Multiple Cardiovascular Risk Factors Research Articles

Invasive Coronary Physiology Study in Multivessel Coronary Artery Disease

AbstractAssessment of relationship between the angiographic stenosis severity and the coronary blood flow is complex. Coronary angiography has many limitations that may impair the judgment of stenosis severity and then affect decision-making regarding intervention. Myocardial perfusion imaging by single-photon emission tomography (MPI-SPECT) is used for a long time to help clinical decisions of interventions, but has limitations, such as issues with identification of extensive coronary artery disease (CAD). Fractional flow reserve (FFR) is a gold standard index for investigating the physiological significance of a coronary stenosis. The instantaneous wave-free ratio (iFR) is a hyperemia-free measurement and easier method to achieve physiological assessment to measure the severity of coronary stenosis. We present a case of multivessel coronary artery disease (MVCAD) patient who was treated with iFR-guided percutaneous coronary intervention (PCI) and emphasize the importance of physiological assessment in PCI.A 63-year-old male with multiple cardiovascular risk factors came to our center with chief complaint of stable angina since 1 year. He underwent MPI-SPECT and the result showed 2.5% of ischemia burden. Coronary angiography showed MVCAD. Surgical conference decided to do PCI. iFR-guided PCI was performed in this case.Our case highlights the importance of iFR as an important cardiology–physiology-based tool as a guide in management decisions for MVCAD. iFR as an alternative approach to physiological study is noninferior compared with FFR-guided PCI.

Sex differences in the prevalence of multiple cardiovascular disease risk factors in schoolchildren: A cross-sectional study.

Childhood obesity is linked to adulthood cardiovascular disease (CVD) risk and mortality. Approximately 32% of Kuwaiti children are obese, particularly boys. Data on other CVD risk factors are limited. This study aimed to determine the prevalence and sex differences of CVD risks in Kuwaiti schoolchildren. Kuwaiti fifth-grade schoolchildren (n=367, 53% girls, age 10.4±0.4 years) were evaluated. Informed parent/guardian consent and child assent were obtained for all participants. Outcome variables included (i) anthropometric: body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHtR), percentage body fat (%BF); (ii) blood lipids: total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, TC:HDL ratio, triglycerides; and (iii) blood pressure (BP): systolic BP (SBP) and diastolic BP (DBP) measurements. ANOVA was conducted, while controlling for moderate-to-vigorous physical activity and screen time (ST); significance level was set at p≤0.05. Overall prevalence of CVD risks included: overweight (21.6%), obesity (39%), WC (10.2%), WHtR (43.3%), %BF (10.1%), TC (26.4%), LDL (13.2%), HDL (36.9%), non-HDL (22.5%), TC:HDL ratio (25.9%), triglycerides (45.5%), and BP (23.3%). More girls (27.1%) than boys (15.5%) were overweight (p=0.007). More girls than boys were at greater risk of elevated triglycerides (52.3% vs. 37.7%, p=0.032), low HDL (20.7% vs. 12.2%, p=0.032) and elevated SBP (21% vs. 10.7%, p=0.008) and DBP (21% vs. 8.8%, p=0.001), respectively. CVD risks are a concern overall in children, especially in girls relative to overweight, dyslipidemia, and prehypertension. Intervention programs for Kuwaiti schoolchildren are recommended to prevent CVD risks.

Les résultats immédiats, à moyen et à long terme de l'angioplastie coronaire par stent actif très long : à propos d'une étude multicentrique observationnelle

IntroductionVery long coronary lesions account for 20% of coronary stenoses in the real world. There are few data on the effectiveness of angioplasty of these lesions with very long active stents (DES) in the literature. We conducted this study to assess the long-term outcomes of angioplasty with DES length ≥ 40 mm in a population with multiple cardiovascular risk factors. Patients and methodsThis is a retrospective, multicenter, descriptive, and prognostic study, conducted between January 2015 and January 2020, in four Tunisian centers, including all patients who underwent angioplasty with a DES of length ≥ 40 mm with a follow-up of at least one year. The primary outcome was a combined criteria (major cardiovascular and Cerebral events: MACCE) (stroke, acute coronary syndrome, revascularization of the target lesion: TLR, cardiovascular death: CVD). ResultsWe included 480 procedures. More than half of the patients had at least three risk factors. The prevalence of high blood pressure, diabetes and smoking were 61.1%, 56.6% and 60.4%, respectively. The treated lesions were complex: 23.54% calcified lesions, 8.75% chronic occlusions, 25% bifurcation lesions and 12.08% ostial lesions. The average length of the stents was 47.72 mm. We noted 17 cases of per-procedural complications (3.55%). The median follow-up was 35 months (extremes 1–60 months). The rate of stent thrombosis was 0.83%. The incidence of MACCE, TLR and CVD were respectively 16.25%, 8.12% and 5.2%. In multivariate analysis, diabetes (HR = 1.7, 95% CI [1.01–2.9]), dyslipidemia (HR = 2.08, 95% CI [1.3–3.3]), familial coronary artery disease (HR = 1.9, 95% CI [1.01–3.6]), left ventricle dysfunction (HR = 2.07, 95% CI [1.1–3.6]) and bifurcation lesions (HR = 1.9, 95% CI [1.2–3.14]) were the independent predictors of MACCE, while statin intake (HR = 0.38, 95% CI [0.19–0.78]) was a protective factor. ConclusionAngioplasty with very long DES is associated with low levels of MACCE, TLR, stent thrombosis and CVD in our population. Therefore, it could be an interesting alternative to cardiac surgery. Randomized comparative studies of the two treatment options are needed.

