Effects of a stepwise, structured LDL-C lowering strategy in patients post-acute coronary syndrome.

OBJECTIVE: Low-density lipoprotein cholesterol (LDL-C) lowering constitutes a cornerstone of secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet a considerable number of patients do not achieve guideline-recommended LDL­C targets. The 2016 European guidelines recommended titration of LDL­C lowering medication in a set number of steps, starting with oral medication. We aimed to investigate the effects of this stepwise approach in post-acute coronary syndrome (ACS) patients. METHODS: In a multicentre, prospective, non-randomised trial, we evaluated a three-step strategy aiming to reduce LDL­C to ≤ 1.8 mmol/l in post-ACS patients with prior ASCVD and/or diabetes mellitus. Steps, undertaken every 4-6 weeks, included: 1) start high-intensity statin (HIST); 2) addition of ezetimibe; 3) addition of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i). The primary outcome was the proportion of patients achieving LDL-C ≤ 1.8 mmol/l after Steps 1 and 2 (using oral medications alone). Secondary outcomes examined the prevalence of meeting the target throughout all steps ( https://onderzoekmetmensen.nl/nl/trial/21157 ). RESULTS: Out of 999 patients, 84% (95% confidence intervals (CI): 81-86) achieved the LDL­C target using only statin and/or ezetimibe. In an intention-to-treat analysis, the percentages of patients meeting the LDL­C target after each step were 69% (95% CI: 67-72), 84% (95% CI: 81-86), and 87% (95% CI: 85-89), respectively. There were protocol deviations for 23, 38 and 23 patients at each respective step. CONCLUSION: Through stepwise intensification of lipid-lowering therapy, 84% of very high-risk post-ACS patients achieved an LDL­C target of ≤ 1.8 mmol/l with oral medications alone. Addition of PCSK9i further increased this rate to 87% (95% CI: 85-89).

Treatment of elderly patients with non-ST-elevation myocardial infarction: the nationwide POPular age registry.

OBJECTIVE: We describe the current treatment of elderly patients with non-ST-elevation myocardial infarction (NSTEMI) enrolled in a national registry. METHODS: The POPular AGE registry is a prospective, multicentre study of patients ≥ 75 years of age presenting with NSTEMI, performed in the Netherlands. Management was at the discretion of the treating physician. Cardiovascular events consisted of cardiovascular death, myocardial infarction and ischaemic stroke. Bleeding was classified according to the Bleeding Academic Research Consortium (BARC) criteria. RESULTS: A total of 646 patients were enrolled between August 2016 and May 2018. Median age was 81 (IQR 77-84) years and 58% were male. Overall, 75% underwent coronary angiography, 40% percutaneous coronary intervention, and 11% coronary artery bypass grafting, while 49.8% received pharmacological therapy only. At discharge, dual antiplatelet therapy (aspirin and P2Y12 inhibitor) was prescribed to 56.7%, and 27.4% received oral anticoagulation plus at least one antiplatelet agent. At 1­year follow-up, cardiovascular death, myocardial infarction or stroke had occurred in 13.6% and major bleeding (BARC 3 and 5) in 3.9% of patients. The risk of both cardiovascular events and major bleeding was highest during the 1st month. However, cardiovascular risk was three times as high as bleeding risk in this elderly population, both after 1 month and after 1 year. CONCLUSIONS: In this national registry of elderly patients with NSTEMI, the majority are treated according to current European Society of Cardiology guidelines. Both the cardiovascular and bleeding risk are highest during the 1st month after NSTEMI. However, the cardiovascular risk was three times as high as the bleeding risk.

Early or Delayed Cardioversion in Recent-Onset Atrial Fibrillation.

