Atherosclerotic Cardiovascular Disease Outcomes Research Articles

Advanced biologic therapies are associated with fewer adverse cardiovascular events in patients with inflammatory bowel diseases

Abstract Background Chronic inflammation is an important contributor to the development of atherosclerotic cardiovascular disease (ASCVD) and associated events. Inflammatory Bowel Diseases (IBD) are chronic inflammatory conditions, and meta-analyses of cohort studies demonstrate an increased risk of ASCVD events in IBD patients. Advanced biologic therapies (ABT) targeting the immune system revolutionized treatment of IBD patients but the impact of these therapies on ASCVD events is not known. Purpose To investigate the impact of ABT on ASVCD events in IBD patients. Methods A retrospective cohort study was performed using the TriNetX Diamond Network, a multi-institutional database providing real-time access to de-identified electronic health records, with data updated on 02/14/2024. ABT were defined as one or more the following: infliximab, adalimumab, golimumab, certolizumab pegol, ustekinumab, risankizumab, vedolizumab, or natalizumab. ASCVD events were based on ICD codes for ischemic heart, cerebrovascular, and peripheral vascular diseases. Individuals >40 years with IBD were included. ASCVD events in (1) patients on ABT and (2) patients not on ABT (NABT) were compared. Propensity score matching was performed on sex, aspirin use, and the following ASCVD risk factors: age, hypertension, hyperlipidemia, tobacco use, and type 2 diabetes mellitus. Results This study includes 72,650 individuals in each of the two matched cohorts. There were no differences in baseline characteristics between the two propensity-score matched cohorts (Table). The probabilities of experiencing any ASCVD event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (8.3% vs. 12.4%, OR 0.64; 13% vs. 18.6%, OR 0.66; and 15% vs. 21.2%, OR 0.65; respectively, all p<0.01). Similarly, the probability of experiencing an ischemic heart disease event at one, three, and five years in the ABT group were all significantly lower than in the NABT group (5.2% vs. 7.9%, OR 0.64; 8% vs. 11.7%, OR 0.66; and 9.2% vs. 13.4% OR 0.66; respectively, all p<0.01). The probability of cerebrovascular disease events at one, three, and five years in the ABT group were all significantly lower than in the NABT group (2% vs. 3.3%, OR 0.59; 3.5% vs. 5.7%, OR 0.59; and 4.2% vs. 6.8% OR 0.60; respectively, all p<0.01) and the probability of a peripheral artery disease event at one, three, and five years in the ABT group were also all significantly lower than in the NABT group event (2.8% vs. 4.5%, OR 0.62; 5.1% vs. 7.6%, OR 0.65; and 6.2% vs. 9.3% OR 0.65; respectively, all p<0.01). Conclusions ABT are associated with significantly fewer ASCVD events in the IBD patient population. Future studies examining the differential benefit of drug subclasses on ASCVD outcomes and mechanisms responsible for the ABT benefit, as well as prospective study designs have the potential to identify new therapeutic targets in IBD patients and with applicability beyond IBD patients.Table

Association of Neutrophil-to-Lymphocyte Ratio with Atherosclerotic Cardiovascular Disease and Kidney Outcomes in CKD

Association of Neutrophil-to-Lymphocyte Ratio with Atherosclerotic Cardiovascular Disease and Kidney Outcomes in CKD

Impact of Guideline-Directed Statin Prescriptions on Cardiovascular Outcomes by Race in a Real-World Primary Prevention Cohort

