Low circulating progenitor cells may also help predict adverse outcomes

Renal insufficiency was tied to lower circulating progenitor cell (CPC) counts in coronary artery disease patients over 70, an observational study showed.

In addition, low CPC count independently predicted adverse cardiovascular outcomes in people with coronary artery disease and renal insufficiency, reported Arshed Quyyumi, MD, of Emory University in Atlanta, Georgia, and coauthors, in JACC: Basic to Translational Science.

Coronary artery disease patients with renal insufficiency and low (below the median) hematopoietic CPCs (CD34+, CD34+/CD133+, and CD34+/CXCR4+) had an increased risk of cardiovascular death or myocardial infarction events during a follow-up of 3.5 years (HRs 1.75-1.80). Patients with renal insufficiency and high CPCs (above the median) had similar risk as those without renal insufficiency.

Patients with coronary artery disease and renal insufficiency are at an increased risk of cardiovascular events, Quyyumi and colleagues noted, and how regenerative capacity—measured as circulating progenitor cell counts—may contribute to this increased risk is unclear.

“We found that the presence of renal insufficiency was associated with lower CPC counts among older participants (>70 years of age) after adjusting for differences in demographic characteristics, risk factors, and medication use,” they wrote.

“We also demonstrated that low CPC count, indicative of impaired endogenous regenerative capacity, was an independent predictor of adverse CV outcomes among participants with renal insufficiency. In contrast, patients with renal insufficiency and higher CPC counts, indicative of preserved regenerative capacity, had similar outcomes as those without renal insufficiency,” they continued.

“These observations suggest that the relatively poor outcomes in patients with coronary artery disease and renal insufficiency are related, at least in part, to impairment of endogenous regenerative capacity.”

In their study, all participants had coronary artery disease and about 35% had renal insufficiency, defined as estimated glomerular filtration rate <60 ml/min/1.73 m2. Those 70 or older had a significant association of renal insufficiency and CPC count, with beta of −14.5 (95% CI −24.4 to –3.4; P=0.012). This relationship was nonsignificant for those younger than 70.

“This novel observation is concordant with previous studies that have shown that presence of cardiovascular risk factors at a relatively young age is associated with either normal or higher CPC counts, reflecting an endogenous reparative response to subclinical vascular injury related to risk factor exposure,” Quyyumi and co-authors observed.

“This mobilization of CPCs into the peripheral circulation is exhausted at an older age after continued exposure to injurious stimuli,” they continued. “Overall, our results indicate that relatively young patients with coronary artery disease and renal insufficiency have similar CPC counts as those with coronary artery disease alone, whereas differences in CPC counts between the two groups become apparent at an older age.”

The findings “confirm the importance of the interplay between chronic kidney disease and CPC-mediated tissue repair in cardiovascular outcomes,” noted Nikolaos Vlachogiannis, MD, and Konstantinos Stellos, MD, both of Newcastle University in England, in an accompanying editorial.

“Further research is warranted to delineate how chronic kidney disease affects the number and function of CPCs and how CPCs support the maintenance of vascular health in patients with chronic kidney disease,” they added.

Bone marrow-derived CD34 + cells have been used to reconstitute the hematopoietic system after radiation or chemotherapy and have attracted attention for potential other therapeutic use. “The consensus is that their number in blood is associated with tissue healing processes,” the editorialists noted.

Despite a conceptually appealing role in diverse settings—CD34+ cells have been employed in limb and organ ischemia and pulmonary hypertension—practical limitations affect clinical use.

“Several liters of blood would be required to isolate sufficient endothelial progenitor cells to treat critical limb ischemia in an average adult patient, which—in combination with the lower number of CPCs in patients with coronary artery disease and especially in those with renal insufficiency as shown in the current study—precludes the use of CD34+ cells in everyday clinical practice,” the editorialists observed.

“Moreover, the differentiation potential and function of endothelial progenitor cells may be severely compromised in patients with coronary artery disease, and especially in those with renal insufficiency, because of increased senescence,” they added. “There is an imperative need for further basic and translational science studies addressing the ’rejuvenation’ of CD34+ cells in ischemic and chronic kidney disease.”

Previous work has shown that even mild renal dysfunction with coronary artery disease worsens prognosis and that, in patients with coronary artery disease, renal dysfunction decreases CD34+ CPCs.

Additional data showing that low CPC counts are associated with adverse cardiovascular outcomes in the setting of coronary artery disease, as well as end-stage renal disease, motivated Quyyumi and coauthors to father explore the intersection of CPCs, renal insufficiency, and coronary artery disease in their institutional registry.

The researchers analyzed data from 1,253 patients with median 3.5-year follow-up in the prospective Emory Cardiovascular Biobank, which includes patients having cardiac catheterization for evaluation of coronary artery disease. Mean age was 66; 39% were women and 21% were black. Participants with higher counts for all CPC types were relatively younger and more frequently men.

Consistent with prior work, coronary artery disease patients with renal insufficiency in this study had higher risk for cardiovascular death or MI (48%) as well as higher risk for all-cause mortality (39%), compared with those without renal insufficiency.

Limitations of the study included its observational design, so causation cannot be determined. The researchers also did not assess the duration of coronary artery disease or renal impairment, which may affect CPC counts.

  1. Renal insufficiency was tied to lower circulating progenitor cell (CPC) counts in coronary artery disease patients over 70 in an observational study.

  2. In addition, low CPC count independently predicted adverse cardiovascular outcomes in people with coronary artery disease and renal insufficiency.

Paul Smyth, MD, Contributing Writer, BreakingMED™

Quyyumi is supported by grants from the National Institutes of Health and American Heart Association.

Editorialists reported they have no relationships relevant to the contents of this paper to disclose.

Cat ID: 308

Topic ID: 74,308,282,494,730,308,914,192