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Aims The HFA-PEFF score was developed to optimize diagnosis and to aid in early recognition of heart failure (HF) with preserved ejection fraction (HFpEF) in patients who present with HF-like symptoms. Recognizing early-HFpEF phenogroups is essential to better understand progression towards overt HFpEF and pave the way for early intervention and treatment. Whether the HFA-PEFF domain scores can identify ‘early-HFpEF’ phenogroups remains unknown. The aims of this pilot study are to (i) identify distinct phenogroups by cluster analysis of HFA-PEFF domain scores in subjects that present with HF-like symptoms and (ii) study whether these phenogroups may be associated with distinct blood proteome profiles. Methods and results Subjects referred to the Cardiology Centers of the Netherlands, location Utrecht, with non-acute possibly cardiac-related symptoms (such as dyspnoea or fatigue) were prospectively enrolled in the HELPFul cohort (N = 507) and were included in the current analysis. Inclusion criteria for this study were (i) age ≥ 45 years and (ii) a left ventricular ejection fraction (LVEF) ≥ 50%, in the absence of a history of HF, coronary artery disease, congenital heart disease, or any previous cardiac interventions. Multinominal-based clustering with latent class model using the HFA-PEFF domain scores (functional, structural, and biomarker scores) as input was used to detect distinct phenotypic clusters. For each bootstrapping run, the 92 Olink proteins were analysed for their association with the identified phenogroups. Four distinct phenogroups were identified in the current analysis (validated by bootstrapping 1000×): (i) no left ventricular diastolic dysfunction (no LVDD, N = 102); (ii) LVDD with functional left ventricular (LV) abnormalities (N = 204); (iii) LVDD with functional and structural LV abnormalities (N = 204); and (iv) LVDD with functional and structural LV abnormalities and elevated BNP (N = 107). The HFA-PEFF total score risk categories significantly differed between the phenogroups (P < 0.001), with an increase of the HFA-PEFF score from Phenogroup 1 to 4 (low/intermediate/high HFA-PEFF risk score: Phenogroup 1: 88%/12%/0%; Phenogroup 2: 9%/91%/0%; Phenogroup 3: 0%/92%/8%; Phenogroup 4: 5%/83%/12%). Thirty-two out of the 92 Olink protein biomarkers significantly differed among the phenogroups. The top eight biomarkers—N-terminal prohormone brain natriuretic peptide, growth differentiation factor-15, matrix metalloproteinase-2, osteoprotegerin, tissue inhibitor of metalloproteinase-4, chitinase-3-like protein 1, insulin-like growth factor-binding protein 2, and insulin-like growth factor-binding protein 7—are mainly involved in inflammation and extracellular matrix remodelling, which are currently proposed key processes in HFpEF pathophysiology. Conclusions This study identified distinct phenogroups by using the HFA-PEFF domain scores in ambulant subjects referred for HF-like symptoms. The newly identified phenogroups accompanied by their circulating biomarkers profile might aid in a better understanding of the pathophysiological processes involved during the early stages of the HFpEF syndrome. [ABSTRACT FROM AUTHOR]

Objective: Women with heart failure with reduced ejection fraction (HFrEF) may reach optimal treatment effect at half of the guideline-recommended medication dose. This study investigates prescription practice and its relation with survival of patients with HF in daily care.Methods: Electronic health record data from 13 Dutch outpatient cardiology clinics were extracted for HF receiving at least one guideline-recommended HF medication. Dose changes over consecutive prescriptions were modelled using natural cubic splines. Inverse probability-weighted Cox regression was used to assess the relationship between dose (reference≥50% target dose) and all-cause mortality.Results: The study population comprised 561 women (29% HFrEF (ejection fraction (EF)<40%), 49% heart failure with preserved ejection fraction (EF≥50%); HFpEF and 615 men (47% and 25%, respectively). During a median follow-up of 3.7 years, 252 patients died (48% women; 167 HFrEF, 84 HFpEF). Nine hundred thirty-four patients (46% women) received ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), 795 (48% women) beta blockers and 178 (42% women) mineralocorticoid receptor antagonists (MRAs). In both sexes, the mean target dose across prescriptions was 50% for ACEI/ARBs and beta blockers, and 100% for MRAs. ACEI/ARB dose of <50% was associated with lower mortality in women but not in men with HFrEF. This was not seen in patients with HFpEF. Beta-blocker dose was not associated with all-cause mortality.Conclusion: Patients with HF seen in outpatient cardiology clinics receive half of the guideline-recommended medication dose. Lower ACEI/ARB dose was associated with improved survival in women with HFrEF. These results underscore the importance of (re)defining optimal medical therapy for women with HFrEF. [ABSTRACT FROM AUTHOR]

