Relationship between dimethylarginine dimethylaminohydrolase gene variants and asymmetric dimethylarginine in patients with rheumatoid arthritis

Objective

The aim of our study was to determine whether Dimethylarginine Dimethylaminohydrolase (DDAH) 1 and 2 gene polymorphisms – the main enzyme involved in ADMA degradation – are associated with high Asymmetric Dimethylarginine (ADMA) levels in Rheumatoid Arthritis (RA).

Methods

Serum ADMA levels were measured in 201 individuals with RA [155 females median age 67 (59–73)]. Four tag SNPs in DDAH1 gene and 2 in the DDAH2 gene were genotyped by using the LightCycler™ System. ADMA was initially compared across the genetic variables using one-way ANOVA and then multivariate analysis examined each of the genes after adjustment for parameters of systemic inflammation and insulin resistance, namely erythrocyte sedimentation rate (ESR) and homeostatic model assessment (HOMA), which we have previously shown affect ADMA levels in RA.

Results

No significant relationship between DDAH genetic variables and ADMA levels was established in ANOVA analysis. Multivariate model adjusted for age, HOMA and ESR did not demonstrate any significant association between DDAH variants and ADMA.

Conclusion

The results of our study give no evidence to suggest that increased ADMA levels in RA relate to DDAH genetic polymorphisms. Better understanding of disease-related factors and their interactions with traditional CV risk factors may represent mechanisms responsible for ADMA accumulation in this population.     

Factors associated with 2-year persistence in fully non reimbursed lipid-lowering treatments

Objective

to evaluate the main factors associated with long-term persistence in fully paid lipid-lowering treatment.

Methods

We selected 628 moderately hypercholesterolemic subjects (M: 307; F: 311, mean age 59 ± 9 years old), to whom we firstly prescribed a statin (N. 397) or different kinds of lipid-lowering nutraceuticals (N. 231). Then, depending on their will, patients took brand statin (N. 194) or generic statins (N. 203).

Results

The main determinants of long-term persistence in therapy are female sex (OR 1.21, 95%CI 1.08–1.42), family history of early cardiovascular disease (OR 1.31, 95%CI 1.13–1.49), baseline LDL-C (OR 1.19, 95%CI 1.02–1.33) and treatment with nutraceuticals versus statins (OR 1.29, 95%CI 1.14–1.38). Persistence appears not to be influenced by patient's age, smoking habit, adverse events during treatment, and estimated cardiovascular risk.

Conclusion

Among self-paying patients with mild hyperlipidemia, medication persistence is highest among those taking nutraceuticals, followed by brand statins, followed by generic statins.     

Increased concentration of circulating angiogenesis and nitric oxide inhibitors induces endothelial to mesenchymal transition and myocardial fibrosis in patients with chronic kidney disease

Background

Sudden cardiovascular death is increased in chronic kidney disease (CKD). Experimental CKD models suggest that angiogenesis and nitric oxide (NO) inhibitors induce myocardial fibrosis and microvascular dropout thereby facilitating arrhythmogenesis. We undertook this study to characterize associations of CKD with human myocardial pathology, NO-related circulating angiogenesis inhibitors, and endothelial cell behavior.

Methods

We compared heart (n = 54) and serum (n = 162) samples from individuals with and without CKD, and assessed effects of serum on human coronary artery endothelial cells (HCAECs) in vitro. Left ventricular fibrosis and capillary density were quantified in post-mortem samples. Endothelial to mesenchymal transition (EndMT) was assessed by immunostaining of post-mortem samples and RNA expression in heart tissue obtained during cardiac surgery. Circulating asymmetric dimethylarginine (ADMA), endostatin (END), angiopoietin-2 (ANG), and thrombospondin-2 (TSP) were measured, and the effect of these factors and of subject serum on proliferation, apoptosis, and EndMT of HCAEC was analyzed.

Results

Cardiac fibrosis increased 12% and 77% in stage 3–4 CKD and ESRD and microvascular density decreased 12% and 16% vs. preserved renal function. EndMT-derived fibroblast proportion was 17% higher in stage 3–4 CKD and ESRD (P_trend = 0.02). ADMA, ANG, TSP, and END concentrations increased in CKD. Both individual factors and CKD serum increased HCAEC apoptosis (P = 0.02), decreased proliferation (P = 0.03), and induced EndMT.

