A study led by Dr. Navakaranbir Bajaj published in Circulation showed that coronary microvascular dysfunction, but not estimated glomerular filtration rate was associated with abnormal cardiac mechanics and an increased risk of cardiovascular events. The findings of this study suggest that coronary microvascular dysfunction may play a role in determining how chronic kidney disease can lead to abnormal cardiac function in patients without ischemic heart disease.
With the prevalence of chronic kidney disease in that United States being around 14%, there is a better need to understand how this can play a role in leading to abnormal cardiac function. Even when the serum creatinine is normal, the abnormal kidney function begins to lead to an increased risk of cardiovascular events. Although patients with chronic kidney disease to have other atherosclerotic risk factors including age, sudden cardiac death and heart failure-related deaths are more common than myocardial infarction related deaths. This may suggest that there are other mechanisms that may contribute to the increased cardiovascular risk in CKD patients. The investigators hypothesized that coronary microvascular dysfunction (CMD) is associated with abnormalities in myocardial structure and function.
In this study, patients who performed a stress myocardial perfusion positron emission tomography (PET) scan who also underwent an echocardiography and creatinine level measurement within 90 days of the PET scan were identified. Patients with known coronary artery disease or a history of cardiovascular and severe valvular disease were excluded. The estimated glomerular filtration rate (GFR) was calculated in these patients. Coronary flow reserve (CFR) was calculated as the ratio of myocardial blood flow during maximal hyperemia over at rest. GFR was used to represent kidney function and CFR was used to represent coronary microvascular function. A higher CFR indicated better microvascular function. The primary clinical outcome in this study was all-cause death, non-fatal myocardial infarction, and hospitalization for heart failure. The investigators aimed to determine whether CFR and GFR had an effect on clinical outcomes as well as cardiac mechanics (as determined by echocardiography).
A total of 352 patients were included in the study. Over a median follow up of 4.4 years, 108 patients met the primary composite outcome. The median age was 65, 63% were women, 22% were black. One-third of patients had chronic kidney disease stage 3 or higher (estimated glomerular filtration rate less than 60 ml/min/1.73m2). More than 75% had hypertension, approximately 66% had diabetes mellitus and one third had diabetes mellitus. Without adjusting for other factors, a lower eGFR and a lower CFR were associated with worse diastolic function and worse systolic strain. However, after adjustment for other variables, only the association between CFR and myocardial function (both systolic and diastolic) remained significant. With regards to the primary clinical outcome, in a multivariable model, the association between CFR and the clinical outcome remained significant.
The study showed that in patients with CKD without overt coronary artery disease, the severity of coronary microvascular dysfunction is a significant predictor of abnormal ventricular function and is associated with an increased risk of adverse events. While discussing the findings of this study, Dr. Bajaj noted, “chronic kidney dysfunction has been independently associated with a graded reduction in coronary microvascular function and abnormal left ventricular structure and function even in the absence of obstructive coronary artery disease. Consequently, the current study was designed to investigate the inter-relationship between coronary microvascular dysfunction, abnormalities in cardiac structure and mechanics, and clinical outcomes. The findings in the current study suggest that coronary microvascular dysfunction is an important link between CKD, adverse left ventricular remodeling, and clinical risk.” However, what this study is unable to address is the underlying mechanism linking microvascular dysfunction to impaired left ventricular mechanics. However, this study does have its limitations. The study identified patients from a clinical database that consisted of patients with symptoms and therefore, these results may not apply to asymptomatic patients. Regardless, the study does shed some light on a potential mechanism linking chronic kidney disease to the increased risk of cardiovascular events that is as a result of non-obstructive cardiovascular disease.