Juvenile idiopathic arthritis polygenic risk scores are associated with cardiovascular phenotypes in early adulthood: a phenome-wide association study

BackgroundThere is growing concern about the long-term cardiovascular health of patients with juvenile idiopathic arthritis (JIA). In this study we assessed the association between JIA polygenic risk and cardiovascular phenotypes (cardiovascular risk factors, early atherosclerosis/arteriosclerosis markers, and cardiac structure and function measures) early in life.MethodsJIA polygenic risk scores (PRSs) were constructed for 2,815 participants from the Avon Longitudinal Study of Parents and Children, using the single nucleotide polymorphism (SNP) weights from the most recent JIA genome wide association study. The association between JIA PRSs and cardiovascular phenotypes at age 24 years was assessed using linear and logistic regression. For outcomes with strong evidence of association, further analysis was undertaken to examine how early in life (from age seven onwards) these associations manifest.ResultsThe JIA PRS was associated with diastolic blood pressure (β 0.062, 95% CI 0.026 to 0.099, P = 0.001), insulin (β 0.050, 95% CI 0.011 to 0.090, P = 0.013), insulin resistance index (HOMA2_IR, β 0.054, 95% CI 0.014 to 0.095, P = 0.009), log hsCRP (β 0.053, 95% CI 0.011 to 0.095, P = 0.014), waist circumference (β 0.041, 95% CI 0.007 to 0.075, P = 0.017), fat mass index (β 0.049, 95% CI 0.016 to 0.083, P = 0.004) and body mass index (β 0.046, 95% CI 0.011 to 0.081, P = 0.010). For anthropometric measures and diastolic blood pressure, there was suggestive evidence of association with JIA PRS from age seven years. The findings were consistent across multiple sensitivity analyses.ConclusionsGenetic liability to JIA is associated with multiple cardiovascular risk factors, supporting the hypothesis of increased cardiovascular risk in JIA. Our findings suggest that cardiovascular risk is a core feature of JIA, rather than secondary to the disease activity/treatment, and that cardiovascular risk counselling should form part of patient care.

A urinary peptidomics approach for early stages of cardiovascular disease risk: The African-PREDICT study.

Cardiovascular disease (CVD) affects individuals across the lifespan, with multiple cardiovascular (CV) risk factors increasingly present in young populations. The underlying mechanisms in early cardiovascular disease development are complex and still poorly understood. We therefore employed urinary proteomics as a novel approach to gain better insight into early CVD-related molecular pathways based on a CVD risk stratification approach. This study included 964 apparently healthy (no self-reported chronic illnesses, free from clinical symptoms of CVD) black and white men and women (aged 20-30 years old) from the African Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT) study. Cardiovascular risk factors used for stratification included obesity, physical inactivity, tobacco use, high alcohol intake, hyperglycemia, dyslipidemia and hypertension. Participants were divided into low (0 risk factors), medium (1-2 risk factors) and high (≥3 risk factors) CV risk groups. We analyzed urinary peptidomics by capillary electrophoresis time-of-flight mass spectrometry. After adjusting for ethnicity, sex and age, 65 sequenced urinary peptides were differentially expressed between the CV risk groups (all q-values ≤ 0.01). These peptides included a lower abundance of collagen type I- and III-derived peptides in the high compared to the low CV risk group. With regard to noncollagen peptides, we found a lower abundance of alpha-1-antitrypsin fragments in the high compared to the low CV risk group (all q-values ≤ 0.01). Our findings indicate lower abundances of collagen types I and III in the high compared to the low CV risk group, suggesting potential early alterations in the CV extracellular matrix.

Patients with Polyvascular Disease: A Very High-risk Group.

