Understanding Cancer Screening Intention Among Physically Active Adults Ages 18-49.

Ideal efforts for cancer prevention would include lifestyle modifications along with routine, age-eligible cancer screening. Employing an asset-based approach within vulnerable populations already engaging in at least one healthy behavior (i.e., physical activity) may be an ideal way to further reduce cancer risk across peer groups with low cancer screening rates. Guided by the theory of planned behavior (TPB), the aim of this study was to identify constructs associated with cancer screening intentions among young to middle aged adults for influencing educational and behavioral interventions designed to promote cancer prevention. A cross-sectional, web-based survey was utilized to assess attitudes, subjective norms, perceived behavioral control, and intention to screen for cancer among physically active adults aged 18-49 years. Descriptive and bivariate analyses were conducted to characterize the sample, and hierarchical linear regression analyses were conducted to assess the influence of sociodemographic variables and TPB constructs on cancer screening intentions. Age, female sex, reporting a routine doctor's visit, reported knowledge of physical activity as a lifestyle behavior to reduce cancer risk, and an increased number of motivating factors for engaging in physical activity were significantly associated with higher cancer screening intention (P < 0.001). With the addition of TPB constructs (i.e., subjective norms and perceived behavioral control), the final analytic model accounted for 31% of the variance in intention to screen for cancer. Findings suggest that the TPB could be used to tailor or design asset-based, cancer education interventions to effectively promote age-eligible cancer screenings among physically active adults. Educational content to increase social support for cancer screening and enhance perceived behavioral control to complete screening is essential in this population.

Risk factors for prehypertension in the community: a prospective analysis from the Western New York Health Study.

BACKGROUND AND AIM: Prehypertension is an increasingly highly prevalent condition in the general population, and is associated with an increased risk for coronary heart disease and stroke. However, evidence from population-based studies of the risk factors for prehypertension is scant. We sought to examine the predictors of progression from normotension to prehypertension in a community-based population from Western New York. METHODS AND RESULTS: A longitudinal analysis, over 6 years of follow-up, among 569 men and women (mean age 51.8 years) who were free of prehypertension, hypertension, cardiovascular disease and diabetes at the baseline examination, in the Western New York Health Study (WNYHS). Incident prehypertension at follow-up was defined as systolic blood pressure of 120-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg. The cumulative six year incidence of prehypertension was 33.5% (189/564). In bivariate analyses, there were several correlates of incident prehypertension, including age, BMI and waist circumference, impaired fasting glucose (IFG), uric acid, and baseline blood pressure levels. After multivariate adjustment, IFG at baseline [odds ratio (OR): 1.70, 95% CI: 1.07-2.69) and weight gain since age 25 (OR: 1.12, 1.04-1.21 per 10 lb increase)] were the strongest significant predictors of prehypertension at follow-up. Neither baseline waist circumference nor change in BMI were predictor variables in models when they were substituted for weight gain. CONCLUSIONS: Results from this study suggest early dysregulation of glucose metabolism and weight gain over the lifespan may represent important risk factors for prehypertension in the general population.

Factors Affecting Perceptual Threshold in Argus II Retinal Prosthesis Subjects.

PURPOSE: The Argus II epiretinal prosthesis has been developed to provide partial restoration of vision to subjects blinded from outer retinal degenerative disease. Participants were surgically implanted with the system in the United States and Europe in a single arm, prospective, multicenter clinical trial. The purpose of this investigation was to determine which factors affect electrical thresholds in order to inform surgical placement of the device. METHODS: Electrode-retina and electrode-fovea distances were determined using SD-OCT and fundus photography, respectively. Perceptual threshold to electrical stimulation of electrodes was measured using custom developed software, in which current amplitude was varied until the threshold was found. Full field stimulus light threshold was measured using the Espion D-FST test. Relationships between electrical threshold and these three explanatory variables (electrode-retina distance, electrode-fovea distance, and monocular light threshold) were quantified using regression. RESULTS: Regression analysis showed a significant correlation between electrical threshold and electrode-retina distance (R2 = 0.50, P = 0.0002; n = 703 electrodes). 90.3% of electrodes in contact with the macula (n = 207) elicited percepts at charge densities less than 1 mC/cm2/phase. These threshold data also correlated well with ganglion cell density profile (P = 0.03). A weaker, but still significant, inverse correlation was found between light threshold and electrical threshold (R2 < 0.52, P = 0.01). Multivariate modeling indicated that electrode-retina distance and light threshold are highly predictive of electrode threshold (R2 = 0.87; P < 0.0005). CONCLUSIONS: Taken together, these results suggest that while light threshold should be used to inform patient selection, macular contact of the array is paramount. TRANSLATIONAL RELEVANCE: Reported Argus II clinical study results are in good agreement with prior in vitro and in vivo studies, and support the development of higher-density systems that employ smaller diameter electrodes. (clinicaltrials.gov identifier: NCT00407602).

