Search

Background and Aims: We aimed to explore the association between remnant cholesterol (RC) level and risks of all-cause and cardiovascular deaths among American diabetic adults., Methods and Results: The data of 4,095 diabetic participants from the National Health and Nutrition Examination Survey (1999-2018) were included for analysis. Deaths were ascertained till December 31, 2019. RC level associated with death was assessed on a continuous scale with restricted cubic splines and by pre-defined quartile groups with Cox regression analysis. After a median follow-up of 6.9 years, 1,060 all-cause and 289 cardiovascular deaths occurred. Association between RC and death was U-shaped, and RC level correlated with the lowest risks of both all-cause and cardiovascular deaths was 0.85 mmol/L. After adjusting for confounders, compared with Quartile 3 (0.66-0.93 mmol/L), hazard ratios for all-cause deaths were 1.43 (95%CI 1.18-1.72, P = 0.0002) in Quartile 1 (≤0.47 mmol/L), 1.20 (95%CI 1.00-1.44, P = 0.05) in Quartile 2 (0.47-0.66 mmol/L), and 1.25 (95%CI 1.05-1.49, P = 0.02) in Quartile 4 (>0.93 mmol/L). Higher risk was also observed for cardiovascular deaths in Quartile 1 (HR 1.66, 95%CI 1.15-2.41, P = 0.007), Quartile 2 (HR 1.39, 95%CI 0.97-2.00, P = 0.08), and Quartile 4 (HR 1.54, 95% CI 1.08-2.19, P = 0.02), as compared with Quartile 3., Conclusion: In US adults with diabetes, low and high levels of RC were associated with increased risks of all-cause and cardiovascular deaths, and the lowest risk was observed at RC level of 0.85 mmol/L. These findings suggested that maintaining appropriate RC level may help reduce risk of death in diabetic patients., Competing Interests: Declaration of competing interest There are no conflicts of interest to report., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC., Methods and Results: This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156)., Conclusion: In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation., Competing Interests: Conflict of interest: M.D.S. has participated in scientific advisory boards with the following entities: Amgen, Agepha, Ionis, Novartis, Precision BioScience, Novo Nordisk, and New Amsterdam; and has served as a consultant for Ionis, Novartis, Regeneron, Aidoc, Kaneka, and Shanghai Pharma Biotherapeutics. C.L.S. has received honoraria from the National Institutes of Health for service on grant review panels. All other authors have nothing to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The 2013 ACC/AHA Guideline was a paradigm shift in lipid management and identified the four statin-benefit groups. Many have studied the guideline's potential impact, but few have investigated its potential long-term impact on MACE. Furthermore, most studies also ignored the confounding effect from the earlier release of generic atorvastatin in Dec 2011., Methods: To evaluate the potential (long-term) impact of the 2013 ACC/AHA Guideline release in Nov 2013 in the U.S., we investigated the association of the 2013 ACC/AHA Guideline with the trend changes in 5-Year MACE survival and three other statin-related outcomes (statin use, optimal statin use, and statin adherence) while controlling for generic atorvastatin availability using interrupted time series analysis, called the Chow's test. Specifically, we conducted a retrospective study using U.S. nationwide de-identified claims and electronic health records from Optum Labs Database Warehouse (OLDW) to follow the trends of 5-Year MACE survival and statin-related outcomes among four statin-benefit groups that were identified in the 2013 ACC/AHA Guideline. Then, Chow's test was used to discern trend changes between generic atorvastatin availability and guideline potential impact., Results: 197,021 patients were included (ASCVD: 19,060; High-LDL: 33,907; Diabetes: 138,159; High-ASCVD-Risk: 5,895). After the guideline release, the long-term trend (slope) of 5-Year MACE Survival for the Diabetes group improved significantly (P = 0.002). Optimal statin use for the ASCVD group also showed immediate improvement (intercept) and long-term positive changes (slope) after the release (P < 0.001). Statin uses did not have significant trend changes and statin adherence remained unchanged in all statin-benefit groups. Although no other statistically significant trend changes were found, overall positive trend change or no changes were observed after the 2013 ACC/AHA Guideline release., Conclusions: The 2013 ACA/AHA Guideline release is associated with trend improvements in the long-term MACE Survival for Diabetes group and optimal statin use for ASCVD group. These significant associations might indicate a potential positive long-term impact of the 2013 ACA/AHA Guideline on better health outcomes for primary prevention groups and an immediate potential impact on statin prescribing behaviors in higher-at-risk groups. However, further investigation is required to confirm the causal effect of the 2013 ACA/AHA Guideline., (© 2024. The Author(s).)

Background: Dyslipidemia is an independent risk factor for coronary heart disease (CHD). Standard lipid panel cannot capture the complexity of the blood lipidome (ie, all molecular lipids in the blood). To date, very few large-scale epidemiological studies have assessed the full spectrum of the blood lipidome on risk of CHD, especially in a longitudinal setting., Methods and Results: Using an untargeted liquid chromatography-mass spectrometry, we repeatedly measured 1542 lipid species from 1835 unique American Indian participants who attended 2 clinical visits (≈5.5 years apart) and followed up to 17.8 years in the Strong Heart Family Study (SHFS). We first identified baseline lipid species associated with risk of CHD, followed by replication in a European population. The model adjusted for age, sex, body mass index, smoking, hypertension, diabetes, low-density lipoprotein cholesterol, estimated glomerular filtration rate, education, and physical activity at baseline. We then examined the longitudinal association between changes in lipid species and changes in cardiovascular risk factors during follow-up. Multiple testing was controlled by the false discovery rate. We found that baseline levels of multiple lipid species (eg, phosphatidylcholines, phosphatidylethanolamines, and ceramides) were associated with the risk of CHD and improved the prediction accuracy over conventional risk factors in American Indian people. Some identified lipids in American Indian people were replicated in European people. Longitudinal changes in multiple lipid species (eg, acylcarnitines, phosphatidylcholines, and triacylglycerols) were associated with changes in cardiovascular risk factors., Conclusions: Baseline plasma lipids and their longitudinal changes over time are associated with risk of CHD. These findings provide novel insights into the role of dyslipidemia in CHD.

Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in the United States and worldwide. Medical management of known modifiable risk factors, such as dyslipidemia, hypertension, and diabetes, is a key aspect to its treatment. Unfortunately, there are substantial sex-based differences in the treatment of ASCVD that result in poor medical management and worse clinical outcomes. The objective of this systematic review was to summarize known disparities in the medical management of ASCVD in females. We included prior studies with specific sex- and sex-based analyses regarding the medical treatment of the following three major disease entities within ASCVD: cerebrovascular disease, coronary artery disease, and peripheral artery disease. A total of 43 articles met inclusion criteria. In our analysis, we found that females were less likely to receive appropriate treatment of dyslipidemia or be prescribed antithrombotic medications. However, treatment differences for diabetes and hypertension by sex were not as clearly represented in the included studies. In addition to rectifying these disparities in the medical management of ASCVD, this systematic review highlights the need to address larger issues, such as underrepresentation of females in clinical trials, decreased access to care, and underdiagnosis of ASCVD to improve overall care for females., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Purpose of Review: The goal of this article is to review algorithms for treating dyslipidemia in youth, discuss pitfalls, propose enhanced algorithms to address pitfalls, and consider future directions., Recent Findings: The presence of modifiable and non-modifiable cardiovascular disease (CVD) risk factors during childhood is associated with CVD-related events in adulthood. Recent data has shown that childhood initiation of statin therapy in youth < 18 years of age with familial hypercholesterolemia reduces the risk of adult CVD. However, pediatric dyslipidemia remains undertreated in part due to a lack of primary health care providers with adequate understanding of screening guidelines and pediatric lipidologists with experience in treatment and follow-up of this unique population. Management algorithms have been published by the National Heart, Lung, and Blood Institute and American Heart Association as tools to empower clinicians to manage dyslipidemia. We propose enhanced algorithms, which incorporate recently approved pharmacotherapy to address the management gaps. Future algorithms based upon clinical risk scores may enhance treatment and improve outcomes. Algorithms for dyslipidemia management which target youth < 18 years of age are tools which empower clinicians to manage dyslipidemia in this unique population. Enhanced algorithms may help address pitfalls. We acknowledge the need for further risk assessment tools in pediatrics for tailored dyslipidemia management., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objectives: This cross-sectional study evaluates the degree of agreement between the 2018 American College of Cardiology/American Heart Association (ACC/AHA2018) and 2020 Philippine Guideline (PG2020) treatment algorithms for the primary prevention of dyslipidemia among Filipinos., Methodology: This review included 159 charts of statin-naive Filipinos who are 45-79 years old. Using risk profile and lipid measurements, statin treatment recommendation was determined through the PG2020 algorithm and ACC/AHA-ASCVD Risk Estimator Plus web application. The degree of agreement was measured by Cohen's kappa statistic with the two algorithms as independent raters., Results: A total of 159 patients were included in the final analysis. There was a slight agreement with a kappa coefficient of 0.209 or 4.4% (95% CI 0.078-0.340, p =0.003). Statin treatment was recommended in 69 out of 159 patients (43.4%) by the PG2020 overlapping with ACC/AHA2018 in 56 cases (81.2%). On the other hand, 109 cases (68.6%) were recommended for statin treatment by ACC/AHA2018 overlapping with PG2020 in only 51.4%., Conclusions: The low degree of agreement between the two treatment algorithms highlights the key demographic and ethnic variations in dyslipidemia management necessitating outcome-based studies to translate these differences. Overestimation of ASCVD risk calculation in the ACC/AHA2018 and consideration of important, unique risk factors among Filipinos favors the applicability of the Philippine guideline., Competing Interests: All the authors declared no conflict of interest., (© 2022 Journal of the ASEAN Federation of Endocrine Societies.)