Polyvascular disease (PolyvascDis) with atherosclerosis occurring in >2 vascular beds (coronary, carotid, aortic, visceral and/or peripheral arteries) is encountered in 15-30% of patients who experience greater rates of major adverse cardiovascular (CV) events. Every patient with multiple CV risk factors or presenting with CV disease in one arterial bed should be assessed for PolyvascDis clinically and noninvasively prior to invasive angiography. Peripheral arterial disease (PAD) can be readily diagnosed in routine practice by measuring the ankle-brachial index. Carotid disease can be diagnosed by duplex ultrasound showing % stenosis and/or presence of plaques. Coronary artery disease (CAD) can be screened by determining coronary artery calcium score using coronary computed tomography angiography; further, non-invasive testing includes exercise stress and/or myocardial perfusion imaging or dobutamine stress test, prior to coronary angiography. Abdominal ultrasound can reveal an abdominal aortic aneurysm. Computed tomography angiography will be needed in patients with suspected mesenteric ischemia to assess the mesenteric arteries. Patients with the acute coronary syndrome and concomitant other arterial diseases have more extensive CAD and poorer CV outcomes. Similarly, PolyvascDis in patients with carotid disease and/or other PAD is independently associated with an increased risk for all-cause and CV mortality during long-term follow-up. Treatment of patients with PolyvascDis should include aggressive management of all modifiable risk factors by lifestyle changes and drug therapy, with particular attention to patients who are commonly undertreated, such as those with PAD. Revascularization should be reserved for symptomatic vascular beds, using the least aggressive strategy in a multidisciplinary vascular team approach.

Long-Term Adiposity and Midlife Carotid Intima-Media Thickness Are Linked Partly Through Intermediate Risk Factors.

This study aims to determine quantitatively the mediation effects of multiple cardiovascular risk factors on the associations of childhood body mass index (BMI) and its cumulative burden with adult carotid intima-media thickness (cIMT). The longitudinal cohort consisted of 1391 adults who had been examined for BMI 4-15 times over 35.0 years on average since childhood and had data on adult cIMT, systolic blood pressure, low-density lipoprotein cholesterol, atherogenic index of plasma, and serum glucose. The area under the curve was used as a measure of cumulative burden of BMI. After adjusting for covariates, the total effects (standardized regression coefficient) of childhood BMI (0.138), adult BMI (0.111), and area under the curve of BMI (0.150) on cIMT were all significant (P<0.001) without mediators included in the model. The mediation effects of adult systolic blood pressure, glucose, atherogenic index of plasma and low-density lipoprotein cholesterol were 8.0%, 4.3%, 3.6%, and 0.0%, respectively, in the model with childhood BMI as the predictor, 23.4%, 15.3%, 12.6%, and 7.2%, respectively, with adult BMI as the predictor, and 14.7%, 8.7%, 6.0%, and 2.0%, respectively, with area under the curve of BMI as the predictor. The direct effects on cIMT were 0.117 (P<0.001) for childhood BMI, 0.046 (P=0.224) for adult BMI, and 0.103 (P<0.001) for area under the curve of BMI after removing the mediation effects. The long-term deleterious impact of adiposity on subclinical changes in vascular structure begins early in life and is accumulated over lifetime. Excess adiposity and higher cIMT are linked partly through other cardiovascular risk factors in later life, especially elevated blood pressure and glucose.

Association of rate pressure product trajectories at an early age with left ventricular hypertrophy in midlife: a prospective cohort study.

The joint effect of blood pressure (BP) and heart rate (HR) on cardiovascular disease is unclear. Rate pressure product (RPP), the product of systolic BP and HR, is assessed in this study. This study aimed to determine the longitudinal patterns of RPP from childhood to adulthood and to explore the relationship between RPP trajectories in early life and left ventricular hypertrophy (LVH) in midlife. We included individuals with 3 or more RPP values from 7 visits over a 30-year follow-up period in the Hanzhong Adolescent Hypertension Study cohort to fit trajectory groups and performed logistic regression to evaluate the relative risk of developing LVH. Three discrete trajectories in RPP were identified among 2412 participants assessed from childhood to middle-aged adulthood, which were tagged as "low stable," "moderate stable," and "moderate increasing". A higher waist-to-hip ratio, smoking, alcohol consumption, hypertension, diabetes, and hyperlipidemia were associated with increased RPP trajectories. The Cornell voltage product was positively correlated with RPP in 2017 and was higher in the moderate-stable and moderate-increasing groups than in the low-stable group in RPP trajectories. Compared with the low-stable group, the ORs of LVH were 1.65 (1.13, 2.92) for the moderate-stable and 3.56 (2.26, 5.44) for the moderate-increasing group. Subjects with moderate-stable and moderate-increasing trajectories showed higher probabilities of LVH at an elderly age than those in the low stable trajectory group even after adjusting for multiple cardiovascular risk factors. RPP trajectories are identifiable from childhood and are associated with LVH in midlife. Monitoring RPP trajectories from early life may be an effective approach to predict cardiovascular health status later in life.