Clinical utility of kallikrein-related peptidases (KLK) in urogenital malignancies.

Kallikrein-related peptidases (KLK), which represent a major tissue-associated proteolytic system, stand for a rich source of biomarkers that may allow molecular classification, early diagnosis and prognosis of human malignancies as well as prediction of response or failure to cancer-directed drugs. International research points to an important role of certain KLKs in female and male urogenital tract malignancies, in addition to cancers of the lung, brain, skin, head and neck, and the gastrointestinal tract. Regarding the female/male urogenital tract, remarkably, all of the KLKs are expressed in the normal prostate, testis, and kidney whereas the uterus, the ovary, and the urinary bladder are expressing a limited number of KLKs only. Most of the information regarding KLK expression in tumour-affected organs is available for ovarian cancer; all of the 12 KLKs tested so far were found to be elevated in the malignant state, depicting them as valuable biomarkers to distinguish between the normal and the cancerous phenotype. In contrast, for kidney cancer, a series of KLKs was found to be downregulated, while other KLKs were not expressed. Evidently, depending on the type of cancer or cancer stage, individual KLKs may show characteristics of a Janus-faced behaviour, by either expanding or inhibiting cancer progression and metastasis.

Circulating biomarker tissue kallikrein-related peptidase KLK5 impacts ovarian cancer patients' survival.

BACKGROUND: Effective cancer biomarkers for early detection, prognosis, or therapy response prediction are urgently needed in ovarian cancer. Kallikrein-related peptidases, including KLK5, have been reported to play an important role in the course of the disease. PATIENTS AND METHODS: KLK5 antigen content was determined by enzyme-linked immunosorbent assay in ovarian cancer patients' [FIGO (International Federation of Gynecology and Obstetrics) stages I-IV, n = 52] serum as well as ascitic fluid and compared with KLK5 content in serum of patients with benign ovarian tumors (n = 45). RESULTS: KLK5 antigen content was significantly elevated in the serum of ovarian cancer patients compared with the serum of patients with benign ovarian tumors. Forty-two of 52 ovarian cancer serum samples, 42 of 43 benign ovarian tumor serum samples, and all 41 ascitic fluid samples were KLK5 positive. Elevated KLK5 antigen in serum and ascitic fluid of ovarian cancer patients was a prognostic factor for progression-free survival. CONCLUSIONS: Our data support the finding that ovarian cancer patients release significant amounts of KLK5 into serum and ascitic fluid but KLK5 antigen is low in serum of patients with benign ovarian tumors. Increased serum and ascitic fluid KLK5 levels are associated with poor patient outcome, thus underlining the importance of KLK5 as a biomarker for early detection as well as for disease management in ovarian cancer.

Impact of expression differences of kallikrein-related peptidases and of uPA and PAI-1 between primary tumor and omentum metastasis in advanced ovarian cancer.

