Comparison of effects of pioglitazone and glimepiride on plasma soluble RAGE and RAGE expression in peripheral mononuclear cells in type 2 diabetes: Randomized controlled trial (PioRAGE)

Objective

The receptor for advanced glycation end-products (RAGE) is involved in vascular complications in diabetic patients. Pioglitazone, in contrast to glimepiride, has been shown to be protective against atherosclerotic disorders. In this study, we directly compared the effects of those drugs on RAGE system.

Methods

Sixty-three type 2 diabetic patients (age 20–80 years, hemoglobin A1c 6.4–10.3%) being treated with sulfonylurea (glimepiride 0.5–2.0 mg/day, glyclazide 20–80 mg/day, glibenclamide 1.25–5.0 mg/day), or with nateglinide or metiglynide were randomly assigned to receive either pioglitazone (n = 31) or glimepiride (n = 32). Levels in plasma of soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE), and RAGE expression in peripheral mononuclear cells were determined at 0, 12, and 24 weeks.

Results

Twenty-seven patients in the pioglitazone group (15–30 mg) and 30 in the glimepiride group (0.5–4 mg) completed the 24-week trial. Increases in plasma esRAGE were significantly greater in the pioglitazone group (12 weeks: 55 ± 15 pg/mL, p = 0.018; 24 weeks: 90 ± 14 pg/mL, p = 0.003) as compared to the glimepiride group (12 weeks: 12 ± 9 pg/mL; 24 weeks: 29 ± 14 pg/mL). Increases in plasma sRAGE were also significantly (p = 0.037) higher in the pioglitazone group at 24 weeks (170 ± 166 vs.74 ± 171 pg/mL). Furthermore, RAGE expression in mononuclear cells was significantly (p = 0.008) decreased to a greater degree in the pioglitazone group at 24 weeks (−7.39 ± 5.18 vs. −3.39 ± 5.72 MFI). Changes in HbA1c, IRI, and insulin resistance index (HOMA) at 24 weeks were not significantly different between the groups.

Conclusion

Pioglitazone suppresses RAGE expression and increases circulating sRAGE/esRAGE, and those activities are not necessarily dependent on plasma glucose or insulin resistance levels.

Clinical trial No

UMIN000002055.     

Association between neutrophil–lymphocyte ratio and impaired myocardial perfusion in patients with known or suspected coronary disease

Objective

To determine whether an elevated neutrophil–lymphocyte ratio (NLR) is associated with chronically impaired myocardial perfusion in patients with known or suspected coronary disease.

Background

Elevated NLRs are positively associated with cardiac events, anatomic coronary disease, and myocardial infarct size. However, no study has evaluated the association between NLR and chronically impaired myocardial perfusion.

Methods

This study included 683 patients undergoing cardiac positron emission tomography (PET) with a calculable NLR within 90 days of PET. The primary outcome was myocardial perfusion defect size measured in percent of left ventricular mass (%LV60).

Results

NLR was independently associated with %LV60 when analyzed as both a continuous and binary outcome (p < 0.001). Individuals with NLR above the 90th percentile had a 5-fold increased likelihood of significant perfusion defects compared to individuals with NLR between the 10th and 25th percentiles (Odds ratio = 4.7, p < 0.001).

Conclusion

An elevated NLR demonstrated strong associations with myocardial perfusion.     

Prognostic value of coronary artery calcium and epicardial adipose tissue assessed by non-contrast cardiac computed tomography

Objective

Epicardial adipose tissue (EAT) accumulation is believed to be associated with development of coronary atherosclerosis. We investigated whether EAT volume as assessed by computed tomography (CT) has value in prediction of future cardiac events.

Methods

We studied 722 patients without proven coronary artery disease (CAD) who underwent non-contrast cardiac CT. EAT volume and coronary artery calcium (CAC) score were measured simultaneously. Patients were followed as to the occurrence of coronary events (cardiac death, nonfatal myocardial infarction, unstable angina requiring hospitalization, and late coronary revascularization ≥3 months after CT examination).