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in the United States (U.S.) and incurs significant cost to the healthcare system. Management of cholesterol remains central for ASCVD prevention and has been the focus of multiple national guidelines. In this review, we compare the American Heart Association (AHA)/American College of Cardiology (ACC) and the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) Cholesterol guidelines. We review the evidence base that was used to generate recommendations focusing on 4 distinct themes: 1) the threshold of absolute 10-year ASCVD risk to start a clinician-patient discussion for the initiation of statin therapy in primary prevention patients; 2) the utility of coronary artery calcium score to guide clinician-patient risk discussion pertaining to the initiation of statin therapy for primary ASCVD prevention; 3) the use of moderate versus high-intensity statin therapy in patients with established ASCVD; and 4) the utility of ordering lipid panels after initiation or intensification of lipid lowering therapy to document efficacy and monitor adherence to lipid lowering therapy. We discuss why the VA/DoD and AHA/ACC may have reached different conclusions on these key issues., Competing Interests: Declaration of Competing Interest Salim S. Virani, Research support: Department of Veterans Affairs, World Heart Federation, Tahir and Jooma Family. Honorarium: American College of Cardiology (Associate Editor for Innovations, acc.org). Vijay Nambi, Site PI for study sponsored by AMGEN. Supported by VA MERIT award. Provisional patent along with BCM, Roche on use of biomarkers in prediction of Heart failure, (Published by Elsevier Inc.)

Aims: Due to improving cancer treatment results, non-cancer mortality is an important issue for cancer survivors. Cardiovascular diseases are the leading causes of death in Korea and globally. In addition to lowering the risk of cardiovascular disease, the use of statins has led to an overall reduction in cancer mortality in recent observational studies. We investigated the status of current dyslipidemia management in cancer survivors with reference to 2018 guidelines., Methods: The study is a cross-sectional analysis of 1460 cancer survivors aged from 40 to 75 years who participated in the Korean National Health and Nutrition Examination Survey from 2007 to 2016. Dyslipidemia management status among cancer survivors was assessed according to 2018 American College of Cardiology/American Heart Association guidelines and Korean Coronary Heart Disease Risk Score guidelines., Results: The rate of treatment for dyslipidemia was 8.5% for males, 13.8% for females, and 11.9% overall. Among cancer survivors who were not receiving treatment for dyslipidemia, 59.6% of males, 34.2% of females and 43.9% of total cancer survivors would have been eligible for statin therapy under the 2018 American College of Cardiology/American Heart Association guidelines and Korean Coronary Heart Disease Risk Score guidelines. The rate of undertreatment of dyslipidemia increased with age and length of time since cancer diagnosis., Conclusion: Nearly 50% of cancer survivors remain untreated although they are eligible for statin therapy. This emphasizes the need for more attention to prevent atherosclerotic cardiovascular disease among cancer survivors., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background Limited data exist on the incremental value of the risk enhancers recommended in the 2018 American Heart Association/American College of Cardiology (ACC/AHA) cholesterol treatment guidelines in addition to the pooled cohort equation. Methods and Results Using pooled individual-level data from 3 epidemiological cohorts involving 22 942 participants (56% women, mean age 59 years), we evaluated the predictive ability of the risk enhancers and coronary artery calcium (CAC) score for atherosclerotic cardiovascular disease, and determined their incremental utility using the C statistic, net reclassification index, and integrated discrimination index. A total of 1960 (8.5%) atherosclerotic cardiovascular disease events were accrued over 10 years. Of the 10 risk enhancers evaluated, only 6 predicted atherosclerotic cardiovascular disease independent of the pooled cohort equation. However, the individual enhancers demonstrated little or no incremental benefit. There was more incremental value from combining the 6 enhancers into an aggregate score (hazard ratio [HR], 1.21; 95% CI, 1.08-1.37 for each additional enhancer), and having ≥3 enhancers represents an optimum threshold for incremental prediction (C statistic, 0.766; net reclassification index, 0.041; integrated discrimination index, 0.010; P ≤0.007). On the other hand, CAC was superior to individual enhancers (C statistic, 0.774; net reclassification index, 0.073; integrated discrimination index, 0.010; P <0.001), reliably reclassifies intermediate-risk participants with <3 risk enhancers (event rate, 3.5% if no CAC and 9.8% if positive CAC), but offered no reclassification among participants with ≥3 enhancers. Conclusions The individual risk enhancers evaluated in this study provided no or only marginal incremental information added to the pooled cohort equation. However, the presence of ≥3 risk enhancers reliably identified intermediate-risk patients that will benefit from statin therapy, and further CAC testing may be considered among those with <3 risk enhancers.

Objective: Few studies have prospectively examined the associations of lipoprotein(a) [Lp(a)] levels with the risk of abdominal aortic aneurysm (AAA), especially in women. Accounting for commonly recognized risk factors, we investigated the baseline Lp(a) levels and the risk of AAA among postmenopausal women participating in the ongoing national Women's Health Initiative., Methods: Women's Health Initiative participants with baseline Lp(a) levels available who were beneficiaries of Medicare parts A and B fee-for-service at study enrollment or who had aged into Medicare at any point were included. Participants with missing covariate data or known AAA at baseline were excluded. Thoracic aneurysms were excluded owing to the different pathophysiology. The AAA cases and interventions were identified using the International Classification of Diseases, 9th and 10th revision, codes and Current Procedural Terminology codes from claims data. Hazard ratios were computed using Cox proportional hazard models according to the quintiles of Lp(a)., Results: The mean age of the 6615 participants included in the analysis was 65.3 years. Of the 6615 participants, 66.6% were non-Hispanic white, 18.9% were black, 7% were Hispanic and 4.7% were Asian/Pacific Islander. Compared with the participants in the lowest Lp(a) quintile, those in higher quintiles were more likely to be overweight, black, and former or current smokers, to have hypertension, hyperlipidemia, and a history of cardiovascular disease, and to use menopausal hormone therapy and statins. During 65,476 person-years of follow-up, with a median of 10.4 years, 415 women had been diagnosed with an AAA and 36 had required intervention. More than one half had required intervention for a ruptured AAA. We failed to find a statistically significant association between Lp(a) levels and incident AAA. Additional sensitivity analyses stratified by race, with exclusion of statin users and alternative categorizations of Lp(a) using log-transformed levels, tertiles, and a cutoff of >50 mg/dL, were conducted, which did not reveal any significant associations., Conclusions: We found no statistically significant association between Lp(a) levels and the risk of AAA in a large and well-phenotyped sample of postmenopausal women. Women with high Lp(a) levels were more likely to be overweight, black, and former or current smokers, and to have hypertension, hyperlipidemia, and a history of cardiovascular disease, or to use hormone therapy and statins compared with those with lower Lp(a) levels. These findings differ from previous prospective, case-control, and meta-analysis studies that had supported a significant relationship between higher Lp(a) levels and an increased risk of AAA. Differences in the association could have resulted from study limitations or sex differences., (Copyright © 2020 Society for Vascular Surgery. All rights reserved.)

Cardiovascular disease is a leading cause of morbidity and mortality in adults in the United States. Cardiovascular health as a child and adolescent is important in setting the path for a heart-healthy life in adulthood. One major impact on cardiovascular health that can have its roots in childhood is dyslipidemia. Universal screening for all children is a newer concept that has emerged over the last decade; previously children and adolescents were screened based only on risk factors. This review addresses who is at risk for dyslipidemia, how and when to screen children and adolescents, why early identification is important, and how to manage dyslipidemia when it is diagnosed. There are many interventions that can be started in childhood to help decrease cardiovascular risk factors in adults, thus decreasing the morbidity and mortality from heart disease in the future. [Pediatr Ann. 2021;50(1):e4-e9.]., (Copyright 2021, SLACK Incorporated.)

Although the mortality from cardiovascular disease has declined, it remains the leading cause of morbidity and mortality in the United States. Dyslipidemia is a modifiable risk factor that plays a significant role in the development of atherosclerotic cardiovascular disease. Treating dyslipidemia by lowering cholesterol, predominately low-density lipoprotein cholesterol, has been shown to reduce cardiovascular events. The first article that provided dyslipidemia bibliographies was published in 2006. Since this time, new therapies have become available and older therapies that were once thought to provide benefit have since been shown to lack positive outcomes and have therefore fallen out of favor for routine use. As the body of evidence continues to expand, clinicians are faced with reevaluating their treatment strategies to ensure optimal outcomes and appropriate use of lipid-lowering therapies. Therefore, this compilation was created to serve as a resource for clinicians. This publication provides an update of key articles in dyslipidemia management including various guidelines and practice-changing randomized controlled trials.

