Risk Of Atherosclerotic Cardiovascular Disease Events Research Articles

The LDL cumulative exposure hypothesis: evidence and practical applications.

The trapping of LDL and other apolipoprotein B-containing lipoproteins within the artery wall causes atherosclerosis. As more LDL becomes trapped within the artery wall over time, the atherosclerotic plaque burden gradually increases, raising the risk of an acute cardiovascular event. Therefore, the biological effect of LDL on the risk of atherosclerotic cardiovascular disease (ASCVD) depends on both the magnitude and duration of exposure. Maintaining low levels of LDL-cholesterol (LDL-C) over time decreases the number of LDL particles trapped within the artery wall, slows the progression of atherosclerosis and, by delaying the age at which mature atherosclerotic plaques develop, substantially reduces the lifetime risk of ASCVD events. Summing LDL-C measurements over time to calculate cumulative exposure to LDL generates a unique biomarker that captures both the magnitude and duration of exposure, which facilitates the estimation of the absolute risk of having an acute cardiovascular event at any point in time. Titrating LDL-C lowering to keep cumulative exposure to LDL below the threshold at which acute cardiovascular events occur can effectively prevent ASCVD. In this Review, we provide the first comprehensive overview of how the LDL cumulative exposure hypothesis can guide the prevention of ASCVD. We also discuss the benefits of maintaining lower LDL-C levels over time and how this knowledge can be used to inform clinical practice guidelines as well as to design novel primary prevention trials and ASCVD prevention programmes.

Analysis of Blood Lipids, Blood Glucose, Blood Uric Acid, and Blood Routine Test Results in Retired Employees of a Unit in the Civil Aviation System

Objective: To investigate and analyze the annual physical examination results of retired employees from a unit in the civil aviation system, focusing on blood lipids, blood glucose, blood uric acid, and blood routine results. The study aims to provide relevant references for formulating reasonable disease management measures for preventing and controlling hyperlipidemia, hyperuricemia, and other conditions in retired employees. Methods: The examination results of 231 participants were collected and analyzed. The participants were divided into four groups based on age: middle-aged group, young-old group, middle-old group, and old-old group. The blood test results were compared across these groups, and an assessment of atherosclerotic cardiovascular disease (ASCVD) risk levels was completed in conjunction with medical history. Blood test results were also compared by gender. Results: There were no significant statistical differences in blood test results when grouped by age. However, the prevalence of hyperuricemia was higher in males than in females, while the prevalence of hypercholesterolemia was higher in females than in males. The LDL-C target achievement rate was lower in the moderate-and-high-risk group as well as the very high-risk group as defined by ASCVD risk levels. Conclusion: Management of hyperuricemia and hyperlipidemia in retired employees (elderly patients) should be strengthened to reduce the risk of ASCVD events and alleviate the potential medical burden associated with disease progression.

Association Between Kidney Stone History and Cardiovascular Event Risk in US Adults

ObjectivesTo determine the association between kidney stone history and predicted 10-year risk of atherosclerotic cardiovascular disease events in a nationally representative US adult sample without existing cardiovascular disease. MethodsThis was a cross-sectional study of the 2017-2020 National Health and Nutrition Examination Survey that included a nationally representative sample of 3,842 adults aged 40-79 free from cardiovascular disease. Kidney stone history was assessed through self-reporting. The 10-year risk of an atherosclerotic cardiovascular disease event was predicted using the American College of Cardiology/American Heart Association (ACC/AHA) Pooled Cohort Equations. ResultsThe weighted prevalence of kidney stones was 12.2% (95% CI: 10.5% to 14.1%). In unadjusted analysis, the odds of borderline or higher (≥5%) atherosclerotic cardiovascular disease risk were higher in stone formers (odds ratio=1.56; 95% CI 1.01-2.40; P=0.046). This association persisted after adjustment for demographics and clinical covariates (adjusted odds ratio=1.57; 95% CI=1.02 to 2.43; P=0.04). A significant interaction by biological sex was identified (p=0.002), with excess risk conferred by kidney stones in men but not women. ConclusionsKidney stone history was independently associated with increased 10-year predicted atherosclerotic cardiovascular disease event risk, with excess risk observed among men but not women. Intensified cardiovascular disease screening may be warranted among stone formers given their increased cardiovascular risk.