BackgroundData on real-world statin prescription in large, private health care networks and impacts on primary prevention of atherosclerotic cardiovascular disease (ASCVD) outcomes across race are scarce. ObjectivesThe purpose of this study was to investigate the impact of statin prescription on ASCVD outcomes within and across race in a large, nongovernmental health care system. MethodsStatin prescription in Black and White patients without ASCVD was evaluated (2013-2019). Guideline-directed statin intensity was defined as at least “moderate” for intermediate and high-risk patients. Statin prescription at index and ASCVD outcomes at follow-up (myocardial infarction/revascularization, stroke, mortality) were assessed via electronic health care records using International Classification of Diseases-9 and 10 codes. Cox regression models, adjusted for CVD risk factors, were used to calculate HRs for association between statin prescription and incident ASCVD events across race. ResultsAmong 270,079 patients, 7.6% (n = 20,477) and 92.4% (n = 249,602) identified as Black and White, respectively. Significantly fewer Black patients were prescribed statin therapy than White patients (13.6% vs 19.0%; P < 0.001). At a mean follow-up of 6 years, patients with “no statin” prescription vs guideline-directed statin intensity showed increased ASCVD in Black patients (HR: 1.40 [95% CI: 1.05-1.86]), and White patients (HR: 1.32 [95% CI: 1.21-1.45]; P < 0.05) and all-cause mortality. Intermediate and high-risk Black patients faced a 17% higher risk of mortality compared to White patients. However, the interaction between race and statin prescription was not a significant predictor of incident ASCVD events. ConclusionsStatins remain underprescribed. Although Black patients received proportionally less statin prescription than White patients, this was not associated with higher risk of mortality in Black patients.

Beyond LDL-C: unravelling the residual atherosclerotic cardiovascular disease risk landscape-focus on hypertriglyceridaemia.

Historically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceridaemia and novel modalities addressing other residual ASCVD risk factors. Hypertriglyceridaemia remains a significant ASCVD risk despite low LDL-C in statin or proprotein convertase subtilisin/kexin type 9 inhibitor-treated patients. Large population-based observational studies have consistently demonstrated an association between hypertriglyceridaemia with ASCVD. This relationship is complicated by the co-existence of low high-density lipoprotein cholesterol. Despite significantly improving atherogenic dyslipidaemia, the most recent clinical trial outcome has cast doubt on the utility of pharmacologically lowering triglyceride concentrations using fibrates. On the other hand, purified eicosapentaenoic acid (EPA), but not in combination with docosahexaenoic acid (DHA), has produced favourable ASCVD outcomes. The outcome of these trials suggests alternate pathways involved in ASCVD risk modulation. Several other pharmacotherapies have been proposed to address other ASCVD risk factors targeting inflammation, thrombotic and metabolic factors. Hypertriglyceridaemia poses a significant residual ASCVD risk in patients already on LDL-C lowering therapy. Results from pharmacologically lowering triglyceride are conflicting. The role of fibrates and combination of EPA and DHA is under question but there is now convincing evidence of ASCVD risk reduction with pure EPA in a subgroup of patients with hypertriglyceridaemia. Clinical guidelines should be updated in line with recent clinical trials evidence. Novel agents targeting non-conventional ASCVD risks need further evaluation.

Coronary Atherosclerotic Plaque Burden Assessment by Computed Tomography and Its Clinical Implications.

Recent studies have demonstrated that coronary plaque burden carries greater prognostic value in predicting adverse atherosclerotic cardiovascular disease outcomes than myocardial ischemia, thereby challenging the existing paradigm. Advances in plaque quantification through both noncontrast and contrast-enhanced computed tomography (CT) methods have led to earlier and more cost-effective detection of coronary disease compared with traditional stress testing. The 2 principal techniques of noninvasive coronary plaque quantification assessment are coronary artery calcium scoring by noncontrast CT and coronary CT angiography, both of which correlate with disease burden on invasive angiography. Plaque quantification from these imaging modalities has shown utility in risk stratification and prognostication of adverse cardiovascular events, leading to increased incorporation into clinical practice guidelines and preventive care pathways. Furthermore, due to their expanding clinical value, emerging technologies such as artificial intelligence are being integrated into plaque quantification platforms, placing more advanced measures of plaque burden at the forefront of coronary plaque evaluation. In this review, we summarize recent clinical data on coronary artery calcium scoring and coronary CT angiography plaque quantification in the evaluation of adverse atherosclerotic cardiovascular disease in patients with and without chest pain, highlight how these methods compare to invasive quantification approaches, and directly compare the performance characteristics of coronary artery calcium scoring and coronary CT angiography.

Early Onset Atherosclerotic Cardiovascular Disease.

