Established Atherosclerotic Cardiovascular Disease Research Articles

Incremental Benefit of Lipid Lowering in a Large Chinese Population Aged 75 Years and Older With Established Atherosclerotic Cardiovascular Disease

ObjectiveTo explore the optimal low-density lipoprotein cholesterol (LDL-C) level in patients aged 75 years and older with established atherosclerotic cardiovascular disease (ASCVD). Patients and MethodsWe conducted a retrospective multicenter cohort study of veterans aged 75 years and older with ASCVD who were regularly hospitalized or medically examined in 15 medical institutions in southern China from January 1, 2006, to December 31, 2013. Follow-up continued through October 1, 2021. The time-weighted average (TWA) LDL-C level represented the average LDL-C level during follow-up. Participants were divided into TWA LDL-C groups of 55.0 mg/dL or lower, 55.1 to 70.0 mg/dL, 70.1 to 85.0 mg/dL, 85.1 to 100.0 mg/dL, and greater than 100.0 mg/dL. The subgroup with LDL-C levels lower than 55.0 mg/dL was further subdivided into groups with LDL-C levels from 40.1 to 55.0 mg/dL and 40.0 mg/dL or less. The association of TWA LDL-C levels with outcomes was evaluated with Cox proportional hazards models. ResultsOverall, 6387 patients aged 75 years or older with ASCVD were included (mean age, 79.4 years). In total, 4267 major adverse cardiovascular events, 1518 stroke events, and 515 myocardial infarction events occurred during a mean follow-up of 12.7 years. Generally, lower TWA LDL-C level was associated with a lower risk of cardiovascular events but was not associated with a higher risk of adverse events in elderly individuals with ASCVD, with the lowest cardiovascular risk observed for LDL-C levels of less than 55.0 mg/dL. After multivariable adjustment, the risk of a major adverse cardiovascular event was 1.30 (95% CI, 1.26 to 1.34; P<.001) for a per SD increment in TWA LDL-C level. Compared with TWA LDL-C levels of 40.1 to 55.0 mg/dL, TWA LDL-C levels of 40.0 mg/dL or less were associated with an increased risk of hemorrhagic stroke (hazard ratio, 3.71; 95% CI, 1.89 to 7.26). ConclusionLow-density lipoprotein cholesterol levels from 40.1 to 55.0 mg/dL exhibited the maximum cardiovascular benefit in patients aged 75 years and older who had ASCVD. Lowering LDL-C levels to 40.0 mg/dL or less might increase the risk of hemorrhagic stroke.

Cardiovascular prevention with glucose-lowering drugs in type 2 diabetes: An evidence-based approach to the categories of primary and secondary prevention.

Whether to recommend specifically the glucose-lowering therapies with cardiovascular benefit only in secondary prevention, or also in patients with multiple risk factors (MRF) but without established atherosclerotic cardiovascular disease (ASCVD), is controversial across the guidelines for diabetes. We performed a meta-analysis of clinical trials with major adverse cardiovascular events (MACE) as an outcome. The definitions of ASCVD and MRF were heterogeneous across trials; nevertheless, the incidence of MACE was 2.8-fold higher in people with ASCVD in trials with sodium-glucose cotransporter 2 inhibitors (SGLT2is), and 3.9-fold in trials with glucagon-like peptide-1 receptor agonists (GLP-1 RA). Both SGLT2i and GLP-1 RA were associated with a significant reduction in the incidence of MACE in people with previous ASCVD [inverse variance-odds ratio 0.91, 95% confidence interval (0.86: 0.97) for SGLT2i, Mantel-Haenszel odds ratio 0.85, 95% confidence interval (0.81: 0.90) for GLP-1 RA], whereas no significant reduction was detected in those without; on the other hand, no significant difference in effect was found between the two groups as well. The sample of patients without ASCVD enrolled in clinical trials is insufficient to draw reliable conclusions in this population; however, even assuming the same benefit detected in people with ASCVD also in those with MRF, the number needed to treat would differ (35 for secondary, 99 for primary prevention of a MACE with a SGLT2i; 21 for secondary, 82 for primary prevention with a GLP-1 RA, respectively), given the difference in absolute cardiovascular risk at baseline. The distinction between patients with ASCVD and those without ASCVD and MRF appears therefore justified by available evidence.

