Risk Factor For Atherosclerotic Cardiovascular Disease Research Articles

A Jordanian Multidisciplinary Consensus Statement on the Management of Dyslipidemia.

Atherosclerotic cardiovascular disease (ASCVD) is the primary contributor to global mortality rates, which significantly escalates healthcare expenditures. Risk factors for ASCVD (including dyslipidemia) frequently present in clusters rather than separately. Addressing these risk factors is crucial in the early initiation of a comprehensive management plan that involves both lifestyle modifications and pharmacotherapy to reduce the impact of ASCVD. A team of Jordanian professionals from various medical organizations and institutes took the initiative to create a set of guidelines for dyslipidemia screening and therapy. A detailed, comprehensive literature review was undertaken utilizing several databases and keywords. This consensus statement provides recommendations for dyslipidemia management in Jordanians on several issues including cardiovascular risk estimation, screening eligibility, risk categories, treatment goals, lifestyle changes, and statin and non-statin therapies. It is recommended that all Jordanian individuals aged 20 years old or older undergo lipid profile testing. This should be followed by determining the level of cardiovascular risk depending on the presence or absence of ASCVD and cardiovascular risk factors, eligibility for lipid-lowering therapy, and the target low-density cholesterol serum level to be achieved. In conclusion, prioritizing the management of dyslipidemia is of the utmost importance in improving public health and reducing the burden of cardiovascular diseases.

443-P: Two-Year Results from a Novel, Patient-Centered, Team-Based Intervention for Patients with Type 2 Diabetes at High Cardiovascular Risk

Background: Atherosclerotic cardiovascular disease (ASCVD) is a major cause of death in patients with type 2 diabetes (T2D). CINEMA is a novel, patient-centered, team-based intervention for patients with T2D/prediabetes with high risk for ASCVD. We present the outcomes from the first 2 years of the CINEMA program. Methods: Patients with T2D or prediabetes at high risk for CV events (established ASCVD, coronary artery calcium >100 AU, chronic heart failure, chronic kidney disease, and/or metabolic syndrome) were included. Linear mixed effects and generalized linear mixed models were used to assess changes in ASCVD risk factors and guideline-based medication prescriptions over time, respectively. Results: From May 2020 to September 2022, 426 patients were enrolled in CINEMA; 47% were women and 37% Black, with mean age 60 yrs, mean BMI 36kg/m2, and 48% with established ASCVD. 54% had ≥ 1 follow up visit with median follow up time of 3 months. There were significant reductions in risk factors including HbA1c (-12.1%), LDL-C (-14.2%), BP (-1.8%), and BMI (-2.2%) (P<0.001 for all). SGLT2 inhibitor and GLP-1 RA prescriptions increased from during follow up (20% to 56% and 17% to 66%, respectively). Conclusion: A multidisciplinary approach to treating patient with type 2 diabetes with the CINEMA program improves ASCVD risk factors and guideline-based medication adherence. Disclosure A.Arafah: None. I.Neeland: Consultant; Nestlé Health Science, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Bayer Inc. B.M.Bourges-sevenier: None. Z.Albar: None. C.Sullivan: None. S.G.Al-kindi: None. S.Rajagopalan: Advisory Panel; Novartis, Novo Nordisk, Speaker's Bureau; Novo Nordisk.

113-OR: The OPTIFAST (OP) Total and Partial Meal Replacement Program Improves Cardiometabolic Risk in Adults With Obesity—Secondary and Exploratory Analysis of the OPTIWIN Study

The effects of weight loss on atherosclerotic cardiovascular disease (ASCVD) risk factors using a partial or total meal replacement program (MRP) are not fully understood. We performed secondary and exploratory analyses of changes in blood pressure (BP), lipids, and global ASCVD risk in a randomized, controlled MRP trial using OP (n=135) compared with a low-calorie food-based (FB) dietary plan (n=138) that resulted in significant weight loss at week (W) 26 (reduction phase) and W52 (maintenance). Baseline characteristics were well balanced (mean [standard deviation] age OP/FB 47 [11]/47 [11] years, BMI 38.4 [5.5]/39.2 [6.2] kg/m2, females 86/79%, 10-year ASCVD risk <5% 87/74%, dysglycemia 52/50%). Changes in risk factors were estimated by a linear mixed model. At W26, systolic/diastolic BP were significantly reduced with OP vs FB (table), and a greater proportion achieved ≤ 130/80 mmHg (66.7% vs 53.6%, OR 2.11 [95% CI 1.10, 4.03], p=0.024). All lipid parameters significantly improved, as did the global ASCVD risk. A similar, but slightly attenuated pattern was observed at W52. In subgroup analysis by age (<40, 40-59, ≥ 60 years), SBP (</≥ 130 mmHg) and sex, greater treatment effects were generally seen with higher SBP and age, and in men. In people with obesity at low ASCVD risk, OP significantly improved CV risk factors and global ASCVD risk. Disclosure J.D.Ard: Advisory Panel; Novo Nordisk, Consultant; Eli Lilly and Company, Intuitive Surgical, Regeneron, Other Relationship; Optum Labs, Weight Watchers International, Research Support; Nestlé Health Science, Boehringer Ingelheim Inc., Epitomee, KVK Tech. I.Neeland: Consultant; Nestlé Health Science, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance, Bayer Inc. A.E.Rothberg: None. R.Chilton: None. D.De luis: None. A.H.Hawkinson: Employee; Nestlé Health Science. S.S.Cohen: Consultant; Nestlé Health Science. O.Johansen: Employee; Nestlé Health Science. Funding Nestlé Health Science

