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Aims: Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence., Methods and Results: A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period., Conclusion: Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For Permissions, please email: journals.permissions@oup.com.)

Aim: Heart disease is a common fatal diabetes-related complication. Early detection of patients at particular risk of heart disease is of prime importance. Soluble urokinase plasminogen activator receptor (suPAR) is a novel biomarker for development of cardiovascular disease. We investigate if suPAR is associated with early myocardial impairment assessed with advanced echocardiographic methods., Methods: In an observational study on 318 patients with type 1 diabetes without known heart disease and with normal left ventricular ejection fraction (LVEF) (biplane LVEF >45%), we performed conventional, tissue Doppler and speckle tracking echocardiography, and measured plasma suPAR levels. Associations between myocardial function and suPAR levels were studied in adjusted models including significant covariates., Results: Patients were 55±12 years (mean±s.d.) and 160 (50%) males. Median (interquartile range) suPAR was 3.4 (1.7) ng/mL and LVEF was 58±5%. suPAR levels were not associated with LVEF (P=0.11). In adjusted models, higher suPAR levels were independently associated with both impaired systolic function assessed with global longitudinal strain (GLS) and tissue velocity s', and with impaired diastolic measures a' and e'/a' (all P=0.034). In multivariable analysis including cardiovascular risk factors and both systolic and diastolic measures (GLS and e'/a'), both remained independently associated with suPAR levels (P=0.012)., Conclusions: In patients with type 1 diabetes with normal LVEF and without known heart disease, suPAR is associated with early systolic and diastolic myocardial impairment. Our study implies that both suPAR and advanced echocardiography are useful diagnostic tools for identifying patients with diabetes at risk of future clinical heart disease, suited for intensified medical therapy., (© 2016 European Society of Endocrinology.)

Aims: To examine trends in the use of diagnostic coronary angiography according to distance from home to the nearest invasive heart centre following implementation of fast-track protocols and extensive pre-hospital triaging of acute coronary syndrome patients., Methods and Results: We performed a register-based cohort study of all patients admitted to Danish hospitals with incident acute coronary syndrome in 2005-2011. Diagnostic coronary angiography within 60 days of admission was investigated according to distance tertiles (DTs) calculated as range from each patient's home to the nearest invasive heart centre (short DT: <22 km, medium DT: 22-65 km, long DT: >65 km). Cox proportional hazards models were applied.Among the 52,409 patients included, diagnostic coronary angiography was increasingly used during 2005-2011 (short DT: 76% to 81%; medium DT: 74% to 81%; long DT: 69% to 78%; all p-values for trend <0.001). Using the short DT as reference the adjusted hazard ratios for medium DT were 0.87 (0.84-0.89) for 2005-2007, 0.94 (0.90-0.98) for 2008-2009 and 0.94 (0.90-0.98) for 2010-2011. Corresponding figures for long DT were 0.74 (0.72-0.76) for 2005-2007, 0.87 (0.83-0.90) for 2008-2009 and 0.94 (0.90-0.98) for 2010-2011. Length of hospital stay, time to coronary angiography, and 60-day mortality decreased in all DT., Conclusions: This nationwide study found significant increases in diagnostic coronary angiography use over time in incident acute coronary syndrome patients with a relatively larger increase in patients residing farthest from an invasive heart centre. Additionally, selected quality of care measures improved in the entire cohort, suggesting a benefit of national clinical protocols., (© The European Society of Cardiology 2014.)

Background: Osteopontin (OPN), a multifunctional glycoprotein, has recently been found to be an important player in cardiovascular diseases and to be implicated in a variety of acute as well as chronic inflammatory processes, including atherosclerosis. This study investigates the association between plasma OPN at admission and the long-term outcome in patients with ST segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI)., Methods: We included a total of 730 consecutive STEMI patients admitted to a single high-volume invasive heart centre between September 2006 and December 2008. Plasma OPN and high sensitivity C-reactive protein (hsCRP) were measured., Results: The median follow-up time was 27 months (interquartile range: 22-33) and endpoints were all-cause mortality, re-infarction and heart failure. Even when adjusted for all baseline variables, increasing OPN was independently associated with increased all-cause mortality, and the combined endpoint, a linear increase in OPN of 10 µg/l, was associated with a hazard ratio (HR) of 1.05 (95% confidence interval (CI): 1.02-1.08; p = 0.002) for all-cause mortality and HR 1.03 (95%CI: 1.01-1.05; p = 0.047) for the combined endpoint. Importantly, OPN interacted with the predictive power of hsCRP, and the combination of high OPN levels and high hsCRP levels (>3 mg/l) were significantly associated with increased risk of all-cause mortality (HR: 2.32; CI: 1.51-3.58; p < 0.001), re-infarction (HR: 2.19; CI: 1.22-3.93; p = 0.006), heart failure (HR: 1.84; CI: 1.08-3.13; p = 0.025) and the combined endpoint (HR: 2.08; CI: 1.53-2.84; p < 0.001)., Conclusions: In conclusion, a high OPN level, especially in combination with a high hsCRP level, was associated with poor long-term outcome in STEMI patients treated with pPCI.