21-LB: Prevalence of Atherosclerotic Cardiovascular Diseases in Women with Type 2 Diabetes across the Middle East and Africa—Primary Gender Analysis of the PACT-MEA Study

Objectives: Contemporary data on cardiovascular (CV) burden in women with type 2 diabetes (T2D) is lacking, particularly in the Middle East and Africa where the incidence and prevalence of T2D is one of the highest globally. We report prevalence of ASCVD/ASCVD risk stratified by gender to identify opportunities for improving T2D care. Methods: PACT-MEA (PACT-MEA; NCT05317845) is a cross-sectional, observational study of adults (≥18 years) with T2D from 55 clinics in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa, and United Arab Emirates. Medical history, demographics, clinical information, and laboratory values were collected from medical charts of patients at a clinic visit in 2022. We report the prevalence (95% CI) of established atherosclerotic cardiovascular disease (eASCVD) and ASCVD risk, the latter defined by the 2021 European Society of Cardiology (ESC) Guidelines on CV Disease Prevention in Clinical Practice (risk categories: moderate, high, very high [including eASCVD]). Prevalence estimates were weighted according to the size of the diabetes population in each country. Results: Of the 3,726 patients enrolled, 47% were female, with a median age of 59.0; 35% were &amp;lt;55 years old. Across the seven PACT-MEA countries, prevalence of eASCVD was 16.0% (95% CI: 13.4-18.6) among females and 26.6% (23.7-29.5) among males. Per ESC guidelines, 0.6% (0.0-1.2) of females were at moderate risk for ASCVD, 72.5% (69.0-75.9) were at high risk, and 26.9% (23.5-30.3) were at very high risk. Among males, 0.7% (0.0-1.5), 65.9% (62.4-69.4), and 33.4% (29.9-36.8) were at moderate, high, and very high ASCVD risk, respectively. Conclusions: We found 1 in 6 women with T2D in the Middle East and Africa have eASCVD and nearly all are at high/very high ASCVD risk. This highlights the need for better screening and timely management of T2D in women and men to minimize CV risk, as well as the importance of gender inclusiveness in clinical studies. Disclosure F. Alawadi: Research Support; Novo Nordisk. E. Mashaki ceyhan: None. H. M. Sabbour: Research Support; Novo Nordisk. S. Salek: None. G. Yadav: Employee; Novo Nordisk. S. Verma: Advisory Panel; Amgen Canada, AstraZeneca, Bayer Inc., Boehringer Ingelheim and Eli Lilly Alliance, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novartis Canada, Novartis, Novo Nordisk, Novo Nordisk Canada Inc., Consultant; AstraZeneca, Other Relationship; Amarin Corporation, AstraZeneca, Bayer Inc., Boehringer Ingelheim and Eli Lilly Alliance, Boehringer Ingelheim International GmbH, Canadian Medical and Surgical Knowledge Translation Research Group, EOCI Pharmacomm, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novartis Canada, Novo Nordisk, Novo Nordisk Canada Inc., Pfizer Inc., PhaseBio Pharmaceuticals, Inc., S &amp; L Solutions Event Management Inc, Sanofi, Sun Pharmaceutical Industries Ltd., Toronto Knowledge Translation Working Group, Research Support; Amarin Corporation, Amgen Canada, AstraZeneca, Bayer Inc., Boehringer Ingelheim International GmbH, HLS Therapeutics Inc., Novartis, Novo Nordisk, Pfizer Inc., PhaseBio Pharmaceuticals, Inc. S. H. Assaad-khalil: Board Member; AstraZeneca, Merck &amp; Co., Inc., Servier Laboratories, Sanofi, Consultant; AstraZeneca, Servier Laboratories, Sanofi, Merck &amp; Co., Inc., Research Support; Novo Nordisk, Eva Pharma. W. Almahmeed: None. N. Alamuddin: Consultant; Novo Nordisk, Speaker's Bureau; Novo Nordisk. H. Alkandari: None. J. A. Haddad: None. L. N. Husemoen: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. L. Lombard: None. R. A. Malik: None.

When Does a Calcium Score Equate to Secondary Prevention?: Insights From the Multinational CONFIRM Registry

