Presence Of Atherosclerotic Cardiovascular Disease Research Articles

Resilient Older Subjects with Heterozygous Familial Hypercholesterolemia, Baseline Differences and Associated Factors.

Despite elevated low-density lipoprotein (LDL) cholesterol levels, some older subjects with heterozygous familial hypercholesterolemia (HeFH) do not develop atherosclerotic cardiovascular disease (ACVD) during their lifetime. The factors related to this resilient state have not been fully established. The aim of this study was to evaluate differential characteristics between older HeFH subjects with and without ACVD and factors associated with the presence of ACVD. Subjects were part of the Spanish Atherosclerosis Society Dyslipidemia Registry, and those ≥ 70 years old and with HeFH were included. Baseline characteristics of these subjects with and without ACVD were compared. A multivariate analysis was performed to assess factors associated with the presence of ACVD. A total of 2148 subjects with HeFH were included. Resilient subjects were mostly female, younger and presented fewer comorbidities with respect to the ACVD group. Subjects without ACVD had higher baseline high-density lipoprotein (HDL) cholesterol (55.8 ± 17.1 vs. 47.9 ± 15.4 mg/dL; p < 0.001) and lower lipoprotein(a) [Lp(a)] (53.4 ± 67.9 vs. 66.6 ± 85.6 mg/dL; p < 0.001) levels with respect to those in the ACVD group. Lp(a) and the presence of ≥3 risk factors were associated with the presence of ACVD.

Diabetes and Coronary Artery Disease as Risk Factors for Dementia.

Diabetes is associated with increased risk of dementia, but it is still debated to which degree this risk depends on the presence of atherosclerotic cardiovascular disease. We hypothesized that patients with diabetes and co-existing coronary artery disease (CAD), as a marker of systemic atherosclerotic cardiovascular disease, have substantially higher risk of developing dementia. Patients ≥65 years, who underwent coronary angiography were stratified by diabetes and CAD. Outcomes were all-cause dementia, Alzheimer's dementia, and vascular dementia. We estimated adjusted hazard ratios (aHRs) using patients with neither diabetes nor CAD as a reference. A total of 103,859 patients were included. Of these, 23,189 (22%) had neither diabetes nor CAD, 3,876 (4%) had diabetes, 61,020 (59%) had CAD, and 15,774 (15%) had diabetes and CAD. During a median follow-up of 6.3 years, 5,592 (5.5%) patients were diagnosed with all-cause dementia. Patients with diabetes and CAD had the highest hazard rate of all-cause dementia (aHR 1.37, 95% CI 1.24-1.51), including Alzheimer's dementia (aHR 1.41, 95% CI 1.23-1.62) and vascular dementia (aHR 2.03, 95% CI 1.69-2.45). Patients with diabetes alone (aHR 1.14, 95% CI 0.97-1.33) or CAD alone (aHR 1.11, 95% CI 1.03-1.20) had a modestly increased rate of all-cause dementia. The combination of diabetes and CAD is associated with increased rate of dementia, in particular vascular dementia, suggesting that the diabetes-related risk of dementia is partly mediated through concomitant atherosclerotic cardiovascular disease. This underscores the importance of atherosclerotic cardiovascular disease prevention in diabetes patients to reduce cognitive decline.

Real-world Use and Outcomes of Sodium-glucose Cotransporter-2 Inhibitors in Adults With Diabetes and Heart Failure: A Population-level Cohort Study in Alberta, Canada

ObjectivesSince 2016, clinical guidelines have recommended sodium-glucose cotransporter-2 inhibitors (SGLT2is) for people with type 2 diabetes with heart failure. We examined SGLT2i dispensation, factors associated with dispensation, and heart failure hospitalization and all-cause mortality in people with diabetes and heart failure. MethodsIn this retrospective, population-based cohort study we identified people with diabetes and heart failure between January 1, 2014 and December 31, 2017 in Alberta, Canada (population ∼4.3 million), and followed them for a minimum of 3 years. Multivariate logistic regression assessed the factors associated with SGTL2i dispensation. Propensity scores were used with regression adjustment to estimate the effect of SGLT2i treatment on heart failure hospitalization. ResultsAmong 22,025 individuals with diabetes and heart failure (43.4% women, mean age 74.7±11.8 years), only 10.2% were dispensed an SGLT2i. Male sex, age <65 years, a higher baseline A1C, no chronic kidney disease, presence of atherosclerotic cardiovascular disease, and urban residence were associated with SGLT2i dispensation. Lower heart failure hospitalization rates were observed in those with SGLT2i dispensation (548.1 per 100 person years) vs those without (813.5 per 1,000 person years; p<0.001) and lower all-cause mortality in those with an SGLT2i than those without (48.5 per 1,000 person years vs 206.1 per 1,000 person years; p<0.001). Regression adjustment found SGLT2i therapy was associated with a 23% reduction in hospitalization. ConclusionsSGLT2is were dispensed to only 10% of people with diabetes and established heart failure, underscoring a significant care gap. SGLT2i use was associated with a real-world reduction in heart failure hospitalization and all-cause death. This study highlights an important opportunity to optimize SGLT2i use.

