Lower ICTP Research Articles

Abstract 12381: Elevated Serum Carboxy-Terminal Telopeptide of Type I Collagen is Associated With Clinical Outcomes in Patients With Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention

Background: Despite high risk of developing cardiovascular events, it was reported to be difficult to predict clinical outcomes in patients with stable angina pectoris (AP). Serum carboxy-terminal telopeptide of type I collagen (I-CTP), a marker of collagen degradation, was reportedly associated with clinical outcomes in patients with acute coronary syndrome. However, clinical usefulness of I-CTP has not yet been elucidated in patients with stable AP. The aim of this study was to examine whether I-CTP can predict clinical outcomes in patients with stable AP. Methods and Results: Serum I-CTP levels were measured in consecutive 360 patients with stable AP undergoing percutaneous coronary intervention. All patients were divided into three groups according to serum I-CTP tertiles: low I-CTP group (≤4.4 ng/ml, n=120), middle I-CTP group (4.5-6.2 ng/ml, n=118), and high I-CTP group (≥6.3 ng/ml, n=122). The high I-CTP group was older and showed higher levels of brain natriuretic peptide (BNP) and lower levels of estimated glomerular filtration rate (eGFR) and left ventricular ejection fraction (LVEF) compared with other groups. During the median follow up period of 1,347 days, there were 68 cardiovascular events including all-cause deaths. Kaplan-Meier analysis showed that the high I-CTP group had the greatest risk for cardiovascular events among 3 groups. Univariate Cox proportional hazard regression analysis showed that age, multivessel disease, BNP, eGFR, LVEF, and I-CTP were significantly associated with cardiovascular events. Multivariate Cox proportional hazard analysis demonstrated that I-CTP was an independent predictor for cardiac events after adjusting for confounding risk factors. Conclusion: I-CTP could be the feasible marker for predicting cardiovascular events in patients with stable AP.

Elevated serum carboxy-terminal telopeptide of type I collagen predicts clinical outcome in patients with acute coronary syndrome who underwent percutaneous coronary intervention

Abstract Introduction Serum carboxy-terminal telopeptide of type I collagen (I-CTP) is a collagen degradation product of type I collagen in the extracellular matrix of the heart, blood vessels, and bone. The serum levels of I-CTP were reportedly a predictive marker for cardiac remodeling after acute myocardial infarction. However, it remains unclear whether I-CTP can predict poor clinical outcome in patient with acute coronary syndrome (ACS). Purpose The aim of this study was to investigate the association between serum levels of I-CTP and clinical outcome in patients with ACS. Methods Serum levels of I-CTP were measured in 200 patients with ACS who underwent percutaneous coronary intervention (PCI). All patients were prospectively followed during the median follow-up period of 1312 days with the end point of major adverse cardiovascular events (MACE). We divided the patients into tertiles according to serum I-CTP level: low I-CTP group (≤4.4 ng/ml, n=72), middle I-CTP group (4.4–6.4 ng/ml, n=65), and high I-CTP group (≥6.5 ng/ml, n=63). Results There were 44 MACE, including 24 all-cause death and 9 rehospitalization due to heart failure. I-CTP was significantly higher in patients with MACE than those without (4.90 [interquartile range (IQR): 3.80–6.38] ng/ml vs. 6.65 [IQR: 5.00–10.08] ng/ml, p<0.001). Kaplan-Meier analysis demonstrated that patients in the highest tertile of I-CTP had the greatest risk of MACE. In a univariate analysis, age, Albumin, estimated glomerular filtration rate (eGFR), low-density lipoprotein cholesterol (LDL-C), brain natriuretic peptide (BNP), high-sensitivity C-reactive protein (hsCRP) and I-CTP were significant predictors of MACE. A multivariate Cox proportional hazard analysis showed that the high I-CTP group had a higher risk for MACE (Hazard ratio [HR] 2.6, p=0.049) compared with the low I-CTP group after adjusting for confounding factors. Conclusions I-CTP was significantly associated with MACE, suggesting that I-CTP could be a reliable marker for clinical outcome in patients with ACS who underwent PCI. Figure 1 Funding Acknowledgement Type of funding source: None

Identifying conflicts tendency between nature-based tourism development and ecological protection in China

