High Atherosclerotic Cardiovascular Disease Risk Research Articles

Polygenic Risk Score and Statin Relative Risk Reduction for Primary Prevention of Myocardial Infarction in a Real-World Population.

Genetic substudies of randomized controlled trials demonstrate that high coronary heart disease (CHD) polygenic risk score modifies statin CHD relative risk reduction; it is unknown if the association extends to statin users undergoing routine care. We sought to determine how statin effectiveness is modified by CHD polygenic risk score in a real-world cohort of participants without previous myocardial infarction. We determined CHD polygenic risk scores in participants of the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Covariate-adjusted Cox regression models were used to compare the risk of cardiovascular outcomes between statin users and matched nonusers. Statin effectiveness on incident myocardial infarction showed no gradient with increasing 10-year Pooled Cohort Equations atherosclerotic cardiovascular disease (ASCVD) risk across low, borderline, intermediate, and high ASCVD risk score groups. In contrast, statin effectiveness by polygenic risk was largest in the high polygenic risk score group (hazard ratio (HR) 0.41, 95% confidence interval (CI), 0.31-0.53; P=1.5E-11), intermediate in the intermediate polygenic risk score group (HR 0.56, 95% CI, 0.47-0.66; P=8.4E-12), and smallest in the low polygenic risk score group (HR 0.67, 95% CI, 0.47-0.97; P=0.03; P for high vs. low=0.01). ASCVD risk and statin low-density lipoprotein cholesterol (LDL-C) lowering did not differ across polygenic risk score groups. In patients undergoing routine care, CHD polygenic risk modified statin relative risk reduction of incident myocardial infarction independent of LDL-C lowering. Our findings extend prior work by identifying a subset (i.e., self-identified White individuals with low CHD polygenic risk scores) with attenuated clinical benefit from statins.

Associations of New-Onset Atrial Fibrillation With Risks of Cardiovascular Disease, Chronic Kidney Disease, and Mortality Among Patients With Type 2 Diabetes.

Atrial fibrillation (AF) frequently occurs in patients with type 2 diabetes (T2D); however, the longitudinal associations of new-onset AF with risks of adverse health outcomes in patients with T2D remain unclear. In this study, we aimed to determine the associations of new-onset AF with subsequent risks of atherosclerotic cardiovascular disease (ASCVD), heart failure, chronic kidney disease (CKD), and mortality among patients with T2D. We included 16,551 adults with T2D, who were free of cardiovascular disease (CVD) and CKD at recruitment from the UK Biobank study. Time-varying Cox regression models were used to assess the associations of incident AF with subsequent risks of incident ASCVD, heart failure, CKD, and mortality. Among the patients with T2D, 1,394 developed AF and 15,157 remained free of AF during the follow-up. Over median follow-up of 10.7-11.0 years, we documented 2,872 cases of ASCVD, 852 heart failure, and 1,548 CKD and 1,776 total death (409 CVD deaths). Among patients with T2D, those with incident AF had higher risk of ASCVD (hazard ratio [HR] 1.85; 95% CI 1.59-2.16), heart failure (HR 4.40; 95% CI 3.67-5.28), CKD (HR 1.68; 95% CI 1.41-2.01), all-cause mortality (HR 2.91; 95% CI 2.53-3.34), and CVD mortality (HR 3.75; 95% CI 2.93-4.80) compared with those without incident AF. Patients with T2D who developed AF had significantly increased risks of developing subsequent adverse cardiovascular events, CKD, and mortality. Our data underscore the importance of strategies of AF prevention to reduce macro- and microvascular complications in patients with T2D.

Underprescribing of statin therapy in people with HIV at risk for atherosclerotic cardiovascular disease.

People with HIV (PWH) are at increased risk for developing atherosclerotic cardiovascular disease (ASCVD). The primary objective of this study was to evaluate adherence to guideline recommendations on statin use in PWH for both primary and secondary ASCVD prevention in a single healthcare institution. A retrospective chart review was performed to evaluate statin use for cardiovascular risk reduction in PWH 40 to 75 years of age at an HIV clinic over a 1-year evaluation period. The study included patients who met one of the 4 criteria for statin therapy defined in the "ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults." Patient demographics were collected and a 10-year ASCVD risk score was calculated. A total of 432 PWH were evaluated for statin therapy; 205 patients (47.5%) met criteria for statin therapy. The majority of patients were male, the average age was 58 years, and the average time since HIV diagnosis was 19 years. The mean ASCVD risk score was 14.2%. Only 79 patients (38.5%) who met criteria were prescribed statin therapy, and only 45 (56.9%) were prescribed statin therapy of appropriate intensity. Use of ART pharmacokinetic enhancer was low and did not affect statin prescribing. Multivariable analysis found that age, diabetes, clinical ASCVD, and an appointment with a pharmacist clinician prescriber predicted statin utilization. A high ASCVD risk score (>20%) did not predict statin treatment. Statin prescribing is low in PWH, who are at increased risk for ASCVD. Future research in PWH should focus on improving ASCVD risk assessment and exploring causes for statin underprescribing.