Recent trends indicate a concerning increase in early-onset atherosclerotic cardiovascular disease (ASCVD) among younger individuals (age < 55 in men and <65 in women). These findings highlight the pathobiology of ASCVD as a disease process that begins early in life and underscores the need for more tailored screening methods and preventive strategies. Increasing attention has been placed on the growing burden of traditional cardiometabolic risk factors in young individuals while also recognizing unique factors that mediate risk of premature atherosclerosis in this demographic such as substance use, socioeconomic disparities, adverse pregnancy outcomes, and chronic inflammatory states that contribute to the increasing incidence of early ASCVD. Additionally, mounting evidence has pointed out significant disparities in the diagnosis and management of early ASCVD and cardiovascular outcomes based on sex and race. Moving toward a more personalized approach, emerging data and technological developments using diverse tools such as polygenic risk scores and coronary artery calcium scans have shown potential in earlier detection of ASCVD risk. Thus, we review current evidence on causal risk factors that drive the increase in early ASCVD and highlight emerging tools to improve ASCVD risk assessment in young individuals.

Fenofibrate’s impact on cardiovascular risk in patients with diabetes: a nationwide propensity-score matched cohort study

BackgroundThe beneficial effects of fenofibrate on atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes and statin treatment are unclear. We investigated the effects of fenofibrate on all-cause mortality and ASCVD in patients with diabetes, high triglyceride (TG) levels and statin treatment.MethodsWe performed a nationwide propensity-score matched (1:1) cohort study using data from the National Health Information Database in the Republic of Korea from 2010 to 2017. The study included 110,723 individuals with diabetes, TG levels ≥ 150 mg/dL, and no prior diagnoses of ASCVD who used statins and fenofibrate, and an equal matched number of similar patients who used statins alone (control group). The study outcomes included newly diagnosed myocardial infarction (MI), stroke, both (MI and/or stroke), and all-cause mortality.ResultsOver a mean 4.03-year follow-up period, the hazard ratios (HR) for outcomes in the fenofibrate group in comparison to the control group were 0.878 [95% confidence interval (CI) 0.827–0.933] for MI, 0.901 (95% CI 0.848–0.957) for stroke, 0.897 (95% CI 0.858–0.937) for MI and/or stroke, and 0.716 (95% CI 0.685–0.749) for all-cause death. These beneficial effects of fenofibrate were consistent in the subgroup with TG 150–199 mg/dL but differed according to low-density lipoprotein cholesterol (LDL-C) levels.ConclusionIn this nationwide propensity-score matched cohort study involving individuals with diabetes and TG ≥ 150 mg/dL, the risk of all-cause death and ASCVD was significantly lower with fenofibrate use in conjunction with statin treatment compared to statin treatment alone. However, this finding was significant only in individuals with relatively high LDL-C levels.Graphical

Associations of genetically predicted vitamin D status and deficiency with the risk of carotid artery plaque: a Mendelian randomization study

Low concentrations of circulating 25-hydroxy-vitamin D are observationally associated with an increased risk of subclinical atherosclerosis and cardiovascular disease. However, randomized controlled trials have not reported the beneficial effects of vitamin D supplementation on atherosclerotic cardiovascular disease (ASCVD) outcomes. Whether genetically predicted vitamin D status confers protection against the development of carotid artery plaque, a powerful predictor of subclinical atherosclerosis, remains unknown. We conducted a two-sample Mendelian randomization (MR) study to explore the association of genetically predicted vitamin D status and deficiency with the risk of developing carotid artery plaque. We leveraged three genome-wide association studies (GWAS) of vitamin D status and one GWAS of vitamin D deficiency. We used the inverse-variance weighted (IVW) approach as our main method, and MR-Egger, weighted-median, and radialMR as MR sensitivity analyses. We also conducted sensitivity analyses using biologically plausible genetic instruments located within genes encoding for vitamin D metabolism (GC, CYP2R1, DHCR7, CYP24A1). We did not find significant associations between genetically predicted vitamin D status (Odds ratio (OR) = 0.99, P = 0.91) and deficiency (OR = 1.00, P = 0.97) with the risk of carotid artery plaque. We additionally explored the potential causal effect of vitamin D status on coronary artery calcification (CAC) and carotid intima-media thickness (cIMT), two additional markers of subclinical atherosclerosis, and we did not find any significant association (βCAC = − 0.14, P = 0.23; βcIMT = 0.005, P = 0.19). These findings did not support the causal effects of vitamin D status and deficiency on the risk of developing subclinical atherosclerosis.

