Multiple studies have demonstrated environmental (e)DNA detections of rare and invasive species. However, invasive species managers struggle with using eDNA results because detections might not ...indicate species presence. We evaluated whether eDNA methods have matured to a point where they can be widely applied to aquatic invasive species management. We have found that eDNA methods meet legal standards for being admissible as evidence in most courts, suggesting eDNA method reliability is not the problem. Rather, we suggest the interface between results and management needs attention since there are few tools for integrating uncertainty into decision-making. Solutions include decision-support trees based on molecular best practices that integrate the temporal and spatial trends in eDNA positives relative to human risk tolerance.
We consider whether eDNA methods have matured to a point where they can go from research to widespread application and be incorporated into aquatic invasive species management.Under the Daubert standard of scientific evidence, eDNA is arguably a sufficiently mature and reliable technique.However, invasive species managers struggle with using eDNA since it is uncertain if detections indicate species presence and the costs of acting can be high.eDNA based, decision support tools for invasive species management are lacking.Manuals on best practices, decision support trees for the interpretation of results, education and training of managers and stakeholders, and communication protocols are necessary outputs before widespread incorporation of eDNA into invasive species management.Many of these outputs are coming into place, which will allow eDNA to better support invasive species management.
Cholesteryl ester transfer protein (CETP) facilitates the exchange of cholesteryl esters and triglycerides (TG) between high-density lipoprotein (HDL) particles and TG-rich, apolipoprotein (apo) ...B-containing particles. Initially, these compounds were developed to raise plasma HDL cholesterol (HDL-C) levels, a mechanism that was previously thought to lower the risk of atherosclerotic cardiovascular disease (ASCVD). More recently, the focus changed and the use of pharmacologic CETP inhibitors to reduce low-density lipoprotein cholesterol (LDL-C), non-HDL-C and apoB concentrations became supported by several lines of evidence from animal models, observational investigations, randomized controlled trials and Mendelian randomization studies. Furthermore, a cardiovascular outcome trial of anacetrapib demonstrated that CETP inhibition significantly reduced the risk of major coronary events in patients with ASCVD in a manner directly proportional to the substantial reduction in LDL-C and apoB. These data have dramatically shifted the attention on CETP away from raising HDL-C instead to lowering apoB-containing lipoproteins, which is relevant since the newest CETP inhibitor, obicetrapib, reduces LDL-C by up to 51% and apoB by up to 30% when taken in combination with a high-intensity statin. An ongoing cardiovascular outcome trial of obicetrapib in patients with ASCVD is expected to provide further evidence of the ability of CETP inhibitors to reduce major adverse cardiovascular events by lowering apoB. The purpose of the present review is to provide an up-to-date understanding of CETP inhibition and its relationship to ASCVD risk reduction.
HDL and cardiovascular disease Nicholls, Stephen J.; Nelson, Adam J.
Pathology,
02/2019, Volume:
51, Issue:
2
Journal Article
Peer reviewed
High-density lipoprotein (HDL) has received increasing interest due to observations of an inverse relationship between its systemic levels and cardiovascular risk and targeted interventions in animal ...models that have had favourable effects on atherosclerotic plaque. In addition to its pivotal role in reverse cholesterol transport, HDL has been reported to possess a range of functional properties, which may exert a protective influence on inflammation, oxidation, angiogenesis and glucose homeostasis. This has led to the development of a range of HDL targeted therapeutics, which have undergone evaluation in clinical trials. The current state of HDL in cardiovascular prevention will be reviewed.
Preventive therapy among patients with established atherosclerotic cardiovascular disease (ASCVD) is generally underused. Whether new guideline recommendations and a focus on implementation have ...improved the use of high-intensity statins is unknown.
This study sought to evaluate the patterns and predictors of statin use among patients with ASCVD.
In this retrospective cohort study, pharmacy and medical claims data from a commercial health plan were queried for patients with established ASCVD between January 31, 2018, and January 31, 2019. Statin use on an index date of January 31, 2019, was evaluated, as was 12-month adherence and discontinuation. Multivariable logistic regression was used to determine independent associations with statin use of varying intensities.
Of the 601,934 patients with established ASCVD, 41.7% were female, and the mean age was 67.5 ± 13.3 years. Overall, 22.5% of the cohort were on a high-intensity statin, 27.6% were on a low- or moderate-intensity statin, and 49.9% were not on any statin. In multivariable analysis, younger patients, female patients, and those with higher Charlson comorbidity score were less likely to be prescribed any statin. Among statin users, female patients, older patients, and those with peripheral artery disease were less likely to be on a high-intensity formulation, whereas a cardiology encounter in the prior year increased the odds. The majority of high-intensity stain users achieved high levels of adherence.
Substantial underuse of statins persists in a large, insured, and contemporary cohort of patients with ASCVD from the United States. In particular, concerning gaps in appropriate statin use remain among younger patients, women, and those with noncoronary ASCVD.