Abstract Developing spatial regulation strategies is important for nature-based tourism, and this procedure could be more rational and scientific with the understanding of the spatial distribution of conflicts tendency between tourism development and ecological protection. In this study, we developed an Indicator of Conflict tendency between nature-based Tourism development and ecological Protection (ICTP), based on the combination of landscape attractiveness and ecological sensitivity. By integrating land cover, topography, climate and other datasets, this paper presents the spatial distribution of the ICTP in the study area in China. The results show that most areas of China have a low or medium ICTP. Areas with very high ICTP account for 13.79% of the studied areas, including the central part of the Inner Mongolia Plateau, northern part of the Loess Plateau, southwestern part of the Northeast Plain, north and south sides of Tianshan Mountains, coast of Bohai Bay and coastal areas of Jiangsu and Zhejiang Province. These areas are mainly confronted with problems of desertification, salinization and soil erosion. 11.09% of studied areas have very low ICTP, mainly located in the Tarim Basin and western part of Inner Mongolia Plateau, characterized by low landscape attractiveness and low ecological sensitivity. Our results can inform decision makers with regard to where are most likely to suffer from ecological problems caused by nature-based tourism activities, and to which types of problems that are likely to arise. Such information can help decision makers forecast the developmental trend of the relationship between nature-based tourism development and ecological protection, further determine the degree of control on nature-based tourism. The study developed the basic framework for measuring the conflict tendency of nature-based tourism development and ecological protection, which can inspire researchers to think about factors that should be considered when measuring such tendency.

Serum Carboxy-Terminal Telopeptide of Type I Collagen (ICTP) Predicts Cardiac Events in Chronic Heart Failure Patients With Preserved Left Ventricular Systolic Function

Clinical markers to predict adverse outcome have not yet been established for patients with preserved left ventricular (LV) systolic function. The present study was designed to examine whether carboxy-terminal telopeptide of type I collagen (ICTP), a marker of collagen degradation, is useful for determining the prognosis of such patients. Serum levels of ICTP were measured at admission in 156 consecutive patients hospitalized for chronic heart failure (CHF). Patients were divided into 2 groups based on the LV ejection fraction (LVEF): reduced LV systolic function group (LVEF <50%, n=92) and preserved LV systolic function group (LVEF > or =50%, n=64). In preserved LV systolic function group, cardiac event-free rates were significantly lower in high ICTP group than in low ICTP group (p<0.001). The area under the receiver operating characteristic curve of ICTP in the preserved LV systolic function group was markedly larger than that in the reduced LV systolic function group. Cox multivariate analysis also revealed that ICTP was an independent predictor of cardiac events in the preserved LV systolic function group. Serum ICTP level is highly reliable for risk stratifying CHF patients with preserved LV systolic function.

The duration of exercise as a regulator of bone turnover.

The relationship between duration of exercise and serum remodeling markers of bone turnover was evaluated by osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), total and bone-specific alkaline phosphatase (ALP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in 24 male premier league soccer players exercising 12 hours/week (range 8-18), 19 third league players exercising 8 hours/week (range 3-18) and 20 sixth league players exercising 6 hours/week (range 2-10). Twenty-seven volunteers served as controls. Forty-six former male soccer players (mean age 38 years, range 19-47), mean 15 years older than the current players, were compared with 41 matched controls. Data is presented as mean +/- SEM. Active male players had 18 +/- 4% higher OC, 37 +/- 9% higher bone ALP and 36 +/- 7% higher ICTP than controls (all P < 0.01). There were no differences in remodeling markers within the three groups of active players but each group had higher OC and ICTP than controls (both P < 0.05). Former players had no difference in bone remodeling markers compared to matched controls, but 39 +/- 4% lower OC and 69 +/- 8% lower ICTP than active players (both P < 0.001). Duration of activity was correlated with bone ALP and ICTP (both r = 0.3, P < 0.05) in individuals exercising 6 hours/week or less. No correlation was found in those exercising above this level. It seems as if the bone turnover, evaluated by serum bone remodeling markers, adapts to the current activity needed to maintain bone strength, and a duration of exercise above that level seems to confer no additional benefits.

Markers of type I and type III collagen turnover, insulin-like growth factors, and their binding proteins in cord plasma of small premature infants: relationships with fetal growth, gestational age, preeclampsia, and antenatal glucocorticoid treatment.

