Evaluation of the QRS score for diagnosing coronary artery disease in women: A Finnish cardiovascular study.

BACKGROUND: Exercise electrocardiography is a widely used diagnostic modality for diagnosing coronary artery disease. This method has been used for both sexes; however, its diagnostic accuracy in women is limited. METHODS: The study analyzed 332 women participating in the Finnish Cardiovascular Study. Among 332 women, 125 with angiographically proven coronary artery disease (mean age 62.1 ± 9.5 years), 91 with a low likelihood of coronary artery disease (mean age 47.3 ± 13.5 years), and 116 without angiographically proven coronary artery disease (mean age 56.3 ± 9.9 years) were analyzed. The Q, R, S, and ST-segment changes and QRS score were determined by subtracting the Q, R, S, and ST-segment amplitudes immediately after the maximal exercise changes from their rest values (Δ). Receiver operating characteristic curve analysis was performed to evaluate the overall diagnostic performance of the parameters for predicting coronary artery disease. RESULTS: The areas under the receiver operating characteristic curve between coronary artery disease and low likelihood of coronary artery disease groups for the QRS score and ΔSTV5, ΔQaVF, and ΔRaVF were 0.75, 0.73, 0.71, and 0.71, respectively. These areas were lower (0.62, 0.57, 0.60, and 0.60, respectively) between the groups with and without angiographically proven coronary artery disease. QRS score demonstrated the highest sensitivity at 80% specificity (61.5%) and the highest specificity at 80% sensitivity (57.6%). CONCLUSIONS: This study suggests that the QRS and ST-segment depression have a moderate diagnostic ability to predict coronary artery disease in women. Q and R waves in lead aVF showed good diagnostic ability.

Serum Proteomic Profiling to Identify Biomarkers of Premature Carotid Atherosclerosis.

To evaluate the presence of serum protein biomarkers associated with the early phases of formation of carotid atherosclerotic plaques, label-free quantitative proteomics analyses were made for serum samples collected as part of The Cardiovascular Risk in Young Finns Study. Samples from subjects who had an asymptomatic carotid artery plaque detected by ultrasound examination (N = 43, Age = 30-45 years) were compared with plaque free controls (N = 43) (matched for age, sex, body weight and systolic blood pressure). Seven proteins (p < 0.05) that have been previously linked with atherosclerotic phenotypes were differentially abundant. Fibulin 1 proteoform C (FBLN1C), Beta-ala-his-dipeptidase (CNDP1), Cadherin-13 (CDH13), Gelsolin (GSN) and 72 kDa type IV collagenase (MMP2) were less abundant in cases, whereas Apolipoproteins C-III (APOC3) and apolipoprotein E (APOE) were more abundant. Using machine learning analysis, a biomarker panel of FBLN1C, APOE and CDH13 was identified, which classified cases from controls with an area under receiver-operating characteristic curve (AUROC) value of 0.79. Furthermore, using selected reaction monitoring mass spectrometry (SRM-MS) the decreased abundance of FBLN1C was verified. In relation to previous associations of FBLN1C with atherosclerotic lesions, the observation could reflect its involvement in the initiation of the plaque formation, or represent a particular risk phenotype.

Electronic Nose in the Detection of Wound Infection Bacteria from Bacterial Cultures: A Proof-of-Principle Study.

BACKGROUND: Soft tissue infections, including postoperative wound infections, result in a significant burden for modern society. Rapid diagnosis of wound infections is based on bacterial stains, cultures, and polymerase chain reaction assays, and the results are available earliest after several hours, but more often not until days after. Therefore, antibiotic treatment is often administered empirically without a specific diagnosis. METHODS: We employed our electronic nose (eNose) system for this proof-of-concept study, aiming to differentiate the most relevant bacteria causing wound infections utilizing a set of clinical bacterial cultures on identical blood culture dishes, and established bacterial lines from the gaseous headspace. RESULTS: Our eNose system was capable of differentiating both methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, and Clostridium perfringens with an accuracy of 78% within minutes without prior sample preparation. Most importantly, the system was capable of differentiating MRSA from MSSA with a sensitivity of 83%, a specificity of 100%, and an overall accuracy of 91%. CONCLUSIONS: Our results support the concept of rapid detection of the most relevant bacteria causing wound infections and ultimately differentiating MRSA from MSSA utilizing gaseous headspace sampling with an eNose.