Differences in predictors of incident heart failure according to atherosclerotic cardiovascular disease status.

Heart failure (HF) is a common cause of morbidity and mortality, related to a broad range of sociodemographic, lifestyle, cardiometabolic, and comorbidity risk factors, which may differ according to the presence of atherosclerotic cardiovascular disease (ASCVD). We assessed the association between incident HF with baseline status across these domains, overall and separated according to ASCVD status. We included 5758 participants from the Baker Biobank cohort without HF at baseline enrolled between January 2000 and December 2011. The primary endpoint was incident HF, defined as hospital admission or HF-related death, determined through linkage with state-wide administrative databases (median follow-up 12.2years). Regression models were fitted adjusted for sociodemographic variables, alcohol intake, smoking status, measures of adiposity, cardiometabolic profile measures, and individual comorbidities. During 65987 person-years (median age 59years, 38% women), incident HF occurred among 784 participants (13.6%) overall. Rates of incident HF were higher among patients with ASCVD (624/1929, 32.4%) compared with those without ASCVD (160/3829, 4.2%). Incident HF was associated with age, socio-economic status, alcohol intake, smoking status, body mass index (BMI), waist circumference, waist-hip ratio, systolic blood pressure (SBP), and low- and high-density lipoprotein cholesterol (LDL-C and HDL-C), with non-linear relationships observed for age, alcohol intake, BMI, waist circumference, waist-hip ratio, SBP, LDL-C, and HDL-C. Risk factors for incident HF were largely consistent regardless of ASCVD status, although diabetes status had a greater association with incident HF among patients without ASCVD. Incident HF is associated with a broad range of baseline sociodemographic, lifestyle, cardiometabolic, and comorbidity factors, which are mostly consistent regardless of ASCVD status. These data could be useful in efforts towards developing risk prediction models that can be used in patients with ASCVD.

The German CaRe high registry for familial hypercholesterolemia – Sex differences, treatment strategies, and target value attainment

Background and aimsFamilial hypercholesterolemia (FH) is among the most common genetic disorders in primary care. However, only 15% or less of patients are diagnosed, and few achieve the goals for low-density lipoprotein cholesterol (LDL-C). In this analysis of the German Cascade Screening and Registry for High Cholesterol (CaRe High), we examined the status of lipid management, treatment strategies, and LDL-C goal attainment according to the ESC/EAS dyslipidemia guidelines. MethodsWe evaluated consolidated datasets from 1501 FH patients diagnosed clinically and seen either by lipid specialists or general practitioners and internists. We conducted a questionnaire survey of both the recruiting physicians and patients. ResultsAmong the 1501 patients, 86% regularly received lipid-lowering drugs. LDL-C goals were achieved by 26% and 10% of patients with atherosclerotic cardiovascular disease (ASCVD) according to the 2016 and 2019 ESC/EAS dyslipidemia guidelines, respectively. High intensity lipid-lowering was administered more often in men than in women, in patients with ASCVD, at higher LDL-C and in patients with a genetic diagnosis of FH. ConclusionsFH is under-treated in Germany compared to guideline recommendations. Male gender, genetic proof of FH, treatment by a specialist, and presence of ASCVD appear to be associated with increased treatment intensity. Achieving the LDL-C goals of the 2019 ESC/EAS dyslipidemia guidelines remains challenging if pre-treatment LDL-C is very high.

The growing clinical effect of SGLT2 inhibitors

In September, 2015, the results of EMPA-REG OUTCOME, the first cardiovascular outcomes study based on a sodium-glucose co-transporter-2 (SGLT2) inhibitor, empagliflozin, were announced at the Annual Meeting of the European Association for the Study of Diabetes. It was the first of a series of cardiovascular outcome studies confirming a significant risk reduction of the three-point MACE (cardiovascular mortality, non-fatal myocardial infarction, and non-fatal stroke) in people with type 2 diabetes and established atherosclerotic cardiovascular disease. It was also the first clinical trial to show potential renal protection: empagliflozin was associated with reduced loss of estimate glomerular filtration rate compared with placebo. Moreover, the trial reported a significant reduction in the risk of hospitalisation for heart failure. 1 Zinman B Wanner C Lachin JM et al. Investigators E-ROEmpagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015; 373: 2117-2128 Crossref PubMed Scopus (7211) Google Scholar The cardiorenal protective effects of SGLT2 inhibitors have been confirmed in subsequent cardiovascular outcomes studies done in people with type 2 diabetes 2 McGuire DK Shih WJ Cosentino F et al. Association of SGLT2 inhibitors with cardiovascular and kidney outcomes in patients with type 2 diabetes: a meta-analysis. JAMA Cardiol. 2021; 6: 148-158 Crossref PubMed Scopus (339) Google Scholar and without diabetes. 3 Vaduganathan M Docherty KF Claggett BL et al. SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis of five randomised controlled trials. Lancet. 2022; 400: 757-767 Summary Full Text Full Text PDF PubMed Scopus (61) Google Scholar Because of these results, current guidelines recommend the use of a SGLT2 inhibitor with proven beneficial effect for people with type 2 diabetes with chronic kidney disease and a history of heart failure. 4 Davies MJ Aroda VR Collins BS et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2022; 65: 1925-1966 Crossref PubMed Scopus (32) Google Scholar Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trialDapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. Full-Text PDF