BACKGROUND: Patients with recent-onset atrial fibrillation commonly undergo immediate restoration of sinus rhythm by pharmacologic or electrical cardioversion. However, whether immediate restoration of sinus rhythm is necessary is not known, since atrial fibrillation often terminates spontaneously. METHODS: In a multicenter, randomized, open-label, noninferiority trial, we randomly assigned patients with hemodynamically stable, recent-onset (<36 hours), symptomatic atrial fibrillation in the emergency department to be treated with a wait-and-see approach (delayed-cardioversion group) or early cardioversion. The wait-and-see approach involved initial treatment with rate-control medication only and delayed cardioversion if the atrial fibrillation did not resolve within 48 hours. The primary end point was the presence of sinus rhythm at 4 weeks. Noninferiority would be shown if the lower limit of the 95% confidence interval for the between-group difference in the primary end point in percentage points was more than -10. RESULTS: The presence of sinus rhythm at 4 weeks occurred in 193 of 212 patients (91%) in the delayed-cardioversion group and in 202 of 215 (94%) in the early-cardioversion group (between-group difference, -2.9 percentage points; 95% confidence interval [CI], -8.2 to 2.2; P = 0.005 for noninferiority). In the delayed-cardioversion group, conversion to sinus rhythm within 48 hours occurred spontaneously in 150 of 218 patients (69%) and after delayed cardioversion in 61 patients (28%). In the early-cardioversion group, conversion to sinus rhythm occurred spontaneously before the initiation of cardioversion in 36 of 219 patients (16%) and after cardioversion in 171 patients (78%). Among the patients who completed remote monitoring during 4 weeks of follow-up, a recurrence of atrial fibrillation occurred in 49 of 164 patients (30%) in the delayed-cardioversion group and in 50 of 171 (29%) in the early-cardioversion group. Within 4 weeks after randomization, cardiovascular complications occurred in 10 patients and 8 patients, respectively. CONCLUSIONS: In patients presenting to the emergency department with recent-onset, symptomatic atrial fibrillation, a wait-and-see approach was noninferior to early cardioversion in achieving a return to sinus rhythm at 4 weeks. (Funded by the Netherlands Organization for Health Research and Development and others; RACE 7 ACWAS ClinicalTrials.gov number, NCT02248753.).

Effect of a treat-to-target intervention of cardiovascular risk factors on subclinical and clinical atherosclerosis in rheumatoid arthritis: a randomised clinical trial.

BACKGROUND: Patients with rheumatoid arthritis (RA) have an increased risk for cardiovascular disease (CVD). No long-term intervention trials on CVD risk factors have been published, and a debate on the efficacy of controlling traditional risk factors in RA is ongoing. We aimed to evaluate a treat-to-target approach versus usual care regarding traditional CVD risk factors in patients with RA. METHODS: In this open-label, randomised controlled trial, patients with RA aged <70 years without prior CVD or diabetes mellitus were randomised 1:1 to either a treat-to-target approach or usual care of traditional CVD risk factors. The primary outcome was defined as change in carotid intima media thickness (cIMT) over 5 years, and the secondary outcome was a composite of first occurrence of fatal and non-fatal cardiovascular events. RESULTS: A total of 320 patients (mean age 52.4 years; 69.7% female) with RA underwent randomisation and 219 patients (68.4%) completed 5 years of follow-up. The mean cIMT progression was significantly reduced in the treat-to-target group compared with usual care (0.023 [95% CI 0.011 to 0.036] mm vs 0.045 [95% CI 0.030 to 0.059] mm; p=0.028). Cardiovascular events occurred in 2 (1.3%) of the patients in the treat-to-target group vs 7 (4.7%) in those receiving usual care (p=0.048 by log-rank test). CONCLUSION: This study provides evidence on the benefit of a treat-to-target approach of traditional CVD risk factors for primary prevention in patients with well-treated RA. TRIAL REGISTRATION NUMBER: NTR3873.

Evidence for increased chylomicron remnants in rheumatoid arthritis.