Sex-based utilization of guideline recommended statin therapy and cardiovascular disease outcomes: Data from a multisite healthcare network primary prevention cohort

BackgroundIn the US, women have similar cardiovascular death rates as men. However, less is known about sex differences in statin use for primary prevention and associated atherosclerotic cardiovascular disease (ASCVD) outcomes. MethodsStatin prescriptions using electronic health records were examined in patients without ASCVD (myocardial infarction (MI), revascularization or ischemic stroke) between 2013 and 2019. Guideline-directed statin intensity (GDSI) at index (at least moderate intensity, defined per pooled-cohort equation) and follow-up visits were compared between sexes across ASCVD risk groups, defined by the pooled-cohort equation. Cox regression hazard ratios were calculated for statin use and outcomes (myocardial infarction, stroke/transient ischemic attack (TIA), and all-cause mortality) stratified by sex. Interaction terms (statin and sex) were applied. ResultsAmong 282,298 patients, (mean age ∼ 50 years) 17.1 % women and 19.5 % men were prescribed any statin at index visit. Time to GDSI was similar between sexes, but the proportion of high-risk women on GDSI at follow-up were lower compared to high-risk men (2-years: 27.7 vs 32.0 %, and 5-years: 47.2 vs 55.2 %, p < 0.05). When compared to GDSI, no statin use was associated with higher risk of MI and ischemic stroke/TIA among both sexes. High-risk women on GDSI had a lower risk of mortality (HR=1.39 [1.22–1.59]) vs. men (HR=1.67 [1.50–1.86]) of similar risk (p value interaction=0.004). ConclusionIn a large contemporary healthcare system, there was underutilization of statins across both sexes in primary prevention. High-risk women were less likely to remain on GDSI compared to high-risk men. GDSI significantly improved the survival in both sexes regardless of ASCVD risk group. Future strategies to ensure continued use of GDSI, specifically among women, should be explored.

Improved lipid-lowering treatment and reduction in cardiovascular disease burden in homozygous familial hypercholesterolemia: The SAFEHEART follow-up study

AimWe aimed to describe clinical and genetic characteristics, lipid-lowering treatment and atherosclerotic cardiovascular disease (ASCVD) outcomes over a long-term follow-up in homozygous familial hypercholesterolemia (HoFH). MethodsSAFEHEART (Spanish Familial Hypercholesterolaemia Cohort Study) is a long-term study in molecularly diagnosed FH. Data analyzed in HoFH were prospectively obtained from 2004 until 2022. ASCVD events, lipid profile and lipid-lowering treatment were determined. ResultsThirty-nine HoFH patients were analyzed. The mean age was 42 ± 20 years and nineteen (49%) were women. Median follow-up was 11 years (IQR 6,18). Median age at genetic diagnosis was 24 years (IQR 8,42). At enrolment, 33% had ASCVD and 18% had aortic valve disease. Patients with new ASCVD events and aortic valve disease at follow-up were six (15%), and one (3%), respectively. Median untreated LDL-C levels were 555 mg/dL (IQ 413,800), and median LDL-C levels at last follow-up was 122 mg/dL (IQR 91,172). Most patients (92%) were on high intensity statins and ezetimibe, 28% with PCSK9i, 26% with lomitapide, and 23% with lipoprotein-apheresis. Fourteen patients (36%) attained an LDL-C level below 100 mg/dL, and 10% attained an LDL-C below 70 mg/dL in secondary prevention. Patients with null/null variants were youngers, had higher untreated LDL-C and had the first ASCVD event earlier. Free-event survival is longer in patients with defective variant compared with those patients with at least one null variant (p=0.02). ConclusionsHoFH is a severe life threating disease with a high genetic and phenotypic variability. The improvement in lipid-lowering treatment and LDL-C levels have contributed to reduce ASCVD events.