What should be the goal of cholesterol-lowering treatment? A quantitative evaluation dispelling guideline myths.

Guidelines for cholesterol-lowering treatment generally include extensive review of epidemiological and clinical trial evidence. However, the next logical step, the translation of evidence into clinical advice, occurs not entirely by reasoning, but by a form of consensus in which the prejudices and established beliefs of the societies with interests in cardiovascular disease convened to interpret the evidence are prominent. Methods, which are the subject of this review, have, however, been developed by which clinical trial evidence can be translated objectively into best practice. Guidelines differ in their recommended goals for cholesterol-lowering treatment in the prevention of atherosclerotic cardiovascular disease (ASCVD). Proposed goals are LDL-cholesterol 2.6 mmol/l (100 mg/dl) or less in lower risk, LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less in higher risk, non-HDL-cholesterol decrease of at least 40% or LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. Evidence from clinical trials of statins, ezetimibe and proprotein convertase subtilisin/kexin type 9-inhibitors can be expressed in simple mathematical terms to compare the efficacy on ASCVD incidence of clinical guidance for the use of cholesterol-lowering medication. The target LDL-cholesterol of 2.6 mmol/l (100 mg/dl) is ineffective and lacks credibility. Cholesterol-lowering medication is most effective in high-risk people with raised LDL-cholesterol. The best overall therapeutic target is LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. The use of non-HDL-cholesterol as a therapeutic goal is less efficacious. Aiming for LDL-cholesterol 1.4 mmol/l (55 mg/dl) or less as opposed to 1.8 mmol/l produces only a small additional benefit. Evidence for apolipoprotein B targets in hypertriglyceridaemia and in very high ASCVD risk should be more prominent in future guidelines. The LDL-cholesterol goal of 2.6 mmol/l or less should be abandoned. Percentage decreases in LDL-cholesterol or non-HDL-cholesterol concentration are better in people with initial concentrations of less than 3.6 mmol/l. The LDL-cholesterol target of 1.8 mmol/l is most effective when initial LDL-cholesterol is more than 3.6 mmol/l in both primary and secondary prevention.

Asymptomatic SARS-CoV-2 Infection Is Common Among ART-Treated People With HIV.

Limited data are available regarding asymptomatic COVID-19 among people with HIV (PWH). Data on a representative subset of PWH enrolled in Randomized Trial to Prevent Vascular Events in HIV, a global clinical trial, are presented here. Randomized Trial to Prevent Vascular Events in HIV is an atherosclerotic cardiovascular disease prevention trial among 7770 PWH on antiretroviral therapy. Beginning April 2020, targeted data on coronavirus disease 2019 (COVID-19) diagnosis and symptoms were collected during routine trial visits. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was defined as either COVID-19 clinical diagnosis or presence of SARS-CoV-2 Immunoglobulin G (IgG) or Immunoglobulin A (IgA) receptor binding domain protein (antispike) antibodies in the absence of prior COVID-19 vaccine. The group (N = 2464) had a median age 53 years, 35% female sex, 47% Black or African American race, median CD4 count 649 c/mm 3 , and 97% with HIV VL <400 cp/m. SARS-CoV-2 infection occurred in 318 persons (13%): 58 with clinical diagnosis and 260 with detectable antibodies. Of these PWH, 304 completed symptom questionnaires: 121 (40%) reported symptoms, but 183 (60%) were asymptomatic. PWH with asymptomatic SARS-CoV-2 infection were more likely to be from low-income or middle-income regions, of Black or African American race, older in age, and with higher atherosclerotic cardiovascular disease risk score. Symptomatic COVID was more common with obesity, metabolic syndrome, and low HDL levels. CD4 counts and HIV viral suppression rates were similar among PWH with symptomatic vs. asymptomatic COVID. Asymptomatic SARS-CoV-2 infection is common among antiretroviral therapy-treated PWH globally. We determined that 60% of infections in PWH were asymptomatic. HIV clinicians must remain vigilant about COVID-19 testing among PWH to identify asymptomatic cases.

Dietary Meat, Trimethylamine N-Oxide-Related Metabolites, and Incident Cardiovascular Disease Among Older Adults: The Cardiovascular Health Study.