Lactase gene c/t(-13910) polymorphism, calcium intake, and pQCT bone traits in Finnish adults.

Genetic lactase nonpersistence may influence calcium intake and thereby bone health. We investigated in the Cardiovascular Risk in Young Finn Study whether young adults aged 31-46 years with the C/C(-13910) genotype are more susceptible to reduced bone phenotypes, low-energy fractures, and low calcium intake than subjects with other lactase genotypes. We also analyzed the gene-environment interactions on bone with calcium intake and physical activity. Peripheral quantitative computed tomography bone traits were measured from the distal and shaft sites of the radius and tibia. The total number of those subjects whose nondominant forearm was measured and the lactase genotype was defined was 1551. Information on diet, lifestyle factors, and fractures was collected with questionnaires. The mean intake of calcium was the lowest in men with the C/C(-13910) genotype (P = 0.001). Men with the T/T(-13910) genotype had ~3% higher trabecular density at the distal radius and distal tibia compared to other lactase genotypes (P = 0.03 and 0.02, respectively). In women, we found no evidence of the gene effect at the radius and tibia. No major interactions of the C/T(-13910) polymorphism with calcium intake or physical activity on bone phenotypes were found in either sex. In conclusion, the C/T(-13910) polymorphism was associated with trabecular density at the distal radius and tibia in men. These differences may be due to the differences in calcium intake between the lactase genotypes.

Coronary artery disease-related genetic variant on chromosome 10q11 is associated with carotid intima-media thickness and atherosclerosis.

OBJECTIVE: To investigate whether chromosome 10q11.21 influences common carotid intima-media thickness (IMT) and atherosclerosis and whether it is associated with stromal cell-derived factor-1α (SDF-1α) plasma levels. METHODS AND RESULTS: Variation on chromosome 10q11.21 has been consistently associated with coronary artery disease. The genetic variant lies upstream of the gene encoding SDF-1α. We genotyped 3 population cohorts (Bruneck [age range, 45 to 94 years; 50.0% men; n=738], Health2000 [age range, 46 to 76 years; 55.4% men; n=1237], and essential hypertension in families collected in the region of Oxford [HTO] [age range, 19 to 88 years; 47.9% men; n=770]) for single-nucleotide polymorphism rs501120 at the 10q11.21 locus and conducted a meta-analysis in these cohorts to ascertain a relationship between the polymorphism and carotid IMT. The analysis showed that individuals with the T/T genotype had a significantly higher carotid IMT than individuals with the C/T or C/C genotype (pooled weighted mean difference, 23 µm [95% CI, 9 to 37 µm], P=0.0014 under a fixed-effects model; and 23 µm [95% CI, 6 to 41 µm], P=0.009 under a random-effects model). In the Bruneck cohort, in which data for carotid atherosclerosis and plasma SDF-1α levels were available, we observed an association of the T/T genotype with a higher burden of atherosclerosis and increased susceptibility to the development of atherosclerosis during a 5-year follow-up (multivariable odds ratio, 1.73 [95% CI, 1.18 to 2.52]; P=0.005 for the recessive model) and an association between the T/T genotype and lower SDF-1α levels (2.62 ng/mL for T/T versus 2.74 ng/mL for C/C or C/T; P=0.023). CONCLUSIONS: The coronary heart disease-related variant at the 10q11.21 locus is associated with carotid IMT and atherosclerosis.

Genetic lactase non-persistence, consumption of milk products and intakes of milk nutrients in Finns from childhood to young adulthood.

Previous evidence suggests that the lactase gene C/T- 13910 polymorphism (rs4988235) is associated with avoidance of milk products and lower Ca intake. We examined whether the consumption of milk and milk products and the intakes of milk nutrients differ between the lactase genotypes from childhood to young adulthood. Subjects belong to the Cardiovascular Risk in Young Finns Study where the first cross-sectional surveys were conducted in 1980 (n 3596), with follow-up studies in 1983, 1986, 1989, 1992 and 2001 (n 2620). The same dietary questionnaire was used throughout the follow-up to collect data on habitual consumption of milk and milk products in all subjects, and daily nutrient intakes were assessed with 48 h dietary recalls in 50 % of the subjects. Subjects with the lactase non-persistence (C/C- 13910) genotype consumed less milk since childhood, but the consumption of other milk products did not differ between the genotypes. In adult females, the lactose content of milk products consumed was lower (P = 0.003), and in both sexes low-lactose and milk-free diets were more common in the C/C- 13910 genotype than in the other genotypes. Inadequate Ca intake was most common in females with the C/C- 13910 genotype as early as in childhood (15-63 %), but in males only in adulthood (24 %). In adult females, preference for low-lactose milk and milk products equalised the differences in Ca intake between the genotypes. Thus, in those with the C/C- 13910 genotype, preference for low-lactose milk and milk products may decrease the risk for inadequate Ca intake.