Conclusions

CKD is associated with an increase in circulating angiogenesis and NO inhibitors, which impact proliferation and apoptosis of cardiac endothelial cells and promote EndMT, leading to cardiac fibrosis and capillary rarefaction. These processes may play key roles in CKD-associated CV disease.     

A gene variant in the Atp10d gene associates with atherosclerotic indices in Japanese elderly population

Background

ATP10D belongs to a subfamily of P-type ATPases implicated in phospholipids translocation from the exoplasmic to the cytoplasmic leaflet of cellular biological membrane. Previous genome-wide association study (GWAS) identified that a variant in Atp10d gene (rs2351791) associates with serum lipid profile and myocardial infarction. The objective of this study is to assess the effect of this variant on atherosclerosis in Japanese elderly population.

Method

Consecutive autopsy cases registered in JG-SNP study were recruited (n = 1536). The samples were pathologically assessed for atherosclerosis using macroscopic examination of the formalin-fixed arteries, and coronary stenotic index (CSI), intracranial atherosclerotic index (ICAI) and pathological atherosclerotic index (PAI), which represent systemic arteries were calculated. The variant rs2351791 (G/T) in Atp10d gene was genotyped by Taqman genotyping assay and association determined.

Result

Both CSI and ICAI were significantly higher in GG genotype than GT genotype and TT genotype (p = 0.003 and p = 0.001, respectively). Both associations remained significant in minor allele dominant model after adjusting for age, hypertension, diabetes, HDL, smoking and drinking (p = 0.001 and p = 0.001, respectively). PAI was not associated with this variant. Consistent with the previous report, plasma HDL cholesterol level was lower in GG genotype compared to GT + TT genotypes (p = 0.001).

Conclusion

The rs2351791 SNP in the Atp10d gene affects the susceptibility for cardiac and intracranial vascular stenosis in the elderly Japanese population.     

Fibroblast growth factor 23, left ventricular mass,and left ventricular hypertrophy in community-dwelling older adults

Objectives

In chronic kidney disease (CKD), high FGF23 concentrations are associated with left ventricular hypertrophy (LVH), cardiovascular events, and death. The associations of FGF23 with left ventricular mass (LVM) and LVH in the general population and the influence of CKD remains uncertain.

Methods

C-terminal plasma FGF23 concentrations were measured, and LVM and LVH evaluated by echocardiogram among 2255 individuals ≥65 years in the Cardiovascular Health Study. Linear regression analysis adjusting for demographics, cardiovascular, and kidney related risk factors examined the associations of FGF23 concentrations with LVM. Analyses were stratified by CKD status and adjusted linear and logistic regression analysis explored the associations of FGF23 with LVM and LVH.

Results

Among the entire cohort, higher FGF23 concentrations were associated with greater LVM in adjusted analyses (β = 6.71 [95% CI 4.35–9.01] g per doubling of FGF23). 32% (n = 624) had CKD (eGFR <60 mL/min/1.73 m² and/or urine albumin-to-creatinine ratio >30 mg/g). Associations were stronger among participants with CKD (p interaction = 0.006): LVM β = 9.71 [95% CI 5.86–13.56] g per doubling of FGF23 compared to those without CKD (β = 3.44 [95% CI 0.77, 6.11] g per doubling of FGF23). While there was no significant interaction between FGF23 and CKD for LVH (p interaction = 0.25), the OR (1.46 95% CI [1.20–1.77]) in the CKD group was statistically significant and of larger magnitude than the OR for in the no CKD group (1.12 [95% CI 0.97–1.48]).

Conclusion

In a large cohort of older community-dwelling adults, higher FGF23 concentrations were associated with greater LVM and LVH with stronger relationships in participants with CKD.     

Reperfusion des infarctus aigus avec sus-décalage du segment ST dans le RENAU/RESURCOR : des recommandations à la pratique

Background

International guidelines have recommendations for selecting the type of reperfusion (fibrinolysis or angioplasty) in the setting of ST-segment elevation myocardial infarction (STEMI), and suggest that emergency-care networks adapt these recommendations according to the local environment.