Effects of dapagliflozin on hospitalisations in people with type 2 diabetes: post-hoc analyses of the DECLARE-TIMI 58 trial

In people with type 2 diabetes at high risk of cardiovascular or kidney disease, sodium-glucose co-transporter 2 (SGLT2) inhibitors consistently reduce the risk of hospitalisations for heart failure. Less is known about their effects on hospitalisation from any cause, especially in people with type 2 diabetes without atherosclerotic cardiovascular disease, which includes most of the global population of people with type 2 diabetes. We aimed to assess the effect of the SGLT2 inhibitor, dapagliflozin, on the risks of hospitalisations for any cause and for specific causes in people with type 2 diabetes with and without atherosclerotic cardiovascular disease. The DECLARE-TIMI 58 trial was a double-blind, multicentre, randomised, placebo-controlled study. People with type 2 diabetes and either risk factors for or established atherosclerotic cardiovascular disease were randomly assigned (1:1) to receive oral dapagliflozin 10 mg or placebo once daily. In these post-hoc analyses, the effects of dapagliflozin on risks of first non-elective any-cause and cause-specific hospitalisation were assessed with Cox proportional hazards regression models overall and in the subset of participants without prevalent atherosclerotic cardiovascular disease. The risk of total (first plus subsequent) non-elective hospitalisations was assessed with Lin-Wei-Ying-Yang model. Investigator-reported System Organ Class terms were used to classify cause-specific hospitalisations. The trial is registered with ClinicalTrials.gov, NCT01730534. Between April 25, 2013, and Sept 18, 2018, 17 160 people (6422 [37·4%] women, 10 738 [62·6%] men; mean age 63·9 years [SD 6·8]) were enrolled in the original trial, of whom 10186 (59·4%) had multiple risk factors for but did not have established atherosclerotic cardiovascular disease, and 6835 (39·8%) had both no evidence of atherosclerotic cardiovascular disease and low KDIGO risk. Over a median follow-up of 4·2 years (IQR 3·9-4·4), dapagliflozin was associated with a lower risk of first non-elective hospitalisation for any cause (2779 [32·4%] of 8582 people in the dapagliflozin group vs 3036 [35·4%] of 8578 people in the placebo group; hazard ratio [HR] 0·89 [95% CI 0·85-0·94]) and total (first plus subsequent) non-elective hospitalisations for any cause (risk ratio 0·92 [95% CI 0·86-0·97]). The association between dapagliflozin use and the risk of first non-elective hospitalisation for any cause was consistent in subgroups of participants with (HR 0·92 [95% CI 0·85-0·99] and without (0·87 [0·81-0·94]) atherosclerotic cardiovascular disease at baseline (p interaction=0·31). Compared with the placebo group, the dapagliflozin group had lower risk of first hospitalisations due to cardiac disorders (HR 0·91 [95% CI 0·84-1·00]), metabolism and nutrition disorders (0·73 [0·60-0·89]), renal and urinary disorders (0·61 [0·49-0·77]), and due to any other cause excluding these three causes (0·90 [0·85-0·96]). Treatment with dapagliflozin was also associated with a lower risk of hospitalisations due to musculoskeletal and connective tissue disorders (HR 0·81 [0·67-0·99]) and infections and infastations (HR 0·86 [0·78-0·96]). Dapagliflozin reduced the risk of first and total non-elective hospitalisations for any cause in people with type 2 diabetes, regardless of the presence of atherosclerotic cardiovascular disease, including hospitalisations not directly attributed to cardiac, kidney, or metabolic causes. These findings might have implications on health-related quality of life for people with type 2 diabetes and on health-care costs attributable this condition. AstraZeneca.

