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Background Most patients with atherosclerotic cardiovascular disease remain at (very) high risk for recurrent events due to suboptimal risk factor control. Aims This study aimed to quantify the potential of maximal risk factor treatment on 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events in patients 1 year after a coronary event. Methods and results Pooled data from six studies are as follows: RESPONSE 1, RESPONSE 2, OPTICARE, EUROASPIRE IV, EUROASPIRE V, and HELIUS. Patients aged ≥45 years at ≥6 months after coronary event were included. The SMART-REACH score was used to estimate 10-year and lifetime risk of recurrent atherosclerotic cardiovascular events with current treatment and potential risk reduction and gains in event-free years with maximal treatment (lifestyle and pharmacological). In 3230 atherosclerotic cardiovascular disease patients (24% women), at median interquartile range (IQR) 1.1 years (1.0–1.8) after index event, 10-year risk was median (IQR) 20% (15–27%) and lifetime risk 54% (47–63%). Whereas 70% used conventional medication, 82% had ≥1 drug-modifiable risk factor not on target. Furthermore, 91% had ≥1 lifestyle-related risk factor not on target. Maximizing therapy was associated with a potential reduction of median (IQR) 10-year risk to 6% (4–8%) and of lifetime risk to 20% (15–27%) and a median (IQR) gain of 7.3 (5.4–10.4) atherosclerotic cardiovascular disease event-free years. Conclusions Amongst patients with atherosclerotic cardiovascular disease, maximizing current, guideline-based preventive therapy has the potential to mitigate a large part of their risk of recurrent events and to add a clinically important number of event-free years to their lifetime.

Analyses from administrative databases have suggested an increased cancer incidence among individuals who experienced a myocardial infarction, especially within the first 6 months. It remains unclear to what extent this represents an underlying biological link, or can be explained by detection of pre-symptomatic cancers and shared risk factors. Cancer incidence among 1809 consecutive patients surviving hospitalization for thrombotic ST-segment-elevation myocardial infarction (STEMI; mean age 62.6 years; 26% women; 115 incident cancers) was compared to the cancer incidence among 10,052 individuals of the general population (Rotterdam Study; mean age 63.1 years; 57% women; 677 incident cancers). Pathology-confirmed cancer diagnoses were obtained through identical linkage of both cohorts with the Netherlands Cancer Registry. Cox models were used to obtain hazards ratios (HRs) adjusted for factors associated with both atherosclerosis and cancer. Over 5-year follow-up, there was no significant difference in the incidence of cancer between STEMI patients and the general population (HR 0.96, 95% CI 0.78–1.19). In the first 3 months after STEMI, cancer incidence was markedly higher among STEMI patients compared to the general population (HR 2.45, 95% CI 1.13–5.30), which gradually dissolved during follow-up (P-for-trend 0.004). Among STEMI patients, higher C-reactive protein, higher platelet counts, and lower hemoglobin were associated with cancer incidence during the first year after STEMI (HRs 2.93 for C-reactive protein > 10 mg/dL, 2.10 for platelet count > 300*109, and 3.92 for hemoglobin Trial registration Registered into the Netherlands National Trial Register and WHO International Clinical Trials Registry Platform under shared catalogue number NTR6831.

BackgroundThoracic aortic diameter may have a role as a biomarker for major adverse cardiovascular events.PurposeTo evaluate the sex-specific association of the diameters of the ascending (AA) and descending (DA) thoracic aorta with risk of stroke, coronary heart disease, heart failure, cardiovascular mortality, and all-cause mortality.Materials and MethodsStudy participants from the population-based Rotterdam Study who underwent multidetector-row CT between 2003 and 2006 were evaluated. Cox proportional hazard models were conducted to evaluate the associations of AA and DA diameters indexed and not indexed for body mass index (BMI) with cardiovascular events and mortality for men and women. Hazard ratios (HRs) were calculated per 1-unit greater SD of aortic diameters.ResultsA total of 2178 participants (mean age, 69 years; 55% women) were included. Mean follow-up was 9 years. Each 0.23-mm/(kg/m2) larger BMI-indexed AA diameter was associated with a 33% higher cardiovascular mortality risk in women (HR, 1.33; 95% CI: 1.03, 1.73). Each 0.16-mm/(kg/m2) larger BMI-indexed DA diameter was associated with a 38% higher risk of stroke (HR, 1.38; 95% CI: 1.07, 1.78) and with a 46% greater risk of cardiovascular mortality (HR, 1.46; 95% CI: 1.10, 1.94) in women. Larger BMI-indexed AA and DA diameters were associated with greater risk of all-cause mortality in both sexes.ConclusionLarger ascending and descending thoracic aortic diameters indexed by body mass index were associated with greater risk of adverse cardiovascular outcomes and mortality in women and men.Clinical trial registration no. NTR6831

Background Sex differences and causality of the association between heart rate variability (HRV) and atrial fibrillation (AF) in the general population remain unclear. Methods 12,334 participants free of AF from the population-based Rotterdam Study were included. Measures of HRV including the standard deviation of normal RR intervals (SDNN), SDNN corrected for heart rate (SDNNc), RR interval differences (RMSSD), RMSSD corrected for heart rate (RMSSDc), and heart rate were assessed at baseline and follow-up examinations. Joint models, adjusted for cardiovascular risk factors, were used to determine the association between longitudinal measures of HRV with new-onset AF. Genetic variants for HRV were used as instrumental variables in a Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary-level data. Results During a median follow-up of 9.4 years, 1302 incident AF cases occurred among 12,334 participants (mean age 64.8 years, 58.3% women). In joint models, higher SDNN (fully-adjusted hazard ratio (HR), 95% confidence interval (CI) 1.24, 1.04–1.47, p = 0.0213), and higher RMSSD (fully-adjusted HR, 95% CI 1.33, 1.13–1.54, p = 0.0010) were significantly associated with new-onset AF. Sex-stratified analyses showed that the associations were mostly prominent among women. In MR analyses, a genetically determined increase in SDNN (odds ratio (OR), 95% CI 1.60, 1.27–2.02, p = 8.36 × 10–05), and RMSSD (OR, 95% CI 1.56, 1.31–1.86, p = 6.32 × 10–07) were significantly associated with an increased odds of AF. Conclusion Longitudinal measures of uncorrected HRV were significantly associated with new-onset AF, especially among women. MR analyses supported the causal relationship between uncorrected measures of HRV with AF. Our findings indicate that measures to modulate HRV might prevent AF in the general population, in particular in women. Graphical abstract AF; atrial fibrillation, GWAS; genome-wide association study, IVW; inverse variance weighted, MR; Mendelian randomization, MR-PRESSO; MR-egger and mendelian randomization pleiotropy residual sum and outlier, RMSSD; root mean square of successive RR interval differences, RMSSDc; root mean square of successive RR interval differences corrected for heart rate, SDNN; standard deviation of normal to normal RR intervals, SDNNc; standard deviation of normal to normal RR intervals corrected for heart rate, WME; weighted median estimator. aRotterdam Study n=12,334 bHRV GWAS n=53,174 cAF GWAS n=1,030,836

Aims: This study aimed to investigate the left ventricular (LV) remodelling and long-term prognosis of patients with new-onset acute heart failure (HF) with reduced ejection fraction who were pharmacologically managed and survived until hospital discharge. We compared patients with ischaemic and non-ischaemic aetiology. Methods and results: This cohort study consisted of 111 patients admitted with new-onset acute HF in the period 2008–2016 [62% non-ischaemic aetiology, 48% supported by inotropes, vasopressors, or short-term mechanical circulatory devices, and left ventricular ejection fraction (LVEF) at discharge 28% (interquartile range 22–34)]. LV dimensions, LVEF, and mitral valve regurgitation were used as markers for LV remodelling during up to 3 years of follow-up. Both patients with non-ischaemic and ischaemic HF had significant improvement in LVEF (P

