Primary prevention efforts are poorly developed in people at high cardiovascular risk: A report from the European Society of Cardiology EURObservational Research Programme EUROASPIRE V survey in 16 European countries

Background: European Action on Secondary and Primary Prevention by Intervention to Reduce Events (EUROASPIRE) V in primary care was carried out by the European Society of Cardiology EURObservational Research Programme in 2016–2018. The main objective was to determine whether the 2016 Joint European Societies’ guidelines on cardiovascular disease prevention in people at high cardiovascular risk have been implemented in clinical practice. Methods: The method used was a cross-sectional survey in 78 centres from 16 European countries. Patients without a history of atherosclerotic cardiovascular disease either started on blood pressure and/or lipid and/or glucose lowering treatments were identified and interviewed 6 months after the start of medication. Results: A total of 3562 medical records were reviewed and 2759 patients (57.6% women; mean age 59.0 11.6 years) interviewed (interview rate 70.0%). The risk factor control was poor with 18.1% of patients being smokers, 43.5% obese (body mass index 30 kg/m2 ) and 63.8% centrally obese (waist circumference 88 cm for women, 102 cm for men). Of patients on blood pressure lowering medication 47.0% reached the target of <140/90 mm Hg (<140/85 mm Hg in people with diabetes). Among treated dyslipidaemic patients only 46.9% attained low density lipoprotein-cholesterol target of <2.6 mmol/l. Among people treated for type 2 diabetes mellitus, 65.2% achieved the HbA1c target of <7.0%. Conclusion: The primary care arm of the EUROASPIRE V survey revealed that large proportions of people at high cardiovascular disease risk have unhealthy lifestyles and inadequate control of blood pressure, lipids and diabetes. Thus, the potential to reduce the risk of future cardiovascular disease throughout Europe by improved preventive cardiology programmes is substantial

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Laser Doppler flowmetry evaluation of skin microvascular endothelial function in patients with metabolic syndrome

Background: Metabolic syndrome (MetS) is associated with high cardiovascular morbidity and mortality, and endothelial dysfunction is an early pathogenetic event in the MetS. Lifestyle changes and pharmacological intervention might partly restore endothelial function in MetS. Whereas an optimal non-invasive test for endothelial dysfunction is still being sought, the aim of this study was to assess the relationship between changes in skin microvascular endothelial function, detected by Laser Doppler flowmetry, and cardiovascular risk factors (CVRFs) of patients with MetS. Design and methods: 3081 patients (1865 women and 1216 men, mean age 53 ± 6 years) with MetS were enrolled in the study, which was conducted during the period of 2010–2014 at Vilnius University Hospital Santaros Klinikos. Skin microvascular endothelial function was evaluated using the Laser Doppler flowmetry in combination with the post-occlusive reactive hyperaemia test. The percentage change of flow from peak to the rest flow (PF-RF) was calculated and used as the main measure of endothelial function. Results: The study showed that decrease in flow-mediated dilatation reflected by PF-RF was associated with increased triglycerides (p = 0.002), male sex (p < 0.001), and diabetes (p = 0.002). Patients with quite a few CVRFs (body mass index ≥25 kg/m2, smoking, diabetes, arterial hypertension, a positive history of dyslipidaemia) had significantly lower PF-RF score than patients only with one of these risk factors (p < 0.001). Conclusions: Changes in skin microvascular endothelial function are significantly associated with most CVRFs and depend on the number of CVRFs

Arterial stiffness in regards to kidney function in middle-aged subjects with metabolic syndrome : Lithuanian high-risk cohort

