Infection by CagA-Positive Helicobacter pylori Strains and Bone Fragility: A Prospective Cohort Study.

Helicobacter pylori (HP) infection is a common and persistent disorder acting as a major cofactor for the development of upper gastrointestinal diseases and several extraintestinal disorders including osteoporosis. However, no prospective study assessed the effects of HP on bone health and fracture risk. We performed a HP screening in a population-based cohort of 1149 adults followed prospectively for up to 11 years. The presence of HP infection was assessed by serologic testing for serum antibodies to HP and the cytotoxin associated gene-A (CagA). The prevalence of HP infection did not differ among individuals with normal bone mineral density (BMD), osteoporosis, and osteopenia. However, HP infection by CagA-positive strains was significantly increased in osteoporotic (30%) and osteopenic (26%) patients respect to subjects with normal BMD (21%). Moreover, anti-CagA antibody levels were significantly and negatively associated with lumbar and femoral BMD. Consistent with these associations, patients affected by CagA-positive strains had a more than fivefold increased risk to sustain a clinical vertebral fracture (HR 5.27; 95% CI, 2.23-12.63; p < .0001) and a double risk to sustain a nonvertebral incident fracture (HR 2.09; 95% CI, 1.27-2.46; p < .005). Reduced estrogen and ghrelin levels, together with an impaired bone turnover balance after the meal were also observed in carriers of CagA-positive HP infection. HP infection by strains expressing CagA may be considered a risk factor for osteoporosis and fractures. Further studies are required to clarify in more detail the underlying pathogenetic mechanisms of this association. © 2020 American Society for Bone and Mineral Research (ASBMR).

Infectious Burden and Semen Parameters.

OBJECTIVE: To investigate the relationship between chronic infections detected in serum and semen quality. The pathogen burden is a concept consisting in the observation that, in patients with heart disease, damaging effects of the coronary arteries increase concomitantly with the number of agents responsible for chronic infections to which patients mounted a serological response. Previous observations that Helicobacter pylori infection may reduce the semen quality prompted us to perform the present study. METHODS: Blood and semen samples were collected from 73 selected men, enrolled from January 2014 to January 2015. Semen characteristics were evaluated by light and transmission electron microscopy. Transmission electron microscopy data were quantified with a mathematical formula providing numerical scores, such as fertility index (FI, number of sperm free from ultrastructural defects) and the percentages of sperm apoptosis, immaturity, and necrosis. Serum samples were examined by enzyme-linked immunosorbent assay for the presence of immunoglobulin G to the most common agents of chronic infections such as H. pylori (HP), Mycoplasma pneumoniae (MP), Chlamydophila pneumoniae (CP), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), and cytomegalovirus (CMV). RESULTS: The prevalence of infections was as follows: HP 43.8%, CP 46.6%, MP 72.6%, EBV 95.9%, HSV-1 74.0%, and CMV 46.6%. Concomitantly with the increased number of pathogens against which the patients mounted a significant antibody response, sperm concentration (P <.05), sperm motility (P <.001), and fertility index (P <.001) were significantly reduced and the percentage of necrotic sperm was increased (P <.01). CONCLUSION: The higher the number of pathogens stimulating an immunoglobulin G systemic response, the lower was the semen quality.

Diagnostic utility of contemporary echo and BNP assessment in patients with acute heart failure during early hospitalization.

