Calciprotein Particles Link Disturbed Mineral Homeostasis with Cardiovascular Disease by Causing Endothelial Dysfunction and Vascular Inflammation.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

Serum and Echocardiographic Markers May Synergistically Predict Adverse Cardiac Remodeling after ST-Segment Elevation Myocardial Infarction in Patients with Preserved Ejection Fraction.

Improvement of risk scoring is particularly important for patients with preserved left ventricular ejection fraction (LVEF) who generally lack efficient monitoring of progressing heart failure. Here, we evaluated whether the combination of serum biomarkers and echocardiographic parameters may be useful to predict the remodeling-related outcomes in patients with ST-segment elevation myocardial infarction (STEMI) and preserved LVEF (HFpEF) as compared to those with reduced LVEF (HFrEF). Echocardiographic assessment and measurement of the serum levels of NT-proBNP, sST2, galectin-3, matrix metalloproteinases, and their inhibitors (MMP-1, MMP-2, MMP-3, TIMP-1) was performed at the time of admission (1st day) and on the 10th-12th day upon STEMI onset. We found a reduction in NT-proBNP, sST2, galectin-3, and TIMP-1 in both patient categories from hospital admission to the discharge, as well as numerous correlations between the indicated biomarkers and echocardiographic parameters, testifying to the ongoing ventricular remodeling. In patients with HFpEF, NT-proBNP, sST2, galectin-3, and MMP-3 correlated with the parameters reflecting the diastolic dysfunction, while in patients with HFrEF, these markers were mainly associated with LVEF and left ventricular end-systolic volume/diameter. Therefore, the combination of the mentioned serum biomarkers and echocardiographic parameters might be useful for the prediction of adverse cardiac remodeling in patients with HFpEF.

Increased Serum Parathyroid Hormone, Osteocalcin and Alkaline Phosphatase Are Associated with a Long-Term Adverse Cardiovascular Outcome after Coronary Artery Bypass Graft Surgery.

Despite the fact that an association of osteopoenia/osteoporosis with elevated risk of coronary artery calcification (CAC) and coronary atherosclerosis (CA) is well-established, it remains unclear whether bone turnover markers can be employed in long-term prognostication of such patients. Here we measured serum calcium, phosphate, calcitonin, parathyroid hormone (PTH), osteoprotegerin, osteocalcin, osteopontin, alkaline phosphatase and its bone isoenzyme, subsequently correlating them with an adverse cardiovascular outcome after 3 years of follow-up. The extent of brachiocephalic artery stenosis, CA, or CAC, as well as prevalence of osteopoenia/osteoporosis before the coronary artery bypass graft (CABG) surgery, did not differ between outcome groups, suggesting that subtle molecular mechanisms might be involved in determining the outcome rather than clinical or subclinical disease. After stepwise logistic regression, serum osteocalcin > 26.8 ng/mL and PTH > 49.1 pg/mL were independent predictors of an adverse outcome. Serum ionised calcium correlated with multivessel coronary artery disease; moreover, patients with severe CA (SYNTAX score > 21) had higher serum ionised calcium than those with mild CA. Likewise, serum alkaline phosphatase was associated with severe CA and CAC (Agatston score > 400). In conclusion, serum PTH, osteocalcin, and alkaline phosphatase are associated with an adverse cardiovascular outcome 3 years after CABG surgery regardless of osteopoenia/osteoporosis, coronary/peripheral atherosclerosis, and CAC.

Serum neutrophil gelatinase-associated lipocalin has an advantage over serum cystatin C and glomerular filtration rate in prediction of adverse cardiovascular outcome in patients with ST-segment elevation myocardial infarction.

BACKGROUND: The aim of this study was to assess significance of serum neutrophil gelatinase-associated lipocalin (sNGAL) and cystatin C (sCC) in prediction of adverse cardiovascular outcome after ST-segment elevation myocardial infarction (STEMI). METHODS: We recruited 357 consecutive patients who were admitted to the hospital within 24 h after onset of STEMI. On the 1st and 12th-14th day after hospital admission, we measured levels of sNGAL and sCC. We also determined presence of renal dysfunction (RD), defined as glomerular filtration rate < 60 mL/min/1.73 m2. After 3 years of follow-up, we performed a logistic regression and assessed the value of RD, sNGAL, and sCC in prediction of combined endpoint, defined as cardiovascular death or any cardiovascular complication. RESULTS: RD, sCC level ≥ 1.9 mg/L, and sNGAL level ≥ 1.25 ng/mL on the 12th-14th day of hospitalization were associated with a 1.6-fold, 1.9-fold, and 2.9-fold higher risk of adverse cardiovascular outcome, respectively. Area under the ROC curve was the highest for the model based on sNGAL level compared to the models based on sCC level or RD presence. CONCLUSIONS: Measurement of sNGAL level in patients with STEMI on the 12th-14th day after hospital admission may improve prediction of adverse cardiovascular outcome.