Associations of dietary magnesium intake with the risk of atherosclerotic cardiovascular disease and mortality in individuals with and without type 2 diabetes: A prospective study in the UK Biobank

BackgroundThe association between dietary magnesium (Mg) intake and the risk of atherosclerotic cardiovascular disease (ASCVD) remains uncertain. We aimed to examine the associations of dietary Mg intake with the risk of ASCVD events and mortality in individuals with and without type 2 diabetes. MethodsA total of 149,929 participants (4603 with type 2 diabetes) from the UK Biobank were included in the analyses. The hazard ratios (HRs) and 95 % confidence intervals (CIs) were estimated using Cox proportional hazard models. Furthermore, interactions of dietary Mg intake with type 2 diabetes status were examined on multiplicative and additive scales. ResultsDuring a median follow-up of 12.0 and 12.1 years, 7811 incident ASCVD events and 5000 deaths (including 599 ASCVD deaths) were documented, respectively. There were significantly negative associations between sufficient dietary Mg intake (equal to or greater than the recommended daily intake) and the risk of ASCVD incidence (HR 0.63 [95 % CI 0.49;0.82]), ASCVD mortality (0.45 [0.24;0.87]), and all-cause mortality (0.71 [0.52;0.97]) in participants with type 2 diabetes, whereas no significant association was observed in participants without type 2 diabetes (1.01 [0.94;1.09] for ASCVD incidence; 1.25 [0.93;1.66] for ASCVD mortality; 0.97 [0.88;1.07] for all-cause mortality). Multiplicative and additive interactions of dietary Mg intake with type 2 diabetes status were both observed. ConclusionSufficient dietary Mg intake was significantly associated with lower risks of ASCVD events and mortality in individuals with type 2 diabetes but not in those without type 2 diabetes. Our findings provide insight into the importance of dietary Mg intake for reducing modifiable cardiovascular burden in individuals with type 2 diabetes, which may inform future personalized dietary guidelines.

Thoracic versus coronary calcification for atherosclerotic cardiovascular disease events prediction

This study compared the prognostic value of quantified thoracic artery calcium (TAC) including aortic arch on chest CT and coronary artery calcium (CAC) score on ECG-gated cardiac CT.MethodsA total of...

Childhood Non-HDL Cholesterol and LDL Cholesterol and Adult Atherosclerotic Cardiovascular Events.

Although low-density lipoprotein cholesterol (LDL-C) remains the primary cholesterol target in clinical practice in children and adults, non-high-density lipoprotein cholesterol (non-HDL-C) has been suggested as a more accurate measure of atherosclerotic cardiovascular disease (ASCVD) risk. We examined the associations of childhood non-HDL-C and LDL-C levels with adult ASCVD events and determined whether non-HDL-C has better utility than LDL-C in predicting adult ASCVD events. This prospective cohort study included 21 126 participants from the i3C Consortium (International Childhood Cardiovascular Cohorts). Proportional hazards regressions were used to estimate the risk for incident fatal and fatal/nonfatal ASCVD events associated with childhood non-HDL-C and LDL-C levels (age- and sex-specific z scores; concordant/discordant categories defined by guideline-recommended cutoffs), adjusted for sex, Black race, cohort, age at and calendar year of child measurement, body mass index, and systolic blood pressure. Predictive utility was determined by the C index. After an average follow-up of 35 years, 153 fatal ASCVD events occurred in 21 126 participants (mean age at childhood visits, 11.9 years), and 352 fatal/nonfatal ASCVD events occurred in a subset of 11 296 participants who could be evaluated for this outcome. Childhood non-HDL-C and LDL-C levels were each associated with higher risk of fatal and fatal/nonfatal ASCVD events (hazard ratio ranged from 1.27 [95% CI, 1.14-1.41] to 1.35 [95% CI, 1.13-1.60] per unit increase in the risk factor z score). Non-HDL-C had better discriminative utility than LDL-C (difference in C index, 0.0054 [95% CI, 0.0006-0.0102] and 0.0038 [95% CI, 0.0008-0.0068] for fatal and fatal/nonfatal events, respectively). The discordant group with elevated non-HDL-C and normal LDL-C had a higher risk of ASCVD events compared with the concordant group with normal non-HDL-C and LDL-C (fatal events: hazard ratio, 1.90 [95% CI, 0.98-3.70]; fatal/nonfatal events: hazard ratio, 1.94 [95% CI, 1.23-3.06]). Childhood non-HDL-C and LDL-C levels are associated with ASCVD events in midlife. Non-HDL-C is better than LDL-C in predicting adult ASCVD events, particularly among individuals who had normal LDL-C but elevated non-HDL-C. These findings suggest that both non-HDL-C and LDL-C are useful in identifying children at higher risk of ASCVD events, but non-HDL-C may provide added prognostic information when it is discordantly higher than the corresponding LDL-C and has the practical advantage of being determined without a fasting sample.