Aims: Exenatide, a glucagon-like-peptide-1 analogue, increases myocardial salvage in experimental settings with coronary occlusion and subsequent reperfusion. We evaluated the cardioprotective effect of exenatide at the time of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (pPCI)., Methods and Results: A total of 172 patients with STEMI and Thrombolysis in Myocardial Infarction flow 0/1 were randomly assigned to exenatide or placebo (saline) intravenously. Study treatment was commenced 15 min before intervention and maintained for 6 h after the procedure. The primary endpoint was salvage index calculated from myocardial area at risk (AAR), measured in the acute phase, and final infarct size measured 90 ± 21 days after pPCI by cardiac magnetic resonance (CMR). In 105 patients evaluated with CMR, a significantly larger salvage index was found in the exenatide group than in the placebo group (0.71 ± 0.13 vs. 0.62 ± 0.16; P= 0.003). Infarct size in relation to AAR was also smaller in the exenatide group (0.30 ± 0.15 vs. 0.39 ± 0.15; P= 0.003). In a regression analysis, there was a significant correlation between the infarct size and the AAR for both treatment groups and an analysis of covariance showed that datapoints in the exenatide group lay significantly lower than for the placebo group (P= 0.011). There was a trend towards smaller absolute infarct size in the exenatide group (13 ± 9 vs. 17 ± 14 g; P= 0.11). No difference was observed in left ventricular function or 30-day clinical events. No adverse effects of exenatide were observed., Conclusion: In patients with STEMI undergoing pPCI, administration of exenatide at the time of reperfusion increases myocardial salvage.

Background: Current recommendations prescribe that every adult should accumulate 30 minutes or more of moderate physical activity in leisure time, preferably every day of the week. The optimal intensity, duration, and frequency still have to be established. The aim of this study was to examine the impact of intensity versus duration of cycling on all-cause and coronary heart disease mortality., Design: Relative intensity and duration of cycling were recorded in 5106 apparently healthy men and women aged 21-90 years drawn from the general population of Copenhagen, and followed for an average of 18 years. Total number of deaths during follow-up was 1172, of these 146 were coronary heart disease deaths. For both sexes we found a significant inverse association between cycling intensity and risk of all-cause and coronary heart disease death, but only a weak association with cycling duration. The difference in expected lifetime in relation to intensity of cycling was calculated. Men with fast intensity cycling survived 5.3 years longer, and men with average intensity 2.9 years longer than men with slow cycling intensity. For women the figures were 3.9 and 2.2 years longer, respectively., Conclusion: Our findings indicate that the relative intensity, and not the duration of cycling, is of more importance in relation to all-cause and coronary heart disease mortality. Thus our general recommendations to all adults would be that brisk cycling is preferable to slow.

Background: Leptin and adiponectin are hormones secreted by adipose tissue, and both hormones are candidate intermediaries between adipose tissue and overweight-related diseases. So far, no prospective study has been published where the independent effects of these two hormones on the development of hypertension have been directly compared. The objective of this study was to investigate the relationships between plasma levels of leptin and adiponectin and new-onset hypertension in the Copenhagen City Heart Study (CCHS)., Methods: In a prospective study design, we examined new-onset hypertension in 620 women and 300 men who were normotensive in the third CCHS examination, which was performed in 1991-1994., Results: Between the third and the fourth CCHS examination, which was performed in 2001-2003, 254 had developed hypertension, defined as systolic blood pressure (SBP) > or = 140 mm Hg, or diastolic blood pressure (DBP) > or = 90 mm Hg, or use of antihypertensive medication. Using logistic regression analysis, adjusting for age, sex, estimated glomerular filtration rate, triglycerides, high-density lipoprotein cholesterol (HDL-C), fibrinogen, and glucose, and with leptin and adiponectin included in the same model, leptin was significantly associated with new-onset hypertension with an odds ratio (95% confidence interval) of 1.28 (1.08-1.53; P < 0.005) for 1 s.d. higher level of log-transformed leptin, whereas adiponectin was not significantly associated with new-onset hypertension having an odds ratio of 1.02 (0.84-1.24; P = 0.83) for 1 s.d. higher level of log-transformed adiponectin., Conclusions: In the CCHS, leptin, but not adiponectin, was a significant independent predictor of new-onset hypertension.