BackgroundElevated coronary artery calcium (CAC) scores in subjects without prior atherosclerotic cardiovascular disease (ASCVD) have been shown to be associated with increased cardiovascular risk. ObjectivesThe authors sought to determine at what level individuals with elevated CAC scores who have not had an ASCVD event should be treated as aggressively for cardiovascular risk factors as patients who have already survived an ASCVD event. MethodsThe authors performed a cohort study comparing event rates of patients with established ASVCD to event rates in persons with no history of ASCVD and known calcium scores to ascertain at what level elevated CAC scores equate to risk associated with existing ASCVD. In the multinational CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry, the authors compared ASCVD event rates in persons without a history of myocardial infarction (MI) or revascularization (as categorized on CAC scores) to event rates in those with established ASCVD. They identified 4,511 individuals without known coronary artery disease (CAC) who were compared to 438 individuals with established ASCVD. CAC was categorized as 0, 1 to 100, 101 to 300, and >300. Cumulative major adverse cardiovascular events (MACE), MACE plus late revascularization, MI, and all-cause mortality incidence was assessed using the Kaplan-Meier method for persons with no ASCVD history by CAC level and persons with established ASCVD. Cox proportional hazards regression analysis was used to calculate HRs with 95% CIs, which were adjusted for traditional cardiovascular risk factors. ResultsThe mean age was 57.6 ± 12.4 years (56% male). In total, 442 of 4,949 (9%) patients experienced MACEs over a median follow-up of 4 years (IQR: 1.7-5.7 years). Incident MACEs increased with higher CAC scores, with the highest rates observed with CAC score >300 and in those with prior ASCVD. All-cause mortality, MACEs, MACE + late revascularization, and MI event rates were not statistically significantly different in those with CAC >300 compared with established ASCVD (all P > 0.05). Persons with a CAC score <300 had substantially lower event rates. ConclusionsPatients with CAC scores >300 are at an equivalent risk of MACE and its components as those treated for established ASCVD. This observation, that those with CAC >300 have event rates comparable to those with established ASCVD, supplies important background for further study related to secondary prevention treatment targets in subjects without prior ASCVD with elevated CAC. Understanding the CAC scores that are associated with ASCVD risk equivalent to stable secondary prevention populations may be important for guiding the intensity of preventive approaches more broadly.

Estimation of 10-year risk of fatal and non-fatal cardiovascular disease in a portuguese population

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease (CVD) is the most common noncommunicable disease and actually the leading cause of death globally. Hence, it is important to identify individuals who may benefit from CVD preventive strategies. The European Society of Cardiology (ESC) has recently updated the European Systematic Coronary Risk Evaluation (SCORE) to SCORE2 and SCORE2-OP risk prediction algorithms. Those tools were recalibrated to four groups of countries (low, moderate, high and very high CVD risk) based on national CVD mortality rates published by the WHO, with Portugal being now considered a moderate risk country. Purpose To evaluate the application of SCORE2 and SCORE2-OP in a Portuguese population sample. Methods We conducted a cross-sectional study, including individuals aged 40-90 years, without known established Atherosclerotic Cardiovascular Disease, Diabetes mellitus, Chronic Kidney Disease or Familial Hypercholesterolemia. The sample was recruited at a local cardiovascular screening event in Portugal that took place in May 2022. The 10-year fatal and non-fatal CVD risk was calculated using SCORE2 (for individuals aged &amp;lt; 70 years) and SCORE2-OP (for individuals aged ≥ 70 years) tools. Based on CVD risk category, patients were stratified into 3 categories: low to moderate, high and very high risk according to new SCORE algorithms. Primary outcome was the assessment of 10-year risk of fatal and non-fatal CVD with SCORE2 e SCORE2-OP in a local Portuguese population. According to the data distribution, appropriate statistical tests were conducted to compare independent samples. Multivariable linear regression was used to analyze 10-year CVD risk. Results This cohort included 431 individuals. Median age was 71 years (Q1-Q3: 65-75) and 66.8% of individuals were women. Regarding baseline characteristics of the included individuals, 48.1% had hypertension, 38.3% had dyslipidemia, 25.5% were obese and 6.6% were smokers. Based on the SCORE2 model 92 (26.1%) individuals were classified into low to moderate risk, 162 (46.0%) into high risk and 98 (27.8%) into very high-risk category. SCORE2 median was 3.43 % (Q1-Q3: 5.5-8.0 p&amp;lt; 0.01) and SCORE2-OP median was 12.70 % (Q1-Q3: 9.7-12.7). Active smoking was the only independent predictor of 10-years CVD risk both in SCORE2 (RR 3.28, 95% CI: 1.93-4.66, p=0.001) and SCORE2-OP (RR 6.31, 95% CI: 2.67-9.52, p&amp;lt;0.001). Conclusions Most individuals in this sample were stratified into high or very high risk of developing 10-year fatal and non-fatal cardiovascular events. This data is in accordance with the updated risk category of Portugal based on World Health Organization cardiovascular mortality rates. These results not only validate the application of SCORE to the Portuguese setting, but also reinforce how this easily applicable tool can help to identify patients who will benefit from CVD preventive strategies.