Background: Despite the increasing availability of clinical data due to the digitalisation of healthcare systems, data often remain inaccessible due to the diversity of data collection systems. In the Netherlands, Cardiology Centers of the Netherlands (CCN) introduced "one-stop shop" diagnostic clinics for patients suspected of cardiac disease by their general practitioner. All CCN clinics use the same data collection system and standardised protocol, creating a large regular care database. This database can be used to describe referral practices, evaluate risk factors for cardiovascular disease (CVD) in important patient subgroups, and develop prediction models for use in daily care.Construction and Content: The current database contains data on all patients who underwent a cardiac workup in one of the 13 CCN clinics between 2007 and February 2018 (n = 109,151, 51.9% women). Data were pseudonymised and contain information on anthropometrics, cardiac symptoms, risk factors, comorbidities, cardiovascular and family history, standard blood laboratory measurements, transthoracic echocardiography, electrocardiography in rest and during exercise, and medication use. Clinical follow-up is based on medical need and consisted of either a repeat visit at CCN (43.8%) or referral for an external procedure in a hospital (16.5%). Passive follow-up via linkage to national mortality registers is available for 95% of the database.Utility and Discussion: The CCN database provides a strong base for research into historically underrepresented patient groups due to the large number of patients and the lack of in- and exclusion criteria. It also enables the development of artificial intelligence-based decision support tools. Its contemporary nature allows for comparison of daily care with the current guidelines and protocols. Missing data is an inherent limitation, as the cardiologist could deviate from standardised protocols when clinically indicated.Conclusion: The CCN database offers the opportunity to conduct research in a unique population referred from the general practitioner to the cardiologist for diagnostic workup. This, in combination with its large size, the representation of historically underrepresented patient groups and contemporary nature makes it a valuable tool for expanding our knowledge of cardiovascular diseases.Trial Registration: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Coronary artery disease affects both men and women. In this study, we examine sex-specific differences in occurrence of major adverse cardiovascular events (MACEs) after coronary angiography. Methods: We analyzed data from the coronary angiography cohort Utrecht Coronary Biobank (n = 1283 men, 480 women). Using Kaplan-Meier and multivariable Cox-regression, we tested for sex differences in MACE occurrence. Additionally, we compared mortality with an age- and sex-matched control group from the general Dutch population. Results: During a median follow-up of 2.1 years (interquartile range 1.6-2.8), MACEs occurred in 265 men and 103 women (20.7% vs 21.3%, P = .744). Women with myocardial infarction (MI) had significantly more MACE during follow-up than men (hazard ratio [HR] 1.66 for female sex, 95% confidence interval [CI] 1.10-2.50, P = .015), which was also the case for women who had multivessel disease (HR 1.41, 95% CI 1.03-1.94, P = .031). During follow-up, mortality in women presenting with MI was higher than mortality of women in the general population; men with MI did not show this disadvantage. Conclusion: MACEs occurred more often in women than in men who presented with MI or who had angiographic multivessel disease upon coronary angiography. Clinical trial registration:Clinicaltrials.gov identifier: NCT02304744. URL: https://clinicaltrials.gov/ct2/show/NCT02304744. [ABSTRACT FROM AUTHOR]

Background GPs need accurate tools for cardiovascular (CV) risk assessment. Abnormalities in resting electrocardiograms (ECGs) relate to increased CV risk. Aim To determine whether measurement of ECG abnormalities on top of established risk estimation (SCORE) improves CV risk classification in a primary care population. Design and setting A cohort study of patients enlisted with academic general practices in the Netherlands (the Utrecht Health Project [UHP]). Method Incident CV events were extracted from the GP records. MEANS algorithm was used to assess ECG abnormalities. Cox proportional hazards modelling was applied to relate ECG abnormalities to CV events. For a prediction model only with SCORE variables, and a model with SCORE+ECG abnormalities, the discriminative value (area under the receiver operator curve [AUC]) and the net reclassification improvement (NRI) were estimated. Results A total of 2370 participants aged 38-74 years were included, all eligible for CV risk assessment. During a mean follow-up of 7.8 years, 172 CV events occurred. In 19% of the participants at least one ECG abnormality was found (Lausanne criteria). Presence of atrial fibrillation/flutter (AF) and myocardial infarction (MI) were significantly related to CV events. The AUC of the SCORE risk factors was 0.75 (95% CI = 0.71 to 0.79). Addition of MI or AF resulted in an AUC of 0.76 (95% CI = 0.72 to 0.79) and 0.75 (95% CI = 0.72 to 0.79), respectively. The NRI with the addition of ECG abnormalities was small (MI 1.0%; 95% CI = -3.2% to 6.9%; AF 0.5%; 95% CI = -3.5% to 3.3%). Conclusion Performing a resting ECG in a primary care population does not seem to improve risk classification when SCORE information - age, sex, smoking, systolic blood pressure, and total cholesterol/HDL ratio - is already available. [ABSTRACT FROM AUTHOR]