Results

During a 3.7 ± 1.7 years follow-up period, 37 coronary events were documented. Annual event rates increased across CAC score categories (0.3%, 1.0%, 2.4%, and 4.3%, in 0, 1–99, 100–399, and ≥400, respectively, p < 0.001); these were significantly higher in the higher EAT volume group (>median; 107.2 mL, 0.7% vs., 2.1%, adjusted hazard ratio; 2.65, p = 0.0090). Cox-proportional hazard analysis demonstrated that a combination of CAC score ≥ 100 and high EAT volume had a significantly higher event rate than CAC score < 100 and low EAT volume group (adjusted hazard ratio 11.6, p < 0.0001). Using Cox regression models, incremental prognostic values were identified by adding high EAT volume to clinical risks plus CAC score ≥ 100 (global χ², 6.7; p = 0.059).

Conclusion

We suggest that high EAT volume may be an independent predictor of future coronary events and increases predictive values of CAC score in patients without proven CAD.     

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.     

The relationship of serum erythropoietin level with coronary collateral grade

Background

Erythropoietin has been shown to induce neovascularization and protect against ischemic vascular injury. We investigated whether a higher serum erythropoietin (EPO) level is related to better coronary collateral vessel grade.

Methods

Ninety-nine patients with stable angina pectoris who have at least 1 coronary stenosis of equal to or greater than 70% at coronary angiography were prospectively enrolled. Serum EPO and vascular endothelial growth factor (VEGF) levels were studied. Coronary collateral degree was graded according to the Rentrop method. Patients with grade 2-3 collateral degree were included in the good collateral group and formed Group I. The patients with grade 0-1 collateral degree were included in the poor collateral group and formed Group II.

Results

The serum EPO level was significantly higher in the good collateral group (17.3 ± 9.3 mU/mL vs 11.7 ± 5.0 mU/mL; P < 0.001). There was also a positive correlation between serum EPO level and Rentrop score (r = 0.39; P < 0.001). In multivariate analysis, serum EPO level (odds ratio [OR] 1.336; 95% confidence interval [CI], 1.120-1.593; P = 0.001), oxygen saturation (OR 0.638; 95% CI, 0.422-0.963; P = 0.033) and presence of chronic total occlusion (CTO) (OR 26.7; 95% CI, 3.874-184.6; P = 0.001) were independently related to well-developed coronary collaterals.

Conclusions

Higher serum EPO level is related to better coronary collateral development. Erythropoietin may have a positive effect on the development of collaterals and may provide a new agent for the treatment strategies to enhance coronary collateral vessel development.     

The effect of homocysteine-lowering therapy with folic acid on flow-mediated vasodilation in patients with coronary artery disease: A meta-analysis of randomized controlled trials

Objective

High level of homocysteine induces injury of endothelial cells and predicts adverse cardiovascular events. The objective was to assess the effect of homocysteine-lowering therapy with folic acid on flow-mediated vasodilation in patients with coronary artery disease.

Methods and results

We conducted a meta-analysis of randomized controlled trials identified from PubMed, Embase, the Cochrane Library. Eight studies were included. Homocysteine-lowering therapy with folic acid in patients with coronary artery disease significantly improve FMD as compared with placebo using random-effect model (SMD = 1.65 with 95% CI 1.12–2.17, p < 0.001). Subgroup analysis of subjects revealed that lipid-lowering therapy, study duration, and Delphi criteria had no effects on FMD.

Conclusion

Our meta-analysis demonstrated that folic acid supplementation can significantly improve endothelial dysfunction as assessed by FMD in the brachial artery in patients with coronary heart disease.     

Inverse correlation between coronary and retinal blood flows in patients with normal coronary arteries and slow coronary blood flow

Background

The “Slow Coronary Flow” (SCF) phenomenon in the presence of angiographically normal coronaries is attributed to microvascular and endothelial dysfunction. The microcirculation can be non-invasively assessed by measuring retinal blood flow velocity.The aim of the present study was to evaluate the efficacy of the “Retinal Functional Imager” (RFI) device as a noninvasive method of diagnosing patients with slow coronary flow.