Is there a role for conicity index in 10-year risk cardiovascular disease prediction?

Abstract Funding Acknowledgements Type of funding sources: None. Background Cardiovascular disease (CVD) is the leading cause of death globally and one of the most frequent causes of disability. Therefore, the complete and correct evaluation of cardiovascular risk factors is essential to timely prevent CVD. Once central obesity is related with the amount of visceral adipose tissue - an independent predictor of CVD risk - its assessment may play an important role in 10-year CVD prediction. The conicity index (C-Index) assesses central adiposity but there is limited data regarding its role in 10-year CVD risk prediction. Purpose To evaluate the role of C-Index in predicting 10-year risk of fatal and non-fatal CVD according to SCORE2 and SCORE2-OP models in a moderate-risk country population. Methods We conducted a cross-sectional study in a Portuguese population sample. Individuals aged 40-90 years without known established Atherosclerotic Cardiovascular Disease, Diabetes mellitus, Chronic Kidney Disease or Familial Hypercholesterolemia were included in the study through a local cardiovascular (CV) screening event in Portugal, during May 2022. The C-Index was calculated for each individual according to the Valdez’s formula. For CVD risk assessment, we used the cut-offs values proposed by Pitanga et al. 1.18 for women and 1.25 for men. The population was divided into two groups according to the C-Index (risk high versus low). The 10-year risk of fatal and non-fatal CVD was calculated using SCORE2 and SCORE2-OP models. Results A total of 431 individuals were enrolled in this study. Median age was 71 years (Q1-Q3: 65-75) and 66.8% of were women. A total of 48.1% had hypertension, 38.3% dyslipidemia, 25.5% obesity and 6.6% were active smokers. Overall, 387 (90.2%) individuals were found to have elevated C-Index (SCORE2/2-OP mean± DP: 14.99± 7.56 versus 09.81± 3.37), of which 259 were female. In the univariate analysis, there was a correlation between C-Index and estimation of the Risk Cardiovascular Disease according to SCORE2/2-OP but was not statistically significant (Exp (beta) 95 % (CI):2.52 (-2.06-7.10, p=0.28)). However, in the multivariable linear regression analyzes the variable waist circumference (Exp (beta) 95 % (CI)18.47 (4.69 – 32.24, p&amp;lt;0.001)) was independent predictive factor related to the Risk of Cardiovascular Disease according to SCORE2 and SCORE2-OP. Conclusions In the present study most of the patients were categorized into high-risk category. Conicity index was not significantly correlated with estimation of the Risk of Cardiovascular Disease according to SCORE2 and SCORE2-OP models, but the variable waist circumference (Exp (beta) 95 % (CI)18.47 (4.69 – 32.24, p&amp;lt;0.001)) was an independent predictive factor related. More studies are needed to assess the role of C-Index in CVD risk prediction.

Lipid-Lowering Nutraceuticals for an Integrative Approach to Dyslipidemia.

Dyslipidemia is a treatable risk factor for atherosclerotic cardiovascular disease that can be addressed through lifestyle changes and/or lipid-lowering therapies. Adherence to statins can be a clinical challenge in some patients due to statin-associated muscle symptoms and other side effects. There is a growing interest in integrative cardiology and nutraceuticals in the management of dyslipidemia, as some patients desire or are actively seeking a more natural approach. These agents have been used in patients with and without established atherosclerotic cardiovascular disease. We provide an updated review of the evidence on many new and emerging nutraceuticals. We describe the mechanism of action, lipid-lowering effects, and side effects of many nutraceuticals, including red yeast rice, bergamot and others.

Clonal Hematopoiesis of Indeterminate Potential Predicts Adverse Outcomes in Patients With Atherosclerotic Cardiovascular Disease