[Display omitted] • It has been suggested that patients with diabetes who experience an ACS present with a broad variety of symptoms which could hamper the urgency allocation during telephone triage. • Among males and females who called OHS-PC with acute chest discomfort, those with diabetes versus those without: • Reported relatively lower rates of chest pain and higher rates of shortness of breath; • Did not receive a high urgency more often; • Had higher odds for ACS and 'ACS or other LTE'. • Triage nurses at the OHS-PC should always ask for diabetes in callers with acute chest discomfort as this helps triage given the substantial increase in risk of ACS and 'ACS or other LTE'. We investigated the differences in prevalence of acute coronary syndrome (ACS) by presence versus absence of diabetes in males and females with chest discomfort who called out-of-hours primary care (OHS-PC). A cross-sectional study performed in the Netherlands. Patients who called the OHS-PC in the Utrecht region, the Netherlands between 2014 and 2017 with acute chest discomfort were included. We compared those with diabetes with those without diabetes. Multivariable logistic regression was used to determine the relation between diabetes and (i) high urgency allocation and (ii) ACS. Of the 2,195 callers with acute chest discomfort, 180 (8.2%) reported having diabetes. ACS was present in 15.3% of males (22.0% in those with diabetes) and 8.4% of females (18.8% in those with diabetes). Callers with diabetes did not receive a high urgency more frequently (74.4% vs. 67.8% (OR: 1.38; 95% CI 0.98–1.96). However, such callers had a higher odds for ACS (OR: 2.17; 95% CI 1.47–3.19). These differences were similar for females and males. Diabetes holds promise as diagnostic factor in callers to OHS-PC with chest discomfort. It might help triage in this setting given the increased risk of ACS in those with diabetes. [ABSTRACT FROM AUTHOR]

Background and Aims: It is still unclear whether a healthy diet can prevent heart failure (HF). Therefore, this study aimed to investigate the association between adherence to a Mediterranean-style diet, reflected by modified Mediterranean Diet Scores (mMDS), and the incidence of HF in men and women., Methods and Results: This observational study comprised 9316 men and 27,645 women from the EPIC-NL cohort free from cardiovascular disease at baseline. Dietary intakes were assessed using a validated food frequency questionnaire. mMDS was calculated using a 9-point scale based on consumption of vegetables, legumes, fruit, nuts, seeds, grains, fish, fat ratio, dairy, meat and alcohol. HF events were ascertained by linkage to nation-wide registries. Multivariable Hazard Ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards regression models. Over a median follow-up of 15 years (IQR 14-16), 633 HF events occurred: 144 in men (1.5%) and 489 in women (1.8%). The median mMDS was 4 (IQR 3-5). There was significant effect modification by sex (P-value for interaction <0.001), therefore results are stratified for men and women. For men, a higher mMDS associated with lower HF risk (HR: 0.88; 95% CI: 0.79, 0.98 per point increase in mMDS; HR upper category: 0.53; 95% CI: 0.33, 0.86), whereas no association was found in women (HR: 0.98; 95% CI: 0.93, 1.04 per point increase; HR upper category: 1.07; 95% CI: 0.83, 1.36)., Conclusion: Adherence to a Mediterranean-style diet may reduce HF risk, particularly in men. The underlying reasons for the differences in findings between men and women need further study., Competing Interests: Declaration of competing interest None., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess the diagnostic value of non-acute chest pain characteristics for coronary artery disease in women and men referred to outpatient cardiology clinics., Design and Setting: This is an observational study performed at outpatient cardiology centres of the Netherlands., Participants: The study population consisted of 1028 patients with non-acute chest pain (505 women)., Analysis and Results: Twenty-four women (5%) and 75 men (15%) were diagnosed with coronary artery disease by invasive coronary angiography or CT angiography during regular care follow-up. Elastic net regression was performed to assess which chest pain characteristics and risk factors were of diagnostic value. The overall model selected age, provocation by temperature or stress, relief at rest and functional class as determinants and was accurate in both sexes (area under the curve (AUC) of 0.76 (95% CI 0.68 to 0.85) in women and 0.83 (95% CI 0.78 to 0.88) in men). Both