Methods

Coronary blood flow velocity assessed by corrected TIMI Frame Count and retinal arterioles blood flow assessed by RFI were measured in 28 consecutive patients with normal coronary arteries. The patients were divided into 2 groups: a slow coronary flow (SCF) and a normal coronary flow (NCF) groups.

Results

Inverse correlation was found between retinal and coronary blood flows so that higher retinal arterial flow velocity was observed in the SCF group (3.8 ± 1.1 mm/s vs. 2.9 ± 0.61 mm/s, respectively, p = 0.022). RFI provided 73% sensitivity and 77% specificity for diagnosing SCF using ROC analysis. Additionally, patients with SCF had higher values of serum LDL cholesterol (104.7 ± 18.93 mg/dl vs. 81.55 ± 14.62 mg/dl in NCF, p = 0.005), Glucose (96.9 ± 23.0 mg/dl vs. 83.55 ± 9.7 mg/dl in NCF, p = 0.024), and lower percentage of statin consumption (40.0% vs. 76.9% in NCF, p = 0.049).

Conclusions

Slow coronary blood flow can be non-invasively diagnosed with Retinal Functional Imager. Patients with normal coronary arteries and slow coronary blood flow have high retinal arteriolar blood flow. Early non-invasive diagnosis of SCF might help detect individuals who are at higher risk to develop coronary atherosclerosis, and to provide them with early preventive measures.     

Incremental prognostic value of coronary computed tomographic angiography over coronary artery calcium score for risk prediction of major adverse cardiac events in asymptomatic diabetic individuals

Background

Coronary artery disease (CAD) diagnosis by coronary computed tomographic angiography (CCTA) is useful for identification of symptomatic diabetic individuals at heightened risk for death. Whether CCTA-detected CAD enables improved risk assessment of asymptomatic diabetic individuals beyond clinical risk factors and coronary artery calcium scoring (CACS) remains unexplored.

Methods

From a prospective 12-center international registry of 27,125 individuals undergoing CCTA, we identified 400 asymptomatic diabetic individuals without known CAD. Coronary stenosis by CCTA was graded as 0%, 1–49%, 50–69%, and ≥70%. CAD was judged on a per-patient, per-vessel and per-segment basis as maximal stenosis severity, number of vessels with ≥50% stenosis, and coronary segments weighted for stenosis severity (segment stenosis score), respectively. We assessed major adverse cardiovascular events (MACE) – inclusive of mortality, nonfatal myocardial infarction (MI), and late target vessel revascularization ≥90 days (REV) – and evaluated the incremental utility of CCTA for risk prediction, discrimination and reclassification.

Results

Mean age was 60.4 ± 9.9 years; 65.0% were male. At a mean follow-up 2.4 ± 1.1 years, 33 MACE occurred (13 deaths, 8 MI, 12 REV) [8.25%; annualized rate 3.4%]. By univariate analysis, per-patient maximal stenosis [hazards ratio (HR) 2.24 per stenosis grade, 95% confidence interval (CI) 1.61–3.10, p < 0.001], increasing numbers of obstructive vessels (HR 2.30 per vessel, 95% CI 1.75–3.03, p < 0.001) and segment stenosis score (HR 1.14 per segment, 95% CI 1.09–1.19, p < 0.001) were associated with increased MACE. After adjustment for CAD risk factors and CACS, maximal stenosis (HR 1.80 per grade, 95% CI 1.18–2.75, p = 0.006), number of obstructive vessels (HR 1.85 per vessel, 95% CI 1.29–2.65, p < 0.001) and segment stenosis score (HR 1.11 per segment, 95% CI 1.05–1.18, p < 0.001) were associated with increased risk of MACE. Beyond age, gender and CACS (C-index 0.64), CCTA improved discrimination by maximal stenosis, number of obstructive vessels and segment stenosis score (C-index 0.77, 0.77 and 0.78, respectively). Similarly, CCTA findings improved risk reclassification by per-patient maximal stenosis [integrated discrimination improvement (IDI) index 0.03, p = 0.03] and number of obstructive vessels (IDI index 0.06, p = 0.002), and by trend for segment stenosis score (IDI 0.03, p = 0.06).