Aim

To assess the proportions of STEMI patients treated with fibrinolysis or angioplasty in accordance with regional guidelines.

Method

Observational study based on a permanent registry of patients with STEMI of <12 h duration in an emergency network in the French North Alps (Isère, Savoie, Haute-Savoie) from January 2009 to December 2012.

Results

The registry included 2620 patients. Reperfusion was given in 2425/2620 (93%) of patients. Reperfusion type was in accordance with recommendations in 1567/2620 (60%) patients. Guideline-recommended fibrinolysis and angioplasty were performed in 47% (656/1385) and 79% (911/1149) respectively, of patients. In multivariable analysis, variables independently associated with guideline-recommended reperfusion were: an age < 65 years (OR 1.60; 95%CI 1.33–1.90), being managed in Haute-Savoie versus Isère or Savoie (OR 1.38; 95%CI 1.12–1.71), an arterial tension < 100 mmHg (OR 1.73; 95%CI 1.27–2.35), a cardiogenic shock (OR 0.50; 95%CI 0.30–0.84), a pacemaker or left bundle branch block (OR 0.49; 95%CI 0.28–0.88), and an initial management outside the network (followed by treatment in an interventional centre in the network) (OR 0.62; 95%CI 0.40–0.94). Patients initially treated by mobile intensive care units were more often reperfused in accordance with recommendations when admitted < 3 (versus ≥ 3) h following symptom onset (adjusted OR 2.05; 95% CI 1.61–2.59), while those initially treated by in-hospital emergency units were less often reperfused in accordance with recommendation when treated < 3 h following symptom onset (adjusted OR 0.67; 95% CI 0.46–0.97). In-hospital major adverse cardiac events (9.1% vs. 8.5%) and in-hospital mortality (6.4% vs. 5.1%) were not significantly different between patients reperfused in accordance with (versus not) recommendations.

Conclusions

Forty percent of patients with STEMI were not reperfused with fibrinolysis or angioplasty in accordance with regional guidelines. Characterization of this population should allow us to improve guideline adherence.     

Chronic kidney disease,lipids and apolipoproteins,and coronary heart disease: The ARIC Study

Background

Chronic kidney disease (CKD) is associated with elevated apolipoprotein B to A-1 ratio (ApoB/A1). It is not known whether these markers are more strongly associated with the risk of coronary heart disease (CHD) in CKD compared to traditionally measured lipids and lipoprotein cholesterol ratios.

Methods

We studied the association of lipids and apolipoproteins including non-HDL-cholesterol to HDL-cholesterol ratio (NonHDLc/HDLc) and ApoB/A1 with incident CHD in 10,137 individuals free of CHD at baseline (visit four) in the Atherosclerosis Risk in Communities (ARIC) study. An estimated glomerular filtration rate of 15 to <60 ml/min/1.73 m² based on a cystatin C measurement was used to define CKD (Stage 3–4). Cox proportional hazards regression models were used to determine the association of lipids and apolipoprotein measurements with the risk of CHD in those with and without CKD after adjustment for demographic and known clinical cardiovascular risk factors.

Results

CKD was present in 1217 (12%) individuals free of CHD at baseline. The median follow-up time was 11.1 years. A CHD event developed in 498 out of 8920 individuals without CKD (incidence rate: 5.2 events per 1000 person-years) and in 138 out of 1217 individuals with CKD (incidence rate: 12.0 events per 1000 person–years; P < 0.001). Those with CKD had a lower concentration of ApoA1: median (in g/L) and interquartile range (IQR) = 1.40 (1.38–1.42) vs. 1.48 (1.47–1.49) P < 0.001; and a higher ApoB/A1 = 0.75 (0.73–0.77) vs. 0.71 (0.70–0.72) P < 0.001; than those without CKD (eGFR ≥ 60 ml/min/1.73 m²). Among individuals with CKD, ApoB/A1 and NonHDLc/HDLc were both associated with the risk of CHD: hazard ratios (HR) and 95% confidence intervals (CI) per one standard deviation increase = 1.22 (1.02–1.46) for ApoB/A1 and 1.30 (1.07–1.57) for NonHDLc/HDLc with no significant differences detected (P for interaction >0.1) when comparing these estimates to those of participants without CKD.

