Anna Calabrò

Circulating Sclerostin Levels and Bone Turnover in Type 1 and Type 2 Diabetes

CONTEXT Previous observations showed a condition of low bone turnover and decreased osteoblast activity in both type 1 and 2 diabetes mellitus (DM1 and DM2). Sclerostin is a secreted Wnt antagonist produced by osteocytes that regulates osteoblast activity and thus bone turnover. Its levels increase with age and are regulated by PTH. OBJECTIVES The aim of the present study was to evaluate circulating sclerostin levels in patients with DM1 or DM2 with normal renal function and to analyze its relationship with PTH, 25-hydroxyvitamin D, and bone turnover markers. DESIGN, AND SETTING: This was a cross-sectional study conducted at a clinical research center. PARTICIPANTS Forty DM2 and 43 DM1 patients were studied and compared with a reference control group (n = 83). RESULTS In the overall cohort, sclerostin levels were higher in males than in females and significantly increased with age in both genders. The positive correlation between sclerostin and age was maintained in DM1 but not in DM2 patients. Moreover, sclerostin levels were higher in DM2 than in controls or DM1 patients, and this difference persisted when adjustments were made for age and body mass index. Consistent with previous clinical and experimental observations, sclerostin was negatively associated with PTH in nondiabetic patients (r = -0.30; P < 0.01), independently of age and gender. Conversely, an opposite but nonsignificant trend between PTH and sclerostin was observed in both DM1 (r = 0.26; P = 0.09) and DM2 (r = 0.32; P = 0.07) cohorts. CONCLUSIONS These findings suggest that sclerostin is increased in DM2. Moreover, the transcriptional suppression of sclerostin production by PTH might be impaired in both DM1 and DM2.

Prevalence of Paget's disease of bone in Italy

We examined the prevalence of PDB in Italy from radiological, scintigraphic, and biochemical surveys in two Italian towns. Prevalence rates varied from 0.7% to 2.4%, were higher in males than in females, and slightly differed between the two towns. Unlike previous studies in populations of British descent, no secular trend for a decreasing prevalence emerged.

Characteristics and Familial Aggregation of Paget's Disease of Bone in Italy

This study examined the characteristics of 147 PDB cases from Italy. Our data showed a reduced clinical severity of PDB with respect to other populations and provided further support of the importance of environmental factors (rural area of residence and animal contact) in the pathogenesis of PDB. Familial aggregation was observed in 15% of cases.

Left ventricular remodelling and systolic function measurement with 64 multi-slice computed tomography versus second harmonic echocardiography in patients with coronary artery disease: A double blind study

The present study evaluated LV volumes, ejection fraction (LVEF) and stroke volume (SV) obtained by 64-MDCT and to compare these data with those obtained by second harmonic 2D Echo, in patients referred for non-invasive coronary vessels evaluation. The most common technique in daily clinical practice used for determination of LV function is two-dimensional echocardiography (2D-TTE). Multi-detector computed tomography (MDCT) is an emerging new technique to detect coronary artery disease (CAD) and was recently proposed to assess LV function. 93 patients underwent to 64-MDCT for LV function and volumes assessment by segmental reconstruction algorithm (Argus) and compared with recent (2 months) 2D-TTE, all images were processed and interpreted by two observers blinded to the Echo and MDCT results. A close correlation between TTE and 64 MDCT was demonstrated for the ejection fraction LVEF (r=0.84), end-diastolic volume LVEDV (r=0.80) and end-systolic volume LVESV (r=0.85); acceptable correlation was recruited for stroke volume LVSV (r=0.58). Optimal results were recruited for inter-observer variability for 64-MDCT measured in 45 patients: LVESV (r=0.82, p<0.001), LVEDV (r=0.83, p<0.001), LVEF (r=0.69, p<0.002) and SV (r=0.66, p<0.001). Our results, showed that functional and temporal information contained in a coronary 64-MDCT study can be used to assess left ventricular (LV) systolic function and LV dimensions with good reproducibility and acceptable correlation respect to 2D-TTE. The combination of non-invasive coronary artery imaging and assessment of global LV function might became in the future a fast and conclusive cardiac work-up in patients with CAD.

