Dataset Information

The transition from hypertension to hypertensive heart disease and heart failure: the PREFERS Hypertension study.

ABSTRACT: AIMS:Despite evidence-based therapeutic approaches, target blood pressure is obtained by less than half of patients with hypertension. Hypertension is associated with a significant risk for heart failure, in particular heart failure with preserved left ventricular (LV) ejection fraction (HFpEF). Although treatment is suggested to be given early after hypertension diagnosis, there is still no evidence-based medical treatment for HFpEF. We aim to study the underlying mechanisms behind the transition from uncomplicated hypertension to hypertensive heart disease (HHD) and HFpEF. To this end, we will combine cardiac imaging techniques and measurements of circulating fibrosis markers to longitudinally monitor fibrosis development in patients with hypertension. METHODS AND RESULTS:In a prospective cohort study, 250 patients with primary hypertension and 60 healthy controls will be characterized at inclusion and after 1 and 6 years. Doppler echocardiography, cardiac magnetic resonance imaging, and electrocardiogram will be used for measures of cardiac structure and function over time. Blood biomarkers reflecting myocardial fibrosis, inflammation, and endothelial dysfunction will be analysed. As a proxy for HFpEF development, the primary endpoint is to measure echocardiographic changes in LV function and structure (E/e' and LAVI) and to relate these measures of LV filling to blood pressure, biomarkers, electrocardiogram, and cardiac magnetic resonance. CONCLUSIONS:We aim to study the timeline and transition from uncomplicated hypertension to HHD and HFpEF. In order to identify subjects prone to develop HHD and HFpEF, we want to find biomarkers and cardiac imaging variables to explain disease progression. Ultimately, we aim at finding new pathways to prevent HFpEF.

SUBMITTER: Ekstrom M

PROVIDER: S-EPMC7160482 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The transition from hypertension to hypertensive heart disease and heart failure: the PREFERS Hypertension study.

Ekström Mattias M Hellman Anna A Hasselström Jan J Hage Camilla C Kahan Thomas T Ugander Martin M Wallén Håkan H Persson Hans H Linde Cecilia C

ESC heart failure 20200219 2

<h4>Aims</h4>Despite evidence-based therapeutic approaches, target blood pressure is obtained by less than half of patients with hypertension. Hypertension is associated with a significant risk for heart failure, in particular heart failure with preserved left ventricular (LV) ejection fraction (HFpEF). Although treatment is suggested to be given early after hypertension diagnosis, there is still no evidence-based medical treatment for HFpEF. We aim to study the underlying mechanisms behind the ...[more]

PMID: 32073753

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Project description:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82±4 to 52±3 %) in compensated vs. failing animals. Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF. Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs. LV papillary muscle force development and shortening velocity decreased, β-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-β and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart.

Project description:Full Title: Transition from Compensated Hypertrophy to Systolic Heart Failure in the Spontaneously Hypertensive Rat: Structure, Function, and Transcript Analysis Gene expression changes and left ventricular remodeling associated with the transition to systolic heart failure (HF) were determined in the spontaneously hypertensive rat (SHR). By combining transcriptomics of left ventricles from six SHR with HF with changes in function and structure we aimed to better understand the molecular events underlying the onset of systolic HF compared to six age-matched, SHR with compensated hypertrophy. Left ventricle (LV) ejection fraction was depressed (82Â±4 to 52Â±3 %) in compensated vs. failing animals.Â Systolic blood pressure decreased and LV end-diastolic and systolic volume increased with HF.Â Failing SHR hearts also demonstrated increases in left and right ventricular mass relative to non-failing SHRs.Â Â LV papillary muscle force development and shortening velocity decreased, Î²-adrenergic responsiveness was depressed, myocardial stiffness and myocardial fibrosis increased with HF relative to non-failing animals. Initial micro-array analysis revealed that 1,431 transcripts were differentially expressed with HF compared to non-failing SHR (p<0.05). Of the identified transcripts, lipopolysaccharide binding protein, the most highly expressed transcript with HF, was negatively correlated to myocardial force while elevated expression of the collagen cross-linking enzyme lysyl oxidase correlated positively with muscle stiffness. Besides these individual transcripts, gene set enrichment analysis (GSEA) identified multiple enriched pathways with HF, most prominent of the altered signaling pathways involved TGF-Î² and insulin signaling. GESA analysis additionally identified altered gene sets involving inflammation, oxidative stress, cell degradation and cell death, among others (all p<0.01). In contrast to diastolic HF where few transcripts are reported to be altered, our data indicate multiple genes and pathways involved in a variety of biological processes characterize the onset of systolic HF, consistent with many functional and structural changes present in the failing hypertensive heart. Comprehensive gene expression profiling of heart failure Rat model vs control.

Dataset Information

The transition from hypertension to hypertensive heart disease and heart failure: the PREFERS Hypertension study.

Publications

The transition from hypertension to hypertensive heart disease and heart failure: the PREFERS Hypertension study.

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