Conclusions

Although CKD is associated with a lower ApoA1 concentration and with a higher ApoB/A1, we found no evidence that these apolipoproteins are more strongly associated with CHD incidence in CKD compared to NonHDLc/HDLc.     

Polymorphisms on Chromosome 9p21 Confer a Risk for Acute Coronary Syndrome in a Chinese Han Population

Background

Genome-wide association studies have identified 2 single-nucleotide polymorphisms (SNPs) on chromosome arm 9p21, rs10757278, and rs2383207 that confer susceptibility to myocardial infarction. However, these data are mostly from Italian, American Caucasian, South Korean, and Japanese cohorts. This study is the first to investigate whether 6 SNPs (rs10757277, rs10757278, rs10757279, rs1333049, rs1333047, and rs10811656) are associated with acute coronary syndrome (ACS) in a Chinese Han population.

Methods

We performed a case-control analysis in 359 patients with ACS diagnosed by coronary angiography and 398 non-ACS controls of Han background between April 2007 and January 2008 to determine whether these 6 SNPs were associated with ACS. Exon fragments were genotyped by polymerase chain reaction–restriction fragment length polymorphism.

Results

After we adjusted for clinical parameters, we found the rs10757278 GG genotype to be associated with a significantly elevated risk of ACS (odds ratio [OR], 1.91; 95% confidence interval [CI], 1.35-2.68; P = 0.00035), the rs10811656 T allele to be associated with a higher risk of ACS (OR, 1.67; 95% CI, 1.26-2.23; P = 0.0016) than the CC genotype, and the rs1333047 TT genotype also to be associated with a higher risk of ACS (OR, 1.57; 95% CI, 1.15-2.06; P = 0.0052) than the CC and CT genotypes. After 14.2 ± 4.5 months of follow-up, the end-point data were obtained: death (cardiac and noncardiac), nonfatal myocardial infarction, and recurrent angina leading to repeated coronary angiography. We found that the rs10757278 GG genotype was significantly associated with recurrent angina compared with the AA and AG genotypes (P = 0.013).

Conclusions

Polymorphisms on 9p21 were associated with ACS in a Chinese Han population. The rs10757278 GG genotype was further associated with adverse cardiac outcomes after ACS.     

Association of the triglycerides to high-density lipoprotein cholesterol ratio with the risk of chronic kidney disease: Analysis in a large Japanese population

Objectives

To investigate the relationship between triglycerides to high-density lipoprotein cholesterol ratio (TG/HDL-C) and chronic kidney disease (CKD).

Methods

We used data from 216,007 Japanese adults who participated in a nationwide health checkup program. Men (n = 88,516) and women (n = 127,491) were grouped into quartiles based on their TG/HDL-C levels (<1.26, 1.26–1.98, 1.99–3.18, and >3.18 in men; <0.96, 0.96–1.44, 1.45–2.22, and >2.22 in women). We cross-sectionally assessed the association of TG/HDL-C levels with CKD [defined as an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m² (low eGFR) and/or proteinuria (defined as urinary protein ≥1+ on dipstick testing)], low eGFR, and proteinuria.

Results

The prevalence of CKD, low eGFR, and proteinuria increased significantly with elevating quartiles of TG/HDL-C in both genders (all P for trend <0.001). Participants in the highest quartile of TG/HDL-C had a significantly greater risk of CKD than those in the lowest quartile after adjustment for the relevant confounding factors (odds ratio: 1.57, 95% confidence interval: 1.49–1.65 in men; 1.41, 1.34–1.48 in women, respectively). Furthermore, there were significant associations with low eGFR and proteinuria. In stratified analysis, the risk of CKD increased linearly with greater TG/HDL-C levels in participants with and without hypertension, diabetes, and obesity. Moreover, higher TG/HDL-C levels were relevant for CKD, especially in participants with hypertension and diabetes (P for interaction <0.001, respectively).