Purpose: This study sought to investigate gender-based disparities in statin prescription rates and adherence among patients with peripheral arterial disease (PAD) and ischemic cerebrovascular disease (ICVD)., Methods: We identified patients with PAD or ICVD seeking primary care between 2013 and 2014 in the VA healthcare system. We assessed any statin use, high-intensity statin (HIS) use, and statin adherence among women with PAD or ICVD compared with men. We also compared proportion of days covered (PDC) as a measure of statin adherence; PDC ≥ 0.8 deemed a patient statin adherent. Association between statin use (or adherence) and odds of death or myocardial infarction (MI) at 12-month follow-up was also ascertained., Results: Our analyses included 192,219 males and 3188 females with PAD and 331,352 males and 10,490 females with ICVD. Women with PAD had lower prescription rates of any statin (68.5% vs. 78.7%, OR 0.68, 95% confidence interval (CI) 0.62-0.75), HIS (21.1% vs. 23.7%, OR 0.88, 95% CI 0.79-0.97), and lower statin adherence (PDC ≥ 0.8: 34.6% vs. 45.5%, OR 0.75, 95% CI 0.69-0.82) compared with men. Similar disparities were seen in ICVD patients. Among female patients with PAD or ICVD, statin adherence was associated with lower odds of MI (OR 0.76, 95% CI 0.59-0.98), while use of any statin (OR 0.71, 95% CI 0.56-0.91) and HIS (OR 0.68, 95% CI 0.48-0.97) was associated with lower odds of death at 12 months., Conclusions: Women with PAD or ICVD had lower odds of receiving any statins, HIS, or being statin adherent. Targeted clinician- and patient-level interventions are needed to study and address these disparities among patients with PAD and ICVD.

Background: Cardiovascular (CV) disease is the leading cause of death among United States women. Rural residence and ethnic-minority status are individually associated with increased CV mortality. Managing dyslipidemia is important in the prevention of CV mortality. However, the impact of race/ethnicity and location of residence on sex differences in dyslipidemia management is not well understood. Therefore, we sought to understand the joint effects of race/ethnicity and location of residence on lipid management differences between veteran men and women with type 2 diabetes (T2D)., Methods: Veterans Health Administration and Centers for Medicare and Medicaid Services data were used to perform a longitudinal cohort study of veterans with T2D (2007-2016). Mixed effects logistic regression with a random intercept was used to model the association between sex and low-density lipoprotein (LDL) > 100 mg/dL and its interaction with race/ethnicity and location of residence after adjusting for all measured covariates., Results: When female sex and rural location of residence were both present, they were associated with an antagonistic harmful effect on LDL. Similar antagonistic harmful effects on LDL were observed when the joint effect of female sex and several minority race/ethnicity groups were evaluated. After adjusting for measured covariates, the odds of LDL > 100 mg/dL were higher for urban women (OR = 2.66, 95%CI 2.48-2.85) and rural women (OR = 3.26, 95%CI 2.94-3.62), compared to urban men. The odds of LDL > 100 mg/dL was the highest among non-Hispanic Black (NHB) women (OR = 5.38, 95%CI 4.45-6.51) followed by non-Hispanic White (NHW) women (OR = 2.59, 95%CI 2.44-2.77), and Hispanic women (OR = 2.56, 95%CI 1.79-3.66)., Conclusion: Antagonistic harmful effects on LDL were observed when both female sex and rural location of residence were present. These antagonistic effects on LDL were also present when evaluating the joint effect of female sex and several minority race/ethnicity groups. Disparities were most pronounced in NHB and rural women, who had 5.4 and 3.3 times the odds of elevated LDL versus NHW and urban men after adjusting for important covariates. These striking effect sizes in a population at high cardiovascular risk (i.e., older with T2D) suggest interventions aimed at improving lipid management are needed for individuals falling into one or more groups known to face health disparities.

Background and Aim: The association of serum cholesterol levels with the occurrence of coronary heart disease (CHD) mortality during a follow-up of 50 years was rarely investigated previously. Thus, we took advantage of results at hand in 10 pooled cohorts of men aged 40-59 years from the Seven Countries Study (9063 individuals and 2057 CHD fatal events) and we assessed this., Methods and Results: Cox proportional hazards models were run with CHD fatal events (as dependent variable) and cholesterol levels (as independent variables) at years 0, 10, and 25 (in 5 cohorts). Cumulative events during subsequent decades (cumulative approach: CA) and separately in each subsequent decade (partitioned approach: PA) were analyzed. The ecological correlation of average baseline serum cholesterol levels with CHD mortality was very high (R = 0.97). Serum cholesterol and CHD mortality for 50 years were associated at the individual level, and the association estimated by the Cox's coefficients (and related hazards ratios) was initially strong in both CA and PA, but slightly declined during later decades. Hazards ratios (for a difference of 40 mg/dl) ranged from 1.39 to 1.20 for CA and from 1.39 to 0.80 for PA. Coefficients were larger for CA than for PA and the decline was more evident for the latter. Partitioned coefficient became negative and significant in the last decade (from year 40-50). Coefficients derived from cholesterol levels measured at year 10 of follow-up showed similar trends but their magnitude was smaller., Conclusion: Thus, the relationship of serum cholesterol levels with CHD mortality remained relatively stable during at least 40 years after a single cholesterol measurement at baseline in middle-aged men., (Copyright © 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background Effective management of cardiovascular risk factors is the foundation of secondary prevention in coronary artery disease. The physician under whose sphere these are managed can vary, primary care physicians, cardiologists, or both, and the optimal management strategy for risk factor control is unknown. Methods and Results The APPEAR (Angina Prevalence and Provider Evaluation of Angina Relief) study was a cross-sectional cohort study of outpatients with coronary artery disease (stable angina, percutaneous coronary intervention, coronary artery bypass grafting, or myocardial infarction) from 25 US cardiology practices. After each patient visit, providers noted who managed each risk factor. Blood pressure and lipid levels were recorded from charts. We compared adherence to guideline-directed risk factor control between management strategies (primary care physician alone, cardiologist alone, or comanaged). Among 1259 outpatients with coronary artery disease (mean [SD] age, 71 [11.1] years; 69% men), blood pressure and lipid management strategy varied. Mean blood pressure was 127.9/72.3 mm Hg, with 74% of patients at <140/90 mm Hg and 46% at <130/80 mm Hg. Mean low-density lipoprotein was 83.5 mg/dL, with 75% of patients at <100 mg/dL and 91% on appropriate statin therapy. Patients managed by cardiologists alone tended to have higher rates of risk factor control for both blood pressure and lipids, even after adjusting for covariates. Conclusions Although comanagement has shown benefit in some clinical situations, we found that risk factor control in patients with coronary artery disease tended to be poorer when care was shared between cardiologists and primary care physicians. Further research is needed to better define which conditions are best comanaged and how to more effectively comanage patients in the fractured US healthcare system.

Background Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) are used to reduce low-density lipoprotein (LDL) cholesterol. PCSK9i use after initiation, as well as persistence with or alterations to other LDL-lowering therapy after PCSK9i initiation, is not well understood. Methods and Results We conducted a retrospective study of alirocumab or evolocumab (PCSK9i) new users from July 2015 to December 2017 in the MarketScan Early View database of US commercial insurance beneficiaries. We determined the prevalence of PCSK9i interruption (≥30-day gap in supply) and LDL-lowering therapy use in the year after PCSK9i initiation. The average age of 6151 patients initiating PCSK9i therapy was 63 years, 44.4% were women, and 76.8% had atherosclerotic cardiovascular disease. Overall, 52.2% (95% CI, 50.8%-53.7%) of patients had an interruption in PCSK9i therapy in the first year after treatment initiation and 62.5% remained on PCSK9i therapy at 1-year postinitiation. Also, 27.7% of patients were taking a statin at the time of PCSK9i initiation, with only 22.4% on statin therapy at 1 year after PCSK9i initiation. Ezetimibe use decreased from 20.9% at the time of PCSK9i initiation to 12.0% a year later. By 1 year after PCSK9i initiation, 44.0% of patients had experienced an interruption in all LDL-lowering therapies, and 26.6% were no longer on any LDL-lowering therapies. Conclusions After PCSK9i initiation, statins were often discontinued, whereas more than half of patients experienced an interruption in PCSK9i therapy. These results suggest that many new PCSK9i users may remain at high risk for cardiovascular events because of interruptions in LDL-lowering therapy.

Background The American Heart Association and American College of Cardiology guidelines defined patient-management groups that would benefit from lowering of low-density lipoprotein cholesterol (LDL-C). We assessed gaps in dyslipidemia care among employees and spouses with health benefits. Methods and Results We studied 17 889 employees and spouses who were covered by an employer-sponsored health plan and participated in an annual health assessment. Using medical claims, laboratory tests, and risk assessment questionnaires, we found that 43% of participants were in one of 4 patient-management groups: secondary prevention, severe hypercholesterolemia (LDL-C ≥190 mg/dL at least once in the preceding 5 years), diabetes mellitus, or elevated 10-year risk of cardiovascular disease. To assess gaps in dyslipidemia care, we used LDL-C ≤70 mg/dL as the goal for both the secondary prevention group and those in the elevated 10-year risk group with >20% risk; LDL-C ≤100 mg/dL was used for the other groups. Among those in patient-management groups, 27.3% were in the secondary prevention group, 7.4% were in the severe hypercholesterolemia group, 29.9% were in the diabetes mellitus group, and 35.4% were in the elevated 10-year risk group. About 74% of those in patient-management groups had above-goal LDL-C levels, whereas only 31% had evidence of a lipid-lowering therapy in the past 6 months: 45% in the secondary prevention group, 31% in the severe hypercholesterolemia group, 36% in the diabetes mellitus group, and 17% in the elevated 10-year risk group. Conclusions The substantial gaps in LDL-C treatment and goal attainment among members of an employer-sponsored medical plan who were mostly aware of their LDL-C levels indicate the need for gap-closure initiatives.