Association between Arousals during Sleep and Subclinical Coronary Atherosclerosis in Patients with Obstructive Sleep Apnea.

(1) Aim: We aim to evaluate the association between arousals during sleep and subclinical coronary atherosclerosis detected by coronary computed tomography angiography (CTA) in patients with obstructive sleep apnea (OSA). (2) Methods: This was a cross-sectional study. Consecutive newly diagnosed OSA patients, who underwent coronary CTA examinations within 3 months of the sleep study, were eligible. We used the arousal index (ArI) derived from polysomnography to assess arousals during sleep and a semi-automated plaque quantification software to characterize and quantify the subclinical coronary atherosclerosis. Multiple regression models were used to evaluate the associations of the ArI with the coronary atherosclerotic plaque presence, volume, and composition. (3) Results: A total of 99 patients with OSA were included in the study. In the multivariable models, patients with a high ArI (ArI > 32.2 events/h) were more likely to have coronary plaques compared to those with a low ArI (ArI ≤ 32.2 events/h) (OR: 3.29 [95% CI: 1.284 to 8.427], p = 0.013). Furthermore, the ArI exhibited significant associations with total (β = 0.015), noncalcified (β = 0.015), and low-attenuation (β = 0.012) coronary plaque volume after accounting for established risk factors (p = 0.008, 0.004, and 0.002, respectively). However, no association between the ArI and calcified plaque volume was found. (4) Conclusion: Repetitive arousals during sleep are associated with an increased coronary plaque burden in patients with OSA, which remained robust after adjusting for multiple established cardiovascular risk factors.

Cardiovascular risk factors in patients with and without a history of atherosclerotic cardiovascular disease in the SANTORINI study and estimation of risk

Abstract Background Strategies for the prevention of atherosclerotic cardiovascular disease (ASCVD) are related to individual risk factors, and according to guidelines the higher the risk, the more intense the treatment required. Identifying patients at highest risk who might benefit the most from interventions is central for tailored solutions and ASCVD prevention, and any underestimation of risk may increase the ASCVD burden in these patients. Purpose To describe demographics and cardiovascular (CV) risk factors of patients with and without prior ASCVD enrolled in the SANTORINI study, as well as their CV risk as assigned by the investigator at the time of enrolment. Methods SANTORINI is an observational study (NCT04271280) conducted in 14 European countries and including patients aged ≥18 years with high- and very-high CV risk, as assessed by the investigator, and requiring lipid-lowering therapy. Patients were recruited between March 2020 and February 2021. The ASCVD status (coronary; cerebral; peripheral/other; polyvascular) of patients was defined based on medical records and the basis for risk classification was documented. For those whose risk was classified by the investigator based on the 2019 ESC/EAS guidelines, the CV risk was re-assessed centrally based on the information present in the study database to assess concordance. Results A total of 9044 patients were included in the analysis; of these, 76.9% had documented history of ASCVD (Table 1). Overall, the majority of patients were male (72.6%) and had a mean (SD) age of 65.3 (10.9) years. Mean (SD) LDL-C was 2.3 (1.13) mmol/L and 2.8 (1.37) mmol/L in the with and without ASCVD groups, respectively. Hypertension was common in both groups, whereas diabetes and familial hypercholesterolaemia were more prevalent in those without than those with ASCVD (44.6% vs 30.3% and 18.6% vs 7.2%, respectively). Patients with and without ASCVD had multiple CV risk factors (Table 1). Overall, ESC/EAS guidelines were cited as the most commonly used basis for risk classification (52.0%). Among all patients, the investigator assessed 26.0% and 84.2% of patients without and with ASCVD, respectively, as being very high-risk. However, central re-estimation for those using ESC/EAS guidelines suggested that 54.7% and 100% of those without and with ASCVD were at very high CV risk (Table 2). Conclusion Analysis of the SANTORINI baseline data shows that CV risk factors are common even in patients without documented ASCVD, and that the CV risk of patients both with and without ASCVD is underestimated in clinical practice, potentially contributing to clinical inertia in risk factor control. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe GmbH, Munich, Germany

How do cardiovascular risk factors and cardiac remodeling type affect left ventricular global longitudinal strain and right ventricular free wall strain in patients with obesity