Effects of animal source foods (ASF) on atherosclerotic cardiovascular disease (ASCVD) and underlying mechanisms remain controversial. We investigated prospective associations of different ASF with incident ASCVD and potential mediation by gut microbiota-generated trimethylamine N-oxide, its L-carnitine-derived intermediates γ-butyrobetaine and crotonobetaine, and traditional ASCVD risk pathways. Among 3931 participants from a community-based US cohort aged 65+ years, ASF intakes and trimethylamine N-oxide-related metabolites were measured serially over time. Incident ASCVD (myocardial infarction, fatal coronary heart disease, stroke, other atherosclerotic death) was adjudicated over 12.5 years median follow-up. Cox proportional hazards models with time-varying exposures and covariates examined ASF-ASCVD associations; and additive hazard models, mediation proportions by different risk pathways. After multivariable-adjustment, higher intakes of unprocessed red meat, total meat, and total ASF associated with higher ASCVD risk, with hazard ratios (95% CI) per interquintile range of 1.15 (1.01-1.30), 1.22 (1.07-1.39), and 1.18 (1.03-1.34), respectively. Trimethylamine N-oxide-related metabolites together significantly mediated these associations, with mediation proportions (95% CI) of 10.6% (1.0-114.5), 7.8% (1.0-32.7), and 9.2% (2.2-44.5), respectively. Processed meat intake associated with a nonsignificant trend toward higher ASCVD (1.11 [0.98-1.25]); intakes of fish, poultry, and eggs were not significantly associated. Among other risk pathways, blood glucose, insulin, and C-reactive protein, but not blood pressure or blood cholesterol, each significantly mediated the total meat-ASCVD association. In this large, community-based cohort, higher meat intake associated with incident ASCVD, partly mediated by microbiota-derived metabolites of L-carnitine, abundant in red meat. These novel findings support biochemical links between dietary meat, gut microbiome pathways, and ASCVD.

Comparison of coronary artery calcium score and its determinants in patients with familial combined hyperlipidemia and type 2 diabetes, in primary cardiovascular prevention

Background and Aims : Familial combined hyperlipidemia (FCH) is a frequent dyslipidemia often associated with metabolic syndrome (MetS). The magnitude of the atherosclerotic cardiovascular disease (ASCVD) risk increase in FCH is not clearly established. We used coronary artery calcium score (CAC) as a surrogate of the intensity of coronary atherosclerosis and as a strong predictor of MACE and compared its results in FCH versus T2D (type 2 diabetes) patients (a control group with a well-established high ASCVD risk).

Recent Updates in Hypertriglyceridemia Management for Cardiovascular Disease Prevention.

Mounting evidence continues to support the causal role of triglyceride-rich lipoproteins (TRL) in the development of atherosclerotic cardiovascular disease (ASCVD). Substantial residual ASCVD risk remains among high-risk patients who have elevated triglycerides despite reduction in low-density lipoprotein cholesterol (LDL-C) with statin therapy. Ongoing research efforts have focused on evaluating triglyceride-lowering therapies among patients with hypertriglyceridemia. The REDUCE-IT trial showed that the addition of icosapent ethyl, a highly purified form of eicosapentaenoic acid (EPA), can reduce vascular events among statin-treated individuals with elevated triglycerides who have either clinical ASCVD or diabetes plus another risk factor. Although additional evidence for EPA has emerged from other trials, conflicting results have been reported by subsequent trials that tested different omega-3 fatty acid formulations. Randomized clinical trials have not demonstrated incremental ASCVD benefit of fibrates on background of statin therapy, but fibrates are used to help prevent pancreatitis in patients with severe hypertriglyceridemia. Selective inhibitors of apolipoprotein C-III (apoC3) and angiopoietin-like protein 3 (ANGPTL3), proteins that are involved in metabolism of TRLs by regulating lipoprotein lipase, have been tested in selected patient populations and showed significant reduction in triglyceride and LDL-C levels. Statin therapy continues to be the cornerstone of pharmacologic reduction of cardiovascular risk. High-dose EPA in the form of icosapent ethyl has been demonstrated to have cardiovascular benefit on top of statins in persons with elevated triglycerides at high ASCVD risk. Ongoing clinical trials are evaluating novel selective therapies such as apoC3 and ANGPTL3 inhibitors.