Conclusion

For asymptomatic diabetic individuals, CCTA measures of CAD severity confer incremental risk prediction, discrimination and reclassification on a per-patient, per-vessel and per-segment basis.     

Long-term coronary arterial response to biodegradable polymer biolimus-eluting stents in comparison with durable polymer sirolimus-eluting stents and bare-metal stents: Five-year follow-up optical coherence tomography study

Objective

The long-term coronary arterial response of biodegradable polymer biolimus-eluting stents (BES) remains unclear. We sought to evaluate the coronary arterial response of biodegradable polymer BES at 5 years after stent implantation using optical coherence tomography (OCT) as compared with that of durable polymer sirolimus-eluting stents (SES) and bare-metal stents (BMS).

Methods

Five-year follow-up OCT was performed in 30 patients with 33 stents (10 with 12 BES; 10 with 11 SES; 10 with 10 BMS). Quantitative parameters and qualitative characteristics of the neointima were evaluated. A total of 5178 struts (BES, n = 2056; SES, n = 1410; BMS, n = 1712) were analyzed.

Results

Uncovered struts were found in 15 out of 2055 struts in the BES (weighted estimate 0.01%, 95% confidence intervals [CI]: 0.00–0.33%) and 54 out of 1410 struts in the SES (0.11%, 95% CI: 0.00–3.33%) (odds ratio [OR] 0.12, 95% CI: 0.01–1.95, p = 0.13). None of 1712 struts were uncovered in the BMS. Cross-sectional qualitative analysis of neointimal tissue showed that the frequency of lipid-laden neointima tended to be lower in the BES (2.26%, 95% CI: 0.38–12.3%) compared with the SES (9.90%, 95% CI: 4.37–20.9%; OR 0.21, 95% CI 0.03–1.16, p = 0.07), and was similar to the BMS (2.23%, 95% CI: 0.54–8.74%; OR 0.98, 95% CI 0.13–7.14, p = 0.98).

Conclusions

Biodegradable polymer BES shows a favorable coronary arterial response compared with SES, but different response with BMS at 5 years follow-up. The observed frequency of in-stent neoatherosclerosis within BES was similar to BMS and tended to be lower than SES.     

Clinical results of percutaneous transluminal angioplasty for thromboangiitis obliterans in arteries above the knee

Objective

This study was designed to retrospectively investigate whether percutaneous transluminal angioplasty (PTA) is efficacious and safe for the treatment of atypical thromboangiitis obliterans (ATAO) in arteries with occlusion of long segments.

Methods

From January 2011 to July 2013, 9 consecutive male patients with ATAO involving the external iliac and superficial femoral arteries were treated by PTA alone, without stent placement. Their mean age was 35 years (range, 24–47 years). Preoperative symptoms included severe claudication (n = 2), ischemic pain at rest (n = 4), and ischemic ulcers (n = 3). No any infrapopliteal interventions were performed besides the proximal intervention.

Results

Technical success using PTA was achieved in 100% of cases with occluded arteries, and there were no periprocedural complications. Clinical improvement was observed postoperatively with a significant improvement in Rutherford categories (range, 2–3) and significantly increased ankle-brachial indexes, from 0.59 ± 0.14 to 0.91 ± 0.17 (p < 0.01). Ischemic ulcers in three patients healed 3–5 months postoperatively. No recurrent ischemic ulcer was observed, and no amputation was performed in these patients. At follow-up examination (average, 20.9 months), restenosis of the superficial femoral artery was diagnosed in only one patient who continued with a conservative medication regimen and refused additional interventional treatment because his physical symptoms were minor.

Conclusion

PTA might be feasible and safe for the treatment of ATAO patients, and appears to provide positive clinical results at an average follow-up of 20.9 months.     