Patterns and gaps in guideline-directed statin use for atherosclerotic cardiovascular disease by race and ethnicity

ObjectiveThere remain disparities by race and ethnicity in atherosclerotic cardiovascular disease (ASCVD). Statins reduce low-density lipoprotein cholesterol (LDL-c) and improve ASCVD outcomes. ASCVD treatment patterns across disaggregated race and ethnicity groups are incompletely understood. We aimed to evaluate statin use and LDL-c control for ASCVD by race and ethnicity. MethodsFrom an electronic health record (EHR)-based cohort from a multisite Northern California health system, we included adults with an ASCVD diagnosis from 2010 to 2021 and at least 2 primary care visits, stratified by race and ethnicity (Non-Hispanic White [NHW], Non-Hispanic Black [Black], Hispanic, and Asian). Hispanic (Mexican, Puerto Rican, Other) and Asian (Asian Indian, Chinese, Filipino, Japanese, Korean, Vietnamese, Other) groups were disaggregated. Primary outcomes were 1-year post-ASCVD statin use (prescription) and LDL-c control (at least one value <70 mg/dL). Adjusted odds ratios (ORs) were estimated using logistic regression. ResultsOf 133,158 patients, there were 89,944 NHW, 6,294 Black, 12,478 (9.4 %) Hispanic and 13,179 (9.9 %) Asian patients. At 1 year after incident ASCVD, there was suboptimal statin use (any statins <60 %, high-intensity <25 %) and LDL-c control (<30 %) across groups, with lowest proportions in Black patients for statin use (46.7 %, any statin) and LDL-c control (10.7 %, OR 0.89 (0.81–0.97), referent NHW). Disaggregation of Asian and Hispanic groups unmasked within-group heterogeneity. ConclusionsIn patients with incident ASCVD, we describe suboptimal and heterogenous 1-year post-ASCVD guideline-directed statin use and 1-year post-ASCVD LDL-c control across disaggregated race and ethnicity groups. Findings may improve understanding of ASCVD treatment disparities and guide implementation.

Inverted U-Shaped Association of Plasma Resolvin D2 With Atherosclerotic Cardiovascular Disease and the Mediation Effects of Serum Cholesterol: A Chinese Community-Based Study.

Resolvin D2 (RvD2) has been reported to protect against the development of atherosclerosis in animal models. The objective of this study was to examine the prospective association between plasma RvD2 and the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level. A cohort of 2633 community-dwelling individuals aged 35-60 years was followed for 8 years in this study. Adjusted hazard ratios and 95% CIs for ASCVD outcomes according to baseline RvD2 levels were calculated using Cox proportional hazards models. Mediation analysis was used to test the indirect effect of serum cholesterol indicators on the association between RvD2 and ASCVD probability. In total, 284 new cases of ASCVD were identified during follow-up. An inverted U-shaped association between natural log (ln)-transformed RvD2 and incident ASCVD was determined, and the threshold value for lnRvD2 was 3.87. Below the threshold, each unit increase in lnRvD2 was associated with a 2.05-fold increased risk of ASCVD (95% CI, 1.13-3.74; P=0.019). Above the threshold, each unit increase in lnRvD2 was associated with a 36% reduced risk of ASCVD (95% CI, 0.51-0.80; P<0.001). In addition, the association between RvD2 and ASCVD probability was partially mediated by high-density lipoprotein cholesterol (15.81%) when lnRvD2 <3.87, but by total cholesterol (30.23%) and low-density lipoprotein cholesterol (30.13%) when lnRvD2 ≥3.87. Both lower and higher RvD2 levels are associated with a reduced risk of ASCVD, forming an inverted U-shaped relationship. Furthermore, this association is partially mediated by total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol.