Rationale and design of a pragmatic trial aimed at improving treatment of hyperlipidemia in outpatients with very high risk atherosclerotic cardiovascular disease: A pragmatic trial of messaging to providers about treatment of hyperlipidemia (PROMPT-LIPID)

Despite guideline recommendations to optimize low-density lipoprotein cholesterol (LDL-C) reduction with intensification of lipid-lowering therapy (LLT) in patients with atherosclerotic cardiovascular disease (ASCVD), few of these patients achieve LDL-C < 70 mg/dL in practice. We developed a real-time, targeted electronic health record (EHR) alert with embedded ordering capability to promote intensification of evidence based LLT in outpatients with very high risk ASCVD. We designed a pragmatic, multicenter, single-blind, cluster randomized trial to test the effectiveness of an EHR-based LLT intensification alert. The study will enroll about 100 providers who will be randomized to either receive the alert or undergo usual care for outpatients with high risk ASCVD with LDL-C > 70 mg/dL. Total enrollment will include 2,500 patients. The primary outcome will be the proportion of patients with LLT intensification at 90 days. Secondary outcomes include achieved LDL-C at 6 months and the proportion of patients with LDL-C < 70 mg/dL or < 55 mg/dL at 6 months. Enrollment of 1,250 patients (50% of goal) was reached within 47 days (50% women, mean age 72, median LDL-C 91). At baseline, 71%, 9%, and 3% were on statins, ezetimibe, or proprotein convertase subtilisin/kexin type 9 inhibitors, respectively. PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia has rapidly reached 50% enrollment of patients with very high risk ASCVD, demonstrating low baseline LLT utilization. This pragmatic, EHR-based trial will determine the effectiveness of a real-time, targeted EHR alert with embedded ordering capability to promote LLT intensification. Findings from this low-cost, widely scalable intervention to improve LDL-C may have important public health implications. clinicaltrials.gov NCT04394715.

Sarcopenia is associated with cardiovascular risk in men with COPD, independent of adiposity

BackgroundSarcopenia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD), but its relationship with chronic obstructive pulmonary disease (COPD) has not been fully determined. This study is aimed to investigate the association between sarcopenia and risk for ASCVD in patients with COPD, independent of central obesity and fat mass.MethodsData regarding 704 men with COPD (mean age: 63.4 years) were extracted from the 2008 to 2011 Korean National Health and Nutrition Examination Surveys. Sarcopenia index and fat mass were assessed using dual-energy X-ray absorptiometry. Sarcopenia was defined according to the presence of sarcopenia index values < 1 standard deviation from the cutoff (0.774) among the study participants. ASCVD risk was evaluated using American College of Cardiology/American Heart Association guidelines. High probability of ASCVD was defined as ASCVD risk > 20%.ResultsThe quartile-stratified sarcopenia index was negatively associated with ASCVD risk (P < 0.001). ASCVD risk and prevalence of high ASCVD risk were significantly greater in sarcopenic participants than in non-sarcopenic participants, regardless of central obesity and fat mass (all P < 0.001). Multivariate regression analyses demonstrated an independent association between sarcopenia and ASCVD risk (estimated ± standard error = 3.63 ± 0.77%, P < 0.001) and high ASCVD risk (odds ratio [OR] = 2.32, 95% confidence interval [CI] 1.05–5.15, P = 0.039). Furthermore, sarcopenia was an independent factor for high ASCVD risk in participants with moderate to very severe airflow limitation (OR = 2.97, 95% CI 1.06–8.36, P < 0.001).ConclusionsSarcopenia was significantly associated with an increased risk for ASCVD in men with COPD, independent of central obesity and fat mass. High ASCVD risk was significantly associated with sarcopenia, particularly in participants with moderate to very severe airflow limitation.

Associations of higher fish consumption and lifestyle with lower monocyte/HDL-C ratio in a Japanese population: Implication for the anti-atherosclerotic effect of fish consumption

BackgroundHigh fish consumption may be involved in lowering inflammation, resulting in the suppression of atherosclerotic cardiovascular disease (ASCVD) development. The monocyte/high-density lipoprotein cholesterol (HDL-C) ratio (MHR) is reported as a novel inflammatory marker of the development of atherosclerosis. We investigated the relationship between fish consumption, MHR, and lifestyle behaviors and explored the foundation of risk stratification of ASCVD using serum HDL-C, MHR, and fish consumption. MethodsWe conducted a cross-sectional study among 6841 adults at the Health Planning Center of Nihon University Hospital between April 2019 and March 2020.We calculated the amount of fish consumption based on Japan's National Nutrition Survey results. ResultsThe median (interquartile range) fish consumption was 111.4 (67.2/169.2) g per week. As fish consumption increased, MHR decreased significantly (p < 0.0001). Multivariate linear regression analysis identified increased fish consumption as an independent negative determinant of a decreased MHR (β = −0.050, p < 0.0001). Additionally, healthier lifestyle behaviors (sleep duration and cigarette smoking habit) were also significantly associated with MHR (β = −0.025, p = 0.027 and β = 0.146, p < 0.0001, respectively). Furthermore, risk stratification of ASCVD could be developed by combining the HDL-C level and fish consumption with the MHR, indicating that even with similar HDL-C levels, higher MHR and lower fish consumption are associated with a higher risk of ASCVD. Multi-logistic regression analysis with the MHR quartile as an independent variable also showed that the increase in quartile was associated with the exacerbation of visceral obesity and glucose/lipid markers. ConclusionsA higher fish consumption may be associated with a lower MHR as well as healthier lifestyle behaviors. Moreover, we proposed the concept of risk stratification through relationships with MHR, HDL-C, and fish consumption to reduce ASCVD risk. Further studies are required to dissect the causal relationships between these results.