Abstract 12444: Pulse Pressure and Cardiovascular and Renal Outcomes by Age in the Chronic Renal Insufficiency Cohort

Pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to end stage kidney disease (ESKD). While PP is known to widen with age, it is less clear what other clinical factors affect PP and whether the risks associated with wide PP are the same across all ages. We used Cox proportional hazards models to investigate the association of PP with development of 1) atherosclerotic cardiovascular disease (ASCVD) events (congestive heart failure hospitalization, myocardial infarction, stroke and peripheral artery disease) or death and 2) 50% reduction in estimated glomerular filtration rate (eGFR) or ESKD in the Chronic Renal Insufficiency Cohort (CRIC) Study. In sensitivity analyses, we evaluated the association of time-updated PP with these outcomes, accounting for potential time-updated confounders using inverse probability of treatment weighting. We evaluated for effect modification by age (divided into tertiles), apparent treatment-resistant hypertension (HTN), baseline diabetes mellitus (DM) status, baseline CKD stage and baseline cardiovascular disease (CVD). Among 5,621 participants with CKD followed for ~5.4 years, mean PP was 57±19 mmHg, 1,396 (25%) had an ASCVD event, 1,186 (21%) died and 1,783 (32%) participants experienced the composite renal outcome. Every 10 mm Hg wider PP was associated with 6% higher risk of an ASCVD event or death (time-updated adjusted hazard ratio [HR]=1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite renal outcome (time-updated adjusted HR=1.17, 95% CI 1.16, 1.18). Wider PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years; Figure 1A ), but a higher risk of the composite renal outcome in the oldest age tertile (71-79 years; Figure 1B ), suggesting PP may be associated with different pathophysiology across ages.

State of current management of the heightened risk for atherosclerotic cardiovascular events in an established cohort of patients with lupus erythematosus

ObjectivePatients with lupus erythematosus (LE) are at heightened risk for clinical events, chiefly heart attacks and strokes, from atherosclerotic cardiovascular disease (ASCVD). We recently proposed new guidelines to assess and...

Prognostic value of coronary artery calcium score for the prediction of atherosclerotic cardiovascular disease in participants with suspected nonalcoholic hepatic steatosis: Results from the multi-ethnic study of atherosclerosis

Nonalcoholic fatty liver disease (NAFLD) is associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD) events; thus, a diagnostic approach to help identify NAFLD patients at high risk is needed. In this study, we hypothesized that coronary artery calcium (CAC) screening could help stratify the risk of ASCVD events in participants with suspected nonalcoholic hepatic steatosis. A total of 713 participants with suspected nonalcoholic hepatic steatosis without previous cardiovascular events from the Multi-Ethnic Study of Atherosclerosis (MESA) were followed for the occurrence of incident ASCVD. Nonalcoholic hepatic steatosis was defined using nonenhanced computed tomography and liver/spleen attenuation ratio <1. Cox proportional hazards regression models were used to estimate hazard ratios (HR). C-statistics and areas under the time-dependent receiver operating characteristic curves (tAUC) were used to compare incremental contributions of CAC score when added to the clinical risk factors. In multivariable analyses, CAC score was found to be independently associated with incident ASCVD (HR=1.33, 95% CI=1.22-1.44, P < .001). The addition of CAC score to clinical risk factors increased the C-statistic from 0.677 to 0.739 (P < .001) and tAUC at 10 years from 0.668 to 0.771, respectively. In subgroup analyses, the incremental prognostic value of CAC score was more significant in participants with low/borderline- (<7.5%) and intermediate- (7.5%-20%) 10-year ASCVD risk scores. The inclusion of CAC score in global risk assessment was found to significantly improve the classification of incident ASCVD events in participants with suspected nonalcoholic hepatic steatosis, indicating a potential role for CAC screening in risk assessment.