Background Inflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high-sensitivity C-reactive protein) is prognostic across various levels of atherogenic lipid measures such as low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high-density lipoprotein cholesterol in primary prevention is unknown. Methods and Results We studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996-1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low-density lipoprotein cholesterol + non-high-density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high-density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow-up of 18.4 (12.8-19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09-1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18-1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use. Conclusions Our findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.

Background: The Southern region of the United States is home to substantial populations with obesity, dyslipidemia, and hypertriglyceridemia, while also housing a large percentage of America's minority, rural, and low socioeconomic status (SES) peoples. Adult-onset cardiovascular disease (CVD) research may be informed by investigating associations(s) between late adolescent demographic variables and lipid values. Our objective was to investigate lipid parameter associations with college-age socioeconomic status, which may improve age-specific screening algorithms for management or prevention of adult-onset CVD., Methods: Using an Analysis of Variance test and a general linear model, associations between gender, race/ethnicity, SES, and athletic participation on lipid parameters (VLDL-C, LDL-C, TG, TC, and HDL-C) were analyzed in 4423 private liberal arts college students enrolled in freshman-level wellness courses at Furman University in Greenville, SC. Comparative data were collected from an age-matched sample (National Health and Nutrition Examination Survey: NHANES 2003-2016). Our main outcomes were statistically significant relationships between any lipid values (TC, HDL-C, LDL-C, TG) and any demographic variables (gender, SES, ethnicity, athlete status)., Results: Males demonstrated lower TC and LDL-C, and higher HDL-C values. HDL-C was highest in athletes. African-American students demonstrated healthier VLDL-C, TG, and HDL-C values. With similar distributions, the age-matched NHANES comparison group showed unhealthier values in nearly all categories., Conclusions: College students may have better lipid health than the general population. African-Americans may have seemingly healthier lipid values than age-matched individuals independent of athletic or college enrollment which has already been demonstrated in other studies. Future research should include SES relationships in lipid screening paradigms along with other appropriate risk factors for cardiovascular disease. Based on our comparative data, pediatric health providers and researchers may consider education as a potential protective factor against poor lipid health when considering lipid screening protocols for students.

Introduction: The 2013 pooled cohort equations (PCE) may misestimate cardiovascular event (CVE) risk, particularly for black patients. Alternatives to the original PCE (O-PCE) to assess potential statin benefit for primary prevention-a revised PCE (R-PCE) and US Preventive Services Task Force (USPSTF) algorithms-have not been compared in contemporary US patients in routine office-based practice., Methods: We performed retrospective, cross-sectional analysis of a nationally representative, US sample of office visits made from 2011 to 2014. Sampling criteria matched those used for PCE development: aged 40 to 79 years, black or white race, no cardiovascular disease. Original PCE, R-PCE, and USPSTF algorithms were applied to biometric and demographic data. Outcomes included estimated 10-year CVE risk, percentage exceeding each algorithm's statin-treatment threshold ( > 7.5% risk for O-PCE and R-PCE, and > 10% O-PCE plus > 1 risk factor for USPSTF), and percentage prescribed statin therapy., Results: In 12 556 visits (representing 285 330 123 nationwide), 10.8% of patients were black, 27.1% had diabetes, and 15.7% were current smokers. Replacing O-PCE with R-PCE decreased mean (95% confidence interval [CI]) estimated CVE risk from 12.4% (12.0%-12.7%) to 8.5% (8.2%-8.8%). Significant ( P < 0.05) racial disparity in the rate of CVE risk > 7.5% was identified using O-PCE (black and white patients [95% CI], respectively: 58.8% [54.6%-62.9%] vs 52.8% [51.1%-54.4%], P = .006) but not R-PCE (41.6% [37.6%-45.7%] vs 39.9% [38.3%-41.5%], P = .448). Revised PCE and USPSTF recommendations were concordant for 90% of patients. Significant racial disparity in guideline-concordant statin prescribing was found using O-PCE (black and white patients, respectively, 35.0% [30.5%-39.9%] vs 41.8% [39.9%-44.4%], P = .013), but not R-PCE (40.6% [35.0%-46.6%] vs 43.0% [40.0%-45.9%], P = .482) or USPSTF recommendations (39.0% [33.8%-44.5%] vs 44.4% [41.5%-47.5%], P = .073)., Conclusions: Use of an alternative to O-PCE may reduce racial disparity in estimated CVE risk and may facilitate shared decision-making about primary prevention.

Purpose: Real-world data may provide insight into relationships between high triglycerides (TG), a modifiable cardiovascular (CV) risk factor, and increased heart failure (HF) risk., Patients and Methods: This retrospective administrative claims analysis included statin-treated patients aged ≥45 years with diabetes and/or atherosclerotic CV disease enrolled in 2010 and followed for ≥6 months to March 2016. Patients with TG ≥150 mg/dL and a comparator cohort with TG <150 mg/dL and high-density lipoprotein cholesterol >40 mg/dL were included. A sub-analysis was conducted in patients with TG 200-499 mg/dL. Hazard ratios (HR) were calculated from multivariate analyses controlled for patient characteristics and comorbidities using Cox proportional hazard modeling. New diagnosis of HF required diagnosis in the follow-up period without prior evidence of HF., Results: Multivariate analyses revealed a 19% higher rate of new HF diagnosis in the TG ≥150 mg/dL cohort (HR=1.192; 95% confidence interval [CI]=1.134-1.252; P <0.001; n=24,043) and a 24% higher rate in the TG 200-499 mg/dL sub-cohort (HR=1.235; 95% CI=1.160-1.315; P <0.001; n=11,657), each versus the comparator cohort (n=30,218)., Conclusion: In a real-world analysis of statin-treated patients with high CV risk, elevated and high TG were significant predictors of new HF diagnosis., Competing Interests: Peter P. Toth is a consultant and/or speaker for Amarin Pharma Inc, Amgen, Kowa, Novo-Nordisk, Regeneron, and Sanofi. He also reports personal fees and non-financial support from Amarin Pharma Inc, during the conduct of the study; personal fees, non-financial support from Amarin Pharma Inc, outside the submitted work. Sephy Philip and Craig Granowitz are employees and stock shareholders of Amarin Pharma Inc. Dr Sephy Philip has a patent compositions and methods for lowering triglycerides in a subject having reduced kidney function pending to Amarin Pharma Inc. Michael Hull is an employee of Optum. The authors report no other conflicts of interest in this work., (© 2019 Toth et al.)

Background: The 2018 US cholesterol management guidelines recommend additional lipid-lowering therapies for secondary prevention in patients with low-density lipoprotein cholesterol ≥70 mg/dL or non-high-density lipoprotein cholesterol ≥100 mg/dL despite maximum tolerated statin therapy. Such patients are considered at very high risk (VHR) based on a history of >1 major atherosclerotic cardiovascular disease (ASCVD) event or a single ASCVD event and multiple high-risk conditions. We investigated the association of US guideline-defined risk categories with the occurrence of ischemic events after acute coronary syndrome and reduction of those events by alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor., Methods: In the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab), patients with recent acute coronary syndrome and residual dyslipidemia despite optimal statin therapy were randomly assigned to alirocumab or placebo. The primary trial outcome (major adverse cardiovascular events, ie, coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) was examined according to American College of Cardiology/American Heart Association risk category., Results: Of 18 924 participants followed for a median of 2.8 years, 11 935 (63.1%) were classified as VHR: 4450 (37.3%) had multiple prior ASCVD events and 7485 (62.7%) had 1 major ASCVD event and multiple high-risk conditions. Major adverse cardiovascular events occurred in 14.4% of placebo-treated patients at VHR versus 5.6% of those not at VHR. In the VHR category, major adverse cardiovascular events occurred in 20.4% with multiple prior ASCVD events versus 10.7% with 1 ASCVD event and multiple high-risk conditions. Alirocumab was associated with consistent relative risk reductions in both risk categories (hazard ratio=0.84 for VHR; hazard ratio=0.86 for not VHR; P interaction =0.820) and by stratification within the VHR group (hazard ratio=0.86 for multiple prior ASCVD events; hazard ratio=0.82 for 1 major ASCVD event and multiple high-risk conditions; P interaction =0.672). The absolute risk reduction for major adverse cardiovascular events with alirocumab was numerically greater (but not statistically different) in the VHR group versus those not at VHR (2.1% versus 0.8%; P interaction =0.095) and among patients at VHR with multiple prior ASCVD events versus a single prior ASCVD event (2.4% versus 1.8%; P interaction =0.661)., Conclusions: The US guideline criteria identify patients with recent acute coronary syndrome and dyslipidemia who are at VHR for recurrent ischemic events and who may derive a larger absolute benefit from treatment with alirocumab., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402.

Context: There is a disturbingly high prevalence of dyslipidemia in youth. Although pediatric endocrinologists are aware of the substantial cardiovascular (CV) risk associated with monogenic disorders of lipid and lipoprotein metabolism, relatively few recognize the CV disease (CVD)-related morbidity and premature mortality incurred by common endocrine disorders associated with dyslipidemia, such as diabetes mellitus, growth hormone deficiency, congenital adrenal hyperplasia, and hypopituitarism., Objective: In this article, we discuss the expanding role of pediatric endocrinologists in CV health and risk prevention., Design: We reviewed available literature and summarized discussions with opinion leaders in pediatric endocrinology to accomplish the following: (i) provide an overview of this timely topic; (ii) identify opportunities for targeted education; and (iii) discuss ways of expanding clinical services to improve outcomes., Results: In addition to well-known genetic disorders of lipid and lipoprotein metabolism, youth with common endocrine disorders, including type 1 and type 2 diabetes, would benefit from cholesterol screening and in some, early intervention, including use of lipid-lowering medications. Despite the growing need, the location and extent of services available to youth with dyslipidemia and the availability of providers with experience in treatment of dyslipidemia are largely unknown but likely inadequate to provide accessible, timely, and cost-effective intervention., Conclusion: With a new awareness of opportunities to prevent premature CVD in youth, including those with common endocrine disorders and CVD-related events during adulthood, there is an urgent need for additional clinical services and targeted education of current as well as future pediatric endocrinologists., (Copyright © 2019 Endocrine Society.)