BACKGROUND: The use of B-type natriuretic peptide (BNP) and echocardiography in acute heart failure (AHF) diagnosis is poorly employed in the Emergency Department. The aim of the present study is to evaluate relation among BNP levels systolic and diastolic dysfunction during early phases of AHF hospitalization. METHODS: We performed contemporary echocardiographic and BNP assessment in 310 patients with AHF within 12h since hospital admission. We studied the correlation among BNP and degree of diastolic dysfunction evaluated by pulsed Doppler transmitral flow and Tissue Doppler flow. Finally we investigated the relation among BNP and the right systolic longitudinal ventricular function (TAPSE) and the systolic pulmonary arterial pressure (PAPs). RESULTS: BNP levels were 1417±1126, 1081±955, 894±901pg/mL, for patients with EF≤25%, EF 25-40% and EF 40-50% (p=0.005), respectively. "BNP levels linearly correlate with the degree of diastolic dysfunction: 582±406pg/mL in altered relaxation pattern, 712±557pg/mL in pseudonormal pattern and 1694±805 in restrictive filling pattern (p<0.001 for all patterns)." BNP levels were significantly increased in patients with right systolic ventricular dysfunction (TAPSE<18mm; p=0.006) and in patients with PAPs≥40mmHg (p=0.001). ROC curve and logistic regression analysis highlighted the power of BNP to detect severe systolic dysfunction, right ventricular (RV) overload and dysfunction and diastolic dysfunction patterns. CONCLUSIONS: BNP levels correlate linearly with LV systolic dysfunction as well as with impaired degree of diastolic dysfunction. Significant PAP increase is a further factor influencing BNP elevation in patients with AHF during early hospitalization phase.

Sperm Parameters and Semen Levels of Inflammatory Cytokines in Helicobacter pylori-infected Men.

OBJECTIVE: To explore the relationships between seminal interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) with semen parameters, sperm apoptosis, and necrosis in subjects infected by Helicobacter pylori (HP) expressing and not expressing CagA. METHODS: In 109 selected patients, HP infection and seminal levels of IL-6 and TNF-α were determined using enzyme-linked immunosorbent assays. Western blotting was used to detect antibodies to CagA. Semen parameters were determined following World Health Organization guidelines and sperm apoptosis and necrosis by annexin V and propidium iodide assay. RESULTS: Twenty-eight subjects were infected by HP (HP+); among them, 12 were CagA seropositive (CagA+) and 16 were negative (CagA-). Eighty-one men were HP seronegative (HP-). Semen TNF-α and IL-6 concentrations were increased in HP+ vs HP- groups (TNF-α: 41 pg/mL vs 27 pg/mL; IL-6: 11 pg/mL vs 5 pg/mL; P <.01). In comparison to the HP- group, CagA+ group showed reduced sperm motility (24% vs 32% motile sperm; P <.05), enhanced necrosis (33.5% vs 21% necrotic sperm; P <.05), and increased cytokines levels (TNF-α: 46 pg/mL vs 27 pg/mL; P <.01; IL-6: 17.5 pg/mL vs 5 pg/mL; P <.01). Sperm motility of CagA+ group was lower vs CagA- group (24% vs 36.5% motile sperm; P <.05). Both IL-6 and TNF-α levels positively correlated with the percentage of necrotic sperm (P <.001). CONCLUSION: CagA+ HP infection increases semen levels of inflammatory cytokines, which may reduce sperm motility and determine sperm damage and contribute to reduce the reproductive potential in men.

Continuous versus bolus intermittent loop diuretic infusion in acutely decompensated heart failure: a prospective randomized trial.

