High Atherosclerotic Cardiovascular Disease Research Articles

High levels of lipoprotein(a) are associated with the severity of coronary disease in patients with acute myocardial infarction. Data from the RICO survey

Abstract Background High level of lipoprotein(a), Lp(a), is a well-recognized independent risk factor for atherosclerotic cardiovascular disease (ASCVD) including acute myocardial infarction (MI). However, limited data are available on the relationship between coronary artery disease (CAD) burden and Lp(a) levels in patients with acute MI. Methods CAD burden was addressed in 1213 consecutive patients hospitalized for an acute MI in 2019–2020 who underwent coronary angiography from the RICO survey. Patients were compared according to Lp(a) levels (Lp(a) <50 mg/dL (normal), ≥50 mg/dL and ≤100 mg/dL (high) and >100 mg/dL (very high)). Results The prevalence of high and very high Lp(a) was elevated (13% and 6%, respectively). Median (IQR) age (normal: 68 (58–79)y; high: 70 (61–80)y; very high: 69 (60–78)y, p=0.502) and rate of diabetes (p=0.448) were similar across the 3 groups. When compared with normal Lp(a), patients with very high Lp(a) had more frequently hypertension, were more often under chronic statin therapy and their corrected LDL-cholesterol was lower. There was a gradual increase in prior ASCVD rates across the 3 Lp(a) groups (p=0.001). When compared with patients with high or normal Lp(a), patients with very high Lp(a) levels had elevated SYNTAX score at coronary angiography, (17 (6–25) vs 12 (6–19) and 10 (5–18), p=0.006, respectively), and had more frequently multivessel disease (74% vs 64% and 56%, p=0.003). By multivariate analysis, very high Lp(a) (OR(95% CI): 1.879 (1.065–3.312)) remained associated with high CAD burden, beyond confounding including age, diabetes and dyslipidemia. Conclusion Among real world patients hospitalized for an acute MI, high Lp(a) levels are common (≈20%) and independently associated with a severe CAD burden, beyond traditional risk factors, identifying a subset of patients with features of high ASCVD risk. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): CHU Dijon Bourgogne ARS Bourgogne Franche Comté

SMARTPHONE APPLICATION TO RISK STRATIFY PATIENTS WITH CORONARY ARTERY DISEASE AND FACILITATE PERSONALIZED GUIDELINE-DIRECTED MEDICAL THERAPY

SMARTPHONE APPLICATION TO RISK STRATIFY PATIENTS WITH CORONARY ARTERY DISEASE AND FACILITATE PERSONALIZED GUIDELINE-DIRECTED MEDICAL THERAPY

Relationship of Noninvasive Assessment of Arterial Stiffness with 10-Year Atherosclerotic Cardiovascular Disease (ASCVD) Risk in a General Middle-Age and Elderly Population.

PurposeAs a powerful indicator of arterial stiffening, the brachial-ankle pulse wave velocity (baPWV) has been extensively validated for predicting cardiovascular events. However, whether and how the brachial-ankle pulse wave velocity (baPWV) is correlated with the 10-year atherosclerotic cardiovascular disease (ASCVD) risk is unclear. This study aimed to investigate the association between baPWV and 10-year ASCVD risk in Chinese population.MethodsA total of 1768 subjects were enrolled from Shanghai, China. They were divided into two groups according to the Pooled Cohorts Equations model made by ACC/AHA as follows: low ASCVD risk (n = 992, 10-year ASCVD risk <7.5%) and high ASCVD risk (n = 776, 10-year ASCVD risk ≥7.5%). The baseline characteristics were obtained via the use of a questionnaire. Measurement of baPWV, laboratory tests, and echocardiography were conducted by trained physicians. The relationship between baPWV and 10-year ASCVD risk was evaluated using multiple logistic regression model and generalized additive model.ResultsThe mean age of the subjects was 58.89±8.60 years, 32.69% of which were male. Non-linear relationship analysis revealed threshold effects between baPWV and 10-year ASCVD risk in which a baPWV of approximately 16 m/s might be the threshold effect of 10-year ASCVD risk. After multivariable adjustment, logistic-regression analysis demonstrated that ankle-brachial index (ABI) (OR 5.28, 95% CI 1.20–12.23) and baPWV (OR 9.09, 95% CI 6.84–12.07) were independently correlated with 10-year ASCVD risk. The AUC for baPWV for predicting 10-year ASCVD risk was 0.80 (95% CI 0.78–0.82).ConclusionIncreased baPWV as an indicator of arterial stiffness correlates strongly with 10-year ASCVD risk in general middle-aged and elderly populations. The association between baPWV and 10-year ASCVD risk is not purely linear but non-linear. Subjects with baPWV above 16 m/s are more likely to encounter a higher 10-year ASCVD risk.