Abstract Background Obesity, defined by the World Health Organization (WHO) as a BMI greater than 30k g/m2, has reached epidemic proportions worldwide, related to approximately 2.8 million deaths/year as of June 2021. WHO sub-classifies obesity based on BMI in Class 1: 30–34.9 kg/m2, Class 2: 35–39.9 kg/m2, and Class 3: ≥40 kg/m2. This state of increased body weight is associated with an increased risk of cardiovascular disease. Cardiac remodeling can be affected by obesity and/or other cardiovascular risk factors (CVRF) as an adaptive physiological response. The remodeling patterns, Normal Geometry (NG), Concentric Remodeling (CR), Concentric Hypertrophy (CH), and Eccentric Hypertrophy, are classified by changes in Relative Wall Thickness (RWT), ≤ or &amp;gt;0.42, and/or Left Ventricular Mass Index (LVMI g/m2), ≤ or &amp;gt;88 for women and ≤ or &amp;gt;102 for men. Left Ventricular Ejection Fraction (LVEF) can remain within normal limits in patients with obesity with multiple CVRF and cardiac remodeling. Left Ventricular Global Longitudinal Strain (LV-GLS) and Right ventricular free wall strain (RV-FWS) can be useful to detect subclinical myocardial dysfunction. The aim of this study was to evaluate if these strain variables are affected in patients with obesity associated to other CVRF in relation to cardiac remodeling type when compared to controls. Methods 2859 patients with BMI ≥30 kg/m2 and 2616 normal-weight controls (BMI between 18.5 and 24.9 kg/m2), with normal and abnormal cardiac geometry, and normal ejection fraction by echocardiography performed between 01/01/2008 and 12/31/2018, were compared. Obesity was classified based on the World Health Organization. CVRF included were Hypertension (HTN), Diabetes Mellitus (DM), Dyslipidemia, history of Vascular Event (myocardial infarction and/or stroke), and Obstructive sleep apnea (OSA). Results BMI, cardiac geometry, CVRF, and the number of comorbidities independently affected GLS and RV-FWS (Figure 1 and Figure 2). LV-GLS and RV-FWS values [mean (SD)] in obesity classes 1, 2, and 3 were −19 (2.9), −18.9 (2.9), −18.7 (2.9) &amp; −24.2 (5.2), −23.8 (6.2), −24.5 (5.9), respectively. In the control group LV-GLS and RV-FWS values [mean (SD)] were −20.1 (3.0) &amp; −27 (5.6), respectively. CH was associated with the greatest decrease in LV-GLS and RV-FWS in males and females, regardless of BMI (Figure 2). LV-GLS values [mean (SD)] associated to CH for obesity class 1, 2, and 3, and controls in females were −18.4 (3.4), −18 (3.1) −17.6 (3.6), and −17.8 (4), respectively, and for obesity class 1, 2, and 3, and controls in males were −16.1 (3.5), 16.5 (3.2), −14.4 (2.7), and −16.6 (4.7), respectively (Figure 1). Conclusion Obesity associated to CVRF and CH have the lowest values of GLS in patients with normal ejection fraction. These values were exceedingly below average compared to other groups. These parameters should be used as reference values for this population. Funding Acknowledgement Type of funding sources: None.

Changes in myocardial tissue velocities over a decade: the Copenhagen City Heart study

Abstract Background The aim of the present study was to investigate the impact of cardiovascular risk factors – age, sex, hypertension, hypercholesterolemia, diabetes, smoking and obesity on Tissue Doppler imaging (TDI) measures of systolic and diastolic tissue velocities in the general population over a 10-year period. Identifying risk factors that are associated with changes in TDI velocities could lead to an improved understanding of the pathophysiology of the deteriorating heart and enable early preventive actions and strategies. Methods The study included 1128 members from the general population who participated in both the 4th and 5th Copenhagen City Heart Study. At both examination rounds, the participants underwent echocardiography. The examinations were 10 years apart. Conventional echocardiographic measures of cardiac structure and function and measures of TDI myocardial tissue velocities were obtained. Results Average change in s', e' and a' were −0.4±1.1 cm/s, −0.9±1.7 cm/s and 0.5±1.7 cm/s, respectively. After multivariable adjustments, older age (P&amp;lt;0.001) and higher systolic blood pressure (BP) (P=0.029) were found to be associated with a decrease in s' at follow-up. Male sex (P&amp;lt;0.001) was found to be associated with an increase in s'. Older age (P&amp;lt;0.001) and greater number of smoking pack-years (P=0.004) were associated with a decrease in e' at follow-up after multivariable adjustments. In addition, greater BMI (P=0.004) was significantly associated with a decrease in a'. Higher diastolic BP (P=0.004) and male sex (P=0.004) were associated with an increase in a'. Conclusion In the general population, overall systolic and diastolic function declined over a 10-year period. Both systolic and diastolic function as assessed by myocardial TDI velocities were affected by multiple conventional cardiovascular risk factors. Funding Acknowledgement Type of funding sources: None.