Lipid-Lowering Therapy for Primary Prevention of Cardiovascular Disease: A Nationwide Analysis of 440,721 Patients

Lead Author's Financial Disclosures AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health. Study Funding Esperion Therapeutics, Inc. Background/Synopsis Statins are indicated for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) in adults with diabetes mellitus (DM), elevated 10-year risk, and those with LDL-C ≥190 mg/dL. Contemporary treatment patterns in community practice are not well described. Objective/Purpose To explore the use and dosing of statin therapy and use of several classes of non-statin lipid lowering therapies (LLT) in adults recommended for statins in primary prevention. Methods We identified adults recommended for primary prevention statin therapy who received outpatient care in 90 US health systems between 2017 and 2018 using a de-identified, electronic health record dataset; Cerner Real World Data. Primary prevention populations included: DM and age 40-75, calculated 10-year ASCVD risk ≥7.5% and age 40-75, and those with LDL-C ≥190 mg/dL or familial hypercholesterolemia based on diagnosis code. Medication data, including self-reported use of supplements, were examined. Based on the 2013 ACC/AHA Cholesterol Guideline (what was active at the time), patients were classified as: on appropriate- intensity statin, on under-dosed statin, or not on a statin. Results We identified 440,721 patients recommended for statins (median age 63 years, 50.1% male, and 75.5% white race), including (by mutually exclusive, hierarchical order) 308,620 (70%) patients with DM, 125,411 (28.5%) with a 10-year risk ≥7.5%, and 6,690 (1.5%) with LDL-C ≥190 mg/dL. Overall, 211,295 (47.9%) were on appropriate statin therapy, 29,039 (6.6%) were on lower-than-recommended statin intensity, and 200,387 (45.5%) were not on any statin (Figure). People with DM had the relative highest percent utilization of appropriate-dose statin (53.8%), while only 35.4% of those recommended for 10-year risk were on appropriate- dose statin, and only 12% of those with LDL-C ≥190 mg/dL were treated appropriately (Figure). Utilization of non-statin LLT was low overall across all three groups (15.8%). However, nearly one in ten (9.4%) of those recommended for primary prevention reported taking non-prescription Omega-3/fish oil supplements (Figure). Conclusions Over half of primary prevention patients at high risk for ASCVD in the US are not on appropriate-dose, guideline-recommended statin therapy. Of these, the majority were not on any statin. Non-statin LDL-C lowering medication use was also low. Despite no data for cardiovascular benefit, a substantial number of adults were taking non-prescription fish oil. There remains a strong national need to improve overall utilization and evaluate barriers to prescription/uptake of evidence based LLT in all patients eligible for primary prevention. AAK was supported by the National Heart, Lung, And Blood Institute of the National Institutes of Health under Award Number T32HL12547. The content is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

Fatal adverse events of rivaroxaban combined with aspirin: an analysis using data from VigiBase

PurposeThe aim of this study was to analyze the clinical characteristics of fatal adverse events (AEs) of rivaroxaban combined with aspirin and to underline the importance of the rational use of drugs.MethodsThe WHO global database of reported potential side effects of medicinal products (VigiBase) was searched for fatal AEs in the combined use of rivaroxaban and aspirin, and the clinical characteristics of those cases with sufficient information (vigiGrade completeness score ≥ 0.80) were analyzed.ResultsBy January 19, 2020, 2309 fatal adverse event reports of rivaroxaban combined with aspirin from 21 countries were entered in VigiBase. One hundred and twenty cases contained further information, of which 42 were female (35%) and 78 were male (65%). The median age was 75 (range 34 to 93) years, and 109 cases (91%) were elderly patients (≥ 65 years). The AEs listed in the fatal case reports included bleeding in 114 cases (mainly intracranial hemorrhage and gastrointestinal hemorrhage, 59 and 46 respectively, accounting for 88%) and ischemic events in six cases (ischemic stroke in three, acute myocardial infarction in two, myocardial infarction combined with acute liver failure in one). Among the patients with bleeding events, 108 (95%) had existing risk factors for bleeding or for interacting with aspirin or rivaroxaban. These may be divided into the following: diseases (hypertension, renal impairment, history of stroke, peptic ulcer, or previous bleeding), drugs (high dose aspirin, antiplatelet drugs, anticoagulants, P-gp inhibitors/CYP3A4 inhibitors, non-steroidal anti-inflammatory drugs, steroids, and selective serotonin reuptake inhibitors), or other factors (e.g., elderly, low body weight, or excessive intake of ginger, fish oil, or alcohol). There were 45 cases with two or more of these risk factors in addition to rivaroxaban and aspirin. Patients with ischemic events are often in very high-risk groups of atherosclerotic cardiovascular disease (ASCVD) or self-discontinuation of treated drugs. Medication errors occurred in 24 patients (20%): excessive treatment in 17 cases, contraindication in three, frequency error in two, excessive treatment combined with contraindication in one, and self-discontinuation in one.ConclusionsFatal AEs related to rivaroxaban combined with aspirin, including bleeding and ischemic events, have been reported mostly in the elderly, and sometimes involved medication errors. The fatal AEs mainly manifested as serious bleeding, and most of them occurred in patients with concurrent multiple risk factors. Monitoring coagulation during rivaroxaban treatment is recommended in very high-risk ASCVD populations, and attention should be paid to prevention of medication errors.