BACKGROUND: Levels of apolipoprotein (apo) B48 may be increased in conditions associated with systemic inflammation and increased cardiovascular disease (CVD) risk such as rheumatoid arthritis (RA). We aimed to evaluate apo B48 levels in patients with RA in relation to subclinical atherosclerosis. METHODS: Patients with RA (without CVD) and controls without RA but with high CVD risk (based on the presence of diabetes mellitus or a history of CVD) and healthy controls were included in this cross-sectional study. Carotid intima-media thickness (cIMT) was measured as a surrogate for vascular damage. RESULTS: In total, 312 patients with RA, 65 controls with high CVD risk and 36 healthy controls were included. Patients with RA had the highest mean apo B48 (10.00 ± 6.65 mg/L) compared to controls with high CVD risk and healthy controls (8.37 ± 5.16 and 5.22 ± 2.46, P < .001). Triglycerides levels were comparable with controls. In RA, apo B48 correlated positively with triglycerides (r = .645; P < .001) but not with cIMT. However, in RA subjects not using lipid or blood pressure lowering medication, a weak correlation was found with cIMT (r = .157; P = .014). RA patients in the highest apo B48 tertile were more often rheumatoid factor positive and anti-CCP positive compared to the lowest tertile. CONCLUSION: Rheumatoid arthritis patients have higher levels of apo B48 compared to controls with high CVD risk and healthy controls, with normal levels of triglycerides. This accumulation of atherogenic chylomicron remnants may contribute to the elevated CVD risk in RA patients.

Acute cardioversion vs a wait-and-see approach for recent-onset symptomatic atrial fibrillation in the emergency department: Rationale and design of the randomized ACWAS trial.

BACKGROUND: Current standard of care for patients with recent-onset atrial fibrillation (AF) in the emergency department aims at urgent restoration of sinus rhythm, although paroxysmal AF is a condition that resolves spontaneously within 24 hours in more than 70% of the cases. A wait-and-see approach with rate-control medication only and when needed cardioversion within 48 hours of onset of symptoms is hypothesized to be noninferior, safe, and cost-effective as compared with current standard of care and to lead to a higher quality of life. DESIGN: The ACWAS trial (NCT02248753) is an investigator-initiated, randomized, controlled, 2-arm noninferiority trial that compares a wait-and-see approach to the standard of care. Consenting adults with recent-onset symptomatic AF in the emergency department without urgent need for cardioversion are eligible for participation. A total of 437 patients will be randomized to either standard care (pharmacologic or electrical cardioversion) or the wait-and-see approach, consisting of symptom reduction through rate control medication until spontaneous conversion is achieved, with the possibility of cardioversion within 48 hours after onset of symptoms. Primary end point is the presence of sinus rhythm on 12-lead electrocardiogram at 4 weeks; main secondary outcomes are adverse events, total medical and societal costs, quality of life, and cost-effectiveness for 1 year. CONCLUSIONS: The ACWAS trial aims at providing evidence for the use of a wait-and-see approach for patients with recent-onset symptomatic AF in the emergency department.

Erythrocyte-bound apolipoprotein B in atherosclerosis and mortality.

BACKGROUND: The binding of apolipoprotein (apo) B-containing lipoproteins to circulating erythrocytes (ery-apoB) is associated with a decreased prevalence of atherosclerosis. In this study, we evaluated ery-apoB as a possible prognostic factor in cardiovascular events and all-cause mortality, in a prospective cohort study. MATERIALS AND METHODS: Ery-apoB was measured by flow cytometry in subjects with and without cardiovascular disease (CVD). The primary endpoint was the cardiovascular event rate. Secondary endpoints were all-cause mortality and the combined endpoint of all-cause mortality and cardiovascular events (any event rate). A Cox regression analysis with univariate and multivariate analyses and Kaplan-Meier survival analysis was performed. RESULTS: Follow-up data were available of 384 subjects. Subjects were divided according to high (> 2·0 au, n = 60), intermediate (0·2-2·0 au, n = 274) or low (< 0·2 au, n = 50) ery-apoB. Median follow-up was 1767 days (IQR 1564-2001). In univariate analysis, low ery-apoB was associated with increased all-cause mortality [HR 9·9 (1·2-79·0), P = 0·031] and any event rate [HR 3·4 (95% CI 1·3-8·7), P = 0·012]. In a Cox regression analysis, only a history of CVD was significantly associated with any event rate [HR 3·6 (1·6-8·0), P = 0·002], while low ery-apoB showed a trend [HR 2·4 (0·9-6·4), P = 0·07]. In a subgroup analysis, in subjects with a history of CVD, ery-apoB was significantly associated with all-cause mortality (log rank P = 0·021) and any event rate (log rank P = 0·009). CONCLUSIONS: Low ery-apoB is associated with increased mortality and cardiovascular risk, especially in patients with a prior history of CVD. These subjects may benefit from more aggressive secondary prevention treatment.

