Clinical trial NCT01992848: MAP-Calcification: MicroRNAs as Potential Biomarkers for Coronary Artery Calcification
Official title: A Case-control Study of MicroRNAs a Potential Biomarkers for Coronary Artery Calcification (CAC) - An Additional Substudy to Determine the Relationship Between CAC and Bone Mineral Density and Markers of Bone Metabolism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Artery Calcification
Coronary Artery Disease
Osteoporosis
Osteopenia
Lead sponsor: University of Surrey
Sponsor class: OTHER
First posted: 2013-11-25
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* Patient is able to provide written, informed consent

Exclusion Criteria:

* Age \> 65 years
* Diabetes mellitus
* Glomerular filtration rate ≤ 60 ml/min
* Abnormal serum calcium
* History or clinical features of cardiac failure
* Systemic inflammatory disease
* Peripheral vascular disease
* Previous history of percutaneous coronary intervention (PCI)
* Previous history of coronary artery bypass grafting (CABG)
* Previous history of reno-vascular disease
* Active infection
* Active malignancy

Additional clinical exclusion criteria for our sub-study are:

* Regular use of sunbeds
* A sun holiday one month prior to or plans for sun holiday within the study
* Use of vitamin D supplements
* Consumption of alcohol above recommended levels
* Pregnancy or planned pregnancy
* Use of a veil

Primary outcomes:
measure: A miRNA signature in the presence and absence of coronary artery calcification (CAC)
timeFrame: 12 months
Secondary outcomes:
measure: mRNA(messenger RNA) targets of identified miRNAs in the presence and absence of CAC
timeFrame: 12 months
measure: Bone Mineral Density (BMD) in the presence and absence of CAC
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
Other outcomes:
Locations:
city: Guildford
country: United Kingdom
facility: The University of Surrey
state: Surrey
city: Guildford
country: United Kingdom
facility: The Royal Surrey County Hospital
state: Surrey
Study officials:
affiliation: The University of Surrey
name: Michael Mahmoudi, MBChB PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Surrey
name: Chris Fry, BSc PhD
role: STUDY_DIRECTOR
References:
citation: 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.