Biomedical Advances in ABCA1 Transporter: From Bench to Bedside

ATP-binding cassette transporter A1 (ABCA1) has been identified as the molecular defect in Tangier disease. It is biochemically characterized by absence of high-density lipoprotein cholesterol (HDL-C) in the circulation, resulting in the accumulation of cholesterol in lymphoid tissues. Accumulation of cholesterol in arteries is an underlying cause of atherosclerosis, and HDL-C levels are inversely associated with the presence of atherosclerotic cardiovascular disease (ASCVD). ABCA1 increases HDL-C levels by driving the generation of new HDL particles in cells, and cellular cholesterol is removed in the process of HDL generation. Therefore, pharmacological strategies that promote the HDL biogenic process by increasing ABCA1 expression and activity have been intensively studied to reduce ASCVD. Many ABCA1-upregulating agents have been developed, and some have shown promising effects in pre-clinical studies, but no clinical trials have met success yet. ABCA1 has long been an attractive drug target, but the failed clinical trials have indicated the difficulty of therapeutic upregulation of ABCA1, as well as driving us to: improve our understanding of the ABCA1 regulatory system; to develop more specific and sophisticated strategies to upregulate ABCA1 expression; and to search for novel druggable targets in the ABCA1-dependent HDL biogenic process. In this review, we discuss the beginning, recent advances, challenges and future directions in ABCA1 research aimed at developing ABCA1-directed therapies for ASCVD.

Association between Achilles Tendon Softness and Atherosclerotic Cardiovascular Disease in Patients with Familial Hypercholesterolemia.

Achilles tendon (AT) xanthomas are a specific physical finding of familial hypercholesterolemia (FH) and AT thickness has been used for its diagnosis and evaluation of its severity. Recently, we reported that the AT of FH patients was softer than that of non-FH patients and the combined use of a cut-off value for AT softness with that for AT thickness improved diagnostic accuracy. However, an association between AT softness and severity of atherosclerosis has not been reported. Accordingly, the present study aimed to investigate whether AT softness was associated with carotid atherosclerosis and presence of atherosclerotic cardiovascular disease (ASCVD) in FH. The AT of 176 genetically diagnosed FH patients and 98 non-FH patients was examined to measure AT thickness and the elasticity index (EI) as an indicator for assessing AT softness using ultrasonography. Increased age was associated with AT softness, and overweight was negatively related to AT softness. There were significant inverse correlations between EI and maximum and mean intima-media thickness (IMT) within the common carotid artery only among FH patients. In multiple linear regression analysis, although the relationship between EI and mean IMT was attenuated, the association between EI and maximum IMT remained robust. In logistic regression analysis adjusted for age, sex and traditional cardiovascular risk factors (smoking history, presence of hypertension, presence of diabetes mellitus, overweight, LDL-cholesterol, HDL-cholesterol, and Log triglycerides), EI was associated with presence of ASCVD (Odds ratio per 1-SD increase, 0.37; 95% CI, 0.15 - 0.86; P=0.0252). The degree of lipid deposition in the AT of FH patients could be assessed by its thickness as well as its softness. AT softness is not only useful in diagnosing FH but is also associated with the severity of carotid atherosclerosis and presence of ASCVD. In addition, these findings suggest that AT softness would be helpful in risk assessment for FH patients.

Lipoprotein(a) testing in clinical practice: real-life data from a large health-care provider

Abstract Background Evidence support a causal role of lipoprotein(a) [Lp(a)] in the development of atherosclerotic cardiovascular disease (ASCVD). Novel treatment options are emerging and recent guidelines recommend screening Lp(a) levels at least once during lifetime. However, significant variance exists regarding the incorporation of Lp(a) into patient care. Purpose To investigate patterns of Lp(a) measurement in a large health maintenance organization (HMO) and describe clinical characteristics associated with elevated Lp(a) levels. Methods Retrospective analysis of all Lp(a) laboratory tests performed between January 2015 and December 2021 in a single HMO providing health care for approximately 4.6 million insured members. Results Overall, 4,539 individuals were tested for Lp(a). Analysis was limited to the adult population (n=3900). Number of persons tested yearly increased progressively from 89 in the year 2015 to 1523 in 2021. Mean age was 55±15 years (39% females), 15% had family history of coronary disease, 40% ischemic heart disease, 7% prior stroke and 9% peripheral artery disease (PAD). Baseline low-density lipoprotein cholesterol (LDL-C) &amp;gt;190 mg/dl was evident in 21% of patients. Lp(a) level &amp;gt;125 nmol/l (∼50 mg/dl) was noted in 21.5%. In a multivariable logistic regression model, prior myocardial infarction (odds ratio 1.38, 95% confidence interval 1.16–1.64), PAD (1.29, 1–1.68), peak LDL-C&amp;gt;190 mg/dl (1.35, 1.12–1.62) and use of statins (1.54, 1.28–1.85), were independently associated with elevated Lp(a) levels &amp;gt;125 nmol/l, whereas an inverse association was seen with obesity (0.74, 0.62–0.88). Of the patients with elevated Lp(a), 72.4% were treated with statin and/or ezetimibe and 1.9% with PCSK9 inhibitors. Conclusions The reporting of Lp(a) levels is increasing, though it is still measured in a small portion of the population. Presence of ASCVD and severe hyperlipidemia may identify patients that should be considered for screening for increased Lp(a) levels. The use of PCSK9 inhibitors in those with elevated Lp(a) is yet considerably low. Funding Acknowledgement Type of funding sources: None.