Conclusions

An elevated TG/HDL-C is associated with the risk of CKD in the Japanese population.     

A systematic review and meta-analysis of 130,000 individuals shows smoking does not modify the association of APOE genotype on risk of coronary heart disease

Background

Conflicting evidence exists on whether smoking acts as an effect modifier of the association between APOE genotype and risk of coronary heart disease (CHD).

Methods and results

We searched PubMed and EMBASE to June 11, 2013 for published studies reporting APOE genotype, smoking status and CHD events and added unpublished data from population cohorts. We tested for presence of effect modification by smoking status in the relationship between APOE genotype and risk of CHD using likelihood ratio test.In total 13 studies (including unpublished data from eight cohorts) with 10,134 CHD events in 130,004 individuals of European descent were identified. The odds ratio (OR) for CHD risk from APOE genotype (ε4 carriers versus non-carriers) was 1.06 (95% confidence interval (CI): 1.01, 1.12) and for smoking (present vs. past/never smokers) was OR 2.05 (95%CI: 1.95, 2.14). When the association between APOE genotype and CHD was stratified by smoking status, compared to non-ε4 carriers, ε4 carriers had an OR of 1.11 (95%CI: 1.02, 1.21) in 28,789 present smokers and an OR of 1.04 (95%CI 0.98, 1.10) in 101,215 previous/never smokers, with no evidence of effect modification (P-value for heterogeneity = 0.19). Analysis of pack years in individual participant data of >60,000 with adjustment for cardiovascular traits also failed to identify evidence of effect modification.

Conclusions

In the largest analysis to date, we identified no evidence for effect modification by smoking status in the association between APOE genotype and risk of CHD.     

Association between Chlamydophila pneumoniae infection and risk of coronary heart disease for Japanese: The JPHC study

Background

Chlamydophila pneumoniae infection is considered a risk factor for atherosclerosis and coronary heart disease in western countries. However, evidence of it being a risk for Japanese is very limited because of a lower risk of coronary heart disease than for western people. The aim of this study was to examine further the association between C. pneumoniae infection and risk of coronary heart disease in Japanese.

Methods

We conducted a nested case–control study of 49,011 Japanese men and women who participated in The Japan Public Health Center (JPHC) study. By the end of 2004, 196 cases of coronary heart disease and 155 cases of myocardial infarction had been documented among the participants. Two controls were selected for each case. For these subjects, we examined the association between serum anti C. pneumoniae IgA and IgG on the one hand and risk of coronary heart disease on the other.

Results

Concentration of C. pneumoniae IgA antibody was positively associated with risk of coronary heart disease and more specifically myocardial infarction. Subjects with the highest quartile of IgA antibody showed 2.29 (95%CI, 1.21–4.33) times higher risk of coronary heart disease and 2.58 (95%CI, 1.29–5.19) times higher risk of myocardial infarction than those with lowest quartile. However, no such association was detected for IgG antibody.

Conclusion

C. pneumoniae infection was found to be positively associated with risk of coronary heart disease.     

Soluble urokinase plasminogen activator receptor is in contrast to high-sensitive C-reactive-protein associated with coronary artery calcifications in healthy middle-aged subjects

Objective

The main objective of this study was to investigate the association between two markers of low-grade inflammation; soluble urokinase plasminogen activator receptor (suPAR) and high-sensitive C-reactive protein (hs-CRP); and coronary artery calcification (CAC) score detected by cardiac computed tomography (CT) scan.

Design

A cross sectional study of 1126 randomly sampled middle-aged men and women.

Methods

CAC score was measured by a non-contrast cardiac CT scan and total 10-year cardiovascular mortality risk was estimated using the Systematic Coronary Risk Evaluation (SCORE). Plasma samples were analysed for suPAR and hs-CRP. The association of suPAR and hs-CRP to CAC was evaluated by logistic regression analyses adjusting for categorised SCORE. The additive effect of suPAR to SCORE was evaluated by comparing area under curve (AUC) and net reclassification improvement (NRI).

