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Aims of our study were to evaluate the prevalence of high lipoprotein (a)[Lp(a)] and homocysteine levels– both in the fasting state (FHcy) and post-methionine (PMHcy)– in young coronary artery disease (CAD) patients, and to investigate the role of genetic and environmental factors for hyperhomocysteinaemia.We studied 140 patients with angiographically documented CAD (24 women≤ 55 years and 116 men≤ 50 years) and 140 healthy subjects as controls.Both FHcy[13·2 (5·4–45·8) vs. 9·0 (5·1–24)µmol L−1);P < 0·0001] and PMHcy[(39·4 (9·0–66·4) vs. 25·2 (16·4–33·9);P < 0·0001] were significantly higher in patients than in controls. Lp(a) levels were significantly higher in patients than in controls (200 (3–1486) mg L−1 vs. 97 (10–412) mg L−1;P < 0·0001). At the multivariate analysis, adjusted for the classical cardiovascular risk factors and creatinine levels, the OR (95% CI) for CAD at young age significantly increased in the fourth quartile of the distribution of FHcy, PMHcy and Lp(a) levels[FHcy: 14·9 (4·1–58),P < 0·0001; PMHcy: 19·2 (4·0–86·3);P < 0·0001; Lp(a): 19·6 (4·7–78·6):< 0·0001]. Vitamin deficiencies were detected in 28/140 (20%) patients. The prevalence of the homozygous C677T (+/+) methylenetetrahydrofolatereductase genotype was higher, but not significantly different, in patients (22·8%) than in controls (18·6%). The allele frequency of the 844ins68 insertion variant in the cystathionine beta-synthase gene was 0·08 in the control group and 0·06 in the patient group.Results of the present study indicate the usefulness of including fasting and post-methionine Hcy, and Lp(a) determination in the diagnostic panels of young CAD patients, in order to obtain a better assessment of their cardiovascular risk profile.Eur J Clin Invest 2005; 35 (1): 1–7 [ABSTRACT FROM AUTHOR]

Abstract Background The renin angiotensin system affects haemostasis through different mechanisms; data on the possible role of angiotensin-converting enzyme I/D polymorphism in the pathogenesis of deep venous thrombosis are conflicting, and no information is available regarding the A1166C polymorphism of the angiotensin type 1 receptor gene. In order to investigate this issue, angiotensin-converting enzyme and AT1R polymorphisms were genotyped in 336 consecutive venous thromboembolism patients and 378 controls. Materials and methods Haemostasis-related risk factors have been evaluated by routine tests. Factor V Leiden, Factor II (G20210A), angiotensin-converting enzyme (I/D), and angiotensin type 1 receptor (A1166C) polymorphisms have been identified by molecular analysis. Results We documented a significant association between angiotensin-converting enzyme DD genotype and venous thromboembolism (OR = 2·19 95%CI 1·51–3·17 adjusted for acquired and haemostasis-related risk factors, P < 0·0001); in patients with haemostasis-related risk factors, angiotensin-converting enzyme DD genotype modified the risk of venous thromboembolism in hyperhomocysteinaemic and Factor V Leiden patients and was associated with the risk of recurrent venous thromboembolism (OR = 1·83 95%CI 1·06–3·17 P = 0·03). In patients without haemostasis-related risk factors the angiotensin-converting enzyme DD genotype was still an independent predictor of venous thromboembolism (OR = 3·29 95%CI 2·17–4·98 adjusted for acquired risk factors, P < 0·0001). No significant association between the angiotensin type 1 receptor CC genotype and venous thromboembolism was found. Conclusions This study shows that angiotensin-converting enzyme DD genotype represents a susceptibility marker of thrombosis in subjects apparently without predisposing factors and traditional thrombophilic alterations, and increases the risk of venous... [ABSTRACT FROM AUTHOR]

Marfan syndrome (MFS) is a multisystemic disease associated with mutations in the fibrillin-1 gene. Most of the reported mutations are missense substitutions mainly affecting the epidermal growth factor (EGF)-like protein domain structure and the calcium-binding (cb) site. The aim of our study was to investigate the correlation between fibrillin-1 frameshift mutations and the clinical phenotype in patients affected by MFS. In 48 out of 66 Marfan patients a pathogenetic mutation was found. We detected novel mutations causing premature termination codon in exons 19, 37, 40 and 41 of four Italian patients. The first mutation in exon 19 (cbEGF #8 domain) results in a clinical phenotype involving mainly the skeletal and cardiovascular systems. Interestingly, we noticed that, while mutations in exons 37 and 41 (eight cysteine domains #4 and #5) are milder, the mutation in exon 40 (cbEGF #24 domain) is more severe and causes major cardiovascular involvement with thoracic and abdominal aortic aneurysms. It is noteworthy that the degree of the severity in the phenotype of one of our patients and another from the literature carrying a mutation in exon 41 could be explained with alterations in mRNA expression. [ABSTRACT FROM AUTHOR]