BACKGROUND: Primary tumor levels of serine proteases of the kallikrein-related peptidases (KLK) family as well as urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1 impact disease course in ovarian cancer. The changes in levels of these factors from primary tumor to omentum metastasis ('level differentials') could thus be associated with metastastic processes. PATIENTS AND METHODS: Protein levels of seven tissue KLK (KLK5-8, 10, 11, 13), uPA, and PAI-1 were determined in extracts of primary tumor tissue and corresponding omentum metastasis of 54 ovarian cancer patients. RESULTS: Higher level differentials of KLK5-8, 10-11, and uPA were associated with residual tumor >10 mm. Residual tumor and larger level differentials of KLK5-7, 10, and uPA were associated with disease progression in the whole cohort. Remarkably, level differentials of KLK5-8 and 10-11 strongly impacted disease progression even in patients with residual tumor mass ≤10 mm; hence, the observed impact of level differentials in KLK5-7 and 10 on disease progression was not simply attributable to their association with surgical success. CONCLUSION: Since they impact both surgical outcome and survival in advanced ovarian cancer, measurement of level differentials could support clinical decisions on surgical and systemic therapy or help in patient selection for novel targeted therapies.

Blind subjects implanted with the Argus II retinal prosthesis are able to improve performance in a spatial-motor task.

BACKGROUND/AIMS: To determine to what extent subjects implanted with the Argus II retinal prosthesis can improve performance compared with residual native vision in a spatial-motor task. METHODS: High-contrast square stimuli (5.85 cm sides) were displayed in random locations on a 19″ (48.3 cm) touch screen monitor located 12″ (30.5 cm) in front of the subject. Subjects were instructed to locate and touch the square centre with the system on and then off (40 trials each). The coordinates of the square centre and location touched were recorded. RESULTS: Ninety-six percent (26/27) of subjects showed a significant improvement in accuracy and 93% (25/27) show a significant improvement in repeatability with the system on compared with off (p<0.05, Student t test). A group of five subjects that had both accuracy and repeatability values <250 pixels (7.4 cm) with the system off (ie, using only their residual vision) was significantly more accurate and repeatable than the remainder of the cohort (p<0.01). Of this group, four subjects showed a significant improvement in both accuracy and repeatability with the system on. CONCLUSION: In a study on the largest cohort of visual prosthesis recipients to date, we found that artificial vision augments information from existing vision in a spatial-motor task. Clinical trials registry no NCT00407602.

Polymorphisms in the platelet-specific collagen receptor GP6 are associated with risk of nonfatal myocardial infarction in Caucasians.

BACKGROUND AND AIMS: Glycoprotein 6 (GP6) is a platelet-specific collagen receptor implicated in the thrombotic pathway to acute myocardial infarction (AMI), but a possible genetic relationship between GP6 and AMI is poorly understood. We tested for the genetic association between AMI and single nucleotide polymorphisms (SNPs) in 24 loci, including GP6. METHODS AND RESULTS: We conducted a case-control study of AMI and GP6 in a community-based population (n = 652 cases, 625 controls). We also examined men and women separately and stratified the latter by use of hormone replacement therapy (HRT). Among both sexes, the strongest association was for a protective missense polymorphism (rs1163662) in the GP6 gene (OR = 0.70; Bonferroni-adjusted p < 0.05). SNPs in GP6 were also strongly associated with AMI among women who reported ever taking HRT, but not among women who never took HRT. Haplotype analyses were consistent with the single-SNP findings. CONCLUSIONS: In this sample of white non-Hispanic men and women, several SNPs in GP6 were significantly related to risk of AMI. Development of pharmacologic therapy directed towards platelet activity and thrombosis may reduce the incidence of AMI among at-risk groups.

Impaired fasting glucose and recurrent cardiovascular disease among survivors of a first acute myocardial infarction: evidence of a sex difference? The Western New York experience.