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Hypertension and dyslipidemia are 2 highly prevalent and modifiable risk factors in patients with stable ischemic heart disease. Multiple lines of evidence demonstrate that lowering blood pressure ...and low-density lipoprotein cholesterol improves clinical outcomes in patients with ischemic heart disease. Accordingly, clinical guidelines recommend intensive treatment targets for these high-risk patients. This article summarizes the pathophysiology, supporting evidence, and treatment recommendations for management of hypertension and dyslipidemia among patients with manifest ischemic heart disease and points to future research and unmet clinical needs.
Non-adherence to medication is a global health problem with far-reaching individual-level and population-level consequences but remains unappreciated and under-addressed in the clinical setting. With ...increasing comorbidity and polypharmacy as well as an ageing population, cardiovascular disease and medication non-adherence are likely to become increasingly prevalent. Multiple methods for detecting non-adherence exist but are imperfect, and, despite emerging technology, a gold standard remains elusive. Non-adherence to medication is dynamic and often has multiple causes, particularly in the context of cardiovascular disease, which tends to require lifelong medication to control symptoms and risk factors in order to prevent disease progression. In this Review, we identify the causes of medication non-adherence and summarize interventions that have been proven in randomized clinical trials to be effective in improving adherence. Practical solutions and areas for future research are also proposed.
Randomized clinical trials have demonstrated that increasingly intensive lowering of low-density lipoprotein cholesterol (LDL-C) reduces the rate of cardiovascular events in the primary and secondary ...prevention setting. Integration of serial coronary imaging within clinical trials has enabled evaluation of medical therapies on the natural history of coronary disease. These studies have extended from early investigation of coronary obstruction with angiography to more contemporary evaluation of plaque burden and composition with imaging modalities that directly visualize the artery wall. The findings of these trials have demonstrated that intensive lipid lowering promotes plaque regression and stabilization. The lessons of this body of research provide a biological rationale underscoring the ability of intensive lipid lowering to reduce cardiovascular risk and have the potential to promote greater uptake in clinical practice.
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•Intensive lipid lowering with statin monotherapy or combination therapy is achievable in most high risk patients.•Intensive lipid lowering slows progression of obstructive disease on coronary angiography.•Intensive lipid lowering promotes plaque regression and stabilization, proportional to LDL-C lowering.•These benefits are likely to underscore the impact of intensive lipid lowering on cardiovascular risk.
Purpose of Review
Bempedoic acid is a novel therapeutic agent that is designed to reduce levels of low-density lipoprotein cholesterol (LDL-C). The purpose of this review is to provide the background ...for development of bempedoic acid, findings from clinical trials and to discuss clinical implications.
Recent Findings
Bempedoic acid inhibits ATP citrate lyase within the liver and reduces cholesterol synthesis, with the potential to avoid muscle symptoms experienced by patients treated with statins. Early clinical studies demonstrated that administration of bempedoic acid resulted in lowering of LDL-C by 20–30% as monotherapy and by 40–50% when combined with ezetimibe, in addition to lowering of high sensitivity C-reactive protein by 20–30%. The CLEAR Outcomes trial of high cardiovascular risk patients, with elevated LDL-C levels and either unable or unwilling to take statins demonstrated that bempedoic acid reduced the rate of major adverse cardiovascular events. A greater incidence of elevation of hepatic transaminase and creatinine, gout, and cholelithiasis were consistently observed in bempedoic acid–treated patients.
Summary
Bempedoic acid presents an additional therapeutic option to achieve more effective lowering of LDL-C levels and reduction in cardiovascular risk.
Objectives The aim of this study was to characterize the relationship between pericardial fat and atrial fibrillation (AF). Background Obesity is an important risk factor for AF. Pericardial fat has ...been hypothesized to exert local pathogenic effects on nearby cardiac structures above and beyond that of systemic adiposity. Methods One hundred ten patients undergoing first-time AF ablation and 20 reference patients without AF underwent cardiac magnetic resonance imaging for the quantification of periatrial, periventricular, and total pericardial fat volumes using a previously validated technique. Together with body mass index and body surface area, these were examined in relation to the presence of AF, the severity of AF, left atrial volume, and long-term AF recurrence after ablation. Results Pericardial fat volumes were significantly associated with the presence of AF, AF chronicity, and AF symptom burden (all p values <0.05). Pericardial fat depots were also predictive of long-term AF recurrence after ablation (p = 0.035). Finally, pericardial fat depots were also associated with left atrial volume (total pericardial fat: r = 0.46, p < 0.001). Importantly, these associations persisted after multivariate adjustment and additional adjustment for body weight. In contrast, however, systemic measures of adiposity, such as body mass index and body surface area, were not associated with these outcomes in multivariate-adjusted models. Conclusions Pericardial fat is associated with the presence of AF, the severity of AF, left atrial volumes, and poorer outcomes after AF ablation. These associations are both independent of and stronger than more systemic measures of adiposity. These findings are consistent with the hypothesis of a local pathogenic effect of pericardial fat on the arrhythmogenic substrate supporting AF.
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