Cost-effectiveness of screening strategies to detect heart failure in patients with type 2 diabetes.

BACKGROUND: Heart failure (HF), especially with preserved ejection fraction (HFpEF) is common in older patients with type 2 diabetes (T2DM), but often not recognized. Early HF detection in older T2DM patients may be worthwhile because treatment may be initiated in an early stage, with clear beneficial treatment in those with reduced ejection fraction (HFrEF), but without clear prognostic beneficial treatment in those with HFpEF. Because both types of HF may be uncovered in older T2DM, screening may improve health outcomes at acceptable costs. We assessed the cost-effectiveness of five screening strategies in patients with T2DM aged 60 years or over. METHODS: We built a Markov model with a lifetime horizon based on the prognostic results from our screening study of 581 patients with T2DM, extended with evidence from literature. Cost-effectiveness was calculated from a Dutch healthcare perspective as additional costs (Euros) per additional quality-adjusted life-year (QALY) gained. We performed probabilistic sensitivity analysis to assess robustness of these outcomes. Scenario analyses were performed to assess the influence of the availability of effective treatment of heart failure with preserved ejection fraction. RESULTS: For willingness to pay values in the range of €6050/QALY-€31,000/QALY for men and €6300/QALY-€42,000/QALY for women, screening-based checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms had the highest probability of being cost-effective. For higher willingness-to-pay values, direct echocardiography was the preferred screening strategy. Cost-effectiveness of all screening strategies improved with the increase in effectiveness of treatment for HFpEF. CONCLUSIONS: Screening for HF in older community-dwelling patients with T2DM is cost-effective at the commonly used willingness-to-pay threshold of €20.000/QALY by checking the electronic medical record for patient characteristics and medical history plus the assessment of symptoms. The simplicity of such a strategy makes it feasible for implementation in existing primary care diabetes management programs.

Leucocyte-bound apolipoprotein B in the circulation is inversely associated with the presence of clinical and subclinical atherosclerosis.

BACKGROUND: Atherosclerosis is a pro-inflammatory condition, in which leucocyte activation plays an important role. The interaction between circulating leucocytes and apolipoprotein (apo) B-containing lipoproteins results in pro-inflammatory changes of these cells. We aimed to evaluate the relationship between apo B bound to circulating leucocytes and atherosclerosis. METHODS: Apo B on circulating leucocytes was measured by flow cytometry in subjects with and without cardiovascular disease (CVD), expressed as mean fluorescent intensity in arbitrary units (au). Carotid intima-media thickness (cIMT) was measured using B-mode ultrasound. Data are given as median (interquartile range). RESULTS: A total of 396 subjects were included, of whom 183 had a history of CVD. Compared to subjects without CVD, patients with CVD had lower apo B bound to neutrophils (12·7 au (9·8-16·2) and 14·2 au (10·1-17·5), respectively, P = 0·038) and to monocytes (2·5 au (1·7-3·1) and 2·7 (1·9-3·6) au, respectively, P = 0·025). No differences were found for lymphocyte-bound apo B. Neutrophil- and monocyte-bound apo B were inversely correlated with cIMT (Spearman's rho: -0·123, P = 0·017 and -0·108, P = 0·035, respectively). Both monocyte- and neutrophil-bound apo B were inversely associated with different factors related to the metabolic syndrome, such as body mass index, triglycerides and complement C3. There was a positive association between erythrocyte-bound apo B and apo B bound to each of the leucocyte classes, possibly reflecting a similar mechanism. Discontinuation of statins in 54 subjects did not influence leucocyte-bound apo B. CONCLUSION: Unexpectedly, the presence of noninternalized apo B-containing lipoproteins on circulating neutrophil and monocyte membranes may represent a protective mechanism against atherosclerosis.

Statins for acute coronary syndrome.