Lipoprotein(a) and coronary artery calcium in comparison with other lipid biomarkers: The multi-ethnic study of atherosclerosis

Coronary artery calcium (CAC) scoring is often used for atherosclerotic cardiovascular disease (ASCVD) risk stratification in individuals with elevated lipoprotein(a) [Lp(a)]. To evaluate associations between Lp(a) and baseline CAC (volume/density) and CAC progression compared to other lipid biomarkers. We utilized data from the Multi-Ethnic Study of Atherosclerosis (MESA), a cohort study of individuals without clinical ASCVD, excluding statin users. We evaluated the associations between Lp(a), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, total cholesterol, apolipoprotein B, and non-HDL-C with baseline CAC and annual CAC progression using multivariable ordinal regression with adjustment for ASCVD risk factors. Analyses were also stratified by median age. In 5,597 participants (2,726 at median 9.5-year follow-up), Lp(a) was not associated with baseline CAC volume or density and was modestly associated with volume progression (OR 1.11, 95% CI 1.03-1.21). However, other biomarkers were positively associated with baseline volume and volume progression (LDL-C: OR 1.26, 95% CI: 1.19-1.33 and OR 1.22, 95% CI: 1.15-1.30, respectively), except HDL-C which was inversely associated. LDL-C, total cholesterol and non-HDL-C were inversely associated with baseline density. In participants <62 years of age, Lp(a) was modestly associated with baseline CAC volume (OR 1.10, 95% CI: 1.00-1.20) and volume progression (OR 1.16 95% CI: 1.04-1.30). In contrast to other lipid biomarkers, Lp(a) was not associated with baseline CAC volume or density and was only modestly associated with volume progression. Our findings suggest that Lp(a) is not as robustly associated with CAC as other lipid biomarkers.

A Review of Progress on Targeting LDL Receptor-Dependent and -Independent Pathways for the Treatment of Hypercholesterolemia, a Major Risk Factor of ASCVD.

Since the discovery of the LDL receptor in 1973 by Brown and Goldstein as a causative protein in hypercholesterolemia, tremendous amounts of effort have gone into finding ways to manage high LDL cholesterol in familial hypercholesterolemic (HoFH and HeFH) individuals with loss-of-function mutations in the LDL receptor (LDLR) gene. Statins proved to be the first blockbuster drug, helping both HoFH and HeFH individuals by inhibiting the cholesterol synthesis pathway rate-limiting enzyme HMG-CoA reductase and inducing the LDL receptor. However, statins could not achieve the therapeutic goal of LDL. Other therapies targeting LDLR include PCSK9, which lowers LDLR by promoting LDLR degradation. Inducible degrader of LDLR (IDOL) also controls the LDLR protein, but an IDOL-based therapy is yet to be developed. Among the LDLR-independent pathways, such as angiopoietin-like 3 (ANGPTL3), apolipoprotein (apo) B, apoC-III and CETP, only ANGPTL3 offers the advantage of treating both HoFH and HeFH patients and showing relatively better preclinical and clinical efficacy in animal models and hypercholesterolemic individuals, respectively. While loss-of-LDLR-function mutations have been known for decades, gain-of-LDLR-function mutations have recently been identified in some individuals. The new information on gain of LDLR function, together with CRISPR-Cas9 genome/base editing technology to target LDLR and ANGPTL3, offers promise to HoFH and HeFH individuals who are at a higher risk of developing atherosclerotic cardiovascular disease (ASCVD).

Double-Trouble: Atherosclerotic Risk Factors and Congenital Heart Disease.