Associations of genetic lactase non-persistence and sex with bone loss in young adulthood.

Some studies have reported that after attainment of peak bone mass (PBM), slow bone loss may occur in both men and women; however, findings are inconsistent. Genetic factors play a significant role in bone loss, but the available evidence is conflicting. Genetic lactase non-persistence (lactase C/C(-13910) genotype) is suggested to increase risk for inadequate calcium intake predisposing to poorer bone health. We investigated whether this genotype is associated with PBM and bone loss in young Finnish adults. Subjects belong to the Cardiovascular Risk in Young Finns Study that is an ongoing multi-centre follow-up of atherosclerosis risk factors. From the original cohort, randomly selected subjects aged 20-29 participated in baseline bone mineral density (BMD) measurements (n=358), and in follow-up measurements 12 years later (n=157). Bone mineral content (BMC) and BMD at lumbar spine (LS) and femoral neck (FN) were measured at baseline and follow-up with dual energy X-ray absorptiometry (DXA). Lactase C/T(-13910) polymorphism was determined by PCR and allele-specific fluorogenic probes. Information on lifestyle was elicited with questionnaires. During the follow-up, bone loss at both bone sites was greater in males (LS BMD: -1.1%, FN BMD: -5.2%) than in females (LS BMD: +2.1%, FN BMD: -0.7%) (both bone sites p=0.001). Younger age predicted greater loss of FN BMC and BMD in females (p=0.013 and p=0.001, respectively). Increased calcium intake predicted FN BMD gain in both sexes (in females B=0.007 g/cm(2)/mg, p=0.002; in males B=0.006, p=0.045), and increased physical activity LS BMD gain in females (B=0.091 g/cm(2)/physical activity point, p=0.023). PBM did not differ between the lactase genotypes, but males with the CC(-13910) genotype seemed to be prone to greater bone loss during the follow-up (LS BMD: C/C vs. T/T p=0.081). In conclusion, bone loss in young adulthood was more common in males than in females and seemed to occur mainly at the femoral neck. Young males with the lactase CC(-13910) genotype may be more susceptible to bone loss; however, calcium intake predicts changes in bone mass more than the lactase genotype.

The influence of smoking and homocysteine on subclinical atherosclerosis is modified by the connexin37 C1019T polymorphism - The Cardiovascular Risk in Young Finns Study.

BACKGROUND: A polymorphism C1019T on the connexin37 (Cx37) gene has been found to associate with coronary artery disease. There are conflicting results on which allele confers risk, and the possibility of interactions between the polymorphism and risk factors has been raised. In this study, we examined interactions between the Cx37 polymorphism and common risk factors and their associations to early vascular parameters of atherosclerosis: carotid artery intima-media thickness (IMT), and carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD). METHODS: A population of 1440 healthy young adults from the Cardiovascular Risk in Young Finns Study was studied. The subjects were genotyped and their cardiovascular risk factor and ultrasound data gathered in 2001 were used for the statistical analyses. RESULTS: In the whole population, homocysteine in subjects with the TT genotype was found to be associated with higher FMD values (p for interaction 0.038) and remained so in three different adjusted models (p for interaction 0.022-0.038). In women with the CC genotype, smoking was found to be associated with higher FMD values and the smoking-by-genotype interaction remained significant in three adjusted models (p for interaction 0.001-0.041). In women with TT genotype, the effect of smoking was opposite, i.e., FMD values for smokers were lower compared to non-smokers. In men, physical activity interacted with Cx37 on CAC in the CT and TT genotypes (p for interaction 0.011). No significant interactions were found to predict IMT. CONCLUSIONS: The effect of smoking and homocysteine levels on arterial endothelial functions and elasticity were modified by the allelic variation of the Cx37 gene. These data suggest that variation in the connexin gene may modify effects risk factors have on vascular function.