Results

The odds of being in a higher CAC category, i.e. having more severe CAC, increased 16% (odds ratio (OR) 1.16, p = 0.02) when plasma suPAR concentration increased 1 ng/ml, and this was more pronounced in women (OR 1.30, p = 0.01) than in men (OR 1.15, p = 0.05). In comparison, hs-CRP was not associated with CAC category (OR 1.00, p = 0.90). When adding suPAR to categorised SCORE, AUC increased from 0.66 to 0.70 (p = 0.04) in women and from 0.65 to 0.68 (p = 0.03) in men. NRI was significant in men (NRI 19.3%, 95% CI 6.1–32.6, p = 0.004) as well as in women (NRI 20.8%, 95%CI 1.0–40.7, p = 0.04), without significant gender difference.

Conclusions

suPAR, but not hs-CRP, appeared to be associated with CAC score independently of SCORE. The association was strongest in women.     

Antibodies to periodontal pathogens are associated with coronary plaque remodeling but not with vulnerability or burden

Objective

Previous studies have suggested positive associations between periodontal infection and cardiovascular disease. We aimed to investigate the associations of circulating antibodies against periodontal pathogens with 1-year cardiovascular outcome, as well as the extent of coronary atherosclerosis, plaque vulnerability and lesion remodeling on intravascular ultrasound (IVUS) imaging.

Methods

Between 2008 and 2011, radiofrequency IVUS imaging of a non-culprit coronary artery was performed in 581 patients who underwent coronary angiography. Immunoglobulin G (IgG) and A (IgA) against Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia and Prevotella intermedia were measured in plasma.

Results

None of the antibody levels were associated with coronary plaque burden, radiofreqeuncy-IVUS-derived thin-cap fibroatheroma lesion morphology or 1-year incidence of major adverse cardiac events (MACE), which included all-cause mortality, acute coronary syndrome and unplanned coronary revascularization. IgA against A. actinomycetemcomitans, T. forsythia and P. intermedia were inversely associated with extent of positive lesion remodeling (OR for highest versus lowest tertile 0.55, 95%CI 0.35–0.88, p = 0.012; 0.53, 95%CI 0.32–0.87, p = 0.012; and 0.64, 95%CI 0.40–1.02, p = 0.061, respectively). In diabetic patients specifically, IgG against P. gingivalis tended to be associated with coronary plaque burden (p = 0.080), while IgA against P. gingivalis tended to be associated with incident MACE (p = 0.060).

Conclusion

Plasma IgG and IgA against major periodontal pathogens were not associated with the extent of coronary atherosclerosis (with the exception of a trend in diabetics) nor with coronary plaque vulnerability. IgA against periodontal pathogens were inversely associated with extent of coronary remodeling. Altogether, these results do not add evidence for a substantial role of systemic exposure to periodontal pathogens in coronary artery disease.     

Damage of the endothelial glycocalyx in chronic kidney disease

Background and objectives

The endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the luminal surface of endothelial cells, is considered as an intravascular compartment that protects the vessel wall against pathogenic insults in cardiovascular disease. We hypothesized that chronic kidney disease (CKD) is associated with reduced eGC integrity and subsequent endothelial dysfunction.

Methods & results

Shedding of two major components of the eGC, namely syndecan-1 (Syn-1) and hyaluronan (HA), was measured by ELISA in 95 patients with CKD (stages 3–5) and 31 apparently healthy controls. Plasma levels of Syn-1 and HA increased steadily across CKD stages (5- and 5.5-fold, respectively P < 0.001) and were independently associated with impaired renal function after multivariate adjustment. Furthermore, Syn-1 and HA correlated tightly with plasma markers of endothelial dysfunction such as soluble fms-like tyrosine kinase-1 (sFlt-1), soluble vascular adhesion molecule-1 (sVCAM-1), von-Willebrand-Factor (vWF) and angiopoietin-2 (P < 0.001). Experimentally, excessive shedding of the eGC, evidenced by 11-fold increased Syn-1 plasma levels, was also observed in an established rat model of CKD, the 5/6-nephrectomized rats. Consistently, an atomic force microscopy-based approach evidenced a significant decrease in eGC thickness (360 ± 79 vs. 157 ± 29 nm, P = 0.001) and stiffness (0.33 ± 0.02 vs. 0.22 ± 0.01 pN/nm, P < 0.001) of aorta endothelial cell explants isolated from CKD rats.