New Strategies for Lowering Low Density Lipoprotein Cholesterol for Cardiovascular Disease Prevention.

The primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD) relies on optimizing cardiovascular health and appropriate pharmacotherapy, a mainstay of which is low-density lipoprotein-cholesterol (LDL-C) lowering. Typically, statin therapy remains the first line approach. Advances in technology and understanding of lipid metabolism have facilitated the development of several novel therapeutic targets and medications within the last decade. This review focuses on medications recently approved by the U.S. Food and Drug Administration (FDA) for the reduction of LDL-C and ASCVD risk, as well as new therapies in the pipeline. Novel lipid therapies aim to lower risk of ASCVD by targeting reduction of atherogenic compounds, such as LDL, lipoprotein(a) (Lp(a)), and triglyceride-rich lipoproteins. Evolocumab and alirocumab, monoclonal antibody proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors which lower LDL-C by approximately 60%, have emerged as important therapies for use in patients with ASCVD as well as familial hypercholesterolemia (FH). Bempedoic acid, an ATP citrate lyase inhibitor, is an oral medication recently approved that can lower LDL-C by approximately 18% alone and 38% when combined with ezetimibe. Inclisiran, a small-interfering RNA (siRNA) molecule which inhibits the translation of PCSK9, is the most recently FDA-approved LDL-C lowering medication, and can reduce LDL-C by approximately 50% with twice yearly subcutaneous dosing. The cardiovascular outcome trials for bempedoic acid and inclisiran are still on-going. Evinacumab, a monoclonal antibody which targets angiopoietin-like protein 3 (ANGPTL3), has been approved for use in patients with homozygous FH. SiRNAs and anti-sense oligonucleotides (ASO) facilitating selective inhibition of the production of targeted proteins including Lp(a) and ANGLPTL3 are active areas of clinical investigation. Recently several novel LDL-C lowering medications have been approved. New therapeutic targets have been identified and present additional means of lowering LDL-C and other atherogenic compounds for patients who remain at high ASCVD risk.

Urine 11-Dehydro-Thromboxane B2 in Aspirin-Naive Males with Metabolic Syndrome.

Urine 11-dehydro-thromboxane B2 (11-dehydro-TXB2), an indirect measure of platelet activity, is elevated in cardiovascular diseases and diabetes. The purpose of our study was to determine whether urine 11-dehydro-TXB2 is elevated in aspirin-naive males with metabolic syndrome (MS) and to determine predictors of 11-dehydro-TXB2 levels. The secondary aim was to evaluate whether these MS patients could be potential candidates for the aspirin-mediated prevention of atherosclerotic cardiovascular diseases (ASCVDs). In 82 males with MS (76 hypertensive), anthropometric measures, urine 11-dehydro-TXB2, platelet count, creatinine, glucose, insulin, estimated insulin resistance, lipid parameters, high-sensitivity C-reactive protein (hs-CRP), adiponectin, homocysteine, and ten-year risk of fatal cardiovascular disease (SCORE) were assessed. Urine 11-dehydro-TXB2 levels were elevated (≥2500 pg/mg creatinine) in two-thirds of patients, including 11 high-risk patients (SCORE ≥ 5%). Homocysteine, adiponectin, hs-CRP, waist-to-hip ratio, and total cholesterol were found to be predictors of urine 11-dehydro-TXB2. In conclusion, there is a high incidence of elevated urine 11-dehydro-TXB2 in males with MS, including in some patients who are at a high or very high risk of ASCVDs. 11-dehydro-TXB2 levels are associated with hyperhomocysteinemia, inflammation, fat distribution, hypercholesterolemia, and adiponectin concentrations. Elevated 11-dehydro-TXB2 levels may support the use of personalised aspirin ASCVD prevention in high-risk males with MS. Giuseppe Patti.

