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Evolving Concepts of Cardiovascular Risk Stratification in Diabetes
by Dr Shreenidhi Venuraju
&
Professor Avijit Lahiri
MB,BS,MSc,MRCP,FACC,FESC Consultant Cardiologist &
Director of the
Cardiac
Imaging and Research Centre at The Wellington Hospital.
Article last updated: April 27th 2010
Overview - Diabetes and Coronary Artery DiseaseDiabetes is reaching epidemic proportions in both the Western and developing worlds. Currently it 
affects nearly 5% of the adult population in UK. Due to the increasing prevalence of obesity the incidence and vascular complications of type-2 diabetes will continue to rise (The Foresight report estimates that by 2015 64% of adults aged 21 to 60 in the UK will be obese, and by 2025 this will rise to 83%). Nearly 80% of patients with type 2 diabetes suffer cardiovascular mortality/morbidity, with coronary artery disease (CAD) representing the major component of this CV disease. Approximately 10 – 15% of patients admitted to hospital with myocardial infarction (MI) and 20% of patients dying from coronary heart disease (CHD) have diabetes as a contributing factor. Thus diabetes places a large socio-economic burden on our health care system directly and indirectly.
Atherosclerotic plaque burden (Artery Clogging)Assessing atherosclerotic plaque burden has long been the goal of cardiologists as it underlies all coronary artery disease and a large percentage of cardiac disease. Despite an increasing understanding of the risk factors and mechanisms of atherosclerosis, a large proportion of patients have their initial presentation with sudden cardiac death and/or myocardial infarction. The gold standard for the assessment of coronary artery disease remains invasive coronary angiography which is essentially a lumenogram providing very little information regarding the plaque itself. Our ability to identify those asymptomatic individuals who will have a rapid progression of CAD leading to myocardial ischaemia, or whose lesions become unstable resulting in myocardial infarction, remains limited. With the advances in CT technology assessing total plaque burden itself with information regarding the morphology and components of the plaque is becoming possible. Diagnostic tests that could be used to screen for individuals needing more intensive management would significantly increase the detection and prevention of CAD. This is particularly important for patients with type 2 diabetes as they are at higher risk compared to the general population. It has been estimated that a patient with diabetes without coronary artery disease has a similar risk score as a non-diabetic patient with a myocardial infarction.
Screening for CAD and limitations with current screening methodsCoronary Artery Calcium Scoring
All the office based screening algorithms like Framingham Risk Score, PROCAM and SCORE assess a patient’s 10-year risk of developing CAD. Over the last few years, coronary artery calcium (CAC) imaging has been increasingly used in further risk stratifying patients, particularly those classed in the intermediate risk category. However, there is a poor anatomical correlation between CAC and degree of coronary stenosis and its ability to predict which patients will go on to have an event though there has been a large amount of data demonstrating its utility in predicting cardiovascular survival over 7 – 10 years. Asymptomatic patients who are assigned to the high-risk group with office-based risk assessment algorithms such as the Framingham Risk Score (FRS) will benefit from intensive risk modification. Patients in the low risk group are advised to follow a healthy lifestyle and their risk factors should be treated as and when diagnosed according to current guidelines. Patients in the intermediate-risk group pose a clinical dilemma and it is this group of patients that benefits most from CAC scoring. Management strategy for patients classified into the intermediate risk category remains predominantly subjective and an evidence free zone. Using CAC score gives us the tool to try and re-classify some of these patients into higher or lower risk groups, making management decisions easier and more evidence based.
Myocardial Perfusion Imaging (MPI)
There is also an extensive body of evidence that has accumulated over the last 2 – 3 decades regarding the utility of myocardial perfusion scintigraphy (MPS) in the diagnosis and short term prognosis of CAD. The limitation of this technique arises from its reliance on the presence of significant (>50%) luminal stenosis causing relative discrepancies in myocardial blood flow. A normal MPS does not provide any information regarding the sub-clinical plaque burden of the coronary arteries per se.
Despite these advances nearly 50% of initial presentation with CAD is with either a myocardial infarction or death. This is probably attributable to the fact that nearly two thirds of culprit plaque lesions responsible for acute coronary syndromes/death are not known to cause any significant coronary stenosis (>50%) and are not identifiable by current screening techniques.