Higher oral porphyromonas gingivalis abundance is associated with the presence of atherosclerotic cardiovascular disease in high-risk patients and in patients with Heterozygous Familial Hypercholesterolemia

Background and Aims : Low-grade chronic inflammation, promoted by dysbiosis of gut and oral microbiota, may contribute to individual susceptibility to ASCVD. High oral Porphyromonas gingivalis (PG) and lower Fusobacterium nucleatum (FN) concentrations have been associated with clinical and experimental atherosclerosis. We assessed oral PG and FN abundance in very high-risk patients with previous ASCVD and with or without heterozygous FH and in healthy control subjects.

Risk of all-cause mortality according to the European Society of Cardiology risk categories in individuals with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

AimsThe 2019 and 2021 European Society of Cardiology (ESC) classifications stratified patients with type 2 diabetes into three categories according to the 10-year risk of death from atherosclerotic cardiovascular disease (ASCVD). The very high-risk category included individuals with established ASCVD, target organ damage (TOD), and/or, in the 2019 classification only, ≥ 3 additional ASCVD risk factors. We assessed risk of all-cause mortality according to the two ESC classifications in the Renal Insufficiency And Cardiovascular Events cohort.MethodsParticipants (n = 15,773) were stratified based on the presence of ASCVD, TOD, and ASCVD risk factors at baseline (2006–2008). Vital status was retrieved in 2015.ResultsLess than 1% of participants fell in the moderate-risk category. According to the 2019 classification, ~ 1/3 fell in the high-risk and ~ 2/3 in the very high-risk category, whereas the opposite occurred with the 2021 classification. Mortality risk increased across categories according to both classifications. Among very high-risk patients, mortality was much lower in those with ≥ 3 additional ASCVD risk factors and almost equal in those with TOD and ASCVD ± TOD, using the 2019 classification, whereas it was much higher in those with ASCVD + TOD and, to a lesser extent, TOD only than in those with ASCVD only, using the 2021 classification.ConclusionsThe negligible number of moderate-risk patients suggests that these classifications might overestimate risk of ASCVD death. Downgrading patients with ≥ 3 additional ASCVD risk factors to the high-risk category is consistent with mortality data. Risk of death is very high in the presence of TOD irrespective of established ASCVD.Trial registration: ClinicalTrials.gov, NCT00715481.

Glucose-lowering drug use, glycemic outcomes, and severe hypoglycemia: 18-Year trends in 0·9 million adults with Diabetes in Hong Kong (2002–2019)

SummaryBackgroundImprovements in glycemic outcomes have stalled since 2010 in several international surveys. We previously reported improvements in glycemic control in 2007-2014 in Hong Kong coinciding with primary care reforms, use of dipeptidyl-peptidase 4 inhibitors (DPP-4is) and metformin. The aim of this study was to estimate more recent trends in drug use and glycemic outcomes following introduction of newer classes of glucose-lowering drugs (GLDs).MethodsUsing population-based data from the Hong Kong Diabetes Surveillance Database, we explored age-specific trends in proportion of patients reaching glycemic targets and incidence rates of severe hypoglycemia (SH) in 963,612 adults with diabetes in 2002-2019. We further assessed patterns of GLDs utilisation by presence of atherosclerotic-cardiovascular disease (ASCVD), heart failure, and estimated-glomerular filtration rate (eGFR).FindingsFollowing rapid decline in HbA1c from 7·7% to 7·2% in 2005-2014 (annual percentage change [APC]= -0·8, 95% CI:-1·0,-0·6), standardized mean HbA1c plateaued since 2014 (HbA1c 7·2% in 2019, APC=0·0, 95% CI:-0·2, 0·2). The incidence rates of SH declined from 3·4 to 0·7 events per 100-person years, but improvements levelled off since 2014. Use of metformin steadily increased (41·1 to 58·7%), sulfonylureas decreased (52·2 to 31·1%) while insulin remained static in 2002-2019. Adoption of DPP-4is slowed following initial rapid uptake in 2007-2011. DPP-4is remained the most widely prescribed newer GLD in all ages (14·3% in 2019). Use of glucagon-like-peptide 1 receptor agonists (GLP1-RAs) and sodium glucose co-transporter-2 inhibitors (SGLT2is) increased rapidly in 2015-2019 with 0·5% and 6% of users respectively in 2019.InterpretationFollowing rapid improvement in 2007-2014, glycemic control and SH rates had plateaued despite changing patterns of newer GLDs use in Hong Kong.FundingDr. Aimin Yang was supported by a CUHK Impact Research Fellowship Scheme.

Real-World Prescription Patterns and Barriers Related to the Use of Sodium-Glucose Cotransporter 2 Inhibitors among Korean Patients with Type 2 Diabetes Mellitus and Cardiovascular Disease.

