Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

BACKGROUND: As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate. METHODS: In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines. RESULTS: Friedewald values were less than ultracentrifugation measurement, with a median difference (25th to 75th percentile) of -2.4 (-7.4 to 0.6) at 50-69 mg/dL, -7.0 (-16.2 to -1.2) at 25-39 mg/dL, and -29.0 (-37.4 to -19.6) at < 15 mg/dL. The respective values by novel estimation were -0.1 (-1.5 to 1.3), -1.1 (-2.5 to 0.3), and -2.7 (-4.9 to 0.0) mg/dL. Among those with Friedewald LDL-C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation. CONCLUSIONS: Estimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method.

Association Between Atrial Fibrillation and Occupational Exposure in Firefighters Based on Self-Reported Survey Data.

Background Exposure to inhaled smoke, pollutants, volatile organic compounds, and polycyclic aromatic hydrocarbons in the firefighting environment has been associated with detrimental respiratory and cardiovascular effects, making firefighters a unique population with both personal and occupational risk factors for cardiovascular disease. Some of these exposures are also associated with development of atrial fibrillation. We aimed to study the association of atrial fibrillation and occupational exposure in firefighters. Methods and Results A cross-sectional survey was conducted between October 2018 and December 2019. Data were gathered electronically and stored in a secure REDCap database through Louisiana State University Health Shreveport. Firefighters who were members of at least 1 of 5 preselected professional organizations were surveyed via electronic links distributed by the organizations. The survey queried the number of fires fought per year as a measure of occupational exposure, as well as self-reported cardiovascular disease. A total of 10 860 active firefighters completed the survey, of whom 93.5% were men and 95.5% were aged ≤60 years. Firefighters who fought a higher number of fires per year had a significantly higher prevalence of atrial fibrillation (0-5 fires per year 2%, 6-10 fires per year 2.3%, 11-20 fires per year 2.7%, 21-30 fires per year 3%, 31 or more fires per year 4.5%; P<0.001). Multivariable logistic regression showed that a higher number of fires fought per year was associated with an increased risk of atrial fibrillation (odds ratio 1.14 [95% CI, 1.04-1.25]; P=0.006). Conclusions Firefighters may have an increased risk of atrial fibrillation associated with the number of fires they fight per year. Further clinical and translational studies are needed to explore causation and mechanisms.

Entrapped Crown of Orbital Atherectomy Device by Intimal Tissue Entanglement During Peripheral Intervention.

Orbital atherectomy is a commonly used procedure for peripheral arterial disease. Crown entrapment is a rare but potentially dangerous complication of orbital atherectomy. We describe a case of crown entrapment by markedly excessive atheromatous intimal tissue attachment to the device and an innovative retrieval technique that may minimize vascular injury. (Level of Difficulty: Beginner.).

Simplified Rapid Protocol for Assessing the Thoracic Aortic Dimensions and Pathology with Noncontrast MR Angiography.

Contrast enhanced magnetic resonance angiography (CE-MRA) is limited by long acquisition time and contrast exposure in aortic emergencies. To compare the effcacy of dark blood (DB) and bright blood (BB) noncontrast sequences with the gold standard CE-MRA using a novel protocol for performing consistent thoracic aortic measurements and thoracic aortic pathologies identifications. A total of 66 patients with suspected or known thoracic aortic pathology who underwent CE-MRA underwent DB and BB imaging prior to CE-MRA for planning purposes. Aortic dimension was measured at 10 standard reference points in the ascending, arch, and descending aorta. Detection of aortic pathologies was recorded individually for each noncontrast sequence. When comparing the CE-MRA to the DB images and CE-MRA to the BB images, a majority of the measurement differences were less than or equal to 2 mm or resulted in no change of diagnostic class (95% for CE-MRA vs. DB and 96% for CE-MRA vs. BB). Of the patients who had major changes in diagnostic class (e.g., changes in two or three classes), the absolute measurements were not clinically significant in any given patient to warrant a change in management. Individually, the DB and BB sequences allowed for accurate recognition of all 47 aortic pathologies. DB and BB sequences produced comparable and consistent measurements of the thoracic aorta when compared with CE-MRA. In a situation where CE-MRA is not readily available or contraindicated, noncontrast MRA using our protocol is a reliable alternative to CE-MRA for assessment of aortic pathologies.

Comparing different assessments of remnant lipoprotein cholesterol: The very large database of lipids.

BACKGROUND: Remnant lipoprotein cholesterol (RLP-C) is a risk factor for atherosclerotic cardiovascular disease, but there is no standard method for measurement. Some studies have used very low-density lipoprotein cholesterol estimated by the Friedewald equation to approximate RLP-C using a basic lipid panel, whereas others have attempted to measure RLP-C with ultracentrifugation. OBJECTIVE: The aim of the study was to compare RLP-C levels estimated from basic lipid parameters to those measured by ultracentrifugation. METHODS: We analyzed 1,350,908 individuals from the Very Large Database of Lipids, comparing one estimate of RLP-C using basic lipid parameters (RLP-Cestimated = non-high-density lipoprotein cholesterol - Friedewald-estimated low-density lipoprotein cholesterol for triglycerides <355 mg/dL [4 mmol/L], or non-high-density lipoprotein - directly measured low-density lipoprotein for triglycerides ≥355 mg/dL) to levels measured by vertical auto profile ultracentrifugation (RLP-Cmeasured = dense subfraction of very low-density lipoprotein cholesterol + intermediate-density lipoprotein cholesterol). We calculated correlations between RLP-Cestimated and RLP-Cmeasured along with median within-subject differences between RLP-Cestimated and RLP-Cmeasured across quintiles of RLP-Cestimated. We also assessed correlations with RLP-C estimated from basic lipid parameters using a novel method of calculating low-density lipoprotein cholesterol with a patient-specific conversion factor (RLP-Cestimated-N). RESULTS: Our cohort was 48% male, and median (interquartile range) age was 59 (49-69) years. Median (interquartile range) RLP-Cestimated and RLP-Cmeasured were 23 (16.4-33.2) and 24 (19-32) mg/dL, respectively. The correlation between RLP-Cestimated and RLP-Cmeasured was 0.76. Based on the specified definition of RLP-Cestimated, the correlation between RLP-Cestimated and triglyceride/5 for triglyceride < 355 mg/dL was exactly 1.0. RLP-Cestimated was lower than RLP-Cmeasured in the first and second quintiles of RLP-Cestimated but greater in the highest quintile. The correlations with RLP-Cestimated-N were 0.98 and 0.81 for RLP-Cestimated and RLP-Cmeasured, respectively. CONCLUSIONS: A previously used estimate of RLP-C using basic lipid parameters correlates weakly with remnants measured by ultracentrifugation. Our findings emphasize the need to standardize definitions and measurements of RLP-C.

