Iperomocisteinemia e rischio cardiovascolare: stato dell’arte

Paola Pezzati*, Fiamma Balboni, Maria Stella Graziani

*Dipartimento Diagnostica di Laboratorio, Laboratorio Generale, Azienda Ospedaliero-Universitaria Careggi, Firenze

Biochimica Clinica: 2010;34(3):173-186 [Article in italian]

ABSTRACT. Hyperhomocysteinemia and cardiovascular risk: state of the art. Several decades ago it was suggested that individuals with elevated concentrations of plasma homocysteine, a sulphur-containing amino acid, have an increased risk of coronary heart disease. Observational studies confirmed the association, although its strength has recently been reconsidered. Whether this association is causal is still uncertain; however, it is highly relevant to answer the clinical question if treatments with B-type vitamins and folate, known to lower plasma homocysteine concentrations, may reduce vascular risk. The present paper reviews the evidence in a historical perspective, from observational studies to randomized controlled trials. Results from recent metanalyses are also presented and discussed. Laboratory professionals should be aware that, although “homocysteine lowering” trials showed no effects on vascular outcomes, the measurement of plasma homocysteine concentrations is still of some value as diagnostic (homocysteinuria, vitamin B deficiencies) and prognostic (cardiovascular disease) tool.

Effect of vitamin supplementation on hyperhomocysteinemia and cardiovascular risk reduction

Chiara Bellia, Giulia Bivona, Bruna Lo Sasso, Marcello Ciaccio

Chair of Clinical Biochemistry, Department of Medical Biotechnologies and Forensic Medicine, Faculty of Medicine, University of Palermo, Italy

Biochimica Clinica: 2010;34(3):187-193 [Article in english]

ABSTRACT. Homocysteine is a sulfur-containing aminoacid produced during methionine metabolism. Since 1969 the relationship between altered homocysteine metabolism and both coronary and peripheral atherotrombosis has been known; in recent years, experimental evidence has shown that elevated plasma concentrations of homocysteine are associated with an increased risk of atherosclerosis and cardiovascular ischemic events. Several mechanisms by which elevated homocysteine concentrations impair vascular function have been proposed, including impairment of endothelial function, production of reactive oxygen species and consequent oxidation of low-density lipoproteins. Folate and B vitamins, required for remethylation of homocysteine to methionine, are the most important dietary determinants of homocysteinemia and daily supplementation typically lowers plasma homocysteine concentrations. Recently, large-scale intervention trials have been conducted to determine whether lowering homocysteine concentrations through B vitamins supplementation can decrease cardiovascular risk in healthy subjects or improve survival in patients with coronary heart disease. Some of these trials found no significant beneficial effects of combined treatment with folate and vitamin B12, with or without vitamin B6, in spite of significant homocysteine lowering. In conclusion, it is still unclear whether decreasing plasma concentrations of homocysteine through diet or vitamin supplementation may be paralleled by a reduction in cardiovascular risk.

Quantificazione del DNA sierico mediante “real time polymerase chain reaction” in pazienti affetti da polipi e da cancro del colon-retto

Elisa Danese*, Martina Montagnana, Anna Maria Minicozzi, Giovanna De Matteis, Giovanni Scudo, Gian Luca Salvagno, Claudio Cordiano, Giuseppe Lippi, Gian Cesare Guidi

*Sezione di Chimica Clinica, Dipartimento di Scienze Morfologico-Biomediche, Università degli Studi, Verona

Biochimica Clinica: 2010;34(3):194-198 [Article in italian]

ABSTRACT. Free DNA quantification by real-time polymerase chain reaction (PCR) in serum of patients with polyps and colorectal cancer. Colorectal cancer (CRC) is one of the most frequent cause of cancer death worldwide. Recently, the evaluation of cell-free DNA as diagnostic tools to identify cancer has been investigated. Aim of this work was to investigate whether circulating DNA could be considered a useful marker for detection of early stage CRC and polyps. 118 patients with CRC were included in the study, along with 49 patients affected by colorectal polyps and 26 control subjects. Cell-free DNA, extracted from 200 µL serum, were quantificated by real time TaqMan-PCR assay. We chose primers and probes to specifically amplify the glyceraldehyde 3-phosphate dehydrogenase gene. Serum DNA concentrations were significantly higher in CRC patients compared with both subjects with polyps (median value, 106 µg/L vs. 40 µg/L, p <0.0001) and controls (median value, 106 µg/L vs. 14 µg/L, p <0.0001). Although the carcinoembryonic antigen (CEA) was above the cut-off in only 13 out of 66 (19.7%) CRC patients at early stage, serum free DNA displayed values above the threshold in 53 out of 66 (80.3%). Our data confirm that serum DNA concentrations are significantly increased in CRC patients, also at early disease stage, and in patients affected by polyps, so that this marker might be useful for identifying high risk individuals.

