among studied subjects across three human populations. Phosphatidylcholines and triacylglycerols (TG) dominated the pattern of hypertension-influenced plasma lipid metabolism. Discriminatory lipid metabolites were analyzed using one-way analysis of variance followed by a post hoc multiple comparison correction. TG lipid class was significantly increased by 49.0% (p < 0.001) in hypertensive vs. normotensive groups while tended to decrease (-21.2%, p = 0.054) in hypertensive patients after treatment. Total cholesteryl esters were significantly decreased by -16.9% (p < 0.001) in hypertensive patients after treatment. In particular, a large number of individual neutral lipid species were significantly elevated in hypertensive subjects but significantly decreased after treatment with antihypertensive agents. The present study applied, for the first time, a systems biology based lipidomics approach to investigate differentiation among plasma lipid metabolism of patients with treated/untreated essential hypertension and subjects with normotension. Our results demonstrate that antihypertensive medications to lower blood pressure of hypertensive patients to target levels produced moderate plasma lipid metabolism improvement of patients with hypertension.