Allelic variants of upstream transcription factor 1 associate with carotid artery intima-media thickness: the Cardiovascular Risk in Young Finns study.

BACKGROUND: Polymorphisms of the upstream transcription factor 1 (USF1) have been associated with familial combined hyperlipidemia and coronary heart disease. The impact of this gene on subclinical atherosclerosis is unknown. Associations of 3 allelic variants of the USF1 gene and their haplotypes with carotid artery intima - media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) were studied in a population of Finnish healthy young adults. METHODS AND RESULTS: The study population comprised 2,281 individuals participating in the Cardiovascular Risk in Young Finns study. IMT, CAC and FMD values were measured by ultrasound examination. Genotypes were analysed using the 5' nuclease assay. A significant difference in IMT was found for usf1s1 (rs3737787) and usf1s8 (rs2516838) genotypes (p-values 0.046 and 0.021, respectively). Moreover, there was a significant difference between groups in haplotype 1 and haplotype 2 for IMT (p-values 0.011 and 0.028 respectively). In multivariate stepwise linear regression models adjusted by age, sex, body mass index, systolic and diastolic blood pressures, smoking, C-reactive protein, glucose, high- and low-density lipoprotein-cholesterols and triglycerides there were significant associations for the usf1s1 minor genotype AA to predict low IMT (p=0.038) and usf1s8 minor genotype GG to predict high IMT (p=0.003). There was also a significant association for haplotype 2 to predict low IMT in the otherwise similar multivariate model (p=0.006). No associations were found for polymorphisms and CAC, FMD or serum lipids. CONCLUSIONS: The rs2516838 and rs3737787 polymorphisms of USF1 influence the carotid artery IMT, which is a new finding.

Measurement of the kidney function in patients with rheumatoid arthritis: plasma cystatin C versus 51Cr-EDTA clearance.

BACKGROUND/AIM: Knowledge of the usefulness of cystatin C measurement in the detection of chronic kidney disease in patients with rheumatoid arthritis (RA) is scant. The purpose of this study was to evaluate the ability of plasma cystatin C- and creatinine-based methods to predict glomerular filtration rate (GFR) and classify chronic kidney disease in RA patients. METHODS: The study population consisted of 64 RA patients aged 41-86 years. Comparisons were made between measured plasma creatinine, cystatin C, creatinine clearance and GFR estimated by the Cockcroft-Gault (CG) and the Modification of Diet in Renal Disease (MDRD) formulas. The plasma clearance of (51)Cr-EDTA served as a reference. RESULTS: The Pearson correlation coefficients between plasma clearance of (51)Cr-EDTA and the markers of GFR were calculated. The correlation coefficients were 0.800 for plasma creatinine, 0.863 for cystatin C, 0.866 and 0.904 for GFR values estimated by MDRD and CG and 0.922 for plasma creatinine clearance. Statistically significant differences were detected between the correlation coefficients of plasma creatinine and GFR estimated by CG (p = 0.0412) and plasma creatinine and creatinine clearance (p = 0.0099). Creatinine clearance and the MDRD and CG formulas proved to be better at identifying GFR <90 ml/min than plasma creatinine or cystatin C. CONCLUSION: We recommend using the CG formula or creatinine clearance for the estimation of the GFR of RA patients instead of solely creatinine or cystatin C in clinical work.

Associations between connexin37 gene polymorphism and markers of subclinical atherosclerosis: the Cardiovascular Risk in Young Finns study.

OBJECTIVE: Connexin37 (cx37) C1019T polymorphism has been shown to associate with coronary artery disease in different populations. We investigated whether this polymorphism associates with carotid artery intima-media thickness (IMT), carotid artery compliance (CAC) and brachial artery flow mediated dilatation (FMD) - i.e., early ultrasound markers of subclinical atherosclerosis - in a clinically healthy population of young Finnish adults. METHODS AND RESULTS: 1440 individuals from the Cardiovascular Risk in Young Finns study were genotyped and studied using cardiovascular risk factor and ultrasound data obtained in 2001. In linear regression models, no significant association between the cx37 polymorphism and carotid IMT, CAC or brachial artery FMD (ANOVA, p=0.159, 0.151 and 0.547), respectively, was found in the whole population or in women and men separately. CONCLUSIONS: The connexin37 C1019T polymorphism is not related with markers of subclinical atherosclerosis in young adults.