Background Current treatment guidelines strongly recommend statin therapy for secondary prevention. However, it remains unclear whether patients' perceptions of cardiovascular risk, beliefs on cholesterol, or the intensity of prescribed statin therapy differs for patients with coronary artery disease (CAD) versus cerebrovascular disease (CeVD) versus both CAD and CeVD (CAD&CeVD). Methods and Results The PALM (Patient and Provider Assessment of Lipid Management) registry collected data on statin use, intensity, and core laboratory low-density lipoprotein cholesterol levels for 3232 secondary prevention patients treated at 133 US clinics. Among individuals with CeVD only (n=403), CAD only (n=2202), and CeVD&CAD (n=627), no significant differences were observed in patient-perceived cardiovascular disease risk, beliefs on cholesterol lowering, or perceived effectiveness and safety of statin therapy. However, patients with CeVD only were less likely to receive any statin therapy (76.2% versus 86.2%; adjusted odds ratio 0.64, 95% CI 0.45-0.91), or guideline-recommended statin intensity (34.6% versus 50.4%; adjusted odds ratio 0.60, 95% CI 0.45-0.81) than those with CAD only. Individuals with CeVD only were also less likely to achieve low-density lipoprotein cholesterol <100 mg/dL (59.2% versus 69.7%; adjusted odds ratio 0.79, 95% CI 0.64-0.99) than individuals with CAD alone. There were no significant differences in the use of any statin therapy or guideline-recommended statin intensity between individuals with CAD&CeVD and those with CAD only. Conclusions Despite lack of significant differences in patient-perceived cardiovascular risk or statin beliefs, patients with CeVD were significantly less likely to receive higher intensity statin or achieve low-density lipoprotein cholesterol <100 mg/dL than those with CAD only.

Background: Female patients have historically received less aggressive lipid management than male patients. Contemporary care patterns and the potential causes for these differences are unknown., Methods and Results: Examining the Patient and Provider Assessment of Lipid Management Registry-a nationwide registry of outpatients with or at risk for atherosclerotic cardiovascular disease-we compared the use of statin therapy, guideline-recommended statin dosing, and reasons for undertreatment. We specifically analyzed sex differences in statin treatment and guideline-recommended statin dosing using multivariable logistic regression. Among 5693 participants (43% women) eligible for 2013 American College of Cardiology/American Heart Association Cholesterol Guideline-recommended statin treatment, women were less likely than men to be prescribed any statin therapy (67.0% versus 78.4%; P<0.001) or to receive a statin at the guideline-recommended intensity (36.7% versus 45.2%; P<0.001). Women were more likely to report having previously never been offered statin therapy (18.6% versus 13.5%; P<0.001), declined statin therapy (3.6% versus 2.0%; P<0.001), or discontinued their statin (10.9% versus 6.1%; P<0.001). Women were also less likely than men to believe statins were safe (47.9% versus 55.2%; P<0.001) or effective (68.0% versus 73.2%; P<0.001) and more likely to report discontinuing their statin because of a side effect (7.9% versus 3.6%; P<0.001). Sex differences in both overall and guideline-recommended intensity statin use persisted after adjustment for demographics, socioeconomic factors, clinical characteristics, patient beliefs, and provider characteristics (adjusted odds ratio, 0.70; 95% CI, 0.61-0.81; P<0.001; and odds ratio, 0.82; 95% CI, 0.73-0.92; P<0.01, respectively). Sex differences were consistent across primary and secondary prevention indications for statin treatment., Conclusions: Women eligible for statin therapy were less likely than men to be treated with any statin or guideline-recommended statin intensity. A combination of women being offered statin therapy less frequently, while declining and discontinuing treatment more frequently, accounted for these sex differences in statin use.

Gut microbiota dysbiosis has been recognized as having key importance in obesity- and metabolic-related diseases. Although there is increasing evidence of the potential benefits induced by probiotics in metabolic disturbances, there is a lack of large cross-sectional studies to assess population-based prevalence of probiotic intake and metabolic diseases. Our aim was to evaluate the association of probiotic ingestion with obesity, type 2 diabetes, hypertension, and dyslipidemia. A cross-sectional study was designed using data from the National Health and Nutrition Examination Survey (NHANES), 1999-2014. Probiotic ingestion was considered when a subject reported consumption of yogurt or a probiotic supplement during the 24-hour dietary recall or during the Dietary Supplement Use 30-Day questionnaire. We included 38,802 adults and 13.1% reported probiotic ingestion. The prevalence of obesity and hypertension was lower in the probiotic group (obesity-adjusted Odds Ratio (OR): 0.84, 95% CI 0.76-0.92, p < 0.001; hypertension-adjusted OR: 0.79, 95% CI 0.71-0.88, p < 0.001). Accordingly, even after analytic adjustments, body mass index (BMI) was significantly lower in the probiotic group, as were systolic and diastolic blood pressure and triglycerides; high-density lipoprotein (HDL) was significantly higher in the probiotic group for the adjusted model. In this large-scale study, ingestion of probiotic supplements or yogurt was associated with a lower prevalence of obesity and hypertension., Competing Interests: The authors declare no conflict of interest.

Background PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors effectively lower LDL (low-density lipoprotein) cholesterol and have been shown to reduce cardiovascular outcomes in high-risk patients. We used real-world electronic health record data to characterize use of PCSK9 inhibitors, in addition to standard therapies, according to cardiovascular risk status. Methods and Results Data were obtained from 18 health systems with data marts within the National Patient-Centered Clinical Research Network (PCORnet) using a common data model. Participating sites identified >17.5 million adults, of whom 3.6 million met study criteria. Patients were categorized into 3 groups: (1) dyslipidemia, (2) untreated LDL ≥130 mg/dL, and (3) coronary artery disease or coronary heart disease. Demographics, comorbidities, estimated 10-year atherosclerotic cardiovascular disease risk, and lipid-lowering pharmacotherapies were summarized for each group. Participants' average age was 62 years, 50% were female, and 11% were black. LDL cholesterol ranged from 85 to 151 mg/dL. Among patients in groups 1 and 3, 54% received standard lipid-lowering therapies and a PCSK9 inhibitor was prescribed in <1%. PCSK9 inhibitor prescribing was greatest for patients with coronary artery disease or coronary heart disease and, although prescribing increased during the study period, overall PCSK9 inhibitor prescribing was low. Conclusions We successfully used electronic health record data from 18 PCORnet data marts to identify >3.6 million patients meeting criteria for 3 patient groups. Approximately half of patients had been prescribed lipid-lowering medication, but <1% were prescribed PCSK9 inhibitors. PCSK9 inhibitor prescribing increased over time for patients with coronary artery disease or coronary heart disease but not for those with dyslipidemia.

Introduction: PTMS-a clustering of hypertension, dyslipidemia, glucose intolerance/diabetes, and obesity-is increasingly recognized as a contributor to long-term morbidity after transplant. We sought to describe pediatric liver transplant center protocols and provider practices in screening for and managing these conditions., Methods: Cross-sectional survey of pediatric liver transplant providers from centers that participate in Studies of Liver Transplantation (SPLIT)., Results: Of 49 survey respondents from 39 centers, 64% were hepatologists or surgeons, 18% nurses/NPs/PAs, 12% coordinators, and 4% other. All providers felt that pediatric liver transplant recipients should be routinely screened for PTMS components. For each condition, at least 70% felt that the liver transplant team should be primarily responsible for routine screening. For each condition, at least 30% of providers reported that their center had no standardized protocol for screening. For diagnostic evaluation and initial management, >60% of providers reported that their center had no standardized protocol for glucose intolerance/diabetes, dyslipidemia, or obesity. Almost 40% had no standardized workup or initial management protocol for hypertension or chronic kidney disease. Of centers that did have screening or workup protocols, most were based on existing center practice, provider consensus, or informal review of published evidence. Screening tools, treatment steps, and thresholds for referral to another specialist varied widely., Conclusions: Transplant providers intend to screen for and initiate management of PTMS components in these children, but protocols and practices vary substantially. This highlights opportunities for multi-center collaboration on protocols or interventions to improve screening and management., (© 2019 Wiley Periodicals, Inc.)

Identification and management of dyslipidemia in childhood can reduce future cardiovascular risk. We performed a retrospective cohort study of children ages 2 to 18 years during 2009 to 2013 to evaluate factors that affect screening and treatment of pediatric dyslipidemia related to 2011 National Heart, Lung, and Blood Institute (NHLBI) guidelines. Logistic regression analysis determined the impact of NHLBI-identified factors on odds of being screened, elevated low-density lipoprotein cholesterol (LDL-C), and receiving pharmacotherapy. A total of 1 736 032 children were included; 113 780 (6.6%) were screened for dyslipidemia. Screening in 9 to 11 year olds increased from 2009 to 2012. Of children screened, 18 801 (16.5%) had elevated LDL-C; 425 (2.3%) were treated pharmacologically. Parental dyslipidemia, diabetes mellitus, chronic kidney disease, Kawasaki disease, human immunodeficiency virus infection, nephrotic syndrome, liver, thyroid, and other endocrine disorders increased odds of screening. Older age, nephrotic syndrome, chronic kidney disease, diabetes mellitus, and hypertension increased odds of having elevated LDL-C and receiving treatment. Pediatric dyslipidemia screening rates remain low.