Place of the Advanced Practice Registered Nurse within the vascular team: a qualitative study of vascular medicine physicians and nurses caring for patients with peripheral artery disease

Abstract Introduction Advanced Practice Registered Nurses (APRNs) treat and diagnose diseases, counsel the public about health problems, manage chronic diseases, and participate in continuing education. In the cardiovascular field, Peripheral Arterial Disease (PAD), one of the manifestations of atherosclerotic cardiovascular disease, is archetypal in combining multiple cardiovascular risk factors (hypertension, hyperlipidemia, diabetes mellitus smoking). Vascular medicine faces the challenge of improving their care and quality of life, but some goals cannot be achieved with all patients. Patients with PAD should benefit from APRN care, but to date there is little published on the place of APRN in vascular medicine worldwide, and none in France. Objective It appeared important to us to assess the perception of their role by physicians and nurses in vascular medicine. As the status of APRN in France has only been enacted by law in 2018, we aim to investigate physicians and nurses working with patients suffering from PAD, to gather their opinions and draw the cooperation outlines these practitioners could have with an APRN. Methods Multicentre exploratory qualitative study by semi-directive interview conducted until data saturation and thematic analysis carried out with healthcare practitioners taking care of patients with PAD: 10 physicians working either in private practice setting or hospital setting or both, and 8 nurses in a vascular unit for hopsitalised patients. Results Three main themes emerged from responders' verbatims: a specific organization of vascular medicine with its inherent challenges, particularly regarding patients with PAD (specific psychosocial profile of patients, lack of therapeutic education, time, knowledge of non-specialist physicians, tedious follow-up outside hospitals, complex care trajectory, and lack of medical-surgical collaboration). Second, a role for APRN, particularly in consultation as part of patient follow-up, with expected benefits for the patient and the care team. The APRN is wanted to fill part of this gap. The expected benefits include a smoother care pathway and increased capacity for cardiovascular education and prevention, especially during consultations. Third, there are certain pitfalls that need to be clarified to integrate these new practitioners into the vascular teams already in place. In particular, the need to inform the vascular medicine teams about this new profession, and the indispensable presence of the conditions necessary for the development of a relationship of trust. Conclusion APRN could be the missing link in a Vascular team by creating a continuum in the care of patients with PAD, ensuring clinical assessment, nursing supervision, adverse event screening, and renewing drug prescriptions with the necessary adjustments, while ensuring an essential part of therapeutic education personalized to each PAD patient. Funding Acknowledgement Type of funding sources: None.

Exploring circulating biomarkers for risk prediction of incident atrial fibrillation – insights from the BiomarCaRE project

Abstract Background Atrial fibrillation (AF) remains a major health issue in Europe and worldwide. Risk prediction is crucial to identify at-risk individuals and prevent subsequent complications of AF such as stroke and heart failure. Biomarker-enriched, personalized risk prediction offers great potential for population-wide prevention beyond traditional cardiovascular risk factors. Purpose We aimed to identify robust predictors for incident AF using classical regressions and machine learning (ML) techniques within a broad spectrum of candidate variables. Methods Three European community cohorts from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) consortium were included to explore the predictive utility of 14 biomarkers mirroring distinct pathophysiological pathways of AF including lipids, inflammation (C-reactive protein [CRP]), renal, and myocardium-specific markers (N-terminal pro B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin I [hsTnI]) within a population-based sample of 42,280 individuals free of AF at baseline. Investigated biomarkers were examined in relation to incident AF using Cox regressions adjusted for multiple cardiovascular risk factors, and additionally by C-indices and net reclassification improvement (NRI) when compared to a reference model incorporating clinical variables. Their predictive utility for incident AF was further analyzed using different ML methods, including Least Absolute Shrinkage and Selection Operator (LASSO) and Random Survival Forest (RSF). Results Of 42,280 individuals (21,843 women [51.7%]; median [interquartile range, IQR] age, 52.2 [42.6, 62.0] years), 1496 (3.5%) developed AF during a median follow-up time of 5.7 years. In multivariable-adjusted Cox regression analysis, NT-proBNP was the strongest circulating predictor of incident AF (hazard ratio [HR] per standard deviation [SD] 1.93, 95% CI 1.82–2.04; P&amp;lt;0.001). Further, hsTnI (HR per SD 1.18, 95% CI 1.13–1.22; P&amp;lt;0.001), cystatin C (HR per SD 1.16, 95% CI 1.10–1.23; P&amp;lt;0.001) and CRP (HR per SD 1.08, 95% CI 1.02–1.14, P=0.012) correlated positively with new-onset AF. NT-proBNP enhanced model discrimination (ΔC-index 0.037, 95% CI 0.029–0.044) markedly and yielded the best reclassification improvement (NRI 0.237, 95% CI 0.187–0.287) when compared to the clinical model. Neither the addition of hsTnI to NT-proBNP, nor a model comprising all investigated biomarkers further increased discrimination or reclassification substantially. In different ML models, NT-proBNP and age were the strongest predictors of incident AF. Conclusions Using a dual approach with both classical regressions and modern ML methods, NT-proBNP consistently remained the strongest blood-based predictor of incident AF with relevant discriminative ability and reclassification yield beyond classical cardiovascular risk factors. The clinical benefit of these findings for AF risk prediction needs to be tested prospectively. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): BiomarCaRE (FP7, HEALTH-F2-2011-278913)European Union's Horizon 2020 research and innovation programme (grant agreement number 847770, AFFECT-EU)