Objective The current study aimed to check whether early vascular aging, measured as carotid-femoral pulse wave velocity (cfPWV), is related to kidney function, measured as creatinine-based estimated glomerular filtration (eGFR) and urinary albumin-to-creatinine ratio (UACR), in middle-aged subjects with metabolic syndrome. Methods Participants were recruited from Lithuanian high-risk cohort (LitHiR). The cohort consists of middle-aged individuals with high cardiovascular risk but without overt cardiovascular disease. Participants underwent baseline and second visit hemodynamics measurement, including aortic mean arterial pressure (MAP), cfPWV, crPWV, carotid-intima media thickness measurement (CIMT) and biochemical analysis and all fulfilled NCEP/ ATPIII criteria for metabolic syndrome diagnosis. First of all, we had determined correlations among hemodynamic measurement and eGFR together with albuminuria, expressed as UACR. Then we compared subjects who experienced significant eGFR decline with the remaining population and determining factors influencing this. Results A total of 689 subject data were eligible for analysis. We observed relationship between cfPWV and MAP, crPWV, glucose, BMI, C-reactive protein, waist circumference except kidney function measured as eGFR at the baseline and at the second visit. eGFR was not associated with MAP or albuminuria. Baseline but not second visit UACR significantly positively correlated with cfPWV (r-spearman = 0.146, P = 0.003) and MAP (r-spearman = 0.142, P = 0.005). eGFR decline was mainly observed in subjects with higher baseline eGFR and was independently influenced by increase in cfPWV. Conclusion In middle-aged subjects with prevalent metabolic syndrome eGFR decline is related to aortic and not peripheral arterial stiffening. Better baseline kidney function could be possibly an effect of glomerular hyperfiltration, and it allows us to conclude that this phenomenon indicates early vascular damage and it should be addressed seriously in metabolic syndrome patients with normal kidney function. Blood Press Monit 26: 191–19

Should we calculate arterial stiffness gradient in middle-aged women with increased cardiovascular risk?

Purpose: The study was designed to evaluate clinical and laboratory determinants pulse wave velocity (PWV) ratio in women at the age of 50–65 years without overt cardiovascular disease but having elevated cardiovascular risk, such as hypertension, obesity, diabetes and hypercholesterolemia. Materials and methods: We analyzed data from 1170 women enrolled in the national-wide primary prevention program. Univariate and multivariate linear regression analysis was used to establish independent risk factors in groups based on clinical data, laboratory values, and comorbidities. Arterial stiffness was evaluated using applanation tonometry technique (SphygmoCor). The PWV ratio was calculated by dividing cfPWV to crPWV. Results: In multivariate logistic regression analysis, age (OR = 1.109, p < .001), waist circumference (OR = 1.021, p = .001) and mean arterial pressure (OR = 1.031, p < .001) were found as independent clinical determinants of PWV ratio, while independent laboratory determinants were urine albumin to creatinine ratio (OR = 1.189, p = .010), triglycerides (OR = 1.161, p = .034), glucose (OR = 1.28, p = .001) and eGFR (OR = 0.998, p = .007). Diabetes (OR = 1.811, p = .029), hypertension (OR = 2.784, p = .042) and menopause (OR = 1.054, p = .018) were established as independent factors in comorbidities group. The analysis confirmed that PWV ratio (R2 = 0.0667, p < .001), as well as carotid radial (R2 = 0.0341, p < .001) and carotid femoral PWV (R2 = 0.1752, p < .001) is affected by mean arterial blood pressure. Conclusions: Age, abdominal obesity, blood pressure, triglycerides, glucose, kidney function parameters and menopause all are associated with PWV ratio. More importance to women with high cardiovascular risk should be given whilst screening and stratifying further progression of the disease

Efficacy and Safety of PCSK9 Inhibition With Evolocumab in Reducing Cardiovascular Events in Patients With Metabolic Syndrome Receiving Statin Therapy: Secondary Analysis From the FOURIER Randomized Clinical Trial.