Background: Adolescent obesity is an important risk factor for cardiovascular disease in part due to its relationship to type 2 diabetes. Therefore, screening for type 2 diabetes is recommended. However, since insulin resistance (IR) is an early precursor of diabetes, it would be beneficial if IR predictors from routine assessments could identify those at greatest metabolic risk before diabetes has developed., Methods: Adolescents aged 14-18 years with normal fasting plasma glucose (n = 252) were selected from the National Health and Nutrition Examination Survey 2013-2014. IR was estimated with homeostatic model assessment (HOMA). Multivariable linear/logistic regressions with demographic covariates assessed HOMA Index (HI)-determined IR associations with common clinical measurements., Results: The constellation of body mass index (BMI) percentile (P < 0.0001), diastolic blood pressure (DBP, P = 0.0056), and serum alanine aminotransferase (ALT, P = 0.0295) predicted log-transformed HI; cholesterol, triglycerides, and high- and low-density lipoprotein cholesterol were not predictive. Secondary gender analyses indicated significant associations in males (BMI percentile, P = 0.0008; DBP, P = 0.0003; ALT, P = 0.0436), but only BMI percentile in females (P = 0.0001). After stratifying predictors at clinical thresholds, logistic regressions had increased specificity at HI's 85th percentile compared with its 75th [85th: area under curve (AUC) = 0.87, 75th: AUC = 0.80]. At the 85th HI percentile, IR was associated with these components [BMI percentile: adjusted odds ratio (aOR) = 34.31, 95% confidence interval (CI): 8.5-139.3; ALT: aOR = 11.36, 95% CI: 3.0-43.7; DBP: aOR = 7.73, 95% CI: 2.4-24.6]. In males, IR was associated with elevated BMI percentile (aOR 24.0) and ALT (aOR 23.9) and in females with elevated BMI percentile (aOR 45.8) and DBP (aOR 17.9)., Conclusions: Three routine clinical assessments, BMI percentile, DBP, and ALT, predicted IR at HI's 75th and 85th percentiles in nondiabetic adolescents. Prospective validation may yield simple gender-specific screening identifying nondiabetic adolescents at greatest need of treatment intervention.

Aims: Relatively little is known about the health outcomes associated with very low plasma concentrations of high-density lipoprotein cholesterol (HDL-C) mainly because of the small numbers of individuals with such extreme values included in clinical trials. We, therefore, investigated the association between low and very low HDL-C concentration at baseline and incident all-cause-mortality, death from malignant disease (i.e. cancer), and with fatal or non-fatal incident coronary heart disease (CHD) in individuals from the Reasons for Geographical And Racial Differences in Stroke (REGARDS) study., Methods and Results: Analysis was based on 21 751 participants from the REGARDS study who were free of CHD, other cardiovascular disease, and cancer at baseline and were categorized by baseline HDL-C into <30 mg/dL (very low), 30-<40 mg/dL (low), and ≥40 mg/dL (reference). A series of incremental Cox proportional hazards models were employed to assess the association between the HDL-C categories and outcomes. Statistical analysis was performed using both complete case methods and multiple imputations with chained equations. After adjustment for age, race, and sex, the hazard ratios (HRs) comparing the lowest and highest HDL-C categories were 1.48 [95% confidence interval (CI) 1.28-1.73] for all-cause mortality, 1.35 (95% CI 1.03-1.77) for cancer-specific mortality and 1.39 (95% CI 0.99-1.96) for incident CHD. These associations became non-significant in models adjusting for demographics, cardiovascular risk factors, and treatment for dyslipidaemia. We found evidence for an HDL paradox, whereby low HDL (30-<40 mg/dL) was associated with reduced risk of incident CHD in black participants in a fully adjusted complete case model (HR 0.63; 95% CI 0.46-0.88) and after multiple imputation analyses (HR 0.76; 95% CI 0.58-0.98). HDL-C (<30 mg/dL) was significantly associated with poorer outcomes in women for all outcomes, especially with respect to cancer mortality (HR 2.31; 95% CI 1.28-4.16) in a fully adjusted complete case model, replicated using multiple imputation (HR 1.81; 95% CI 1.03-3.20)., Conclusion: Low HDL-C was associated with reduced risk of incident CHD in black participants suggesting a potential HDL paradox for incident CHD. Very low HDL-C in women was significantly associated with cancer mortality in a fully adjusted complete case model.

Aims: The European Society of Cardiology (ESC) guideline on cardiovascular risk assessment considers coronary artery calcium a class B indication for risk assessment. We evaluated the degree to which coronary artery calcium can change the recommendation for individuals based on a change in estimated risk., Methods and Results: We stratified 5602 MESA participants according to the ESC recommendation as: no lipid-lowering treatment recommended ( N = 2228), consider lipid-lowering treatment if uncontrolled ( N = 1686), or lipid-lowering treatment recommended ( N = 1688). We evaluated the ability of coronary artery calcium to reclassify cardiovascular risk. Among the selected sample, 54% had coronary artery calcium of zero, 25% had coronary artery calcium of 1-100 and 21% had coronary artery calcium greater than 100. In the lipid-lowering treatment recommended group 31% had coronary artery calcium of zero, while in the lipid-lowering treatment if uncontrolled group about 50% had coronary artery calcium of zero. The cardiovascular mortality rate was 1.7%/10 years in the lipid-lowering treatment if uncontrolled, and 7.0%/10 years in the lipid-lowering treatment recommended group. The absence of coronary artery calcium was associated with 1.4%/10 years in the lipid-lowering treatment if uncontrolled group and 3.0%/10 years in the lipid-lowering treatment recommended group. Compared with coronary artery calcium of zero, any coronary artery calcium was associated with significantly higher cardiovascular mortality in the lipid-lowering treatment recommended group (9.0%/10 years), whereas only coronary artery calcium greater than 100 was significantly associated with a higher cardiovascular mortality in the lipid-lowering treatment if uncontrolled group (3.2%/10 years)., Conclusion: The absence of coronary artery calcium is associated with a low incidence of cardiovascular mortality or coronary heart disease events even in individuals in whom lipid-lowering therapy is recommended. A significant proportion of individuals deemed to be candidates for lipid-lowering therapy might be reclassified to a lower risk group with the use of coronary artery calcium.

Background: The ACC/AHA cholesterol guidelines recommend patients with peripheral artery disease (PAD) be treated with a moderate to high-intensity statin. The extent to which patients with new or worsening PAD symptoms are offered guideline therapy is unknown., Hypothesis: There is significant variability in rate of guideline-directed statin intensification across clinical practices., Methods: In the PORTRAIT registry, patterns of statin therapy were assessed in 1144 patients at 16 PAD specialty clinics between June 2011 and December 2015 before and after an evaluation for new or worsening claudication symptoms. We documented whether patients were treated with a guideline statin as well as the incidence of statin intensification. Statin intensification was defined as transitioning from no statin or low-intensity statin to moderate or high-intensity statin treatment. Patient factors associated with intensification were examined. Site and provider-level variation in intensification was summarized using an adjusted median odds ratio (aMOR)., Results: Among 1144 patients, 810 (70.8%) were initially on guideline therapy compared to 334 (29.2%) that were not. In the latter, 103 (30.8%) received intensification following evaluation. Patients with typical symptoms displayed greater odds of intensification (OR 3.74; 95% CI: 1.23-11.41) while older patients had lower odds of intensification (OR 0.60/decade; 95% CI: 0.41-0.88). Site variability for statin intensification was observed across sites (aMOR = 3.15; 95% CI 1.22-9.60, [P = 0.02]) but not providers (aMOR = 1.89; 95% CI 1.00-3.90, [P = 0.14])., Conclusions: Most patients evaluated at a PAD specialty clinic for new or worsening claudication symptoms arrived on guideline statin therapy. Only 31% not receiving appropriate therapy underwent statin intensification. These findings highlight an important opportunity to optimize medical therapy for patients with PAD., (© 2018 Wiley Periodicals, Inc.)

Background: Patients with diabetes mellitus (DM) have a high risk for cardiovascular disease (CVD) events after an acute myocardial infarction (AMI). High-intensity statins reduce CVD risk following AMI among patients with and without DM., Methods: We determined the proportion of Medicare beneficiaries 66 to 75 years of age taking a low/moderate-intensity statin with (n = 6718) and without (n = 6414) DM who titrated to a high-intensity statin dosage (i.e., atorvastatin 40 or 80 mg, or rosuvastatin 20 or 40 mg) following an AMI hospitalization in 2014-2015. All patients had a pharmacy claim for a statin fill within 365 days prior to, and within 30 days after their AMI hospitalization. We excluded beneficiaries without Medicare fee-for-service coverage including pharmacy benefits during the study period and those with a pharmacy claim for a high-intensity statin prior to their AMI., Results: The first statin fill following hospital discharge was for a high-intensity dosage among 37.7% and 44.4% of patients with and without DM, respectively. After multivariable adjustment, the risk ratio (RR) for titrating to a high-intensity statin comparing patients with versus without DM was 1.01 (95% CI 0.96, 1.06). Among patients whose first statin fill post-AMI was for a low/moderate-intensity dosage, 7.5% of those with DM titrated to a high-intensity statin within 182 days, compared with 9.2% of those without DM (multivariable-adjusted RR 0.90 [95% CI 0.75, 1.08])., Conclusions: Most patients taking a low/moderate-intensity statin were not titrated to a high-intensity dosage following AMI irrespective of their diabetes status, potentially leaving substantial residual risk for recurrent CVD events.