Background: Low-grade chronic inflammation has been proposed to play a major role in the pathogenesis of hypertension. Low-grade chronic inflammation is also closely associated with obesity, an established causative factor in the development of hypertension. The purpose of this study was to investigate the relationship between two markers of inflammation, C-reactive protein (CRP) and fibrinogen, and blood pressure (BP) and other hemodynamic variables in obese subjects., Methods: From a large cardiovascular study based in the general population, we selected subjects with a body mass index (BMI) > or =30 kg/m2, free of major cardiovascular diseases, not taking BP-lowering or lipid-lowering drugs (n = 487; women = 51.1%; median (5th to 95th percentile) age = 62 years (36-80)). The cardiovascular study included measurements of traditional and new risk factors, including ankle brachial BP index, a measure of subclinical atherosclerosis. CRP was determined by a high-sensitive assay., Results: In partial Spearman rank correlation analysis, adjusted for age and sex, we found no significant relationships between either CRP or fibrinogen and systolic BP, diastolic BP, pulse pressure, or ankle brachial index (rho: -0.057 to 0.068; P > 0.13). However, fibrinogen and CRP were found to be significantly related to heart rate (rho: 0.127-0.169; P < 0.01)., Conclusions: In this study of generally healthy obese subjects from the general population, we found no significant relationships between markers of inflammation and systolic BP or diastolic BP, showing that obese subjects with higher levels of inflammatory markers do not have higher BP levels than their obese counterparts with lower levels of inflammatory markers.

Aims: To test the hypothesis that echocardiographic tissue Doppler imaging (TDI) reveals reduced myocardial function in hypertension, diabetes, and ischaemic heart disease (IHD) in the general population., Methods and Results: Within a large, community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and colour TDI. Peak systolic (s') and early diastolic (e') velocities, longitudinal displacement (LD), and the ratio of mitral inflow E-wave to e' (E/e') were measured. TDI revealed significantly impaired parameters of systolic and diastolic cardiac function in hypertension [n = 345; LD 10.1 (+/-standard deviation, SD 2.0 mm), P < 0.001; E/e' 12.4 (x/SD 1.4), P < 0.001], diabetes [n = 65; LD 9.8 (+/-SD 2.2 mm), P < 0.001; E/e' 12.7 (x/SD 1.5), P < 0.001], and IHD [n = 93; LD 9.4 (+/-SD 2.5 mm), P < 0.001; E/e' 13.0 (x/SD 1.5), P < 0.001] compared with controls [n = 533; LD 11.4 (+/-SD 2.0 mm); E/e' 9.0 (x/SD 1.3)]. This pattern remained significant after adjusting for age, sex, body mass index, heart rate, and the results of conventional echocardiography., Conclusion: In the general population, persons with hypertension, diabetes, or IHD have impaired cardiac function by TDI independently of the result of conventional echocardiography.

Context: Rare mutations in APOB cause hypercholesterolemia. Whether common polymorphisms in APOB have similar effects remains controversial., Objective: We tested the hypothesis that the APOB 7673C>T polymorphism (T2488T) is associated with variation in low-density lipoprotein (LDL) levels and with risk of ischemic heart disease (IHD), ischemic cerebrovascular disease (ICVD), and total mortality in the general population., Design: The design was a cohort study with 22-yr follow-up (166,232 person years) and two case-control studies, The Copenhagen City Heart Study., Settings: The study was performed within the Danish general population and at a university hospital., Participants: The study was comprised of 9185 individuals from the general population, 2157 patients with IHD, and 378 patients with ICVD., Main Outcome Measures: The main outcome measures were lipids, lipoproteins, apolipoproteins (apo), IHD, ICVD, and total mortality., Results: Genotype was associated with increases in total cholesterol (women/men), LDL cholesterol, and apoB of 0.20/0.26 mmol/liter (3.3%/4.4%), 0.22/0.28 mmol/liter (5.9%/7.8%), and 5.0/5.6 mg/dl (5.9%/6.7%) in TT vs. CC homozygotes, respectively. These results were consistent over time. Despite this, the 7673C>T polymorphism was not associated with risk of IHD, ICVD, or total mortality prospectively or in case-control studies., Conclusion: The APOB 7673C>T polymorphism is associated with moderate increases in total cholesterol, LDL cholesterol, and apoB in both genders in the general population, but not with risk of IHD, ICVD, or total mortality.