BACKGROUND: The early period following the onset of acute coronary syndrome (ACS) represents a critical stage of coronary heart disease, with a high risk of recurrent events and deaths. The short-term effects of early treatment with statins on patient-relevant outcomes in patients suffering from ACS are unclear. This is an update of a review previously published in 2011. OBJECTIVES: To assess the effects, both harms and benefits, of early administered statins in patients with ACS, in terms of mortality and cardiovascular events. SEARCH METHODS: We updated the searches of CENTRAL (2013, Issue 3), MEDLINE (Ovid) (1946 to April Week 1 2013), EMBASE (Ovid) (1947 to 2013 Week 14), and CINAHL (EBSCO) (1938 to 2013) on 12 April 2013. We applied no language restrictions. We supplemented the search by contacting experts in the field, by reviewing the reference lists of reviews and editorials on the topic, and by searching trial registries. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing statins with placebo or usual care, with initiation of statin therapy within 14 days following the onset of ACS, follow-up of at least 30 days, and reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Two authors independently assessed risk of bias and extracted data. We calculated risk ratios (RRs) for all outcomes in the treatment and control groups and pooled data using random-effects models. MAIN RESULTS: Eighteen studies (14,303 patients) compared early statin treatment versus placebo or no treatment in patients with ACS. The new search did not identify any new studies for inclusion. There were some concerns about risk of bias and imprecision of summary estimates. Based on moderate quality evidence, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction, and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) or four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up when compared to placebo or no treatment. There were no statistically significant risk reductions from statins for total death, total myocardial infarction, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month or at four months, although there were favorable trends related to statin use for each of these endpoints. Moderate quality evidence suggests that the incidence of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels more than 10 times the upper limit of normal) in statin-treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg. AUTHORS' CONCLUSIONS: Based on moderate quality evidence, due to concerns about risk of bias and imprecision, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS. Serious side effects were rare.

Conservative versus Invasive Strategy in Elderly Patients with Non-ST-Elevation Myocardial Infarction: Insights from the International POPular Age Registry.

This registry assessed the impact of conservative and invasive strategies on major adverse clinical events (MACE) in elderly patients with non-ST-elevation myocardial infarction (NSTEMI). Patients aged ≥75 years with NSTEMI were prospectively registered from European centers and followed up for one year. Outcomes were compared between conservative and invasive groups in the overall population and a propensity score-matched (PSM) cohort. MACE included cardiovascular death, acute coronary syndrome, and stroke. The study included 1190 patients (median age 80 years, 43% female). CAG was performed in 67% (N = 798), with two-thirds undergoing revascularization. Conservatively treated patients had higher baseline risk. After propensity score matching, 319 patient pairs were successfully matched. MACE occurred more frequently in the conservative group (total population 20% vs. 12%, adjHR 0.53, 95% CI 0.37-0.77, p = 0.001), remaining significant in the PSM cohort (18% vs. 12%, adjHR 0.50, 95% CI 0.31-0.81, p = 0.004). In conclusion, an early invasive strategy was associated with benefits over conservative management in elderly patients with NSTEMI. Risk factors associated with ischemia and bleeding should guide strategy selection rather than solely relying on age.

Statins for acute coronary syndrome.

BACKGROUND: The early period following the onset of acute coronary syndromes (ACS) represents a critical stage of coronary heart disease with a high risk for recurrent events and deaths. The short-term effects of early treatment with statins in patients suffering from ACS on patient-relevant outcomes are unclear. OBJECTIVES: To assess the benefits and harms of early administered statins in patients with ACS from randomized controlled trials (RCTs). SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, and CINAHL (to 1 February 2010). No language restrictions were applied. We supplemented the search by contacting experts in the field, by reviewing reference lists of reviews and editorials on the topic, and by searching trial registries. SELECTION CRITERIA: RCTs comparing statins with placebo or usual care, initiation of statin therapy within 14 days following the onset of ACS, and follow-up of at least 30 days reporting at least one clinical outcome. DATA COLLECTION AND ANALYSIS: Two authors independently assessed study quality and extracted data. We pooled treatment effects and calculated risk ratios (RRs) for all outcomes in the treatment and control groups using a random effects model. MAIN RESULTS: Eighteen studies (14,303 patients) compared early statin treatment versus placebo or usual care in patients with ACS. Compared to placebo or usual care, early statin therapy did not decrease the combined primary outcome of death, non-fatal myocardial infarction (MI), and stroke at one month (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.80 to 1.08) and four months (RR 0.93, 95% CI 0.81 to 1.06) of follow-up. There were no statistically significant risk reductions from statins for total death, total MI, total stroke, cardiovascular death, revascularization procedures, and acute heart failure at one month and at four months, although there were favorable trends related to statin use for each of these endpoints. The incidence of episodes of unstable angina was significantly reduced at four months following ACS (RR 0.76, 95% CI 0.59 to 0.96). There were nine individuals with myopathy (elevated creatinine kinase levels > 10 times the upper limit of normal) in statin treated patients (0.13%) versus one (0.015%) in the control groups. Serious muscle toxicity was mostly limited to patients treated with simvastatin 80 mg. AUTHORS' CONCLUSIONS: Based on available evidence, initiation of statin therapy within 14 days following ACS does not reduce death, myocardial infarction, or stroke up to four months, but reduces the occurrence of unstable angina at four months following ACS.