Objective: This study sought to characterise the main dyslipidaemic phenotypes present in chronic kidney disease (CKD) and their association with coronary heart disease (CHD) risk., Methods: Analyses included 6612 individuals in the multiethnic study of atherosclerosis free of CHD at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) of 15 to <60 mL/min/1.73 m 2 (stages 3-4). Principal component analyses were used to characterise the main dyslipidaemic phenotypes of CKD accounting for the correlation among different lipoproteins and lipoprotein particles. CHD was defined as incident myocardial infarction, angina followed by revascularisation, resuscitated cardiac arrest or CHD death., Results: CHD developed in 303 individuals (5%) with eGFR ≥60 and in 72 individuals (12%) with CKD (p for difference <0.001). A dyslipidaemic phenotype (principal component 1 (PC1)) consisting of elevations in triglycerides, triglyceride-rich lipoproteins (VLDL particles), small LDL particles and reductions in HDL particles, was more common in those with CKD, compared with those without CKD (p for difference <0.001). This phenotype was also more strongly associated with CHD in those with CKD: adjusted HRs (95% CIs) per SD increase in PC1 1.13 (95% CI 1.00 to 1.27; P=0.05) and 1.51 (95% CI 1.17 to 1.94; P<0.001) in eGFR ≥60 and CKD, respectively (P for interaction=0.05)., Conclusion: In individuals with mainly stage 3 CKD, a dominant lipid phenotype consisting of triglyceride-rich lipoproteins and other closely correlated lipoproteins is strongly associated with CHD risk. Future studies should investigate whether modification of the components of this phenotype leads to a reduction in the CHD burden in individuals with CKD., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background and Aims: Two weight gain prevention strategies, one targeting small changes to diet and physical activity and a second targeting large changes, significantly reduced weight gain in young adulthood. We examined whether weight gain prevention blunts genetic risk for body weight increase and/or high density lipoprotein cholesterol (HDL-C) lowering over two years., Methods and Results: Participants were 524 male and female young adults (mean age = 28.2, SD = 4.3; mean BMI = 25.5, SD = 2.6). Obesity-related SNPs accounting for ≥ 0.04% of the variance were genotyped and combined into a genetic risk score. For HDL-C, SNPs within CETP, LIPC and FADS2 were genotyped. The obesity-related genetic risk score did not predict change in BMI independently or in interaction with treatment arm. However, consistent with the prior literature, each copy of the HDL-C risk, C, allele at CETP rs3764261 was associated with lower HDL-C at baseline. Moreover, significant interaction between SNP and treatment arm for change in HDL-C was observed (p = 0.02). In the control group, HDL-C change was dependent upon rs3764261 (p = 0.004) with C allele carriers showing a continued reduction in HDL-C. In contrast, within the two intervention groups, HDL-C increased on average with no differential effect of rs3764261 (p > 0.24). Notably, even among carriers of the CC genotype, small and large change arms were associated with increased HDL-C and the control arm a reduction (p = 0.013)., Conclusions: The C allele at CETP rs3764261 is a strong risk factor for low HDL-C in young adulthood but weight gain prevention may mitigate this risk. CLINICAL TRIAL REGISTRY NUMBER AND WEBSITE: clinicaltrials.gov Identifier: NCT01183689, https://clinicaltrials.gov/., (Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background and Aims: The prevalence and correlates of subclinical atherosclerosis when low-density lipoprotein cholesterol (LDL-C) levels are low remain unclear. Therefore, we examined the association of cardiovascular risk factors and subclinical atherosclerosis among individuals with untreated LDL-C <70 mg/dL., Methods: We included participants from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) cohorts. To optimize accuracy, LDL-C was calculated by the validated Martin/Hopkins equation that uses an adjustable factor for the ratio of triglycerides to very low-density lipoprotein cholesterol. We defined subclinical atherosclerosis as a coronary artery calcium (CAC) score >0 in the combined cohort or common carotid intima media thickness (cIMT) in the 4 th quartile, using cohort-specific cIMT distributions at baseline. Logistic regression models examined the cross-sectional associations of cardiovascular risk factors and subclinical atherosclerosis., Results: Among 9411 participants not on lipid lowering therapy, 263 (3%) had LDL-C <70 mg/dL (MESA: 206, ELSA: 57). Mean age in this population was 58 (SD 12) years, with 43% men, and 41% Black. The prevalence of CAC >0 in those with untreated LDL-C<70 mg/dL was 30%, and 18% were in 4th quartile of cIMT. In demographically adjusted models, only ever smoking was significantly associated with both CAC and cIMT. Similar results were obtained in risk factor-adjusted models (smoking: OR, 2.29; 95% CI, 1.10-4.80 and OR, 3.44; 95% CI, 1.41-8.37 for CAC and cIMT, respectively)., Conclusions: Among middle-aged to older individuals with untreated LDL-C <70 mg/dL, subclinical atherosclerosis remains moderately common and is associated with cigarette smoking., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: The potential impact of the 2016 United States Preventive Services Task Force (USPSTF) guidelines on statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) warrants further analysis., Methods and Results: We studied participants from MESA (Multi-Ethnic Study of Atherosclerosis) aged 40 to 75 years and not on statins. We compared statin eligibility at baseline (2000-2002) and over follow-up between USPSTF and the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines. Coronary artery calcium (CAC) was measured at baseline. Absolute ASCVD event rates were calculated according to eligibility categories for each guideline. Among 4962 MESA participants (aged 59.3±8.8 years, 47.2% female), compared with ACC/AHA guidelines, baseline statin eligibility by USPSTF was significantly lower (34.4% versus 49.1%) and increased less over time (39.1% versus 59.1%) at examination 5 [years 2010-2012]). Compared with ACC/AHA, participants eligible by USPSTF were less likely to have zero CAC at baseline (36.6% versus 41.2%) and had higher rates of hard ASCVD events per 1000 person-years (11.6 [95% confidence interval, 10.2-13.3] versus 10.0 [8.9-11.3]). The hard ASCVD event rate in those eligible by ACC/AHA but not USPSTF was 6.5 (4.9-8.5) events per 1000 person-years, with the rate varying significantly according to baseline CAC (4.2 [2.7-6.7] events in those with CAC=0, 12.8 [8.3-19.9] events in those with CAC >100)., Conclusions: In MESA, compared with ACC/AHA, the USPSTF statin guidelines resulted in a 15% absolute decrease in eligibility. Participants with discordant eligibility had ASCVD rates that varied significantly according to baseline CAC, suggesting CAC could aid clinical decision making for statins in these individuals., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Current statin use and symptoms among older adults in routine community practice have not been well characterized since the release of the 2013 American College of Cardiology/American Heart Association guideline., Methods and Results: We compared statin use and dosing between adults >75 and ≤75 years old who were eligible for primary or secondary prevention statin use without considering guideline-recommended age criteria. The patients were treated at 138 US practices in the Patient and Provider Assessment of Lipid Management (PALM) registry in 2015. Patient surveys also evaluated reported symptoms while taking statins. Multivariable logistic regression models examined the association between older age and statin use and dosing. Among 6717 people enrolled, 1704 (25%) were >75 years old. For primary prevention, use of any statin or high-dose statin did not vary by age group: any statin, 62.6% in those >75 years old versus 63.1% in those ≤75 years old ( P =0.83); high-dose statin, 10.2% versus 12.3% in the same groups ( P =0.14). For secondary prevention, older patients were slightly less likely to receive any statin (80.1% versus 84.2% [ P =0.003]; adjusted odds ratio, 0.81; 95% confidence interval, 0.66-1.01 [ P =0.06]), but were much less likely to receive a high-intensity statin (23.5% versus 36.2% [ P <0.0001]; adjusted odds ratio, 0.54; 95% confidence interval, 0.45-0.65 [ P =0.0001]). Among current statin users, older patients were slightly less likely to report any symptoms (41.3% versus 46.6%; P =0.003) or myalgias (27.3% versus 33.3%; P <0.001)., Conclusions: Overall use of statins was similar for primary prevention in those aged >75 years versus younger patients, yet older patients were less likely to receive high-intensity statins for secondary prevention. Statins appear to be similarly tolerated in older and younger adults., (© 2018 The Authors and Mayo Clinic. Published on behalf of the American Heart Association, Inc., by Wiley.)

