Loss of capillary density, and thus flow of blood through tissues, is a known feature of aging, though the causes of this change in tissue maintenance are far from completely explored. It is proposed to be quite important in loss of tissue function, particularly in organs with high metabolic demands, such as muscle and the brain. Researchers here provide evidence to suggest that this loss of capillary density is a noteworthy mediating mechanism linking the age-related impairment of heart function with the presence of chronic kidney disease. The latter is already known to correlate with impaired capillary structure in the heart, and here data from patients shows that this is a factor in the progression to heart disease.
People with chronic kidney disease have a higher risk for heart disease and heart-disease death. Coronary microvascular dysfunction, or CMD, is decreased blood flow in the small blood vessels inside the heart muscle that provide oxygen and fuel to feed the pumping heart. A new study links kidney disease to progressive heart disease via this mechanism. In healthy hearts, visualized postmortem, these blood vessels look like a tight filigree network that fills the heart muscle tissue. A diseased postmortem heart has lost much of this network. In living patients, however, those small blood vessels inside the heart muscle cannot be visualized; blood flow scans of living patients visualize only the larger, exterior coronary arteries.
Thus researchers needed an indirect way to gauge CMD. That measure is coronary flow reserve, or CFR, assessed via positron emission tomography. CFR is the maximum increase in blood flow through the coronary arteries above the normal resting volume. In a longitudinal study of 352 patients with chronic kidney disease, all with healthy heart function as measured by ejection fraction and none with signs of overt coronary artery disease, the researchers measured CFR and also measured signs of subclinical heart dysfunction. The patients were then followed a median of 4.4 years for major adverse cardiac events. A total of 108 patients had such major events, including death and hospitalization for non-fatal heart attack or heart failure.
The researchers found that CMD was a significant predictor of abnormal mechanics of the left ventricle – the heart’s major pumping chamber – and a significant predictor of clinical risk of adverse cardiovascular outcomes. A statistical model called mediation analysis examined the relationship between impaired kidney function and heart disease. It showed that CMD accounted for 19 to 24 percent of left ventricle diastolic dysfunction, 19 to 42 percent of left ventricle systolic dysfunction and 32 percent of major adverse cardiovascular events. This evidence suggests that the development of severe microvascular dysfunction likely signals the transition from physiological to pathological left ventricle remodeling that increases the risk of heart failure and death in patients with chronic kidney disease.