Evolution of renal function and predictive value of serial renal assessments among patients with acute coronary syndrome: BIOMArCS study.

BACKGROUND: Impaired renal function predicts mortality in acute coronary syndrome (ACS), but its evolution immediately following index ACS and preceding next ACS has not been described in detail. We aimed to describe this evolution using serial measurements of creatinine, glomerular filtration rate [eGFRCr] and cystatin C [CysC]. METHODS: From 844 ACS patients included in the BIOMArCS study, we analysed patient-specific longitudinal marker trajectories from the case-cohort of 187 patients to determine the risk of the endpoint (cardiovascular death or hospitalization for recurrent non-fatal ACS) during 1-year follow-up. Study included only patients with eGFRCr ≥ 30 ml/min/1.73 m2. Survival analyses were adjusted for GRACE risk score and based on data >30 days after the index ACS (mean of 8 sample per patient). RESULTS: Mean age was 63 years, 79% were men, 43% had STEMI, and 67% were in eGFR stages 2-3. During hospitalization for index ACS (median [IQR] duration: 5 (3-7) days), CysC levels indicated deterioration of renal function earlier than creatinine did (CysC peaked on day 3, versus day 6 for creatinine), and both stabilized after two weeks. Higher CysC levels, but not creatinine, predicted the endpoint independently of the GRACE score within the first year after index ACS (adjusted HR [95% CI] per 1SD increase: 1.68 [1.03-2.74]). CONCLUSION: Immediately following index ACS, plasma CysC levels deteriorate earlier than creatinine-based indices do, but neither marker stabilizes during hospitalization but on average two weeks after ACS. Serially measured CysC levels predict mortality or recurrence of ACS during 1-year follow-up independently of patients' GRACE risk score.

Early recognition of heart failure in patients with diabetes type 2 in primary care. A prospective diagnostic efficiency study. (UHFO-DM2).

BACKGROUND: We hypothesize that the prevalence of unknown heart failure in diabetic patients aged 60 years and over is relatively high (15% or more) and that a cost-effective strategy can be developed to detect heart failure in these patients. The strategy is expected to include some signs and symptoms (such as dyspnoea, orthopnoea, pulmonary crepitations and laterally displaced apical beat), natriuretic peptide measurements (Amino-terminal B-type natriuretic peptide) and possibly electrocardiography. In a subset of patients straightforward echocardiography may show to be cost-effective. With information from our study the detection of previously unknown heart failure in diabetic patients could be improved and enable the physician to initiate beneficial morbidity and mortality reducing heart failure treatment more timely. PRIMARY OBJECTIVES: - To assess the prevalence of (previously unrecognised) heart failure in primary care patients with diabetes type 2.- To establish the most cost-effective diagnostic strategy to detect unrecognised heart failure in these patients. SECONDARY OBJECTIVES: - To assess the impact of heart failure, and the combination of a new diagnosis with accordingly treatment in patients with diabetes type 2 on health status. DESIGN: A prospective diagnostic efficiency study. PATIENT POPULATION: Patients aged 60 years and older with diabetes type 2 from primary care, enlisted with the diabetes service of the Diagnostic Center in Etten-Leur (SHL)All participants will be investigated at the cardiology out-patient department of the regional hospital (Oosterschelde Hospital in Goes, Zeeland, the Netherlands) during a single 1.5 hour standardised diagnostic assessment, including history taking, physical examination, electrocardiography, echocardiography, blood tests, and Health status questionnaires. Patients will be asked if we can contact them afterwards for follow-up and for repeating the questionnaires after three and 12 months.Main study parameters/endpoints: Prevalence (with exact 95% confidence intervals) of (previously unrecognised) heart failure (systolic and 'isolated' diastolic) and the diagnostic value of signs and symptoms, NT-proBNP, electrocardiography and a combination of these items. The cost-effectiveness of different diagnostic strategies. Impact of heart failure and the combination of a new diagnosis with accordingly treatment on health status. TRIAL REGISTRATION: CCMO register NL2271704108.