Evolving Management of Low-Density Lipoprotein Cholesterol: A Personalized Approach to Preventing Atherosclerotic Cardiovascular Disease Across the Risk Continuum.

Management of elevated low-density lipoprotein cholesterol (LDL-C) is central to preventing atherosclerotic cardiovascular disease (ASCVD) and key to reducing the risk of ASCVD events. Current guidelines on the management of blood cholesterol recommend statins as first-line therapy for LDL-C reduction according to an individual's ASCVD risk and baseline LDL-C levels. The addition of nonstatin lipid-lowering therapy to statins to achieve intensive LDL-C lowering is recommended for patients at very high risk of ASCVD events, including patients with familial hypercholesterolemia who have not achieved adequate LDL-C lowering with statins alone. Despite guideline recommendations and clinical trial evidence to support the use of lipid-lowering therapies for ASCVD risk reduction, most patients at high or very high risk do not meet LDL-C thresholds. This review explores the challenges associated with LDL-C lowering in contemporary clinical practice and proposes a framework for rethinking the binary definition of ASCVD, shifting from "primary" versus "secondary" prevention to a "continuum of risk." The approach considers the role of plaque burden and progression in subclinical disease and emphasizes the importance of early risk assessment and treatment for preventing first cardiovascular events. Patients at high risk of ASCVD events who require significant LDL-C lowering should be considered for combination therapies comprising statin and nonstatin agents. Practical guidance for the pharmacological management of elevated LDL-C, both now and in the future, is provided.

Red Yeast Rice for the Improvement of Lipid Profiles in Mild-to-Moderate Hypercholesterolemia: A Narrative Review.

Reducing low-density lipoprotein cholesterol (LDL-C) levels is a key target for lowering cardiovascular risk and preventing atherosclerotic cardiovascular disease (ASCVD). Red yeast rice (RYR) is a nutraceutical widely used as a lipid-lowering dietary supplement. The main cholesterol-lowering components of RYR are monacolins, particularly monacolin K, which is structurally identical to lovastatin and targets the same key enzyme of cholesterol biosynthesis. RYR supplementation reduces LDL-C levels by approximately 15-34% versus placebo, with a similar effect to low-dose, first-generation statins in subjects with mild-to-moderate dyslipidemia. RYR has also demonstrated beneficial reductions of up to 45% versus placebo in the risk of ASCVD events in secondary prevention studies. RYR at a dose that provides about 3 mg/d of monacolin K is well tolerated, with an adverse event profile similar to that of low-dose statins. RYR is therefore a treatment option for lowering LDL-C levels and ASCVD risk for people with mild-to-moderate hypercholesterolemia who are ineligible for statin therapy, particularly those who are unable to implement lifestyle modifications, and also for people who are eligible for statin therapy but who are unwilling to take a pharmacologic therapy.