sex-specific models selected age, pressuring nature, radiation, duration, frequency, progress, provocation and relief at rest as determinants. The female model additionally selected dyspnoea, body mass index, hypertension and smoking while the male model additionally selected functional class and diabetes. The sex-specific models performed better than the overall model, but more so in women (AUC: 0.89, 95% CI 0.81 to 0.96) than in men (AUC: 0.84, 95% CI 0.73 to 0.90)., Conclusions: In both sexes, the diagnostic value of non-acute chest pain characteristics and risk factors for coronary artery disease was high. Provocation, relief at rest and functional class of chest pain were the most powerful diagnostic predictors in both women and men. When stratified by sex the performance of the model improved, mostly in women., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Left ventricular diastolic dysfunction (LVDD) is a common condition in both sexes that may deteriorate into heart failure (HF) with preserved ejection fraction (pEF), although this seems to happen more often in women than in men. Both LVDD and HFpEF often go unrecognised, necessitating the discovery of biomarkers that aid both the identification of individuals with LVDD at risk of developing HF and identification of individuals most likely to benefit from treatment., Methods and Analysis: HELPFul is an ongoing case-cohort study at a Dutch cardiology outpatient clinic enrolling patients aged 45 years and older without history of cardiovascular disease, who were referred by the general practitioner for cardiac evaluation. We included a random sample of patients and enriched the cohort with cases (defined as an E/e' ≥8 measured with echocardiography). Information about medical history, cardiovascular risk factors, electrocardiography, echocardiography, exercise test performance, common carotid intima-media thickness measurement and standard cardiovascular biomarkers was obtained from the routine care data collected by the cardiology outpatient clinic. Study procedure consists of extensive venous blood collection for biobanking and additional standardised questionnaires. Follow-up will consist of standardised questionnaires by mail and linkage to regional and national registries. We will perform cardiac magnetic resonance imaging and coronary CT angiography in a subgroup of patients to investigate the extent of macrovascular and microvascular coronary disease., Ethics and Dissemination: The study protocol was approved by the Institutional Review Board of the University Medical Center Utrecht. Results will be disseminated through national and international conferences and in peer-reviewed journals in cardiovascular disease., Trial Registration: NTR6016;Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The incidence of diabetes is rapidly increasing and diabetes is associated with an increased risk of peripheral artery disease. Recent studies have shown a time dependent decline in vulnerable plaque features and secondary cardiovascular events in iliofemoral endarterectomy (IFE) patients. IFE patients with diabetes have a high risk of cardiovascular events. It is not known, however, whether vulnerable plaque features and cardiovascular events reduce over time in IFE patients with diabetes., Methods: Between 2003 and 2014, 691 atherosclerotic plaques were obtained by IFE, from 212 patients with and 479 patients without diabetes. Plaques were immunohistochemically stained and analysed for the presence of intraplaque haemorrhage, lipid core, calcification, collagen, smooth muscle cells, and macrophages. Patients were stratified according to their diabetic status and year of inclusion. All patients had a follow up of three years in which cardiovascular adverse events were recorded., Results: A time dependent decrease was observed in intraplaque haemorrhage, plaque lipid core, and percentage of macrophages in IFE patients with diabetes. After multivariable correction for changes in risk factors over time, intraplaque haemorrhage (64.2% [2002-2005] vs. 39.6% [2012-2014], p = .01) became significantly less prevalent. Interestingly, the percentage of severely calcified plaques remained high over time. The number of secondary events decreased over time in patients without diabetes (HR 1.80, 95% CI 1.15-2.81 (p = .010) for 2002-2005 vs. 2012-2014), but remained high and unchanged in patients with diabetes., Conclusion: In patients with diabetes undergoing IFE, a time dependent stabilisation of atherosclerotic plaque features was found in line with previous observations in patients with severe atherosclerosis. The presence of severely calcified lesions remained high and unchanged. The secondary event rate remained high in patients with diabetes in contrast to a significant decrease in patients without diabetes. These findings stress the need for improvement of care in IFE patients with diabetes., (Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Background: The HEART score is a simple and effective tool to predict short-term major adverse cardiovascular events in patients suspected