Youth with congenital heart disease (CHD) are uniquely vulnerable to genetic and acquired atherosclerotic cardiovascular disease (ASCVD) risk factors. With the increasingly successful management of CHD, it is important to prevent or optimally managed risk factors with the goal of improving outcomes and longevity. This review summarizes guidelines for the evaluation and management of obesity, dyslipidemia, and hypertension in youth (< 18years of age), focusing on the special vulnerabilities associated with the type of repair and the presence of residual disease in those who undergo cardiac surgery. Clinicians must focus on targeting these highly prevalent ASCVD risk factors to protect CHD survivors from preventable ASCVD morbidity and mortality by applying lifestyle, pharmacologic, or surgical therapies as needed. Future work should examine interventions to identify and treat ASCVD risk factors in CHD patients. Given the increased prevalence of ASCVD risk factors in youth and the morbidity and premature mortality associated with CHD, it is important for clinicians to assess global risk factors in these patients frequently, encourage adherence to lifestyle changes, and recommend pharmacotherapy and surgical interventions when clinically indicated. Future efforts should identify barriers and opportunities for improving risk factor assessment and timely intervention as a routine part of clinical care.

Statin use for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) in breast cancer (BC) patients (pts).

e24051 Background: CVD is the leading cause of non-cancer mortality for BC survivors. Clinical practice guidelines support the assessment and management of ASCVD risk factors among BC pts, including lipid-lowering therapy when indicated. We performed a single-institution, retrospective, longitudinal study of ASCVD risk factors and statin use for primary and secondary ASCVD prevention among BC pts. Methods: Pts diagnosed with BC from 2009-2015 were identified from the institutional cancer registry. Pts with non-metastatic BC or ductal carcinoma in situ and at least 2 years of follow up were included. Records were reviewed at 12-month intervals from BC diagnosis until last follow up or the study end date of 12/31/19. BC characteristics and treatment, prevalent and incident CV risk factors, CV diagnoses, CV medications, and CV events were manually abstracted and confirmed by a second reviewer. 10-year estimated ASCVD risk, based on non-laboratory predictors, was calculated for each pt. Chi-square tests were performed to assess the relationship between race/ethnicity, age category, and statin exposure. Results: 326 pts were included (median age at diagnosis 60.7 yrs; 67% White, 16% Asian (Chinese), 10% Black; 54% with stage I disease). At baseline, 53% had hypertension, 40% had hyperlipidemia, 37% were former or current smokers, 32% had a BMI ≥30, 7% had a history of ASCVD, and 5% had a family history of premature coronary artery disease. 52% received radiation therapy. 114 pts had radiation dosimetry available; 59 (18%) received a mean heart dose ≥1 Gy. Median follow up was 6.5 yrs. At the time of BC diagnosis, 64% of pts had an established indication for lipid-lowering therapy: history of ASCVD, diabetes, or estimated 10-year ASCVD risk ≥7.5% (Table). Of these pts with an indication for statin, 35% were prescribed a statin at baseline and 57% were prescribed a statin at any time during the study period. No association between baseline statin exposure and pt age category (X2 = 3.75, p = 0.290) or race/ethnicity (X2 = 2.64, p = 0.562) was observed. Among 11% of pts with ASCVD at any time, 83% were prescribed a statin but only 40% received a guideline-recommended high-intensity statin. Conclusions: A majority of pts in our study were candidates for statin therapy for primary or secondary ASCVD prevention at the time of BC diagnosis. 43% were never prescribed a statin, predominantly pts whose indication was primary prevention. There is opportunity for improvement in ASCVD prevention during BC treatment and follow up. [Table: see text]

Impact of Statin Therapy in Heart Failure Patients: Results of a Large Real-World Experience

BackgroundThe use of statins in patients with heart failure (HF) is controversial. In patients without HF, statins reduce atherosclerotic cardiovascular disease (ASCVD) risk, including HF-related events. However, in some large studies, no benefit was seen in statin-treated HF patients. ObjectivesThe purpose of this study was to determine the impact of statin therapy in HF with reduced ejection fraction (HFrEF). MethodsIntermountain Healthcare medical records identified patients with a HF diagnosis and an ejection fraction of ≤40%. Patients prescribed and not prescribed a statin were compared for major adverse cardiovascular events (MACE) (death, myocardial infarction, stroke) (median of 4.5 years follow-up). Statin use was defined as use at or after a HF diagnosis but at least 60 days before MACE or end of follow-up. Cox proportional hazards regression was used to determine the relationship between statin use and outcomes. ResultsA total of 15,010 patients (n = 9,641 [64%] on statins) were studied. Statin use was associated with more frequent ASCVD risk factors yet a lower risk of MACE risk (adjusted HR: 0.53; 95% CI: 0.51-0.56; P < 0.0001). Benefit was similar for primary and secondary prevention patients and for prior and new statin prescriptions. Using time-varying hazard ratio analysis, the longer the patient was on a statin, the greater the reduction in risk of MACE (P < 0.0001). ConclusionsThese results suggest a potential benefit of selective statin use in the real-world management of HFrEF patients with ASCVD or at high ASCVD risk.

HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy.