IMPORTANCE: The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Patients with metabolic syndrome (MetS) are at increased cardiovascular risk. OBJECTIVE: To investigate outcomes with evolocumab in patients with and without MetS. DESIGN, SETTING, AND PARTICIPANTS: The FOURIER trial randomized patients worldwide with stable atherosclerotic cardiovascular disease receiving statin to evolocumab vs placebo with follow-up for a median of 2.2 years. Data were collected February 2013 to November 2016. For this prespecified analysis, patients with the requisite data were stratified based on the National Cholesterol Education Program Adult Treatment Panel III MetS criteria; in secondary analyses, patients were further substratified by diabetes at baseline. Analysis was intention to treat. Analysis began March 2018 and ended April 2020. INTERVENTIONS: Patients were randomized to evolocumab or placebo. MAIN OUTCOMES AND MEASURES: The primary end point was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point was cardiovascular death, myocardial infarction, or stroke. RESULTS: Of 27 342 patients (mean [SD] age, 63 [9] years; 20 623 men [75.4%]) included in this analysis, 16 361 (59.8%) with baseline MetS were, when compared with patients without MetS, at higher risk of cardiovascular events (adjusted hazard ratio [95% CI], 1.31 [1.18-1.46]; P < .001 for the primary and 1.38 [1.20-1.57]; P < .001 for the key secondary end point). Evolocumab reduced low-density lipoprotein cholesterol similarly in patients with MetS (median [interquartile range], 92 [79-109] mg/dL vs 30 [19-48] mg/dL; P < .001) and without MetS (median [interquartile range], 92 [81-108] mg/dL vs 29 [18-44] mg/dl; P < .001). For the primary end point, the hazard ratios (95% CI) with evolocumab vs placebo were 0.83 (0.76-0.91) and 0.89 (0.79-1.01) in patients with and without MetS (P for interaction = .39). For the key secondary end point, the corresponding hazard ratios (95% CIs) were 0.76 (0.68-0.86) and 0.86 (0.74-1.01) (P for interaction = .23), respectively. Evolocumab did not increase the risk of new-onset diabetes or other major safety outcomes including worsening glycemic control, compared with placebo in patients with MetS. CONCLUSIONS AND RELEVANCE: Patients with atherosclerotic cardiovascular disease and MetS have substantial residual risk of cardiovascular events despite statin therapy. Evolocumab significantly reduced low-density lipoprotein cholesterol and cardiovascular risk in patients with MetS without increasing new-onset diabetes, worsening glycemic control, or other major safety events. These data suggest the addition of evolocumab to statin therapy in patients with atherosclerotic cardiovascular disease and MetS is safe and efficacious to reduce residual cardiovascular risk. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01764633

Arterial stiffness and influences of the metabolic syndrome: A cross-countries study

Specific clusters of metabolic syndrome (MetS) components impact differentially on arterial stiffness, indexed as pulse wave velocity (PWV). Of note, in several population-based studies participating in the MARE (Metabolic syndrome and Arteries REsearch) Consortium the occurrence of specific clusters of MetS differed markedly across Europe and the US. The aim of the present study was to investigate whether specific clusters of MetS are consistently associated with stiffer arteries in different populations. We studied 20,570 subjects from 9 cohorts representing 8 different European countries and the US participating in the MARE Consortium. MetS was defined in accordance with NCEP ATPIII criteria as the simultaneous alteration in &gt;= 3 of the 5 components: abdominal obesity (W), high triglycerides (T), low HDL cholesterol (H), elevated blood pressure (B), and elevated fasting glucose (G). PWV measured in each cohort was “normalized” to account for different acquisition methods. MetS had an overall prevalence of 24.2% (4985 subjects). MetS accelerated the age-associated increase in PWV levels at any age, and similarly in men and women. MetS clusters TBW, GBW, and GTBW are consistently associated with significantly stiffer arteries to an extent similar or greater than observed in subjects with alteration in all the five MetS components - even after controlling for age, sex, smoking, cholesterol levels, and diabetes mellitus - in all the MARE cohorts. In conclusion, different component clusters of MetS showed varying associations with arterial stiffness (PWV). (C) 2014 Elsevier Ireland Ltd. All rights reserved

Prolonged antithrombotic therapy in patients after acute coronary syndrome : A critical appraisal of current European Society of Cardiology guidelines

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials

AMS :: ATX August 2014 Blog Archive 

Contents: Grad Research: Carrie Andersen publishes article on drones and Call of Duty in Surveillance and Society -- Faculty Research: Janet Davis wins Constance Rourke Prize for Best Essay in American Quarterly -- Grad Research: Eric Covey’s Intro AMS course creates photography Tumblr -- Welcome back from AMSAMS :: ATX is a blog dedicated to representing the many activities and interests of the department of American Studies at The University of Texas at Austin. Together with the department’s Twitter feed, this blog exists to serve the AMS and Austin communities by acting as a hub for up-to-date information on events and opportunities at UT and beyond.American Studie