The early onset of atherosclerosis and the involvement of physiological biochemical, and environmental factors in its pathogenesis is well documented. Few data are available on the role of risk factors related to hemostasis in the pathogenesis of atherosclerosis in the young and, in particular, little information is available on adolescent populations. In the Study of Preventive Medicine and Education Program (Floren-teen Study), von Willebrand factor, a risk factor for cardiovascular disorder, was studied, together with classical cardiovascular risk factors, in apparently healthy students from two high schools in Florence. Familial and personal history, physical examination, and cardiovascular risk factors were evaluated in 144 students (aged 17–19 years). Blood was withdrawn to assess von Willebrand factor (ELISA) and lipid parameters. Levels of von Willebrand factor were significantly higher ( P<0.044) in smokers than in nonsmokers and were correlated with the number of cigarettes per day in the whole group ( P=0.01) and in females ( P=0.006). In females a positive correlation was observed between von Willebrand factor and high-density lipoprotein cholesterol ( P=0.0365). There was no significant correlation between von Willebrand factor and blood pressure or between von Willebrand factor and physical activity. In conclusion, this study shows an association between levels of von Willebrand factor and smoking habits and is the first show that even a brief period of smoking affects levels of von Willebrand factor in healthy adolescent females independently of other risk factors. These results stress the relevance of extending prevention programs to reduce smoking in high school students. [ABSTRACT FROM AUTHOR]

The acute-phase response is the answer of the organism to a disturbance of its homeostasis and is characterized by dramatic changes in the concentration of some plasma proteins defined as acute-phase proteins. In recent years several data have shown that interleukin-6 (IL-6) is the major inducer of acute-phase protein synthesis in human hepatocytes. Recently, we demonstrated higher IL-6 serum levels in head and neck cancer (HNC) patients than in healthy subjects. In the present study we examined the relationship between levels of IL-6 and of several acute-phase proteins, including C-reactive protein (CRP), α-antitrypsin (AAT), α-acid glycoprotein (AAG), haptoglobin (HPT) and fibrinogen. Eighteen patients were studied and had squamous cell carcinoma of the larynx ( n = 9), oral cavity ( n = 4), oropharynx ( n = 3) and hypopharynx ( n = 2). Proteins were measured at three time points before and three time points after surgery. Significant ( P < 0.0001) relationships were found between IL-6 and CRP ( r = 0.69), and fibrinogen ( r = 0.51), whereas no correlation was found with AAT ( r = 0.13, P = 0.56), AAG ( r = 0.38; P = 0.07) and HPT ( r = 0.16; P = 0.46). These data strongly suggest that IL-6 may play a key role in acute-phase protein synthesis in HNC and in regulation of the complex host response to malignancies. [ABSTRACT FROM AUTHOR]

Mild hyperhomocysteinemia is associated to mutations either in cystathionine ß-synthase (CBS) or in 5,10-methylenetetrahydrofolate reductase (MTHFR) genes. In 1995, Sebastio et al. characterized a 68 bp insertion in cis with the most common CBS mutation (T833C) detected in homocystinuric patients. Recently, this double mutation has been detected in Italian and North-American controls. Compared to a group of patients affected by coronary artery disease, North-American controls showed not statistically significant difference. Moreover, Italian controls displayed a microheterogeneity in the mutant allele frequency distribution depending on their geographical origin (North or South of Italy). Aim of our study was to evaluate the prevalence of the double in cis mutation in different populations. We studied 377 healthy subjects belonging to various human groups. Genomic DNA, extracted from peripheral blood samples, was amplified using specific primers; PCR fragments were digested with Bsr I restriction enzyme to detect the double mutation. Our data show a significant heterogeneity among the populations studied, therefore this mutation turned out to be a reliable anthropogenetic marker. The distribution of the double mutation will contribute, with other DNA polymorphisms, to evaluate the genetic admixture of mixed populations such as Afro-Americans [ABSTRACT FROM AUTHOR]