BACKGROUND AND AIMS: There is little epidemiological evidence regarding the association of impaired glucose metabolism with recurrent cardiovascular events. We therefore examined potential sex differences in the effect of impaired fasting glucose (IFG) on recurrent cardiovascular disease (CVD) in a community-based study of survivors of a first acute myocardial infarction (MI). METHODS AND RESULTS: This report focuses on 1226 incident MI cases (28.4% women) discharged alive from area hospitals in the Western New York Acute MI Study (1996-2004). Deaths and underlying cause of death were determined via query of the National Death Index (Plus) Retrieval Program with follow-up through December 31, 2004. Outcomes reported included fatal or non-fatal coronary heart disease (CHD) or coronary revascularization surgery and total stroke. Traditional CHD risk factors and other explanatory variables were determined by clinical examination after the first acute event. Impaired fasting glucose was defined as fasting blood glucose between 100 and 125mg/dl. During a mean follow-up of 4.5 years, there were 91 recurrent events (26.1%) in women and 173 recurrent events (19.7%) in men. After multivariable adjustment, the hazard ratios for recurrent cardiovascular events were 1.96 (95% CI: 1.15-3.16) and 2.59 (1.56-4.30) in women with IFG and with diabetes, respectively, compared to normoglycemic women. Among men, neither IFG nor diabetes was independently related to risk of recurrence. CONCLUSIONS: In this study, IFG was a strong risk factor for recurrent cardiovascular events only among women. These results suggest that increased cardiovascular risk in MI survivors begins at lower glucose levels in women than men.

Tissue factor gene polymorphisms and haplotypes and the risk of ischemic vascular events: four studies and a meta-analysis.

OBJECTIVE: The exposure of tissue factor (TF) to blood flow is the initial step in the coagulation process and plays an important role in thrombogenesis. We investigated the role of genetic polymorphisms and haplotypes of the TF gene in the risk of ischemic vascular disease. METHODS: Four hundred and twenty-two Italian patients with juvenile myocardial infarction (MI) and 434 controls, 808 US cases with MI and 1005 controls, 267 Italian cases with juvenile ischemic stroke and 209 controls and 148 German cases with juvenile ischemic stroke and 191 controls were studied. rs1361600, rs3917629 (rs3354 in the US population), rs1324214 and rs3917639 Tag single nucleotide polymorphisms were genotyped. Additionally, a meta-analysis of all previous studies on TF loci and the risk of ischemic coronary disease (ICD) was performed. RESULTS: After multivariable analysis none of the SNPs, major SNP haplotypes or haplotype-pairs showed any consistent association with MI. Pooled meta-analysis of six studies also suggested that TF polymorphisms are not associated with CHD. A significant, independent association between SNP rs1324214 (C/T) and juvenile stroke was found in Italian and German populations (OR for TT homozygotes = 0.47, 95% CI 0.24-0.92, in combined analysis). Pooled analysis also showed a significant association for haplotype H3 (OR = 0.76, 95% CI 0.57-1.00) and haplotype-pair H3-H3 (OR = 0.43, 95% CI 0.20-0.92). CONCLUSIONS: TF genetic variations were associated with the risk of ischemic stroke at young age, but did not affect ischemic coronary disease.

Drinking habits and health in Northern Italian and American men.

BACKGROUND AND AIM: The aim of this study was to investigate alcohol drinking habits in two male cohorts, one Italian and one American, and to investigate whether cardiovascular disease risk factors are related to different drinking patterns. Furthermore, socio-demographic characteristics were taken into account. METHODS: The Italian sample was drawn from the National Alpines Association. A dietary questionnaire was sent to the members of this association as an additional supplement to their monthly magazine. Eleven thousand one hundred and thirty-four men, 18-94 years, from Northern Italy were included in this analysis. The American sample is part of the Western New York Health Study (WNYHS) including 1927 male participants. RESULTS: In both populations, those who drank more than 4 drinks/day were the least educated and showed the highest percentage of current smokers; the highest prevalence of hypertension occurred in heavier drinkers and those who mostly drank without food. By contrast, lifetime abstainers exhibited the lowest percentage of hypertension and the highest level of serum cholesterol; in both populations the highest prevalence of diabetes was present in lighter drinkers. CONCLUSIONS: The current study shows that drinking habits are quite different in the two countries and are basically linked with socio-demographic and behavioral variables and support the notion that excess volume of alcohol consumed, and drinking without food, are associated with a higher risk of hypertension and hyperlipidaemia, particularly for Italians.

Estimation of the maximum flow-mediated brachial artery response using local regression methods.

