Heart Failure and Related Risk-factors After Preeclampsia

NCT02347540 | Unknown DMC

• 2 other identifiers: METC 14-02-0132013T084
• Study Type: observational
• Target: 2,580
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a cross-sectional case-control study where classical as well as more innovative risk factors for CVD will be explored. In western countries, more women than men die of cardiovascular disease (CVD), making CVD in women an important public health issue. Misdiagnosis of CVD in women is frequently observed, posing the clinician for diagnostic and therapeutic dilemmas that can easily result in inadequate treatment and worse prognosis. Despite these challenges, CVD in women has been underexposed in scientific research. Women have gender-specific risk factors like a history of preeclampsia (PE) that contribute to their risk for CVD. PE complicates 5-10% of pregnancies, recurs in \~25% and is associated with a 2-4 fold increased risk for CVD. Moreover, pre-symptomatic heart failure (HF) stage B occurs in 40% of women with a history of PE. HF stage B is thought to precede the development of the, mortality related, clinical HF stages C and D (structural heart disease in combination with symptomatic disease). Early detection and tailored intervention of women with stage B HF decreases progression to the clinical stages and might therefore improve clinical outcome and cardiovascular related mortality. Phenotypic presentation of HF is currently split up between systolic HF also called HF with reduced ejection fraction (HFrEF) and diastolic HF or HF with preserved ejection fraction (HFpEF). Women more often have HFpEF in contrast to men. Different pathophysiology and disease progression in women compared to men seems to be an important underlying factor. The current clinical HF diagnostic tools (e.g. natriuretic hormones and high sensitivity troponins) fail to identify early changes that prelude adverse cardiac remodelling and HF, and do not discriminate between HFrEF and HFpEF. Moreover, there are sex-related differences in biomarker levels for detection of CVD. As a result, clinicians are forced to wait for the failing heart to become clinically evident before they can intervene. Therefore, there is an urgent need to assess novel biomarkers that could help select high risk women needing further follow up and intervention. Biomarkers may not only improve early diagnosis but may also unravel disease pathways of HFpEF. Especially when combined with measurements of subclinical, surrogate risk markers. Objectives

• To determine the impact of PE on incidence of macro-and micro-vascular dysfunction reflected by surrogate measures for coronary artery disease (CAD) and HFpEF.
• To perform a genome wide association study (GWAS) and associate novel biomarker expression levels with endothelial function, cardiac diastolic function and IMT measurement.
• To identify risk factors and surrogate measures for CVD in a) former PE patients without HFpEF, b) former PE patients with HFpEF and c) healthy parous controls. Study population Cases: women with a history of PE Controls: women with uncomplicated pregnancies in the history. Measurements will be performed in clusters at postpartum intervals of: ½-2, 5-10, 10-15 and 15-30 years. Number of inclusions will be: 425, 350, 282 and 233 for each follow-up group respectively. Primary endpoints The prevalence of macro- and microvascular dysfunction in former PE patients. Novel biomarker detection in former PE patients associated with HF in general and HFpEF in particular. Secondary endpoints
• Lifestyle (questionnaire)
• Cognitive ability (questionnaire)
• Depression score (questionnaire)
• Metabolic syndrome (MetS)
• Arterial endothelial function (Flow mediated dilation (FMD))
• Intima Media Thickness (IMT)
• Glycocalyx thickness (by means of the Glycocheck)
• Venous function (plethysmograph)
• Electrocardiogram (ECG)
• Ergometry

Conditions

Heart Failure; Cardiovascular Diseases; Pre-Eclampsia

Keywords

Heart Failure; Diastolic Dysfunction; Pre-Eclampsia; Endothelial dysfunction; Biological Markers; MicroRNAs; Circulating cells

Outcome Measures

Primary Outcomes (1)

• The prevalence of Heart Failure (number with percentage)

  Heart Failure will be assessed with the transthoracic echocardiography based on the criteria of the American Heart Association. The sub classification for Heart Failure with preserved ejection fraction (EF) will be made (EF \>55%)

  At time of assessment

Secondary Outcomes (6)

• Structural en Functional Cardiac Measurements

  At time of assessment

• Metabolic syndrome

  At time of assessment

• Arterial endothelial function (Flow mediated dilation (FMD))

  At time of assessment

• Common Carotid Intima media thickness

  At time of assessment

• Glycocalyx thickness en microvascular tortuosity

  At time of assessment

Study Arms (2)

Women with a history of preeclampsia (cases)

Cases: women with a history of preeclampsia. Measurements will be performed in a postpartum interval from 0.5 years until 30 years after the first complicated pregnancy. This group will further be subdivided in a subgroup with Heart Failure and a group without Heart Failure.

Women with a history of uncomplicated pregnancy (controls)

Controls include women with a history of uncomplicated pregnancies. The controlgroup will further be subdivided in a subgroup with Heart Failure and a group without Heart Failure.

