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Coronary artery disease (CAD) remains the leading cause of mortality in the UK with an estimated 80,000 fatalities in 2010. Coronary artery calcification (CAC) is associated with atherosclerotic plaque burden and cardiovascular mortality. Mechanisms underlying isolated CAC have not been as yet been fully explained. MicroRNAs (miRNAs), known to act as regulators of gene expression, have also emerged as powerful biomarkers in the diagnosis and prognosis of cardiovascular disorders and may be used in the detection of CAC. We aim to investigate the potential for a "microRNA-signature" in patients with CAC by performing a prospective, case-controlled study to identify pathways associated with CAC in humans. Previous research has demonstrated an inverse relationship between CAC and bone mineral density (BMD), suggesting that these processes may be linked. In a further substudy we plan to define the relationship between CAC and BMD as well as a number of markers of bone metabolism.
Patients will be prospectively enrolled whilst attending for elective coronary CT (computed tomography) angiography including a coronary calcium score, at the Royal Surrey County Hospital. Data regarding demographic and clinical characteristics of patients will be collected. Peripheral venous blood sampling will take place on this occasion. Coronary artery calcification scores will be estimated by a Radiologist using default software. Patients eligible for the bone metabolism substudy will be required to attend the University of Surrey for peripheral Quantitative Computed Tomography (pQCT) of bone mineral composition of the radius. In the intervening period we will ask them to complete a 4-day food diary and wear a UV dosimeter, the latter to assess typical UV exposure, for one week.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| All participants | Experimental | Venous blood sampling 4-day food diary 1 week UV Dosimeter Peripheral Quantitative Computed Tomography of the radius |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Venous blood sampling | Other | 40ml venous blood sampling will be undertaken during participants' attendance for CT coronary angiography (the latter being performed as part of routine clinical investigation). |
| Measure | Description | Time Frame |
|---|---|---|
| A miRNA signature in the presence and absence of coronary artery calcification (CAC) | 12 months |
| Measure | Description | Time Frame |
|---|---|---|
| mRNA(messenger RNA) targets of identified miRNAs in the presence and absence of CAC | 12 months | |
| Bone Mineral Density (BMD) in the presence and absence of CAC | 12 months | |
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Inclusion Criteria:
Exclusion Criteria:
Additional clinical exclusion criteria for our sub-study are:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Mahmoudi, MBChB PhD | The University of Surrey | Principal Investigator |
| Chris Fry, BSc PhD | The University of Surrey | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Surrey | Guildford | Surrey | GU2 7XH | United Kingdom | ||
| The Royal Surrey County Hospital |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29531756 | Derived | Howlett P, Cleal JK, Wu H, Shah N, Horton A, Curzen N, Mahmoudi M. MicroRNA 8059 as a marker for the presence and extent of coronary artery calcification. Open Heart. 2018 Jan 31;5(1):e000678. doi: 10.1136/openhrt-2017-000678. eCollection 2018. |
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| 4-day food diary | Other |
|
| 1 week UV dosimeter | Other | To be worn on outerwear for one week week prior to attendance for pQCT |
|
| Peripheral Quantitative Computed Tomography of the radius | Radiation | To be performed within one month of attendance for CT coronary angiography |
|
| Markers of bone metabolism in the presence and absence of CAC to include: serum 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, serum calcium, albumin, parathyroid hormone, C-terminal telopeptide/CTX, and lipid profile. |
| 12 months |
| Guildford |
| Surrey |
| GU2 7XX |
| United Kingdom |
| ID | Term |
|---|---|
| D003324 | Coronary Artery Disease |
| D010024 | Osteoporosis |
| D001851 | Bone Diseases, Metabolic |
| ID | Term |
|---|---|
| D003327 | Coronary Disease |
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D001161 | Arteriosclerosis |
| D001157 | Arterial Occlusive Diseases |
| D014652 | Vascular Diseases |
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D001800 | Blood Specimen Collection |
| D015930 | Diet Records |
| ID | Term |
|---|---|
| D013048 | Specimen Handling |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
| D011677 | Punctures |
| D013514 | Surgical Procedures, Operative |
| D008919 | Investigative Techniques |
| D011996 | Records |
| D009934 | Organization and Administration |
| D006298 | Health Services Administration |
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