We consider methods for estimating the maximum from a sequence of measurements of flow-mediated diameter of the brachial artery. Flow-mediated vasodilation (FMD) is represented using the maximum change from a baseline diameter measurement after the release of a blood pressure cuff that has been inflated to reduce flow in the brachial artery. The influence of the measurement error on the maximum diameter from raw data can lead to overestimation of the average maximum change from the baseline for a sample of individuals. Nonparametric regression models provide a potential means for dealing with this problem. When using this approach, it is necessary to make a judicious choice of regression methods and smoothing parameters to avoid overestimation or underestimation of FMD. This study presents results from simulation studies using kernel-based local linear regression methods that characterize the relationship between the measurement error, smoothing and bias in estimates of FMD. Comparisons between fixed or constant smoothing and automated smoothing parameter selection using the generalized cross validation (GCV) statistic are made, and it is shown that GCV-optimized smoothing may over-smooth or under-smooth depending on the heart rate, measurement error and measurement frequency. We also present an example using measured data from the Buffalo Cardio-Metabolic Occupational Police Stress (BCOPS) pilot study. In this example, smoothing resulted in lower estimates of FMD and there was no clear evidence of an optimal smoothing level. The choice to use smoothing and the appropriate smoothing level to use may depend on the application.

Phenotypic clustering of yeast mutants based on kinetochore microtubule dynamics.

MOTIVATION: Kinetochores are multiprotein complexes which mediate chromosome attachment to microtubules (MTs) of the mitotic spindle. They regulate MT dynamics during chromosome segregation. Our goal is to identify groups of kinetochore proteins with similar effects on MT dynamics, revealing pathways through which kinetochore proteins transform chemical and mechanical input signals into cues of MT regulation. RESULTS: We have developed a hierarchical, agglomerative clustering algorithm that groups Saccharomyces cerevisiae strains based on MT-mediated chromosome dynamics measured by high-resolution live cell microscopy. Clustering is based on parameters of autoregressive moving average (ARMA) models of the probed dynamics. We have found that the regulation of wildtype MT dynamics varies with cell cycle and temperature, but not with the chromosome an MT is attached to. By clustering the dynamics of mutants, we discovered that the three genes IPL1, DAM1 and KIP3 co-regulate MT dynamics. Our study establishes the clustering of chromosome and MT dynamics by ARMA descriptors as a sensitive framework for the systematic identification of kinetochore protein subcomplexes and pathways for the regulation of MT dynamics. AVAILABILITY: The clustering code, written in Matlab, can be downloaded from http://lccb.scripps.edu. ('download' hyperlink at bottom of website). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Yeast kinetochore microtubule dynamics analyzed by high-resolution three-dimensional microscopy.

We have probed single kinetochore microtubule (k-MT) dynamics in budding yeast in the G1 phase of the cell cycle by automated tracking of a green fluorescent protein tag placed proximal to the centromere on chromosome IV and of a green fluorescent protein tag fused to the spindle pole body protein Spc42p. Our method reliably distinguishes between different dynamics in wild-type and mutant strains and under different experimental conditions. Using our methods we established that in budding yeast, unlike in metazoans, chromosomes make dynamic attachments to microtubules in G1. This makes it possible to interpret measurements of centromere tag dynamics as reflecting k-MT dynamics. We have examined the sensitivity of our assay by studying the effect of temperature, exposure to benomyl, and a tubulin mutation on k-MT dynamics. We have found that lowering the temperature and exposing cells to benomyl attenuate k-MT dynamics in a similar manner. We further observe that, in contrast to previous reports, the mutant tub2-150 forms k-MTs that depolymerize faster than wild type. Based on these findings, we propose high-resolution light microscopy of centromere dynamics in G1 yeast cells as a sensitive assay for the regulation of single k-MT dynamics.

Oxidative stress and glucose levels in a population-based sample.