Prognostic significance of six-minute walk test in non-group 1 pulmonary hypertension

Objective

To assess the value of the six-minute walk test (6MWT) to predict outcome in non-group 1 pulmonary hypertension (PH).

Background

Distance walked during 6MWT has been widely used as a prognostic test in pulmonary arterial hypertension (group 1 pulmonary hypertension); however, little is known regarding its prognostic value in other groups of PH.

Methods

This was a retrospective study of 60 patients diagnosed of PH, Dana Point classification groups 2–5. 6MWT and echocardiography were performed in all cases.

Results

Forty patients (66.6%) were females. Mean age was 70.8 ± 10.7 years (range: 32–85). Seven patients died after a mean follow-up of 23.2 ± 16.7 months. Distance <400 m during 6MWT was associated with a higher risk for death (RR: 4.39; 95% CI: 1.13-17.05; p = 0.03) and for clinical deterioration (death or need for hospitalization) (RR: 2.76; 95% CI: 1.18–6.42; p = 0.02).

Conclusions

6MWT is useful to predict outcome in non-group 1 PH.     

Low exercise blood pressure and risk of cardiovascular events and all-cause mortality: Systematic review and meta-analysis

Objective

The independent prognostic significance of abnormally low systolic blood pressure (SBP) during exercise stress testing (LowExBP) across different clinical and exercise conditions is unknown. We sought by systematic review and meta-analysis to determine the association between cardiovascular/all-cause outcomes and LowExBP across different patient clinical presentations, exercise modes, exercise intensities and categories of LowExBP.

Methods

Seven online databases were searched for longitudinal studies reporting the association of LowExBP with risk of fatal and non-fatal cardiovascular events and/or all-cause mortality. LowExBP was defined as either: SBP drop below baseline; failure to increase >10 mmHg from baseline or; lowest SBP quantile among reporting studies.

Results

After review of 13,257 studies, 19 that adjusted for resting SBP were included in the meta-analysis, with a total of 45,895 participants (average follow-up, 4.4 ± 3.0 years). For the whole population, LowExBP was associated with increased risk for fatal and non-fatal cardiovascular events and all-cause mortality (hazard ratio [HR]: 2.01, 95% confidence interval [CI]: 1.59–2.53, p < 0.001). In continuous analyses, a 10 mmHg decrease in exercise SBP was associated with higher risk (n = 9 HR: 1.13, 95% CI: 1.06–1.20, p < 0.001). LowExBP was associated with increased risk regardless of clinical presentation (coronary artery disease, heart failure, hypertrophic cardiomyopathy or peripheral artery disease), exercise mode (treadmill or bike), exercise intensity (moderate or maximal), or LowExBP category (all p < 0.05). However, bias toward positive results was apparent (Eggers test p < 0.001 and p = 0.009).

Conclusion

Our data show that irrespective of clinical or exercise conditions, LowExBP independently predicts fatal and non-fatal cardiovascular events and all-cause mortality.     

Smoking and infarct size among STEMI patients undergoing primary angioplasty

Background

Prior studies have found that smokers with STEMI have lower mortality rates and a more favorable response to fibrinolytic therapy than nonsmokers, phenomenon defined as “the smoker's paradox”. Still poorly explored is the impact of cigarette smoking in patients undergoing primary percutaneous coronary intervention. Aim of the current study was to evaluate the impact of cigarette smoking on scintigraphic infarct size in STEMI patients undergoing primary PCI.

Methods

Our population is represented by 830 STEMI patients undergoing primary PCI. Infarct size was evaluated at 30 days by technetium-99m-sestamibi.

