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A high burden of preoperative cerebral artery atherosclerosis is associated with the occurrence of stroke following coronary artery bypass grafting (CABG), according to an analysis published in the May 3, 2011, issue of the Journal of the American College of Cardiology.

However, carotid stenosis by itself does not appear to be implicated in stroke risk, and experts questioned whether the overall correlation with cerebral disease is strong enough to justify preoperative imaging and, if positive, alteration of the surgical approach.

To investigate the possible link between cerebral atherosclerosis and stroke within 14 days of CABG, investigators led by Sun U. Kwon, MD, of Asan Medical Center (Seoul, South Korea), looked at 1,367 consecutive patients who underwent bypass surgery at their institution between August 2004 and December 2007. All patients received preoperative magnetic resonance angiography (MRA), most within 1 month before CABG.

Scoring Atherosclerosis

Disease severity was evaluated using an atherosclerosis score, determined by the number and degree of steno-occlusions of the intracranial and extracranial (including extracranial carotid) cerebral arteries. The extent of atherosclerosis was visually graded as:

• 0 (< 50% stenosis)
• 1 (50-99% stenosis)
• 2 (occlusion)

After surgery, 45 patients underwent brain imaging, and 33 were diagnosed with ischemic stroke (31 by diffusion-weighted imaging [DWI]) and 2 by CT). Fifteen of the events occurred within 24 hours of the procedure.

Although stroke patients tended to be older, hypertensive, and hypercholesterolemic and to have a history of stroke, none of these associations was statistically significant. Multiple logistic regression analysis showed that only preoperative atrial fibrillation and higher atherosclerosis score independently predicted stroke, although hypercholesterolemia showed a trend toward an association (table 1).

Table 1. Predictors of Post-CABG Stroke

An atherosclerosis score of at least 2 was determined to be the most appropriate cut-off value to predict post-CABG stroke, with a sensitivity of 81.8% (95% CI 64.5-93.0%) and a specificity of 58.4% (95% CI 55.7-61.1).

Importantly, analysis of the association between stroke and the site of atherosclerosis showed that disease of the extracranial carotid artery had no influence on risk. However, when carotid disease was combined with atherosclerosis of other extracranial cerebral arteries, the link became significant (table 2).

Table 2. Incidence of Stroke According to Sites of Cerebral Atherosclerosis

Among the 33 stroke patients, 15 were diagnosed with atherosclerotic stroke, and these patients had a higher atherosclerosis score. Extracranial carotid disease was present in 7, but in only 3 could stroke be fully explained by carotid atherosclerosis alone.

Why Strokes Occur After CABG

According to the authors, post-CABG strokes can occur in a number of ways. For example, manipulation of an atherosclerotic aortic arch may trigger early embolism. On the other hand, delayed embolism may be due to postoperative atrial fibrillation, MI, or coagulopathy, none of which are related to atherosclerosis.

Nonetheless, almost half of the study patients who experienced delayed stroke had atherosclerotic strokes. The researchers say that stresses such as physical trauma and inflammation may trigger plaque rupture or platelet aggregation in patients with severe atherosclerosis in cervical and cranial vessels.

Dr. Kwon and colleagues suggest that “preoperative MRA evaluation of extracranial and intracranial cerebral arteries can provide information on the risks of post-CABG stroke, thereby allowing patients at high risk to be more carefully selected and managed.” Previous studies have shown that modification of surgical strategy in light of the presence of cerebral atherosclerosis may reduce the incidence of post-CABG stroke, they add.

Limitations Raise Questions

In an accompanying editorial, Steven Shea, MD, and Marco Di Tullio, MD, both of Columbia University Medical Center (New York, NY), point out that the underlying level of stroke risk in the patient cohort was not identified. For example, the percentage of urgent/emergent vs. elective surgeries was not reported, nor was the number of procedures that also involved valve replacement. “Both nonelective status and combined cardiac procedures are associated with higher stroke risk,” they observe.

In addition, strokes occurring in the territory of a vessel with greater than 50% stenosis were classified as atherosclerotic. However, the editorialists note, it is possible that such strokes were instead the result of transient atrial fibrillation and embolization to these territories.