Background: The potential bidirectional causal association between kidney function and atrial fibrillation (AF) remains unclear. Methods: We conducted a bidirectional two-sample Mendelian randomization (MR) analysis. From multiple genome-wide association studies (GWAS), we retrieved genetic variants associated with kidney function (estimated glomerular filtration rate based on creatinine (eGFRcreat), blood urea nitrogen (BUN), chronic kidney disease (CKD stage ≥G3): n = 1,045,620, eGFR based on cystatin C: n = 24,063-32,861, urine albumin-tocreatinine ratio (UACR), and microalbuminuria: n = 564,257), and AF (n = 1,030,836). The inverse-variance weighted method was used as our main analysis. Results: MR analyses supported a causal effect of CKD (n = 9 SNPs, odds ratio (OR): 1.10, 95% confidence interval (CI): 1.04–1.17, p-value = 1.97 × 10− 03), and microalbuminuria (n = 5 SNPs, OR: 1.26, 95% CI: 1.10–1.46, pvalue = 1.38 × 10− 03) on AF risk. We also observed a causal effect of AF on eGFRcreat (n = 97 SNPs, OR: 1.00, 95% CI: 1.00–1.00, p-value = 6.78 × 10− 03), CKD (n = 107 SNPs, OR: 1.06, 95% CI: 1.03–1.09, p-value = 2.97 × 10− 04), microalbuminuria (n = 83 SNPs, OR: 1.07, 95% CI: 1.04–1.09, p-value = 2.49 × 10− 08), and a suggestive causal effect on eGFRcys (n = 103 SNPs, OR: 0.99, 95% CI: 0.99–1.00, p-value = 4.61 × 10− 02). Sensitivity analyses, including weighted median estimator, MR-Egger, the MR pleiotropy residual sum and outlier test, and excluding genetic variants associated with possible confounders and/or horizontal mediators (myocardial infarction/coronary artery disease, heart failure) indicated that these findings were robust. Conclusions: Our results supported a bidirectional causal association between kidney function and AF. The shared genetic architecture between kidney dysfunction and AF might represent potential important therapeutic targets to prevent both conditions in the general population.

Sex differences and causality of the association between heart rate variability (HRV) and atrial fibrillation (AF) in the general population remain unclear.12,334 participants free of AF from the population-based Rotterdam Study were included. Measures of HRV including the standard deviation of normal RR intervals (SDNN), SDNN corrected for heart rate (SDNNc), RR interval differences (RMSSD), RMSSD corrected for heart rate (RMSSDc), and heart rate were assessed at baseline and follow-up examinations. Joint models, adjusted for cardiovascular risk factors, were used to determine the association between longitudinal measures of HRV with new-onset AF. Genetic variants for HRV were used as instrumental variables in a Mendelian randomization (MR) analysis using genome-wide association studies (GWAS) summary-level data.During a median follow-up of 9.4 years, 1302 incident AF cases occurred among 12,334 participants (mean age 64.8 years, 58.3% women). In joint models, higher SDNN (fully-adjusted hazard ratio (HR), 95% confidence interval (CI) 1.24, 1.04-1.47, p = 0.0213), and higher RMSSD (fully-adjusted HR, 95% CI 1.33, 1.13-1.54, p = 0.0010) were significantly associated with new-onset AF. Sex-stratified analyses showed that the associations were mostly prominent among women. In MR analyses, a genetically determined increase in SDNN (odds ratio (OR), 95% CI 1.60, 1.27-2.02, p = 8.36 × 10Longitudinal measures of uncorrected HRV were significantly associated with new-onset AF, especially among women. MR analyses supported the causal relationship between uncorrected measures of HRV with AF. Our findings indicate that measures to modulate HRV might prevent AF in the general population, in particular in women. AF; atrial fibrillation, GWAS; genome-wide association study, IVW; inverse variance weighted, MR; Mendelian randomization, MR-PRESSO; MR-egger and mendelian randomization pleiotropy residual sum and outlier, RMSSD; root mean square of successive RR interval differences, RMSSDc; root mean square of successive RR interval differences corrected for heart rate, SDNN; standard deviation of normal to normal RR intervals, SDNNc; standard deviation of normal to normal RR intervals corrected for heart rate, WME; weighted median estimator.

Aim The long-term value of coronary artery calcium (CAC) scanning has not been studied extensively in symptomatic patients, but was evaluated by us in 644 consecutive patients referred for stable chest pain. Methods We excluded patients with a history of cardiovascular disease and with a CAC score of zero. CAC scanning was done with a 16-row MDCT scanner. Endpoints were: (a) overall mortality, (b) mortality or non-fatal myocardial infarction and (c) the composite of mortality, myocardial infarction or coronary revascularisation. Revascularisations within 1 year following CAC scanning were not considered. Results The mean age of the 320 women and 324 men was 63 years. Follow-up was over 8 years. There were 58 mortalities, while 22 patients suffered non-fatal myocardial infarction and 24 underwent coronary revascularisation, providing 104 combined endpoints. Cumulative 8‑year survival was 95% with CAC score 100 and 100 and ≥400 units was 2.6 [95% confidence interval (CI) 1.23–5.54], and 4.6 (95% CI 2.1–9.47) respectively. After correction for clinical risk factors, CAC score remained independently associated with increased risk of cardiac events. Conclusions Risk increased with increasing CAC score. Patients with CAC >100 or ≥400 Agatston units were at increased risk of major adverse cardiac events and are eligible for preventive measures. CAC scanning provided incremental prognostic information to guide the choice of diagnostic and therapeutic options in many subjects evaluated for chest pain.

Objectives This study assessed whether adenosine stress-only perfusion cardiac magnetic resonance (CMR) following a positive coronary artery calcium (CAC) score improved the diagnostic yield of invasive coronary angiography (CAG) in patients with stable chest pain. The study also established the association between positive CAC scores and stress-induced myocardial ischemia. Background The diagnostic yield of catheterization among patients with suspected coronary artery disease (CAD) is low. Improved patient selection and diagnostic testing are necessary. The CAC score can minimize unnecessary diagnostic testing, and in low-risk patients, normal CMR results have a high negative predictive value. Less comprehensive protocols may be sufficient to guide further work-up. Methods A total of 642 consecutive patients (mean age: 63 years; 50% women) with stable chest pain and CAC scores of >0 who were referred for CMR were enrolled. Patients with a perfusion defect were subsequently examined by CAG. Patients were followed up for 1 year. Outcome was obstructive CAD. Results Obstructive CAD was present in 12% of patients. For CAD diagnosis, the sensitivity of adenosine CMR was 90.9% (95% confidence interval [CI]: 88.7 to 93.1), specificity was 98.7% (95% CI: 97.9 to 99.6), positive predictive value was 92.0% (95% CI: 89.8 to 94.1), and negative predictive value was 98.6% (95% CI: 97.6 to 99.5). A CAC score between 0.1 and 100 without typical angina was associated with obstructive CAD in only 3% of patients. Patients with nonanginal chest pain and a CAC score ≥400 had obstructive CAD (16%). Conclusions Stress-only adenosine CMR had high diagnostic accuracy and served as an efficient gatekeeper to CAG in stable patients with a CAC score >0. Patients with CAC scores between 0.1 and 100 could be deferred from further testing in the absence of clinical features that suggested high risk. However, in patients with CAC score ≥400, functional testing should be indicated, regardless of the type of chest pain.