Remnant cholesterol and atherosclerotic disease in high cardiovascular risk patients. Beyond LDL cholesterol and hypolipidemic treatment

BackgroundRemnant cholesterol (RC) is an emerging factor contributing to residual risk for the development of atherosclerotic cardiovascular disease (ASCVD). We aimed to investigate the association of RC with ASCVD in high ASCVD risk patients. MethodsRC was calculated in 906 participants (178 low/moderate-risk and 728 high-risk) consecutively recruited from a vascular registry. Subclinical carotid atherosclerosis was assessed by B-mode carotid ultrasonography. Maximal carotid wall thickness (maxWT) and carotid atherosclerotic burden (n ≥ 2 atherosclerotic plaques) were set as the vascular outcomes. An independent cohort of 87 consecutively recruited high-risk patients who were followed for their lipid profile for 3 months was also analyzed. ResultsRC was increased in the high-risk group as compared to controls (26 ± 17 vs. 21 ± 11 mg/dl, respectively, p < 0.001). Increased RC levels were independently associated with increased maxWT and carotid atherosclerotic burden (p < 0.05), after adjustment for traditional cardiovascular risk factors (TRF) and ASCVD. RC levels were associated with the presence of flow-limiting ASCVD and coronary artery disease (CAD) (p < 0.05), after adjustment for TRFs. These associations remained significant in those not receiving hypolipidemic treatment and in treated individuals achieving LDL-C<100 mg/dl. In the prospective cohort, there was no significant interaction between change in RC levels and hypolipidemic status, as contrasted to LDL-C levels (p < 0.001). ConclusionIn a high-risk population, RC was associated with subclinical and clinically overt ASCVD, particularly in patients with the most adverse lipid phenotype (untreated) or in treated patients with a low LDL-related risk profile. These findings support a residual pro-atherosclerotic role of RC in high-risk patients.

Workers' Activity Profiles Associated With Predicted 10-Year Cardiovascular Disease Risk.

Background There is a need to explore common activity patterns undertaken by workers and the association between these activity profiles and cardiovascular disease (CVD). This study explored the number and type of distinct profiles of activity patterns among workers and the association between these profiles and predicted 10-year risk for a first atherosclerotic CVD event. Methods and Results Distinct activity patterns from a cross-section of workers' accelerometer data were sampled from Canadian Health Measures Survey participants (5 cycles, 2007-2017) and identified using hierarchical cluster analysis techniques. Covariates included accelerometer wear time, work factors, sociodemographic factors, clinical markers, and lifestyle variables. Associations between activity profiles and high atherosclerotic CVD risk >10% were estimated using robust Poisson regression models. Six distinct activity profiles were identified from 8909 workers. Compared with the "lowest activity" profile, individuals in the "highest activity" and "moderate evening activity" profiles were at 42% lower risk (relative risk [RR], 0.58; 95% CI, 0.47, 0.70) and 33% lower risk (RR, 0.67; 95% CI, 0.44, 0.87) of predicted 10-year atherosclerotic CVD risk of >10%, respectively. "Moderate activity" and "fluctuations of moderate activity" profiles were also associated with lower risk estimates, whereas the "high daytime activity" profile was not statistically different to the reference profile. Conclusions Workers accumulating physical activity throughout the day and during recreational hours were found to have optimal CVD risk profiles. Workers accumulating physical activity only during daytime work hours were not associated with reduced CVD risk. Findings can inform alternative strategies to conferring the cardiovascular benefits of physical activity among workers. Large prospective studies are needed to confirm these findings.

