I just took advantage of Cambridge's online repository service for research documents. I uploaded my PhD thesis from 2003 - 'Imaging atherosclerosis using FDG PET'. In it, I describe the first prospective study if FDG PET for measuring real-time inflammation in the carotid arteries.
Feel free to download it by visiting this page.
Excellent webcast of an ESC 2012 presentation by Perry Elliot of the Heart Hospital. He's an expert in HCM. He covers the prediction of risk in that disease using genetic, clinical and imaging factors. He mentions the ESC and ACC guidelines and the development of a new web-based tool for refining risk on an individual patient basis.
A stimulating roundtable discussion of PURE, FAST-MI, WOEST, ACCESS-EU, TRILOGY, and other top trials from ESC 2012, presented by theheart.org.
My talk at ESC 2012 in Munich is now available for watching via webcast if you're so inclined.
I'm presenting some data about the imaging of early atherosclerosis, at the ESC in Munich this Saturday link to session. The session will be webcast should you be at a loose end.
The heart.org, as always, has a great preview of what to expect from the meeting:
Munich, Germany - This year's European Society of Cardiology (ESC) 2012 Congress is back in Bavaria after a four-year absence. Organizers of the meeting say the line-up of hot-line trials offers a mix of new treatments as well as several seeking to prove once and for all whether certain treatments, used for years, are really the best approach.
In all, this year's program includes 18 hot lines, grouped in three sessions over three days. Among the studies garnering the biggest buzz in the lead-up to the ESC meeting is TRILOGY-ACS, a comparison of prasugrel and clopidogrel in the setting of medically managed unstable angina/NSTEMI.
Read their full preview here.
Hopefully there'll be time for beer and sausages too. And I know from experience that there are some great parks where I can jog for miles.
I'll keep you posted, probably via Twitter
From the BBC website:
A few relatively short bursts of intense exercise, amounting to only a few minutes a week, can deliver many of the health and fitness benefits of hours of conventional exercise, according to new research, says Dr Michael Mosley. But how much benefit you get from either may well depend on your genes.
This seems unbelievable to me. But there is some limited data to back up the claims.
For a fuller explanation and some fascinating videos of the technique in action, checkout the Horizon broadcast (only for UK viewers I suspect).
From Circulation, the Physical Activity and Inflammatory Markers Over 10 Years: Follow-Up in Men and Women from the Whitehall II Cohort Study
Background—Inflammatory processes are putative mechanisms underlying the cardio-protective effects of physical activity. An inverse association between physical activity and inflammation has been demonstrated but no long-term prospective data are available. We therefore examined the association between physical activity and inflammatory markers over a 10-year follow-up period.
Methods and Results—Participants were 4289 men and women (mean age 49.2 years) from the Whitehall II cohort study. Self-reported physical activity and inflammatory markers (serum high-sensitivity C-reactive protein [CRP] and interleukin-6 [IL-6]) were measured at baseline (1991) and follow-up (2002). Forty-nine percent of the participants adhered to standard physical activity recommendations for cardiovascular health (2.5 hours per week moderate to vigorous physical activity) across all assessments. Physically active participants at baseline had lower CRP and IL6 levels and this difference remained stable over time. In comparison to participants that rarely adhered to physical activity guidelines over the 10 years follow-up, the high adherence group displayed lower logeCRP (β=-0.07, 95% CI, -0.12, -0.02) and logeIL-6 (β=-0.07, 95% CI, -0.10, -0.03) at follow up after adjustment for a range of covariates. Compared to participants that remained stable, those that reported an increase in physical activity of at least 2.5 hours/wk displayed lower loge CRP (B coefficient =-0.05, 95% CI, -0.10, -0.001) and loge IL-6 (B coefficient =-0.06, 95% CI, -0.09, -0.03) at follow up.
Conclusions—Regular physical activity is associated with lower markers of inflammation over 10 years of follow-up and thus may be important in preventing the pro-inflammatory state seen with ageing.
Keep running. The only way out is through.
ACCF/AHA guidelines - nice summary of current thoughts.
Similar guidelines were published recently by the European Society of Cardiology.
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Images above show non-invasive cardiac imaging using CT, compared (bottom) to invasive coronary angiography - 'A'. Note the distal left main stem 'soft' plaque visible on the contrast CT - 'C', invisible on the non-contrast calcium scoring CT scan in 'B'.
Dangerous plaques are missed by calcium scoring alone in maybe 5% scans in symptomatic subjects.
Clinical trials are very expensive, time consuming and frequently yield inconclusive results.
An article in Wired magazine described a computer simulation model that can predict the results of drug trials in humans, without actually giving a single patient a pill.
The model is called Archimedes, and is based at the San Francisco company of the same name. Its creator, David Eddy, spent two decades programming information about anatomy, physiology, disease, risk factors and their response to different drugs. The article explains how Archimedes was able to almost exactly predict the true results of the CARDS trial (examining the effects of statin therapy on cardiovascular outcomes in diabetic patients) ahead of unblinding of that study.
Whilst the underlying algorithms and assumptions of Archimedes are a trade secret, do you think it gives us a glimpse into the future of clinical trials? Where studies of drug efficacy will be simulated on hundreds of thousands of patients? There’s also evidence that the adverse effects of drugs (for example hepatotoxicity) can also be predicted with reasonable accuracy. This is achieved by comparing the molecular structure of the drug in question with millions of others that have a known side effect profile.
Personally, I think these developments are fascinating, but I think the era of the large-scale clinical trial will be here for a while yet. Whether big pharma can leverage these types of simulations to screen for likely efficacious molecules with few adverse effects on human physiology remains to be seen.
What do you think? Let me know in the comments below.
A multi-biomarker blood and urine test designed to estimate future cardiovascular risk is in the news at present, having been featured at the prestigious TedMed conference and written up on theheart.org.
The test comprises a panel of five biomarkers, each focussing on different phases on the atherosclerotic plaque development and rupture process. This seems to me to be an interesting and novel approach.
The company that provides the test, Cleveland Heart Lab, suggests that the F2-Isoprostane/Creatinine urinary ratio highlights oxidation and unhealthy lifestyles such as smoking, lack of exercise and obesity, apparently representing a long-term marker of cardiovascular risk.
The next two of the markers estimate intermediate cardiovascular risk. These are hS-CRP and urinary microalbumin.
Finally, in terms of assessing very near-term risk of cardiovascular events, myeloperoxidase and Lipoprotein-Associated Phospholipase-A2 are markers of a vulnerable plaque phenotype.
On the company's website there are several supportive studies.
On the whole I think this is an interesting approach, but of course much remains to be done. Generally, with the biomarker approach, only small incremental benefits over and above Framingham scoring have been demonstrated. I am more of an advocate for atherosclerosis imaging which is generally associated with a far higher relative risk of cardiovascular events if the test is positive.
Whilst the idea of a simple, relatively inexpensive blood test is appealing to both patients and their doctors, be positive and negative predictive values of the test must be known. It must also (or they must also) provide added value to Framingham risk scoring if it is to be of any use.
Does the biomarker panel change with either lifestyle modification or drug therapy?
Although not directly testing this particular panel of biomarkers, the HRP Bioimage study should hopefully provide some firm ground for the recommendation of either blood biomarkers, structural atherosclerosis imaging tests or both in the asymptomatic high-risk population.
If you have any thoughts on this please feel free to jot them down below.