Atherothrombotic factors and atherosclerotic cardiovascular events: the multi-ethnic study of atherosclerosis.

Traditional atherosclerotic cardiovascular disease (ASCVD) risk factors fail to address the full spectrum of the complex interplay of atherosclerotic and atherothrombotic factors integral to ASCVD events. This study sought to examine the association between atherothrombotic biomarkers and ASCVD events. The association between atherothrombotic biomarkers and 877 ASCVD events with and without adjustment for traditional risk factors was evaluated via Cox proportional hazards models and factor analysis in 5789 Multi-Ethnic Study of Atherosclerosis participants over a median follow-up of 14.7 years. Factor analysis accounted for multidimensional relationship and shared variance among study biomarkers, which identified two new variables: a thrombotic factor (Factor 1), principally defined by shared variance in fibrinogen, plasmin-antiplasmin complex, factor VIII, D-dimer, and lipoprotein(a), and a fibrinolytic factor (Factor 2), principally defined by shared variance of plasminogen and oxidized phospholipids on plasminogen. In a model including both factors, the thrombotic factor was associated with the higher risk of ASCVD events [hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45, 1.70], while the fibrinolytic factor was associated with the lower risk of ASCVD events (HR 0.76, 95% CI 0.70, 0.82), with estimated ASCVD free survival highest for low atherothrombotic Factor 1 and high atherothrombotic Factor 2. Two atherothrombotic factors, one representative of thrombotic propensity and the other representative of fibrinolytic propensity, were significantly and complementarily associated with incident ASCVD events, remained significantly associated with incident ASCVD after controlling for traditional risk factors, and have promise for identifying patients at high ASCVD event risk specifically due to their atherothrombotic profile.

The Effects of Statin Dose, Lipophilicity, and Combination of Statins plus Ezetimibe on Circulating Oxidized Low-Density Lipoprotein Levels: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background Elevated plasma low-density lipoprotein cholesterol (LDL-C) is the main risk factor for atherosclerotic cardiovascular disease (ASCVD). Statins are the drugs of choice for decreasing LDL-C and are used for the prevention and management of ASCVD. Guidelines recommend that subjects with high and very high ASCVD risk should be treated with high-intensity statins or a combination of high-intensity statins and ezetimibe. The lipophilicity or hydrophilicity (solubility) of statins is considered to be important for at least some of their LDL-C lowering independent pleiotropic effects. Oxidative modification of LDL (ox-LDL) is considered to be the most important atherogenic modification of LDL and is supposed to play a crucial role in atherogenesis and ASCVD outcomes. Objective The aim of this systematic review and meta-analysis was to find out what are the effects of statin intensity, lipophilicity, and combination of statins plus ezetimibe on ox-LDL. Methods PubMed, Scopus, Embase, and Web of Science were searched from inception to February 5, 2021, for randomized controlled trials (RCTs). Two independent and blinded authors evaluated eligibility by screening the titles and abstracts of the studies. Risk of bias in the studies included in this meta-analysis was evaluated according to the Cochrane instructions. Meta-analysis was performed using Comprehensive Meta-Analysis (CMA) V2 software. Evaluation of funnel plot, Begg's rank correlation, and Egger's weighted regression tests were used to assess the presence of publication bias. Results Among the 1427 published studies identified by a systematic databases search, 20 RCTs were finally included in the systematic review and meta-analysis. A total of 1874 patients are included in this meta-analysis. This meta-analysis suggests that high-intensity statin treatment is associated with a significant decrease in circulating concentrations of ox-LDL when compared with low-to-moderate treatment (SMD: -0.675, 95% CI: -0.994, -0.357, p < 0.001; I2: 55.93%). There was no difference concerning ox-LDL concentration between treatments with hydrophilic and lipophilic statins (SMD: -0.129, 95% CI: -0.330, -0.071, p = 0.206; I2: 45.3%), but there was a significant reduction in circulating concentrations of ox-LDL associated with statin plus ezetimibe combination therapy when compared with statin monotherapy (SMD: -0.220, 95% CI: -0.369, -0.071, p = 0.004; I2: 0%). Conclusion High-dose statin or combination of statins with ezetmibe reduces plasma ox-LDL in comparison low-to-moderate intensity statin therapy alone. Statin lipophilicity is not associated with reduction in ox-LDL plasma concentrations.