Unstable angina and myocardial infarction are prevalent manifestations of acute coronary artery disease, combined in the term ‘acute coronary syndromes’. The introduction of sensitive markers for myocardial necrosis has led to confusion regarding the distinction between small myocardial infarctions and ‘true’ unstable angina, and the application of ever more sensitive markers has accelerated the pace at which patients with unstable angina are being re-classified to non-ST-segment elevation myocardial infarction. But in how many patients with acute chest pain is myocardial ischaemia really the cause of their symptoms? Numerous studies have shown that most have

Background The performance of current diagnostic algorithms of the American College of Cardiology/American Heart Association (ACC/AHA), National Institute for Health and Care Excellence (NICE) and European Society of Cardiology (ESC) in patients with stable chest pain and coronary artery calcium (CAC) remains a matter of debate. We compared their merits in patients with CAC and investigated the additional value of the CAC score to improve diagnostic accuracy and risk stratification. Methods and results Patient data were obtained from a prospective registry of 642 consecutive patients. Mean age 63 (SD 11) years, 50% male. According to the guidelines, low and intermediate/high pre-test probability groups were constructed. Patients were reclassified based on their CAC score. Obstructive coronary artery disease (CAD) was observed in 14%. All models performed modestly in accurately predicting CAD (c-statistic

Background It is unclear to what extent the 2019 European Society of Cardiology (ESC), 2018 American College of Cardiology/ American Heart Association (ACC/AHA), 2016 US Preventive Services Task Force (USPSTF), and 2016 Canadian Cardiovascular Society (CCS) guidelines differ in assigning levels of evidence and classes of recommendations (LOE/class) to lipid-lowering treatment recommendations in primary prevention of cardiovascular disease (CVD). Purpose To compare LOE/class from four commonly used guidelines at population level. Methods A total of 7262 participants, aged 45–75 years of age and without history of CVD, from the prospective population-based Rotterdam Study were included. Per guideline, proportions of the population recommended statin therapy by LOE/class, sensitivity and specificity, and numbers needed to treat at 10 years (NNT10y) were calculated. Results Mean age was 61.1 (SD 6.9) years, and 58.2% were women. ESC, ACC/AHA, USPSTF and CCS strongly recommended statin use for a respective 33.8%, 48.1%, and 40.2% and 73.0% of the eligible population based on high-quality evidence, while in an additional 55.3%, 7.1%, 8.4% and 9.2% of participants statins use could or should be considered based on varying LOE/class. The sensitivity for treatment recommendations supported with strong, high quality evidence was 61.6% for ESC (“IA”), 74.6% for ACC/AHA (“IA or IB”), 69.4% for USPSTF (“USPSTF-B”) and 92.5% for CCS (“strong”). Specificity was highest for the ACC/AHA at 46.8% and lowest for ESC at 11.4%. Estimated NNT10y for those with the strongest LOE/class were comparable across all guidelines, ranging from 18 to 26 for moderate-intensity statin use, and 11 to 16 for high-intensity statin use. NNT10y reflective of recommendations supported with moderate strength of LOE/class varied substantially among guidelines for both moderate-intensity and high-intensity statin use, ranging from 33 for ESC and USPSTF to 91 for CCS. Conclusions Assigned LOE/class varied greatly among four clinical practice guidelines for primary prevention of CVD. Efforts for harmonized and comparable evidence grading system for clinical practice guidelines in primary prevention of CVD may reduce ambiguity, and reinforce updated evidence-based recommendations for appropriate treatment of populations for whom clear evidence for benefit of statin use is available. Funding Acknowledgement Type of funding source: None

Contains fulltext : 220823.pdf (Publisher’s version ) (Closed access) Before 2015, endovascular treatment (EVT) for acute ischemic stroke was considered a promising treatment option. Based on limited evidence, it was performed in several dedicated stroke centers worldwide on selected patients. Since 2015, EVT for patients with intracranial large vessel occlusion has quickly been implemented as standard treatment in many countries worldwide, supported by the revised international guidelines based on solid evidence from multiple clinical trials. We describe the development in use of EVT in the Netherlands before, during, and after the pivotal EVT trials. We used data from all patients who were treated with EVT in the Netherlands from January 2002 until December 2018. We undertook a time-series analysis to examine trends in the use of EVT using Poisson regression analysis. Incidence rate ratios per year with 95% CIs were obtained to demonstrate the impact and implementation after the publication of the EVT trial results. We made regional observation plots, adjusted for stroke incidence, to assess the availability and use of the treatment in the country. In the buildup to the MR CLEAN (Multicenter Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands), a slow increase of EVT patients was observed, with 0.2% of all ischemic stroke patients receiving EVT. Before the trial results were formally announced, a statistically significant increase in EVT-treated patients per year was observed (incidence rate ratio, 1.72 [95% CI, 1.46-2.04]), and after the trial publication, an immediate steep increase was seen, followed by a more gradual increase (incidence rate ratio, 2.14 [95% CI, 1.77-2.59]). In 2018, the percentage of ischemic stroke patients receiving EVT increased to 5.8%. A well-developed infrastructure, a pragmatic approach toward the use of EVT in clinical practice, in combination with a strict adherence by the regulatory authorities to national evidence-based guidelines has led to successful implementation of EVT in the Netherlands. Ongoing efforts are directed at further increasing the proportion of stroke patients with EVT in all regions of the country.

Long term survival after endovascular aortic aneurysm repair (EVAR) in octogenarians remains unclear. This was evaluated by comparing octogenarians after EVAR with a matched group of octogenarians without an abdominal aortic aneurysm (AAA) from the Rotterdam Study (RS). The influence of complications after EVAR on survival was also studied with the aim of identifying risk factors for the development of complications in octogenarians.Using propensity score matching (PSM), 83 EVAR octogenarians were matched for comorbidities with 83 octogenarians from the RS, and survival was compared between these two groups using Cox proportional hazard analysis. Then, complications were studied, defined as cardiac or pulmonary, renal deterioration, access site bleeding, acute limb ischaemia or bowel ischaemia, within 30 days of surgery between 83 EVAR octogenarians and 475 EVAR non-octogenarians. Also, the difference in baseline characteristics between the octogenarians with and without complications after EVAR were studied, and survival was compared between the RS controls and the complicated and uncomplicated EVAR octogenarians separately.The total EVAR octogenarian population did not show an increased mortality risk compared with RS octogenarian controls (hazard ratio [HR] 1.28, 95% confidence interval [CI] 0.84-1.97). Post-operative complications occurred in 22 octogenarians (27%) and 59 non-octogenarians (12.4%, p .001), mainly cardiac, pulmonary, and bleeding complications. All baseline characteristics were similar in the complicated EVAR octogenarians compared with the uncomplicated EVAR octogenarians. After uncomplicated EVAR, octogenarians had a similar survival compared with the RS controls (HR 1.09, 95% CI 0.68-1.77), but after complicated EVAR their mortality risk increased significantly (HR 1.93, 95% CI 1.06-3.54).After standard EVAR, the life expectancy of octogenarians is the same as that of a matched group from the general population without an AAA, provided they do not develop early post-operative complications. Patient selection and meticulous peri-operative care are key.

Because the occurrence of infective endocarditis (IE) continues to be associated with high mortality, a working group was created by the Dutch Society of Cardiology to examine how the most recent European Society of Cardiology (ESC) guidelines for IE management could be implemented most effectively in the Netherlands. In order to investigate current Dutch IE practices, the working group conducted a country-wide survey. Based on the results obtained, it was concluded that most ESC recommendations could be endorsed, albeit with some adjustments. For instance, the suggested pre-operative screening and treatment of nasal carriers of Staphylococcus aureus as formulated in the ESC guideline was found to be dissimilar to current Dutch practice, and was therefore made less restrictive. The recently adapted ESC diagnostic criteria for IE were endorsed, while the practical employment of the relevant diagnostic techniques was simplified in an adapted flowchart. In addition, the presence of a multidisciplinary, so-called ‘endocarditis team’ in tertiary centres was proposed as a quality indicator. An adapted flowchart specifically tailored to Dutch practice for microbiological diagnostic purposes was constructed. Lastly, the working group recommended the Stichting Werkgroep Antibioticabeleid (SWAB; Dutch Working Party on Antibiotic Policy) guidelines for IE treatment instead of the antibiotic regimens proposed by the ESC.