Serial assessment of thrombogenicity and hemodynamics in patients with type II diabetes in a clinical research unit: Evidence for circadian variations in clot formation

Circadian fluctuations in thrombogenicity and hemostasis play a role in acute cardiovascular thrombotic events occurring in the early morning hours. There is a lack of data assessing thrombogenicity, platelet function, and hemodynamics to investigate diurnal variations in a high cardiovascular risk population. This was an exploratory, single-center study conducted in aspirin-treated patients with Type II Diabetes Mellitus (T2DM) (n = 37) with documented vascular disease and/or multiple cardiovascular risk factors. Hemodynamic monitoring and blood sample collection for thromboelastography (TEG) and platelet function testing were done serially at 7-9 AM (morning), 7-9 PM (evening), 11 PM-1 AM (night), and at 5-7 AM (awakening). R-value measured by TEG was shorter during awakening hours than during the night and day hours (p < 0.05). There were no changes in platelet reactivity in response to arachidonic acid, adenosine diphosphate, and collagen between time points. Pulse pressure (PP) was highest during awakening hours (p < 0.05). Study findings provide a mechanistic explanation for increased thrombotic events observed in the early waking hours among diabetics with multiple cardiovascular risk factors. The role of chronotherapy in reducing coagulability and PP to improve clinical outcomes should be explored.

Cardiovascular effects of incretins: focus on glucagon-like peptide-1 receptor agonists.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been used to treat patients with type 2 diabetes since 2005 and have become popular because of the efficacy and durability in relation to glycaemic control in combination with weight loss in most patients. Today in 2022, seven GLP-1 RAs, including oral semaglutide are available for treatment of type 2 diabetes. Since the efficacy in relation to reduction of HbA1c and body weight as well as tolerability and dosing frequency vary between agents, the GLP-1 RAs cannot be considered equal. The short acting lixisenatide showed no cardiovascular benefits, while once daily liraglutide and the weekly agonists, subcutaneous semaglutide, dulaglutide, and efpeglenatide, all lowered the incidence of cardiovascular events. Liraglutide, oral semaglutide and exenatide once weekly also reduced mortality. GLP-1 RAs reduce the progression of diabetic kidney disease. In the 2019 consensus report from European Association for the Study of Diabetes/American Diabetes Association, GLP-1 RAs with demonstrated cardio-renal benefits (liraglutide, semaglutide and dulaglutide) are recommended after metformin to patients with established cardiovascular diseases or multiple cardiovascular risk factors. European Society of Cardiology suggests starting with a sodium-glucose cotransprter-2 inhibitor or a GLP-1 RA in drug naïve patients with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (CVD) or high CV Risk. However, the results from cardiovascular outcome trials (CVOT) are very heterogeneous suggesting that some GLP-1RAs are more suitable to prevent CVD than others. The CVOTs provide a basis upon which individual treatment decisions for patients with T2D and CVD can be made.

Longitudinal multivariable trajectory risk clusters and sex-specific association with MRI-derived cardiac function and structure in a population-based sample

Background and Aims : This study aimed to relate longitudinal trajectory clusters of multiple cardiovascular risk factor levels from different examination cycles to MRI-measures of cardiac structure and function of the left and right ventricle in women and men of a population-based cohort.

Consensus statement on the current pharmacological prevention and management of heart failure.