Population health management of low-density lipoprotein cholesterol via a remote, algorithmic, navigator-executed program

Implementation of guideline-directed cholesterol management remains low despite definitive evidence establishing such measures reduce cardiovascular (CV) events, especially in high atherosclerotic CV disease (ASCVD) risk patients. Modern electronic resources now exist that may help improve health care delivery. While electronic medical records (EMR) allow for population health screening, the potential for coupling EMR screening to remotely delivered algorithmic population-based management has been less studied as a way of overcoming barriers to optimal cholesterol management. In an academically affiliated healthcare system, using EMR screening, we sought to identify 1,000 high ASCVD risk patients not meeting guideline-directed low-density lipoprotein-cholesterol (LDL-C) goals within specific system-affiliated primary care practices. Contacted patients received cholesterol education and were offered a remote, guideline-directed, algorithmic cholesterol management program executed by trained but non-licensed "navigators" under professional supervision. Navigators used telephone, proprietary software and internet resources to facilitate algorithm-driven, guideline-based medication initiation/titration, and laboratory testing until patients achieved LDL-C goals or exited the program. As a clinical effectiveness program for cholesterol guideline implementation, comparison was made to those contacted patients who declined program-based medication management, and received education only, along with their usual care. 1021 patients falling into guideline-defined high ASCVD risk groups warranting statin therapy (ASCVD, type 2 diabetes, LDL ≥ 190 mg/dL, calculated 10-year ASCVD risk ≥7.5%) and not achieving guideline-defined target LDL-C levels and/or therapy were identified and contacted. Among the 698 such patients who opted for program medication management, significant LDL-C reductions occurred in the total cohort (mean -65.4 mg/dL, 45% decrease), and each high ASCVD risk subgroup: ASCVD (-57.2 mg/dL, -48.0%); diabetes mellitus (-53.1 mg/dL, -40.0%); severe hypercholesterolemia (-76.3 mg/dL, -45.7%); elevated ASCVD 10-year risk (-62.8 mg/dL, -41.1%) (P<0.001 for all), without any significant complications. Among 20% of participants with reported statin intolerance, average LDL-C decreased from baseline 143 mg/dL to 85 mg/dL using mainly statins and ezetimibe, with limited PCSK9 inhibitor use. In comparison, eligible high ASCVD risk patients who were contacted but opted for education only, a 17% LDL-C decrease occurred over a similar timeframe, with 80% remaining with an LDL-C over 100 mg/dL. A remote, algorithm-driven, navigator-executed cholesterol management program successfully identified high ASCVD risk undertreated patients using EMR screening and was associated with significantly improved guideline-directed LDL-C control, supporting this approach as a novel strategy for improving health care access and delivery.

Prevalence and Risk Factors of Cardiovascular Disease in Patients with Chronic Hepatitis B

The association between chronic hepatitis B (CHB) and cardiovascular disease (CVD) remains unclear. We investigated the prevalence and risk factors of CVD in patients with CHB. Data from the Korean National Health and Nutrition Examination Surveys 2008-2011 were analyzed. Significant liver fibrosis was defined as the highest nonalcoholic fatty liver disease fibrosis score quartile, highest Forns index quintile, or fibrosis-4 ≥ 2.67. The CVD risk was calculated using the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score from the 2013 ACC/AHA Guidelines. Among the 506 subjects with CHB, 15 (3.0%) and 150 (29.6%) patients had a CVD history and significant liver fibrosis, respectively. Patients with CVD history were significantly older; showed a significantly higher prevalence of hypertension, metabolic syndrome, and significant liver fibrosis; and had a significantly higher platelet count, lower aspartate and alanine aminotransferase levels, higher triglyceride level, lower high-density lipoprotein level, and higher ASCVD risk than those without (all p < 0.05). In multivariate analysis, higher ASCVD risk (odds ratio [OR] = 1.090) and significant liver fibrosis (OR = 4.341) independently predicted the risk of CVD history (p < 0.05). The prevalence of CVD risk (6.7% vs. 1.4%; OR = 5.014) and high ASCVD risk (> 15%) (34.0% vs. 7.3%; OR = 6.538) was significantly higher in patients with significant liver fibrosis than in those without (all p < 0.05). Significant liver fibrosis was independently associated with the risk of CVD history in patients with CHB. Prospective studies are needed to validate the longitudinal association between fibrotic burden and CVD development in patients with CHB.

