James Ruddweb 560x315

From left to right, CT, PET and combined PET/CT images of the heart arteries. The areas in white on the left and right panels demonstrate calcification of the arteries, whilst the orange spots on the middle and right panels demonstrate actively calcifying areas of atherosclerosis. These have accumulated significant amounts of NaF, and we believe that these areas represent high-risk areas for future heart attacks. Further work is, of course, needed to prove this hypothesis.

Building on work pioneered in Cambridge 10 years ago, scientists have developed a new imaging approach that could help improve how doctors predict a patient’s risk of having a heart attack.

The British Heart Foundation (BHF) funded project, a collaboration between scientists from the Universities of Cambridge and Edinburgh, is the first to demonstrate the potential of combined PET and CT imaging to highlight the disease processes causing heart attacks directly within the coronary arteries.

The research, published last week in the Journal of the American College of Cardiology (JACC), involved imaging over 100 people with a CT calcium scan to measure the amount of calcified or hardened plaques in their coronary arteries. This is a standard test, which is commonly used to predict heart attack risk but cannot distinguish calcium that has been there for some time from calcium that is actively building up.

The patients were also injected with two contrast agents that show up on PET imaging scans, and which can be used to track various metabolic pathways in the body. One of these tracers, 18F-sodium fluoride (18F-NaF), is a molecule taken up by cells in which active calcification is occurring. The 18F-NaF can then be visualised and quantified during a PET scan.

The researchers wanted to see if they could identify patients with active, ongoing calcification because these patients may be at higher risk of heart attack than patients in whom the calcium developed a long time ago. The results showed that increased 18F-NaF activity could be observed in specific coronary artery plaques in patients who had many other high-risk markers of cardiovascular disease.

Dr James Rudd, HEFCE Senior Lecturer at the Department of Medicine and joint senior author of the paper, said: “Our results show, for the first time, that certain areas of atherosclerosis within the coronary arteries, previously thought to be inert, are actually highly active and have the potential to cause heart attack. Once identified, they might be targeted with drug therapy more effectively.

“Additionally, we might be able to improve our ability to predict an individual person’s future risk of heart attack using this fairly straightforward imaging test in selected people.

“This research exploits longstanding scientific links between my research team in Cambridge and Professor Newby’s in Edinburgh, with core support from the Cambridge NIHR Biomedical Research Centre, HEFCE and the British Heart Foundation.”

Dr Marc Dweck, lead author on the research paper and a BHF Clinical Research Fellow at the University of Edinburgh, said:

“Predicting heart attacks is very difficult and the methods we’ve got now are good but not perfect. Our new technique holds a lot of promise as a means of improving heart attack prediction although further ongoing work is needed before it becomes routine clinical practice.

“If we can identify patients at high risk of a heart attack earlier, we can then use intensive drug treatments, and perhaps procedures such as stents, to reduce the chances of them having a heart attack.”

Dr Shannon Amoils, Research Advisor at the (BHF), which funded the study, said:

“For decades cardiologists have been looking for ways to detect the high-risk plaques found in coronary arteries that could rupture to cause a heart attack, but it’s been difficult to develop a suitable imaging test that can focus in on these small vessels.

“This research is a technical tour de force as it allows us to assess active calcification happening right in the problem area – inside the wall of the coronary arteries and this active calcification may correlate with a higher risk of a heart attack.”

There are nearly 2.7 million people living with coronary heart disease (CHD) in the UK and it kills 88,000 people each year. Most of these deaths are caused by a heart attack. Each year there are around 124,000 heart attacks in the UK.

 

Progress and challenges in translating the biology of atherosclerosis-Libby et al Nature, 2011

Statins effectively lower LDL and CRP levels in humans. Analyses of several large studies of statins in primary- and secondary-prevention populations suggest that some of their clinical benefit accrues from an anti-inflammatory action distinct from LDL lowering. The hypothesis that an anti-inflammatory intervention can reduce cardiovascular events independent of lipoprotein effects still requires rigorous testing. Thus, despite hundreds of studies affirming a role for inflammation in atherosclerosis in mice, and many intriguing observations in humans, Koch’s postulates remain unfulfilled.

 

A very comprehensive review from an eminent group of authors appeared in EHJ recently.

Non-invasive anatomic and functional imaging of vascular inflammation and unstable plaque

It covers:

  1. Pathobiology of plaque, including lipid accumulation, oxidation, inflammation, matrix breakdown, apoptosis and calcification (both macro- and micro-).

  2. Imaging techniques PET, SPECT, CT, MRI and ultrasound

There were some interesting comments on the increasing use of FDG PET imaging for detection of inflammation in atherosclerosis : –

“Despite these attractions, some issues require resolution before embracing FDG uptake in this regard. Firstly, only limited prospective data correlate FDG uptake, or changes in FDG uptake, with cardiovascular events or altered rates of such complications,42 and we eagerly await the results of larger prospective cohort studies, such as the High Risk Plaque Initiative and BioImage studies.”

“In this regard, nuclear agents that image hypoxia, already in use in oncology, may be useful in imaging atherosclerosis, as hypoxic conditions may prevail in the core of lesions.”

I quite agree on point 1 and keep watching this space for point 2!

 

Microsoft Word: 5 misuses and 7 alternatives:

If you work on a Windows PC your life most likely revolves around Microsoft Word. It does not need to be so on a Mac. I still need MS Word to exchange files with Windows-based colleagues and also because it … Continue reading

(Via Academic workflows on Mac)

 

Computed Tomography Myocardial Perfusion Imaging with 320-Row Detector CT Accurately Detects Myocardial Ischemia in Patients with Obstructive Coronary Artery Disease [Original Article]:

Background—Computed tomography coronary angiography (CTA) has been shown to be accurate in detecting anatomic coronary arterial obstruction, but is limited for the detection of myocardial ischemia. The primary aim of this study was to assess the accuracy of 320-row CT perfusion imaging (CTP) to detect atherosclerosis causing myocardial ischemia.