Epidemiologic studies detected an inverse relationship between HDL (high-density lipoprotein) cholesterol (HDL-C) levels and atherosclerotic cardiovascular disease (ASCVD), identifying HDL-C as a major risk factor for ASCVD and suggesting atheroprotective functions of HDL. However, the role of HDL-C as a mediator of risk for ASCVD has been called into question by the failure of HDL-C-raising drugs to reduce cardiovascular events in clinical trials. Progress in understanding the heterogeneous nature of HDL particles in terms of their protein, lipid, and small RNA composition has contributed to the realization that HDL-C levels do not necessarily reflect HDL function. The most examined atheroprotective function of HDL is reverse cholesterol transport, whereby HDL removes cholesterol from plaque macrophage foam cells and delivers it to the liver for processing and excretion into bile. Indeed, in several studies, HDL has shown inverse associations between HDL cholesterol efflux capacity and ASCVD in humans. Inflammation plays a key role in the pathogenesis of atherosclerosis and vulnerable plaque formation, and a fundamental function of HDL is suppression of inflammatory signaling in macrophages and other cells. Oxidation is also a critical process to ASCVD in promoting atherogenic oxidative modifications of LDL (low-density lipoprotein) and cellular inflammation. HDL and its proteins including apoAI (apolipoprotein AI) and PON1 (paraoxonase 1) prevent cellular oxidative stress and LDL modifications. Importantly, HDL in humans with ASCVD is oxidatively modified rendering HDL dysfunctional and proinflammatory. Modification of HDL with reactive carbonyl species, such as malondialdehyde and isolevuglandins, dramatically impairs the antiatherogenic functions of HDL. Importantly, treatment of murine models of atherosclerosis with scavengers of reactive dicarbonyls improves HDL function and reduces systemic inflammation, atherosclerosis development, and features of plaque instability. Here, we discuss the HDL antiatherogenic functions in relation to oxidative modifications and the potential of reactive dicarbonyl scavengers as a therapeutic approach for ASCVD.

Determinants of Incident Atherosclerotic Cardiovascular Disease Events and All-Cause Mortality in Patients With Age-Related Macular Degeneration: Prospective Cohort Study of UK Biobank.

Major risk factors of atherosclerotic cardiovascular disease (ASCVD) and mortality have been well-established in the general population. Our study is aimed at assessing longitudinal relationships between ASCVD risk factors and incident ASCVD events or all-cause mortality in patients with age-related macular degeneration (AMD). Multivariable-adjusted Cox proportional hazards models were used to study the association between cardiovascular risk factors with adjudicated incident ASCVD events and all-cause mortality outcomes followed until 2021. A restricted cubic spline approach was utilized to assess nonlinear associations between potential cardiovascular risk factors and ASCVD or mortality. We identified 3508 eligible patients [mean (SD) age = 61.45 (6.43) years; 37.76% males] with AMD at baseline. During a median follow-up year of 12, there were 110 cases of ASCVD events and 186 cases of all-cause mortality. After multivariable adjustment, each 10 U/L increase of serum gamma-glutamyl transferase level was linearly associated with incident ASCVD [hazard ratio (HR) = 1.03, 95% CI = 1.00-1.07, Pnonlinear = 0.85)] in AMD. A history of chronic kidney disease (HR = 1.94, 95% CI = 1.09-3.46) and lower vitamin D [HR = 0.98, 95% CI = 0.97-0.99, per nanomoles per liter (nmol/L)] were significantly associated with all-cause mortality in patients with AMD, with the association between vitamin D and all-cause mortality presenting a U shape (Pnonlinear = 0.02). In contrast, risk factors significantly associated with ASCVD and all-cause mortality in healthy controls differed from patients with AMD. Our findings demonstrate risk factors associated with ASCVD events and all-cause mortality among individuals with AMD differed from healthy controls and suggest the long-term management of risk factors in patients with AMD.

Adjusting background insulin therapy in type 2 diabetes when initiating a glucagon-like peptide 1 receptor agonist: A case series

