PROSPECT Substudy: Persistently High CRP Predicts Future MACE in ACS Patients After PCI
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In patients with acute coronary syndromes (ACS) who undergo successful percutaneous coronary intervention (PCI), the likelihood of recurrent adverse events due to disease progression in nonculprit lesions depends largely on the presence of both high-risk plaque and persistently elevated levels of C-reactive protein (CRP).
These findings emerged from a subanalysis of the PROSPECT trial published online May 19, 2014, ahead of print in the American Journal of Cardiology.
| Methods |
| In the main study, 697 ACS patients underwent 3-vessel angiography post-PCI as well as grayscale and virtual histology IVUS imaging. At a median of 3.4 years, MACE (cardiac death or arrest, MI, or rehospitalization due to unstable or progressive angina) were equally attributable to recurrence at the culprit site (12.9%) and nonculprit lesions (12.6%). Most of the latter were thin-cap fibroatheromas or lesions characterized by a large plaque burden (≥ 70%), a minimal luminal area ≤ 4.0 mm2), or some combination of these traits. |
For the substudy, investigators led by Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), looked at the 571 patients who had follow-up CRP measurements at 1 month and the 462 who had CRP values at both 1 and 6 months. At each time point, CRP was categorized as:
|
| Patients with higher baseline CRP levels were more likely to have presented with STEMI or NSTEMI rather than unstable angina. In contrast, patients with higher 6-month CRP were more likely to be smokers and to have diabetes, hypertension, heart failure, and higher Framingham risk scores. One-month CRP levels demonstrated a weaker association with baseline characteristics, but at all times higher CRP was associated with greater BMI and waist circumference. CRP levels were not linked with use of aspirin, statins, or other medications at any time. |
The number of nonculprit lesions was unrelated to initial CRP level or the number of thin-cap fibroatheromas or minimal luminal area ≤ 4.0 mm2. The same held true for 6-month CRP levels.
For patients with high CRP at baseline or 1 month, rates at which high-risk lesion types resulted in nonculprit lesion MACE did not vary (all P ≥ .25). In contrast, at 6 months, rising CRP levels from normal to elevated to very elevated correlated with increased event rates for both thin-cap fibroatheromas (1.9%, 4.2%, 13.8%; P = .002) and lesions with small minimal luminal area (2.2%, 8.3%, and 15.6%; P = .0003)—but not those with higher plaque burden or lower-risk lesions.
For the entire cohort, 3-year rates of total MACE and nonculprit lesion-related MACE were 20.4% and 11.6%, respectively.
Rates of total and nonculprit lesion-related MACE were unaffected by CRP levels at both presentation (P = .87 and .78, respectively) and 1 month (P = .755 and .529, respectively). However, all 6-month CRP levels were associated with increased total and nonculprit-related MACE (table 1).
Table 1. Subsequent MACE According to 6-Month CRP Level
|
Normal |
Elevated |
Very Elevated |
P Value |
Total MACE |
11.5% |
22.5% |
25.9% |
.008 |
Nonculprit Lesion-Related MACE |
7.2% |
13.0% |
19.0% |
.039 |
On multivariable analysis, the only independent predictor of nonculprit lesion-related MACE was CRP level (HR 1.02; 95% CI 1.01-1.03; P = .0005).
Shift Toward ‘Vulnerable Patient’ Concept
“The effect of CRP on lesion-specific event rates is consistent with the recent shift in focus from vulnerable plaque to the ‘vulnerable patient,’ a concept that encompasses vulnerable plaque, vulnerable myocardium (ie, prone to ischemia and/or arrhythmia), and vulnerable blood (ie, prone to thrombosis),” the authors say. “Chronic inflammation likely has a role in all of these domains.”
In a telephone interview with TCTMD, Sergio Waxman, MD, of Tufts University School of Medicine (Boston, MA), said the results “suggest that CRP is not related to local or diffuse plaque burden itself but rather is a marker of disease activity or vulnerability. Therefore, it can give you an idea of the likelihood of a recurrent event.
“In terms of the implications for medical vs mechanical therapy,” Dr. Waxman continued, “it all depends [on whether] persistently elevated CRP is a systemic manifestation of a systemic problem or a systemic manifestation of a local problem. At this point, we don’t really know. But we do know that having a high-risk lesion substrate—for example, a thin-cap fibroatheroma or a minimal luminal area less than 4—by itself is not enough. You also need a heightened inflammatory milieu.”
How to Treat Elevated CRP Patients Unknown
Based on the study, Dr. Waxman said that if a patient has a focal thin-cap fibroatheroma in the absence of a marker of inflammatory activity such as CRP “you can make an argument that you don’t need to treat locally because the risk of progression or an event is relatively small.” On the other hand, with inflammation, he added, “treating this plaque might make sense.
“How you treat such plaques, however, is a different matter,” Dr. Waxman insisted. “Should you treat them locally by, for example, putting in a bioresorbable scaffold, or should you treat systemically by more aggressive lipid lowering, or somehow addressing the inflammatory state?
“A lot depends on future information,” he said, emphasizing the need for further trials.
Serial monitoring to track CRP would be useful only it were linked to a change in treatment or management, Dr. Waxman said, but at least the current findings “set the stage” for designing new trials. For example, he suggested, “a prudent next step” might be to randomize patients with persistently elevated CRP levels and a thin-cap fibroatheroma to stenting vs no stenting, or to aggressive vs conventional medical treatment. After all, “local treatment may be overtreatment,” he cautioned, noting that in PROSPECT, most MACE were not hard events.
A corollary message of the study, Dr. Waxman concluded, is that if CRP is not related to disease burden per se, it is important to flag patients with persistently elevated CRP levels and look at other risk factors such as diabetes or smoking.
Note: Dr. Stone and several other coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Source:
Kelly CR, Weisz G, Maehara A, et al. Relation of C-reactive protein levels to instability of untreated vulnerable coronary plaques (from the PROSPECT study). Am J Cardiol. 2014;Epub ahead of print.
Disclosures:
- PROSPECT was funded by Abbott Vascular and Volcano.
- Dr. Stone makes no statement regarding conflicts of interest.
- Dr. Waxman reports no relevant conflicts of interest.
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PROSPECT Substudy: Persistently High CRP Predicts Future MACE in ACS Patients After PCI
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