Characterization of lipoprotein profiles in patients with hypertriglyceridemic Fredrickson-Levy and Lees dyslipidemia phenotypes: the Very Large Database of Lipids Studies 6 and 7.

INTRODUCTION: The association between triglycerides (TG) and cardiovascular diseases is complex. The classification of hypertriglyceridemic (HTG) phenotypes proposed by Fredrickson, Levy and Lees (FLL) helps inform treatment strategies. We aimed to describe levels of several lipoprotein variables from individuals with HTG FLL phenotypes from the Very Large Database of Lipids. MATERIAL AND METHODS: We included fasting samples from 979,539 individuals from a contemporary large study population of US adults. Lipids were directly measured by density-gradient ultracentrifugation using the Vertical Auto Profile test while TG levels were measured in whole plasma using the Abbott ARCHITECT C-8000 system. Hyperchylomicronemic (Hyper-CM) and non-chylomicronemic (non-CM) phenotypes were defined using computationally derived models. Individuals with FLL type IIa phenotype were excluded. Distributions of lipid variables were compared using medians and Kruskal-Wallis test. RESULTS: A total of 11.9% (n = 116,925) of individuals met criteria for HTG FLL phenotypes. Those with hyper-CM phenotypes (n = 5, < 0.1% of population) had two-fold higher TG levels compared with non-chylomicronemic (non-CM) individuals (11.9% of population) (p < 0.001). Type IIb individuals had the highest non-HDL-C levels (median 242 mg/dl). Cholesterol in large VLDL1+2 particles was higher than in small VLDL3 particles in all phenotypes except FLL type III. Hyper-CM phenotypes had significantly lower HDL-C levels but greater HDL2/HDL3-C ratio compared to non-CM phenotypes. Cholesterol content of the lipoprotein (a) peak was significantly higher in the hyper-CM groups compared to non-CM phenotypes (p < 0.0001). CONCLUSIONS: This observational hypothesis-generating study provides insight into the complexity of lipid metabolism in HTG phenotypes, including less traditional lipid measures such as LDL density, HDL subclasses and Lp(a)-C.

Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure: A Systematic Review and Meta-analysis.

Importance: Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. Objectives: To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. Data Sources: PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. Study Selection: Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. Data Extraction and Synthesis: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. Main Outcomes and Measures: The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. Results: In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, -0.43 to 3.24; P = .13). Conclusions and Relevance: Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.

Dyslipidemia management in primary prevention of cardiovascular disease: Current guidelines and strategies.

Cardiovascular disease is the leading cause of death in the United States. In 2010, the Centers for Disease Control and Prevention estimated that $444 billion was spent on cardiovascular diseases alone, about $1 of every $6 spent on health care. As life expectancy continues to increase, this annual cost will also increase, making cost-effective primary prevention of cardiovascular disease highly desirable. Because of its role in development of atherosclerosis and clinical events, dyslipidemia management is a high priority in cardiovascular prevention. Multiple major dyslipidemia guidelines have been published around the world recently, four of them by independent organizations in the United States alone. They share the goal of providing clinical guidance on optimal dyslipidemia management, but guidelines differ in their emphasis on pharmacotherapy, stratification of groups, emphasis on lifestyle modification, and use of a fixed target or percentage reduction in low density lipoprotein cholesterol. This review summarizes eight major guidelines for dyslipidemia management and considers the basis for their recommendations. Our primary aim is to enhance understanding of dyslipidemia management guidelines in patient care for primary prevention of future cardiovascular risk.

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: evolocumab.

Patients with familial hypercholesterolemia or statin intolerance are especially challenging to manage since LDL cholesterol levels often remain considerably elevated despite clinicians' best efforts. With statins regarded as first-line pharmacologic therapy by the current American College of Cardiology/American Heart Association guidelines to reduce LDL cholesterol and cardiovascular risk, there is now a critical need to determine when other agents will play a role beyond maximally tolerated statin therapy and lifestyle changes. In this review, we take a closer look at evolocumab (Repatha(®)), one of the new injectable human monoclonal antibodies to PCSK9 and its efficacy and safety properties from the results of various trials.

PCSK9 inhibitors and their role in high-risk patients in reducing LDL cholesterol levels: alirocumab.

In this review, we examine alirocumab (Praluent(®)), a monoclonal antibody to PCSK9 and its role in reducing LDL-C levels. By comparing the results of various studies and trials we discuss the efficacy and safety of alirocumab. We aim to guide clinicians of the role of alirocumab in clinical practice. Overall, PCSK9 inhibitors are promising new agents in further reducing LDL-C levels in addition to diet and maximally tolerated statin therapy. Long-term outcome studies are currently ongoing and will further delineate the role of PCSK9 inhibitors.