Sex Differences in Diagnosis, Treatment, and Cardiovascular Outcomes in Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by extremely increased low-density lipoprotein (LDL) cholesterol levels and premature atherosclerotic cardiovascular disease (ASCVD). Heterozygous familial hypercholesterolemia (HeFH) is more common than HoFH, and women with HeFH are diagnosed later and undertreated compared to men; it is unknown whether these sex differences also apply to HoFH. To investigate sex differences in age at diagnosis, risk factors, lipid-lowering treatment, and ASCVD morbidity and mortality in patients with HoFH. Sex-specific analyses for this retrospective cohort study were performed using data from the HoFH International Clinical Collaborators (HICC) registry, the largest global dataset of patients with HoFH, spanning 88 institutions across 38 countries. Patients with HoFH who were alive during or after 2010 were eligible for inclusion. Data entry occurred between February 2016 and December 2020. Data were analyzed from June 2022 to June 2023. Comparison between women and men with HoFH regarding age at diagnosis, presence of risk factors, lipid-lowering treatment, prevalence, and onset and incidence of ASCVD morbidity (myocardial infarction [MI], aortic stenosis, and combined ASCVD outcomes) and mortality. Data from 389 women and 362 men with HoFH from 38 countries were included. Women and men had similar age at diagnosis (median [IQR], 13 [6-26] years vs 11 [5-27] years, respectively), untreated LDL cholesterol levels (mean [SD], 579 [203] vs 596 [186] mg/dL, respectively), and cardiovascular risk factor prevalence, except smoking (38 of 266 women [14.3%] vs 59 of 217 men [27.2%], respectively). Prevalence of MI was lower in women (31 of 389 [8.0%]) than men (59 of 362 [16.3%]), but age at first MI was similar (mean [SD], 39 [13] years in women vs 38 [13] years in men). Treated LDL cholesterol levels and lipid-lowering therapy were similar in both sexes, in particular statins (248 of 276 women [89.9%] vs 235 of 258 men [91.1%]) and lipoprotein apheresis (115 of 317 women [36.3%] vs 118 of 304 men [38.8%]). Sixteen years after HoFH diagnosis, women had statistically significant lower cumulative incidence of MI (5.0% in women vs 13.7% in men; subdistribution hazard ratio [SHR], 0.37; 95% CI, 0.21-0.66) and nonsignificantly lower all-cause mortality (3.0% in women vs 4.1% in men; HR, 0.76; 95% CI, 0.40-1.45) and cardiovascular mortality (2.6% in women vs 4.1% in men; SHR, 0.87; 95% CI, 0.44-1.75). In this cohort study of individuals with known HoFH, MI was higher in men compared with women yet age at diagnosis and at first ASCVD event were similar. These findings suggest that early diagnosis and treatment are important in attenuating the excessive cardiovascular risk in both sexes.

Lipid lowering therapy: implications ofrecent clinical trials.

Recent lipid lowering therapy trials have provided important insights on certain agents while also continuing to expand our understanding of atherosclerotic cardiovascular disease (ASCVD) risk. Findings from current trials include the impact of statin therapy on ASCVD among populations with HIV, the benefit of lowering low-density lipoprotein cholesterol with bempedoic acid among patients considered statin intolerant, the safety and efficacy of inclisiran over a 4-year period, another failed attempt for fibrates to reduce ASCVD risk, which omega-3 fatty to utilize for lowering cardiovascular events, 'n-of-1'trials evaluating statin intolerance, and how low-dose rosuvastatin compared with commonly utilized supplements for lowering lipid parameters. Such data help inform so clinicians can optimize lipid lowering therapy and improve ASCVD outcomes.

Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease.

Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. Population-based cohort study in Ontario, Canada. A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02]). Medication use was not available at the population level. The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. Canadian Institutes of Health Research.

Evolution of More Aggressive LDL-Cholesterol Targets and Therapies for Cardiovascular Disease Prevention

Over the last half-century, discussions on the exact targets for low-density lipoprotein cholesterol (LDL-C) reduction have evolved towards a more aggressive approach with lower LDL-C targets, particularly for high-risk patients with pre-existing atherosclerotic cardiovascular disease (ASCVD). A wealth of cardiovascular outcome trials have shown the efficacy of statin therapy in general, as well as the incremental impact of high-intensity statin therapy in particular. More recent trials have further demonstrated the impact of non-statin therapies, including ezetimibe, proprotein convertase subtilisin/kexin type 9 inhibitors, and, most recently, bempedoic acid, on reducing ASCVD outcomes. The availability of these and other newer therapies has prompted clinicians to strive for lower LDL-C targets to address residual ASCVD risk after statin therapy. This paper will provide an overview of the historical trends in lipid management and therapeutics and review the current state of evidence for lower LDL-C targets in clinical guidelines and recommendations.