Conclusion

Our findings provide evidence for damage of the atheroprotective eGC as a consequence of CKD and potentially open a new avenue to pathophysiology and treatment of cardiovascular disease in renal patients.     

Culture-negative Prosthetic Joint Arthritis Related to Coxiella burnetii

Background

The number of hip and knee arthroplasty procedures is steadily increasing as life expectancy increases. Coxiella burnetii may be responsible for culture-negative prosthetic joint arthritis and is associated with antibiotic failure and repeated surgeries. We report the first case series of C. burnetii–related culture-negative prosthetic joint arthritis.

Methods

Cases were retrieved from the French National Referral center for Q fever. Diagnosis was based on ¹⁸fluorodeoxyglucose positron emission tomography, serology, broad-range polymerase chain reaction, and C. burnetii–specific polymerase chain reaction.

Results

Four cases of C. burnetii–related culture-negative prosthetic joint arthritis were found. Standard bacteriologic procedures would have missed the diagnosis in all cases. Etiologic diagnosis improved the outcome in all but 1 case.

Conclusions

A systematic, comprehensive diagnostic strategy should be used in culture-negative prosthetic joint arthritis, including testing for C. burnetii in endemic areas.     

Role of bone mineral density in the inverse relationship between body size and aortic calcification: Results from the Baltimore Longitudinal Study of Aging

Objective

There is a J-shaped relationship between body mass index (BMI) and cardiovascular outcomes in elderly patients (obesity paradox). Whether low BMI correlates with aortic calcification (AC) and whether this association is accounted for by bone demineralization is uncertain.

Methods

Presence of AC was evaluated in 687 community-dwelling individuals (49% male, mean age 67 ± 13 years) using CT images of the thoracic, upper and lower abdominal aorta, and scored from 0 to 3 according to number of sites that showed any calcification. Whole-body bone mineral density (BMD) was evaluated by dual-energy X-ray absorptiometry. Predictors of AC were assessed by logistic regression, and the role of BMD using mediation analysis.

Results

Age and cardiovascular risk factors were positively associated while both BMI (r = −0.11, p < 0.01) and BMD (r = −0.17, p < 0.0001) were negatively associated with AC severity. In multivariate models, lower BMI (OR 0.96, 95%CI 0.92–0.99, p = 0.01), older age, higher systolic blood pressure, use of lipid-lowering drugs and smoking were independent predictors of AC. A nonlinear relationship between BMI and AC was noticed (p = 0.03), with decreased AC severity among overweight participants. After adjusting for BMD, the coefficient relating BMI to AC was reduced by 14% and was no longer significant, whereas BMD remained negatively associated with AC (OR 0.82, 95%CI 0.069–0.96, p = 0.01), with a trend for a stronger relationship in older participants.

Conclusion

Low BMI is associated with increased AC, possibly through calcium mobilization from bone, resulting in low BMD. Prevention of weight loss and bone demineralization with aging may help reducing AC.     

Tumor necrosis factor-α (TNF-α) −863C/A promoter polymorphism is associated with type 2 diabetes in Tunisian population

Aims

Tumor necrosis factor α (TNFα) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF α has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The aim of the present study was to investigate the association between the −863C/A polymorphism in the promoter of the TNFα gene and type 2 diabetes in the Tunisian population.

Methods

The polymorphism −863C/A in the TNFα gene was determined in 211 type 2 diabetes patients and 345 healthy controls using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis.

Results

A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with type 2 diabetes had significantly higher frequency of the CA + AA genotypes compared to controls [35.5% vs. 22.3%; OR (95%CI), 1.91 (1.31–2.8); p = 0.001]. The type 2 diabetes patient group showed a significant higher frequency of the A allele compared to the controls (0.19 vs. 0.11; p = 0.001). After adjustment by a stepwise logistic regression method, hypertension, dyslipidemia, and CA + AA genotype were found to be significantly associated with T2D.

Conclusion

The present study showed a significant and independent association between the −863C/A polymorphism of the TNFα gene and type 2 diabetes in the Tunisian population.     

PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals

Background

Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3 I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n = 4047).

Methods

We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity.

Results

A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value = 0.001), but not in the surgery group (log-rank P-value = 0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5–23.8; P-value = 0.013) of developing hepatocellular carcinoma was observed only in the control group.

Conclusion

The current study is the first prospective report showing the association of the PNPLA3 I148M genetic variant and hepatocellular carcinoma in severely obese individuals.     

Accumulation of oxidative stress-related gene polymorphisms and the risk of coronary heart disease events in patients with type 2 diabetes – An 8-year prospective study

Objective

Oxidative stress, which is provoked in patients with diabetes, plays critical roles in the pathogenesis of coronary heart disease (CHD). We simultaneously determined 5 relatively common genetic variants related to oxidative stress and evaluated the combined effect on CHD.

Methods

We enrolled 1977 Japanese type 2 diabetic subjects without history of CVD (males 66.1%, 59.5 ± 10.0 years old), determined their genotypes regarding glutamate-cysteine ligase modifier subunit (GCLM) C-588T, manganese superoxide dismutase (SOD2) Val16Ala, endothelial nitric oxide synthase (NOS3) G894T, NAD(P)H oxidase p22phox (CYBA) C242T, and myeloperoxidase (MPO) G-463A polymorphisms, and prospectively evaluated the association between these polymorphisms and CHD events.

Results

The median follow-up period was 7.5 years and there were 85 new CHD events. The single association analysis revealed that there were no statistically significant associations between each polymorphism and the prevalence of CHD. Interestingly, the risk of CHD event was higher with the increase of the total number of 10 concomitant unfavorable “pro-oxidant alleles” in each subject (p for trend = 0.018, log-rank test). Especially, the carriers of ≥8 pro-oxidant alleles had a significantly increased risk as compared to the carriers of <8 pro-oxidant alleles, whether the other clinical variables were adjusted (HR 2.92 with 95%CI 1.50–5.67, p = 0.002) or not (HR 2.89 with 95%CI 1.49–5.59, p = 0.002)..

Conclusions

Accumulation of gene polymorphisms related to oxidative stress is likely associated with the development of CHD in patients with type 2 diabetes, suggesting that the combined information about these variants is useful to assess the risk of CHD.     

Diagnosis performance of high sensitivity troponin assay in out-of-hospital cardiac arrest patients

Purpose

Early identification of the cause of out-of-hospital cardiac arrest (OHCA) remains a challenge. Our aim was to determine whether high-sensitivity cardiac troponin T (HsTnT) was useful to diagnose a recent coronary artery occlusion as the cause of OHCA.

Methods

Retrospective study including OHCA patients evaluated by systematic coronary angiogram at hospital admission. HsTnT was assessed at ICU admission. Predictive factors of a recent coronary occlusion were identified by logistic regression. Net reclassification improvement (NRI) was calculated to estimate the potential enhancement of prediction with HsTnT.

Results

During the 5 year study period, 272 patients (median age 60y, 76.5% men) were included, and a culprit coronary occlusion was found in 133 (48.9%). The optimum HsTnT cut-off to predict a recent coronary occlusion was 575 ng/l (sensitivity 65.4%, specificity 65.5%). In multivariate analysis, current smoking (OR 3.2 95%, 95%CI 1.62–6.33), time from collapse to BLS < 3 min (OR 2.11, 95%CI 1.10–4.05), initial shockable rhythm (OR 5.29, 95%CI 2.06–13.62), ST-segment elevation (OR 2.44, 95%CI 1.18–5.03), post-resuscitation shock onset (OR 2.03, 95%CI 1.01–4.07) and HsTnT ≥ 575 ng/l (OR 2.22, 95%CI 1.16–4.27) were associated with the presence of a recent coronary occlusion. Nevertheless, adding HsTnT to established risk factors of recent coronary occlusion identified above provided a non-significant NRI of − 0.43%.

Conclusions

Admission HsTnT is increased after OHCA and is an independent factor of a recent coronary occlusion. However, HsTnT does not seem to be a strong enough diagnostic tool to select candidates for emergent coronary angiogram in OHCA survivors.