Background The purpose of this study was to determine how American College of Cardiology/American Heart Association (ACC/AHA) 2013 and European Society of Cardiology 2016 guidelines for the primary prevention of atherosclerotic cardiovascular disease (CVD) compare in reflecting the totality of accrued randomised clinical trial evidence for statin treatment at population level. Methods From 1997–2008, 7279 participants aged 45–75 years, free of atherosclerotic cardiovascular disease, from the population-based Rotterdam Study were included. For each participant, we compared eligibility for each one of 11 randomised clinical trials on statin use in primary prevention of CVD, with recommendations on lipid-lowering therapy from the ACC/AHA and European Society of Cardiology (ESC) guidelines. Atherosclerotic cardiovascular disease incidence and cardiovascular disease mortality rates were calculated. Results The proportion of participants eligible for each trial ranged from 0.4% for ALLHAT-LLT to 30.8% for MEGA. The likelihood of being recommended for lipid-lowering treatment was lowest for those eligible for low-to-intermediate risk RCTs (HOPE-3, MEGA, and JUPITER), and highest for high-risk individuals with diabetes (MRC/BHF HPS, CARDS, and ASPEN) or elderly PROSPER. Eligibility for an increasing number of randomised clinical trials correlated with a greater likelihood of being recommended lipid-lowering treatment by either guideline ( p Conclusion Compared to RCTs done in high risk populations, randomised clinical trials targeting low-to-intermediate risk populations are less well-reflected in the ACC/AHA, and even less so in the ESC guideline recommendations. Importantly, the low-to-intermediate risk population targeted by HOPE-3, the most recent randomised clinical trial in this field, is not well-captured by the current European prevention guidelines and should be specifically considered in future iterations of the guidelines.

Background Meta-analyses of cardiac rehabilitation trials up to 2010 showed a significant reduction in all-cause mortality but many of these trials were conducted before the modern management of acute coronary syndromes. Methods We undertook a meta-analysis of contemporary randomised controlled trials published in the period 2010 to 2015, including patients with other forms of atherosclerotic cardiovascular disease, to investigate the impact of cardiovascular prevention and rehabilitation on hard outcomes including survival. Results 18 trials randomising 7691 patients to cardiovascular prevention and rehabilitation or usual care were selected. All-cause mortality was not reduced (RR 1.00, 95% CI 0.88 to 1.14), but cardiovascular mortality was by 58% (95% CI 0.21, 0.88). Myocardial infarction was also reduced by 30% (95% CI 0.54, 0.91) and cerebrovascular events by 60% (95% CI 0.22, 0.74). Comprehensive programmes managing six or more risk factors reduced all-cause mortality in a subgroup analysis (RR 0.63, 95% CI 0.43, 0.93) but those managing less did not. In the three programmes that prescribed and monitored cardioprotective medications for blood pressure and lipids all-cause mortality was also reduced (RR 0.35, 95% CI 0.18, 0.70). Conclusions Comprehensive prevention and rehabilitation programmes managing six or more risk factors, and those prescribing and monitoring medications within programmes to lower blood pressure and lipids, continue to reduce all-cause mortality. In addition, these comprehensive programmes not only reduced cardiovascular mortality and myocardial infarction but also, for the first time, cerebrovascular events, and all these outcomes across a broader spectrum of patients with atherosclerotic disease.

Background Thoracic aortic diameters have been associated with cardiovascular risk factors and atherosclerosis. However, limited evidence regarding the role of thoracic aortic diameters as risk markers for major cardiovascular outcomes among women and men exist. Purpose To evaluate the independent associations between crude and indexed ascending and descending aortic (AA and DA) diameters with major cardiovascular outcomes among women and men and to provide optimal cutoff values associated with increased cardiovascular risk. Methods and results 2178 women and men ≥55 years from the prospective population-based Rotterdam Study underwent multi-detector CT scan of thorax. Crude diameters of the AA and DA were measured and indexed by height, weight, body surface area (BSA) and body mass index (BMI). Incidence of stroke, coronary heart disease (CHD), heart failure (HF), cardiovascular and all-cause mortality were evaluated during 13 years of follow-up. Weight-, BSA-, or BMI-indexed AA diameters showed significant associations with total or cardiovascular mortality in both sexes and height-indexed values showed association with HF in women. Crude AA diameters were associated with stroke in men and HF in women. For DA, crude and almost all indexed diameters showed significant associations with either stroke, HF, cardiovascular or total mortality in women. Only weight-, BSA- and BMI-indexed values were associated with total mortality in men. For crude DA diameter, the risk for stroke increased significantly at the 75th percentile among men while the risks for HF and cardiovascular mortality increased at the 75th and 85th percentiles respectively in women. Conclusions Our study suggests a role for descending thoracic aortic diameter as a marker for increased cardiovascular risk, in particular for stroke, heart failure and cardiovascular mortality among women. The cut points for increased risk for several of cardiovascular outcomes were below the 95th percentile of the distribution of aortic diameters.

Background In 2013, the American College of Cardiology (ACC) and the American Heart Association (AHA) developed a score for assessment of cardiovascular risk. Due to between study variability in ascertainment and adjudication of heart failure (HF), incident HF was not included as an endpoint in the ACC/AHA risk score. Purpose To assess the performance of the ACC/AHA risk score for HF risk prediction in a large population-based cohort and to compare its performance with the existing HF risk prediction models including the Atherosclerosis Risk in Communities (ARIC) model and the Health Aging and Body Composition (Health ABC) model. Methods The study included 2743 men and 3646 women from a prospective population-based cohort study. Cox proportional hazards models were fitted using risk factors applied by the ACC/AHA model for cardiovascular risk, the ARIC model and the Health ABC model. Independent relationship of each predictor with 10-year HF incidence was estimated in men and women. Next, N-terminal pro-b-type natriuretic peptide (NT-pro-BNP) was added to the ACC/AHA model. The performance of all fitted models was evaluated and compared in terms of discrimination, calibration and the Akaike Information Criterion (AIC). In addition, area under the receiver operator characteristic curve (AUC), sensitivity and specificity of each model in predicting 10-year incident of HF was assessed. The incremental value of NT-pro-BNP to the ACC/AHA model, was assessed using the continuous net reclassification improvement index (NRI). Results During a median follow-up of 13 years (63127 person-years), 387 HF events in women and 259 in men were recorded. The Optimism-corrected c-statistic for ACC/AHA model was 0.76 (95% confidence interval (CI): 0.73–0.79) for men and 0.76 (95% CI: 0.74–0.79) for women. The ARIC model provided the largest c-statistic for both men [0.82 (95% CI: 0.80–0.84)] and women [95% CI: 0.81 (0.79–0.83)] among the three models. Calibration of the models was reasonable. Addition of NT-pro-BNP to the ACC/AHA model considerably improved model fitness for men and for women. The AIC improved from 3104.62 to 2976.28 among men and from 5161.63 to 4921.51 among women. The c-statistic also improved to 0.81 (0.78–0.84) in men and 0.79 (0.77–0.81) in women. The continuous NRI for the addition of NT-pro-BNP to the base model was 5.3% (95% CI: −12.3–28.6%) for men and 15.9% (95% CI: 2.7–24.7%) for women. Conclusions Compared to HF-specific models, the ACC/AHA model, containing routine clinically available risk factors, had a reasonable performance in prediction of HF risk. Inclusion of NT-pro-BNP in the ACC/AHA model strongly increased the model performance. To achieve a better model performance for 10-year prediction of incident HF, updating the simple ACC/AHA risk score with the addition of NT-pro-BNP is recommended.

