New Cholesterol Research from Dr. Rohatgi at UTSW: HDL-efflux

This morning, the New England Journal of Medicine published an article by our own Dr. Anand Rohatgi concerning HDL-efflux as a measure of cardiovascular disease risk. The cholesterol-efflux study was presented today at the American Heart Association (AHA) 2014 Scientific Sessions. Through observational analyses, higher levels of HDL cholesterol have previously been associated with a lower risk of coronary events. However, various studies (AIM-HIGH, HPS2-THRIVE, ILLUMINATE, dal-OUTCOMES) aimed at increasing HDL levels have not shown an improvement in clinical outcomes. This study focuses on the idea that HDL particles participate in the cholesterol-efflux pathway, whereby the particles remove cholesterol from macrophages within arterial walls. The group hypothesized that measuring the cholesterol-efflux capacity of HDL would allow for greater understanding of CVD risk. Importantly, the study notes that HDL-cholesterol levels are not reflective of HDL functionality. rohatgi

Why are we checking that d-dimer?

An interesting question was posed at the VA: when is a d-dimer helpful. The question of venous thromboembolic disease aside, the lab test can also be helpful when consider aortic dissection in your differential. Take a look at the review below,

Introduction

  • Aortic Dissection is a cleavage of the aortic media layer created by a dissecting column of blood. This is different pathologically than an aortic aneurysm but the two terms are frequently interchanged incorrectly
  • Uncommon => 2-4 per 100,000 person-years (Acute Coronary Syndromes is about 100-200 times more common)
  • About 1 of every 2,000 ED patients presenting with any symptom associated with thoracic aortic dissection (TAD) will have TAD
  • Life-threatening – mortality rate of 1.2% per hour in the first 48hr

Recap / Basics

  • Three variants
    • Intimal Flap tear  – ~70-80% of cases
    • Intramural hematoma (believed to start from rupture of the vasa vasorum) – ~10-15%
    • Penetrating atherosclerotic ulcer – ~10-15%
  • Risk Factors
    • Hypertension – 72%
    • Collagen disorders – Marfan’s, Ehlers-Danlos
    • Inflammatory vasculitis disorders – Giant cell arteritis, Takayasu arteritis, rheumatoid arthritis
    • Instrumentation or structural abnormalities – cardiac cath / CABG, bicuspid valve, aortic coarctation, valve replacement
  • Classification
    • Stanford
      • Type AAscending and Arch
        • Higher Mortality
        • Surgical Management
      • Type  B – descending; Below the left subclavian
        • Lower Mortality
        • Often medical management
    • DeBakey
      • I – Ascending, arch and possible descending
      • II – Ascending only
      • III – Descending aorta
  • Pain is common >90%
    • Abrupt ~85%,  excruciating (“worst ever”) ~90% and most severe at onset
    • Chest or Back
    • Sharp, tearing, ripping but may be pressure or crushing
    • Migration suggests dissection but occurs only ~ 30% of cases
  • Physical exam, ECG, and chest x-ray are insufficiently sensitive to help with diagnosis
  • Other advanced imaging needed
    • Contrast CT Chest – sensitivity ~100%, specificity ~98%
    • MRI – sensitivity ~98%, specificity ~98%
    • Transesophageal Echocardiography (TEE) – sensitivity ~98%, specificity ~95%
  • Treatment
    • ED treatment is to reduce blood pressure to target systolic BP = 100-120
      • β-blockers – Esmolol or labetalol
      • Sodium nitroprusside
    • Surgery generally performed for Type A and complicated Type B dissections and possibly other Type Bs
    • Medication management for uncomplicated Type B

What’s New

  • Can the D-dimer help to include or exclude patients who might need advanced imaging?
  • The D-dimer is a fibrin degradation product indicating recent or ongoing coagulation
  • The D-dimer is very sensitive for picking up most dissections. Data from several different pooled studies show sensitivity 94-97%, specificity 34-100%
  • This has led several authors to suggest the D-dimer seems to have value as a screening tool for “ruling out” acute aortic dissection; i.e. if the D-dimer result is below a threshold level (generally below 400 – 500 ng/mL), then TAD is unlikely
  • However, false negatives (D-dimer levels below the threshold in patient with documented TAD) have been reported in several papers and one paper (Paparella) reported a surprising high false negative rate of 18% (11/61) with time of symptom onset to diagnosis ranging from 2 – 72 hours
  • Other authors have suggested the D-dimer should be part of the work-up if TAD is suspected. However using the D-dimer alone would lead to an unacceptably high number of false positives and follow-up advanced imaging
  • Higher d-dimer levels correlate with more segments of the aorta involved, with false lumen type dissections, and with higher mortality rates
  • D-dimers seem to be lower in patients with intramural hematomas

Bottom Line / Pearls & Pitfalls

  • A negative D-dimer (< 400 ng/mL) makes TAD unlikely but it is not 100% and false negatives occur
  • A positive D-dimer occurs in a very high percent of patients with TAD but also occurs in many other conditions
  • What is needed is a well-tested clinical decision rule to help select patients for further testing; that is when should we order, or not order, a D-dimer and/or when should we order, or not order, advanced imaging

Copyright Tim Schaefer, at emdocs.net

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What do I do with this Pulmonary Embolism?

Today at Parkland Morning Report we had a great discussion about incidental pulmonary embolisms and how to manage them, especially when their clinical relevance to the patient is questionable. Below are two links to articles that address this issue as this remains a growing area of research.

Key Points:

– Meta-analysis performed and published in 2010 in Thrombosis Research which looked at 12 studies that included over ten thousand patients who received diagnosis of pulmonary embolism based on imaging that was ordered for another reason.

– Weighted mean prevalence of incidental pulmonary embolism was 2.6%. Inpatient status and malignancy were factors that were associated with a significant increased risk of pulmonary embolism.

– Incidental pulmonary embolisms may be associated with higher mortality rate, high recurrence rate if left untreated, and poorer prognosis in patients with cancer.

– The authors were unable to comment on the risk and benefit ratio of antithrombotic therapy due to lack of data.

– The other article is a survey of physicians and how they would manage incidental pulmonary embolisms in The Journal of Thrombosis and Haemostasis.

– Majority of physicians would treat incidental pulmonary embolism if it was centrally located compared to sub-segmental in the survey. However, if patient had malignancy then even more physicians would treat the pulmonary embolism (central and sub-segmental).

http://ejournals.ebsco.com.foyer.swmed.edu/Direct.asp?AccessToken=9III9IX8XIMEDKZP9PJ1RK5EEDID8151MJ&Show=Object&ErrorURL=http%3A%2F%2Flinksource.ebsco.com%2Ferror.aspx

http://onlinelibrary.wiley.com/doi/10.1111/jth.12040/pdf