What is the clinical evidence from this study?

Study design: Case-Control. Population: Essential hypertension (n=19). Intervention: Essential hypertension vs. Normotensive controls. Primary outcome: Plasma levels of asymmetric dimethylarginine (ADMA) (p=<0.001).

What question did this study set out to answer?

To determine whether patients with essential hypertension have increased circulating levels of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and the oxidative stress marker 13-hydroxyoctadecadienoic acid (HODE).

August 7, 2008AJP Regulatory Integrative and Comparative Physiology

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Q: What are the key findings of this study?

Patients with essential hypertension had significantly elevated plasma levels of asymmetric dimethylarginine (766 vs 393 nmol/l) and oxidative stress markers compared to normal controls.

Q: What question did this study set out to answer?

To determine whether patients with essential hypertension have increased circulating levels of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and the oxidative stress marker 13-hydroxyoctadecadienoic acid (HODE).

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Key result

Patients with essential hypertension had significantly elevated plasma levels of asymmetric dimethylarginine (766 vs 393 nmol/l) and oxidative stress markers compared to normal controls.

Why the study?

Do patients with essential hypertension have increased circulating levels of ADMA and HODE compared to normal controls, and do these correlate with microvascular endothelial dysfunction?

Population

19 Caucasian subjects. Hypertensive patients had systolic blood pressure ≥140 mmHg or diastolic ≥90 mmHg…

Design

Case-control

Authors

DWDan WangGuiyang Medical University SSSvend StrandgaardHerlev Hospital JIJens IversenCopenhagen University Hospital

Discussion

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Implication

ADMA elevation may mark endothelial dysfunction in hypertension; leaves open causal role and therapeutic targeting.

Key Points

To determine whether patients with essential hypertension have increased circulating levels of the nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) and the oxidative stress marker 13-hydroxyoctadecadienoic acid (HODE).
Compared 9 patients with essential hypertension to 10 normal controls.
Measured plasma concentrations, renal excretion, and renal clearance rates of ADMA, symmetric dimethylarginine (SDMA), L-arginine, and HODE.
Evaluated correlations between plasma biomarker levels, subcutaneous microvascular endothelium-derived relaxation factor/nitric oxide (EDRF/NO) activity, and mean blood pressure.
Hypertensive patients had significantly higher plasma ADMA (766 ± 217 vs. 393 ± 57 nmol/l, P < 0.001) and SDMA (644 ± 140 vs. 399 ± 70 nmol/l, P < 0.001), alongside increased renal ADMA excretion (21 ± 9 vs. 14 ± 5 nmol/μmol creatinine, P < 0.015) and reduced renal clearance (18 ± 3 vs. 28 ± 5 ml/min).
Plasma HODE (309 ± 30 vs. 226 ± 24 nmol/l, P < 0.001) and renal HODE excretion (433 ± 93 vs. 299 ± 67 nmol/μmol creatinine) were significantly elevated in hypertensive patients compared to controls.
Across all subjects, plasma levels of ADMA and HODE were inversely correlated with microvascular EDRF/NO (P < 0.001) and positively correlated with mean blood pressure.

Study Design

Type

Case-Control (n=19)

Multicenter

Structured PICO

Do patients with essential hypertension have increased circulating levels of ADMA and HODE compared to normal controls, and do these correlate with microvascular endothelial dysfunction?

Population

19 Caucasian adults aged 23-60 years, comprising 9 patients with uncomplicated essential hypertension and 10 age-matched normotensive controls.

Comparator

Age-matched normal controls

Outcome

Plasma levels of asymmetric dimethylarginine (ADMA) and 13-hydroxyoctadecadienoic acid (HODE), and their correlation with microvascular EDRF/NO and mean blood pressuresurrogate

Main Result

Absolute Event Rate: 766% vs 393%

p-value: p=<0.001

Elevated levels of ADMA and oxidative stress markers in patients with essential hypertension correlate with microvascular endothelial dysfunction and elevated blood pressure.

Limitations

Relatively small number of patients restricted the ability to detect significant correlations within the hypertensive group.
Patients with essential hypertension were receiving antihypertensive therapy until 24 hours before the study.
The associative, cross-sectional method of study cannot prove causality between elevated ADMA/oxidative stress and impaired endothelial function.
Small sample size due to the relatively invasive method to assess directly the EDRF/NO responses and cNOS activity
Patients with essential hypertension were receiving antihypertensive therapy until 24 h before study
Associative nature of the study cannot prove causality

Cite This Study

Wang et al. (2008) conducted a case-control in Essential hypertension (n=19). Essential hypertension vs. Normotensive controls was evaluated on Plasma levels of asymmetric dimethylarginine (ADMA) (p=<0.001). Patients with essential hypertension had significantly elevated plasma levels of asymmetric dimethylarginine (766 vs 393 nmol/l) and oxidative stress markers compared to normal controls.

synapsesocial.com/papers/6a785655df493903fd1f8fbf https://doi.org/10.1152/ajpregu.90506.2008

Topics

Hypertension management

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Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Topics

Asymmetric dimethylarginine, oxidative stress, and vascular nitric oxide synthase in essential hypertension

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Topics

Also Consider