Introduction: Guidelines recommend preferential use of antihyperglycemic medications with proven cardiovascular benefit for the treatment of patients with type 2 diabetes with established atherosclerotic cardiovascular disease (ASCVD), high risk factors for ASCVD, kidney disease, or heart failure. However, current guidelines offer little to no practical recommendations for adding these therapies to a patient’s current regimen while avoiding hyperglycemia or hypoglycemia. Nevertheless, considering background therapy in a proactive effort to avoid undesirable glycemic excursions when initiating any new antidiabetic medication remains paramount. Case Series: A six-patient case series investigates adjustments to background therapies and glycemic outcomes surrounding the initiation and titration of long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to shed light on practical methods to manage patient care during this tenuous phase. Overarching findings regarding background therapy adjustments to avoid hypoglycemia when initiating a GLP-1 RA include: (1) safe continuation of metformin regardless of baseline A1C or concurrent glycemic background therapy; (2) continuation of background therapy when the baseline A1C is above 9%; (3) consideration of a proactive 15–20% basal insulin dose reduction when the baseline A1C is below 7.5%; (4) proactive bolus insulin dose reduction by 25% or complete discontinuation at the time of GLP-1 RA initiation. Conclusion: No dose adjustments are necessary when A1C &gt; 9%, and possibly &gt;8%. When A1C is &lt;7.5% and possibly &lt;8%, discontinue or reduce bolus insulin by 25% and/or reduce basal insulin by 15–25%. Adjust background therapy using shared-decision making while considering fasting blood glucose, A1C, hypoglycemia risk, and chosen GLP-1 RA therapy.

Adjusting background insulin therapy in type 2 diabetes when initiating a glucagon-like peptide 1 receptor agonist: A case series

Introduction: Guidelines recommend preferential use of antihyperglycemic medications with proven cardiovascular benefit for the treatment of patients with type 2 diabetes with established atherosclerotic cardiovascular disease (ASCVD), high risk factors for ASCVD, kidney disease, or heart failure. However, current guidelines offer little to no practical recommendations for adding these therapies to a patient’s current regimen while avoiding hyperglycemia or hypoglycemia. Nevertheless, considering background therapy in a proactive effort to avoid undesirable glycemic excursions when initiating any new antidiabetic medication remains paramount. Case Series: A six-patient case series investigates adjustments to background therapies and glycemic outcomes surrounding the initiation and titration of long-acting glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to shed light on practical methods to manage patient care during this tenuous phase. Overarching findings regarding background therapy adjustments to avoid hypoglycemia when initiating a GLP-1 RA include: (1) safe continuation of metformin regardless of baseline A1C or concurrent glycemic background therapy; (2) continuation of background therapy when the baseline A1C is above 9%; (3) consideration of a proactive 15–20% basal insulin dose reduction when the baseline A1C is below 7.5%; (4) proactive bolus insulin dose reduction by 25% or complete discontinuation at the time of GLP-1 RA initiation. Conclusion: No dose adjustments are necessary when A1C &gt; 9%, and possibly &gt;8%. When A1C is &lt;7.5% and possibly &lt;8%, discontinue or reduce bolus insulin by 25% and/or reduce basal insulin by 15–25%. Adjust background therapy using shared-decision making while considering fasting blood glucose, A1C, hypoglycemia risk, and chosen GLP-1 RA therapy.

Cardiovascular risk profiles in patients with inflammatory bowel disease differ from matched controls from the general population.

Inflammatory bowel disease (IBD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). We compared cardiovascular disease (CVD) risk factors and 10-year risk in IBD patients to the general population. In this cross-sectional study, consecutive IBD patients ≥45 years were included. History of ASCVD and CVD risk factors (smoking, hypertension, overweight, hypercholesterolaemia, diabetes, and metabolic syndrome) were assessed. The Systematic COronary Risk Evaluation (SCORE2) algorithm was used to estimate 10-year CVD risk. One to four age/sex-matched controls were derived from the prospective population-based Rotterdam Study cohort. In total, 235 IBD patients were included {56% women, median age 59 years [interquartile range (IQR) 51-66]} and matched to 829 controls [56% women, median age 61 years (IQR 56-67)]. Inflammatory bowel disease patients experienced ASCVD events more often compared with matched controls [odds ratio (OR) 2.01, 95% confidence interval (CI) 1.23-3.27], specifically heart failure (OR 2.02, 95% CI 1.02-4.01) and coronary heart disease (OR 2.01, 95% CI 1.7-3.13). Inflammatory bowel disease patients showed lower odds of overweight (OR 0.48, 95% CI 0.35-0.66) and hypercholesterolaemia (OR 0.45, 95% CI 0.31-0.65) and higher odds of hypertension (OR 1.67, 95% CI 1.19-2.32), as well as higher waist circumference (+4 cm, P = 0.006) and triglyceride levels (+0.6 mmol/L, P < 0.001) as compared with controls. Mean 10-year CVD risk was 4.0% [standard deviation (SD) ±2.6] in 135 IBD patients vs. 6.0% (SD ±1.6) in 506 controls. The increased CVD risk in IBD is discrepant with the 10-year CVD risk estimate. Systematic COronary Risk Evaluation may underestimate CVD risk in IBD patients due to differing CVD risk profiles compared with the general population, including a lower prevalence of hypercholesterolaemia and overweight and a higher prevalence of hypertension, abdominal obesity, and hypertriglyceridaemia.

