We measured plasma MPO and sCD40L in 1524 patients with ACS treated with tirofiban and randomized to early invasive vs. conservative management in the TACTICS-TIMI 18 trial who survived to 180 days. Patients with elevated baseline MPO (>884 pM) were at higher risk of non-fatal myocardial infarction or rehospitalization for ACS at 30 days (9.3 vs. 4.6%, P < 0.001). In contrast, no difference was observed with higher sCD40L (>989 pg/mL, 7.6 vs. 6.3%, P = 0.31). MPO remained associated with recurrent ischaemic events after adjustment for age, ST-deviation, diabetes, prior coronary artery disease, heart failure, cTnI, hsCRP, and sCD40L (OR 2.10; 95% CI 1.36–3.23, P = 0.001). This association was attenuated by 180 days (OR 1.26; 0.95–1.68). Stratification using baseline MPO, BNP, and cTnI identified a >3-fold gradient of risk.

MPO adds to BNP and cTnI for short-term risk assessment for recurrent ischaemic events in non-ST elevation ACS. sCD40L was not associated with risk in this population treated with a platelet GPIIb/IIIa receptor antagonist.

We examined acute medication and invasive cardiac procedure use and in-hospital outcomes among 101 078 patients with NSTE ACS included in the CRUSADE registry. On admission, 7201 patients (7%) were on home warfarin therapy. Compared with non-anticoagulated patients, these patients were older and had more comorbidities, but were less likely to receive acute antiplatelet and antithrombin medications. Patients on warfarin were also less likely to undergo coronary angiography (adjusted OR 0.77, 95% CI 0.70–0.86) and percutaneous coronary intervention (adjusted OR 0.80, 95% CI 0.75–0.86), and had longer waiting times for these procedures when performed. Although patients on warfarin had higher rates of death and major bleeding compared with non-anticoagulated patients, these differences were no longer significant after multivariable adjustment [ORs 0.90 (95% CI 0.80–1.02) and 1.02 (95% CI 0.93–1.11)]. Among patients on warfarin, however, early use of antiplatelet medications was associated with increased transfusion risk.

Despite higher-risk characteristics, warfarin-anticoagulated patients are often more conservatively managed, as early use of antithrombotic therapies may be associated with increased bleeding. Further investigation is needed to determine the optimal choice of therapies for this population.

Depression status (Beck Depression Inventory, BDI), selected CHD risk factors, inflammation markers, measures of heart rate variability (HRV), and indices of endothelial function (flow-mediated dilation, FMD) were evaluated in 415 subjects free of CHD, diabetes mellitus, and other life-threatening conditions, with at least two CHD risk factors among the following: older age, male gender, current smoking, hypertension, and dislipidaemia. Overall, 51.7% of the participants were males, aged 57.6 ± 8.8 years on average (minimum 30, maximum 70). Almost half were hypertensive, 43.9% were dyslipidemic, 30.4% current smokers, and 23.1% showed a depressive symptomatology (BDI ≥ 10). Logistic regression showed that, as compared with non-depressed individuals and after adjustment for age, gender, and hypertension, depressive subjects were significantly more likely to be smokers, to have higher total cholesterol, higher C-reactive protein, and Interleukin-6. In addition, depressed subjects were more likely to have altered HRV and their FMD was severely impaired (adjusted odds ratio of 1% increase = 0.72; 95% CI: 0.61–0.86).

Our data indicate an independent association between depression and impaired HRV, systemic inflammatory, and endothelial function. These mechanisms play a role not only in the complication of advanced forms of disease, but also promote and/or accelerate the early disease and connect depression and CHD.

Sixteen untreated dyslipidaemic subjects with moderately increased cardiovascular risk (National Cholesterol Education Program, Adult Treatment Panel III) were studied before and during long-term (1 year) simvastatin treatment. Neutrophils from dyslipidaemic subjects generated more ROS in comparison with cells from healthy control subjects. After 1 year of simvastatin treatment, ROS production (delta N-formyl-Met-Leu-Phe-induced generation and area under the curve) was significantly reduced. At baseline, AT₁-R mRNA expression was also higher in dyslipidaemic subjects than in healthy controls and it was reduced after clinical treatment with simvastatin. In a subgroup of patients, a reduced angiotensin II-induced ROS generation was also observed upon clinical simvastatin treatment. Moreover, a direct effect of statin on the upregulated AT₁-R expression was demonstrated in vitro in neutrophils of untreated dyslipidaemic subjects.

A consistent reversion of pro-inflammatory oxidative functional response and reduction of AT₁-R expression in primed PMNs was observed in patients during long-term statin treatment. The AT₁-R reduction over treatment may contribute to the normalization of dysregulated neutrophil activation which occurs in the pre-clinical phase of atherosclerosis.