Persistent inflammatory residual risk despite aggressive cholesterol-lowering therapy: what is next?

To briefly summarize recently published evidence on the possible therapeutic modulation of inflammatory processes in atherosclerotic cardiovascular disease (ASCVD), focusing on the rationale for an additional randomized clinical trial, targeting both persistently elevated cholesterol and inflammatory residual risk and critically discuss still open issues and future perspectives with regard to treatment allocation. Several large-scale clinical trials over the past few years have advanced our understanding of the role of inflammation in atherosclerosis, demonstrating that targeting the NLRP3 inflammasome and the IL-1β pathway indeed represent a new avenue to reduce residual risk in patients with ASCVD. However, despite optimal lipid-lowering therapy and novel options to modulate residual inflammatory risk, there are still a large number of individuals, being at high risk for recurrent ASCVD events. The integration of a dual target strategy aimed at lowering the inflammatory burden in combination with aggressive lipid-modifying for those at high/very high ASCVD risk may hold potential to significantly improve patient care. However, a number of questions related to the design of such 2 × 2 factorial trial still needs to be answered.

Use of Computed Tomography Coronary Calcium Score for Coronary Artery Disease Risk Stratification During Liver Transplant Evaluation

End-stage liver disease (ESLD) is not considered a risk factor for atherosclerotic cardiovascular disease (ASCVD). However, lifestyle characteristics commonly associated with increased ASCVD risk are highly prevalent in ESLD. Emerging literature shows a high burden of asymptomatic coronary artery disease (CAD) in patients with ESLD and a high ASCVD risk in liver transplantation (LT) recipients. Coronary artery calcium score (CAC) is a noninvasive test providing reliable CAD risk stratification. We implemented an LT evaluation protocol with CAC playing a central role in triaging and determining the need for further CAD assessment. Here, we inform our results from this early experience. Patients with ESLD referred for LT evaluation were prospectively studied. We compared accuracy of CAC against that of CAD risk factors/scores, troponin I, dobutamine stress echocardiogram (DSE), and single-photon emission computed tomography (SPECT) to detect coronary stenosis ≥70 (CAD≥70) per left heart catheterization (LHC). Thirty-day post-LT cardiac outcomes were also analyzed. One hundred twenty-four of 148 (84%) patients underwent CAC, 106 (72%) DSE/SPECT, and 50 (34%) LHC. CAC≥400 was found in 35 (28%), 100 to 399 in 17 (14%), and <100 in 72 (58%). LHC identified CAD≥70% in 8 of 29 (28%), 2 of 9 (22%), and 0 of 4, respectively. Two acute coronary syndromes occurred after LT in a patient with CAC 811 (CAD<70%), and one with CAC 347 (CAD≥70%). No patients with CAC<100 presented with acute coronary syndrome after LT. When using CAD≥70% as primary endpoint of LT evaluation, CAC≥346 was the only test showing predictive usefulness (negative predictive value 100%). CAC is a promising tool to guide CAD risk stratification and need for LHC during LT evaluation. Patients with a CAC<100 can safely undergo LT without the need for LHC or cardiac stress testing, whereas a CAC<346 accurately rules out significant CAD stenosis (≥70%) on LHC, outperforming other CAD risk-stratification strategies.

Predicted cardiovascular risk for United States adults with diabetes, chronic kidney disease, and at least 65 years of age.

The 2017 American College of Cardiology/American Heart Association blood pressure (BP) guideline recommends using 10-year predicted atherosclerotic cardiovascular disease (ASCVD) risk to guide decisions to initiate antihypertensive medication. We included adults aged 40-79 years from the National Health and Nutrition Examination Survey 2013-2018 (n = 8803). We computed 10-year predicted ASCVD risk using the Pooled Cohort risk equations. Clinical CVD was self-reported. Analyses were conducted overall and among those with stage 1 hypertension, defined by a mean SBP of 130-139 mmHg or DBP of 80-89 mmHg. In subgroups defined by diabetes, chronic kidney disease (CKD), and age at least 65 years, we estimated the proportion of United States adults with high ASCVD risk (i.e. 10-year predicted ASCVD risk ≥10% or clinical CVD) and estimated age-adjusted probability of having high ASCVD risk. Among United States adults, an estimated 72.3, 64.5, and 83.9 of those with diabetes, CKD, and age at least 65 years had high ASCVD risk, respectively. Among United States adults with stage 1 hypertension, an estimated 55, 36.7, and 72.6% of those with diabetes, CKD, and age at least 65 years had high ASCVD risk, respectively. The probability of having high ASCVD risk increased with age and exceeded 50% for United States adults with diabetes and CKD at ages 52 and 57 years, respectively. For those with stage 1 hypertension, these ages were 55 and 64 years, respectively. Most United States adults with diabetes, CKD, or age at least 65 years had high ASCVD risk. However, many with stage 1 hypertension did not.