Lipoprotein(a) and the Risk for Recurrent Atherosclerotic Cardiovascular Events Among Adults With CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study

Many adults with chronic kidney disease (CKD) and atherosclerotic cardiovascular disease (ASCVD) have high lipoprotein(a) levels. It is unclear whether high lipoprotein(a) levels confer an increased risk for recurrent ASCVD events in this population. We estimated the risk for recurrent ASCVD events associated with lipoprotein(a) in adults with CKD and prevalent ASCVD. Observational cohort study. We included 1,439 adults with CKD and prevalent ASCVD not on dialysis enrolled in the Chronic Renal Insufficiency Cohort study between 2003 and2008. Baseline lipoprotein(a) mass concentration, measured using a latex-enhanced immunoturbidimetric assay. Recurrent ASCVD events (primary outcome), kidney failure, and death (exploratory outcomes) through2019. We used Cox proportional-hazards regression models to estimate adjusted HR (aHRs) and 95% CIs. Among participants included in the current analysis (mean age 61.6 years, median lipoprotein(a) 29.4 mg/dL [25th-75th percentiles 9.9-70.9 mg/dL]), 641 had a recurrent ASCVD event, 510 developed kidney failure, and 845 died over a median follow-up of 6.6 years. The aHR for ASCVD events associated with 1 standard deviation (SD) higher log-transformed lipoprotein(a) was 1.04 (95% CI, 0.95-1.15). In subgroup analyses, 1 SD higher log-lipoprotein(a) was associated with an increased risk for ASCVD events in participants without diabetes (aHR, 1.23; 95% CI, 1.02-1.48), but there was no evidence of an association among those with diabetes (aHR, 0.99; 95% CI, 0.88-1.10, P comparing aHRs=0.031). The aHR associated with 1 SD higher log-lipoprotein(a) in the overall study population was 1.16 (95% CI, 1.04-1.28) for kidney failure and 1.02 (95% CI, 0.94-1.11) for death. Lipoprotein(a) was not available in molar concentration. Lipoprotein(a) was not associated with the risk for recurrent ASCVD events in adults with CKD, although it was associated with a risk for kidney failure.

HDL - Quo vadis

Many epidemiological studies found low plasma levels of high-density lipoprotein (HDL) cholesterol (HDL-C) associated with an increased risk of atherosclerotic cardiovascular disease (ASCVD). In cell culture and animal models, HDL particles show many anti-atherogenic actions. However, until now, clinical trials did not find any prevention of ASCVD events by drugs elevating HDL-C levels, at least not beyond statins. Also, genetic studies show no associations of HDL-C levels altering variants with cardiovascular risk. Therefore, the causal role and clinical benefit of HDL-C elevation in ASCVD are questioned. However, the interpretation of previous data has important limitations: First, the inverse relationship of HDL-C with the risk of ASCVD is limited to concentrations < 60 mg/dl (< 1.5 mmol/l). Higher concentrations do not reduce the risk of ASCVD events and are even associated with increased mortality. Therefore, neither the higher-the-better strategies of earlier drug developments nor the assumption of linear cause-and-effect relationships in Mendelian randomization trials are justified. Second, most of the drugs tested so far do not act specifically on HDL metabolism. Therefore, the futile endpoint studies question the clinical benefit of the investigated drugs, but not the importance of HDL in ASCVD. Third, the vascular functions of HDL are not exerted by its cholesterol content (i.e. HDL-C), but by a variety of other molecules. Comprehensive knowledge of the structure-function-disease relationships of HDL particles and their molecules is a prerequisite for testing their physiological and pathogenic relevance and possibly for optimizing the diagnosis and treatment of persons with HDL-associated risk of ASCVD, but also for other diseases, such as diabetes, chronic kidney disease, infections, autoimmune and neurodegenerative diseases.

Abstract P667: Association of Number of Calcified Coronary Arteries and Cardiovascular Outcomes Stratified by Calcification Volume: The Multi-Ethnic Study of Atherosclerosis (MESA)

Background: Coronary artery calcium (CAC) is a risk factor for atherosclerotic cardiovascular disease (ASCVD). Data suggests number of vessels with CAC independently improves risk prediction but impact by CAC volume remains unknown. Methods: Using data from 3256 MESA participants with CAC&gt;0 and clinical follow-up, we evaluated the association between number of arteries with CAC and risk for coronary heart disease (CHD), myocardial infarction (MI), and CVD events stratified by CAC volume (above/below median) using multivariable-adjusted Cox proportional hazards models. Results: Mean age was 63.3 years (SD 9.5) with 1363 (41.9%) women. There were 1079 (33%) with single-vessel, 822 (25%) with 2-vessel, and 1355 (42%) with 3-4 vessel CAC. Median CAC volume was 84.7 [IQR 24.5, 267.2] mm 3 . CAC in 3-4 vessels was independently associated with higher CHD risk ( Figure ) compared to 1-vessel (HR 2.01, 95% CI 1.1-3.6; p=0.018) and 2-vessels (HR 1.69, 95% CI 1.0-2.8; p=0.04) for lower CAC volumes, with similar findings for MI and CVD outcomes ( Table ). Conclusions: Number of arteries with CAC independently increases risk for ASCVD events only for those with lower CAC volumes.

