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Biomedical subjects

C Falcone

Publications and source records attributed to C Falcone.

At least 19 recordsLinked to original sources

Markers of eosinophilic inflammation and risk prediction in patients with coronary artery disease.

BACKGROUND: The eotaxin family comprises three distinct peptides (eotaxin, eotaxin-2 and eotaxin-3) which have been implicated in eosinophilic inflammation. In vitro and clinical studies suggest that eotaxins could play a role in vascular inflammation, but no data are available on their prognostic significance in patients with angiographically documented coronary artery disease (CAD). MATERIALS AND METHODS: Baseline plasma samples were obtained from 1014 patients with documented CAD. We tested the predictive effect of markers of eosinophilic inflammation and C-reactive protein (CRP) on death from cardiovascular causes and nonfatal myocardial infarction over a 2.7-4.1-year follow-up period. RESULTS: Unexpectedly, lower eotaxin-3 concentrations were observed in patients with adverse cardiovascular events, whereas both eotaxin and eotaxin-2 showed no association with risk. After adjustment for most potential confounders, patients in the upper-quartile of eotaxin-3 levels had a 0.42 hazard-ratio (95% CI, 0.29-0.61, P < 0.001) for adverse events compared with subjects in the lower-quartile. The highest risk of future cardiovascular events was observed in subjects with combined elevation of CRP and reduction of eotaxin-3; 4.4 hazard-ratio (95% CI, 2.1-9.5, P < 0.001). Importantly, receiver-operating-characteristic curves analysis suggested a superior prognostic value of eotaxin-3 compared with CRP for predicting cardiac events in patients with CAD. CONCLUSIONS: Low levels of eotaxin-3 are an independent predictor of future adverse cardiovascular events in patients with CAD and may be useful for risk stratification.

Aged↗

Early carotid atherosclerosis in normotensive severe obese premenopausal women with low DHEA(S).

The aim of this study was to investigate the direct involvement of hyperinsulinaemia, DHEA and DHEA-S [DHEA(S)] in severe obesity in early carotid atherosclerosis, measured as intima-media thickness (IMT). Seventeen normotensive premenopausal women with very high BMI (43.5 +/- 1.6 kg/m2) were recruited for the study. Six women were also evaluated 12 months after laparoscopic adjustable silicone gastric banding (LASGB). Dietary intake, fasting plasma lipid profile, glycemic and insulinemic response to the OGTT, adrenal secretion, at baseline and after ACTH stimulation test, were measured. IMT, common carotid diameter (CD) and left ventricular mass index (LVMi) were measured by B-mode echotomography. All obese subjects showed higher fasting and stimulated insulin levels, but lower DHEA(S) levels than controls, showing a negative correlation between both fasting and stimulated insulin and DHEA(S), either at baseline or after ACTH testing. IMT was higher (p < 0.05) than controls, with a positive correlation with stimulated insulin (p < 0.05) and a strong negative correlation with DHEA(S) (p < 0.001). In a multiple linear regression analysis, insulin response to OGTT maintained an association with DHEA(S) independent of fasting insulin, while DHEA maintained the association with IMT independent of stimulated insulin (p < 0.0001). In the six patients evaluated 12 months after LASGB, fasting insulin levels decreased, while DHEA(S) levels increased (p < 0.05). In conclusion, an early cardiovascular involvement was detected in this group of severe obese with hyperinsulinaemia and low DHEA(S), even in the absence of other well known CVD risk factors.

Adult↗

Silent myocardial ischemia in diabetic and nondiabetic patients with coronary artery disease.

BACKGROUND: Patients with diabetes mellitus are at increased risk for CAD; silent ischemia is reported to be frequent in diabetic populations. The aim of the present study was to evaluate the prevalence of silent ischemia in diabetic and nondiabetic patients with assessed CAD. METHODS AND RESULTS: We recruited a total of 618 patients with CAD: 309 were consecutive diabetic patients and 309 were age- and gender-matched nondiabetic patients. Myocardial ischemia was evaluated both during daily life and during exercise testing. Angina pectoris during daily life was more frequent in diabetic than in nondiabetic patients (80% vs. 74%, P<0.05). The anginal pain intensity either during daily life or acute myocardial infarction (MI), the prevalence of a previous MI, the extent of CAD and ergometric parameters were similar in diabetics and nondiabetics. Silent ischemia during exercise was documented in 179 (58%) diabetics and in 197 (64%) nondiabetics (nonsignificant, ns). Both diabetics and nondiabetics with silent exertional myocardial ischemia differed from symptomatic subjects in higher heart rate values (P<0.01), systolic blood pressure (P<0.01), rate-pressure product (P<0.001), work load (P<0.01) and maximum ST-segment depression at peak exercise (P<0.05). CONCLUSIONS: The incidence of silent myocardial ischemia during exercise was similar in diabetic and nondiabetic CAD patients. Surprisingly, diabetics showed a higher prevalence of angina pectoris during daily activity than nondiabetics. A significant association between the presence of symptoms during daily life and exercise was observed in both groups. Our results may contribute to the planning of the clinical management of diabetic CAD patients and confirm the individual attitude to pain of CAD patients independent of the presence of diabetes.