Heightened risks of cardiovascular disease in South Asian populations: causes and consequences

ABSTRACT Introduction South Asian individuals comprise almost a quarter of the world’s population and have an excess risk of atherosclerotic cardiovascular disease (ASCVD) compared to other ethnicities. In part, this can be explained by higher prevalence, earlier onset, and suboptimal control of traditional cardiovascular risk factors, such as insulin resistance, metabolic syndrome, and dyslipidaemia. However, there remains a significant residual excess risk associated with South Asian ethnicity after controlling for traditional risk factors. Areas covered In this review, we describe the epidemiology of ASCVD in both native and diaspora South Asian populations. We explore how traditional cardiovascular risk factors, novel cardiovascular risk factors, and social determinants of health may contribute to the excess ASCVD risk seen in South Asian populations. Expert opinion There should be increased awareness of the relative importance of South Asian ethnicity and related social determinants of health, as risk factors for ASCVD. Systematic screening processes should be tailored to this population, and modifiable risk factors should be treated aggressively. Further research is required to quantify determinants of the excess ASCVD risk seen in South Asian populations and to develop targeted interventions to address these factors.

Lipoprotein(a) levels in children with homozygous familial hypercholesterolaemia: A cross-sectional study

Homozygous familial hypercholesterolaemia (HoFH) is a life-threatening disorder characterized by extremely elevated low-density lipoprotein cholesterol (LDL-C) levels. Untreated, severe atherosclerotic cardiovascular disease (ASCVD), including aortic valve stenosis (AVS), may already occur in childhood. Another important genetic risk factor for ASCVD and AVS is elevated lipoprotein(a) [Lp(a)], which is highly prevalent in the general paediatric population. However, data on Lp(a) in children with HoFH are scarce. Therefore, we performed a cross-sectional study to evaluate Lp(a) levels in children with HoFH and compared them to children with heterozygous FH (HeFH) and unaffected children. Adjusted least-square mean (95% CI) Lp(a) levels in HoFH (n=29), HeFH (n=101) and unaffected children (n=102) were 18.7 (12.0-29.1), 15.3 (11.8-19.8) and 10.5 (8.3-13.2) mg/dL, respectively (p-for-trend=0.007). Lp(a) levels in children with HoFH were higher than in children with HeFH and in unaffected children. Given the very high ASCVD risk with HoFH, identifying other risk factors such as elevated Lp(a) in these children is important. Therefore, Lp(a) levels should be measured at least once in all children with HoFH.

Association of Major Adverse Cardiac Events and Beta-Blockers in Patients with and without Atherosclerotic Cardiovascular Disease: Long-Term Follow-Up Results of the T-SPARCLE and T-PPARCLE Registry in Taiwan

Beta-blockers are widely used, but the benefit is now challenged in patients at risk of atherosclerotic cardiovascular disease (ASCVD) in the present coronary reperfusion era. We aimed to identify the risk factors of a major adverse cardiac event (MACE) and the long-term effect of beta-blockers in two large cohorts in Taiwan. Two prospective observational cohorts, including patients with known atherosclerosis cardiovascular disease (T-SPARCLE) and patients with at least one risk factor of ASCVD but without clinically evident ASCVD (T-PPARCLE), were conducted in Taiwan. The primary endpoint is the time of first occurrence of a MACE (cardiovascular death, nonfatal stroke, nonfatal myocardial infarction, and cardiac arrest with resuscitation). Between December 2009 and November 2014, with a median 2.4 years follow-up, 11,747 eligible patients (6921 and 4826 in T-SPARCLE and T-PPARCLE, respectively) were enrolled. Among them, 273 patients (2.3%) met the primary endpoint. With multivariate Cox PH model analysis, usage of beta-blocker was lower in patients with MACE (42.9% vs. 52.4%, p < 0.01). In patients with ASCVD, beta-blocker usage was associated with lower MACEs (hazard ratio 0.72; p < 0.001), but not in patients without ASCVD. The event-free survival of beta-blocker users remained higher during the follow-up period (p < 0.005) of ASCVD patients. In conclusion, in ASCVD patients, reduced MACE was associated with beta-blocker usage, and the effect was maintained during a six-year follow-up. Prescribing beta-blockers as secondary prevention is reasonable in the Taiwanese population.

