Barts Sex-CAD Database

Coronary Artery Disease Clinical Trial

Official title:

Do Female Sex Hormone Levels Inform Inflammatory Status and Susceptibility in Women Suffering Coronary Artery Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06327984
• Other study ID #: 157354
• Status: Not yet recruiting
• Start date: May 2024
• Est. completion date: May 2027

Study information

• Verified date: March 2024
• Source: Queen Mary University of London
• Contact: Krishnaraj Rathod, MBBS PhD
• Phone: 02078828377
• Email: k.s.rathod[@]qmul.ac.uk
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

There is a lack of understanding of how Coronary Artery Disease (CAD) - meaning the blocking or furring up of the arteries of the heart - starts and progresses in women. In both men and women, CAD is the most common cause of heart attacks, which occur when the blood supply in the heart is interrupted (these are also known medically as 'acute coronary syndromes').

Before the menopause women appear to be protected from CAD; however, after the menopause that protection is lost. Also, those women who do suffer a heart attack have twice the risk of further heart attacks compared to men despite having the same treatment that works well in men. Biological differences between men and women are probably playing an important role in the way CAD develops. However, due to a lack of research there is currently little understanding of how the female body works in this area.

Inflammation is the body's natural response to injury or infection. Importantly it is also involved in the development of CAD. Hormones such as oestrogen and testosterone are also likely to be contributory factors. We think the differences between the way these hormones and inflammation play a part in CAD in both men and women are important, but the role they play is not yet fully understood.

In this study we wish to measure the 'markers' of inflammation in the blood of patients attending Barts Heart Centre with chest pain. We will also conduct questionnaires with these patients, to understand their hormone status and how parts of their medical history may be a contributory factor. For patients who have previously attended Barts Heart Centre will will contact them to conduct the questionnaire over the telephone only. We will combine this data with the data that is routinely collected during hospital admission. In this way we hope to understand whether inflammation together with hormone status plays an important role in CAD. Our hope is that through this research we will address an under researched area and find new ways of treating women and men with coronary artery disease.

Description:

Inclusion Criteria

Any patient presenting with chest pain ≥16 years old presenting to Barts Heart Centre will be included.

Exclusion Criteria

1. Patients <16 years old and Adults lacking capacity will be excluded.

2. Patients where the cause of their chest pain presentation is not related to coronary artery disease e.g musculoskeletal chest pain, aortic dissection, gastrointestinal, pulmonary embolism.

Study Procedures

1. We will collect data on sex hormone status (FSH, LH, oestradiol, progesterone and testosterone) of patients admitted to BHC. These tests will be added onto admission blood samples via the Barts Path Lab service. Sex hormone data will be gathered as part of a quality improvement project which has been approved through the Barts Clinical Excellence Unit (CEU ID: 13140). Data will subsequently be entered into a dedicated secure (Excel) database by a member of the clinical team. A member of the clinical team will review hormone profiles and, if relevant abnormalities in hormone profiles are detected, appropriate follow up will be arranged for the patient. In addition, the following blood markers will also be extracted from the patients routine admission blood tests: Haemoglobin, white blood cell count, platelet count, haematocrit, neutrophil count, lymphocyte count, monocyte count, eosinophil count, coagulation results, d-dimer (if done), sodium, potassium, chloride, urea, creatinine, eGFR, bilirubin, ALT, ALP, protein, albumin, calcium, corrected calcium, phosphate, magnesium, troponin, hs-CRP. These data points will be logged in the secure database.

2. We have composed a short questionnaire to examine aspects of patients' history relevant to their sex hormone status. For female patients this includes menstrual history, as well as relevant medications and medical conditions that may influence sex hormone status. For males an abbreviated form of the questionnaire includes relevant medications and medical conditions that my influence sex hormone status. This questionnaire will be delivered retrospectively to patients following their discharge from hospital. Clinical data has been gathered into the BartsREVASC database since 2016 therefore we aim to retrospectively include these patients and contact them via telephone to conduct the questionnaire only. Patients will be identified via the BartsREVASC database, and the electronic patient record and NHS Spine record will be checked to ensure the patient is still living and has appropriate capacity to consent. An invitation letter and participant information sheet will be sent to retrospective patients outlining the study information and advising that they will receive a phone call from a clinical member of the research team to conduct the questionnaire over the telephone. A telephone number for the research team will be provided if they wish to call us sooner at their own convenience to conduct the questionnaire rather than receive a call. We will obtain their verbal consent (which will be documented in a database) prior to proceeding with the questionnaire; data will be directly entered into the secure database. Questionnaires will be administered by a member of the clinical team who will also be responsible for entering the data into the database. In addition, we will consent patients to be contacted regarding future research studies examining sex differences in CAD and inflammation.