Disorders affecting fetal growth are commonly associated with premature birth. IGFs and their binding proteins (IGFBPs) are potent regulators of fetal growth. In vitro evidence suggests that they regulate collagen turnover. Collagen turnover can be monitored by serum markers of type I collagen synthesis (PINP) and degradation (ICTP) and a marker of type III collagen synthesis (PIIINP). We examined whether these markers in fetal circulation reflect intrauterine growth and maturity, and whether any interrelationship exists between them and fetal IGFs and IGFBPs in preterm infants before 32 wk of gestation. Cord plasma PINP, ICTP, PIIINP, IGF-I, IGF-II, IGFBP-1, and IGFBP-3 were determined for 98 preterm infants. To express birth weight in units adjusted for gestational age, a birth weight SD score (SDS) was calculated. Negative correlations existed between gestational age and PINP (r = -0.43; p < 0.0001), ICTP (r = -0.34; p = 0.002), and PIIINP (r = -0.34; p = 0.0001). Positive correlations existed between birth weight SDS and PINP (r = 0.40; p = 0.0002) and ICTP (r = 0.48; p < 0.0001) but not PIIINP. Moreover, birth weight SDS was positively correlated with IGF-I (r = 0.58; p < 0.0001) and IGFBP-3 (r = 0.44; p < 0.0001) and negatively correlated with IGF-II (r = -0.36; p = 0.003) and IGFBP-1 (r = -0.50; p < 0.0001). Gestational age correlated with IGFBP-3 (r = 0.25; p = 0.03). In preeclampsia, IGF-I was lower (p = 0.002) and IGFBP-1 higher (p < 0.0001), also after adjustment for fetal size. The number of antenatal glucocorticoid treatments was associated with lower ICTP (p = 0.04), higher IGF-I (p = 0.002), lower IGF-II (p = 0.02), lower IGFBP-1 (p = 0.05), and higher IGFBP-3 (p = 0.004), also after adjustment for potential confounders. In multiple regression analysis, the factors significantly associated with PINP (R:(2) = 0.47) were gestational age and IGF-I, and those associated with ICTP (R:(2) = 0.54) were IGF-I, gestational age, and antenatal glucocorticoid treatment. We conclude that IGF-I may be involved in regulation of type I collagen turnover in the growing fetus. Cord blood PINP and ICTP reflect both fetal growth and maturity and deserve evaluation as potential indicators of postnatal growth velocity in preterm infants, whereas PIIINP reflects fetal maturity.

Inability of bone turnover marker as a strong prognostic indicator in prostate cancer patients with bone metastasis: comparison with the extent of disease (EOD) grade.

Although clinical investigations of bone turnover markers in prostate cancer patients have been conducted, the relationships of pretreatment levels of the markers to the prognosis of patients with bone metastasis has not been fully examined. The serum levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP), alkaline phosphatase (ALP), and prostate-specific antigen (PSA) were examined in 48 untreated prostate cancer patients with bone metastasis, and the prognoses of the patients were evaluated using univariate and multivariate analyses. The patients with low PICP or ALP values had significantly better outcomes in terms of cause-specific survival compared to the patients with high PICP or ALP values. There was no significant difference in survival between patients with high and low ICTP or PSA values. The multivariate analysis of PICP, ICTP, ALP, PSA, and extent of disease (EOD) grade revealed that only the EOD grade was an important prognostic indicator for survival. These results demonstrate that the extent of bone metastasis evaluated by bone scintigrams is a more important prognostic indicator than are the serum biochemical markers of bone turnover.

Increased degradation of type I collagen in patients with inflammatory bowel disease.

To assess the mechanisms of osteopenia in inflammatory bowel disease (IBD), the serum markers of bone formation (osteocalcin and carboxyterminal propeptide of type I procollagen (PICP)) and bone degradation (carboxyterminal telopeptide of type I collagen (ICTP)), the bone mineral density (BMD) of the lumbar spine and the proximal femur and calcium intake of 150 unselected IBD patients and 73 healthy controls were investigated. The patients had higher ICTP values (3.69 (SD 1.40) microgram/l) than the healthy controls (3.25 (1.00) microgram/l, p = 0.035), but no differences in serum PICP and osteocalcin between these groups were detected. In the patients, the ICTP, PICP, and osteocalcin values did not have any significant correlation with BMD, but the patients with ICTP values above 3.6 microgram/l had significantly lower Z scores than those with lower ICTP. In the controls, however, a positive correlation between serum ICTP and BMD was found. The ulcerative colitis patients with total colitis had higher values of ICTP (3.96 (1.58) microgram/l) than those with a left sided disease (3.04 (0.86) micrograms/l, p = 0.009). The patients with a history of clinically active disease (n = 20) had higher ICTP (4.58 (1.55) microgram/l) and osteocalcin (12.56 (5.64) microgram/l) values than the patients (n = 130) with quiescent disease (ICTP 3.56 (1.33), p = 0.002, and osteocalcin 9.76 (3.62), p = 0.017). Increased serum osteocalcin, PICP, and ICTP concentrations and reduced BMD Z scores were found in a subgroup of Crohn's disease patients with a history of an active disease (n = 11). Raised serum ICTP and normal values of osteocalcin and PICP in IBD patients show increased breakdown of type I collagen without a compensatory increase in its synthesis suggesting an increased rate of bone degradation as a probable mechanism for osteopenia in IBD. Raised ICTP values are related to reduced bone mineral densities.