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Cases: women with a history of PE. Control group: women with uncomplicated pregnancies in the history H1: PP interval ½ -2 years: n = 2x 425 H2: PP interval 5-10 years: n = 2x 350 H3: PP interval 10-15 years: n = 2x 282 H4: PP interval 15-30 years: n = 2x 233

You may qualify if:

• Cases
• Women aged ≥ 18 years
• ½ till 30 years after the complicated pregnancy
• Experienced PE in any pregnancy. PE defined as hypertension (systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg) developed after 20 weeks of pregnancy with the development of proteinuria (≥ 300 mg/ 24 hours).
• Women who had their last delivery at least 6 months ago.
• Controls
• Women aged ≥ 18 years
• ½ till 30 years after the pregnancy that matches the sequence number of pregnancy of the specifically matched case.
• Experienced pregnancies that were not complicated by foetal or maternal placental syndrome (pregnancy induced hypertension, preeclampsia, HELLP-syndrome).
• Women who had their last pregnancy at least 6 months ago.
• Women with a negative family history for PE (mother and sisters did not experience PE).

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• Cases
• Women with auto-immune diseases prior to the complicated pregnancy.
• Chronic hypertension prior to the complicated pregnancy.
• Renal disease prior to the complicated pregnancy.
• Pregnant women
• Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results.
• Control group:
• Women with auto-immune diseases
• Chronic hypertension prior to the matched pregnancy.
• Women with IUGR in the matching pregnancy (p\<10)
• Solutio placentae in the matching pregnancy
• Pregnant women
• Women who do not want to be informed about the results of the tests, or women who do not want their general practitioner and specialist(s) to be informed about the test results.

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• UMC Utrecht: collaborator
• Leiden University Medical Center: collaborator
• University Medical Center Groningen: collaborator
• Amsterdam UMC, location VUmc: collaborator
• Dutch Heart Foundation: collaborator

Study Sites (1)

Maastricht University Medical Center

Maastricht, Limburg, 6202 AZ, Netherlands

Location

Related Publications (4)

• Brandt Y, Alers RJ, Canjels LPW, Jorissen LM, Jansen G, Janssen EBNJ, van Kuijk S, Went TM, Koehn D, Gerretsen SC, Jansen J, Backes W, Hurks PPM, van de Ven V, Kooi ME, Spaanderman MEA, Ghossein-Doha C. DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT): research protocol for a cross-sectional pilot study. BMJ Open. 2024 Mar 4;14(3):e077534. doi: 10.1136/bmjopen-2023-077534.

  PMID: 38443087 DERIVED

• Mohseni-Alsalhi Z, B N J Janssen E, Delmarque J, van Kuijk SMJ, Spaanderman MEA, Ghossein-Doha C. Prediction Model Based on Easily Available Markers for Aberrant Cardiac Remodeling in Women After Pregnancy. Hypertension. 2023 Aug;80(8):1707-1715. doi: 10.1161/HYPERTENSIONAHA.122.19187. Epub 2023 Jan 25.

  PMID: 37470772 DERIVED

• Alers RJ, Ghossein-Doha C, Canjels LPW, Muijtjens ESH, Brandt Y, Kooi ME, Gerretsen SC, Jansen JFA, Backes WH, Hurks PPM, van de Ven V, Spaanderman MEA. Attenuated cognitive functioning decades after preeclampsia. Am J Obstet Gynecol. 2023 Sep;229(3):294.e1-294.e14. doi: 10.1016/j.ajog.2023.02.020. Epub 2023 Feb 28.

  PMID: 36863645 DERIVED

• Janssen EBNJ, Hooijschuur MCE, Lopes van Balen VA, Morina-Shijaku E, Spaan JJ, Mulder EG, Hoeks AP, Reesink KD, van Kuijk SMJ, Van't Hof A, van Bussel BCT, Spaanderman MEA, Ghossein-Doha C. No accelerated arterial aging in relatively young women after preeclampsia as compared to normotensive pregnancy. Front Cardiovasc Med. 2022 Jul 28;9:911603. doi: 10.3389/fcvm.2022.911603. eCollection 2022.

  PMID: 35966519 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

The investigators will perform an unbiased screen for the human genome content of circulating microRNAs. HF biomarkers will be included so that the added value of these novel HFpEF miRNAs can directly be compared to established HF biomarkers. In this cohort of women who experienced pre-eclampsia and matched controls, the investigators will profile miRNAs on a genome-wide scale using total RNA from plasma. Differentially expressed miRNAs will be further investigated in relation to the pathogenesis of micro- and macrovascular disease. Selected miRNAs will be placed on a custom megaplex array and used to screen a cohort of patients with HFpEF. In patients with HFpEF the investigators will relate miRNA expression level to the circulating levels of angiopoietin-2/ang-1ratio's and micro-albuminuria. Part of the obtained blood and urine will be stored at the Biobank in Maastricht for future studies.

MeSH Terms

Conditions

Heart Failure; Cardiovascular Diseases; Pre-Eclampsia

Condition Hierarchy (Ancestors)

Heart Diseases; Hypertension, Pregnancy-Induced; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Marc EA Spaanderman, MD, PhD

  Maastricht University Medical Center

  STUDY CHAIR

• Gerard Pasterkamp, PhD

  UMC Utrecht

  STUDY CHAIR

• Hester HM den Ruijter, PhD

  UMC Utrecht

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 30, 2014
• First Posted: January 27, 2015
• Study Start: December 1, 2014
• Primary Completion: December 1, 2024
• Study Completion: July 1, 2025
• Last Updated: July 28, 2022

Record last verified: 2022-07

Locations

NL (1)