Temporal Pattern of Growth Differentiation Factor-15 Protein After Acute Coronary Syndrome (From the BIOMArCS Study).

Growth differentiation factor-15 (GDF-15) has appeared as a promising biomarker with strong predictive abilities in acute coronary syndrome (ACS). However, studies are solely based on single measurements in the acute phase of an ACS event. The way GDF-15 patterns in post-ACS patients behave on the long term is largely unknown. We conducted a nested case-control study within our multicenter, prospective, observational biomarker study (BIOMArCS) of 844 ACS patients. Following an index ACS event, high-frequency blood sampling was performed during 1-year of follow-up. GDF-15 was determined batchwise by electrochemiluminescence immunoassays in 37 cases with a recurrent event during 1-year follow-up, and in 74 event-free controls. Cases and controls had a mean ± standard deviation age of 66.9 ± 11.3 years and 81% were men. From 30 days onwards, patients showed stable levels, which were on average 333 (95% confidence interval 68 to 647) pg/mL higher in cases than controls (1704 vs 1371 pg/mL; p value 0.013). Additionally, in the post 30-day period, GDF-15 showed low within-individual variability in both cases and controls. In conclusion, post-ACS patients experiencing a recurrent event had stable and systematically higher GDF-15 levels during 30-day to 1-year follow-up than their event-free counterparts with otherwise similar clinical characteristics. Thus, postdischarge blood sampling might be used throughout the course of 1 year to improve prognostication, whereas, in view of the low within-individual variation, the number of repeated sampling moments might be limited.

Liver chemistry abnormalities and leg oedema in rheumatoid arthritis.

A 66-year-old man with seronegative, erosive rheumatoid arthritis for 12 years presented with malaise, elevated alkaline phosphatase and gamma-glutamyl transferase, and leg oedema. He subsequently developed ascites. No liver pathology was found, but cardiac analysis including right heart catheterisation revealed constrictive pericarditis. Rheumatoid constrictive pericarditis is a rare condition, but, despite current effective treatment for rheumatoid arthritis, still occurs. Diagnostic delay is frequent. Although mortality of the intervention is high, pericardiectomy is needed for most patients.

A Rapid (Differential) Effect of Rosuvastatin and Atorvastatin on High-Sensitivity Cardiac Troponin-I in Subjects With Stable Cardiovascular Disease.

Serum troponin within the normal range is an emerging predictor of cardiovascular mortality. We aimed to determine how rapidly high-sensitivity troponin-I (hs-cTnI) levels are lowered by statin therapy in patients with stable cardiovascular disease. In the RADAR substudy, patients were randomized to atorvastatin 20 mg/day (n = 39) or rosuvastatin 10 mg/day (n = 39) and up-titrated at 6-week intervals to 80 mg of atorvastatin or 40 mg of rosuvastatin. Hs-cTnI concentrations were measured at baseline and at 6 and 18 weeks of follow-up. Statin treatment resulted in a mean change of serum hs-cTnI of -8.2% (P = 0.010) after 6 weeks and -12.3% (P = 0.001) after 18 weeks. After 18 weeks, hs-cTnI levels were lowered by 21.8% with atorvastatin and by 4.1% with rosuvastatin (P = 0.001 and P = 0.133, respectively). During statin therapy, serum hs-cTnI levels decreased rapidly within weeks of treatment, suggesting an effect beyond long-term atherosclerosis regression. Mechanisms that mediate this effect require further study.