Background: Contact with the healthcare system represents an opportunity for individuals who discontinue statins to re-initiate treatment. To help identify opportunities for healthcare providers to emphasize the risk-lowering benefits accrued through restarting statins, we determined the types of healthcare utilization associated with statin re-initiation among patients with history of a myocardial infarction., Methods and Results: Medicare beneficiaries with a statin pharmacy fill claim within 30 days of hospital discharge for a myocardial infarction in 2007 to 2012 (n=158 795) were followed for 182 days postdischarge to identify treatment discontinuation, defined as 60 continuous days without statins (n=24 461). Re-initiation was defined as a statin fill within 365 days of the discontinuation date (n=13 136). Using a case-crossover study design and each beneficiary as their own control, healthcare utilization during 0 to 14 days before statin re-initiation (case period) was compared with healthcare utilization 30 to 44 days before statin re-initiation (control period). The mean age of beneficiaries was 75.4 years; 52.8% were women and 81.9% were white. For routine healthcare utilization, the odds ratio (95% confidence interval) for statin re-initiation associated with lipid panel testing was 2.65 (1.93-3.65), outpatient primary care was 1.31 (1.23-1.40), and outpatient cardiologist care was 1.38 (1.28-1.50). For acute healthcare utilization, the odds ratio (95% confidence interval) for statin re-initiation associated with emergency department visits was 1.77 (1.31-2.40), coronary heart disease (CHD) hospitalizations was 3.16 (2.41-4.14) and non-coronary heart disease hospitalizations was 1.73 (1.49-2.01)., Conclusions: The weaker association of routine versus acute healthcare utilization with statin re-initiation suggests missed opportunities to reinforce the importance of statin therapy for secondary prevention., (© 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.)

Models of care for people living with HIV (PLWH) have varied over time due to long term survival, development of HIV-associated non-AIDS conditions, and HIV specific primary care guidelines that differ from those of the general population. The objectives of this study are to assess how often infectious disease (ID) physicians provide primary care for PLWH, assess their practice patterns and barriers in the provision of primary care. We used a 6-item survey electronically distributed to ID physician members of Emerging Infections Network (EIN). Of the 1248 active EIN members, 644 (52%) responded to the survey. Among the 644 respondents, 431 (67%) treated PLWH. Of these 431 responders, 326 (75%) acted as their primary care physicians. Responders who reported always/mostly performing a screening assessment as recommended per guidelines were: (1) Screening specific to HIV (tuberculosis 95%, genital chlamydia/gonorrhoea 77%, hepatitis C 67%, extra genital chlamydia/gonorrhoea 47%, baseline anal PAP smear for women 36% and men 34%); (2) Primary care related screening (fasting lipids 95%, colonoscopy 95%, mammogram 90%, cervical PAP smears 88%, depression 57%, osteoporosis in postmenopausal women 55% and men >50 yrs 33%). Respondents who worked in university hospitals, had <5 years of ID experience, and those who cared for more PLWH were most likely to provide primary care to all or most of their patients. Common barriers reported include: refusal by patient (72%), non-adherence to HIV medications (43%), other health priorities (44%), time constraints during clinic visit (43%) and financial/insurance limitations (40%). Most ID physicians act as primary care providers for their HIV infected patients especially if they are recent ID graduates and work in university hospitals. Current screening rates are suboptimal. Interventions to increase screening practices and to decrease barriers are urgently needed to address the needs of the aging HIV population in the United States.

Background: Patients with low-density lipoprotein cholesterol (LDL-C) ≥190 mg/dL are at high risk of atherosclerotic cardiovascular disease events. Treatment guidelines recommend intensive treatment in these patients. Variation in the use of lipid-lowering therapies (LLTs) in these patients in a national sample of cardiology practices is not known., Methods and Results: Using data from the American College of Cardiology National Cardiovascular Data Registry-Practice Innovation and Clinical Excellence registry, we assessed the proportion of patients with LDL-C ≥190 mg/dL (n=49 447) receiving statin, high-intensity statin, LLT associated with ≥50% LDL-C lowering, ezetimibe, or a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor between January 2013 and December 2016. We assessed practice-level rates and variation in LLT use using median rate ratio (MRR) adjusted for patient and practice characteristics. MRRs represent the likelihood that 2 random practices would differ in treatment of identical patients with LDL-C ≥190 mg/dL. The proportion of patients receiving a statin, high-intensity statin, LLT associated with ≥50% LDL-C reduction, ezetimibe, or PCSK9 inhibitor were 58.5%, 31.9%, 34.6%, 8.5%, and 1.5%, respectively. Median practice-level rates and adjusted MRR for statin (56% [interquartile range, 47.3%-64.8%]; MRR, 1.20 [95% confidence interval [CI], 1.17-1.23]), high-intensity statin (30.2% [interquartile range, 12.1%-41.1%]; MRR, 2.31 [95% CI, 2.12-2.51]), LLT with ≥50% LDL-C lowering (31.8% [interquartile range, 15.3%-45.5%]; MRR, 2.12 [95% CI, 1.95-2.28]), ezetimibe (5.8% [interquartile range, 2.8%-9.8%]; MRR, 2.42 [95% CI, 2.21-2.63]), and PCSK9 inhibitors (0.16% [interquartile range, 0%-1.9%]; MRR, 2.38 [95% CI, 2.04-2.72]) indicated significant gaps and >200% variation in receipt of several of these medications for patients across practices. Among those without concomitant atherosclerotic cardiovascular disease, even larger treatment gaps were noted (proportion of patients on a statin, high-intensity statin, LLT with ≥50% LDL-C reduction, ezetimibe, or PCSK9 inhibitor were 50.8%, 25.25%, 26.8%, 4.9%, and 0.74%, respectively)., Conclusions: Evidence-based LLT use remains low among patients with elevated LDL-C with significant variation in care. System-level interventions are needed to address these gaps and reduce variation in care of these high-risk patients., (© 2018 American Heart Association, Inc.)

Background: Patient participation in clinical research is low, in part because of the length and complexity of the informed consent process. Video informed consent may enhance the appeal of research and help break down barriers to participation., Methods and Results: The PALM study (Patient and Provider Assessment of Lipid Management) enrolled 7904 patients at cardiology, endocrinology, and primary care clinics across the United States to evaluate cholesterol management practices. Of 153 participating clinics, 67 (43.8%) secured institutional review board approval to use a tablet-based video informed consent tool that patients could select to navigate through the informed consent process instead of traditional text-based informed consent. At sites without institutional review board approval of video consent, all patients read a text-based informed consent document. Site activation times and enrollment volumes, as well as characteristics of enrolled patients, were compared between sites with and without video consent capability. Sites with video consent capability more often used a central institutional review board (89.6% versus 73.3%), were more often rural (16.7% versus 3.8%), and tended to have fewer providers. Compared with sites without video consent capability, sites with video consent capability had shorter times from site approach to first patient enrollment (median 178 versus 207 days; P =0.02). Sites with video consent capability enrolled similar numbers of patients as sites without video consent capability ( P =0.48) but enrolled a greater proportion of patients who were ≥75 years old (27.5% versus 23.6%; P <0.001) and nonwhite (17.7% versus 14.2%; P <0.001)., Conclusions: In this observational study of recruitment in a multicenter registry, sites approved for video consent use enrolled the same number of patients as sites with only traditional text-based informed consent but had faster speed to first patient enrolled and more often enrolled older and nonwhite patients. Future randomized trials are needed to assess the impact of video consent on enrollment mechanics and demographics., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02341664., (© 2018 American Heart Association, Inc.)

Background: Data suggest that the prediction of adult cardiovascular disease using a model comprised entirely of adult nonlaboratory-based risk factors is equivalent to an approach that additionally incorporates adult lipid measures. We assessed and compared the utility of a risk model based solely on nonlaboratory risk factors in adolescence versus a lipid model based on nonlaboratory risk factors plus lipids for predicting high-risk carotid intima-media thickness (cIMT) in adulthood., Methods: The study comprised 2893 participants 12 to 18 years of age from 4 longitudinal cohort studies from the United States (Bogalusa Heart Study and the Insulin Study), Australia (Childhood Determinants of Adult Health Study), and Finland (The Cardiovascular Risk in Young Finns Study) and followed into adulthood when cIMT was measured (mean follow-up, 23.4 years). Overweight status was defined according to the Cole classification. Hypertension was defined according to the Fourth Report on High Blood Pressure in Children and Adolescents from the National High Blood Pressure Education Program. High-risk plasma lipid levels were defined according to the National Cholesterol Education Program Expert Panel on Cholesterol Levels in Children. High cIMT was defined as a study-specific value ≥90th percentile. Age and sex were included in each model., Results: In univariate models, all risk factors except for borderline high and high triglycerides in adolescence were associated with high cIMT in adulthood. In multivariable models (relative risk [95% confidence interval]), male sex (2.7 [2.0-2.6]), prehypertension (1.4 [1.0-1.9]), hypertension (1.9 [1.3-2.9]), overweight (2.0 [1.4-2.9]), obesity (3.7 [2.0-7.0]), borderline high low-density lipoprotein cholesterol (1.6 [1.2-2.2]), high low-density lipoprotein cholesterol (1.6 [1.1-2.1]), and borderline low high-density lipoprotein cholesterol (1.4 [1.0-1.8]) remained significant predictors of high cIMT ( P <0.05). The addition of lipids into the nonlaboratory risk model slightly but significantly improved discrimination in predicting high cIMT compared with nonlaboratory-based risk factors only (C statistics for laboratory-based model 0.717 [95% confidence interval, 0.685-0.748] and for nonlaboratory 0.698 [95% confidence interval, 0.667-0.731]; P =0.02)., Conclusions: Nonlaboratory-based risk factors and lipids measured in adolescence independently predicted preclinical atherosclerosis in young adulthood. The addition of lipid measurements to traditional clinic-based risk factor assessment provided a statistically significant but clinically modest improvement on adolescent prediction of high cIMT in adulthood., (© 2017 American Heart Association, Inc.)