A team of Korean scientists led by Minjoo Kim1 used ultra-high performance liquid chromatography coupled with mass spectrometry and multivariate data analysis to identify prehypertension-associated plasma metabolites. Prehypertension, defined by blood pressure measurements of 120-139 mmHg (systolic) and 80-89 mmHg (diastolic), can precede hypertension and atherosclerosis on the road to cardiovascular disease.

The researchers identified 53 individuals with prehypertension along with age- and sex-matched controls with normal blood pressure. They measured body weight, height, circumference, blood pressure, and dietary intake, as well as a range of metabolic syndrome-related factors such as serum lipids, fasting glucose and other plasma and serum metabolites. As expected, there were differences between the two groups.

The mean systolic/diastolic blood pressure measurements were 134/84 mmHg for the prehypertensive group and 107/65 mmHg for the control group. Compared to the control group, prehypertensive subjects presented significantly higher body mass indexes (BMI) and waist to hip ratios, as well as greater levels of LDL-cholesterol, total cholesterol, and triglycerides. They also exhibited much higher levels of oxidative stress markers including lipoprotein-associated phospholipase A2 activity, plasma malondialdehyde and urinary excretion of 8-epi-PGF2a.  The prehypertensive group also showed arterial stiffness as measured by brachial-ankle pulse wave velocity. Diets were similar in both groups as were the ratios of total energy intake to total energy expenditure.

The most interesting part of the study was the non-targeted, global metabolic profiling. The researchers analysed plasma samples from the prehypertensive and control subjects using mass spectrometry to identify metabolites.

When the researchers applied a partial least squares discriminant analysis to the data, clear differences emerged. Of the 932 metabolites observed in the plasma samples, there were 52 metabolites with significant differences between the control and prehypertensive groups. Ten lysophosphatidylcholine (lysoPC) compounds were higher in prehypertensive subjects than in controls, even after adjusting for BMI, waist to hip ratio, smoking, alcohol consumption, serum lipid profiles, glucose and insulin. Differences in the levels of the lysoPC in the two groups are highly significant, suggesting an important role of lysoPCs in prehypertension. Most of these LysoPCs have long chain acyl groups, which are associated with impaired vasodilation.

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After multiple regression analysis, the researchers identified lysoPC (16:0) as the most important plasma metabolite for evaluating the difference between the prehypertensive group and individuals with normal blood pressure. LysoPC (16:0) was also positively and independently associated with both systolic and diastolic blood pressure. Additionally, in prehypertensive subjects, lysoPC (16:0) correlated with ox-LDL, Lp-PLA2 activity and 8-epi-PGF2a, indicating increased oxidative stress in these individuals.

Much work has been devoted to finding ways to detect and intervene in the early physiological changes that lead to metabolic syndrome. This study provides some insights into the metabolic alterations occurring during the prehypertensive period prior to the development hypertension or atherosclerosis. Although Kim and colleagues identified a number of new metabolomics markers, 32 of the metabolites have yet to be identified. We look forward to further results from their research.

1Kim M, Jung S, Kim SY, Lee S-H, Lee JH. Prehypertension-associated elevation in circulating lysophosphatidlycholines, Lp-PLA2 activity, and oxidative stress. PLoS One. 2014 May 6;9(5):e96735. doi: 10.1371/journal.pone.0096735.  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011750/pdf/pone.0096735.pdf