Analysis of Variance↗

Reliability and validity of a modified gait scoring system and its use in assessing tibial dyschondroplasia in broilers.

1. The gait scoring system for broilers developed by Kestin et al. (Veterinary Record, 131: 190-194, 1992) has been widely used to evaluate leg problems. The many factors and measures associated with this scale have empirically established its external (biological) validity. However, published test-retest (within-observer) reliabilities are poor, and inter-observer reliabilities are unknown. We evaluated several modifications to this scale aimed at improving its objectivity and reliability. 2. Eighteen naïve observers scored a standardised video of birds exhibiting varying degrees of lameness, either using Kestin et al.'s system, or our modified system. 3. Test-retest reliability (0.906) for Kestin et al.'s system was higher than previously reported. Inter-rater reliability was also good (0.892). The modified system offered significantly better test-retest (0.948) and inter-rater reliabilities (0.943), without incurring costs in terms of time taken or difficulty of use. The systems were consistent, assigning individual birds the same score on average. 4. It is concluded that the modified system offers the advantages of reduced error within and between studies. 5. In a second experiment, we used our modified scoring system to examine the relationship between tibial dyschondroplasia (TD) and gait score in 267 selected broilers. 6. Neither the presence nor severity of TD affected gait score, suggesting that, at least in this strain of broilers, other leg problems like slipped tendons or torsional deformities had more influence on gait impairment than did TD.

Animals↗

Isolation and study of KlLSM4, a Kluyveromyces lactis gene homologous to the essential gene LSM4 of Saccharomyces cerevisiae.

We have isolated the KlLSM4 gene as a multicopy suppressor of a Kluyveromyces lactis mutant which shows a rag(-) phenotype (resistance to antimycin A on glucose). This gene is homologous to the ScLSM4 of Saccharomyces cerevisiae, which codes for an essential 187 amino acid protein containing Sm-like domains. These motifs are present in the evolutionarily conserved family of the Sm-like proteins, which are involved in a large number of cellular processes, including pre-mRNA splicing and mRNA decapping. We demonstrated that the first 72 amino acids of KlLsm4p, which contain the Sm-like domains, can restore cell viability in both K. lactis and S. cerevisiae cells lacking the wild-type protein. However, the absence of the carboxy-terminal region resulted in a remarkable loss of cell viability in the stationary phase. The KlLSM4 sequence has been deposited in the EMBL Data library under Accession No. AJ311719.

Amino Acid Sequence↗

Multiple unfolded states of alcohol dehydrogenase I from Kluyveromyces lactis by guanidinium chloride.

Inactivation, dissociation, and unfolding of tetrameric alcohol dehydrogenase I from Kluyveromyces lactis (KlADH I) were investigated using guanidinium chloride (GdmCl) as denaturant. Protein transitions were monitored by enzyme activity, intrinsic fluorescence and gel filtration chromatography. At low denaturant concentrations (less than 0.3 M), reversible transformation of enzyme into tetrameric inactive form occurs. At denaturant concentrations between 0.3 and 0.5 M, the enzyme progressively dissociates into structured monomers through an irreversible reaction. At higher denaturant concentrations, the monomers unfold completely. Refolding studies indicate that a total reactivation occurs only with the enzyme denatured between 0 and 0.3 M GdmCl concentrations. The enzyme denatured at GdmCl concentrations higher than 0.3 M refolds only partially. All together, our results indicate that unfolding of the KlADH I is a multistep process, i.e., inactivation of the structured tetramer, dissociation into partially structured monomers, followed by complete unfolding.

Alcohol Dehydrogenase↗

Increased production of inflammatory cytokines in patients with silent myocardial ischemia.