INTRODUCTION: Intravenous loop diuretics are a cornerstone of therapy in acutely decompensated heart failure (ADHF). We sought to determine if there are any differences in clinical outcomes between intravenous bolus and continuous infusion of loop diuretics. METHODS: Subjects with ADHF within 12 hours of hospital admission were randomly assigned to continuous infusion or twice daily bolus therapy with furosemide. There were three co-primary endpoints assessed from admission to discharge: the mean paired changes in serum creatinine, estimated glomerular filtration rate (eGFR), and reduction in B-type natriuretic peptide (BNP). Secondary endpoints included the rate of acute kidney injury (AKI), change in body weight and six months follow-up evaluation after discharge. RESULTS: A total of 43 received a continuous infusion and 39 were assigned to bolus treatment. At discharge, the mean change in serum creatinine was higher (+0.8 ± 0.4 versus -0.8 ± 0.3 mg/dl P <0.01), and eGFR was lower (-9 ± 7 versus +5 ± 6 ml/min/1.73 m(2) P <0.05) in the continuous arm. There was no significant difference in the degree of weight loss (-4.1 ± 1.9 versus -3.5 ± 2.4 kg P = 0.23). The continuous infusion arm had a greater reduction in BNP over the hospital course, (-576 ± 655 versus -181 ± 527 pg/ml P = 0.02). The rates of AKI were comparable (22% and 15% P = 0.3) between the two groups. There was more frequent use of hypertonic saline solutions for hyponatremia (33% versus 18% P <0.01), intravenous dopamine infusions (35% versus 23% P = 0.02), and the hospital length of stay was longer in the continuous infusion group (14. 3 ± 5 versus 11.5 ± 4 days, P <0.03). At 6 months there were higher rates of re-admission or death in the continuous infusion group, 58% versus 23%, (P = 0.001) and this mode of treatment independently associated with this outcome after adjusting for baseline and intermediate variables (adjusted hazard ratio = 2.57, 95% confidence interval, 1.01 to 6.58 P = 0.04). CONCLUSIONS: In the setting of ADHF, continuous infusion of loop diuretics resulted in greater reductions in BNP from admission to discharge. However, this appeared to occur at the consequence of worsened renal filtration function, use of additional treatment, and higher rates of rehospitalization or death at six months. TRIAL REGISTRATION: ClinicalTrials.gov NCT01441245. Registered 23 September 2011.

The associations of body composition and fat distribution with bone mineral density in elderly Italian men and women.

This study aimed to investigate the associations of body composition and fat distribution with bone mineral density (BMD) in elderly Italian subjects. In 866 women (age 64.2±6.5yr) and 168 men (age 65.1±6.1yr), we measured BMD at lumbar spine, at femur, at the total body, and at the right hand. In all subjects, we also measured sex hormones, 25-hydroxyvitamin D, bone markers, and calcium intake. In both men and women, all body composition parameters had significant positive correlations with BMD at all sites after adjusting for age only; after adjusting also for body weight only lean mass (LM) remained positively associated with BMD at all sites except BMD at lumbar spine. In males, LM was associated with BMD at all sites, whereas android fat was associated with BMD at lumbar spine, at femur, and at whole body. In females, fat mass (FM) was positively and age inversely associated with BMD at all sites, whereas gynoid fat and alkaline phosphatase were inversely associated with BMD at lumbar spine and at femur. In conclusion, the role of LM seems more important in males, whereas in women the role of FM prevails with negative associations between gynoid fat and BMD.

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.

Influence of Helicobacter pylori infection on levels of ghrelin and obestatin in human semen.

Helicobacter pylori (HP) infection might have negative effects on the semen parameters of infertile men. We explored the possibility that this infection can influence systemic and seminal levels of ghrelin and obestatin, hormones mainly produced by the stomach. Ghrelin and obestatin exert many activities, including the regulation of reproductive biology, and are present in many organs and fluids, including human semen. In 78 men, we determined HP infection and cytotoxin-associated gene A protein (CagA) status by enzyme-linked immunosorbent assay and Western blotting, semen quality following World Health Organization guidelines, and ghrelin and obestatin levels in the blood stream (47 subjects) and semen by radioimmunoassay. Twenty-seven men (34.6%) were infected (HP+) and 11 out of 27 infected men (40.7%) were seropositive for CagA (CagA+). Sperm motility was significantly reduced in HP+/CagA+ men compared with HP+/CagA- men (P < .01). Ghrelin semen levels were decreased in HP+ men compared with uninfected individuals (P < .05), whereas they were increased in HP+/CagA+ men compared with HP+/CagA- subjects (P < .01). Ghrelin semen concentrations in HP+/CagA- men were lower than those measured in uninfected subjects (P < .001). Semen obestatin concentration was increased, in a nonsignificant manner, in HP+/CagA+ men. The obestatin levels were approximately 4 times higher than those of ghrelin in semen and approximately half the levels of ghrelin in serum specimens of all the analyzed groups. No significant differences were found in systemic levels of ghrelin and obestatin in HP+ to uninfected individuals. HP infection may influence the ghrelin seminal concentrations, probably as a response to a negative effect of infection on the semen quality.