Among 5745 patients enrolled in the trial, 1018 underwent independent quantitative angiographic evaluation by a core laboratory. Successful epicardial reperfusion was defined as TIMI (thrombolysis in myocardial infarction) flow grade 3 or corrected TIMI frame count (cTFC) <28 frames, and successful myocardial reperfusion as TIMI myocardial perfusion grade (TMPG) 2 or 3. TIMI 3 flow after PCI occurred in 85%, cTFC < 28 in 58% (mean cTFC was 27 ± 20), and TMPG 2 or 3 in 91%. Overall 90 day clinical outcomes were 2.7% for mortality and 8.2% for the composite of death, congestive heart failure (CHF), or shock. After adjustment for baseline characteristics, TMPG 2/3 after PCI was associated with younger age [odds ratio (OR) for 10 year increase 0.75, 95% confidence interval (CI) 0.59–0.96, P = 0.023], pre-PCI TIMI flow 2/3 (OR 3.5, 95% CI 1.7–7.1, P = 0.001), and ischaemic time [for every hour, OR 0.81 (0.69–0.96), P = 0.015]. TMPG 2/3 after PCI was significantly associated with 90 day mortality (adjusted hazard ratio 0.26, 95% CI 0.09–0.78, P = 0.013). Neither post-PCI TMPG nor TIMI flow grade was significantly associated with 90 day death/CHF/shock.

Younger age, patent infarct-related artery at presentation, and ischaemic time predicted higher likelihood of successful myocardial perfusion, which was associated with improved survival.

In 56 patients with angina, 126 plaques identified by IVUS findings were analysed using both VH-IVUS and OCT. IVUS-derived TCFA was defined as an abundant necrotic core (>10% of the cross-sectional area) in contact with the lumen (NCCL) and %plaque-volume >40%. OCT-derived TCFA was defined as a fibrous cap thickness of <65 µm overlying a low-intensity area with an unclear border. Plaque meeting both TCFA criteria was defined as definite-TCFA. Sixty-one plaques were diagnosed as IVUS-derived TCFA and 36 plaques as OCT-derived TCFA. Twenty-eight plaques were diagnosed as definite-TCFA; the remaining 33 IVUS-derived TCFA had a non-thin-cap and eight OCT-derived TCFA had a non-NCCL (in discord with NCCL visualized by VH-IVUS, mainly due to misreading caused by dense calcium). Based on IVUS findings, definite-TCFA showed a larger plaque and vessel volume, %plaque-volume, higher vessel remodelling index, and greater angle occupied by the NCCL in the lumen circumference than non-thin-cap IVUS-derived TCFA.

Neither modality alone is sufficient for detecting TCFA. The combined use of OCT and VH-IVUS might be a feasible approach for evaluating TCFA.

Eighteen studies with a total of 1755 patients, stratifying survival, and cardiac events in patients with HF by MIBG, were eligible for analysis. The pooled hazard ratio (HR) estimates for cardiac death and cardiac events associated with washout showed no significant heterogeneity and were 1.72 [95%CI (confidence interval), 1.72–2.52; P = 0.006] and 1.08 (95%CI: 1.03–1.12; P < 0.001), respectively. The pooled HR estimates for cardiac death and cardiac events associated with early H/M and late H/M showed significant heterogeneity (I² ≥ 75%). Limiting the pooling to the qualitative best three studies rendered I² insignificant (I² = 0) and resulted in a pooled HR of late H/M for cardiac death of 1.82 (95%CI: 0.80–4.12; P = 0.15) and for cardiac events of 1.98 (95%CI: 1.57–2.50; P < 0.001).

Our results indicate that patients with HF and decreased late H/M or increased myocardial MIBG washout have a worse prognosis compared with those with normal semi-quantitative myocardial MIBG parameters.

Cohort study from six regional centres of paediatric cardiology, including children presenting with sudden death; n = 150 (59% = male; 39% familial HCM). Age- and gender-specific mortality was calculated, and compared with rates calculated from the Swedish National Cause of Death Registry. There were 56 deaths within the cohort, 39 were sudden arrhythmia deaths, with 31 at <19 years of age. Between 9–13.9 years of age annual sudden death mortality averages 7.2%, vs. 1.7% after 16 years of age; P = 0.025, odds ratio for proportions 3.75 [95% confidence intervals (CI) 1.18–11.91], similar in both familial and idiopathic HCM. The risk for sudden death peaks earlier in girls (10–11 years), with male preponderance after the age of 15. National cause of death statistics confirm that the mortality rate from HCM is significantly higher in the 8–16 year olds (0.112 per 100 000 age-specific population) than in the 17–30 year olds (0.055 per 100 000; 95% CI 0.011–0.099).

In families with HCM, children should be screened at an early age.

