Coronary artery PET imaging with NaF - the debate continues

The paper we published in JACC with colleagues in Edinburgh continues to be discussed. A letter and our reply were recently aired on the JACC website.

It’s certainly true that we don’t fully understand the dynamics of NaF uptake into coronary atherosclerosis. And we are still working on ex-vivo experiments to determine the binding characteristics of the tracer in atherosclerosis, which will likely be similar to that expressed in bone tissue. We do know that the degree of NaF uptake correlates with cardiovascular risk, and there is only a weak relationship between NaF and FDG uptake. So it is likely telling us something different from metabolic activity of the plaque.

Whether it is predictive of future cardiovascular events, can be altered with therapy or is reproducible - time (and lots of research efforts) will tell.


On my way to ESC 2012

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, 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

Can three minutes of exercise a week help make you fit?

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).

Physical exercise and vascular risk

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.

Guidelines For Assessment Of Cardiovascular Risk In Asymptomatic Adults

ACCF/AHA guidelines - nice summary of current thoughts.

Similar guidelines were published recently by the European Society of Cardiology.

CT ClinImage Cardiac 4

Figure 6  2

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.

Predicting the outcome of clinical trials by computer?

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.