Coronary Microvascular Dysfunction Is Linked to Cardiovascular Risk in CKD

In people with chronic kidney disease (CKD), the risk of cardiovascular events is independently related to coronary microvascular dysfunction—and not to estimated glomerular filtration rate (eGFR), according to a study by Navkaranbir S. Bajaj and colleagues in a recent issue of Circulation.

The longitudinal study included 352 patients referred for stress myocardial perfusion positron emission tomography (PET) at the authors’ hospital from 2006 through 2016. Other evaluations included two-dimensional echocardiography and serum creatinine measurement. Patients with overt obstructive coronary artery disease were excluded from the analysis.

The patients’ median age was 55 years; 63% were women and 22% were black. Their median left ventricular ejection fraction was 62% on echocardiography and 59% on PET, and more than 70% had abnormal left ventricular remodeling. CKD was present in 35% of patients, who had a mean eGFR of 41.0 mL/min/1.73 m2.

Those patients with stage 3 or higher CKD were more likely to have hypertension and diabetes, and they also had a lower body mass index. On PET, patients with CKD had lower stress myocardial blood flow (1.7 versus 2.1 mL/min/g) and lower coronary flow reserve (1.5 versus 1.9). The authors considered these findings to represent coronary microvascular dysfunction. Both eGFR and coronary flow reserve were associated with diastolic and systolic echocardiographic indexes, as was the risk of adverse cardiovascular events.

On multivariable analysis, however, coronary flow reserve was independently associated with cardiac mechanics and cardiovascular event risk whereas GFR was not. And on stratified analysis, a severely abnormal coronary flow reserve of less than 1.5 was associated with a 1.61 adjusted hazard ratio for major adverse cardiovascular events.

In this study, coronary microvascular dysfunction was a significant mediator of the associations among eGFR, cardiac mechanics, and cardiovascular events. In fact, in fully adjusted models, coronary microvascular dysfunction accounted for 32% of the relationship between impaired renal function and major adverse cardiovascular events, the authors noted.

Even in the absence of overt coronary artery disease, patients with CKD are at elevated risk of cardiac dysfunction and cardiovascular events. Coronary microvascular dysfunction might help to explain the impaired cardiac function and increased cardiovascular risk associated with abnormal renal function, according to the authors.

The new study suggests that coronary microvascular dysfunction is associated with cardiovascular risk in CKD patients without overt coronary artery disease and might mediate the effects of eGFR on cardiac function and cardiovascular events.

“The presence of coronary microvascular dysfunction signals the transition from physiological to pathological left ventricular remodeling that increases the risk of heart failure and death in patients with chronic kidney disease,” Bajaj and colleagues write.

“[O]ur study raises the possibility that efforts to attenuate microvascular disease could produce benefits on myocardial dysfunction and cardiovascular events,” they state.

February 2020 (Vol. 12, Number 2)

References

1. Bajaj NS, et al. Coronary microvascular dysfunction, left ventricular remodeling, and clinical outcomes in patients with chronic kidney impairment. Circulation 2020; 141:21–33.