Implication of thoracic aortic calcification over coronary calcium score regarding the 2018 ACC/AHA Multisociety cholesterol guideline: results from the CAC Consortium

ObjectiveTAC is associated with an increased atherosclerotic cardiovascular disease (ASCVD) risk, but it is unclear how to interpret thoracic aortic calcification (TAC) findings in conjunction with ASCVD risk and coronary artery calcium (CAC) score according to 2018 ACC/AHA Multisociety cholesterol guidelines. We evaluate the incremental value of thoracic aortic calcification TAC over CAC for predicting and reclassifying ASCVD mortality risk. MethodThe study included 30,630 asymptomatic individuals (mean age: 55 ± 8 years, male: 64%) from the CAC Consortium. TAC was categorized as TAC 0, 1-300, and >300. Patients were categorized as low (<5%), borderline (5–7.5%), intermediate (7.5–20%), or high (≥20%) 10-year ASCVD risk according to the Pooled Cohorts Equation. In the intermediate risk group, the utility of TAC beyond CAC for statin eligibility was assessed according to the guideline. CAC was categorized as CAC=0 (no statin), CAC 1-100 (favors statin), or CAC>100 (initiate stain). ResultsDuring the median 11.2 years (IQR 9.2–12.4) follow-up, 345 (1.1%) CVD deaths occurred. TAC>300 was associated with increased CVD mortality after adjusting for ASCVD risk and CAC (HR:4.72, 95% CI: 3.39–6.57, p<0.001). In borderline and intermediate risk groups, TAC improved discrimination when added to a model included ASCVD risk and CAC (C-statistic: 0.77 vs. 0.68 in borderline group; 0.67 vs. 0.63 in intermediate group, both p < 0.05). The addition of TAC over CAC improved risk reclassification in borderline, intermediate and high-risk groups (categorical net reclassification index: 0.40, 0.29, and 0.49, respectively, all p < 0.001). Of intermediate risk participants for whom consideration of CAC was recommended based on the guideline, TAC >300 was associated with an increased CVD mortality risk across each statin eligibility group (all p < 0.001, compared to TAC 0). ConclusionTAC was independently associated with CVD death. Among individuals with borderline or intermediate ASCVD risk, a TAC threshold of 300 may provide added prognostic and reclassification value beyond the current guideline-based approach.

Cascade Screening and Treatment Initiation in Young Adults with Heterozygous Familial Hypercholesterolemia.

Heterozygous familial hypercholesterolemia (HeFH) creates elevated low-density lipoprotein cholesterol (LDL-C), causing premature atherosclerotic cardiovascular disease (ASCVD). Guidelines recommend cascade screening relatives and starting statin therapy at 8–10 years old, but adherence to these recommendations is low. Our purpose was to measure self-reported physician practices for cascade screening and treatment initiation for HeFH using a survey of 500 primary care physicians and 500 cardiologists: 54% “always” cascade screen relatives of an individual with FH, but 68% would screen individuals with “strong family history of high cholesterol or premature ASCVD”, and 74% would screen a child of a patient with HeFH. The most likely age respondents would start statins was 18–29 years, with few willing to prescribe to a pediatric male (17%) or female (14%). Physicians who reported previously diagnosing a patient with HeFH were more likely to prescribe to a pediatric patient with HeFH, either male (OR = 1.34, 95% CI = 0.99–1.81) or female (OR = 1.31, 95% CI = 0.99–1.72). Many physicians do not cascade screen and are less likely to screen individuals with family history of known HeFH compared to “high cholesterol or premature ASCVD”. Most expressed willingness to screen pediatric patients, but few would start treatment at recommended ages. Further education is needed to improve diagnosis and treatment of HeFH.

Cardiovascular Risk Is Elevated in Lean Subjects with Nonalcoholic Fatty Liver Disease.

