Chronic Kidney Disease a Precursor to Heart Disease

Navkaranbir S. Bajal, MD

A chronic kidney disease diagnosis could spell trouble for patients by increasing the risk of heart disease and heart failure.

A team, led by Navkaranbir S. Bajaj, MD, a University of Alabama at Birmingham assistant professor in the Division of Cardiovascular Disease, Department of Medicine and Department of Radiology, investigated the relations between chronic kidney disease, coronary microvascular dysfunction (CMD), cardiac dysfunction, and adverse cardiovascular outcomes.

Of the 352 patients in the study, 35% had an estimated glomerular filtration rate (eGFR) of greater than 60 ml/min^-1/1.73m^-2, a median left ventricular ejection fraction of 62%, and a median coronary flow reserve (CFR) of 1.8. The investigators found eGFR and CFR was associated with diastolic and systolic indices, as well as future cardiovascular events (all P <.05).

In multivariable models, CFR was independently linked with cardiac mechanics and cardiovascular events, while eGFR was not. The associations between eGFR, cardiac mechanics, and cardiovascular events were partly mediated through CFR.

Cardiac dysfunction and cardiovascular events are common in patients with chronic kidney disease without overt obstructive coronary artery disease. However, the mechanisms of this connection are poorly understood.

Coronary microvascular dysfunction is thought to be a link between abnormal renal function and impairment of cardiac function and cardiovascular events.

Following death, blood vessels in a healthy heart looks like a tight filigree network that fills the heart muscle tissue. However, diseased postmortem hearts lose much of the network.

The blood vessels are too small inside the heart muscle to be visualized in living patients.

The investigators examined patients undergoing cardiac stress positron emission tomography, echocardiogram, and renal function ascertainment at Brigham and Women’s Hospital longitudinally.

Patients free of overt coronary—which was defined as a summed stress score greater than 3 and without a history of ischemic heart disease&mdash;valvular, and end-organ disease were followed up for the adverse composite outcome of death or hospitalization for myocardial infarction or heart failure.

The patients were followed for a median of 4.4 years for major adverse cardiac events, with a total of 108 patients suffering from a major event, including death and hospitalization for non-fatal heart attack or heart failure.

Coronary flow reserve (CFR) was determined from positron emission tomography, while echocardiograms was used to measure cardiac mechanics—diastolic (lateral and septal E/e’) and systolic (global longitudinal, radial, and circumferential strain).

The investigators blinded image analyses and event adjudication and the associations between estimated glomerular filtration rate (eGFR), CFR, diastolic and systolic indices, and adverse cardiovascular outcomes were assessed in adjusted models and mediation analyses.

“Coronary microvascular dysfunction, but not eGFR, was independently associated with abnormal cardiac mechanics and an increased risk of cardiovascular events,” the authors wrote. “Coronary microvascular dysfunction may mediate the effect of chronic kidney disease on abnormal cardiac function and cardiovascular events in those without overt coronary artery disease.”

The investigators developed a statistical model called mediation analysis and found CMD accounted for 19-24% of left ventricle diastolic dysfunction, 19-42% of left ventricle systolic dysfunction, and 32% of all major adverse cardiovascular events.

Earlier this year, investigators presented data from a community-based study, which included more than 9000 US adults and a median follow-up of 17.5 years, that showed patients with cardiovascular disease had a higher risk of kidney failure, with heart failure patients at an 11.4-fold increased risk of developing kidney failure.

Results of the investigators’ analyses revealed all cardiovascular disease events included were associated with an increased risk of developing end-stage kidney disease. Specifically, heart failure was associated with an 11.4-fold increased risk (HR, 11.4; 95% CI, 8.4-15.5), coronary heart disease increased risk 3.7-fold (HR, 3.7; 95% CI, 2.5-5.3), atrial fibrillation resulted in a 2.7-fold increase (HR, 2.7; 95% CI, 1.9-3.8), and stroke correlated with a 1.4-fold increase in end-stage kidney disease (HR, 1.4; 95% CI, .9-2.4).

The study, “Coronary Microvascular Dysfunction, Left Ventricular Remodeling, and Clinical Outcomes in Patients With Chronic Kidney Impairment,” was published online in Circulation.