Osteoprotegerin and B-type natriuretic peptide in non-ST elevation acute coronary syndromes : Relation to coronary artery narrowing and plaques number

BACKGROUND To analyse osteoprotegerin (OPG), and B-type natriuretic peptide (BNP) levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. OPG has been found in several tissues, including the cardiovascular system, BNP is selectively produced by myocardial cells. METHODS 178 consecutive patients were classified in three groups: stable angina (SA), unstable angina/non-ST elevation myocardial infarction (NSTE-ACS) and control group, measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-, 2- , 3- or 4- vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS OPG levels were higher in patients respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with NSTE-ACS had higher OPG level with respect to SA patients (11.8+/-7.1 pmol/l p<0.001). A positive relation was found between OPG levels and number of coronary plaques by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with NSTE-ACS respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in multivessels vs 1-vessel disease (p<0.001). CONCLUSIONS Patients with NSTE-ACS show high OPG levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the coronary disease progression. BNP is also increased during NSTE-ACS and more associated to coronary narrowing.

Laboratory parameters of cardiac and kidney dysfunction in cardio-renal syndromes.

Abstract“Cardio-Renal Syndromes” (CRS) are disorders of the heart and kidneys in which acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other. The pathophysiology of CRS is complex, and there is accumulating evidence that various novel biomarkers are useful for diagnosis, prognostication, and risk stratification in patients with heart failure and chronic kidney disease (CRS). When both the heart failure (HF) and CKD occur together, it is important to have biomarkers that are able to risk stratify patients by looking at both their heart and kidney aspects. There are some promising newer renal biomarkers that may contribute to a better evaluation and prediction of prognosis in CRS patients. Most of the renal biomarkers studies in CRS have been performed in the setting of cardiac surgery, acute coronary syndrome (ACS), HF or after exposure to radiocontrast media in diagnostic and/or therapeutic percutaneous coronary procedures. Natriuretic peptides (NPs) have been validated as an important cardiac biomarker for risk stratification and prognostication in HF patients with or without CKD. However, the best cutoff values for each stage of CKD, including those on renal replacement therapy, are yet to be ascertained. In this context, it is likely that panels of multiple biomarkers will be needed for optimal evaluation, risk stratification, timely treatment initiation, and follow-up of patients with CRS.

B-type natriuretic peptide as an independent predictor of coronary disease extension in non-ST elevation coronary syndromes with preserved systolic function

Objective: B-type natriuretic peptide (BNP) has been employed as a risk marker in patients with coronary artery disease (CAD) with ST elevation and non-ST elevation. It is not yet established if early BNP measurements provide additional information to troponin and electrocardiographic analysis in patients without ventricular enlargement and systolic dysfunction. Design: This study compared BNP levels in patients with stable angina (SA) and acute coronary syndromes with non-ST elevation in relation to angiographic lesions (NSTEMI-ACS). Moreover, the diagnostic utility of BNP was determined using the receiver operating characteristic curve. Patients: 280 patients with CAD without ST elevation and preserved systolic function were studied. BNP samples were measured in all recruited patients within 24 hours of hospitalization. Results: BNP values increased progressively with the severity of diagnosis: SA (n = 85; 50.4 ± 50 pg/ml) NSTEMI-ACS (n = 195; 283 ± 269 pg/ml; p < 0.0001). The analysis of BNP in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1- or 2-vessel disease (p < 0.001 and p < 0.003). Values of BNP >80 pg/ml were shown to be able to predict CAD severity and coronary vessel involvement (AUC = 0.80; p = 0.0001) with a sensitivity of 78% and a specificity of 72%. In multivariate analysis, BNP levels >80 pg/ml, CAD history, and ST deviation >2 mm were confirmed as independent predictors of CAD severity. Conclusions: Circulating BNP levels appear elevated in NSTEMI-ACS, without left ventricular systolic dysfunction. A BNP cut-off value of 80 pg/ml is a good predictor of CAD extension.

B-type natriuretic peptide levels predict extent and severity of coronary disease in non-ST elevation coronary syndromes and normal left ventricular systolic function.