Introduction: This consensus statement of Australian clinicians provides new recommendations for the pharmacological management of heart failure based on studies reported since the publication of the 2018 Australian heart failure guidelines. Main recommendations: ▪Use of sodium–glucose cotransporter 2 (SGLT2) inhibitors to prevent hospitalisation for heart failure in type 2 diabetes mellitus can be extended to patients with multiple cardiovascular risk factors, albuminuric chronic kidney disease, or atherosclerotic cardiovascular disease.▪New evidence supports the use of a mineralocorticoid receptor antagonist (finerenone) to prevent heart failure in type 2 diabetes mellitus associated with albuminuric chronic kidney disease.▪In addition to renin angiotensin system inhibitors (angiotensin receptor neprilysin inhibitor preferred), beta blockers and mineralocorticoid receptor antagonists, an SGLT2 inhibitor (dapagliflozin or empagliflozin) is recommended in all patients with heart failure with reduced left ventricular ejection fraction (LVEF ≤ 40%) (HFrEF). Lower quality evidence supports these therapies in patients with heart failure with mildly reduced LVEF (41‐49%) (HFmrEF).▪A soluble guanylate cyclase stimulator (vericiguat), selective cardiac myosin activator (omecamtiv mecarbil) and, if iron deficient, intravenous iron (ferric carboxymaltose) provide additional benefits in persistent HFrEF.▪An SGLT2 inhibitor (empagliflozin) should be considered in patients with heart failure with preserved LVEF (≥ 50%) (HFpEF). Key changes in management from this statement: This document broadens the scope of angiotensin receptor neprilysin inhibitor use in patients with HFrEF and HFmrEF. SGLT2 inhibitor use expands to become a cornerstone therapy in HFrEF, with increasing evidence to support its use in HFmrEF and HFpEF.

Lessons Learned From a Patient‐Centered, Team‐Based Intervention for Patients With Type 2 Diabetes at High Cardiovascular Risk: Year 1 Results From the CINEMA Program

BackgroundThe care for patients with type 2 diabetes necessitates a multidisciplinary team approach to reduce cardiovascular risk, but implementation of effective integrated strategies has been limited.Methods and ResultsWe conceptualized and initiated a patient‐centered, team‐based intervention called Center for Integrated and Novel Approaches in Vascular‐Metabolic Disease (CINEMA) at University Hospitals Cleveland Medical Center. Patients with type 2 diabetes at high risk for cardiovascular events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score >100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2 to 4 were included. Herein, we present the year 1 results for the program. From May 2020 through August 2021, there were 417 referrals. Among 206 eligible patients, 113 (55%) completed a baseline and ≥1 follow‐up visit through December 2021, with mean (SD) time of 105 (34) days between baseline and first follow‐up visits. Mean age was 59 years, with 49% women and 37% Black patients. Patients had significant reductions from baseline in glycosylated hemoglobin (−10.8%), total cholesterol (−7.9%), low‐density lipoprotein cholesterol (−13.5%), systolic blood pressure (−4.0%), and body mass index (−2.7%) (P≤0.001 for all). In addition, among the 129 (63%) eligible patients not on sodium‐glucose cotransporter 2 inhibitor or glucagon‐like peptide‐1 receptor agonist at baseline, 81% were prescribed evidence‐based therapy with sodium‐glucose cotransporter 2 inhibitor (n=66 [51%]) and/or glucagon‐like peptide‐1 receptor agonist (n=67 [52%]) to reduce the risk of cardiovascular disease in the initial 3‐month follow‐up period.ConclusionsA team‐based, patient‐centered approach to high‐risk disease management appears to be a promising paradigm for care delivery associated with greater use of evidence‐based therapies and improved control of multiple cardiovascular risk factors.

Identification of protective biologic factors in patients with high cardiovascular risk, but normal coronary arteries (NormCorn).

Endothelial progenitor cells (EPCs) have an important role in repair following vascular injury. Telomere length has been shown to be correlated with genome stability and overall cell health. We hypothesized that both EPCs and telomere size are related to protective mechanisms against coronary artery disease. Our aim was to evaluate the level and function of circulating EPCs and telomere length in patients with multiple cardiovascular risk factors and anatomically normal coronary arteries vs. matched controls. We included 24 patients, with coronary CTA demonstrating normal coronaries and a high risk of CAD of >10% by ASCVD risk estimator. Control groups included 17 patients with similar cardiovascular profiles but with established CAD and a group of 20 healthy volunteers. Circulating EPCs levels were assessed by flow cytometry for expression of vascular endothelial growth factor receptor 2, CD34 and CD133. The capacity of the cells to form colony forming units (CFUs) was quantified after 1 week of culture. Telomere length was determined by the southern blotting technique. Patients with high risk for CVD and normal coronaries had augmented EPCs function, compared with the CAD group (1.1 vs. 0.22 CFU/f; P = 0.04) and longer telomeres compared with the CAD group (10.7 kb vs. 2.8 kb P = 0.015). These patients displayed a similar profile to the healthy group. Patients with a high risk for CAD, but normal coronary arteries have EPCs function and telomere length which resemble healthy volunteers, and augmented compared with patients with established CAD, which could serve as a protective mechanism against atherosclerosis development in these high-risk patients.