Background Intensive blood pressure lowering is increasingly gaining attention. Besides higher baseline blood pressure, visit-to-visit variability has showed association with target organ damage and major adverse cardiovascular outcomes in multiple medical reports. Purpose Our aim was to assess the effect of intensive treatment on systolic blood pressure (SBP) visit-to-visit variability in the SPRINT trial population during follow-up. Methods We included 9068 SPRINT participants with 128139 repeated SBP measurements. Participants were randomly assigned to intensive (SBP Results CVs in intensive treatment groups were higher in total population and in all groups under study (See table). While second and third CV quartile showed a larger tendency to increase the risk for the primary SPRINT outcome in the intensive treatment compared to the standard treatment group, fourth CV quartiles were significantly associated with increase in primary SPRINT outcome in both intensive and standard treatment groups. Coefficient of variation in SPRINT trial Group Intensive treatment Standard treatment Total population 9.80 (3.22)* 8.52 (2.96) Females 10.46 (3.29)* 9.18 (3.15) Black person 9.99 (3.38)* 8.82 (3.15) Prevalence CKD 10.14 (3.22)* 9.12 (3.06) Prevalence CVD 10.28 (3.32)* 8.93 (3.23) ≥75 year 10.40 (3.18)* 9.01 (3.07) SAEs 10.30 (3.39)* 9.08 (3.13) (CKD: chronic kidney disease; CVD: cardiovascular disease; SAEs: serious adverse events. *P Conclusions Intensive blood pressure treatment significantly increases SBP visit-to-visit variability in total SPRINT population and in all subgroups under study. Additional longitudinal studies with long-term follow-up are warranted to evaluate the impact of increases in SBP visit-to-visit variability due to intensive treatment on risk of major cardiovascular events.

BACKGROUND Intensive blood pressure lowering is increasingly gaining attention. In addition to higher baseline blood pressure, cumulative SBP, visit-to-visit variability, and treatment-induced serious adverse events (SAEs) could impact treatment efficacy over time. Our aim was to assess the impact of cumulative SBP and SAEs on intensive hypertension treatment efficacy in the Systolic Blood Pressure Intervention Trial (SPRINT) population during follow-up. METHODS Secondary analysis of the SPRINT study: a randomized, controlled, open-label trial including 102 clinical sites in the United States. We included 9068 SPRINT participants with 128 139 repeated SBP measurements. Participants were randomly assigned to intensive (target SBP

Background: Hypertension is the most prevalent major independent risk factor for developing coronary heart disease (CHD). The present analysis aimed to assess blood pressure (BP) distribution and factors associated with insufficient BP control in coronary patients from 24 countries participating in the European Society of Cardiology (ESC) EURoObservational Research Programme (EORP) EUROASPIRE IV survey. Methods: EUROASPIRE IV is a cross-sectional study conducted in 2012-2013 in patients aged 80 years or less hospitalized for CHD with a follow-up visit at a median of 16 months later. Logistic regression analysis was applied to confirm factors associated with BP control defined as less than 140/90 mmHg for nondiabetic patients and less than 140/85 mmHg for diabetic patients. Results: A total of 7998 patients (response rate, 48.7%) attended the follow-up visit. Complete data were available in 7653 participants (mean age 62.5 +/- 9.6 years). The BP goal was achieved in 57.6%. Patients failing to achieve the BP goal were older, had higher BMI, had more often a history of coronary artery bypass grafting (CABG) and reported diabetes more frequently. Logistic regression confirmed the following independent significant predictors of not achieving the BP goal: a history of diabetes [odds ratio (OR) 1.75], obesity (OR 1.70 vs. normal BMI), overweight (OR 1.28 vs. normal BMI), age at least 65 years (OR 1.53) and CABG as the index event (OR 1.26 vs. acute MI). Conclusion: EUROASPIRE IV found insufficient BP control in a large proportion of patients with stable CHD, with diabetes, increased BMI, older age and CABG as the index event being independent predictors of poor BP control.

Aims The aim of this study was to determine whether the Joint European Societies guidelines on secondary cardiovascular prevention are followed in everyday practice. Design A cross-sectional ESC-EORP survey (EUROASPIRE V) at 131 centres in 81 regions in 27 countries. Methods Patients (Results A total of 8261 patients (females 26%) were interviewed. Nineteen per cent smoked and 55% of them were persistent smokers, 38% were obese (body mass index ≥30 kg/m2), 59% were centrally obese (waist circumference: men ≥102 cm; women ≥88 cm) while 66% were physically active Conclusion A large majority of coronary patients have unhealthy lifestyles in terms of smoking, diet and sedentary behaviour, which adversely impacts major cardiovascular risk factors. A majority did not achieve their blood pressure, low-density lipoprotein cholesterol and glucose targets. Cardiovascular prevention requires modern preventive cardiology programmes delivered by interdisciplinary teams of healthcare professionals addressing all aspects of lifestyle and risk factor management, in order to reduce the risk of recurrent cardiovascular events.

Background The predictive value of coronary artery calcium ( CAC ) has been widely studied; however, little is known about specific characteristics of CAC that are most predictive. We aimed to determine the independent associations of Agatston score, CAC volume, CAC area, CAC mass, and CAC density score with major adverse cardiac events in patients with suspected coronary artery disease. Methods and Results A total of 379 symptomatic participants, aged 45 to 85 years, referred for invasive coronary angiography, who underwent coronary calcium scanning and computed tomography angiography as part of the CORE 320 (Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography) study, were included. Agatston score, CAC volume, area, mass, and density were computed on noncontrast images. Stenosis measurements were made on contrast‐enhanced images. The primary outcome of 2‐year major adverse cardiac events (30 revascularizations [>182 days of index catheterization], 5 myocardial infarctions, 1 cardiac death, 9 hospitalizations, and 1 arrhythmia) occurred in 32 patients (8.4%). Associations were estimated using multivariable proportional means models. Median age was 62 (interquartile range, 56–68) years, 34% were women, and 56% were white. In separate models, the Agatston, volume, and density scores were all significantly associated with higher risk of major adverse cardiac events after adjustment for age, sex, race, and statin use; density was the strongest predictor in all CAC models. CAC density did not provide incremental value over Agatston score after adjustment for diameter stenosis, age, sex, and race. Conclusions In symptomatic patients, CAC density was the strongest independent predictor of major adverse cardiac events among CAC scores, but it did not provide incremental value beyond the Agatston score after adjustment for diameter stenosis.

