Coronary Revascularization and Cognitive Decline

Patients who undergo coronary revascularization are at increased risk for postprocedure cognitive impairment. Whether this outcome is due to the revascularization procedure or to the underlying shared vascular risk factors known to cause both coronary artery disease and dementia is unclear. Hypertension, diabetes, hyperlipidemia, smoking, and obesity all contribute to the development of coronary artery disease, and thus the need for revascularization, but also are known to increase the risk of cognitive decline and dementia, especially when present in middle age.^1–3 Furthermore, cardiac disease appears to be a risk factor for poor cognition,⁴ and sequelae of cardiac disease, such as atrial fibrillation⁵ or heart failure,⁶ may increase the risk of poor cognitive outcomes. As a result, it can be challenging to disentangle the long-term cognitive effects related to coronary revascularization procedures, which are commonly performed among individuals with these vascular risk factors, from the effects associated with these underlying risk factors.

In this issue of JAMA,⁷ Whitlock and colleagues analyzed data from the community-based, observational Health and Retirement Study to begin to answer this question. Importantly, the authors evaluated cognitive trajectories after coronary revascularization procedures and also considered the cognitive trajectory of participants before these procedures. In this study, a memory score was generated for 1680 older adults who had undergone either coronary artery bypass grafting (CABG; n = 665) or percutaneous coronary intervention (PCI; n = 1015). This composite score was generated by combining direct performance on cognitive testing with proxy reports on cognitive status; patients with scores 3 years before as well as 3 years after a revascularization procedure were included. The memory score was normalized as a z score (ie, mean of 0, SD of 1 in a reference population of adults aged ≥72 years), and the minimum clinically important difference was a rate of memory decline of 0.048 memory units/y.

When the rate of change in this memory score was compared before vs after the specified coronary procedure, not only was the change in the 2 procedure groups comparable, but there was no significant difference between the pre- and postprocedure time periods. In the PCI group, the mean rate of adjusted memory decline was 0.064 memory units/y (95% CI, 0.052 to 0.078) before the procedure and 0.060 memory units/y (95% CI, 0.048 to 0.071) after the procedure (within-group change, 0.004 memory units/y [95% CI, −0.010 to 0.018]). In the CABG group, the mean rate of memory decline was 0.049 memory units/y (95% CI, 0.033 to 0.065) before the procedure and 0.059 memory units/y (95% CI, 0.047 to 0.072) after the procedure (within-group change, −0.011 memory units/y [95% CI, −0.029 to 0.008]). The between-group difference-in-differences estimate for memory decline for PCI vs CABG was 0.015 memory units/y (95% CI, −0.008 to 0.038; P = .21). In addition, postprocedure dementia rates were not significantly different between the procedure groups, occurring in 10.5% of patients who had undergone CABG compared with 9.6% of those who had undergone PCI.

In any observational study of coronary revascularization procedures, the indication for the procedure must be considered. For example, is it possible that those individuals undergoing PCI were at higher risk of surgery (because of a greater cardiovascular risk) than those undergoing CABG, leading to the decision to proceed with the potentially less risky procedure? If this is true, then it is possible that any favorable difference in cognition post-PCI would be offset by these subtle group differences. There were between-group differences in the baseline study characteristics in the study by Whitlock et al, but the authors undertook careful measures to minimize the potential bias from these differences. By using inverse probability of treatment weighting, a method that allows for reweighting of a population to better approximate its distribution, thereby helping control for bias, as well as use of propensity scores to understand the differences in procedure indication, the authors reduced the likelihood that results are simply a result of these factors. Furthermore, because preprocedure cognitive trajectories were nearly identical between the 2 groups, it is unlikely that the groups were different enough to cause a possible dilution of a true postprocedure difference.

Prior studies have provided mixed results as to whether revascularization procedures are associated with an increased risk of cognitive decline and dementia. Patients may experience an early decline in cognition that has been termed postoperative neurocognitive disorder (referring to impairment lasting >30 days but <1 year).^8,9 Usually this resolves within the first 6 months, but for some patients, cognition may decline even further in the ensuing years. A 2001 study estimated that 42% of 261 patients who had undergone CABG surgery had cognitive decline at 5 years.¹⁰ This study, however, did not include a control group, and thus it may be that this high rate of cognitive decline was not specific to the procedure, but perhaps due to the underlying vascular risk. A 2009 study¹¹ compared patients with coronary artery disease who had undergone CABG surgery (n = 152 on pump) with those who did not (n = 99), and also included healthy controls without coronary artery disease (n = 69). It found that cognitive decline was greater in the coronary artery disease groups (vs healthy controls) but did not differ between the patients with coronary artery disease who had undergone CABG surgery vs those who had not. The findings emphasized that it may be more important to consider the individual risk of the patient, rather than the risk of the procedure.

Similar results have been supported by more recent studies. Patients who had undergone CABG (n = 111 335) in the SWEDEHEART registry compared with matched controls from the general population (n = 222 396) had similar rates of dementia, especially in older patients. Further, among patients who had undergone CABG, vascular risk factors, such as hypertension and diabetes, remained important factors associated with dementia.¹² In contrast, other studies have found support for an association between CABG and risk of dementia,¹³ although importantly, in these observational studies, there was the potential for residual confounding. The study by Whitlock et al⁷ demonstrated no significant difference in the rate of memory decline before and after revascularization, as well as no significant difference in the rate of memory decline in both intervention groups. These findings support the idea that it is the individual patient’s risk factor status, rather than the procedure, that is the most important indicator of future risk of cognitive decline and dementia.

These data also suggest that risk of postprocedure cognitive decline need not be considered in determining the optimal procedure for an individual patient who requires coronary revascularization. However, preprocedural cognitive status may influence decisions about which revascularization procedures to undertake. In a systematic review of 215 studies involving 91 829 patients, 19% of the patients who had undergone CABG had some evidence of cognitive impairment prior to surgery,⁹ and patients with dementia were less likely to be referred either for diagnostic cardiaccatheterization or for PCI or CABG.¹⁴ Thus, data such as those reported by Whitlock et al from the Health and Retirement Study may not be generalizable to a population with a greater prevalence of dementia.

This study adds evidence that the risk of cognitive impairment is not necessarily from the procedure, but rather is related to the reasons (ie, vascular risk factors) the patient required the procedure. Therefore, it is likely that the best way to prevent cognitive decline, whether post- or prerevascularization, is ultimately to prevent, identify, treat, and control these risk factors.

Improving risk factor control for dementia prevention has been difficult because most of the available data linking vascular risk with cognitive decline and dementia are observational, and thus do not prove that treatment, when initiated, improves outcomes. The SPRINT-MIND trial,¹⁵ which included 9361 patients with hypertension, provided clinical trial evidence that treating hypertension aggressively reduced the composite outcome of mild cognitive impairment and dementia but had no significant effect on the primary outcome of probable dementia. Furthermore, additional trial data supporting risk factor control for cognitive benefits are generally lacking. Despite the lack of consistent trial data, however, many known risk factors for coronary artery disease (hypertension, obesity, smoking, diabetes, and physical inactivity) have been identified as potential targets for prevention of dementia.¹⁶ Most important, any successful reductions in these factors that increase risk for postprocedural cognitive decline are likely to mitigate the need for revascularization, thereby avoiding the risk. Improving public health messaging about the importance of aggressively controlling cardiovascular health risk factors is critical not only for cardiac health, but also brain health.