La determinazione della troponina T con il metodo ad alta sensibilità migliora la sensibilità di rilevazione della cardiomiopatia nell’amiloidosi AL

Gabriele Sarais*, Alessandra Barassi, Giovanni Palladini, Ruggero Capra, Andrea Foli, Paola Russo, Riccardo Albertini, Letizia Zenone Bragotti, Laura Obici, Remigio Moratti, Gian Vico Melzi D’Eril, Giampaolo Merlini

* Laboratori Sperimentali di Ricerca di Biotecnologie, Fondazione IRCCS Policlinico San Matteo e Dipartimento di Biochimica, Università di Pavia

Biochimica Clinica: 2010;34(3):199-202 [Article in italian]

ABSTRACT. Determination of troponin T with high-sensitivity assay improves the sensitivity for detection of cardiac involvement in AL amyloidosis. In AL amyloidosis cardiac involvement dictates prognosis. It has been demonstrated that cardiac dysfunction is best assessed by measuring serum concentrations of N-terminal B-type natriuretic peptide (NT-proBNP) and cardiac troponins. Recently, a new generation of more sensitive assays for troponin measurement has been developed, aiming at identifying minimal cardiac damage. We report the impact of the introduction of a highly sensitive cardiac troponin T (hs-cTnT) assay (Roche Diagnostics) on the detection of cardiac involvement in 109 consecutive newly diagnosed patients with AL amyloidosis. The hs-cTnT was determined on the Modular E system. Cardiac troponin I (cTnI) (Siemens TnI-Ultra) and NT-proBNP (Roche Diagnostics) were also measured. Sixty nine (63%) patients had cardiac involvement at presentation, as detected by echocardiography. The diagnostic sensitivity of the biomarkers to detect cardiac involvement at diagnosis was 74% for cTnI, 96% for hs-cTnT, and 100% for NT-proBNP, respectively. In additional 15 patients, echographic evidence of amyloid heart involvement developed during 6 months following diagnosis: cTnI was elevated at presentation in 5 cases (33%), hs-cTnT in 12 (80%, P=0,01 versus cTnI) and NT-proBNP in 11 cases (73%). We conclude that hs-cTnT may improve the sensitivity for detection of cardiac damage caused by AL amyloidosis.

Utilizzo di un pool di sangue umano fresco congelato per la valutazione intralaboratorio dell’imprecisione della determinazione dell’emoglobina glicata

Federica Braga*°, Alberto Dolci, Luisa Scapellato, Andrea Mosca, Mauro Panteghini
* Centro Interdipartimentale per la Riferibilità Metrologica in Medicina di Laboratorio (CIRME), Università degli Studi, Milano
°Laboratorio Analisi Chimico-Cliniche, Ospedale ‘Luigi Sacco’ e Cattedra di Biochimica Clinica e Biologia Molecolare Clinica, Dipartimento di Scienze Cliniche, Università degli Studi, Milano

Biochimica Clinica: 2010;34(3):203-206 [Article in italian]

ABSTRACT. Fresh-frozen human whole blood for intralaboratory evaluation of imprecision of glycated hemoglobin determination. Glycated hemoglobin (HbA1c) has a key role for the assessment of glycemic state in diabetic subjects. To guarantee the clinical reliability of HbA1c methods regular IQC programs are mandatory. These programs may give immediate information on the reliability of the analytical system used in the laboratory, providing that employed materials are stable and commutable. In this study we investigated two different preparations to be used as IQC material for HbA1c, i.e. a classical lyophilized material (CQI1) and a freshly collected whole blood pool stored at -20 °C (CQI2). We also checked the stability of CQI2 at -20 °C compared to -80 °C storage. HbA1c was determined by an immunoturbidimetric assay on Roche Cobas Integra. The mean (±SD) HbA1c concentrations in the two materials were 9.1%±0.05 in CQI1 and 6.9%±0.05 in CQI2, respectively. In a following period of 20 weeks the HbA1c recovery was between 94.6% and 105.7% for CQI1 and between 94.4% and 109.4% for CQI2. Most of CQI1 fluctuations were paired to similar fluctuations of CQI2, proving that these changes were independent of the material properties. When compared with results obtained at -80 °C storage, the HbA1c concentrations in the CQI2 at -20 °C were stable over the whole study period. In conclusion, our findings demonstrate that fresh-frozen pooled whole blood stored at -20 °C is a suitable and cheap material for use in the IQC programmes for HbA_1c.

Il coinvolgimento del medico curante e la ricerca delle crioglobuline nella gestione del paziente con sospetta componente monoclonale

Roberto Cesati, Silvia Besana, Pierluigi Tramacere
Laboratorio Patologia Clinica, Azienda Ospedaliera di Desio e Vimercate, Presidio Ospedaliero di Carate Brianza

Biochimica Clinica: 2010;34(3):207-211 [Article in italian]

ABSTRACT. The role of general practitioner and cryoglobulin testing in the evaluation of patients with suspected monoclonal band at electrophoresis. Serum protein electrophoresis (SPE) is the recommended laboratory test for the detection of monoclonal immunoglobulins (MC). When the general practitioner is informed of any MC not previously recorded in the laboratory database, for its characterization and for clinical evaluation of the monoclonal gammopathy, he can require four additional tests: serum immunoglobulin determination, immunofixation electrophoresis, detection of Bence Jones protein in urine and cryoglobulin characterization. In this study, over a period of 18 months, we tested the outcome of this approach in our setting. On 31,559 routine SPE, we detected 851 MC not previously known (2.7%). About 35% of the suspected MC were not further investigated, because the practitioner thought to stop investigations for several reasons, such as MC already known, patient aged or in critical conditions. 69 out of the remaining 551 patients (12.5%) were positive for cryoglobulins, mostly with low cryocrit, and were identified as subpopulation at risk for vasculitis. The engagement of the general practitioner and the cryoglobulin testing may represent an improvement in the clinical evaluation of the patient with newly detected MC.