Results

Smoking was associated with younger age (p < 0.001), a lower prevalence of female gender (p < 0.001), hypertension (p < 0.001), diabetes (p = 0.003), shorter ischemia time (p = 0.037), but higher rates of previous PCI (p = 0.016). No differences were observed in other clinical or angiographic characteristics. In particular, smoking did not affect the rate of postprocedural TIMI 3 flow. As shown in Fig. 1, smoking did not affect infarct size (12.5% [3.3%–23.7%] vs 12.7% [4.9%–25.9%], p = 0.12). Similar results were observed in subanalyses according to infarct location (anterior STEMI, p int = 0.33), gender (p int = 0.95) age, (p Int = 0.96), diabetes (p int = 0.85). The absence of any impact of smoking on infarct size was confirmed after correction for baseline characteristics, such as age, gender, hypertension, diabetes, previous PCI, ischemia time (OR [95% CI] = 0.80 [0.59–1.09], p = 0.15).

Conclusions

This study shows that among STEMI patients undergoing primary PCI smoking status does not affect infarct size.     

GNB3 gene 825 TT variant predicts hard coronary events in the population-based Heinz Nixdorf Recall study

Objective

The C825T polymorphism of the gene encoding the human G protein beta-3 subunit (GNB3) is associated with hypertension and obesity. Moreover, genotypes of the GNB3 polymorphism have been associated with development of coronary artery disease, and the 825T allele is thought to influence the process of atherosclerosis. However, the potential of the C825T polymorphism to predict coronary events has been poorly explored in a longitudinal setting at the population level.

Methods

In 4159 Caucasian subjects from the Heinz Nixdorf Recall study cohort (age: 45–75 years, 48% male), genotypes of the GNB3 C825T polymorphism (rs5443) were determined and associated with fatal and non-fatal myocardial infarction (hard coronary events). Established cardiovascular risk factors were used to adjust for confounders.

Results

The median follow-up time was 9.9 years (1st/3rd quartiles 9.5/10.2). 148 subjects (3.6%) experienced a hard coronary event. The 10-year event-free survival rate was CC, 96.1%; CT 96.9%, TT, 93.7% (p = 0.018). Multivariable analysis showed that the TT genotype is a significant risk factor for hard coronary events (hazard ratio (HR) = 1.9 (95% confidence interval (CI) 1.2–2.9); p = 0.008) after adjustment for age, sex, diabetes, systolic blood pressure, body mass index, high-density lipoprotein, and coronary artery calcification as determined by electron beam computed tomography at baseline. While prognosis in females was independent of GNB3 genotypes, analysis in males even elevated the HR for TT versus C-allele to 2.6 (95% CI 1.6–4.2; p < 0.001).

Conclusion

The GNB3 825 TT genotype is a significant and independent risk factor for hard coronary events independent of other established cardiovascular risk factors at a population level in males.     

Low serum level of secreted frizzled-related protein 5, an anti-inflammatory adipokine,is associated with coronary artery disease

Objective

Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine that is associated with insulin resistance in animals. To extend these observations to humans, we investigated the association of serum SFRP5 levels in subjects with and without coronary artery disease (CAD).

Methods

Subjects (n = 185, 68 ± 11 years, 79% male) suspected of having CAD were enrolled in the study and were divided into two groups, CAD and non-CAD subjects, according to the results of their coronary angiographies. Serum SFRP5 levels of the subjects were measured by an enzyme-linked immunosorbent assay.

Results

The serum SFRP5 levels in the subjects with CAD were significantly lower than those in the non-CAD subjects (median [interquartile range]: 47.7 [26.6] vs. 52.4 [29.6] ng/mL, respectively; p = 0.02). The serum SFRP5 levels significantly correlated with body mass index, the homeostasis model of assessment of insulin resistance, adiponectin levels, and CAD severity. Multivariate logistic regression analysis revealed that a decreased serum SFRP5 level (log transformed) was independently associated with CAD for all subjects (adjusted odds ratio, 0.36; 95% confidence interval, 0.14–0.94; p = 0.03).

Conclusion

Serum SFRP5 levels are significantly associated with CAD in humans, suggesting that low SFRP5 levels may contribute to CAD.     

Association of Lp-PLA2 with digital reactive hyperemia,coronary flow reserve,carotid atherosclerosis and arterial stiffness in coronary artery disease

Background

Lipoprotein-associated Phospholipase A2 (Lp-PLA2), has a powerful inflammatory and atherogenic action in the vascular wall and is an independent marker of poor prognosis in coronary artery disease (CAD). We investigate the association of Lp-PLA2 with markers of vascular dysfunction and atherosclerosis with proven prognostic value in CAD.