Abstract 16212: Sex-Based Statin Utilization and Cardiovascular Disease Outcomes: A Real World Secondary Prevention Cohort

Introduction: Current guidelines recommend using high-intensity statins in patients with clinical ASCVD.However, real world adherence to GDSI use and recurrent events remains less known. Sex difference in statin use have been previously reported. We evaluated sex-based disparities in GDSI use and recurrent ASCVD outcomes in a large healthcare network. Methods: Using EMR, we assessed statin use and intensity amongst patients with established prior ASCVD events (MI, ischemic stroke/TIA) and PAD from 2010-2022. Statins were categorized into GDSI (high intensity), &lt;gdsi (moderate="" or="" low="" intensity)="" or no statin use. Outcomes of interest included repeat MI, stroke/TIA and all-cause mortality. Incident rates (IR) and Cox regression hazard ratios (HR) of ASCVD outcomes were calculated across statin categories stratified by sex. Results: Amongst 45,949 patients,31% were women. Women had more diabetes (29% vs 24%) and higher LDL-C (94.9 ± 40.8 vs 87.6 ± 37.1 mg/dL) than men. During a follow-up period of 5 years, women were less likely to be started on GDSI (61.6% vs 65.8%, p&lt;0.01) and achieve LDL-C&lt;70mg/dL (41% vs and 49%, p&lt;0.01) as compared to men. GDSI use lowered IRs for all outcomes in both sexes (Table 1). Women on GDSI had higher risk of MI (HR 1.21 [1.12-1.31)],stroke (1.21 [1.08-1.34] and mortality (1.12 [1.05-1.20]), all p&lt;0.01) than men. Conclusions: In a contemporary cohort of secondary prevention patients, women were less likely to be prescribed GDSI than men and less likely to achieve guideline concordant LDL-C&lt;70mg/dL. This was associated with a higher risk of recurrent ASCVD events in women as compared to men. More sex specific interventions are needed to ensure adequate preventive treatment for both sexes. Abbreviations: Atherosclerotic cardiovascular disease (ASCVD), guideline directed statin intensity (GDSI), Electronic medical records (EMR),Myocardial Infarction (MI), Peripheral arterial disease (PAD), Transient Ischemic attack (TIA)

Abstract 14786: Disparities in Composite Cardiovascular Risk Factor Control in US Adults With Diabetes in the NIH Precision Medicine Initiative All of Us Research Program

Background/Objective: There are limited contemporary data in real-world populations on composite cardiovascular risk factor (RF) control in adults with diabetes mellitus (DM). We studied the proportions of patients with DM at target for individual and multiple cardiovascular RFs including HbA1c, LDL-C, BMI, blood pressure, and smoking status. Methods: We included adults ≥18 years of age with DM from the NIH Precision Medicine Initiative All of Us Research Program 2018-2022. RFs and target values were defined as 1) HbA1c (&lt;7% w/ atherosclerotic cardiovascular disease (ASCVD) or &lt;8% w/o ASCVD), 2) LDL-C (&lt;55mg/dL w/ ASCVD or &lt;70mg/dL w/o ASCVD), 3) blood pressure (&lt;130/80 mmHg), 4) BMI (&lt;25 kg/m 2 ), and 5) smoking status (never or former smoker). We investigated the proportion (%) of patients at target for individual RFs, ≥3 RFs, ≥4 RFs, and mean number at target by sex, race/ethnicity, and ASCVD status. Results: Individual and composite cardiovascular RF control was found to be low among the 83,093 participants with DM. Control of &gt; 3 RFs and ≥ 4 RFs was only 25% and 5% overall, respectively, with fewer than 1% at target for all 5 RFs; female sex, Asian race/ethnicity, and those with prior ASCVD were more likely to have multiple RFs at target. Non-Hispanic black participants had the lowest proportion of RFs at target. In a multiple logistic regression, higher income, higher education level, employment, female sex, and Non-Hispanic White &amp; Asian race/ethnicity positively predicted control of ≥ 4 RFs with p-value &lt; 0.001. Conclusions: Individual and composite RF control remains suboptimal in many patients with DM, with disparities across certain demographic subsets. Further efforts are required to address social determinants that may be responsible for continuing gaps in adequate RF control and to educate clinicians and patients on the importance of controlling key RFs that impact ASCVD and other outcomes in those with DM.