Background/AimsNonalcoholic fatty liver disease (NAFLD) and obesity are independently associated with an increased risk for atherosclerotic cardiovascular disease (ASCVD), the leading cause of mortality in patients with NAFLD. Many NAFLD patients are lean, but their ASCVD risk compared to obese subjects with NAFLD is unclear.MethodsData from the 2008 to 2011 Korea National Health and Nutrition Examination Surveys database were analyzed (n=4,786). NAFLD was defined as a comprehensive NAFLD score ≥40 or a liver fat score ≥–0.640. ASCVD risk was evaluated using the American College of Cardiology/American Heart Association guidelines.ResultsThe frequency of subjects without NAFLD, with obese NAFLD, and with lean NAFLD was 62.4% (n=2,987), 26.6% (n=1,274), and 11.0% (n=525), respectively. Subjects with lean NAFLD had a significantly higher ASCVD score and prevalence of a high ASCVD risk (mean 15.6±14.0, 51.6%) than those with obese NAFLD and without NAFLD (mean 11.2±11.4, 39.8%; mean 7.9±10.9, 25.5%; all p<0.001). Subjects with lean NAFLD and significant liver fibrosis showed a significantly higher odds ratio for a high risk for ASCVD than those with obese NAFLD with or without significant liver fibrosis (odds ratio, 2.60 vs 1.93; p=0.023).ConclusionsSubjects with lean NAFLD had a significantly higher ASCVD score and prevalence of high risk for ASCVD than those with obese NAFLD. Similarly, lean subjects with significant liver fibrosis had a higher probability of ASCVD than obese subjects in the subpopulation with NAFLD.

Residential greenness and atherosclerotic cardiovascular disease risk in a rural Chinese adult population

Residential greenness may be beneficial for cardiovascular health, but the evidence is still scarce, especially in developing countries. This study aimed to assess the associations between exposure to residential greenness and 10-year atherosclerotic cardiovascular disease (ASCVD) risk in a large rural Chinese adult population. This was a cross-sectional study based on 31,162 participants aged 35–74 years with complete data on predictors of the 10-year ASCVD risk from the Henan Rural Cohort Study. The satellite-derived Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI) were used to quantify residential greenness in a buffer radius of 500 m, 1000 m, and 3000 m. The high 10-years ASCVD risk was defined as the estimated risk ≥10% based on prediction equations from the China-PAR Project for Chinese populations. Multivariable-adjusted logistic regression models were performed to estimate the associations of greenness exposures with high 10-year ASCVD risk, and mediation analyses were employed to the potential mediators. For per interquartile range (IQR) increase in NDVI500−m, NDVI1000−m, NDVI3000−m, EVI500−m, EVI1000−m, and EVI3000−m, the adjusted OR (95% CI) of high 10-years ASCVD risk was 0.828 (0.793–0.866), 0.850 (0.817–0.885), 0.823 (0.792–0.855), 0.848 (0.809–0.889), 0.863 (0.826–0.901), 0.843 (0.805–0.883), respectively. Strong associations of NDVI500−m and EVI500−m with high 10-years ASCVD risk were found among participants with lower education level and lower averaged monthly income. The associations of greenness exposures with high 10-year ASCVD risk were partially explained by particulate matter with an aerodynamic diameter ≤1 µm, BMI, and physical activity. Enhancing residential greenness exposure may be beneficial for reducing the high 10-year ASCVD risk in rural Chinese adults.

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study

Rationale & ObjectiveThe 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories.Study DesignObservational cohort study.Setting & ParticipantsAdults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753).Exposure2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events.OutcomeAdjudicated ASCVD events after the year 1 study visit.Analytical ApproachWe calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death.ResultsThere were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively.LimitationsData on whether participants were taking a maximally tolerated statin dosage were unavailable.ConclusionsThe 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.

Triglyceride–Rich Lipoproteins, Apolipoproteins, and Atherosclerotic Cardiovascular Events Among Patients with Diabetes Mellitus and End–Stage Renal Disease on Hemodialysis

