Can We Eliminate Low-Density Lipoprotein Cholesterol-Related Cardiovascular Events Through More Aggressive Primary Prevention Therapy?

Intravascular levels of low-density lipoprotein cholesterol (LDL-C) at approximately ≤ 0.6 mmol/L are likely to minimize, and perhaps eliminate, LDL-C-related vascular toxicity while having no effect on essential, intracellular cholesterol homeostatic pathways, according to accumulated knowledge from basic science. Randomized clinical trials, observational reports, and Mendelian randomization trials are also forcing a reconsideration of what “normal” LDL-C means. Recent trials of secondary prevention have substantiated that such levels are safe and associated with a decreased risk of cardiovascular events (CVEs) compared with patients with higher levels of LDL-C. Similarly, treatment to this low range is associated with regression and stabilization of established atherosclerosis. Primary prevention trials also show that low levels of LDL-C are safe and associated with decreased risk of CVEs through cholesterol-lowering in adults with LDL-C ≥ 3.5 mmol/L or when levels are < 3.5 mmol/L in association with other cardiovascular risks. Although there are no randomized clinical outcome trials of familial hypercholesterolemia patients, such patients have very high, lifetime risk of CVE, and registry studies show that LDL-C reduction has nearly normalized their CVE rates. The possibility of familial hypercholesterolemia should be considered if LDL-C is > 4.5 and > 4.0 mmol/L at ages 18-39 years and younger than 18 years, respectively. On the basis of these convergent and internally consistent lines of evidence, in this article we speculate on a translational paradigm aimed at eliminating LDL-C-related CVEs through aggressive primary prevention strategies that are already proven and well accepted in principle.     

Contemporary Emergency Department Management of Patients with Chest Pain: A Concise Review and Guide for the High-Sensitivity Troponin Era

This article synthesizes current best evidence for the evaluation of patients with suspected acute coronary syndrome (ACS) using high-sensitivity troponin assays, enabling physicians to effectively incorporate them into practice. Unlike conventional assays, high-sensitivity assays can precisely measure blood cardiac troponin concentrations in the vast majority of healthy individuals, facilitating the creation of rapid diagnostic algorithms. Very low troponin concentrations on presentation accurately rule out acute myocardial infarction (AMI) and enable the discharge of approximately 20% of patients after a single test, whereas an additional 30%-40% of patients can be safely discharged after short-interval serial sampling in as little as 1 or 2 hours. In contrast, highly abnormal troponin concentrations on presentation (more than 5 times the upper reference limit) or rapidly rising levels on serial testing can rapidly rule in AMI with high specificity. However, approximately one-third of patients remain in a biomarker-indeterminate “observation zone” even after serial sampling. These patients pose a disposition challenge to clinicians because although the differential diagnosis of elevated troponin concentrations is broad, these patients have an increased risk for short-term major adverse cardiac events. Use of repeated serial troponin sampling and structured clinical prediction tools may assist disposition for these patients, because no validated pathways currently exist to guide clinicians. Ongoing research to tailor diagnostic thresholds to individual patient characteristics may enable improved diagnostic accuracy and usher in a new era of personalized medicine in the evaluation of suspected ACS.