BackgroundClonal hematopoiesis of indeterminate potential (CHIP)—the age-related clonal expansion of blood stem cells with leukemia-associated mutations—is a novel cardiovascular risk factor. Whether CHIP remains prognostic in individuals with established atherosclerotic cardiovascular disease (ASCVD) is less clear. ObjectivesThis study tested whether CHIP predicts adverse outcomes in individuals with established ASCVD. MethodsIndividuals aged 40 to 70 years from the UK Biobank with established ASCVD and available whole-exome sequences were analyzed. The primary outcome was a composite of ASCVD events and all-cause mortality. Associations of any CHIP (variant allele fraction ≥2%), large CHIP clones (variant allele fraction ≥10%), and the most commonly mutated driver genes (DNMT3A, TET2, ASXL1, JAK2, PPM1D/TP53 [DNA damage repair genes], and SF3B1/SRSF2/U2AF1 [spliceosome genes]) with incident outcomes were compared using unadjusted and multivariable-adjusted Cox regression. ResultsOf 13,129 individuals (median age: 63 years) included, 665 (5.1%) had CHIP. Over a median follow-up of 10.8 years, any CHIP and large CHIP at baseline were associated with adjusted HRs of 1.23 (95% CI: 1.10-1.38; P < 0.001) and 1.34 (95% CI: 1.17-1.53; P < 0.001), respectively, for the primary outcome. TET2 and spliceosome CHIP, especially large clones, were most strongly associated with adverse outcomes (large TET2 CHIP: HR: 1.89; 95% CI: 1.40-2.55; P <0.001; large spliceosome CHIP: HR: 3.02; 95% CI: 1.95-4.70; P < 0.001). ConclusionsCHIP is independently associated with adverse outcomes in individuals with established ASCVD, with especially high risks observed in TET2 and SF3B1/SRSF2/U2AF1 CHIP.

Response by O’Donoghue et al to Letter Regarding Article, “Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease”

Response by O’Donoghue et al to Letter Regarding Article, “Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease”

Abstract P629: Influenza Vaccine Uptake is Associated With Cholesterol Treatment Adherence: An Analysis of the Behavioral Risk Factor Surveillance System Survey

Introduction: Misinformation, distrust, and other sociocultural factors that influence vaccine uptake may also influence adherence to cholesterol treatment. Hypothesis: Among American adults with hyperlipidemia, individuals who receive influenza vaccination are more likely to report use of cholesterol lowering medication. Methods: We pooled 2017 and 2019 survey data from the Behavioral Risk Factor Surveillance System (BRFSS). Our sample included all respondents aged 40 to 75 years with self-reported high cholesterol. We used logistic regression models adjusted for potential confounders to examine the association between influenza vaccine uptake and use of cholesterol medication. We also evaluated whether the association was different among those with and without established atherosclerotic cardiovascular disease (ASCVD). All analyses accounted for survey weighting. Results: Of 228,338 (weighted = 107,893,277) participants with hyperlipidemia, 51% reported influenza vaccination and 61% reported taking cholesterol medication. Vaccine uptake was associated with cholesterol medication use (OR 2.08, 95% CI 2.00-2.16, p &lt;0.001). Although slightly attenuated, this association persisted after adjustment for socio-demographics, access to care, comorbidities, and adherence to hypertension treatment (OR 1.53, 95% CI 1.42-1.65, p-value &lt;0.001). The association was similar in those with ASCVD (OR 1.63, 95% CI 1.32-2.03, p-value &lt;0.001) and those without ASCVD (OR 1.52, 95% CI 1.40-1.64, p-value &lt;0.001), p-value for interaction = 0.89. Conclusions: Influenza vaccine uptake is associated with cholesterol medication use among American adults with high cholesterol, including those with ASCVD. The sociocultural factors affecting vaccine avoidance, such as misinformation and distrust, merit investigation as potential targets of cardiovascular prevention efforts.

Effects of the Sodium-Glucose Cotransporter Inhibitors on Cardiovascular Death and All-Cause Mortality: A Systematic Review and Meta-analysis of Randomized Placebo-Controlled Clinical Trials.

Patients with diabetes mellitus are at an increased risk of cardiovascular morbidity and all-cause mortality. Heart failure and type 2 diabetes often occur concomitantly, and each disease independently increases the risk for the other. Emerging data have revealed that some sodium-glucose cotransporter inhibitors (SGLTi) improve cardiovascular and renal outcomes, particularly in patients with type 2 diabetes. The magnitude of this effect in patients without any underlying condition remains unclear. As a result, we conducted a meta-analysis of the mortality outcomes of available SGLTi in patients with or without cardiovascular diseases, type 2 diabetes, cardiovascular risk factors, and heart failure. We performed a systematic review and meta-analysis of randomized, placebo-controlled major cardiovascular outcome trials of SGLTi in patients regardless of their cardiovascular disease or risk status. PubMed, Cochrane, Google Scholar, MEDLINE, and EMBASE were searched for the relevant studies. Three reviewers extracted study data and three reviewers summarized the strength of the evidence. Efficacy outcomes included all-cause mortality, major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of all-cause mortality, cardiovascular death, or hospitalization for heart failure. Odds ratios with 95% confidence intervals were pooled across trials to calculate the overall effect size. A total of 5043 all-cause mortality events were observed in the study groups. In 42,050 patients who received SGLTi, 2581 events were reported, and 2462 events were reported in 35,491 patients who received placebo (odds ratio = 0.86, 95% confidence interval 0.80-0.93, p = 0.0003). The use of SGLTi significantly reduced cardiovascular mortality compared with control across the patients' population (odds ratio = 0.86, 95% confidence interval 0.79-0.93, p = 0.0001). There was a consistent pattern of mortality beneficial estimates for all patients with different co-morbid conditions in the SGLTi-treated arm compared with the placebo-treated group. The presence or absence of significant cardiovascular disease risk factors (including a family history of premature coronary artery disease, baseline estimated glomerular filtration rate, dyslipidemia, hypertension, smoking, history of cardiovascular disease, and older age) did not affect the estimated mortality benefits. Sodium-glucose cotransporter inhibitorssignificantly reduced major adverse cardiovascular events, including hospitalization and all-cause mortality in patients with or without established atherosclerotic cardiovascular disease. We observed a beneficial trend in patients with heart failure with preserved ejection fraction, and no benefits in patients with stroke or myocardial infarction.