Oligonucleotide microarray analysis was performed on endomyocardial biopsies (EMBs) from patients with early DCM (LVEDD ≥ 55 mm, LVEF ≤ 55%, n = 5) and control subjects (LVEDD < 55 mm, LVEF > 60%, no cardiac pathology, n = 4). Adiponectin, an adipocytokine involved in cellular metabolism, survival, and immunmodulation, was six-fold downregulated in DCM patients. Microarray data for adiponectin were confirmed by TaqMan-PCR (9.2-fold downregulation, control n= 9 vs. DCM n= 9, respectively, P < 0.05). Immunohistological analysis of EMBs showed significant downregulation of cardiac adiponectin protein expression independent of serum adiponectin (P = 0.36, ns) or serum TNF concentrations (P = 0.46, ns). Neither the adiponectin receptor 1 (adipo-R1) nor adipo-R2 was deregulated in early DCM. Adiponectin mRNA and protein downregulation were confirmed in explanted hearts of patients with advanced DCM (LVEF < 25%, n= 8). In vitro, adiponectin incubation of neonatal rat ventricular myocytes led to activation of the pro-survival kinase PKB/Akt, increased eNOS-phosphorylation, and prevented stress-induced apoptosis of cardiomyocytes in an Akt-dependent manner. Moreover, inhibition of adiponectin secretion was accompanied by an increase in the expression of the cytokine and its receptors.

These data indicate the existence of a local cardiac adiponectin system regulated independent of adiponectin and TNF serum levels and its disturbance in cardiac pathology. The study suggests a role for adiponectin in the pathogenesis of DCM and implicates the adipocytokine as a possible future therapeutic target in DCM.

The EHS enrolled 5333 AF patients in 2003–2004. One-year follow-up data were available for 80%. Of first detected AF patients, 46% did not have a recurrence during 1 year, paroxysmal AF largely remained paroxysmal AF (80%), and 30% of persistent AF progressed to permanent AF. Many treatment changes occurred since baseline. Oral anticoagulation was started in 19% and discontinued in 16% of all patients. Of patients initially on rhythm control 27% did not receive rhythm control during follow-up, whereas 15% of patients initially on rate control received rhythm control. Mortality was highest in permanent AF (8.2%), but also substantial in first detected AF (5.7%). In multivariable analysis, sinus rhythm at baseline was associated with lower mortality, but no significant effect was observed regarding the application of either rhythm or rate control.

The EHS on AF provides unique prospective observational data on AF progression, long-term treatment, prognosis, and determinants of adverse outcome of the total clinical spectrum of AF in a European cardiology-based patient cohort.

Atrial myocytes were isolated from right atrial appendages obtained from 86 adult patients in sinus rhythm with coronary artery disease, aortic valve disease, or mitral valve disease (MVD). Current was recorded in isolated myocytes using the whole-cell patch-clamp technique. The I_CaL recorded in the 172 myocytes studied showed a marked variability of peak density ranging from 0.1 to 9.0 pA/pF. The I_CaL peak density did not correlate with membrane capacitance or changes in current biophysical properties. The I_CaL peak density was homogeneous for a given sample. Small I_CaL values were recorded in patients with MVD or with a low left ventricular ejection fraction (<45%). Small I_CaL values were more sensitive to the β-adrenergic agonist, isoproterenol (1 µM), and to the phosphodiesterase inhibitor, 3-isobutyl-1-methyl-xanthine (10 µM).

In human atrial myocytes, the variability of I_CaL is related to the clinical history of the donors. The downregulation of I_CaL is already observed in patients in sinus rhythm with a high risk of AF and is associated with the greatest response to β-adrenergic agonist.

We measured IMT, CAC, and FMD with ultrasound in 2265 subjects aged 24–39 years. The mean values (mean ± SD) in men and women were 0.592 ± 0.10 vs. 0.572 ± 0.08 mm (P < 0.0001) for IMT, 2.00 ± 0.66 vs. 2.31 ± 0.77%/10 mmHg (P < 0.0001) for CAC, and 6.95 ± 4.00 vs. 8.83 ± 4.56% (P < 0.0001) for FMD. The sex differences in IMT [95% confidence interval (CI) for sex difference –0.013 to 0.004 mm, P = 0.37] and CAC (–0.01 to 0.18%/10 mmHg, P = 0.09) became non-significant after adjustments with risk factors and carotid diameter. In FMD, the sex difference was unaltered after adjustments for risk factors, but was reversed after adjustment with brachial diameter (95% CI 0.18–1.32%, P < 0.01). With aging, IMT increased 5.7 ± 0.4 µm/year and CAC decreased 0.042 ± 0.003%/10 mmHg/year. The association of age with IMT and CAC was slightly attenuated (12 and 22%, respectively) after adjustments with risk factors, but remained significant (both P < 0.0001). Aging was not significantly related to brachial FMD (P = 0.16).

Reference values produced in the present study can be utilized in the cardiovascular risk stratification among young people. Sex differences in the markers of subclinical atherosclerosis were mostly explained by differences in risk factors and vessel size. This emphasizes the importance of risk factor control in the prevention of atherosclerosis in young adults.