Asymptomatic Individuals With a Positive Family History for Premature Coronary Artery Disease and Elevated Coronary Calcium Scores Benefit From Statin Treatment: A Post Hoc Analysis From the St. Francis Heart Study

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

Thoughts? Blunt tool?

Chocolate and CV risk - small and dark is best

For those that celebrated Easter with chocolate Eggs, a timely study in the European Heart Journal.

This large, observational study of over 19,000 Germans had a mean follow-up of 8 years. The authors (Buijsse and colleagues) demonstrated that those eating the most chocolate had fewer MI and strokes than more modest consumers (by 39%). Participants were free from cardiovascular disease at baseline.

On average, blood pressure measures were 1 mmHg/0.9 mmHg lower in the highest quartile of chocolate consumption versus the lowest.

It must be said, however, that we are talking about small amounts of chocolate here. Those in the highest quartile consumed 7.5g daily compared with 1.7g daily in the lowest quartile.

This work adds to already published data demonstrating that chocolate can lower blood pressure and improve both endothelial and platelet function.

It's thought that the active ingredient is the cocoa - a flavonoid - also present in red wine, citrus fruits and tea.

Of course the downside is that chocolate is largely sugar - which equals calories - and so must be consumed in small amounts to get the CV benefit.

And it's the expensive stuff, with the highest cocoa content, that would be expected to deliver the most protection.

Sadly, this blog post is not endorsed by Cadbury's, Mars or Godiva.

A larger, more recent meta-analysis is described here.

Any thoughts on this issue? Should we file this under the "All things in moderation" category?

The central role of hypoxia in atherosclerosis

This instructive image shows the central role that hypoxia is believed to play in atherosclerotic plaque development and destabilisation.

It is taken from an editorial by Peter Libby in the journal Circulation Research.

Automated citation tracking from ISI Web of Knowledge

Here's a link to ISI Web Of Knowledge, from where you can easily retrieve publications and set up citation alerts for them.

I get weekly emails that enclose the abstracts of any publications that cite my work. This helps me stay in touch with the research field that I'm interested in.

Imaging atherosclerosis presentation - Barcelona November 2011

Here's a link to the PDF of a talk I gave today in Barcelona at a vulnerable plaque conference, hosted by Valentin Fuster.

What do you think - is it even worthwhile looking for high-risk plaques given that IVUS-VH shows us so many of them?

http://www.evernote.com/shard/s3/sh/cbbc7b18-7871-478b-85a0-f3f934de3cd3/832d02e0abcfb85cdd8d647b95253b2c

 "Detection of the High Risk Atherosclerotic Plaque - The role of PET/CT Imaging".

Aberrant right coronary artery - what next?

Our hypothetical patient is a 30 year old male construction worker who complained of chest pains at rest, had inferior ST depression and elevated troponin. He settled with medical therapy.

X-ray angiography revealed smooth coronaries without atherosclerosis, but an aberrant RCA.

Subsequent cardiac CT revealed RCA arising from the left coronary sinus of the aorta, but with a separate origin to the left main artery (Image 1). The RCA course was between the ascending aorta and the pulmonary artery. initially the calibre was small (Image 2), widening out once it was in the 'normal' position (Image 3).

The working diagnosis was inferior NSTEMI secondary to compression of the RCA.

What are your views on therapy for this patient?

Is surgery needed? If so, which operation ? Re-implantation of the RCA, or bypass of the RCA?

Is there a role for stenting of the segment lying between PA and Aorta?

Let us know your opinions on how to manage these rare but important patients.

ESC Wrap Up - The End Of The Road For Warfarin In AF?

I thought I'd finish the coverage of ESC by discussing briefly 2 studies that were part of the congress and asking for your opinion.

First, there were further data released from the RE-LY study, covered in depth over at HeartWire - here. This study compared a new oral anticoagulant, dibigatran, head-to-head with warfarin in patients with atrial fibrillation. The results showed that the new drug was non-inferior at low dose and superior at high dose in reducing the number of strokes in the population studied, regardless of the INR control achieved with warfarin. This was a post-hoc analysis from the main study of over 18,000 subjects.