OBJECTIVES: To examine the relationship between markers of oxidative status and glucose on a population basis. STUDY DESIGN AND SETTING: We report here on a population-based sample of 1315 women and 981 men, aged 35-79 years, randomly selected from residents of Erie and Niagara Counties in western New York between 1996 and 1999. Thiobarbituric reactive substances (TBARS), erythrocyte glutathione (GSH) and plasma glutathione peroxidase (GSH-Px) were measured as markers of oxidative status. Study sample was categorized by quartiles of glucose, degree of abnormality of fasting glucose, and level of metabolic control in patients with diabetes. RESULTS: Men and women in the uppermost quartiles of glucose had higher levels of TBARS (men: Quartile 4 = 1.55 +/- 0.03, Quartile 1 = 1.36 +/- 0.03, women: 1.49 +/- 0.02, 1.30 +/- 0.02 nmol/ml) and lower levels of GSH (men: Quartile 4 = 1.57 +/- 0.03, Quartile 1 = 1.69 +/- 0.03, women: 1.71 +/- 0.03, 1.97 +/- 0.0 mmol/l packed RBCs). In women, compared with normal fasting glucose, impaired fasting glucose was associated with higher levels of TBARS (1.29 +/- 0.01 vs. 1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.85 +/- 0.02 vs. 1.76 +/- 0.05 mmol/l packed RBCs), and higher GSH-Px activity (618.94 +/- 2.64 vs. 644.77 +/- 8.90 IU/l). In women, abnormal fasting glucose was associated with higher levels of TBARS (1.84 +/- 0.04 nmol/ml), lower levels of GSH (1.68 +/- 0.06 mmol/l packed RBCs), and higher levels of GSH-Px (647.72 +/- 9.87 IU/l) than normal or impaired fasting glucose. In men, abnormal fasting glucose was associated with higher TBARS (1.76 +/- 0.04 vs. 1.37 +/- 0.07 nmol/ml), and lower GSH (1.62 +/- 0.05 vs. 2.78 +/- 0.02 mmol/l packed RBCs), than normal fasting glucose. Poor metabolic control was associated with higher TBARS (men: 2.07 +/- 0.08 vs. 1.33 +/- 0.14 nmol/l, women: 2.02 +/- 0.09 vs. 1.35 +/- 0.18 nmol/l) and GSH-Px activity (men: 654.34 +/- 13.45 vs. 599.86 +/- 24.76, women: 660.61 +/- 13.25 vs. 579.42 +/- 27.42 IU/l). CONCLUSIONS: Glucose levels play a role in determining oxidative status in a population sample. The balance between oxidative and antioxidant processes appears to be sensitive to glucose levels with moderate elevations of glucose affecting the oxidative status.

Automatic fluorescent tag localization II: Improvement in super-resolution by relative tracking.

We present an algorithm for the three-dimensional (3D) tracking of multiple fluorescent subresolution tags with super-resolution in images of living cells. Recently, we described an algorithm for the automatic detection of such tags in single frames and demonstrated its potential in a biological system. The algorithm presented here adds to the tag detector a module for relative tracking of the signals between frames. As with tag detection, the main problem in relative tracking arises when signals of multiple tags interfere. We propose a novel multitemplate matching framework that exploits knowledge of the microscope point spread function to separate the intensity contribution of each tag in image regions with signal interferences. We use this intensity splitting to reconstruct a template for each tag in the source frame and a patch in the target frame, which are both free of intensity contributions from other tag signals. Tag movements between frames are then tracked by seeking, for each template-patch pair, the displacement vector providing the best signal match in terms of the sum of squared intensity differences. Because template and patch generation of tags with overlapping signals are interdependent, the matching is carried out simultaneously for all tags, and in an iterative manner. We have examined the performance of our approach using synthetic 3D data and observed a significant increase in resolution and robustness as compared with our previously described detector. It is now possible to localize and track tags separated by a distance three times smaller than the Rayleigh limit with a relative positional accuracy of better than 50 nm. We have applied the new tracking system to extract metaphase trajectories of fluorescently tagged chromosomes relative to the spindle poles in budding yeast.

Increased carotid intima-media thickness in children-adolescents, and young adults with a parental history of premature myocardial infarction.