Machine Learning Models for ASCVD Risk Prediction in an Asian Population - How to Validate the Model is Important.

Atherosclerotic cardiovascular disease (ASCVD) is prevalent worldwide including Taiwan, however widely accepted tools to assess the risk of ASCVD are lacking in Taiwan. Machine learning models are potentially useful for risk evaluation. In this study we used two cohorts to test the feasibility of machine learning with transfer learning for developing an ASCVD risk prediction model in Taiwan. Two multi-center observational registry cohorts, T-SPARCLE and T-PPARCLE were used in this study. The variables selected were based on European, U.S. and Asian guidelines. Both registries recorded the ASCVD outcomes of the patients. Ten-fold validation and temporal validation methods were used to evaluate the performance of the binary classification analysis [prediction of major adverse cardiovascular (CV) events in one year]. Time-to-event analyses were also performed. In the binary classification analysis, eXtreme Gradient Boosting (XGBoost) and random forest had the best performance, with areas under the receiver operating characteristic curve (AUC-ROC) of 0.72 (0.68-0.76) and 0.73 (0.69-0.77), respectively, although it was not significantly better than other models. Temporal validation was also performed, and the data showed significant differences in the distribution of various features and event rate. The AUC-ROC of XGBoost dropped to 0.66 (0.59-0.73), while that of random forest dropped to 0.69 (0.62-0.76) in the temporal validation method, and the performance also became numerically worse than that of the logistic regression model. In the time-to-event analysis, most models had a concordance index of around 0.70. Machine learning models with appropriate transfer learning may be a useful tool for the development of CV risk prediction models and may help improve patient care in the future.

Comparison of Atherosclerotic Cardiovascular Risk Factors and Cardiometabolic Profiles Between Current and Never Users of Marijuana.

The relationship between marijuana use and cardiovascular health remains uncertain, with several observational studies suggesting a potential association with increased adverse atherosclerotic cardiovascular disease (ASCVD) outcomes. This study examined the relationship between marijuana use, ASCVD risk factors, and cardiometabolic risk profiles. US adults (18-59 years) without cardiovascular disease were identified from the National Health And Nutrition Examination Survey (2005-2018) based on self-reported marijuana use. Current users (used within the past month) and never users were compared with assess the burden and control of traditional ASCVD risk factors and biomarkers, using inverse probability of treatment weighting to adjust for sociodemographic and lifestyle factors, including tobacco use. Of the 13 965 participants identified (mean age, 37.5; 51.2% female; 13% non-Hispanic Black), 26.6% were current users. Current users were predominantly male, low-income, and more likely to be concurrent tobacco users. Inverse probability of treatment weighting analysis showed no significant differences in the burden and control of hypertension (19.3% versus 18.8%, P=0.76; 79.8% versus 77.8%, P=0.75), dyslipidemia (24.0% versus 19.9%, P=0.13; 82% versus 75%, P=0.95), diabetes (4.8% versus 6.4%, P=0.19; 52.9% versus 50.6%, P=0.84), obesity (35.8% versus 41.3%, P=0.13), and physical activity levels (71.9% versus 69.3%, P=0.37) between current and never users. Likewise, mean 10-year ASCVD risk scores (2.8% versus 3.0%, P=0.49), 30-year Framingham risk scores (22.7% versus 24.2%, P=0.25), and cardiometabolic profiles including high-sensitivity C-reactive protein (3.5 mg/L versus 3.7 mg/L, P=0.65), neutrophil-lymphocyte ratio (2.1 versus 2.1, P=0.89), low-density lipoprotein (114.3 mg/dL versus 112.2 mg/dL, P=0.53), total cholesterol (191.2 mg/dL versus 181.7 mg/dL, P=0.58), and hemoglobin A1C (5.4% versus 5.5%, P=0.25) were similar between current and never users. This cross-sectional study found no association between self-reported marijuana use and increased burden of traditional ASCVD risk factors, estimated long-term ASCVD risk, or cardiometabolic profiles. Further studies are needed to explore potential pathways between adverse cardiovascular disease outcomes and marijuana use.