Comparison of cardiovascular and renal outcomes between dapagliflozin and empagliflozin in patients with type 2 diabetes without prior cardiovascular or renal disease.

BackgroundCardiovascular and renal benefits of sodium glucose co-transporter 2 inhibitors (SGLT2i) have been clearly demonstrated. However, studies comparing the effects of dapagliflozin and empagliflozin are scarce. In addition, relatively few studies have analyzed the effects of SGLT2i in diabetic patients without established atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), or heart failure (HF), and current guidelines recommend SGLT2i and other antidiabetic drugs equally in this population. Therefore, we aimed to compare the clinical outcomes between dapagliflozin, empagliflozin, and dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with type 2 diabetes without prior ASCVD, CKD, or HF.MethodsUsing a propensity-score matching method, we retrospectively analyzed 921 patients treated with dapagliflozin, 921 patients treated with empagliflozin, and 1842 patients treated with DPP4i (control group). Study outcomes comprised composite coronary events (acute coronary syndrome and coronary revascularization), composite ischemic events (coronary events and stroke), and composite heart failure and renal events.ResultsDuring follow up (median, 43.4 months), the incidence of composite coronary events was significantly lower in the SGLT2i groups than in the control group, and the incidence of composite ischemic events was lower in the dapagliflozin group than in the control group. Dapagliflozin and empagliflozin both demonstrated significant benefits in terms of HF and renal outcomes, supported by renoprotective effects, as assessed by the change in glomerular filtration rate. At 24–36 months of treatment, the empagliflozin group had higher low-density lipoprotein cholesterol levels, and lower glycated hemoglobin levels, compared to those in the dapagliflozin and control groups.ConclusionSGLT2i use was associated with a significantly reduced risk of ASCVD, HF hospitalization, and renal events, compared to that with DPP4i use among diabetic patients without prior ASCVD, CKD, or HF. There were no significant differences in clinical outcomes between dapagliflozin and empagliflozin, supporting a SGLT2i class effect.

Key updates to the management of type 2 diabetes in adults: how to embrace and embed the new NICE guidance

Key updates to the management of type 2 diabetes in adults: how to embrace and embed the new <scp>NICE</scp> guidance

Chronic kidney disease as cardiovascular risk factor in routine clinical practice: a position statement by the Council of the European Renal Association.

The European Society of Cardiology 2021 guideline on cardiovascular (CV) disease (CVD) prevention in clinical practice has major implications for both CV risk screening and kidney health of interest to primary care physicians, cardiologists, nephrologists, and other professionals involved in CVD prevention. The proposed CVD prevention strategies require as first step the categorization of individuals into those with established atherosclerotic CVD, diabetes, familiar hypercholesterolaemia, or chronic kidney disease (CKD), i.e. conditions that are already associated with a moderate to very-high CVD risk. This places CKD, defined as decreased kidney function or increased albuminuria as a starting step for CVD risk assessment. Thus, for adequate CVD risk assessment, patients with diabetes, familiar hypercholesterolaemia, or CKD should be identified by an initial laboratory assessment that requires not only serum to assess glucose, cholesterol, and creatinine to estimate the glomerular filtration rate, but also urine to assess albuminuria. The addition of albuminuria as an entry-level step in CVD risk assessment should change clinical practice as it differs from the current healthcare situation in which albuminuria is only assessed in persons already considered to be at high risk of CVD. A diagnosis of moderate of severe CKD requires a specific set of interventions to prevent CVD. Further research should address the optimal method for CV risk assessment that includes CKD assessment in the general population, i.e. whether this should remain opportunistic screening or whether systematic screening.