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.

Comparison of intravenous and intramuscular neridronate regimens for the treatment of Paget disease of bone.

Aminobisphosphonates actually represent the most common treatment for Paget disease of bone (PDB). In a previous study we demonstrated that either zoledronic acid (4 mg) or neridronate (200 mg) given as a single intravenous infusion showed a similar short-term efficacy in achieving biochemical remission in up to 90% of patient nonresponders to pamidronate. In this study we compared the long-term (36 months) effects of a same neridronate dose (200 mg) given as an intravenous (100-mg infusion for 2 consecutive days) or intramuscular (25-mg injection weekly for 2 months) regimen in 56 patients with active PDB. All patients were advised to receive calcium plus vitamin D supplementation throughout the study period. At 6 months, 92.6% and 96.5% of patients receiving intravenous and intramuscular neridronate, respectively, achieved a therapeutic response [defined as normalization of alkaline phosphatase (ALP) levels or a reduction of at least 75% in total ALP excess]. The response to treatment was significantly correlated with baseline ALP and 25-hydroxyvitamin D [25(OH)D] levels at 6 months. The decrease in ALP levels was highest in patients with higher baseline total or bone-specific ALP levels and with higher 25(OH)D levels at 6 months. Response rates were maintained at 12 months but decreased progressively at 24 and 36 months without significant differences between the two neridronate regimens. Both regimens were well tolerated. The only relevant side effect was an acute-phase response occurring in 14% of the patients. In conclusion, these results indicate that a 200-mg intramuscular neridronate course has a similar efficacy as an intravenous infusion of the same dose for the treatment of PDB and might be of particular value for patients intolerant to oral bisphosphonates and unwilling or unable to undergo intravenous infusions.

Infection by CagA-positive Helicobacter pylori strains may contribute to alter the sperm quality of men with fertility disorders and increase the systemic levels of TNF-alpha.

This study was aimed to address the possibility that Helicobacter pylori infection may play a detrimental role in semen quality of men with idiopathic infertility. Infection by H. pylori and by strains expressing CagA was determined in 80 male infertile patients by Western blotting and ELISA. Semen analysis was performed by light microscopy and transmission electron microscopy quantitatively elaborated (fertility index, immaturity, necrosis, and apoptosis percentages). Systemic levels of IL-6 and TNF-alpha were evaluated. Infertile patients infected with H. pylori showed a low sperm quality respective to uninfected patients. Particularly, in CagA-positive patients we observed a significant reduction in sperm motility and in the fertility index, while apoptosis and necrosis were increased. In these patients, the means of systemic TNF-alpha levels were higher than those of uninfected patients. The negative influence of CagA-positive H. pylori infection on sperm quality may help to understand the role of chronic infections in reproductive disorders.

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.

Prevalence of risk factors, coronary and systemic atherosclerosis in abdominal aortic aneurysm: comparison with high cardiovascular risk population.