Decreased Cathepsin K Plasma Level may Reflect an Association of Osteopoenia/Osteoporosis with Coronary Atherosclerosis and Coronary Artery Calcification in Male Patients with Stable Angina.

BACKGROUND: The aim of this study was to evaluate the plasma levels of bone turnover markers (BTMs) in male patients with stable angina depending on the bone mineral density (BMD), coronary atherosclerosis (CA) and coronary artery calcification (CAC). METHODS: We recruited 112 males with verified stable angina. All the patients underwent coronary angiography, multislice spiral computed tomography, and dual-energy X-ray absorptiometry. Plasma levels of BTMs were measured by enzyme-linked immunosorbent assay. RESULTS: Osteopoenia and osteoporosis were reported in 90 (80.4%) and 34 (30.4%) patients, respectively. Multivessel coronary artery disease, severe CA and CAC, decreased cathepsin K plasma level, and increased osteocalcin plasma level were significantly more prevalent in patients with osteopoenia/osteoporosis compared to the subjects with normal BMD. Patients with severe CA and CAC had significantly reduced cathepsin K plasma levels. CONCLUSIONS: We revealed a significant association of osteopoenia/osteoporosis with severe CA and CAC in males with stable angina. Cathepsin K and osteocalcin plasma levels may be suggested as the significant markers of osteopoenia/osteoporosis. In addition, cathepsin K plasma level can be also a valuable marker of severe CA and CAC.

Serum Galectin and Renal Dysfunction in ST-Segment Elevation Myocardial Infarction.

This study aimed to evaluate the association between serum galectin levels and renal dysfunction in relation to in-hospital prognosis and unfavorable prognosis 1 year after ST-elevated myocardial infarction (STEMI). Patients were assigned to two groups according to the cystatin C-based estimate of GFR on day 12 after STEMI: (1) STEMI patients with normal renal function (GFR based on cystatin C levels = 60 mL/min/1.73 m(2)) and (2) those with renal dysfunction (RD) (GFR based on cystatin C levels <60 mL/min/1.73 m(2)). A decrease in GFR estimated from the CKD-EPI equation on day 12 was more frequently found in patients with a reduced GFR based on cystatin C levels (41.9%) compared with those without RD (21.3%). Galectin levels exceeded the cut-off value (17.8 ng/mL) in 50.6% of cases in the group with GFR <60 mL/min/1.73 m(2) and in 32% of cases in the group with a normal GFR. The presence of RD and elevated galectin levels >17.8 ng/mL on day 12 after MI are independent predictors of an adverse prognosis at 1 year in STEMI patients. Elevated galectin levels are directly correlated with the presence of early postinfarction angina.

Impact of recipient-related factors on structural dysfunction of xenoaortic bioprosthetic heart valves.

OBJECTIVE: To analyze the influence of recipient-related metabolic factors on the rate of structural dysfunction caused by the calcification of xenoaortic bioprostheses. MATERIALS AND METHODS: We retrospectively analyzed clinical status, calcium-phosphorus metabolism, and nonspecific markers of inflammatory response in bioprosthetic mitral valve recipients with calcific degeneration confirmed by histological and electron microscopic studies (group 1, n=22), and in those without degeneration (group 2, n=48). RESULTS: Patients with confirmed calcification of bioprostheses were more likely to have a severe clinical state (functional class IV in 36% in group 1 versus 15% in group 2, P=0.03) and a longer cardiopulmonary bypass period (112.8±18.8 minutes in group 1 versus 97.2±23.6 minutes in group 2, P=0.02) during primary surgery. Patients in group 1 demonstrated moderate hypovitaminosis D (median 34.0, interquartile range [21.0; 49.4] vs 40 [27.2; 54.0] pmol/L, P>0.05), osteoprotegerin deficiency (82.5 [44.2; 115.4] vs 113.5 [65.7; 191.3] pg/mL, P>0.05) and osteopontin deficiency (4.5 [3.3; 7.7] vs 5.2 [4.1; 7.2] ng/mL, P>0.05), and significantly reduced bone-specific alkaline phosphatase isoenzyme (17.1 [12.2; 21.4] vs 22.3 [15.5; 30.5] U/L, P=0.01) and interleukin-8 levels (9.74 [9.19; 10.09] pg/mL vs 13.17 [9.72; 23.1] pg/mL, P=0.045) compared with group 2, with an overall increase in serum levels of proinflammatory markers. CONCLUSION: Possible predictors of the rate of calcific degeneration of bioprostheses include the degree of decompensated heart failure, the duration and invasiveness of surgery, and the characteristics of calcium-phosphorus homeostasis in the recipient, defined by bone resorption and local and systemic inflammation. The results confirm the hypothesis that cell-mediated regulation of pathological calcification is caused by dysregulation of metabolic processes, which are in turn controlled by proinflammatory signals.