In patients with non-alcoholic fatty liver disease, liver stiffness directly correlates with the carotid plaque burden

Background and Aims : It is now well established that non-alcoholic fatty liver disease (NAFLD) is associated with a significant increase in the risk of adverse cardiovascular events. NAFLD-specific cardiovascular risk scores, considering traditional and nontraditional risk factors, are needed to improve patient care. Liver fibrosis may be an integrative indicator of the burden of cardiometabolic risk factors. Liver fibrosis may also represent the burden of subclinical atherosclerosis. The aim of the study was to investigate the relationships between liver stiffness and carotid plaque burden in patients with NAFLD without established atherosclerotic cardiovascular disease.

2022 Canadian Cardiovascular Society Guideline for Use of GLP-1 Receptor Agonists and SGLT2 Inhibitors for Cardiorenal Risk Reduction in Adults.

This guideline synthesizes clinical trial data supporting the role of glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors (SGLT2i) for treatment of heart failure (HF), chronic kidney disease, and for optimizing prevention of cardiorenal morbidity and mortality in patients with type 2 diabetes. It is on the basis of a companion systematic review and meta-analysis guided by a focused set of population, intervention, control, and outcomes (PICO) questions that address priority cardiorenal end points. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system and a modified Delphi process were used. We encourage comprehensive assessment of cardiovascular (CV) patients with routine measurement of estimated glomerular filtration rate, urinary albumin-creatinine ratio, glycosylated hemoglobin (A1c), and documentation of left ventricular ejection fraction (LVEF) when evaluating symptoms of HF. For patients with HF, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy for the reduction of hospitalization for HF when LVEF is > 40% and for the reduction of all-cause and CV mortality, hospitalization for HF, and renal protection when LVEF is ≤ 40%. In patients with albuminuric chronic kidney disease, we recommend integration of SGLT2i with other guideline-directed pharmacotherapy to reduce all-cause and CV mortality, nonfatal myocardial infarction, and hospitalization for HF. We provide recommendations and algorithms for the selection of glucagon-like peptide-1 receptor agonists and SGLT2i for patients with type 2 diabetes and either established atherosclerotic CV disease or risk factors for atherosclerotic CV disease to reduce all-cause and CV mortality, nonfatal stroke, and for the prevention of hospitalization for HF and decline in renal function. We offer practical advice for safe use of these diabetes-associated agents with profound cardiorenal benefits.

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.

425-P: 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

Background: Persons with type 2 diabetes mellitus (T2DM) often experience fragmented and complex care and across multiple specialties. We implemented a patient-centered, multidisciplinary team-based intervention called CINEMA to improve care delivery and outcomes. Methods: Patients with T2DM at high-risk for cardiovascular disease events, including those with established atherosclerotic cardiovascular disease, elevated coronary artery calcium score &amp;gt;100, chronic heart failure with reduced ejection fraction, and/or chronic kidney disease stages 2-4 were included in the program in Cleveland, OH. The program included 5 cardiologists with a special focus on T2DM, a pharmacist, a certified diabetes care and education specialist/dietician, a nurse navigator, and collaboration with endocrinologists and nephrologists. Data was collected from baseline within 3 months prior to patients’ first visit to up to 1 month after the follow-up visit. From May 2020 through May 2021, there were 316 referrals to the program. Of those referred, 47% met inclusion criteria. Among eligible patients, 96 (64%) completed a baseline and follow-up visit, with mean (std dev) follow-up time of 1 (34) days. Among patients completing the initial 3-month visit, 50% were ≥age 60 years with 48% female and 34% Black patients. Patients had significant reductions from baseline in Hb A1c (-8.7%) , total (-10.4%) , LDL (-15.7%) , and non-HDL (-14.9%) cholesterol, body weight (-3.7%) , and body mass index (-3.8%) (p&amp;lt;0.0for all) . In addition, among eligible patients, 87.5% were started on evidenced-based therapy with SGLT2i (n=24) , GLP-1 RA (n=40) , or both (n=20) to reduce the risk of CVD. Conclusions: A 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 CV risk factors. Disclosure I. Neeland: Advisory Panel; Boehringer Ingelheim International GmbH, Merck &amp; Co., Inc. Consultant; Nestlé Health Science. S.G. Al-Kindi: None. N. Tashtish: None. S. Rahmani: None. D. Berg: None. M.N. Rana: None. C. Sullivan: None. B. Hatipoglu: None.