BACKGROUND: Abdominal aortic aneurysm (AAA) is considered a manifestation of atherosclerosis, however there are epidemiologic, biochemical, and structural differences between occlusive atherosclerosis and AAA. The pathogenesis of AAA involves several factors, first of all destruction of collagen and elastin in the aortic wall. Classical risk factors may influence the evolution and development of AAA, though no consistent association has been found. Aims of the study were to evaluate associations between risk factors and to establish the prevalence of carotid, peripheral vascular and coronary atherosclerosis in patients with AAA. METHODS: We studied 98 patients with AAA (Group 1) awaiting surgery compared with high cardiovascular risk population having two or more risk factors (n=82 Group 2). We evaluated traditional risk factors and we studied by eco-doppler and echocardiography the presence of carotid peripheral and coronaric atherosclerosis in two groups. RESULTS: We found a higher incidence of AAA in males (p < 0.01). The prevalence of infrarenal AAA was significantly higher than suprarenal AAA (81 vs. 17 p < 0.001). No differences in total cholesterol (199 +/- 20 vs. 197 +/- 25 mg/dl), low-density lipoprotein (142 +/- 16 vs. 140 +/- 18 mg/dl), triglycerides (138 +/- 45 vs. 144 +/- 56 mg/dl), glycemia (119 +/- 15 vs. 122 +/- 20 mg/dl), and fibrinogen (388 +/- 154 vs. 362 +/- 92 mg/dl) were found between groups. We demonstrated significant differences for cigarette smoking (p < 0.002), systolic and diastolic blood pressure (150 +/- 15 vs. 143 +/- 14 mmHg and 88 +/- 6 vs. 85 +/- 7 mmHg, p < 0.0001 and p < 0.05, respectively) and high sensititivity C reactive protein (2.8 +/- 1.3 vs. 1.3 +/- 0.7 mg/dl, p < 0.001). High-density lipoprotein (HDL) cholesterol levels were significant greater in Group 1 than Group 2 (p < 0.003). Subgroups of patients with AAA and luminal thrombus showed higher fibrinogen levels (564 +/- 235 vs. 341 +/- 83 mg/dl, p < 0.001) and lower HDL than in controls (46.6 +/- 6.5 vs. 52.1 +/- 7.8 mg/dl, p < 0.01). We did not find any difference in body mass index, or prevalence of coronary and peripheral atherosclerosis between groups. Conversely, we found higher prevalence of carotid atherosclerosis in Group 2 (9% vs. 25%, p < 0.004). CONCLUSION: Our AAA patients had fewer and different risk factors respect to patients with atherosclerosis. Only elevated blood pressure, C reactive protein, and smoking showed a significant association with AAA. Atherosclerosis in other arterial districts did not differ respect to subjects with high cardiovascular risk. Our results confirm the hypothesis that AAA and atherosclerosis are two different pathological entities with different risk profiles.

The effects of zoledronic acid on serum lipids in multiple myeloma patients.

Nitrogen-containing bisphosphonates (N-BPs) inhibit osteoclast-mediated bone resorption and are widely used for tumor-associated osteolysis. The mechanism of action of these drugs has not been completely clarified, but it has been observed that N-BPs may inhibit squalene synthase or farnesyl pyrophosphate synthase. Zoledronic acid (ZA) represents a novel N-BP which also has antitumor activity. To explore the effects of ZA on serum lipids, we studied 26 patients with smoldering myeloma at diagnosis. Sixteen patients were treated with ZA (4 mg) at baseline and at months 1, 2, 4, and 6. The remaining 10 served as controls. In all subjects, total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and C-terminal telopeptide of type I collagen (CTX) were measured at baseline and after 1, 3, and 6 months. In treated patients, we observed a progressive and significant reduction of TC, with a maximum decrease of 13% at 6 months. Moreover LDL-C decreased by 21% at 6 months, while no significant difference was appreciated in HDL-C and TGs. Also, the indexes of cardiovascular risk improved after ZA administration: TC/HDL-C ratio progressively decreased by 17% and HDL-C/LDL-C ratio increased by 36%, showing an effect that appears to be cumulative. In conclusion, ZA given intravenously at high doses in patients with smoldering myeloma seems to be able to modify the lipid profile with an improvement of atherosclerotic risk index.

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.

Brain natriuretic peptide and other risk markers for outcome assessment in patients with non-ST-elevation coronary syndromes and preserved systolic function.