Hypertriglyceridemia may be implicated in the high atherosclerotic cardiovascular disease (ASCVD) risk experienced by patients with end-stage renal disease (ESRD). In this post-hoc analysis of the "Die Deutsche Diabetes Dialyse Studie (4D)" clinical trial, we examined incident ASCVD events, defined as myocardial infarction, ischemic stroke, or a coronary revascularization procedure, among 1255 participants with type 2 diabetes and ESRD treated with hemodialysis. Cox-regression methods were used to evaluate the association of triglycerides, very-low density lipoprotein cholesterol (VLDL-C), and apolipoproteins B (Apo B) and C-III (Apo C-III) with ASCVD. During a median follow-up time of 2.3 years, 340 (27%) participants experienced an ASCVD event. Higher concentrations of triglycerides were not associated with ASCVD risk: Hazard ratio (HR) 0.95; 95% CI (0.83, 1.10) per doubling concentration. Similarly, VLDL-C HR 1.01; 95% CI (0.90, 1.13); Apo B HR 1.04; 95% CI (0.93, 1.16); and Apo C-III HR 0.97; 95% CI (0.86, 1.09) (per one standard deviation higher concentrations), were not associated with ASCVD events. These associations did not differ by allocation to treatment to atorvastatin or by concentrations of markers of inflammation or malnutrition. In conclusion, we found no evidence that triglycerides, triglyceride-rich lipoproteins, or apolipoproteins B or C-III were associated with risk of ASCVD events among patients with type 2 diabetes and ESRD on hemodialysis. These results suggest that lowering triglycerides may not decrease atherosclerotic cardiovascular risk in this population.

Familial Hypercholesterolemia in the Arabian Gulf Region: Clinical results of the Gulf FH Registry.

Background and aimsFamilial hypercholesterolemia (FH) is a common autosomal dominant disorder that can result in premature atherosclerotic cardiovascular disease (ASCVD). Limited data are available worldwide about the prevalence and management of FH. Here, we aimed to estimate the prevalence and management of patients with FH in five Arabian Gulf countries (Saudi Arabia, Oman, United Arab Emirates, Kuwait, and Bahrain).MethodsThe multicentre, multinational Gulf FH registry included adults (≥18 years old) recruited from outpatient clinics in 14 tertiary-care centres across five Arabian Gulf countries over the last five years. The Gulf FH registry had four phases: 1- screening, 2- classification based on the Dutch Lipid Clinic Network, 3- genetic testing, and 4- follow-up.ResultsAmong 34,366 screened patient records, 3713 patients had suspected FH (mean age: 49±15 years; 52% women) and 306 patients had definite or probable FH. Thus, the estimated FH prevalence was 0.9% (1:112). Treatments included high-intensity statin therapy (34%), ezetimibe (10%), and proprotein convertase subtilisin/kexin type 9 inhibitors (0.4%). Targets for low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol were achieved by 12% and 30%, respectively, of patients at high ASCVD risk, and by 3% and 6%, respectively, of patients at very high ASCVD risk (p <0.001; for both comparisons).ConclusionsThis snap-shot study was the first to show the high estimated prevalence of FH in the Arabian Gulf region (about 3-fold the estimated prevalence worldwide), and is a “call-to-action” for further confirmation in future population studies. The small proportions of patients that achieved target LDL-C values implied that health care policies need to implement nation-wide screening, raise FH awareness, and improve management strategies for FH.

1228-P: Cardiovascular Risk of Patients with Overweight and Obesity: A Predictive Model

Obesity is the most common chronic disease in the U.S. Patients with obesity have many cardiovascular risk factors, often modifiable. It is important to identify patients with obesity at high risk of atherosclerotic cardiovascular disease (ASCVD) to be able to appropriately direct treatment and resources. We conducted an observational study of EMR data of 399,360 adults with BMI ≥ 25 kg/m2 and without baseline ASCVD between 2000 and 2019. We first identified a literature-based pool of risk factors for ASCVD onset and conducted variable selection by applying least absolute shrinkage and selection operator (LASSO) penalized Cox regression with ten-fold cross-validation on an 80% training dataset. We estimated a regular Cox model on the training dataset with selected variables and evaluated model performance on the remaining 20% dataset. Over the mean of 7.4 years of follow-up, 37,424 (11.7%) of study patients developed ASCVD. The predictive model achieved a Harrell’s C-statistic of 0.81. The greatest risk of ASCVD onset was associated with older age (HR 2.16 per 1 SD = 15.4 years; 95% CI 2.13- 2.20), heart failure (HR 1.85; 95% CI 1.74-1.97), valvular heart disease (HR 1.61; 95% CI 1.53-1.68) and stimulant abuse (HR 1.60; 95% CI 1.41-1.81). Female sex was associated with a lower risk of ASCVD (HR 0.64; 95% CI 0.63-0.65). Patient characteristics found in &amp;gt;5% of patients that carried additional risk included history of smoking (39.9% of patients; HR 1.40; 95% CI 1.37-1.43), proteinuria (5.5%; HR 1.33; 95% CI 1.29-1.38) and hypertension (23.6%; HR 1.29; 95% CI 1.26-1.32). Each standard deviation increase in BMI (5.3 kg/m2) was associated with a 1.15-fold (95% CI 1.14-1.16) increase in the risk of ASCVD onset. It is feasible to use predictive modeling to identify patients with overweight and obesity at high ASCVD risk. This approach could be utilized to guide population management and clinical treatment decisions. Disclosure A. Turchin: Consultant; Self; Proteomics International, Research Support; Self; AstraZeneca, Eli Lilly and Company, Novo Nordisk, Pfizer Inc., Sanofi, Stock/Shareholder; Self; Brio Systems. F. J. Morrison: None. M. Shubina: None. S. Shinde: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. N. Ahmad: Employee; Self; Eli Lilly and Company. H. Kan: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Bristol-Myers Squibb Company, GlaxoSmithKline plc. Funding Eli Lilly and Company