Methods and Results—Fifty symptomatic patients with recent single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) underwent a comprehensive cardiac CT protocol that included 320-CTA followed by adenosine stress CTP. CTP images were analyzed quantitatively for the presence of subendocardial perfusion deficits. All analyses were blinded to imaging and clinical results. CTA alone was a limited predictor of myocardial ischemia compared with SPECT with a sensitivity, specificity, positive (PPV) and negative predictive value (NPV) of 56%, 75%, 56%, 75%, and the AUC was 0.65 (95%CI: 0.51-0.78, p=0.07). CTP was a better predictor of myocardial ischemia with a sensitivity, specificity, PPV, and NPV of 72%, 91%, 81%, 85%, with an AUC of 0.81 (95%CI: 0.68-0.91, p<0.001) and was an excellent predictor of myocardial ischemia on SPECT-MPI in the presence of stenosis (≥50% on CTA) with a sensitivity, specificity, PPV, and NPV of 100%, 81%, 50%, 100%, with an AUC of 0.92 (95%CI: 0.80-0.97, p<0.001). The radiation dose for the comprehensive cardiac CT protocol and SPECT were 13.8±2.9 and 13.1±1.7; respectively (p=0.15).

Conclusions—CTP imaging with rest and adenosine stress 320-row CT is accurate in detecting obstructive atherosclerosis causing myocardial ischemia.

(Via Circulation: Cardiovascular Imaging Publish Ahead of Print)

 

Here’s a link to my Website at the University of Cambridge. It’s built on WordPress, and I have started using Markdown for writing my posts, both on this site and over there. To do this, I use Byword, Marked, Simplenote, NV Alt and Scrivener for the really long posts. MarsEdit is a great way of posting to WordPress without having to face the daunting interface.

 

This is a view of the corkboard layout of a document in Scrivener for Mac. It’s really useful for outlining grant applications and journal articles. It was designed for novelists but works successfully for other long-form writing projects.

Each index card is an individual section of text, and these can be rearranged at will if you change your mind about something, without the bother of cutting and pasting that you’d have to do in a traditional word processing programme.

I also like Scrivener because I can keep all my research articles in the same programme, and refer to them easily whilst writing.

Once you’re finished writing, there are many export options for getting your words out into the wild. These include export to Microsoft Word, direct to PDF, eBook, HTML and novel format.

Scrivener is now available for Windows too. Give it a whirl and let me know what you think.

 

The goal of this study was to evaluate whether individuals with a positive family history for premature coronary artery disease (CAD) and coronary calcium scoring (CCS) above the 80th percentile might benefit from preventive treatment.

Background

First-degree relatives of patients with premature CAD have an increased risk for cardiovascular disease (CVD), whereas events are poorly predicted in these individuals. Surrogate markers, such as CCS, might refine risk scoring. Nevertheless, the outcome of the St. Francis Heart trial, which investigated the effect of atorvastatin 20 mg/day in asymptomatic individuals with CCS above the 80th percentile, did not reach statistical significance.

Methods

We performed a post hoc analysis on the database of the St. Francis trial to assess efficacy of treatment with atorvastatin 20 mg/day in those with CCS above the 80th percentile and presence (n = 543) or absence (n = 462) of a positive family history for premature CAD. All participants received aspirin 81 mg/day. Primary outcome included coronary death, myocardial infarction, coronary revascularization, stroke, and arterial surgery.

Results

A total of 1,005 individuals, with a mean age of 59.0 ± 5.9 years and a median absolute CCS of 370 Agatston units (interquartile range: 183 to 662) participated in the trial. After a follow-up of 4.3 (interquartile range: 3.5 to 4.5) years, 7.2% of the treated individuals with a positive family history had a cardiovascular event versus 12.5% of the placebo group (hazard ratio [HR]: 0.55; 95% confidence intervals [CI]: 0.31 to 0.97; p = 0.040). This is comparable with a number needed to treat of 18.9. In individuals without a family history, events were minimally reduced: 6.6% in the treated versus 6.8% in the placebo group (HR: 1.04; 95% CI: 0.51 to 2.13; p = 0.912).

Conclusions

The combination of a positive family history and CCS above the 80th percentile identifies a subgroup within the primary prevention population that receives greater benefit from statin treatment than the population at large. These results have important implications for future guidelines concerning individuals with a positive family history for premature CAD.

Via Journal of the American College of Cardiology: Cardiovascular Imaging

 

This study, just published in the highly respected journal ‘Annals of Neurology’ lends support to the concept of persisting inflammation, as detected by 18FDG PET, portends early stroke recurrence. In fact, 18FDG uptake was the only factor on multivariate analysis to predict recurrence, out-performing stenosis degree and age. If the SUV was above 2.1, 80% of subjects had recurrent events within 90 days.

What we need of course is a prospective study of an FDG PET-guided approach to risk stratification and management compared with standard medical/surgical care.

This study provides a counterpart to the one I published here yesterday.

Any thoughts?

 

What surprised me the most about this elegant study was the very low rate of healing of complex plaques that had caused cerebrovascular events. We know that the risk of recurrent events is very high immediately after TIA but drops off rapidly. Presumably, even high-resolution structural imaging takes some time to reflect this change in risk.

I believe this is the first longitudinal study to address this issue in humans.

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