Personalized statin treatment plan using counterfactual approach with multi-objective optimization over benefits and risks

BackgroundStatins are a class of drugs that lower cholesterol levels in the blood by inhibiting an enzyme called 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. High cholesterol levels can lead to plaque buildup in the arteries, which can cause Atherosclerotic Cardiovascular Disease(ASCVD). Statins can reduce the risk of ASCVD events by about 25–35% but they might be associated with symptoms such as muscle pain, liver damage, or diabetes. As a result, this leads to a strong reason to discontinue statin therapy, which increases the risk of cardiovascular events and mortality and becomes a public-health problem.To solve this problem, in the previous work, we proposed a framework to produce a proactive strategy, called a personalized statin treatment plan (PSTP) to minimize the risks of statin-associated symptoms and therapy discontinuation when prescribing statin. In our previous PSTP framework, three limitations remain, and they can influence PSTP usability: (1) Not taking the counterfactual predictions and confounding bias into account. (2) The balance between multiple drug-prescribing objectives (especially trade-off objectives), such as tradeoff between benefits and risks. (3) Evaluating PSTP in retrospective data. ObjectivesThis manuscript aimed to provide solutions for the three abovementioned problems to improve PSTP robustness to produce a proactive strategy for statin prescription that can maximize the benefits (low-density lipoprotein cholesterol (LDL-C) reduction) and minimize risks (statin-associated symptoms and therapy discontinuation) at the same time. MethodsWe applied overlapping weighting counterfactual survival risk prediction (CP), multiple objective optimization (MOO), and clinical trial simulation (CTS) which consists of Random Arms, Clinical Guideline arms, PSTP Arms, and Practical Arms to improve the PSTP framework and usability. ResultsIn addition to highly balanced covariates, in the CTS, the revised PSTP showed improvements in lowering the SAS risks overall compared to other arms across all time points by at most 7.5% to at least 1.0% (Fig. 8(a)). It also has the better flexibility of identifying the optimal Statin across all time points within one year. ConclusionWe demonstrated feasibility of robust and trustworthy counterfactual survival risk prediction model. In CTS, we also demonstrated the PSTP with Pareto optimization can personalize optimal balance between Statin benefits and risks.

Coronary Artery Calcium Scoring for Risk Assessment in Patients With Severe Hypercholesterolemia

The American College of Cardiology and the American Heart Association guidelines recommend treatment of patients with severe hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] ≥190 mg/100 ml) with a high-intensity statin. However, atherosclerotic cardiovascular disease (ASCVD) risk, even among those with severe hypercholesterolemia, is heterogeneous, and coronary artery calcium (CAC) scoring may be used to clarify risk. We sought to evaluate CAC in patients with severe hypercholesterolemia and measure its impact on real-world statin prescriptions. We identified patients with at least 1 LDL-C ≥190 mg100 ml who had a CAC scoring in the Community Benefit of No-Charge Calcium Score Screening Program (CLARIFY) study (NCT04075162) between 2014 and 2020. We explored the CAC distribution, factors associated with CAC >0, and ASCVD risk (myocardial infarction, stroke, revascularization, death). A total of 1,904 patients (1.257 women, aged 57.8 ± 9.3 years) with severe hypercholesterolemia were included. LDL-C ranged from 190 to 524 mg100 ml (mean 215.5 ± 27 mg100 ml). A total of 864 patients (45.4%) had CAC=0 and 1,561 (82%) had CAC <100. In patients with LDL-C ≥250 mg100 ml, 67 (36.6%) had CAC=0. Age, male gender, smoking, diabetes, systolic blood pressure, and obesity (ps ≤0.001) were associated with CAC >0. In patients with LDL-C ≥190 mg100 ml, CAC was associated with a higher risk for ASCVD events (CAC ≥100 vs CAC <100, hazard ratio 3.57 [1.81 to 7.04], p <0.001). A higher CAC category was associated with increased statin use after CAC scoring (p <0.001). In patients with severe hypercholesterolemia, 45% had CAC=0, which was associated with a significantly lower ASCVD risk. CAC was associated with statin prescription and cholesterol lowering. In conclusion, CAC scoring may be used to clarify ASCVD risk in this heterogeneous population with severe hypercholesterolemia.