Several emerging cardiac markers constitute strong predictors among patients with coronary artery disease. In particular, brain natriuretic peptide (BNP), troponin T (TnT), and C-reactive protein (CRP) are related to increased risk of recurrent ischemic events and death. However, little is known about the utility of these biomarkers in combination. This study examined risk assessment in patients with coronary artery disease and preserved systolic function. We studied 208 consecutive patients (138 men, 70 women) with stable angina, unstable angina, and non-Q-wave myocardial infarction whose plasma BNP, TnT, and CRP levels were measured at hospital admission. All recruited patients underwent echocardiographic examination, and selective coronary angiography was performed. After adjusting for clinical presentation, age, gender, and common risk factors, BNP was demonstrated as a strong predictor of heart failure (6 months, odds ratio [OR] 2.03, 95% confidence interval [CI] 1.24 to 2.9, p <0.01; 12 months, OR 2.65, 95% CI 1.69 to 3.5, p <0.001) and mortality at 3, 6, and 12 months (p <0.001). BNP was also significantly related to extent of coronary artery disease and left anterior descending artery involvement (p <0.01). Patients with a BNP level >80 pg/ml in all 3 groups had a significantly poorer prognosis with increased incidence of heart failure and death. CRP was related to recurrent ischemic events (infarct or recurrent angina, OR 1.4, 95% CI 1.14 to 2.08, p <0.01) and was associated with major cardiac revascularization at 12 months (OR 1.51, 95% CI 1.29 to 1.73, p <0.001). TnT demonstrated a mild correlation with recurrent infarct or angina at 12 months (OR 1.1, 95% CI 0.96 to 1.22, p <0.05) but appeared related to multivessel coronary artery disease (OR 1.47, 95% CI 1.05 to 1.99, p <0.01). In conclusion, BNP appears to be associated with a long-term increased risk of mortality and heart failure in patients with apparently mild risk. BNP is also associated with a larger extent and greater severity of myocardial ischemia. Early BNP measurement could provide incremental information to TnT and CRP, and it may be the strongest independent predictor of cardiac outcome in subjects without left ventricular dysfunction or enlargement.

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

BACKGROUND: Recently, it was shown that B-type natriuretic peptide levels are increased in patients with acute coronary syndromes. AIMS: To 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. METHODS: Fifty-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. RESULTS: Patients 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). CONCLUSIONS: B-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.

H pylori infection and systemic antibodies to CagA and heat shock protein 60 in patients with coronary heart disease.

AIM: to determine the overall prevalence of H pylori and CagA positive H pylori infection and the prevalence of other bacterial and viral causes of chronic infection in patients with coronary heart disease (CHD), and the potential role of anti-heat-shock protein 60 (Hsp60) antibody response to these proteins in increasing the risk of CHD development. METHODS: Eighty patients with CHD and 160 controls were employed. We also compared the levels of anti-heat-shock protein 60 (Hsp60) antibodies in the two groups. The H pylori infection and the CagA status were determined serologically, using commercially available enzyme-linked immunosorbent assays (ELISA), and a Western blotting method developed in our laboratory. Systemic antibodies to Hsp60 were determined by a sandwich ELISA, using a polyclonal antibody to Hsp60 to sensitise polystyrene plates and a commercially available human Hsp60 as an antigen. RESULTS: The overall prevalence of H pylori infection was 78.7% (n = 63) in patients and 76.2% (n = 122) in controls (P = 0.07). Patients infected by CagA-positive (CagA+) H pylori strains were 71.4% (n = 45) vs 52.4% of infected controls (P = 0.030, OR = 2.27). Systemic levels of IgG to Hsp60 were increased in H pylori-negative patients compared with uninfected controls (P < 0.001) and CagA-positive infected patients compared with CagA-positive infected controls (P = 0.007). CONCLUSION: CagA positive H pylori infection may concur to the development of CHD; high levels of anti-Hsp60 antibodies may constitute a marker and/or a concomitant pathogenic factor of the disease.