Association of triglyceride-glucose index with atherosclerotic cardiovascular disease and mortality among familial hypercholesterolemia patients

BackgroundFamilial hypercholesterolemia (FH) is an inherited metabolic disorder with a high level of low-density lipoprotein cholesterol and the worse prognosis. The triglyceride-glucose (TyG) index, an emerging tool to reflect insulin resistance (IR), is positively associated with a higher risk of atherosclerotic cardiovascular disease (ASCVD) in healthy individuals, but the value of TyG index has never been evaluated in FH patients. This study aimed to determine the association between the TyG index and glucose metabolic indicators, insulin resistance (IR) status, the risk of ASCVD and mortality among FH patients.MethodsData from National Health and Nutrition Examination Survey (NHANES) 1999–2018 were utilized. 941 FH individuals with TyG index information were included and categorized into three groups: < 8.5, 8.5–9.0, and > 9.0. Spearman correlation analysis was used to test the association of TyG index and various established glucose metabolism-related indicators. Logistic and Cox regression analysis were used to assess the association of TyG index with ASCVD and mortality. The possible nonlinear relationships between TyG index and the all-cause or cardiovascular death were further evaluated on a continuous scale with restricted cubic spline (RCS) curves.ResultsTyG index was positively associated with fasting glucose, HbA1c, fasting insulin and the homeostatic model assessment of insulin resistance (HOMA-IR) index (all p < 0.001). The risk of ASCVD increased by 74% with every 1 unit increase of TyG index (95%CI: 1.15–2.63, p = 0.01). During the median 114-month follow-up, 151 all-cause death and 57 cardiovascular death were recorded. Strong U/J-shaped relations were observed according to the RCS results (p = 0.0083 and 0.0046 for all-cause and cardiovascular death). A higher TyG index was independently associated with both all-cause death and cardiovascular death. Results remained similar among FH patients with IR (HOMA-IR ≥ 2.69). Moreover, addition of TyG index showed helpful discrimination of both survival from all-cause death and cardiovascular death (p < 0.05).ConclusionTyG index was applicable to reflect glucose metabolism status in FH adults, and a high TyG index was an independent risk factor of both ASCVD and mortality.

Coordinated Care to Optimize Cardiovascular Preventive Therapies in Type 2 Diabetes

Evidence-based therapies to reduce atherosclerotic cardiovascular disease risk in adults with type 2 diabetes are underused in clinical practice. To assess the effect of a coordinated, multifaceted intervention of assessment, education, and feedback vs usual care on the proportion of adults with type 2 diabetes and atherosclerotic cardiovascular disease prescribed all 3 groups of recommended, evidence-based therapies (high-intensity statins, angiotensin-converting enzyme inhibitors [ACEIs] or angiotensin receptor blockers [ARBs], and sodium-glucose cotransporter 2 [SGLT2] inhibitors and/or glucagon-like peptide 1 receptor agonists [GLP-1RAs]). Cluster randomized clinical trial with 43 US cardiology clinics recruiting participants from July 2019 through May 2022 and follow-up through December 2022. The participants were adults with type 2 diabetes and atherosclerotic cardiovascular disease not already taking all 3 groups of evidence-based therapies. Assessing local barriers, developing care pathways, coordinating care, educating clinicians, reporting data back to the clinics, and providing tools for participants (n = 459) vs usual care per practice guidelines (n = 590). The primary outcome was the proportion of participants prescribed all 3 groups of recommended therapies at 6 to 12 months after enrollment. The secondary outcomes included changes in atherosclerotic cardiovascular disease risk factors and a composite outcome of all-cause death or hospitalization for myocardial infarction, stroke, decompensated heart failure, or urgent revascularization (the trial was not powered to show these differences). Of 1049 participants enrolled (459 at 20 intervention clinics and 590 at 23 usual care clinics), the median age was 70 years and there were 338 women (32.2%), 173 Black participants (16.5%), and 90 Hispanic participants (8.6%). At the last follow-up visit (12 months for 97.3% of participants), those in the intervention group were more likely to be prescribed all 3 therapies (173/457 [37.9%]) vs the usual care group (85/588 [14.5%]), which is a difference of 23.4% (adjusted odds ratio [OR], 4.38 [95% CI, 2.49 to 7.71]; P < .001) and were more likely to be prescribed each of the 3 therapies (change from baseline in high-intensity statins from 66.5% to 70.7% for intervention vs from 58.2% to 56.8% for usual care [adjusted OR, 1.73; 95% CI, 1.06-2.83]; ACEIs or ARBs: from 75.1% to 81.4% for intervention vs from 69.6% to 68.4% for usual care [adjusted OR, 1.82; 95% CI, 1.14-2.91]; SGLT2 inhibitors and/or GLP-1RAs: from 12.3% to 60.4% for intervention vs from 14.5% to 35.5% for usual care [adjusted OR, 3.11; 95% CI, 2.08-4.64]). The intervention was not associated with changes in atherosclerotic cardiovascular disease risk factors. The composite secondary outcome occurred in 23 of 457 participants (5%) in the intervention group vs 40 of 588 participants (6.8%) in the usual care group (adjusted hazard ratio, 0.79 [95% CI, 0.46 to 1.33]). A coordinated, multifaceted intervention increased prescription of 3 groups of evidence-based therapies in adults with type 2 diabetes and atherosclerotic cardiovascular disease. ClinicalTrials.gov Identifier: NCT03936660.