AIMS: The present study was designed to test whether early carotid structural changes are demonstrable (by high resolution B-mode ultrasound) in children, adolescents and young adults with a history of premature parental myocardial infarction. METHODS AND RESULTS: One hundred and fourteen healthy young (5 to 30 years) subjects with a parental history of premature myocardial infarction and 114 age- and sex-matched control subjects were enrolled in the study. They were divided into two age groups: children and adolescents (age 5 to 18 years) (54 individuals with a parental history of premature myocardial infarction and their control subjects; mean age 12.8+/-3.8 years) and young adults (age 19 to 30 years) (60 individuals with a parental history and their controls; mean age 23.8+/-3.3 years). All subjects underwent high resolution B-mode ultrasonographic evaluation of common carotid artery intima-media thickness. Lipid profile, resting blood pressure, body mass index and smoking status were also evaluated. In both age groups, compared to controls, subjects with a parental history of premature myocardial infarction had increased intima-media thickness of common carotid arteries (mean of combined sites: age 5-18 years: 0.45+/-0.076 mm vs 0.40+/-0.066 mm in controls, P=0.008; age 19-30 years: 0.48+/-0.077 mm vs 0.45+/-0.078 mm in controls,P =0.007) Offspring of coronary patients showed an unfavourable lipid profile, however, the association between a parental history of premature myocardial infarction and carotid intima-media thickness was independent of lipids, apolipoproteins and other traditional risk factors. CONCLUSIONS: Vascular structural changes associated with a parental history of premature myocardial infarction are already detectable in childhood and adolescence and occur independently of several traditional cardiovascular risk factors.

Minimal and best linear combination of oxidative stress and antioxidant biomarkers to discriminate cardiovascular disease.

BACKGROUND AND AIM: Free radicals have been implicated in the atherosclerotic process of coronary heart disease (CHD). Well-developed laboratory methods may make available a large number of biomarkers of individual oxidative stress and antioxidant status. Such markers are able to quantify different phases of the oxidative stress and antioxidant status of an individual. However, limited knowledge is available on how to combine these biomarkers to best discriminate between individuals with and without CHD. METHODS AND RESULTS: We evaluated combined discrimination properties of six biomarkers of oxidative stress and antioxidant status, as indicators of CHD, in a cross-sectional random sample of 968 white men and women from Buffalo, New York. Individuals with CHD had significantly higher levels of thiobarbuturic acid reacting substances (TBARS) and uric acid, and significantly lower levels of high-density lipoproteins (HDL) after adjusting for age and gender, when compared to healthy subjects. There were no significant differences in erythrocyte glutathione (GSH), trolox equivalent antioxidant capacity (TEAC), and glutathione peroxidase (GSHPx) levels. TBARS were found to be the best discriminating of the biomarkers when it was individually evaluated. TBARS discriminate 76.2% (95% C.I. 0.66-0.82) of the CHD cases from healthy controls. When combining TBARS, GSH, TEAC, HDL, uric acid and GSHPx, they discriminate 81.5% (95% C.I.: 0.67-0.90) of the area under the curve. CONCLUSIONS: These preliminary findings suggest that the combination of multiple markers of oxidative stress does not greatly improve ability to differentiate between individuals with and without CHD compared to the use of TBARS alone.

TBARS and cardiovascular disease in a population-based sample.

BACKGROUND: Oxygen radicals might play a crucial role in the pathogenesis of various diseases, including atherosclerosis. Thiobarbituric acid reaction substances (TBARS), a biomarker of oxidative stress, have been proposed as a summary measure of total circulating oxidation. However, there is no strong indication that circulating levels of TBARS are increased in patients with atherosclerosis. DESIGN: We evaluated the relation between TBARS and cardiovascular disease (CVD) in a cross-sectional random sample of white men and women from Buffalo, New York. METHODS: Logistic regression was used to estimate the risk associated with high levels of TBARS. The area under the ROC curve was used to evaluate the discriminating power of TBARS. RESULTS: After adjusting for age and gender, TBARS levels were significantly higher in those with prevalent CVD (OR= 1.73, 95% CI=1.32-2.38), compared to those without a CVD diagnosis. These OR were almost 50% higher after correcting for measurement error (ME) (OR=1.93, 95% CI=1.07-3.40). The area under the ROC curve was 0.69 (95% CI=0.62-0.77) and when corrected for ME reached 0.80 (95% CI=0.65-0.89). CONCLUSIONS: Our results indicate that elevated levels of TBARS were associated with increase risk of the prevalence of CVD, but this effect was no longer significant after adjusting for glucose.