BACKGROUND B-type natriuretic peptide (BNP) has been used recently as a biological marker in patients with coronary artery disease (CAD) with ST-elevation, as well as without ST-elevation. BNP is able to predict systolic dysfunction, adding new prognostic information to existing traditional markers. However is not known if there is a relation between the quantity of BNP levels and the severity of coronary artery disease. METHODS This study compared B-type natriuretic peptide (BNP) levels in patients with stable angina (SA) and acute coronary syndromes (ACS) without ST-elevation in relation to angiographic lesions using TIMI and Gensini Scores. We studied 282 patients with CAD without ST elevation and preserved systolic function. BNP samples were measured in all recruited patients within 24 hours of hospitalization. RESULTS BNP values were progressively increased in relation to the severity of diagnosis: SA (52.6±49.4 pg/mL ) UA (243.3±212 pg/mL) NSTE-ACS (421.7±334 pg/mL) (p<0.0001 and p<0.007 respectively). No statistically significant difference was observed between patients with SA and controls (21.2±6.8 pg/mL). The analysis of BNP levels in relation to the number of involved vessels demonstrated significantly increased levels in patients with multivessel disease compared to patients with 1 or 2 vessel disease (1-86.2±46.3 pg/mL; 2-127±297 pg/mL; 3-295±318 pg/mL; 4-297±347 pg/mL p<0.001 and p<0.003). Evaluation of BNP using Gensini Score showed a strong relation between BNP and coronary disease extension (r=0.38 p<0.0001).This trend was maintained in all CAD groups (SA=r 0.54; UA r=0.36 NSTE-ACS r=0.28). CONCLUSIONS Circulating BNP levels appear elevated in ACS with diffuse coronary involvement, even in the absence of systolic dysfunction. BNP is also associated with multi-vessel disease and the extension of coronary disease.

Osteoprotegerin and B-type natriuretic peptide in acute coronary syndromes with preserved systolic function: Relation to coronary artery disease extension

OBJECTIVES To analyze Osteoprotegerin (OPG), and BNP plasma levels in patients with non-ST elevation acute coronary syndrome (NSTE-ACS), in relation to clinical presentation and to coronary atherosclerosis diffusion. METHODS 155 CAD patients were classified in four groups: stable angina (SA n=42), unstable angina (UA n=35) non-ST elevation myocardial infarction (NSTEMI n=45) and control group (n=33), measuring OPG and BNP at hospital admission. We compared both biomarkers in relation to the number of coronary narrowed vessels (1-,2-,3 or more vessels disease), and to the stenoses degree by Duke Jeopardy score. RESULTS OPG levels were higher in patients with CAD respect to controls (p<0.0001). Patients with SA showed more elevated levels than controls (2.6+/-1.2 vs 7.4+/-5.0 pmol/l p<0.01). However patients with UA and NSTEMI had higher OPG level with respect to SA patients (12.2+/-7.8 and 11.6+/-6.1 respectively pmol/l p<0.001). A positive relation was found between OPG levels and coronary plaques extension by Duke Jeopardy score (r=0.65). BNP levels were higher in patients with UA/NSTEMI respect to controls and SA patients (p<0.001). Besides, BNP was significantly higher in patients with multi-vessels vs 1-vessel disease (p<0.001). CONCLUSIONS Patients with UA and NSTEMI show high OPG and BNP levels. OPG increase seems related to the number of plaques in the coronary vessels, suggesting its involvement in the CAD progression.

Rise and fall of B-type natriuretic peptide levels in patients with coronary artery disease and normal left ventricular function after cardiac revascularization.

BackgroundRecently, it was shown that B-type natriuretic peptide levels are increased in patients with acute coronary syndromes. AimsTo assess the relation between B-type natriuretic peptide and ischemia in patients with stable and unstable angina pectoris with normal left ventricular function in relation to the extent of ischemia and response to revascularization. MethodsFifty-nine consecutive patients were enrolled in the study, patients were divided into two groups: stable angina patients (group I, n=18), and unstable coronary patients (group II, n=41). Baseline characteristics were compared with 15 age-matched and sex-matched participants. B-type natriuretic peptide levels were measured at baseline and 3, 7 and 90 days after coronary revascularization in group I and II. ResultsPatients with unstable angina pectoris had increased B-type natriuretic peptide levels compared with stable angina pectoris patients (B-type natriuretic peptide levels: controls 15.5±13 pg/ml, stable angina pectoris group 28.4±19 pg/ml, unstable angina pectoris group 104±81 pg/ml; P<0.01). A relationship between the number of affected coronary vessels and B-type natriuretic peptide was assessed (one-vessel 29.9±21 pg/ml, two-vessel 93.8±87 pg/ml, three-vessel 119±88 pg/ml; P<0.01). After revascularization, B-type natriuretic peptide levels decreased in groups I and II (25±20 vs. 39±28 pg/ml) and were similar after 90 days in percutaneous transluminal coronary angiograghy and in coronary artery bypass grafting groups (percutaneous transluminal coronary angiography 26±22 pg/ml, coronary artery bypass grafting 36±26 pg/ml; NS). ConclusionsB-type natriuretic peptide levels increase in unstable angina pectoris patients and are linked to the extent of coronary disease in patients with normal left ventricular systolic function, and returned to baseline level after surgical or catheter revascularization.