BackgroundTo evaluate prescription trends and clinical factors of the sodium-glucose cotransporter 2 inhibitors (SGLT2i) use according to the presence of atherosclerotic cardiovascular disease (ASCVD) or heart failure (HF) in Korean patients with type 2 diabetes mellitus (T2DM).MethodsPrescription patterns of SGLT2i use between 2015 and 2019 were determined using the Korean National Health Insurance Service database of claims.ResultsOf all patients with T2DM (n=4,736,493), the annual prescription rate of SGLT2i increased every year in patients with ASCVD (from 2.2% to 10.7%) or HF (from 2.0% to 11.1%). After the first hospitalization for ASCVD (n=518,572), 13.7% (n=71,259) of patients initiated SGLT2i with a median of 10.6 months. After hospitalization for HF (n=372,853), 11.2% (n=41,717) of patients initiated SGLT2i after a median of 8.8 months. In multivariate regression for hospitalization, older age (per 10 years, odds ratio [OR], 0.57; 95% confidence interval [CI], 0.56 to 0.57), lower household income (OR, 0.93; 95% CI, 0.92 to 0.95), rural residents (OR, 0.95; 95% CI, 0.93 to 0.97), and dipeptidyl peptidase-4 inhibitor (DPP-4i) users (OR, 0.82; 95% CI, 0.81 to 0.84) were associated with lesser initiation of SGLT2i in ASCVD. Additionally, female gender (OR, 0.97; 95% CI, 0.95 to 0.99) was associated with lesser initiation of SGLT2i in HF.ConclusionThe prescription rate of SGLT2i increased gradually up to 2019 but was suboptimal in patients with ASCVD or HF. After the first hospitalization for ASCVD or HF, older age, female gender, low household income, rural residents, and DPP-4i users were less likely to initiate SGLT2i.

934-P: Real-World Evidence of Glucose Lowering Drug Use, Glycemic Outcomes, and Severe Hypoglycemia in Hong Kong: Eighteen-Year Trends in 0.9 Million Adults with Diabetes

Introduction: Improvements in glycemic outcomes have stalled since 20in some international surveys. We examined the latest trends in drug use and glycemic outcomes following recent introduction of newer classes of glucose lowering drugs (GLDs) in a territory-wide analysis. Methods: Using data from the Hong Kong Diabetes Surveillance Database, we estimated age-specific trends in the proportion of patients reaching different glycemic targets, and rates of severe hypoglycemia (SH) in 963,612 patients between 2002-2019. We assessed patterns of GLDs use by age, sex, presence of atherosclerotic cardiovascular disease (ASCVD) and estimated glomerular filtration rate (eGFR) . Results: HbA1c improved most markedly between 2007-2014 but plateaued since 2014, with 53.1% patients achieving HbA1c &amp;lt;7% in 2019. The 20-44 age group had the highest proportion with HbA1c ≥9% (22.1% in 2002 and 16.8% in 2019) compared with the ≥75 age-group (14.9% in 2002 and 5.5% in 2019) . SH rates declined between 2002-20 and further in 2010-2014. Between 2002-2019, metformin use increased steadily from 41.1% to 58.7%, sulfonylurea use decreased from 52.2% to 31.1% while insulin use remained static. Use of dipeptidyl-peptidase 4 inhibitors (DPP4i) experienced rapid growth between 2007-20equally in all age groups, with a slower rise between 2011-2019. DPP4i remains the most widely prescribed newer oral GLDs (14.3%) compared with sodium glucose co-transporter 2 inhibitors (SGLT2is) (4.2%) and glucagon like peptide-1 receptor agonists (GLP1-RAs) (0.6%) in 2019. Compared with over 75s, higher proportions of the 20-44 age-group were treated with SGLT2is (6.4% versus 1.7%) and GLP-1RAs (1.5% versus 0.1%) and thiazolidinediones (8.1% versus 3.4%) in 2019, irrespective of ASCVD status. Conclusions: Following rapid improvement in 2007-2014, glycemic control and SH rates had plateaued despite the increasing use of SGLT2is and GLP-1RA in Hong Kong. Disclosure A.Yang: None. J.C.Chan: Board Member; Asia Diabetes Foundation, Consultant; Bayer AG, Boehringer Ingelheim International GmbH, Celltrion, Merck Sharp &amp; Dohme Corp., Roche Diabetes Care, Viatris Inc., Research Support; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Hua Medicine, Servier Laboratories, Stock/Shareholder; GemVCare Ltd. E.Chow: Research Support; Hua Medicine, Medtronic, Powder Pharmaceuticals Inc., Speaker's Bureau; Novartis AG, Sanofi. H.Wu: None. E.S.H.Lau: None. X.Zhang: None. M.Shi: None. B.Fan: None. A.P.Kong: Advisory Panel; Abbott, Kyowa Kirin Co., Ltd., Other Relationship; AstraZeneca, Novo Nordisk, Research Support; Boehringer Ingelheim, Speaker's Bureau; AstraZeneca, Bayer, Eli Lilly and Company, Sanofi, Stock/Shareholder; Aptorum Group Limited. A.Luk: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc.