Trends in comorbidity in patients hospitalised for cardiovascular disease.

BACKGROUND: We determined trends over time in cardiovascular and non-cardiovascular comorbidity in patients hospitalised for cardiovascular disease (CVD). METHODS: The Dutch nationwide hospital register was used to identify patients hospitalised for CVD during 2000-2010. Comorbidity was defined as a previous hospital admission for CVD other than the index CVD, cancer, diabetes, musculoskeletal and connective tissue disorders, respiratory disorders, thyroid gland disorders, kidney disorders and dementia in the five years previous to hospital admittance for the index CVD. Trends were calculated in strata of age and sex and for different types of CVD: coronary heart disease (CHD), cerebrovascular disease (CVA), heart failure (HF) and peripheral arterial disease (PAD). RESULTS: We identified 2,397,773 admissions for CVD between 2000 and 2010. Comorbidity was present in 38%. In HF, PAD, CHD and CVA this was 54%, 46%, 40%, and 32%, respectively. Between 2000 and 2010, the percentage of patients with comorbidity increased (+1.1%), this increase was most pronounced in patients ≥75years (+3.0%). Cardiovascular disease was the most frequent comorbid condition, though became less prevalent over time (men -5%; women: -2%), whereas non-cardiovascular comorbidity increased in men (+4%), and remained similar in women (-1%). Cancer was the most common non-cardiovascular comorbid condition and increased in men and women (men: +5%; women: +4%). CONCLUSIONS: Comorbid conditions are highly prevalent in patients hospitalised for CVD, especially HF and PAD patients. In older patients, prevalences increased over time. Cardiovascular diseases were the most common comorbid condition, though the prevalence decreased over the study period whereas the prevalence of cancer increased.

Characterization and cholesterol management in patients with cardiovascular events and/or type 2 diabetes in the Netherlands.

OBJECTIVE: To describe clinical characteristics and cholesterol management of patients with cardiovascular events (CVEs) and/or type 2 diabetes mellitus (T2DM) with high low-density lipoprotein cholesterol (LDL-C) > 1.8 mmol/L in the Netherlands. RESEARCH DESIGN AND METHODS: From the PHARMO Database Network a cross-sectional cohort was constructed. The descriptive study included patients on lipid modifying therapy (LMT) in 2009, classified as high cardiovascular risk based on a history of T2DM or CVE, with 2010 LDL-C levels above 1.8 mmol/L (2011 European Society of Cardiology [ESC] target). Sub-cohorts were created: T2DM + CVE from the T2DM cohort and multiple CVE from the CVE only cohort. MAIN OUTCOME MEASURES: Clinical characteristics and drug treatment were determined at the time of the last LDL-C measurement in 2010. RESULTS: Of 10,864 very high risk patients, 66% had T2DM, 37% of whom also had CVE. In the CVE only cohort (34%), 18% had multiple events. More regular check-ups skewed inclusion towards diabetes patients. T2DM vs. CVE cohort characteristics were: 53% vs. 63% male, 42% vs. 27% obese, 19% vs. 24% current smoker, 54% vs. 51% systolic blood pressure <140 mmHg, with similar proportions in the sub-cohorts. Proportions reaching the Dutch guideline LDL-C target of <2.5 mmol/L were 56% (T2DM), 57% (T2DM + CVE), 48% (CVE only) and 53% (multiple CVE only). Frequencies of high intensity dose statin (simvastatin ≥80 mg, atorvastatin ≥40 mg or rosuvastatin ≥20 mg) were 6% (T2DM), 9% (T2DM + CVE, CVE only) and 14% (multiple CVE only); 1-2% received additional ezetimibe and 3-5% received non-statin LMT only, including ezetimibe. CONCLUSION: Despite LMT, >40% of the patients above ESC target also failed to reach the less stringent Dutch target, even in the higher risk groups. Therefore, management of hypercholesterolemia after CVE or T2DM should be optimized to improve cardiovascular outcomes. There is substantial room for improving other cardiovascular risk factors.