Second, today, there was new data from a competitor product, apixaban, in the same patient group although not directly against warfarin, but against aspirin. The new agent was successful at lowering risk of stroke and systemic embolus (by 34%) without excessive bleeding risk. Head to head studies against warfarin are underway (ARISTOTLE study - reports in 2011).

Is the writing on the wall for warfarin in atrial fibrillation? We don't yet know how the newer drugs will stack up against warfarin for those with rheumatic heart disease and AF. But the ease of use and low bleeding rates will certainly be very attractive to clinicians once the drugs come to the marketplace. Presumably more patients will receive these drugs than currently get warfarin, because of the perceived problems (bleeding, monitoring, drug interactions) with warfarin use.

What do you think? Are you eagerly awaiting warfarin replacements? Or is more evidence required?

Day 4 - ESC

As a change, I thought I'd cover this Day in Stockholm using Twitter feeds. This will give you multiple opinions from a cross section of delegates. Simply click on the links to read more!

Safety of 2 intravenous heparin doses with PCI in ACS patients treated with fondaparinux - here.

ISAR REACT 3A: Reduced dose of unfractionated heparin in patients undergoing percutaneous coronary interventions - here.

Today's hotline press releases - here.

Nurses can reduce the risk of recurrent complications in heart patients: results from the RESPONSE trial - here.

REACH: Comparative Determinants of 4-Yr CV Event Rates in Stable Outpatients at Risk of or with Atherothrombosis - here.

A pill costing less than £1.50 a day has the potential to save thousands of heart failure patients - here.

Hot arteries: Marion Hoffman, Chicago - Vascular muscle cell factor implicated in aortic aneurysms - here.

Future of myocardial perfusion imaging - here.

Day 3 ESC

A very well attended session at the ESC today concerned novel approaches to imaging the vulnerable plaque.

We heard from Zahi Fayad (New York), Jagat Narula (Orange, Ca) and Beat Kaufmann from Basel in Switzerland. I gave an over-view of vascular PET imaging, both with FDG and novel targeted ligands against plaque macrophages.

The session tried to communicate not only the state of play in 2010, but also to predict what may be around the corner for imaging. There seems to be a move towards more platform integration, with the appearance of combined PET/MR hardware. This will allow high sensitivity/high resolution imaging of the artery wall. I guess this will have large impact in brain imaging and likely also in cardiology for myocardial imaging.

For CT, as well as a move to lower radiation dose, Zahi Fayad talked about multi-color CT, something that holds great promise in separating out the various plaque elements, to a much greater extent than currently feasible with single energy imaging with iodine contrast agents. This work was recently published in Radiology (Cormode D et al - see image below).

We also heard a great review of ultrasound imaging of vulnerable plaque, using targeted microbubbles against selectins and adhesion molecules. Whilst very exciting, the field is confined right now to small animal models of disease, and to epitopes expressed on endothelial cells. But there is promise of eventual human translation.

What caught your eye in Stockholm today?

Day 2 - ESC

The day was dominated by the first hotline trial results. The one that caught my eye in particular was the STAR-heart study, covered in depth on Heartwire. In summary, in a group of patients with chronic heart failure due to CAD, the intracoronary infusion of bone marrow-derived stem cells had a significant survival benefit maintained out to 5 years. Accompanying this were improvements in ejection fraction and other measures of functional capacity. A similar size control group received no stem cells but identical follow-up.

Although somehow the results of the study were published a few months before this Hotline Session in the European Heart Journal, the presentation here in Stockholm still caused considerable interest on the conference floor.

The mechanism of such a sustained benefit was the topic of much discussion, given a single administration of cells down the infarct-related artery. Also of note was the improvement in electrical stability seen in the treatment group - with an increase in heart rate variability.

One postulated mechanism was that the transplanted cells act as a scaffold for the resident cardiac stem cells, with direct paracrine effects on these cells another possibility.

What do you think of this landmark study? How about the publication embargo being broken by the European Heart Journal?

What about the mechanism of efficacy here?

Do you envisage a primary PCI procedure eventually involving a shot of stem cells down the infarct related artery after successful PCI?

Your answers to these questions, and others, are most welcome!