3. Will seek also written consent from female and male patients prospectively included in this study during their hospital admission to obtain an additional blood test for specialised inflammatory profiling including but not limited to inflammatory cell count, white blood cell activation markers, markers of apoptosis, markers of cell death, inflammatory cytokine levels. These blood samples will be analysed at the William Harvey Research Institute, Queen Mary University of London using standard laboratory techniques. We will also seek written consent from these patients to take part in the questionnaires outlined above for females and males. The questionnaires will be delivered in person at the time of blood sampling or over the telephone after discharge. In addition, we will consent patients to be contacted regarding future research studies examining sex differences in CAD and inflammation. All data will be added to the secure database.

4. In the circumstance where additional blood tests reveal significant results that require action. We will inform the patient and the patients direct care team if applicable (e.g for current inpatients). If necessary, a referral to an appropriate specialist will be done with the patients consent. We will also write to the patients' general practitioner in this circumstance to inform them of the results and action performed or required.

5. Novel data held in the secure database will be cross analysed with routine clinical data from the BartsREVASC database, electronic patient record and other relevant databases if required such as the MINOCA database in order to establish relationships,for follow up and MACE outcome data (see below),. Protecting patient's data is important and therefore data will be pseudonymised before being used for research purposes.

6. Patients will be followed up at 30 days/1 year using electronic patient records at to determine outcomes including but not limited to medication data, all-cause mortality, readmission rates and further cardiovascular events.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 6000
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Any patient presenting with chest pain =16 years to Barts Heart Centre Will be included.

Exclusion Criteria:

• Patients <16 years will be excluded and adults lacking capacity will be excluded.

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atherosclerosis
• Coronary Artery Disease
• Coronary Disease
• Infarction
• Inflammation
• Myocardial Infarction
• Myocardial Ischemia

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Queen Mary University of London

References & Publications (3)

Lee MT, Mahtta D, Ramsey DJ, Liu J, Misra A, Nasir K, Samad Z, Itchhaporia D, Khan SU, Schofield RS, Ballantyne CM, Petersen LA, Virani SS. Sex-Related Disparities in Cardiovascular Health Care Among Patients With Premature Atherosclerotic Cardiovascular Disease. JAMA Cardiol. 2021 Jul 1;6(7):782-790. doi: 10.1001/jamacardio.2021.0683. — View Citation

Rathod KS, Jones DA, Jain AK, Lim P, MacCarthy PA, Rakhit R, Lockie T, Kalra S, Dalby MC, Malik IS, Whitbread M, Firoozi S, Bogle R, Redwood S, Cooper J, Gupta A, Lansky A, Wragg A, Mathur A, Ahluwalia A. The influence of biological age and sex on long-te — View Citation

Shabbir A, Rathod KS, Khambata RS, Ahluwalia A. Sex Differences in the Inflammatory Response: Pharmacological Opportunities for Therapeutics for Coronary Artery Disease. Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:333-359. doi: 10.1146/annurev-pharmtox-010919-023229. Epub 2020 Oct 9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	Mortality at 30 days and 1 year and relation to sex hormone/menstrual status/inflammatory profile	30 days/1 year
Primary	Re-admission	Re-admission rates post revascularization and relation to sex hormone/menstrual status/inflammatory profile	30 days/1 year
Primary	MACE	MACE post revascularisation and relation to sex hormone/menstrual status/inflammatory profile	30 days/1 year
Secondary	Relationship with specific MI types	Relationship of sex hormone/menstrual status/inflammatory profile with specific types of ACS such as MINOCA	30 days/1 year
Secondary	Relationship with inflammation	Relationship of sex hormone/menstrual status with markers of inflammation (e.g white cell count, CRP, D-dimer) and severity of disease (e.g troponin, extent of coronary disease)	30 days/1 year