Association of calciprotein particles measured by a new method with coronary artery plaque in patients with coronary artery disease: A cross-sectional study

Abstract

Background: Calciprotein particles (CPPs) have been suggested to be associated with the degree of coronary atherosclerosis, and have also been established as a molecular marker for clinical outcome in patients with chronic kidney disease (CKD). However, there are several concerns with regard to conventional measurement of CPPs. We therefore developed a new CPP measurement system that can detect both smaller and lower-density CPPs. Methods: We analyzed 71 consecutive patients who underwent percutaneous coronary intervention for acute coronary syndrome (ACS, n = 29) and/or stable angina pectoris (AP, n = 42) who did not have CKD of stage 4 or greater. CPP measurement was made using an infrared fluorescent bisphosphonate (OsteoSense, PerkinElmer, Waltham, MA, USA) and a gel filtration method. The coronary artery plaque was analyzed by gray-scale intravascular ultrasound (IVUS) and integrated backscatter (IB)-IVUS. Results: The median CPP level (interquartile range) was 40,953 (19,171-74,131) arbitrary units (AU). When we divided the CPP level into quintiles, the total and lipid plaque volume were incrementally higher with increasing quintile from lowest to highest (both p < 0.02). After adjustment by age, body mass index, and estimated glomerular filtration rate, which factors were correlated with the abovedescribed plaque components, the top quintile of CPP (>86,751 AU) had significantly higher total plaque (263 mm 3 vs. 161 mm 3 ; p = 0.001) and lipid plaque volume (156 mm 3 vs. 89 mm 3 ; p < 0.001) than the other quintiles. However, these associations were not found for the fibrous or calcified plaque volume. The CPP level was higher in the ACS group than the stable AP group (p = 0.02), and the total and lipid plaque volume were also higher in the ACS group than the stable AP group (both p < 0.05). Conclusions:The results suggested that a high CPP level, as measured by the novel assay, is a surrogate marker for coronary atherosclerosis, especially in lipid-rich plaques, contributing to an increased risk of plaque vulnerability.

Calciprotein particles: A mineral biomarker in need of better measurement

“…Regardless of these limitations -and given the dismal outcomes of patients on dialysis -there does appear to be a signal that is worth pursuing in future studies. Taken together with other recent studies which showed that plasma CPP levels correlated with coronary artery plaque volume and lipid content [12], these data support the idea that measurement of CPP may hold predictive value for atherosclerotic events in CKD, but this will need to be demonstrated empirically.…”

Calcium Phosphate Bions Cause Intimal Hyperplasia in Intact Aortas of Normolipidemic Rats through Endothelial Injury

“…Patients with ESRD had elevated risk of all-cause and cardiovascular death, myocardial infarction, and peripheral artery disease in the case of enhanced formation of CPBs [9,10,11,12]. Augmented serum propensity to produce CPBs correlated with severe coronary artery calcification and its progression in patients with CKD stages 2 to 4 [50]; this was partially verified by a recent study showing that higher CPB serum levels are more frequently observed in patients with acute coronary syndrome as compared to those with stable angina (without pre-dialysis CKD or ESRD) and is associated with the total and lipid plaque volume [15]. Hence, serum CPB concentration might be considered as a surrogate marker of coronary atherosclerosis and coronary artery calcification.…”

“…Despite clinical investigations in this field having been primarily focused on kidney transplant recipients [9,10,11] and patients with end-stage renal disease [12] or pre-dialysis chronic kidney disease (CKD) [13], an elevated serum propensity to form CPBs was also observed in non-CKD patients with arterial hypertension, a major risk factor of coronary artery disease, in comparison with healthy blood donors [14]. Further, an increased CPB count in the serum is associated with the progression of stable angina to acute coronary syndrome and also with the lipid and total plaque volume in patients without detectable CKD [15]. Our unpublished data also indicated that serum levels of CPBs are higher in patients with coronary artery disease requiring bypass surgery than in healthy individuals.…”

Formation of calcium phosphate bions in patients with carotid and coronary atherosclerosis

“…Последние ис-следования также демонстрируют, что повышенная склонность сыворотки к формированию КФБ ассоциирована с более выраженным коронарным кальцинозом и более высоким риском прогрессирования этого патологического процесса у пациентов с ХПН на различных стадиях, исключая начальную и терминальную [10]. Это косвенно подтверждается данными о том, что высокое содержание КФБ в системном кровотоке может служить суррогатным маркером КоА, коррелируя как с объемом бляшки в целом, так и с объемом ее липидного компонента, а также превалируя у пациентов с острым коронарным синдромом в сравнении с субъектами со стабильной стенокардией [14]. Полученные результаты позволяют выдвинуть гипотезу о том, что причиной увеличенной склонности крови пациентов с КаА и ИМ к формированию КФБ является снижение (до "низкого нормального" уровня) сывороточной концентрации общего белка и альбумина, роль которых в поддержании минерального гомеостаза заключается в связывании свободных ионов кальция.…”