Abstract P213: Characterizing The Distribution Of Coronary Artery Calcification In The 75-and-older Population: The Atherosclerosis Risk In Communities Study

Introduction: The coronary artery calcium (CAC) score is a strong predictor of atherosclerotic cardiovascular disease (ASCVD) events. Current clinical practice guidelines recommend using a CAC score of 100 or age-, sex-, and race-specific 75 th percentile as thresholds of high risk for guiding preventive therapy for ASCVD. On the low end of the spectrum, zero CAC attracts attention as a potent negative predictor of ASCVD and may be used to “de-risk” individuals who may safely defer aggressive preventive therapy. However, due to sparse data on CAC in the age 75+ population, the value of these CAC thresholds in older adults is uncertain. Objective: To understand the distribution of CAC (75 th percentile, CAC 100, and zero CAC) in adults aged 75+. Methods: We assessed 2,303 ARIC Visit 7 (2018-2019) participants age 75+ years without clinical coronary heart disease (CHD) who underwent CAC scanning (median age 80 years, 39% males). Demographic-specific percentiles of the CAC distribution across age were estimated nonparametrically with pooled residual ranking and locally weighted regressions. Results: Male-white and male-black participants had lower prevalence of zero CAC than female-white and female-black participants (4% and 10% versus 13% and 16%, respectively). CAC scores tended to increase with age across race and sex strata but appeared to peak at an old age threshold (between age~85-95) ( Figure ). Regardless of age, sex, and race, a majority of individuals in this age range had CAC &gt;100 ( Figure , green 50 th percentile line exceeds red dashed CAC 100 line at most ages). Conclusions: In the largest US cohort of community-dwelling adults aged 75+ free of clinical CHD with CAC data, the prevalence of zero CAC was approximately 4-16%. We also confirmed a general age-dependent increase in CAC. Using CAC &gt;100 as a threshold for high ASCVD risk would categorize the majority of older adults age 75+ as high risk. Alternatively, our demographic-specific CAC percentiles may be a valuable tool for interpreting CAC in the age 75+ population.

Autoimmune Rheumatic Diseases: An Update on the Role of Atherogenic Electronegative LDL and Potential Therapeutic Strategies.

Atherosclerosis has been linked with an increased risk of atherosclerotic cardiovascular disease (ASCVD). Autoimmune rheumatic diseases (AIRDs) are associated with accelerated atherosclerosis and ASCVD. However, the mechanisms underlying the high ASCVD burden in patients with AIRDs cannot be explained only by conventional risk factors despite disease-specific factors and chronic inflammation. Nevertheless, the normal levels of plasma low-density lipoprotein (LDL) cholesterol observed in most patients with AIRDs do not exclude the possibility of increased LDL atherogenicity. By using anion-exchange chromatography, human LDL can be divided into five increasingly electronegative subfractions, L1 to L5, or into electropositive and electronegative counterparts, LDL (+) and LDL (−). Electronegative L5 and LDL (−) have similar chemical compositions and can induce adverse inflammatory reactions in vascular cells. Notably, the percentage of L5 or LDL (−) in total LDL is increased in normolipidemic patients with AIRDs. Electronegative L5 and LDL (−) are not recognized by the normal LDL receptor but instead signal through the lectin-like oxidized LDL receptor 1 (LOX-1) to activate inflammasomes involving interleukin 1β (IL-1β). Here, we describe the detailed mechanisms of AIRD-related ASCVD mediated by L5 or LDL (−) and discuss the potential targeting of LOX-1 or IL-1β signaling as new therapeutic modalities for these diseases.