17-LB: Antihyperglycemic Use in Hemodialysis-Dependent Kidney Failure

Background: At least two-thirds of people with hemodialysis-dependent kidney failure have comorbid diabetes which associates with higher mortality. Some GLP-1 receptor agonists (RA) do not require renal dosing and could uniquely benefit dialysis patients, individuals with tremendous cardiovascular disease burden. Methods: Using data from a national surveillance system for kidney failure in the U.S. that includes Medicare Part D prescription drug claims, we: 1) calculated the quarterly prevalence of antihyperglycemic use among diabetic hemodialysis patients from 2012 to 2017 and 2) characterized antihyperglycemic users in October 2017. Results: Among the 129,865 hemodialysis patients with comorbid diabetes, insulin was the most prescribed agent (33%) , followed by sulfonylureas (SU, 7%) and DPP4 inhibitors (DPP4i, 5%) in October 2017. SU use fell, and DPP4i use rose from 2012 to 2017. Less than 5% of patients received combination therapy (insulin + a 2nd agent; Figure 1) . Disregarding kidney disease as an atherosclerotic cardiovascular disease (ASCVD) risk factor, 64% of patients met American Diabetes Association ASCVD criteria and 98% were at high risk for ASCVD in 2017. GLP-1 RA were prescribed to &amp;lt;1% of patients, 20% of whom had an endocrinology claim in the prior 6 months. Conclusions: GLP-1 RA use by hemodialysis patients is limited. There is compelling need to establish the safety and efficacy of GLP-1 RA in this high-risk population. Disclosure K. Klein: None. V. Pate: None. M. M. Assimon: None. T. Stürmer: Research Support; Novo Nordisk. Stock/Shareholder; Novartis AG, Novo Nordisk, Roche Pharmaceuticals. Other Relationship; AbbVie Inc., Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Takeda Pharmaceutical Company Limited, UCB, Inc. J. B. Buse: Consultant; Alkahest, Anji, AstraZeneca, Boehringer Ingelheim International GmbH, Cirius Therapeutics, Inc., Eli Lilly and Company, Fortress biotech, GentiBio, Glycadia, Glyscend, Janssen Pharmaceuticals, Inc., Mellitus Health, Moderna, Inc., Pendulum Therapeutics, Praetego, LLC, Stability Health, Valo, Zealand Pharma A/S. Research Support; AstraZeneca, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, vTv Therapeutics. Stock/Shareholder; Glyscend, Mellitus Health, Pendulum Therapeutics, PhaseBio Pharmaceuticals, Inc., Praetego, LLC, Stability Health. Other Relationship; Adocia, AstraZeneca, Eli Lilly and Company, Intarcia Therapeutics, Inc., MannKind Corporation, Novo Nordisk, Sanofi, Senseonics, vTv Therapeutics. J. Flythe: Advisory Panel; Fresenius Medical Care. Consultant; AstraZeneca. Research Support; Fresenius Medical Care.

Carotid ultrasonography improves residual risk stratification in guidelines-defined high cardiovascular risk patients.

The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established. We aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients. We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n = 751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n = 2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology guidelines (clinical ESCrisk). Intima-media thickness excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As primary endpoint of the study was defined the composite of cardiac death, acute myocardial infarction and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort. MaxWT &gt; 2.00 mm and avg.maxWT &gt; 1.39 mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (P &lt; 0.05 for net reclassification index, integrated discrimination index and Delta Harrell's C index). MaxWT &lt; 0.9 mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort. Integration of carotid ultrasonography in guidelines-defined risk stratification may identify patients at very high-risk in need for further residual risk reduction or at very low probability for events.

Association Between Serum Uric Acid Levels and Traditional Cardiovascular Risk Factors in Xiamen Residents of China: A Real-World Study.

BackgroundSerum uric acid (SUA) levels was associated with cardiovascular diseases and cardiovascular events. However, the relationship between SUA levels and traditional cardiovascular risk factors has not been well-established among Xiamen residents. Our study aimed to estimate the relationship between SUA levels and cardiovascular risk factors among Xiamen residents using real-world data.MethodsParticipants were enrolled from eight community health service centers in Xiamen, China. Participants were divided into four groups according to quartiles of the SUA levels. The history of diseases, the use of medications and the levels of laboratory parameters were collected. The China-PAR equation was used to evaluate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk.ResultsA total of 1,322 participants were enrolled. About 568 (43.0%) were men and 754 (57.0%) were women. The prevalences of hypertension, elderly, current smokers, and obesity were higher in the quartile 4 (Q4) group than the quartile 1 (Q1) group (all p < 0.001). Multivariable logistic regression analysis showed the OR for hypertension was 2.671 (95% CI 1.777–4.015, p < 0.001) in the Q4 group compared with that in the Q1 group. Further logistic regression showed the OR for hypertension was 3.254 (95% CI 1.756–6.031, p < 0.001) in men and 2.314 (95% CI 1.354–3.955, p = 0.002) in women in the Q4 group compared with that in the Q1 group, respectively. In addition, the percentage of participants with low 10-year ASCVD risk calculated by China-PAR was higher in the Q1 group than that in the Q4 group (55.86 vs. 31.82%, p < 0.001). The percentage of participants with high 10-year ASCVD risk was lower in the Q1 group compared with the Q4 group (15.32 vs. 25.45%, p < 0.001). Multiple linear logistic regression showed the 10-year China-PAR ASCVD risk scores was positively correlated with SUA after adjusting for various factors (β = 0.135, p = 0.001).ConclusionSerum uric acid was associated with several cardiovascular risk factors in Xiamen residents. The percentage of high 10-year ASDVD risk was higher in participants with hyperuricemia. Participants with hyperuricemia may experience cardiovascular benefit from uric acid-lowering therapy.