Abstract 10917: Bone Mineral Density for Stratification and Prediction of Risk for Cardiovascular Outcomes in Women

Introduction: Atherosclerotic Cardiovascular disease ( ASCVD) in women remains understudied, under-diagnosed, and under-treated. It is known that traditional risk factors have varied effects on men's vs. women's hearts. However, the current risk stratification tools tend to underestimate or not consider such sex-specific factors. We aimed to investigate the utility of bone mineral density (BMD) with DEXA scoring as a predictor of ASCVD in women. Methods: Patients who underwent DEXA scanning from 2012 to 2014 at multiple centers within our health system were collected and categorized using International Classification of Diseases (ICD) diagnosis codes to identify comorbidities and outcomes. Age, Sex, Race, history of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), body mass index (BMI), and smoking status were noted. Results: Of the 2,254 patients who underwent DEXA scanning, 1,995 participants were female (88.5%), and 1,929 were white (85.6%) with an average age of 72.8 years. The primary outcome was any ASCVD event (stroke, MI and cardiac death). During the mean follow-up of 9 years, 245 patients (10.8%) experienced ASCVD events. Patients with osteoporosis defined by a T score &lt;-2.5 had higher odds of ASCVD events (OR - 3.82 [2.370-6.172], P&lt;0.0001). Osteopenia was defined by a T score between -1 and -2.5 and was not associated with an increased risk of ASCVD events (OR 1.2 [0.782-1.957] P &lt;0.36). Conclusions: BMD measurement with DEXA scanning may be useful for the stratification and prediction of risk for ASCVD events in women, with no additional economic strain on the healthcare system. Further wide-scale studies are needed to utilize this potentially promising predictor and commonly used diagnostic test. .

Baseline cardiovascular risk in subjects with type 2 diabetes and chronic kidney disease from the FLOW trial

Abstract Background Patients with chronic kidney disease and type 2 diabetes (T2D) have a high risk of progression to kidney failure as well as cardiovascular (CV) events. It is established that glucagon-like peptide-1 receptor agonists (GLP-1RAs) improve glycaemic control and reduce body weight. Some CV outcomes trials have shown that GLP-1RAs reduce CV risk in people with T2D at high CV risk; for example, the SUSTAIN 6 trial demonstrated that the GLP-1RA semaglutide significantly lowered the rate of major CV events (CV death, non-fatal myocardial infarction and non-fatal stroke) versus placebo. Some trials have also indicated that GLP-1RAs reduce albuminuria and estimated glomerular filtration rate (eGFR) decline. Based on these previous results indicating potential kidney-protective effects, the FLOW trial (NCT03819153) is evaluating once-weekly, subcutaneous semaglutide 1.0 mg versus placebo on kidney- and CV-related outcomes in participants with T2D. We describe the baseline characteristics and the calculated CV risk of this patient population using the atherosclerotic CV disease (ASCVD) and second manifestations of arterial disease (SMART) risk calculators. Methods FLOW is an ongoing, multicentre, randomised, double-blind, parallel-group, event-driven, phase 3b trial, with participants randomised 1:1 to semaglutide or placebo, each in addition to standard of care. Recruitment is complete and 3,535 participants with T2D, an eGFR ≥25–≤75 mL/min/1.73 m2, and urine albumin-to-creatinine ratio ≥100–≤5,000 mg/g have been enrolled. The primary endpoint is time to first occurrence of a kidney composite that includes ≥50% persistent eGFR reduction, kidney failure (persistent eGFR &amp;lt;15 mL/min/1.73 m2 or initiation of chronic dialysis or kidney transplantation), and kidney-related death, or CV death. Key secondary outcomes include time to first occurrence of CV death, myocardial infarction or stroke. Results The baseline clinical characteristics and demographics are shown (Table 1). Median age was 68 years, 30% were female, mean diabetes duration was 17 years, and 98% had a history of hypertension. Overall, 52% of participants had a previous CV event. The calculated 10-year risk for ASCVD events in those without prior ASCVD was 31% in males and 18% in females, and in those with previous CV events was 37–56% in males and 35–53% in females depending on the type of CV disease reported in the calculator (Table 2). Conclusions The FLOW trial has completed enrolment. Based on the ASCVD and SMART risk calculators, the enrolled population has a substantial risk for adverse CV outcomes. Event ascertainment is ongoing, and the FLOW trial will provide evidence for the potential of semaglutide to improve kidney and CV outcomes in the T2D population. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novo Nordisk