of acute coronary syndrome. Patients are assigned to three risk categories using History, ECG, Age, Risk factors and Troponin (HEART). The purpose is early rule out and discharge is considered safe for patients in the low risk category. Its performance in patients of Asian ethnicity is unknown. We evaluated the performance of the HEART score in patients of Caucasian, Chinese, Indian and Malay ethnicity., Methods: The HEART score was assessed retrospectively in 3456 patients presenting to the emergency department with suspected acute coronary syndrome (1791 Caucasians, 1059 Chinese, 344 Indians, 262 Malays), assigning them into three risk categories., Results: The incidence of major adverse cardiovascular events within six weeks after presentation was similar between the ethnic groups. A smaller proportion of Caucasians was in the low risk category compared with Asians (Caucasians 35.8%, Chinese 43.5%, Indians 45.3%, Malays 44.7%, p<0.001). The negative predictive value of a low HEART score was comparable across the ethnic groups, but lower than previously reported (Caucasians 95.3%, Chinese 95.0%, Indians 96.2%, Malays 96.6%). Also the c-statistic for the HEART score was not significantly different between the groups., Conclusions: These results show that the overall performance of the HEART score is equal among Caucasian and Asian ethnic groups. The event rate in the low risk group, however, was higher than reported in previous studies, which queries the safety of early discharge of patients in the low risk category.

Background Prevalence of undetected heart failure in older individuals is high in the community, with patients being at increased risk of morbidity and mortality due to the chronic and progressive nature of this complex syndrome. An essential, yet currently unavailable, strategy to pre-select candidates eligible for echocardiography to confirm or exclude heart failure would identify patients earlier, enable targeted interventions and prevent disease progression. The aim of this study was therefore to develop and validate such a model that can be implemented clinically. Methods and results Individual patient data from four primary care screening studies were analysed. From 1941 participants >60 years old, 462 were diagnosed with heart failure, according to criteria of the European Society of Cardiology heart failure guidelines. Prediction models were developed in each cohort followed by cross-validation, omitting each of the four cohorts in turn. The model consisted of five independent predictors; age, history of ischaemic heart disease, exercise-related shortness of breath, body mass index and a laterally displaced/broadened apex beat, with no significant interaction with sex. The c-statistic ranged from 0.70 (95% confidence interval (CI) 0.64-0.76) to 0.82 (95% CI 0.78-0.87) at cross-validation and the calibration was reasonable with Observed/Expected ratios ranging from 0.86 to 1.15. The clinical model improved with the addition of N-terminal pro B-type natriuretic peptide with the c-statistic increasing from 0.76 (95% CI 0.70-0.81) to 0.89 (95% CI 0.86-0.92) at cross-validation. Conclusion Easily obtainable patient characteristics can select older men and women from the community who are candidates for echocardiography to confirm or refute heart failure.

Objective: This study aims to investigate whether plasma matrix Gla protein (MGP) species, desphospho-uncarboxylated (dp-uc) MGP, and total uncarboxylated (t-uc) MGP are associated with plaque levels of uncarboxylated (uc) MGP, markers of plaque stability, and cardiovascular disease (CVD) risk., Methods: From the Athero-Express biobank, we selected carotid plaque samples of 100 patients who underwent carotid endarterectomy. The level of agreement between plasma MGP species and plaque ucMGP levels was assessed using weighted kappa (κ). We analyzed histological characteristics of plaque composition (plaque hemorrhage, lipid and calcification content). Logistic regression analyses were used to assess the association between plasma MGP and plaque characteristics. Furthermore, CVD endpoints (n = 20) were collected over a mean follow-up of 2.6 years., Results: Weighted κ statistics of plasma dp-ucMGP and t-ucMGP and plaque ucMGP were 0.10 (95% CI -0.31 to 0.52) and 0.14 (95% CI -0.20 to 0.48). Higher dp-ucMGP levels tended to be associated with less plaque hemorrhage (ORper 500 nM 0.96; 95% CI 0.92-1.00). No association was found for lipid and calcification content. Cox proportional hazards models showed no association between dp-ucMGP (HRper 200 pM 0.92; 95% CI 0.75-1.11) and an inverse association between t-ucMGP (HRper 500 nM 0.79; 95% CI 0.62-0.99) and cardiovascular events., Conclusions: Plasma dp-ucMGP and t-ucMGP concentrations do not reflect plaque ucMGP levels. Elevated dp-ucMGP levels may be associated with less plaque hemorrhage, suggestive of more stable plaques. T-ucMGP was not related with markers of plaque stability; however, elevated plasma t-ucMGP levels were associated with a reduced CVD risk., (© 2018 The Author(s) Published by S. Karger AG, Basel.)