Methods

In 111 patients with angiographically documented chronic CAD, we measured 1) carotid intima-media thickness (CIMT), 2) reactive hyperemia using fingertip peripheral arterial tonometry (RH-PAT), 3) coronary flow reserve (CFR), by Doppler echocardiography 4) pulse wave velocity (PWV) and 5) blood levels of Lp-PLA2.

Results

Patients with Lp-PLA2 concentration >234.5 ng/ml (50th percentile) had higher CIMT (1.44 ± 0.07 vs. 1.06 ± 0.06 mm), PWV (11.0 ± 2.36 vs. 9.7 ± 2.38 m/s) and lower RH-PAT(1.24 ± 0.25 vs. 1.51 ± 0.53) and CFR (2.39 ± 0.75 vs. 2.9 ± 0.86) compared to those with lower Lp-PLA (p < 0.05 for all comparisons). Lp-PLA2 was positively associated with CIMT (regression coefficient b: 0.30 per unit of Lp-PLA2, p = 0.02), PWV (b:0.201, p = 0.04) and inversely with RHI-PAT (b: −0.371, p < 0.001) and CFR (b:−0.32, p = 0.002). In multivariate analysis, Lp-PLA2 was an independent determinant of RHI-PAT, CFR, CIMT and PWV in a model including age, sex, smoking, diabetes, dyslipidemia and hypertension (p < 0.05 for all vascular markers). Lp-PLA2, RHI-PAT and CFR were independent predictors of cardiac events during a 3-year follow-up.

Conclusions

Elevated Lp-PLA2 concentration is related with endothelial dysfunction, carotid atherosclerosis, impaired coronary flow reserve and increased arterial stiffness and adverse outcome in CAD patients. These findings suggest that the prognostic role of Lp-PLA2 in chronic CAD may be explained by a generalized detrimental effect of this lipase on endothelial function and arterial wall properties.     

Comparison of blind intubation through the I-gel and ILMA Fastrach by nurses during cardiopulmonary resuscitation: A manikin study

Objectives

To investigate whether nursing staff can successfully use the I-gel and the intubating laryngeal mask Fastrach (ILMA) during cardiopulmonary resuscitation.

Background

Although tracheal intubation is considered to be the optimal method for securing the airway during cardiopulmonary resuscitation, laryngoscopy requires a high level of skill.

Methods

Forty five nurses inserted the I-gel and the ILMA in a manikin, with continuous and without chest compressions.

Results

Mean intubation times for the ILMA and I-gel without chest compressions were 20.60 ± 3.27 and 18.40 ± 3.26 s, respectively (p < 0.0005). ILMA proved more successful than the I-gel regardless of compressions. Continuation of compressions caused a prolongation in intubation times for both the I-gel (p < 0.0005) and the ILMA (p < 0.0005).

Conclusion

In this mannequin study, nursing staff can successfully intubate using the I-gel and the ILMA as conduits with comparable success rates, regardless of whether chest compressions are interrupted or not.     

Association of virtual histology characteristics of the culprit plaque with post-fibrinolysis flow restoration in ST-elevation myocardial infarction

Objectives

We sought to test the hypothesis that virtual histology characteristics of the culprit lesion in patients with ST-elevation myocardial infarction are associated with blood flow restoration after thrombolysis.

Methods

Consecutive patients referred for coronary angiography after successful thrombolysis were included in this correlational cross-sectional study. Evaluation with intravascular ultrasound (IVUS) and virtual histology of the culprit arterial segment was performed in all cases.