CAC and MPI
The clinical role of CAC scoring in asymptomatic diabetic patients was clearly illustrated by Anand et al. (published: European Heart Journal (2006) 27, 713–721) from our group, in an asymptomatic diabetic population. We showed that pre-selection of patients with CAC score > 100 Au yielded far more significantly abnormal myocardial perfusion scans, confirming increased probability of significant CAD, than an unselected cohort of patients with diabetes. Thus combining Coronary Artery Calcium Imaging and Myocardial Perfusion Scanning provides an excellent method of detecting those at high risk of cardiac events (eg. death, heart attacks etc).
CT coronary angiography
Intravascular ultrasonography (IVUS) is the current gold standard for assessment and characterisation of atherosclerotic plaque burden and morphology. As the mortality/serious morbidity rate associated with conventional coronary angiography is small yet tangible (0.1-0.2%), there has been a steady push to find a non-invasive imaging modality capable of visualising the coronary vessel wall and thus sub-clinical atherosclerotic plaque lesions more effectively.
CTCA Technique
CT Coronary angiography (CTCA) requires the injection of 80-100 ml of iodine-based contrast agent (350-400 mg/ml of iodine) into the patient through a large vein at a rate of 4.5-6 ml/second. Images are acquired in a cranio-caudal direction using a retrospective ECG-gated technique. The actual scan time is less than 15 seconds in greater than 90% of patients.
Image quality is improved with the use of sub-lingual glyceryl tri-nitrate (GTN) spray approximately five minutes prior to the scan and also beta-blockers (oral or intravenous used in 60 – 70% of patients prior to the scan) to get a heart rate ideally of <65 beats per minute. Though it is possible to image the coronary tree with reasonably diagnostic images with heart rates of > 70 bpm with the Dual-Source CT scanner, image quality is definitely better when the heart rate is less than 70 bpm.
Clinical role of CT angiographyContrast-enhanced coronary angiography is a relatively new application for CT scanners. Unlike the two-dimensional lumenogram of conventional invasive angiography, this technique also allows us to visualise the vessel wall and the plaque itself, and has the potential for plaque characterisation, bringing us a step closer to identifying the characteristics of a vulnerable plaque (Plaque prone for rupture), which is the ‘holy grail’ of cardiology. There have been a couple of studies published which have identified some of the characteristics of a vulnerable plaque; non-calcified with spotty calcification and {napkin-ring appearance’ of plaque which signifies thin-cap fibro-atheroma.
In order to get high quality diagnostic images of the heart in a reproducible manner, newer scanners such as the Dual-source CT scanner or 320 slice scanner, are better suited for imaging the coronary arteries and are superior to the 64-slice CT scanners. Though CTCA is able to identify the sub-clinical plaque, we are still at the early stages of research into plaque morphology and its clinical relevance. Though a combination of Dual-source CT-coronary angiography (DS-CTCA) and measurement of specific biomarkers may help to assess not only the total coronary artery disease plaque burden , but also the ‘stability’ of the plaque and possibly identify those at higher risk of rapid progression of the disease. We will shortly begin recruiting for the PROCEED trial in our centre, focussing on the early detection of CAD and evaluation of progression of the disease in asymptomatic high risk diabetic patients using combination of DS-CTCA and novel biomarkers.
NICE Guidelines for chest painThe new NICE Guidelines relating to “Chest Pain” (April 2010) has provided clear cut guidelines regarding the use of Cardiac CT (both calcium imaging and CT coronary angiography) in combination with Myocardial Perfusion Scanning when required. We are at present conducting a large clinical trial (RADICAL) assessing the clinical and cost-effectiveness of Dual-source CT coronary angiography in patients from 3 NHS hospitals referred to the {Chest Pain Clinics’. These patients are recruited at the NHS site and then sent to the Wellington Hospital for CTCA and MPI (If needed). The DS-CTCA is combined with Myocardial Perfusion scanning when intermediate stenosis (narrowing) of the coronary arteries is noted on CTCA to guide management strategies.
ConclusionIn summary, diabetic patients have a 4-fold increase in the chance of developing silent coronary artery disease compared to the general population. By 2020 there will be over 400 million diabetics worldwide, 70-80% of whom will suffer cardiovascular mortality/morbidity and coronary artery disease will become the number one killer worldwide (according to WHO). It is therefore imperative that methods of early detection of coronary artery disease are established to combat this growing threat.
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