The EUROASPIRE surveys (EUROpean Action on Secondary Prevention through Intervention to Reduce Events) demonstrated that most European coronary patients fail to achieve lifestyle, risk factor and therapeutic targets. Here we report on the 2-year incidence of hard cardiovascular (CV) endpoints in the EUROASPIRE IV cohort. EUROASPIRE IV (2012-2013) was a large cross-sectional study undertaken at 78 centres from selected geographical areas in 24 European countries. Patients were interviewed and examined at least 6 months following hospitalization for a coronary event or procedure. Fatal and non-fatal CV events occurring at least 1 year after this baseline screening were registered. The primary outcome in our analyses was the incidence of CV death or non-fatal myocardial infarction, stroke or heart failure. Cox regression models, stratified for country, were fitted to relate baseline characteristics to outcome. Our analyses included 7471 predominantly male patients. Overall, 222 deaths were registered of whom 58% were cardiovascular. The incidence of the primary outcome was 42 per 1000 person-years. Comorbidities were strongly and significantly associated with the primary outcome (multivariately adjusted hazard ratio HR, 95% confidence interval): severe chronic kidney disease (HR 2.36, 1.44-3.85), uncontrolled diabetes (HR 1.89, 1.50-2.38), resting heart rate ≥ 75 bpm (HR 1.74, 1.30-2.32), history of stroke (HR 1.70, 1.27-2.29), peripheral artery disease (HR 1.48, 1.09-2.01), history of heart failure (HR 1.47, 1.08-2.01) and history of acute myocardial infarction (HR 1.27, 1.05-1.53). Low education and feelings of depression were significantly associated with increased risk. Lifestyle factors such as persistent smoking, insufficient physical activity and central obesity were not significantly related to adverse outcome. Blood pressure and LDL-C levels appeared to be unrelated to cardiovascular events irrespective of treatment. In patients with stabilized CHD, comorbid conditions that may reflect the ubiquitous nature of atherosclerosis, dominate lifestyle-related and other modifiable risk factors in terms of prognosis, at least over a 2-year follow-up period.

Importance The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) guidelines both recommend lipid-lowering treatment for primary prevention based on global risk for cardiovascular disease (CVD). However, randomized clinical trials (RCTs) for statin use have included participants with specific risk-factor profiles. Objective To evaluate the overlap between the ACC/AHA and ESC guideline recommendations and available evidence from RCTs for statin use in primary prevention of CVD. Design, Setting, and Participants We calculated the 10-year risk for hard atherosclerotic CVD (ASCVD) following the ACC/AHA guideline, 10-year risk of CVD mortality following the ESC guideline, and we determined eligibility for each of 10 major RCTs for primary prevention of CVD. Conducted from July 2014 to August 2015, this study included 7279 individuals free of CVD, aged 45 to 75 years, examined between 1997 and 2008 for the Rotterdam Study, a prospective population-based cohort. Main Outcomes and Measures Proportions of individuals qualifying for lipid-lowering treatment per guidelines, proportions of individuals eligible for any of the 10 RCTs, overlap between these groups, and corresponding ASCVD incidence rates. Results Of the 7279 individuals included in the study, 58.2% were women (n = 4238) and had a mean (SD) age of 61.1 (6.9) years. The ACC/AHA guidelines would recommend statin initiation in 4284 participants (58.9%), while the ESC guidelines would in 2399 participants (33.0%) (overlapping by 95.8% with ACC/AHA). A total of 3857 participants (53.0%) met eligibility criteria for at least 1 RCT. Recommendations from both guidelines and trial evidence overlapped for 1546 participants (21.2%), who were at high risk for ASCVD (21.5 per 1000 person-years). A further 1703 participants (23.4%) would be recommended for statins by the guidelines in the absence of direct trial evidence, while 1176 (16.2%) would have been eligible for at least 1 trial without being recommended statin treatment by any guideline. Finally, 1719 participants (23.6%) would not be recommended a statin, nor would qualify for any of the trials. These individuals had low incidence of ASCVD (3.3 per 1000 person-years). Conclusions and Relevance Based on this European population study, ACC/AHA and ESC prevention guidelines often did not align at the individual level. However, for one-fifth of the general population, guidelines on both sides of the Atlantic recommend statin initiation, with trial data supporting the efficacy. There should be no controversy about providing optimal preventive medication to these individuals.

BackgroundSubclinical cardiac dysfunction has been associated with increased mortality, and heart failure increases the risk of sudden cardiac death (SCD). Less well known is whether subclinical cardiac dysfunction is also a risk factor for SCD. Our objective was to assess the association between echocardiographic parameters and SCD in a community-dwelling population free of heart failure.Methods and ResultsWe computed hazard ratios (HRs) for left atrium diameter, left ventricular (LV) end-diastolic dimension, LV end-systolic dimension, LV mass, qualitative LV systolic function, LV fractional shortening, and diastolic function. During a median follow-up of 6.3 years in 4,686 participants, 68 participants died because of SCD. Significant associations with SCD were observed for qualitative LV systolic function and LV fractional shortening. For moderate/poor qualitative LV systolic function, the HR for SCD was 2.54 (95% confidence interval [CI] 1.10–5.87). Each standard deviation decrease in LV fractional shortening was associated with an HR of 1.36 (95% CI 1.09–1.70).ConclusionsSubclinical abnormalities in LV systolic function were associated with SCD risk in this general population. Although prediction of SCD remains difficult and traditional cardiovascular risk factors are of greatest importance, this knowledge might guide future directions to prevent SCD in persons with subclinical cardiac dysfunction.

Physicians visiting the European Society of Cardiology (ESC) congress in London could not miss the extensive marketing of new low-density lipoprotein (LDL)-lowering therapies with ezetimibe and the PCSK-9 inhibitors. However, we think and will argue that a word of caution on their use in clinical practice is appropriate. The European guidelines on cardiovascular disease prevention and management of stable coronary artery disease recommend a spectrum of measures to limit the risk of a first or recurrent coronary event, including abstinence from smoking, balanced nutrition, moderate exercise as well as drugs to control blood pressure, lipids and glucose levels.1,2 Specific targets are mentioned for blood pressure (130–139/80–85 mmHg) and LDL-cholesterol (1.8–3.0 mmol/L). However, these targets for LDL-cholesterol—based on the observations that lower LDL levels are associated with ever-lower risk for cardiovascular events—are quite arbitrary. In clinical practice, these targets are often not reached, in spite of intensive medical therapy.3,4 For instance, in the EUROASPIRE-IV survey, 64% of males and 78% of females had LDL levels higher than 2.0 mmol/L.3 Furthermore, 18% of these patients continued smoking after an acute coronary event or revascularization procedure, while 42% had an elevated blood pressure. The usefulness of specific targets for LDL cholesterol levels has been questioned and has been abandoned in recent American guidelines.5 Nevertheless, European opinion leaders continue to emphasize the value of targets to improve adherence to therapy and to consider additional therapy, such as combination of statin and ezetimibe, in a small group of very high-risk patients .6 Such targeting is supported by the recently published results of IMPROVE-IT7 as will be discussed below. Furthermore, we …

BACKGROUND: The association between thyroid function and cardiovascular disease is well established, but no study to date has assessed whether it is a risk factor for sudden cardiac death (SCD). Therefore, we studied the association of thyroid function with SCD in a prospective population-based cohort. METHODS: Participants from the Rotterdam Study ≥45 years with thyroid-stimulating hormone or free thyroxine (FT4) measurements and clinical follow-up were eligible. We assessed the association of thyroid-stimulating hormone and FT4 with the risk of SCD by using an age- and sex-adjusted Cox proportional-hazards model, in all participants and also after restricting the analysis to euthyroid participants (defined by thyroid-stimulating hormone 0.4–4.0 mIU/L). Additional adjustment included cardiovascular risk factors, notably hypertension, serum cholesterol, and smoking. We stratified by age and sex and performed sensitivity analyses by excluding participants with abnormal FT4 values (reference range of 0.85–1.95 ng/dL) and including only witnessed SCDs as outcome. Absolute risks were calculated in a competing risk model by taking death by other causes into account. RESULTS: We included 10 318 participants with 261 incident SCDs (median follow-up, 9.1 years). Higher levels of FT4 were associated with an increased SCD risk, even in the normal range of thyroid function (hazard ratio, 2.28 per 1 ng/dL FT4; 95% confidence interval, 1.31–3.97). Stratification by age or sex and sensitivity analyses did not change the risk estimates substantially. The absolute 10-year risk of SCD increased in euthyroid participants from 1% to 4% with increasing FT4 levels. Conclusions: Higher FT4 levels are associated with an increased risk of SCD, even in euthyroid participants.