OBJECTIVES: The aim of the study was to examine the inflammatory cytokines in patients with myocardial ischemia to evaluate whether silent ischemia patients exhibit any particular cytokine pattern. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Various endogenous mechanisms control a patient's perceived intensity of pain. Among them, the inflammatory process and the related cytokine production are known to modulate the threshold for activating the primary afferent nociceptors. METHODS: Seventy-eight patients with reproducible exercise-induced myocardial ischemia were studied: 34 symptomatic patients, with rest and/or stress angina; 44 asymptomatic patients, with no symptoms during daily life activities or during positive exercise stress test. Venous blood samples were taken from all patients to evaluate the expression of CD11b receptors both on neutrophils and monocytes. Frozen plasma samples (at -80 degrees C) were used to quantify the anti-inflammatory (interleukin-4 and -10, transforming growth factor-beta) and the proinflammatory cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-1beta and -6). RESULTS: In asymptomatic patients lower CD11b receptor expression and higher concentration of anti-inflammatory cytokines were observed. Proinflammatory cytokine production was similar in the two groups. CONCLUSIONS: The data suggest that an "anti-inflammatory pattern" of cytokine production correlates with silent ischemia and that the immune and inflammatory system activation may be crucial for angina symptoms.

Aged↗

Association of lipoprotein(a) levels and apolipoprotein(a) phenotypes with coronary artery disease in Type 2 diabetic patients and in non-diabetic subjects.

AIMS: We investigated whether in Type 2 diabetic patients lipoprotein(a) (Lp(a)) levels and apolipoprotein(a) (apo(a)) polymorphism are associated with angiographically documented coronary artery disease (CAD). We also examined whether there are differences in the distributions of Lp(a) levels and apo(a) phenotypes between CAD patients with and without diabetes. METHODS: A hundred and seven diabetic patients with CAD, 274 diabetic patients without CAD, 201 non-diabetic patients with CAD, and 358 controls were enrolled. RESULTS: Diabetic patients with CAD showed Lp(a) levels (21.2 +/- 17.7 vs. 15.1 +/- 17.8 mg/dl; P = 0.0018) and a percentage of subjects with at least one apo(a) isoform of low molecular weight (MW) (67.2% vs. 27.7%; P = 0.0000) significantly greater than diabetic patients without CAD. Multivariate analysis showed that in diabetic patients Lp(a) levels and apo(a) phenotypes were significantly associated with CAD; odds ratios (ORs) of high Lp(a) levels for CAD were 2.17 (1.28-3.66), while ORs of the presence of at least one apo(a) isoform of low MW were 5.35 (3.30-8.60). Lp(a) levels (30.2 +/- 23.7 vs. 21.2 +/- 17.7 mg/dl; P = 0.0005) and the percentage of subjects with at least one apo(a) isoform of low MW (87.0% vs. 67.2%; P = 0.0001) were significantly higher in CAD patients without than in those with diabetes. CONCLUSIONS: Our data suggest that Lp(a) levels and apo(a) phenotypes are independently associated with CAD in Type 2 diabetic patients; thus both these parameters may be helpful in selecting diabetic subjects at high genetic cardiovascular risk. However, Lp(a) levels and apo(a) polymorphism seem to be cardiovascular risk factors less important in diabetic than in non-diabetic subjects. Diabet. Med. 18, 589-594 (2001)

Apolipoproteins↗

Skeletal reconstruction with a free vascularized fibula graft associated to bone allograft after resection of malignant bone tumor of limbs.

Over the last twenty years, progress in diagnosis and in adjuvant therapy in the field of malignant bone tumor treatment has allowed for development of limb-saving surgical techniques after oncological excision. In this context, the use of vascularized fibula for transplantation represents an important instrument in the reconstruction of bone, either with or without allografts.Moreover, in pediatric cases, the vascularized transplant of the proximal fibula with its open physis allows for an adequate reconstruction of the bone loss and the possibility of conserving the growth potential of the segment. The purpose of this article is to illustrate the various reconstructive possibilities that the use of the combined graft technique (VFT plus allograft) offers in the treatment of large-scale bone loss. In our department from 1988 to 2000, 142 vascularized fibula transplants were performed in oncological cases. Surgical reconstruction was carried out on the tibia in 70 cases, on the femur in 40, on the humerus in 26 and on the radius in 6. Combined graft intercalary reconstructions were 92. In 22 pediatric cases the fibula was transplanted, including the proximal growing epiphysis in the graft; in two of these cases massive allograft was associated to the VFG. Because of its biological properties, the grafted vascularized fibula allowed for fast bone fusion at the level of the osteotomy. It has also demonstrated a tendency of progressive hypertrophy and osteointegration with the allograft, when used. In 22 pediatric cases, the fibula graft with the proximal epiphysis maintained its ability to grow. Unsuccessful outcomes caused by vascular, mechanical, or septic failure were equal to 8.2 %. The fibula graft in the reconstruction of bone loss secondary to oncological excision is a trustworthy and versatile technique.