Background: In 2020 the largest number of patients with coronary artery disease (CAD) will be found in Asia. Published epidemiological and clinical reports are overwhelmingly derived from western (White) cohorts and data from Asia are scant. We compared CAD severity and all-cause mortality among 4 of the world's most populous ethnicities: Whites, Chinese, Indians and Malays., Methods: The UNIted CORoNary cohort (UNICORN) simultaneously enrolled parallel populations of consecutive patients undergoing coronary angiography or intervention for suspected CAD in the Netherlands and Singapore. Using multivariable ordinal regression, we investigated the independent association of ethnicity with CAD severity and interactions between risk factors and ethnicity on CAD severity. Also, we compared all-cause mortality among the ethnic groups using multivariable Cox regression analysis., Results: We included 1,759 White, 685 Chinese, 201 Indian and 224 Malay patients undergoing coronary angiography. We found distinct inter-ethnic differences in cardiovascular risk factors. Furthermore, the associations of gender and diabetes with severity of CAD were significantly stronger in Chinese than Whites. Chinese (OR 1.3 [1.1-1.7], p = 0.008) and Malay (OR 1.9 [1.4-2.6], p<0.001) ethnicity were independently associated with more severe CAD as compared to White ethnicity. Strikingly, when stratified for diabetes status, we found a significant association of all three Asian ethnic groups as compared to White ethnicity with more severe CAD among diabetics, but not in non-diabetics. Crude all-cause mortality did not differ, but when adjusted for covariates mortality was higher in Malays than the other ethnic groups., Conclusion: In this population of individuals undergoing coronary angiography, ethnicity is independently associated with the severity of CAD and modifies the strength of association between certain risk factors and CAD severity. Furthermore, mortality differs among ethnic groups. Our data provide insight in inter-ethnic differences in CAD risk factors, CAD severity and mortality.

Background: Time-dependent trends in the incidence of cardiovascular disease have been reported in high-income countries. Because atherosclerosis underlies the majority of cardiovascular diseases, we investigated temporal changes in the composition of atherosclerotic plaques removed from patients undergoing carotid endarterectomy., Methods and Results: The Athero-Express study is an ongoing, longitudinal, vascular biobank study that includes the collection of atherosclerotic plaques of patients undergoing primary carotid endarterectomy in the province of Utrecht from 2002 to 2011. Histopathologic features of plaques of 1583 patients were analyzed in intervals of 2 years. The analysis included quantification of collagen, calcifications, lipid cores, plaque thrombosis, macrophages, smooth muscle cells, and microvessels. Large atheroma, plaque thrombosis, macrophages, and calcifications were less frequently observed over time, with adjusted odds ratios of 0.72 (95% confidence interval, 0.650-0.789), 0.62 (95% confidence interval, 0.569-0.679), 0.87 (95% confidence interval, 0.800-0.940), and 0.75 (95% confidence interval, 0.692-0.816) per 2-year increase in time, respectively. These changes in plaque characteristics were consistently observed in patient subgroups presenting with stroke, transient ischemic attack, ocular symptoms, and asymptomatic patients. Concomitantly, risk factor management and secondary prevention strategies among vascular patients scheduled for carotid endarterectomy significantly improved over the past decade., Conclusions: In conclusion, over the past decade, atherosclerotic plaques harvested during carotid endarterectomy show a time-dependent change in plaque composition characterized by a decrease in features currently believed to be causal for plaque instability. This appears to go hand in hand with improvements in risk factor management., (© 2014 American Heart Association, Inc.)