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Shared biomarkers between female diastolic heart failure and pre-eclampsia: a systematic review and meta-analysis.

ABSTRACT: Evidence accumulates for associations between hypertensive pregnancy disorders and increased cardiovascular risk later. The main goal of this study was to explore shared biomarkers representing common pathogenic pathways between heart failure with preserved ejection fraction (HFpEF) and pre-eclampsia where these biomarkers might be potentially eligible for cardiovascular risk stratification in women after hypertensive pregnancy disorders. We sought for blood markers in women with diastolic dysfunction in a first literature search, and through a second search, we investigated whether these same biochemical markers were present in pre-eclampsia.This systematic review and meta-analysis presents two subsequent systematic searches in PubMed and EMBASE. Search I yielded 3014 studies on biomarkers discriminating women with HFpEF from female controls, of which 13 studies on 11 biochemical markers were included. Cases had HFpEF, and controls had no heart failure. The second search was for studies discriminating women with pre-eclampsia from women with non-hypertensive pregnancies with at least one of the biomarkers found in Search I. Search II yielded 1869 studies, of which 51 studies on seven biomarkers were included in meta-analyses and 79 studies on 12 biomarkers in systematic review.Eleven biological markers differentiated women with diastolic dysfunction from controls, of which the following 10 markers differentiated women with pre-eclampsia from controls as well: C-reactive protein, HDL, insulin, fatty acid-binding protein 4, brain natriuretic peptide, N terminal pro brain natriuretic peptide, adrenomedullin, mid-region pro adrenomedullin, cardiac troponin I, and cancer antigen 125.Our study supports the hypothesis that HFpEF in women shares a common pathogenic background with pre-eclampsia. The biomarkers representing inflammatory state, disturbances in myocardial function/structure, and unfavourable lipid metabolism may possibly be eligible for future prognostic tools.

SUBMITTER: Alma LJ

PROVIDER: S-EPMC5396047 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aldosterone infusion results in left ventricular hypertrophy (LVH) and hypertension and may involve profibrotic and proinflammatory mechanisms. In turn, hypertension is the major cause of diastolic heart failure (HF). Adiponectin, an adipose-derived plasma protein, exerts antiinflammatory and anti-hypertrophic effects and is implicated in the development of hypertension and systolic HF. We thus tested the hypothesis that hypoadiponectinemia in aldosterone-induced hypertension exacerbated cardiac remodeling and diastolic HF. Wild-type (WT) or adiponectin-deficient (APNKO) mice underwent saline or aldosterone infusion and uninephrectomy and were fed 1% salt water for 4 wk. Blood pressure was increased in aldosterone-infused WT (132 +/- 2 vs. 109 +/- 3 mm Hg; P < 0.01) and further augmented in APNKO mice (140 +/- 3 mm Hg; P < 0.05 vs. aldosterone-infused WT). LVH was increased in aldosterone-infused WT vs. WT mice (LV/body weight ratio, 4.8 +/- 0.2 vs. 4.1 +/- 0.2 mg/g) and further increased in aldosterone-infused APNKO mice (LV/body weight ratio, 6.0 +/- 0.4 mg/g). Left ventricular ejection fraction was not decreased in either aldosterone-infused WT or APNKO hearts. Pulmonary congestion however was worse in APNKO mice (P < 0.01). The ratio of early ventricular filling over late ventricular filling (E/A) and the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity (E/e'), measures of diastolic function, were increased in aldosterone-infused WT hearts and further increased in APNKO hearts (P < 0.05 for both). Renal function and cardiac fibrosis were no different between both aldosterone-infused groups. Aldosterone increased matrix metalloproteinase-2 expression in WT hearts (P < 0.05 vs. WT and P < 0.01 vs. APNKO). Myocardial atrial natriuretic peptide, interferon-gamma, and TNF-alpha expression were increased in aldosterone-infused WT hearts. Expression of these proteins was further increased in aldosterone-infused APNKO hearts. Therefore, hypoadiponectinemia in hypertension-induced diastolic HF exacerbates LVH, diastolic dysfunction, and diastolic HF. Whether or not adiponectin replacement prevents the progression to diastolic HF will warrant further study.

Project description:BackgroundWith the rapid development of molecular biology, the kind of mircoRNA (miRNA) has been introduced into emerging role both in cardiac development and pathological procedure. Thus, we conduct this meta-analysis to find out the role of circulating miRNA as a biomarker in detecting heart failure.MethodsWe searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and World Health Organization clinical trials registry center to identify relevant studies up to August 2016. We performed meta-analysis in a fixed/random-effect model using Meta-disc 1.4. We used STATA 14.0 to estimate the publication bias and meta-regression. Besides, we took use of SPSS 17.0 to evaluate variance between several groups. Information on true positive, false positive, false negative, and true negative, as well as the quality of research was extracted.ResultsWe use results from 10 articles to analyze the pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.74 (95% confidence interval [CI], 0.72 to 0.75); pooled specificity, 0.69 (95%CI, 0.67 to 0.71); and area under the summary receiver operating characteristic curves value (SROC), 0.7991. The miRNA-423-5p (miR-423-5p) detection was: pooled sensitivity, 0.81 (95%CI, 0.76 to 0.85); pooled specificity, 0.67 (95%CI, 0.61 to 0.73); and SROC, 0.8600. However, taken the same patients population, we extracted the data of BNP for detecting heart failure and performed meta-analysis with acceptable SROC as 0.9291. Among the variance analysis, the diagnostic performance of miR-423-5p claimed significant advantages of other pooled results. However, the combination of miRNAs and BNP could increase the accuracy of detecting of heart failure. Unfortunately, there was no dramatic advantage of miR-423-5p compared to BNP protocol.ConclusionDespite interstudy variability, the performance test of miRNA for detecting heart failure revealed that miR-423-5p demonstrated the potential to be a biomarker. However, other miRNAs were not able to provide enough evidence on promising diagnostic value for heart failure based on the current data. Moreover, the combination of miRNAs and BNP could work as a better method to detection. Unfortunately, BNP was still the most convinced biomarker for such disease.

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Shared biomarkers between female diastolic heart failure and pre-eclampsia: a systematic review and meta-analysis.

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