Adolescent↗

Regulation of primary carbon metabolism in Kluyveromyces lactis.

In the recent past, through advances in development of genetic tools, the budding yeast Kluyveromyces lactis has become a model system for studies on molecular physiology of so-called "Nonconventional Yeasts." The regulation of primary carbon metabolism in K. lactis differs markedly from Saccharomyces cerevisiae and reflects the dominance of respiration over fermentation typical for the majority of yeasts. The absence of aerobic ethanol formation in this class of yeasts represents a major advantage for the "cell factory" concept and large-scale production of heterologous proteins in K. lactis cells is being applied successfully. First insight into the molecular basis for the different regulatory strategies is beginning to emerge from comparative studies on S. cerevisiae and K. lactis. The absence of glucose repression of respiration, a high capacity of respiratory enzymes and a tight regulation of glucose uptake in K. lactis are key factors determining physiological differences to S. cerevisiae. A striking discrepancy exists between the conservation of regulatory factors and the lack of evidence for their functional significance in K. lactis. On the other hand, structurally conserved factors were identified in K. lactis in a new regulatory context. It seems that different physiological responses result from modified interactions of similar molecular modules.

Journal Article↗

Isolation and molecular characterization of KlCOX14, a gene of Kluyveromyces lactis encoding a protein necessary for the assembly of the cytochrome oxidase complex.

The yeast Kluyveromyces lactis was mutagenized with ethyl methane sulphonate and mutants unable to grow on respiratory carbon sources were isolated. Functional complementation of one of these mutants led to the isolation of KlCOX14, a gene encoding a 64 amino acid protein which is the functional homologue of Saccharomyces cerevisiae Cox14p, a protein necessary for the assembly of the cytochrome oxidase holoenzyme (Glerum et al., 1995). The disruption of KlCOX14 resulted in the absence of the absorption bands relative to cytochromes a and a(3) and in the complete loss of respiratory activity. Klcox14 mutants display the typical phenotype of pet mutants and have a reduced growth rate. In addition, unlike the wild-type, Klcox14 mutants are able to grow by fermentation also in the presence of low glucose. The nucleotide sequence of KlCOX14 has been deposited in the EMBL databank with Accession No. AJ238801.

Alleles↗

Disruption of six novel genes from chromosome VII of Saccharomyces cerevisiae reveals one essential gene and one gene which affects the growth rate.

Six ORFs of unknown function located on chromosome VII of Saccharomyces cerevisiae were disrupted in two different genetic backgrounds, and the phenotype of the generated mutants was analysed. Disruptions of ORFs YGR256w, YGR272c, YGR273c, YGR275w and YGR276c were carried out using the disruption marker kanMX4 flanked by short homology regions, whereas ORF YGR255c was inactivated with a long flanking homology (LFH) disruption cassette (Wach et al., 1994). Tetrad analysis of the heterozygous disruptants revealed that ORF YGR255c, previously identified as COQ6 and encoding a protein involved in the biosynthesis of coenzime Q (Tzagoloff and Dieckmann, 1990), is an essential gene. The same analysis also revealed that sporulation of the ygr272cDelta heterozygous diploid produced two small colonies per ascus that were also G418-resistant, indicating that the inactivation of ORF YGR272c could result in a slower growth rate. This result was confirmed by growth tests of the haploid disruptants and by complementation of the phenotype after transformation with a plasmid carrying the cognate gene. No phenotypes could be associated to the inactivation of ORFs YGR256w, YGR273c, YGR275w and YGR276c. Two of these genes have recently been further characterized: ORF YGR255w, renamed RTT102, encodes a regulator of the Ty1-element transposition, whereas ORF YGR276c was found to encode the 70 kDa RNase H activity and was renamed RNH70 (Frank et al., 1999).

Chromosomes, Fungal↗

Increased expression of peripheral benzodiazepine receptors on leukocytes in silent myocardial ischemia.