During the past years, several clinical studies demonstrated associations of the amount of epicardial fat (i.e., adipose tissue surrounding the myocardium) with the burden of atrial fibrillation (AF) and outcomes after AF ablation [(1)][1]. However, as was recently pointed out in major reviews on

ObjectiveTo evaluate changes in left ventricular diastolic function (LVDF) parameters and their associated risk factors over a period of 11 years among community-dwelling women and men.MethodsEchocardiography was performed three times among 870 women and 630 men (age 67±3 years) from the prospective population-based Rotterdam Study during a period of 11-year follow-up. Changes in six continuous LVDF parameters were correlated with cardiovascular risk factors using a linear-mixed effect model (LMM).ResultsIn women, smoking was associated with deleterious longitudinal changes in deceleration time (DT) (Beta (β): 7.73; 95% CI 2.56 to 12.9) and high-density lipoprotein cholesterol was associated with improvement of septal e′ (β: 0.37; 95% CI 0.13 to 0.62) and E/e′ ratio (β: −0.46; 95% CI −0.84 to –0.08) trajectories. Among men, diabetes was associated with deleterious longitudinal changes in A wave (β: 3.83; 95% CI 0.06 to 7.60), septal e′ (β: −0.40; 95% CI −0.70 to –0.09) and E/e′ ratio (β: 0.60; 95% CI 0.14 to 1.06) and body mass index was associated with deleterious longitudinal changes in A wave (β: 1.25; 95% CI 0.84 to 1.66), E/A ratio (β: −0.007; 95% CI −0.01 to –0.003), DT (β: 0.86; 95% CI 0.017 to 1.71) and E/e′ ratio (β: 0.12; 95% CI 0.06 to 0.19).ConclusionsSmoking among women and metabolic factors (diabetes mellitus and body mass index) among men showed larger deleterious associations with longitudinal changes in LVDF parameters. The favourable association of HDL was mainly observed among women. This study, for the first time, evaluates risk factors associated with changes over time in continuous LVDF parameters among women and men and generates new hypothesis for further medical research.

OBJECTIVE We studied differences in long-term (i.e., 10 year) prognosis among patients with acute heart failure (HF) with and without diabetes over the last three decades. In addition, we investigated whether the degree of prognostic improvement in that period was comparable between patients with and without diabetes. RESEARCH DESIGN AND METHODS This prospective registry included all consecutive patients aged 18 years and older admitted to the Intensive Coronary Care Unit with acute HF in the period of 1985–2008. A total of 1,810 patients were included; 384 patients (21%) had diabetes. The outcome measure was the composite of all-cause mortality, heart transplantation, and left ventricular assist device implantation after 10-year follow-up. RESULTS The 10-year outcome in patients with diabetes was significantly worse than in those without diabetes (87% vs. 76%; adjusted hazard ratio [HR] 1.17 [95% CI 1.02–1.33]). Patients admitted in the last decade had a significantly lower 10-year event rate than patients admitted in the first two decades, both among patients without diabetes (adjusted HR 0.86 [95% CI 0.75–0.99]) and patients with diabetes (adjusted HR 0.80 [95% CI 0.63–1.00]). CONCLUSIONS The long-term outcome of patients with diabetes is worse than that of patients without diabetes. However, the long-term prognosis improved over time in both groups. Importantly, this improvement in long-term prognosis was comparable in patients with and without diabetes. Despite these promising results, more awareness for diabetes in patients with acute HF is necessary and there is still need for optimal treatment of diabetes in acute HF.

Background Renal dysfunction and anaemia are common in patients with acute heart failure (HF). It is not known whether their combined presence has additive prognostic value. We investigated their prognostic value separately and in combination, on prognosis in acute HF patients. Furthermore, we examined whether the improvement in prognosis was comparable between patients with and without renal dysfunction. Methods and results This prospective registry includes 1783 patients admitted to the (Intensive) Coronary Care Unit for acute HF in the period of 1985–2008. The outcome measure was the composite of all-cause mortality, heart transplantation and left ventricular assist device implantation. In patients without renal dysfunction, anemia was associated with worse 30-day outcome (HR 2.91; [95% CI 1.69–5.00]), but not with 10-year outcome (HR 1.13 [95% CI 0.93–1.37]). On the contrary, anemia was found to influence prognosis in patients with renal dysfunction, both at 30 days (HR 1.93 [95% CI 1.33–2.80]) and at 10 years (HR 1.27 [95% CI 1.10–1.47]). Over time, the 10-year survival rate improved in patients with preserved renal function (HR 0.73 [95% CI 0.55–0.97]), but not in patients with renal dysfunction. Conclusion The long-term prognosis of acute HF patients with a preserved renal function was found to have improved significantly. However, the prognosis of patients with renal dysfunction did not change. Anemia was a strong prognosticator for short-term outcome in all patients. In patients with renal dysfunction, anemia was also associated with impaired long-term prognosis.

A prolonged heart rate corrected QT interval (QTc) increases the risk of sudden cardiac death. Some methods of heart rate correction (notably Bazett) overestimate QTc in people with high heart rates. Studies suggest that tricyclic antidepressants (TCAs) can prolong the QTc and increase heart rate. Therefore, we aimed to study whether TCA-induced QTc prolongation is a false-positive observation due to overestimation at high heart rates. For this, we included 12,734 participants from the prospective population-based Rotterdam Study, with a total of 27,068 electrocardiograms (ECGs), of which, 331 during TCA use. Associations between use of TCAs, QTc, and heart rate were studied with linear repeated measurement analyses. QT was corrected for heart rate according to Bazett (QTc(Bazett)), Fridericia (QTc(Fridericia)), or a correction based on regression coefficients obtained from the Rotterdam Study data (QTc(Statistical)). On ECGs recorded during TCA use, QTc(Bazett) was 6.5 milliseconds (95% confidence interval, 4.0-9.0) longer, and heart rate was 5.8 beats per minute (95% confidence interval, 4.7-6.9) faster than during nonuse. QTc(Fridericia) and QTc(Statistical) were not statistically significantly longer during TCA use than during nonuse. Furthermore, QTc(Bazett) was similar for ECGs recorded during TCA use and nonuse after statistical adjustment for heart rate. According to our results, TCA use does not seem to be associated with QTc prolongation. Therefore, the current advice of regulatory authorities to restrict the use of these drugs and to do regular checkups of the QTc may need to be revised. Other formulas, like Fridericia's, might be preferred.