In a telephone interview with TCTMD, Robert A. Guyton, MD, of the Emory University School of Medicine (Atlanta, GA), likewise underlined the “poor correlation between the location of strokes and the location of atherosclerosis in the head. [In addition,] we haven’t really sorted out whether atherosclerosis in the head is just a marker for atherosclerosis in the aorta.” The latter is an established cause of post-CABG stroke, he noted, and the researchers did not report on its prevalence.

Another drawback of the study, the editorialists say, is that it does not provide separate data on patients who underwent off-pump vs. traditional CABG, so it is impossible to evaluate whether the degree of aortic manipulation, which is lower in off-pump CABG, impacts stroke risk. In fact, a previous study (Kapetanakis EI. Ann Thorac Surg. 2004;78:1564-1571) reported an 80% reduction in perioperative strokes with off-pump CABG compared with conventional surgery.

Louis R. Caplan, MD, of Beth Israel Deaconess Medical Center (Boston, MA), singled out several unique aspects of the study during a telephone interview with TCTMD.

In a positive vein, it is the first to assess the cerebral arteries prior to surgery, he noted. However, the study focuses exclusively on Korean patients, and research indicates that Asians tend to have more intracranial disease, which makes them more susceptible to atherosclerotic stroke, he explained. Finally, about half of subjects were treated off-pump, suggesting that these patients may have had significant aortic disease, he said. However, the reason for the treatment choice and the associated stroke rates were not reported.

Dr. Caplan also suggested that carotid disease is relevant to stroke risk only if it is symptomatic, noting, “If you had a recent stroke, then you are at risk.” Brain imaging to detect evidence of a previous brain infarct may be helpful in Asians but probably not in Caucasians, he added.

Like the editorialists, Dr. Guyton faulted the investigators for drawing conclusions about the significance of carotid disease in light of their practice of offering revascularization to patients with significant stenosis. “They say [carotid atherosclerosis] doesn’t matter, yet when they found tight carotid stenoses in patients, they stented it [before surgery]. That’s pretty confounding,” he stressed.

Getting to the Heart of Stroke Risk

For post-CABG stroke risk, the real issue is the aorta, Dr. Guyton said. “Most surgeons are coming around to the feeling that the aorta is the main culprit and that specific focus on imaging of the aorta is what’s going to lead us to the holy grail of minimal stroke rate after bypass.”

In addition to off-pump surgery, Dr. Caplan noted that measures used to minimize risk include inserting an embolic filter into the aorta. And when aortic lesions are localized, intraoperative ultrasound enables the surgeon to place the aortic clamp in a less vulnerable spot.

“Then there are studies in which surgeons have done bypass using just mammary arteries without even touching the aortas, and the stroke rate in those patients is less than half a percent,” Dr. Guyton commented.

Beyond aortic atherosclerosis, if a patient has a low ejection fraction or poor cardiac function, anticoagulation may be altered, Dr. Caplan said. And if there are severe, symptomatic cerebral lesions and the patient is a borderline candidate for surgery, the procedure might be called off and PCI recommended instead.

The More Information the Better

“What we’re all searching for is which subgroup of [CABG] patients we need to drill down on,” Dr. Guyton said.

Dr. Caplan agreed, adding that the more information doctors have about factors contributing to stroke risk, the better decision they can make.

“I think the message is that at referral centers they need to take a good history, have studies of the heart and aorta, and brain imaging. Then taking all that [data] into consideration, the cardiologist and surgeon can better plan the operation,” he advised. “That can save brains, and probably money, because if patients have a stroke and they stay in the hospital a long time or they have encephalopathy, it costs a lot.”

Study Details

The mean age of patients was 63.2 ± 8.8 years, and 65.4% had steno-occlusive lesions in the intracranial or extracranial cerebral arteries. Off-pump or conventional CABG was performed at the discretion of the attending surgeon, with the former procedure typically preferred when severe atherosclerosis was suspected along the aortic arch.

Patients with suspected stroke were referred to stroke neurologists and evaluated by DWI or CT. Strokes were diagnosed as newly developed neurological deficits within 14 days of CABG or high-signal lesions on postoperative DWI or low-density lesions on postoperative CT that were not observed preoperatively.

2. Shea S, Di Tullio M. Post-coronary artery bypass grafting stroke: Where is it coming from? J Am Coll Cardiol. 2011;57:1819-1820.

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