PREDICTORS OF CHRONIC HEART FAILURE WITH PRESERVED EJECTION FRACTION IN PATIENTS WITH TYPE 2 DIABETES MELLITUS TREATED WITH EMPAGLIFLOZIN

Objective: Currently, it’s not well known what factors influenced the incidence of heart failure with preserved ejection (HFpEF) fraction in patients receiving sodium glucose co-transporter 2 inhibitors (SGLT2i). Objective: To evaluate predictors of HFpEF in patients with type 2 diabetes mellitus (T2DM) receiving SGLT2i Design and method: It was a prospective study in patients with T2DM. Inclusion criteria were: male and female, age 40–65 years, T2DM with duration at least for 1 year, absence of established atherosclerotic cardiovascular disease and HF. Exclusion criteria were: type 1 diabetes mellitus, glycated hemoglobin (HbA1c)&gt; 11% at screening, insulin therapy, atrial fibrillation, clinically significant valvular heart disease, chronic kidney disease, other serious conditions that would make the patient unsuitable for participation in the study. Clinical, laboratory (including biomarkers such as NT-proBNP, sST2, galectin-3, PICP,PIIINP,MMP-9,TIMP-1) and instrumental (echocardiography) data were collected at baseline. Empagliflozin 10 mg daily was prescribed for all patients. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by cardiologist), other clinically important data were obtained. Results: Seventy-five patients were included in the study. The mean age was 58 (47.9;65.1) years, 45,1% were female. Most patients had T2DM for more than 4 years. Mean HbA1c was 8.6% (7.6;9.5), all patients received oral antihyperglycemic medications. After 3 years of follow-up HFpEF was established in 16 patients. The HF group had higher waist circumference values, higher Nt-proBNP, galectin-3 and P1CP levels at baseline than patients without HF (all p &lt; 0.05). The threshold for galectin-3 level associated with increased risk of HFpEF in this population was 10.3 ng/ml (AUC area = 0.86; sensitivity, 87%; and specificity, 73%; p &lt; 0.001). Multiple logistic regression analysis identified significant risk factors for new onset of HFpEF: age&gt; 60 years, diabetes duration&gt; 10 years and presence of abdominal obesity were independent predictors of HFpEF. Galectin-3 level &gt; 10 ng/ml was associated with increased risk of HF incidence (OR = 2.15; 95% CI, 1.80–5.21; p = 0.01). Conclusions: Predictors for incidence HFpEF in patients with T2DM were age, diabetes duration, presence of abdominal obesity and galectin-3 levels higher than 10 ng/ml.

Associations between Circulating VEGFR2hi-Neutrophils and Carotid Plaque Burden in Patients Aged 40-64 without Established Atherosclerotic Cardiovascular Disease.

Background Neutrophils expressing vascular endothelial growth factor receptor (VEGFR) represent a distinct subtype of neutrophils with proangiogenic properties. The purpose of this study was to identify the interrelations between circulating CD16hiCD11bhiCD62LloCXCR2hiVEGFR2hi-neutrophils and indicators of carotid plaque burden in patients without atherosclerotic cardiovascular diseases (ASCVD). Methods The study included 145 patients, 51.7% men and 48.3% women, median age—49.0 years. All patients underwent carotid duplex ultrasound scanning. The maximal carotid plaque thickness was used as an indicator of carotid plaque burden. Also, carotid intima-media thickness (cIMT) and femoral IMT were measured. The phenotyping of neutrophil subpopulations was executed by the flow cytometry via the Navios 6/2. Results. The subpopulation of VEGFR2hi-neutrophils accounted for about 5% of the total pool of circulating neutrophils. A decrease in VEGFR2hi-neutrophils with an increase in carotid plaque burden was statistically significant (p = 0.036). A decrease in VEGFR2hi-neutrophils < 4.52% allowed to predict the presence of plaque with a maximum height > 2.1 mm (Q4), with sensitivity of 78.9% and specificity of 61.5% (AUC 0.693; 95% CI 0.575-0.811; p = 0.007). Inverse correlations were established between the carotid and femoral IMT and the absolute and relative number of VEGFR2hi-neutrophils (p < 0.01). Conclusion In patients aged 40-64 years without established ASCVD, with an increase in indicators of the carotid plaque burden, a significant decrease in the proportion of circulating VEGFR2hi-neutrophils was noticed. A decrease in the relative number of VEGFR2hi-neutrophils of less than 4.52% made it possible to predict the presence of extent carotid atherosclerosis with sensitivity of 78.9% and specificity of 61.5%.