OBJECTIVES: The purpose of this study was to evaluate benzodiazepine receptor expression on leukocytes from patients with symptomatic or silent myocardial ischemia. BACKGROUND: Silent myocardial ischemia is frequently observed in patients with coronary artery disease. Pain can be effectively controlled by various endogenous mechanisms. Benzodiazepines and their receptors play key roles in pain, in interactions with peptide opioids, in inflammation and in the response to stress. METHODS: The study group consisted of 57 patients with reproducible exercise-induced myocardial ischemia. The presence of a constant behavior in the anginal pain perception during both exercise-induced ischemia and daily life was the most important inclusion criterion. Venous blood samples were taken from all patients to evaluate the expression of peripheral benzodiazepine receptors by flow cytometry. The study cohort was classified into two groups: 24 patients who had anginal pain both at home and during the exercise stress test and 33 patients who were asymptomatic during both daily life and exercise-induced ischemia. RESULTS: Flow cytometry analysis showed increased expression of peripheral benzodiazepine receptors on all types of leukocytes in the asymptomatic patients. The difference was statistically significant for lymphocytes (p < 0.005), monocytes (p < 0.001) and granulocytes (p < 0.001). CONCLUSIONS: These data show that expression of peripheral benzodiazepine receptors was higher in patients with silent myocardial ischemia than in symptomatic patients.

Activities of Daily Living↗

[A cardiac embolic stroke due to malposition of the pacemaker lead in the left ventricle. A case report].

Misplacement of a permanent pacemaker lead has been described in several locations but rarely in the left ventricle. Less commonly, as described in our report, malposition may occur when the lead perforates the interatrial septum and extends across the left atrium and through the mitral valve into the left ventricle. The actual incidence of this pacemaker complication is unknown. Consequences may include perforation and systemic or cerebral thromboembolic events. We report the case of a patient with unintentionally misplaced left heart pacemaker lead admitted for neurological symptoms consistent with embolic stroke. The patient was on aspirin when symptoms occurred. The lead misplacement was not recognized at the time of implantation. Pacing threshold was normal. A 12-lead electrocardiogram showed right bundle branch block configuration paced complexes. By two-dimensional and transesophageal echocardiography, the pacemaker lead was carefully evaluated. The pacemaker lead crossed the interatrial septum, the left atrium, the mitral valve to be implanted in the left ventricular endocardium. To avoid the risk of future embolization, it was felt that the lead should be removed and right ventricular pacing established, once anticoagulation treatment was initiated. Successful percutaneous lead replacement was accomplished without sequelae. Measures to avoid lead misplacement are suggested.

Electrodes↗

Use of the KlADH4 promoter for ethanol-dependent production of recombinant human serum albumin in Kluyveromyces lactis.

KlADH4 is a gene of Kluyveromyces lactis encoding a mitochondrial alcohol dehydrogenase activity which is specifically induced by ethanol. The promoter of this gene was used for the expression of heterologous proteins in K. lactis, a very promising organism which can be used as an alternative host to Saccharomyces cerevisiae due to its good secretory properties. In this paper we report the ethanol-driven expression in K. lactis of the bacterial beta-glucuronidase and of the human serum albumin (HSA) genes under the control of the KlADH4 promoter. In particular, we studied the extracellular production of recombinant HSA (rHSA) with integrative and replicative vectors and obtained a significant increase in the amount of the protein with multicopy vectors, showing that no limitation of KlADH4 trans-acting factors occurred in the cells. By deletion analysis of the promoter, we identified an element (UASE) which is sufficient for the induction of KlADH4 by ethanol and, when inserted in the respective promoters, allows ethanol-dependent activation of other yeast genes, such as PGK and LAC4. We also analyzed the effect of medium composition on cell growth and protein secretion. A clear improvement in the production of the recombinant protein was achieved by shifting from batch cultures (0.3 g/liter) to fed-batch cultures (1 g/liter) with ethanol as the preferred carbon source.

Alcohol Dehydrogenase↗

Association between apolipoprotein(a) phenotypes and coronary heart disease at a young age.

