Key result
Hypertensive patients had significantly higher plasma ET-1 concentrations compared to controls (mean difference 1.57 pg/mL; 95% CI 0.47-2.68; P=0.005), driven by those with severe hypertension.
Why the study?
Are plasma ET-1 concentrations elevated in patients with untreated essential hypertension compared to controls?
Meta-Analysis (n=778)
Are plasma ET-1 concentrations elevated in patients with untreated essential hypertension compared to controls?
Mean Difference: 1.57 (95% CI 0.47–2.68)
p-value: p=0.005
Plasma ET-1 concentrations are elevated in patients with hypertension, particularly those with severe hypertension, likely reflecting secondary endothelial cell damage.
May indicate ET-1 involvement in severe hypertension; hypothesis-generating and requires prospective validation before clinical use.
BACKGROUND/AIMS: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. METHODS: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. RESULTS: Eleven studies fulfilling our in- and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95%CI [0.47∼2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. CONCLUSIONS: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage.
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Xu et al. (2017) conducted a meta-analysis in Hypertension (n=778). Untreated essential hypertension vs. Controls was evaluated on ET-1 plasma concentrations (MD 1.57 pg/mL, 95% CI 0.47-2.68, p=0.005). Hypertensive patients had significantly higher plasma ET-1 concentrations compared to controls (mean difference 1.57 pg/mL; 95% CI 0.47-2.68; P=0.005), driven by those with severe hypertension.
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