Results

Forty-eight patients (60.5 ± 10.7 years) were included. TIMI flow grade 3 was found in 24 (50%). Diabetes was strongly associated with lower TIMI flow 3 rate (26.7% vs 60.6%; p = 0.029) and there was a significant difference in the time to thrombolysis (2.0 ± 0.8 hours in those with TIMI flow 3 vs 3.0 ± 0.7 hours in TIMI flow grades 1–2; p < 0.001). Patients with TIMI flow grades 3 and 1–2 had similar absolute total plaque volume (152.8 ± 59.3 mm³ vs 147.5 ± 92.3 mm³; p = 0.817) and absolute necrotic core (NC) volume (31.2 ± 13.9 mm³ vs 33.6 ± 23.2 mm³; p = 0.671). However, there were significant differences in the relative NC content, both in proportion to the whole plaque volume (26.3% vs 29.9%; p = 0.016) and as an area fraction at the largest NC site (31.5% vs 40.3%; p < 0.001).

Conclusion

The NC content of atherosclerotic plaques is meaningful for flow restoration after the occurrence of a coronary event. This finding highlights the importance of plaque composition, as studied with virtual histology, not only for the sequence of processes leading to an acute plaque-related event, but also for thrombus formation and lysis, following the occurrence of such an event.     

Associations of matrix metalloproteinase-9 and monocyte chemoattractant protein-1 concentrations with carotid atherosclerosis,based on measurements of plaque and intima–media thickness

Purpose

To examine associations of matrix metalloproteinase-9 (MMP-9) and monocyte chemoattractant protein-1 (MCP-1) concentrations with the severity of carotid atherosclerosis, based on measurements of carotid plaque and intima–media thickness (IMT).

Methods

This cross-sectional study included 116 stroke-free participants (45.7% males, 54.3% females; mean age, 64.73 ± 14.53 years). Serum MMP-9 and MCP-1 concentrations were measured, and plaque morphology, including total plaque score (PS), plaque stability, and IMT, was assessed ultrasonographically. Participants were grouped according to total PS (0, 1–2, ≥3), plaque stability (no plaque, stable, unstable) and IMT tertiles (<0.8 mm, 0.8–1 mm, >1 mm). Multinomial logistic regression models were used to assess the associations of MMP-9 and MCP-1 concentrations with plaque and IMT values after adjusting for vascular risk factors.

Results

MMP-9 quartiles (vs. quartile 1) were significantly associated with a greater prevalence of plaque instability [Q2: odds ratio (OR) = 5.13, 95% confidence interval (CI) = 1.01–24.9, p = 0.042; Q3: OR = 15.5, 95% CI = 3.1–78.1, p = 0.001; Q4: OR = 13.2, 95% CI = 2.7–64.97, p = 0.001] and high total PS (Q3: OR = 10.02, 95% CI = 1.5–65.33, p = 0.016; Q4: OR = 21.5, 95% CI = 3.5–132.1, p = 0.001). MCP-1 concentration was significantly associated with IMT (OR = 22.94, 95% CI = 2.14–245.66, p = 0.01).

Conclusions

Elevated serum MMP-9 concentration was independently associated with high total carotid artery PS, plaque instability, and large IMT value. MCP-1 concentration was independently associated with IMT, but not with plaque morphology.     

Undercarboxylated osteocalcin relates to cardiovascular risk markers in offspring of families with metabolic syndrome

Background

The undercarboxylated form of osteocalcin (ucOC) is an emerging marker of cardiovascular disease. It is unknown if ucOC in related to common cardiovascular risk markers in children. In offspring of families with and without metabolic syndrome (MetS+ and MetS− families), we assessed whether ucOC was related to a continuous metabolic syndrome score (MetS score) and to carotid intima–media thickness (cIMT).

Methods

ucOC and total OC, MetS score and cIMT were assessed in 203 asymptomatic prepubertal children (age 7.6 ± 0.1 yr; 49% girls), of whom 99 were from MetS+ families.

Results

In children from MetS+ families, percent ucOC was higher than in children from MetS− families (p < 0.01). In offpring from MetS+ families, higher ucOC and especially higher percent ucOC was independently associated with both the MetS score and cIMT (both p ≤ 0.01).

Conclusions

The undercarboxylated form of OC is related to common cardiovascular risk markers in children at risk for cardiovascular disease.