OBJECTIVES: The purpose of this study was to investigate lipoprotein(a) [Lp(a)] levels and apolipoprotein(a) [apo(a)] phenotypes in relation to age of onset of coronary heart disease (CHD). BACKGROUND: Although Lp(a) levels have been extensively analyzed in relation to age of CHD, apo(a) phenotypes have not. METHODS: Three hundred and thirty-five consecutive CHD patients were enrolled and grouped according to their age of CHD onset (<45 years; 45 to 54 years; > or = 55 years). RESULTS: In each patient group Lp(a) levels were higher than in an age-matched control group, but among the patient groups no differences in Lp(a) levels were observed. Apolipoprotein(a) phenotype distributions showed significant differences between patients and age-matched control subjects. Among the patient groups the difference in percentage of subjects with two apo(a) isoforms of low molecular weight (MW) was highly significant (p < 0.001). Multivariate analysis showed that apo(a) phenotypes were the best predictors of early CHD (p < 0.000001). The age-specific odds ratios (ORs) of the presence of at least one apo(a) isoform of low MW for CHD declined with age; in particular apo(a) phenotypes had their highest predictive value in younger persons (OR: 14.62). The OR for the presence of two isoforms of low MW/presence of only isoforms of high MW was 40.88 in the younger age group, 27.17 in age group of 45 to 54 years and 15.83 in the older age group. CONCLUSIONS: The present article reports the first evidence of a strong independent association of apo(a) phenotypes with the age of onset of CHD. Thus, if our data are confirmed by larger studies, apo(a) phenotypes might be used together with Lp(a) levels as powerful genetic markers in assessing the actual risk of developing CHD at a young age.

Adult↗

Clinical and metabolic effects of different parenteral nutrition regimens in patients undergoing allogeneic bone marrow transplantation.

BACKGROUND: Nutrients may interfere with physiological and pathophysiologic mechanisms. The present study was aimed at evaluating whether the differences in the quality of energy substrates administered with total parenteral nutrition (TPN) after cytoreductive therapy may influence the clinical outcome of patients undergoing bone marrow transplantation (BMT). METHODS: Sixty-six consecutive allogeneic BMT patients with hematologic malignancies were randomized to receive either a glucose-based (100% glucose) or a lipid-based (80% lipid, using an omega-6 long-chain triacylglycerol emulsion + 20% glucose) TPN, providing 146.3 kJ/kg body weight, 1.4 g of protein/kg of body weight, administered from day +1 to day +15 after BMT. Time to engraftment (EGT), incidence of sepsis and metabolic complications (hyperglycemia and hypertriglyceridemia), incidence of acute graft-versus-host-disease (A-GVHD) and relapse, survival at 18 months, incidence of deaths for A-GVHD and relapse were evaluated. RESULTS: Six patients dropped out before completing the study period. Thirty-one patients in the glucose-based TPN group and 29 patients in the lipid-based TPN group were evaluated. The incidence of hyperglycemia was significantly lower in the lipid-based TPN group than in the glucose-based TPN group (3.4% vs. 32%, respectively; P=0.004). Five patients in the glucose group and none in the lipid group died for A-GVHD (P<0.05). Survival at 18 months tended to be higher in the lipid group than in the glucose group (62% vs. 42%, P=NS). Rate of bone-marrow EGT, time to EGT, incidence of sepsis and fungal infections during TPN, incidence of A-GVHD, and rate of relapse at 18 months were not different in the two groups. CONCLUSIONS: The results obtained suggest that the use of lipid-based TPN after allogeneic BMT is associated with lower incidence of lethal A-GVHD and hyperglycemia, without negatively affecting the EGT of infused cells. Intravenously administered lipids might have influenced the severity of A-GVHD likely via modulation of immune response and synthesis of cytokines, prostaglandins, and leukotrienes that participate in the pathogenesis of graft-versus-host disease.

Adolescent↗

Apolipoprotein(a) phenotypes as genetic markers of coronary atherosclerosis severity.

We investigated Lp(a) levels and apo(a) polymorphism in relation to the severity of coronary artery disease, expressed both by the number of coronary arteries stenosed and three different coronary scoring systems. In a sample of 267 patients with coronary artery disease, a Mono-, Bi- or Multi-vessel coronary stenosis was documented by angiography. Twenty-five apo(a) isoforms were detected by a high resolution phenotyping method. Lp(a) levels did not show any differences among subgroups of patients. Both the percentage of apo(a) isoforms of low molecular weight (<655 kDa) (P=0.00015) and the percentage of subjects with at least one apo(a) isoform of low molecular weight (P=0.00027) were significantly correlated with increasing number of coronary vessels stenosed. In multivariate analysis, only apo(a) isoforms of low molecular weight were predictors of coronary atherosclerosis severity, when we used as the dependent variable both the '1-2-multi-vessels' categorization (P=0.000067) and the Gensini (P=0.008767), or Green Lane (P= 0.000001) or Dahlen (P=0.000102) coronary scoring system. Our data show that apo(a) isoforms of low molecular weight are associated with a greater severity of coronary atherosclerosis. If these data are confirmed by prospective studies, apo(a) phenotypes might be used as genetic markers of a greater severity of coronary atherosclerotic lesions.

Analysis of Variance↗