Abstract P336: Early Metabolic Imbalance in Young Adults is a Hidden Risk Factor for Midlife Cardiovascular Disease: CARDIA 35-year Follow Up

Introduction: The U.S. population includes a prevalent group of teens and young adults with early metabolic imbalance or EMI. This insidious condition includes markers of insulin resistance, particularly its interaction with adiposity, as well subclinical inflammation and oxidative stress. High circulating insulin compensates for insulin resistance in tissues, keeping fasting glucose, triglycerides and HDL within normal limits. Thus, individuals with EMI do not meet the criteria for metabolic syndrome or prediabetes. Previously, we reported that compensatory hyperinsulinemia in young adults is an independent risk factor for atherosclerotic cardiovascular disease (ASCVD), based on an analysis of 30-year data from CARDIA: Coronary Artery Risk Development in Young Adults. Here, we expand the analysis to include other components of EMI and the latest 35-year follow up data. Hypothesis: In young adults, EMI increases the risk for midlife ASCVD. Methods: This is a retrospective cohort study of CARDIA. The parent study enrolled 5,114 participants, ages 18-30 at baseline. In this retrospective analysis, the baseline exclusion criteria were hyperglycemia, hypertriglyceridemia, low HDL, diabetes, CVD, pregnancy or fasting &lt;8 hours, yielding 3,292 participants without metabolic syndrome or prediabetes. The data were analyzed using Cox proportional hazard regression in Stata 17.0 and JMP 16.2. The primary exposures were markers of insulin resistance, inflammation and oxidative stress at baseline; the covariates were the 2019 ACC/AHA risk factors for ASCVD: increased waist circumference (WC), hypertension, poor fitness, LDL ≥160, nicotine use (serum cotinine), family history of premature ASCVD, race, sex and estimated glomerular filtration rate (eGFR) &lt;60. The primary outcome was time to incident ASCVD (or censor), defined as any fatal or nonfatal MI, coronary revascularization, acute coronary syndrome, CHF, stroke, TIA, carotid or peripheral artery disease. Cox results were reported as hazard ratio (HR) and Harrell’s c-statistic (c). Results: All reported Cox models met the proportional hazards and linearity assumptions. Model 1 includes the ACC/AHA risk factors, yielding a Harrell’s c of 0.714. For WC, the HR for tertile 3 vs. 1 was 2.1, 95% CI 1.4, 3.1, p&lt;0.0001. Cox Model 2 replaces WC with a categorical variable with both WC and HOMA2-IR, a marker of insulin resistance. The HR for both measures in tertile 3 vs. both in tertile 1 was 2.1, 95% CI: 1.3, 2.5, p&lt;0.0001; Harrell’s c increased to 0.728. Cox model 3 adds markers of inflammation and oxidative stress to Model 2, increasing C to 0.735. In models 2 and 3, high WC was a significant risk factor only in combination with high HOMA2-IR, indicative of effect modification. Conclusion: After accounting for canonical risk factors, early metabolic imbalance in otherwise healthy young adults in CARDIA is a hidden risk factor for midlife ASCVD.

Abstract P432: Statin Initiation for Primary Prevention and Dose Intensity According to Age in the Women’s Health Initiative

Introduction: Over 50% of US adults older than 75 live free of atherosclerotic cardiovascular disease (ASCVD) and diabetes (DM), yet data on incident statin use among this population are lacking. Our objective was to assess statin initiation by age among the Women’s Health Initiative cohort free of ASCVD and DM at baseline (1993). Hypothesis: Statin initiation is higher at older ages and differs by race/ethnicity. Methods: Exclusions were statin use at baseline, known ASCVD, DM, and no follow-up after baseline. Self-reported medication use was assessed in 1996 and 2008. Specific statin and dose prescribed at the time of initiation were identified using National Drug Codes and determined statin intensity, defined by the ACC/AHA guidelines. We estimated the adjusted association between age group (&lt;65, 65-74, and ≥75) and statin initiation and assessed for heterogeneity by race/ethnicity. We also assessed statin dose at the time of initiation. Results: Over 12 years of follow-up, 27% of 99,631 women free of ASCVD and DM at baseline initiated a statin; initiation was lower with older age (Table). This association remained after adjustment for ASCVD risk factors and did not differ by race/ethnicity (p for interaction &gt;0.5). Moderate intensity dose was most common at statin initiation overall, and moderate and high intensity dose were both lower with older age. Conclusion: Of women free of ASCVD and DM, women older than 75 were least likely to start a statin and most likely to start low intensity statin therapy at initiation than younger women. We identified a potential clinical gap for investigation: whether lower overall use of statins and lower intensity statin therapy among older women are associated with preventable ASCVD.