Bone Mineral Density as a Predictor of Cardiovascular Disease in Women: A Real-World Retrospective Study

Background: Atherosclerotic cardiovascular disease (ASCVD) in women remains understudied, under-diagnosed, and under-treated. Traditional risk factors affect men’s and women’s hearts differently. However, the current risk stratification tools do not consider such sex-specific factors. We aimed to investigate the utility of bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA) scoring as a predictor of ASCVD in women. Methods: Data of 1,995 patients who underwent DXA scanning from 2012 to 2014 at multiple centers within our health system were collected through a chart review and using the SlicerDicer tool of Epic electronic medical records (EMR) to identify comorbidities and outcomes. Age, sex, race, history of hypertension (HTN), hyperlipidemia (HLD), diabetes mellitus (DM), body mass index (BMI), and smoking status were noted. The primary outcome was the composite of ASCVD events (stroke, myocardial infarction (MI) and cardiac death). Osteoporosis was defined as a T score of &lt; -2.5, and osteopenia was defined as a combined T score between -1.5 to -2.5 in either hip, one of the femurs or combined. Results: Of the 1,995 female participants who underwent DXA scanning, 245 patients (10.8%) experienced ASCVD events during the mean follow-up of 9 years. After adjusting covariables, women with osteoporosis and combined low BMD have higher odds of the composite ASCVD events compared to normal BMD (odds ratio (OR) 4.60 (2.783 - 7.867), P &lt; 0.0001). Low BMD in each site, the right femur, left femur, and hip is associated with an increased risk of ASCVD events (OR 6.50 (3.637 - 11.608), P &lt; 0.0001; OR 5.07 (3.166 - 8.108), P &lt; 0.000; OR 3.36 (2.127 - 5.312), P &lt; 0.0001, respectively). Osteoporosis is independently linked to a 4.25-fold rise in MI incidence and a 3.64-fold rise in stroke. Osteopenia was not associated with ASCVD events (OR 1.29 (0.754 - 2.204), P = 0.35416). Conclusions: BMD measurement with DXA scan could stratify and predict the risk of ASCVD events in women, with no additional economic strain on healthcare. Further wide-scale studies are needed to utilize this potentially promising predictor and a commonly used test. J Endocrinol Metab. 2022;12(4-5):125-133 doi: https://doi.org/10.14740/jem840

148 Management of the heightened risk for clinical events from atherosclerotic cardiovascular disease (ASCVD) in an established cohort of lupus erythematosus patients

Lupus erythematosus (LE) patients are at heightened risk of clinical events, chiefly heart attacks and strokes, caused by ASCVD. To address this problem, we recently proposed new guidelines for categorization of levels of risk for ASCVD events in LE patients, with corresponding recommendations for management of conventional risk factors, chiefly hypercholesterolemia, hypertension, smoking, and diabetes mellitus (Keyes E et al. 2021). Here, we performed a single-center study of our established cohort of cutaneous LE patients without or with concurrent systemic LE (n=370).