Association of Statin and Antiplatelet Use with Survival in Patients with AAA with and without Concomitant Atherosclerotic Occlusive Disease

Statin therapy has been associated with improved clinical outcomes in patients undergoing treatment for vascular disease. Current guidelines do not address statin therapy in isolated abdominal aortic aneurysm (AAA) in the absence of other atherosclerotic cardiovascular disease (ASCVD). This study aims to elucidate effects of statin therapy, either as monotherapy or combined with antiplatelet agents, on the long-term mortality of patients with and without ASCVD who undergo elective AAA repair. A retrospective review was performed on all AAA patients treated electively with endovascular (EVAR) and open aortic repair (OAR) in the Society for Vascular Surgery Vascular Quality Initiative from 2003-2020. Long-term mortality was evaluated based on the presence of statin and antiplatelet medication use at discharge stratified by those with and without a history of ASCVD. Unadjusted survival was estimated by Kaplan Meier methodology. Cox proportional hazards modeling was used to determine mortality risk after adjusting for key factors. A total of 47,012 AAA repairs were selected for analysis: 80.7% EVAR (N=40,153) and 19.3% OAR (N=6,859). EVAR patients on combined statin/antiplatelet (AP) therapy had significantly better survival irrespective of whether they had known ASCVD. In the presence of ASCVD, EVAR patients on statin alone had improved survival compared to those not on a statin (10.9 ± 0.5 vs. 10.5 ± 0.4 years, Log Rank < 0.001), with survival being even greater among those receiving combined statin/AP therapy (12.2 ± 0.2 vs. 10.5 ± 0.4 years, Log Rank < 0.001). In the absence of ASCVD, EVAR patients on statin alone also had better mean survival compared to patients not on a statin (8.7 ± 0.5 vs. 8.4 ± 0.4 years, Log Rank<.001), with higher survival among statin/AP therapy patients (9.4 ± 0.2 years vs. 8.7 ± 0.5 years, Log Rank < 0.001). Comparison of adjusted survival via Cox multivariable regression demonstrated a protective effect of statins (HR=0.737, P=0.04, vs. no medication) and combined statin/AP therapy (HR=0.659, P=0.001, vs no medication) in patients with ASCVD history. A similar protective effect (statin: HR 0.826, P=0.05. Combination statin/AP: HR 0.726, P < 0.001, vs. no medication) was identified in patients without ASCVD history. Within the OAR cohort, statin therapy was not associated with improved survival among patients without ASCVD; however, combined statin/AP therapy had a protective effect for patients with a known ASCVD diagnosis. Based on KM analysis, OAR patients with ASCVD on combined statin/AP therapy had significantly higher mean survival compared to isolated statin therapy (12.7 ± 0.2 vs. 10.3 ± 0.65 years) and no medical therapy (10.5 ± 0.8 years, Log Rank < 0.001). In KM analysis, OAR patients without known ASCVD indications (N=3591) had no significant survival differences based on the presence of combined statin/AP therapy (8.4 ± .07 vs. 8.5 ± .11 years, Log Rank=0 638). Isolated statin therapy and combined statin/AP therapy showed significant survival benefit in all EVAR and OAR patients with ASCVD indications, as well as among EVAR patients without a known ASCVD diagnosis. OAR patients without ASCVD did not have a significant survival benefit from statin therapy, but low numbers in this group may have confounded the findings. Combined statin/AP therapy appears to have significant post-repair survival benefits even in isolated AAA without ASCVD, as demonstrated in post-EVAR patients in this study. Expansion of statin use recommendations within aneurysm treatment guidelines may be warranted.

58 Effects of sodium–glucose co-transporter 2 (SGLT2) inhibitors on major cardiovascular events in Type 2 diabetic patients: a meta-analysis of randomized controlled trials

Abstract Aims Sodium–glucose co-transporter-2 inhibitors (SGLT2i) reduce cardiovascular (CV) events in diabetic patients, with a consistent effect on heart failure (HF) related outcomes. However, the effects on ischaemic CV events appear less certain, in particular in patients with history of HF. The aim of this meta-analysis is to investigate CV benefit of SGLT2i and to assess the effects in patients with and without established atherosclerotic cardiovascular disease (ASCVD), with and without HF, and with estimated glomerular filtration rate &amp;lt; or ≥ 60 mL/min. Methods We searched PubMed, Embase, Cochrane, ISI Web of Science, SCOPUS, and clinicaltrial.gov databases. We performed a systematic review and meta-analysis of randomized, placebo-controlled, cardiovascular outcome trials (CVOT) of SGLT2i in diabetic patients, assessing the effects of SGLT2i on 3-point MACE [CV death, non-fatal myocardial infarction (MI), non-fatal stroke] and composite of HF hospitalization or CV death. Results Of 205 articles, 7 CVOTs were included in the meta-analysis. Compared to placebo, SGLT2i significantly reduced by 10% the risk of 3-point MACE (HR 0.90; P = 0.025) (Figure panel A) and the risk of CV death or HF hospitalization by 24% (HR 0.76; P &amp;lt; 0.001) (Figure panel B). SGLT2i significantly reduced HF hospitalization by 30% (HR 0.70; P &amp;lt; 0.001), with consistent effects in all subgroups analysed, CV death by 17% (HR 0.83; P = 0.035) and all-cause mortality by 18% (HR 0.82; P = 0.024). No significant effects were observed on MI and stroke. Conclusions SGLT2i significantly reduce CV outcome in diabetic patients. SGLT2i remarkably and consistently reduce HF hospitalization, in patients with and without HF at baseline and independently on the presence of ASCVD.