Background: Angiotensin-converting-enzyme inhibition reduces the risk of cardiovascular events at a group level. Presumably, the absolute effect of treatment varies between individuals. We sought to develop multivariable prediction scores to estimate individual treatment effect of perindopril in patients with stable coronary artery disease (sCAD). Methods: In EUROPA trial participants, we estimated the individual patient 5-year absolute risk reduction (ARR) of major adverse cardiovascular events(MACE) by perindopril. Predictions were based on a new Coxproportional-hazards model with clinical characteristics and an external risk score in combination with the observed relative risk reduction. Second, a genetic profile modifying the relative efficacy of perindopril was added. The individual patient ARR was defined as the difference in MACE risk with and without treatment. The group level impact of selectively treating patients with the largest predicted treatment effect was evaluated using net benefit analysis. Results: The risk score combining clinical and genetic characteristics estimated the 5-year absolute treatment effect to be absent or adverse in 27% of patients. On the other hand, the risk score estimated a small 5-year ARR of = 50) in 20% of patients, a modest ARR of 2-4% (NNT5 25-50) in 26%, and a large ARR of >= 4% (NNT5

Background: Fibroblast activation protein (FAP) is a transmembrane glycoprotein with dipeptidyl-peptidase and endopeptidase activities and circulates in blood in a truncated, soluble form (sFAP). Fibrinolysis inhibitor alpha 2-antiplasmin (alpha 2AP) has been described as a potential in vivo substrate of sFAP. We aimed to investigate sFAP levels and alpha 2AP cleavage in young arterial thrombosis patients and in control individuals, study the correlation between sFAP levels and alpha 2AP cleavage and investigate determinants of these variables. Methods: sFAP levels and alpha 2AP cleavage were determined by ELISA in the plasma samples of 391 coronary heart disease (CHD) patients, 221 ischemic stroke patients, 51 peripheral arterial disease patients and 501 control individuals. Results: Median sFAP levels were similar in arterial thrombotic patients and in control individuals, but in CHD patients sFAP levels significantly increased with time (number of months) between the event and study inclusion (Spearman's rho: 0.209, p < 0.001), indicating reduced sFAP levels at time of event. sFAP levels and percentage a2AP cleavage significantly correlated in controls and in patients. Furthermore, sex, use of oral contraceptives and hyperlipidemia were significant determinants of sFAP levels. Conclusions: sFAP levelswere reduced in the CHD patient population, but only in the first months after the event, indicating that over time sFAP levels may normalize. The significant correlation between sFAP level and alpha 2AP cleavage indicates that in vivo sFAP (at least partly) regulates cleavage of alpha 2AP, irrespective of disease status. Differences in sFAP level due to sex, use of oral contraceptives and hyperlipidemia might suggest hormonal control of sFAP levels. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

Background A prolonged heart rate-corrected QT (QTc) interval is a well-known risk indicator for sudden cardiac death (SCD) and a contraindication for drugs with potentially arrhythmogenic adverse effects. Objective We aimed to study the consistency of QTc interval prolongation and whether a consistent QTc interval prolongation correlates differently with SCD than does an inconsistently prolonged QTc interval. Methods We used a population-based cohort study of persons 55 years and older. We excluded participants using QTc-prolonging drugs or with bundle branch block. The QT interval was corrected for heart rate using Bazett and Fridericia formulas. Using a Cox regression model, we assessed the association between QTc interval prolongation consistency and the occurrence of SCD. Results A total of 3484 participants had electrocardiograms (ECGs) recorded on 2 consecutive visits. In 96%-98% of participants with a normal QTc interval on the first ECG, the QTc interval remained normal, but only in 27%-35% of those with a prolonged QTc interval, the QTc interval was prolonged on the second ECG after a median of 1.8 years. A consistently prolonged QTc interval was associated with an increased risk of SCD as compared with a consistently normal QTc interval (Bazett: hazard ratio 2.23; 95% confidence interval 1.17-4.24, Fridericia: hazard ratio 6.67; 95% confidence interval 2.96-15.06). A prolonged QTc interval preceded or followed by a normal QTc interval was not significantly associated with an increased risk of SCD. Conclusion Persons with an inconsistently prolonged QTc interval did not have a higher risk of SCD than those with a consistently normal QTc interval. Persons with a consistently prolonged QTc interval did have a higher risk of SCD. Our results suggest that repeated measurements of the QTc interval could enhance risk stratification.

Aims Both sudden cardiac death (SCD) and chronic obstructive pulmonary disease (COPD) are common conditions in the elderly. Previous studies have identified an association between COPD and cardiovascular disease, and with SCD in specific patient groups. Our aim was to investigate whether there is an association between COPD and SCD in the general population. Methods and results The Rotterdam study is a population-based cohort study among 14 926 subjects aged 45 years and older with up to 24 years of follow-up. Analyses were performed with a (time dependent) Cox proportional hazard model adjusted for age, sex, and smoking. Of the 13 471 persons included in the analysis; 1615 had a diagnosis of COPD and there were 551 cases of SCD. Chronic obstructive pulmonary disease was associated with an increased risk of SCD (age- and sex-adjusted hazard ratio, HR, 1.34, 95% CI 1.06–1.70). The risk particularly increased in the period 2000 days (5.48 years) after the diagnosis of COPD (age- and sex-adjusted HR 2.12, 95% CI 1.60–2.82) and increased further to a more than three-fold higher risk in COPD subjects with frequent exacerbations during this period (age- and sex-adjusted HR 3.58, 95% CI 2.35–5.44). Analyses restricted to persons without prevalent myocardial infarction or heart failure yielded similar results. Conclusion Chronic obstructive pulmonary disease is associated with an increased risk for SCD. The risk especially increases in persons with frequent exacerbations 5 years after the diagnosis of COPD. This risk indicator could provide new directions for better-targeted actions to prevent SCD.

Objective The ATP-binding cassette B1 ( ABCB1 ) gene encodes P-glycoprotein, a transport protein, which plays an important role in the bioavailability of digoxin. We aimed to investigate the interaction between variants within the ABCB1 gene and digoxin on the risk of sudden cardiac death (SCD). Methods Within the Rotterdam Study, a population-based cohort study in persons 45 years of age and older, we used Cox regression to analyse the association between three polymorphisms that have been associated with digoxin bioavailability, extracted from 1000-Genomes imputed ABCB1 genotypes and the risk of SCD, stratified by digoxin use. Results In a total study population of 10 932 persons, 419 SCDs occurred during a median follow-up of 9.8 years. In non-users of digoxin, the risk of SCD was not different across genotypes. In digoxin users, homozygous T allele carriers of C1236T (HR 1.90; 95% CI 1.09 to 3.30; allele frequency 0.43), G2677T (HR 1.89; 95% CI 1.10 to 3.24; allele frequency 0.44) and C3435T (HR 1.72; 95% CI 1.03 to 2.87; allele frequency 0.53) had a significantly increased risk of SCD in a recessive model. Interaction between the ABCB1 polymorphisms and digoxin use was significant for C1236T and G2677T in the age-adjusted and sex-adjusted model. Conclusions In this study, we showed that in digoxin users variant alleles at each of the three loci in the ABCB1 gene were associated with an increased risk of SCD compared with digoxin users with none or one T allele. If replicated, the findings imply that the ABCB1 genotype modifies the risk of cardiac digoxin toxicity.

OBJECTIVE: We investigated smoking cessation rates in coronary heart disease (CHD) patients throughout Europe; current and as compared to earlier EUROASPIRE surveys, and we studied characteristics of successful quitters.METHODS: Analyses were done on 7998 patients from the EUROASPIRE-IV survey admitted for myocardial infarction, unstable angina and coronary revascularisation. Self-reported smoking status was validated by measuring carbon monoxide in exhaled air.RESULTS: Thirty-one percent of the patients reported being a smoker in the month preceding hospital admission for the recruiting event, varying from 15% in centres from Finland to 57% from centres in Cyprus. Smoking rates at the interview were also highly variable, ranging from 7% to 28%. The proportion of successful quitters was relatively low in centres with a low number of pre- event smokers. Overall, successful smoking cessation was associated with increasing age (OR 1.50; 95% CI 1.09-2.06) and higher levels of education (OR 1.38; 95% CI 1.08-1.75). Successful quitters more frequently reported that they had been advised (56% vs. 47%, p CONCLUSION: Our study shows wide variation in cessation rates in a large contemporary European survey of CHD patients. Therefore, smoking cessation rates in patients with a CHD event should be interpreted in the light of pre-event smoking prevalence, and caution is needed when comparing cessation rates across Europe. Furthermore, we found that successful quitters reported more actions to make healthy lifestyle changes, including participating in a cardiac rehabilitation programme, as compared with persistent smokers.