Cardiovascular disease (CVD) is the second most common cause
of death in the UK with 27% of all death attributable to this (all cancer
caused 29% of mortality). It was responsible for 25% of premature death in men
and 17% in women.(1)
Current primary prevention strategies rely on risk
stratification which is generally undertaken in primary care. This is
recommended in all patients older than 40. Tools such as JBS, QRISK2 and Framingham
combine multiple variables to produce a 10 year risk for developing clinically
evident CVD. If the CVD risk is greater than 10% then a range of medical
therapies including statin therapy, aspirin and blood pressure reduction
medications should be offered if appropriate. In addition patients are advised
on lifestyle modification which includes weight reduction, smoking cessation,
diet modification, alcohol reduction and exercise.
High risk plaque
The concept of high risk or vulnerable plaque has been
around for over two decades. Despite major advances in our ability to image and
characterize these plaques there is little data to suggest that the primary
prevention strategies affect the outcomes of these plaques.
Plaque rupture is responsible for 75% of ST elevation
myocardial infarction (STEMI) with plaque erosion responsible for 25%. The
classic morphology of a plaque rupture shows thrombus overlying the thin
fibrous cap of the plaque.(2) The identification of plaque rupture as being
the major contributor to acute coronary syndromes has driven the development of
multiple imaging modalities to help identify such lesions.
VH-IVUS (Virtual histology
intravascular ultrasound) is routinely used to help delineate complex coronary lesions
and help with stent sizing in some PCI settings. The technique has also been
use to help identify thin-capped fibroatheromas (TCFA’s) and has been
extensively used in research into vulnerable plaque.
PROSPECT (Prospective Natural
History Study of Coronary Atherosclerosis) followed up 697 patients who
underwent PCI for ACS.(3) The 3 year cumulative MACE rate was 20.4%
of which 11.6% was at a non-culprit lesion. The study concludes that the
majority of these lesions showed angiographically mild luminal stenosis but
were associated with TCFA, large plaque burden, small luminal area or a combination
of these risk factors. Those that had a combination of these three risks had
the greatest rate of MACE.
In their serial VH-IVUS paper Kubo
et al studied 245 lesions in 99 patients.
There were 20 lesions characterized as TCFA on initial investigation of
which 15 had “healed” at 12 month follow
up but there was development of further 6 TCFA. (4) Similarly data
from PROSEPCT suggests that not all TCFA plaque is vulnerable to causing ACS.
There were 595 such lesions at baseline in the non-culprit group and at follow
up only 26 (4.4%) were responsible for MACE at a median of 3.5 years.
This data plays into the knowledge
of what occurs in the development of atherosclerosis. There is a dynamic
ongoing process involving a biologically active plaque. There is a constant
balance of plaque rupture and healing with subsequent plaque progression. The
balance by which plaque rupture goes on to form huge platelet activation (ACS
plaque rupture) and those which result in plaque healing and progression is
complicated and attributable to multiple factors. These include inflammation,
plaque characteristics (location, volume, composition) and haemostasis.(5)
CT and High Risk Plaque
CT Coronary Angiography (CTCA) has significantly improved
over the last decade. Technological advancements have achieved higher rates of
temporal and spatial resolution in combination with lower radiation exposure. Lesions
predictive of future events have been characterized by CT and include positive
remodelling (PR), low attenuation (LAP) and spotty calcification. Low
attenuation plaques (<30 Hounsfield units) correlate closely with IVUS verified
Motoyama et al assessed 3158 patients who were referred for
CTCA for assessment of chest pain.(6) The mean follow up was 3.9
years. In patients who had high risk plaque the event rate was 16.3% (48 out of
294) and in patients with low risk plaque the event rate was 1.4% (40 out of
2864). The overall event rate for the population group was 2.8%.
This represents an enormously high adverse risk profile.
High cardiovascular risk based on Framingham tools and its modern derivatives
place suggest a 10 year risk of 20% as being high risk. The use of CTCA is able
to reclassify patients as having a 16% risk of ACS in 4 years. The study by
Motoyama et al doesn’t give levels of primary prevention but statin therapy has
been shown to reduce high risk plaque.
CTCA is becoming an even more powerful tool in terms of
reclassifying patients at risk of adverse events. The staggering event rate as
reported by Motoyama et al must surely indicate that these patients are targets
for aggressive primary prevention. But even whilst we dole out our usual
package of statin, aspirin, weight management, blood pressure management and
healthy diet is this really enough in this patient group? The question of
stenting vulnerable plaques has been around and one pilot, SECRETT Study, aimed
at addressing this.(7) However, with the advent of pressure wire
guided therapy no full randomized control trial has addressed this issue. The
changeable state of high risk plaque illustrated in PROMISE and in IVUS studies
suggests that while any one plaque could be deemed high risk there could be
little net patient benefit from “plaque sealing” with PCI. In addition every
PCI procedure comes with a risk which should not be overlooked in this setting.
At present aggressive primary prevention is the only
treatment option for high risk plaque but further work needs to be done to
reduce adverse outcome in this ultra-high risk group. Further data is required to
assess how these plaques change and behave in patients undergoing aggressive
primary prevention strategies, and if this is enough, in its current form to
stave off this ultra-high risk.
Nemerson Y. A Simple Experiment and a weakening
paradigm: the contribution of blood to propensity for thrombus formation.
Arterioscler Thromb Vasc Biol. 2002;22(9):1369
Stone GW, Maehara A, Lansky AJ et al. A Prospective Natural History Study of
Coronary Atheroscelrosis. N Engl J Med 2011;364:226-235
Kubo T, Maehara, Mintz GS et al. The dynamic
nature of coronary artery lesion morphology assessed by serial virtual
histology intravascular ultrasound tissue characterization. J Am Coll Cardiol
Arbab-Zadeh A, Nakano M, Virmani R and Fuster V.
Acute Coronary Events. Circulation. 2012;125:1147-1156
Motoyama S, Ito H, Sarai M et al. Plaque
characterization by coronary computed tomography angiography and the likelihood
of acute coronary events in mid-term follow up. JACC 2015;337-46
Wykrzykowska JJ, Diletti R, Guitierrez-Chico JL
et al. Plaque sealing and passivation with mechanical self expanding low
outward force nitnol vShield device for the treatment of IVUS and OCT-derived
thin cap fibroatheromas (TCFAs) in native coronary arteries: report of the
pilot study (SECRITT) EuroIntervention. 2012;8:945-54