Moving from the stratification of primary and secondary prevention of cardiovascular risk in diabetes towards a continuum of risk: need for a new paradigm.

Traditionally, patients with type 2 diabetes have been stratified according to cardiovascular (CV) risk to requiring either primary prevention (those without atherosclerotic CV disease) or secondary prevention (those with atherosclerotic CV disease in any of the vascular beds). However, this classification is misleading and arbitrary, as not all patients requiring secondary prevention have the same risk for such events, which also holds true for those requiring primary prevention (i.e. CV risk ranges from moderate to very high). In addition, in some cases, the definitions of primary and secondary prevention do not rely on symptoms but rather on the results of supplementary tests. Furthermore, patients with type 2 diabetes may also develop heart failure or chronic kidney disease. Importantly, reducing CV risk stratification to primary and secondary prevention does not provide a comprehensive approach for the management of patients with diabetes, leading to an underuse of drugs with proven CV benefit regardless of the presence of atherosclerotic CV disease. Therefore, patients with diabetes should be treated according to their CV risk considered as a continuum and not simply as falling within primary or secondary prevention.

Contemporary National Patterns of Eligibility and Use of Novel Cardioprotective Antihyperglycemic Agents in Type 2 Diabetes Mellitus.

BackgroundSGLT‐2 (sodium glucose transporter‐2) inhibitors and GLP‐1RAs (glucagon‐like peptide‐1 receptor agonists) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes mellitus at high risk for these complications, and have been recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice.Methods and ResultsIn the National Health and Nutrition Examination Survey for 2017 to 2018, we defined compelling indications for SGLT‐2 inhibitors by the presence of atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, and for GLP‐1RAs by the presence of established or high‐risk atherosclerotic cardiovascular disease, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology and American Diabetes Association. We then evaluated use of these medications among patients with physician‐diagnosed type 2 diabetes mellitus. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes mellitus, representing 10.6% (95% CI, 9.7%–11.6%) of the US population or 33.2 million adults nationally. Of these, 52.6% (95% CI, 47.7%–57.5%) had an indication for SGLT‐2 inhibitors, 32.8% (95% CI, 28.8%–37.2%) for GLP‐1RAs, and 26.6% (95% CI, 22.2%–31.7%) for both medications. During 2017 to 2018, 4.5% (95% CI, 2.4%–8.2%) were treated with SGLT‐2 inhibitors and 1.5% (95% CI, 0.7%–3.2%) with GLP‐1RAs. Atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease were not independently associated with SGLT‐2 inhibitor or GLP‐1RA use in patients with diabetes mellitus.ConclusionsDespite a large number of patients being eligible for guideline‐recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT‐2 inhibitors and GLP‐1RAs, limiting their public health benefits.

CONTEMPORARY NATIONAL PATTERNS OF ELIGIBILITY AND UTILIZATION OF NOVEL CARDIOPROTECTIVE ANTI-HYPERGLYCEMIC AGENTS IN TYPE 2 DIABETES

Background Sodium glucose transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes at high risk for these complications, and have recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice. Methods and Results In the National Health and Nutrition Examination Survey for 2017-2018, we defined compelling indications for SGLT-2 inhibitors by the presence of atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease (CKD), and for GLP-1RAs by the presence of established or high risk ASCVD, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology (ACC) and American Diabetes Association (ADA). We then evaluated utilization of these medications among patients with physician-diagnosed type 2 diabetes. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes, representing 10.6% (95% CI 9.7-11.6) of the US population or 33.2 million adults nationally. Of these, 52.6% (47.7-57.5) had an indication for SGLT-2 inhibitors, 32.8% (28.8-37.2) for GLP-1RAs, and 26.6% (22.2-31.7) for both medications. During 2017-2018, 4.5% (2.4-8.2) were treated with SGLT-2 inhibitors and 1.5% (0.7-3.2) with GLP-1RAs. ASCVD, heart failure, or CKD were not independently associated with SGLT-2 inhibitor or GLP-1RA use in patients with diabetes. Conclusions Despite a large number of patients being eligible for guideline recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT-2 inhibitors and GLP-1RAs, limiting their public health benefits.