What’s the connection between elevated troponins and Covid-19?

Elevated cardiac troponins or myocardial injury (defined as troponin levels above the 99th percentile upper reference range) are not uncommon in Covid-19, having been reported in ~10-30% of hospitalized patient and usually observed in the absence of acute coronary syndrome (ACS) (1-4).

 
Elevated troponins have been associated with increased risk of in-hospital mortality in Covid-19. The prevalence of elevated troponins among patients who died was 76% compared to 10% among survivors in 1 Chinese study (3). Another study from China found increasing troponin levels over a 22 day period among those who died while troponin levels remained low in those who survived (5).

 
Risk factors for elevated troponins in Covid-19 include older age, cardiovascular comorbidities (eg, hypertension, coronary heart disease, heart failure), diabetes, chronic obstructive pulmonary disease, chronic renal failure, and the presence of a high inflammatory state, as indicated by elevated inflammatory markers such as C-reactive protein (CRP) (3).

 
Several mechanisms have been proposed to explain elevated troponins in Covid-19, including cytokine-induced myocardial injury, microangiopathy due to prothrombotic state, myocardial infarction (type I due to plaque rupture or type II due to oxygen supply/demand imbalance), and myocarditis either due to direct viral invasion or indirectly through immune-mediated mechanisms (1,2).

 
Patients with Covid-19 and modest troponin elevation with rapid fall in the absence of signs or symptoms of ACS, may have type II myocardial infarction due to demand ischemia, particularly in the setting of coronary disease. In contrast, more protracted elevation of troponins associated with high inflammatory markers such as CRP is suggestive of hyperinflammatory myocardial injury (1).

 

It will be interesting to see if trials of anti-inflammatory agents, such as colchicine and anti-interleukin-I, will have an impact on the troponin levels in Covid-19 patients (1).

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References
1. Cremer PC. SARS-CoV-2 and myocardial injury: few answers, many questions. Clev Clin J Med. Posted April 8, 2020. Doi:10.3949/ccjm.87a.ccc001 https://www.ccjm.org/content/early/2020/05/12/ccjm.87a.ccc001
2. Tersalvi G, Vicenzi M, Calabretta D, et al. Elevated troponin in patients with coronavirus disease 2019:possible mechanisms. J Card Failure 2020; https://pubmed.ncbi.nlm.nih.gov/32315733/
3. Shi S, Qin M, Cai Y, et al. Characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019. Eur Heart J 2020. https://pubmed.ncbi.nlm.nih.gov/32391877/
4. Richardson S, Hirsch JS, Narasimhan M, et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA 2020;323:2052-59. https://jamanetwork.com/journals/jama/fullarticle/2765184
5. Zhou F, YU T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet 2020;395:1054-62. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30566-3/fulltext

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Massachusetts General Hospital, Harvard Catalyst, Harvard University, its affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

What’s the connection between elevated troponins and Covid-19?

Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

Short answer: often not! This is because most studies have shown frequently high ESR’s in stable “uninflamed” patients with chronic renal failure (CRF) (including those on dialysis) at levels often associated with infection, connective tissue disease, or malignancy. 1-4  

In fact, in a study involving patients with CRF, 57% of patients had markedly elevated ESR (greater than 60 mm/h), with 20% having ESR greater than 100 mm/h; type or duration of dialysis had no significant effect on ESR levels.1 Another study reported a specificity for abnormal ESR of only 35% for commonly considered inflammatory conditions (eg, infections or malignancy) among patients with CRF. 2

But is it the chronic inflammation in diseased kidneys or the uremic environment that elevates ESR? A cool study compared ESR in CRF in patients who had undergone bilateral nephrectomies with those with retained kidneys and found no significant difference in the ESR between the 2 groups. 4  So it looks like it’s the uremic environment, not diseased kidneys themselves that result in elevated ESR in these patients.

The mechanism behind these observations seem to reside entirely within the patients’ plasma, not the erythrocytes. Within the plasma, fibrinogen (not gammaglobulins) seem to be the most likely factor explaining elevated ESR among patients with CRF. 1,2

Bonus pearl:  Did you know that ESR is nearly 100 years old, first described in 1921? 5

References

  1. Barthon J, Graves J, Jens P, et al. The erythrocyte sedimentation rate in end-stage renal failure. Am J Kidney Dis 1987;10: 34-40. https://www.ncbi.nlm.nih.gov/pubmed/3605082
  2. Shusterman N, Morrison G, Singer I. The erythrocyte sedimentation rate and chronic renal failure. Ann Intern Med 1986;105:801. http://annals.org/aim/fullarticle/700910
  3. Arik N, Bedir A, Gunaydin M, et al. Do erythrocyte sedimentation rate and C-reactive protein levels have diagnostic usefulness in patients with renal failure? Nephron 2000;86:224. https://www.ncbi.nlm.nih.gov/pubmed/11015011
  4. Warner DM, George CRP. Erythrocyte sedimentation rate and related factors in end-stage renal failure. Nephron 1991;57:248. https://www.karger.com/Article/PDF/186266
  5. Fahraeus R. The suspension stability of the blood. Acta Med Scan 1921;55:70-92. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.0954-6820.1921.tb15200.x

 

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Does erythrocyte sedimentation rate (ESR) have diagnostic utility in my patient with chronic renal failure?

What is the significance of Terry’s or Lindsay’s nails in my hospitalized patient?

Terry’s nails were first described in 1954 in patients with hepatic cirrhosis (prevalence 82%, majority related to alcohol abuse) (1). Since then, they have been reported in a variety of other conditions, including adult-onset diabetes mellitus (AODM), chronic congestive heart failure, chronic renal failure, pulmonary tuberculosis, and Reiter’s syndrome (2).

A 1984 study found Terry’s nails in 25% of hospitalized patients (3).  In this study, cirrhosis, chronic congestive heart failure, and AODM were significantly associated with Terry’s nails, while pulmonary tuberculosis, rheumatoid arthritis and cancer were not. The presence of Terry’s nails may be particularly concerning in patients 50 y of age or younger as it increases the relative risk of cirrhosis, chronic congestive heart failure or AODM by 5-fold (18-fold for cirrhosis alone) in this age group (3).

Terry’s nails should be distinguished from Lindsay’s nails or “half and half” nails. Although both nail abnormalities are characterized by an opaque white proximal portion, Terry’s nails have a thinner distal pink to brown transverse band no more than 3 mm wide (3) (Fig 1), while the same anomaly is wider and occupies 20%-60% of the nail bed in Lindsay’s nails (Fig 2). Of interest, Lindsay’s nails have been reported in up to 40% of patients with chronic kidney disease (4,5).

References

1. Terry R. White nails in hepatic cirrhosis. Lancet 1954;266:757-59. https://www.ncbi.nlm.nih.gov/pubmed/13153107 
2. Nia AM, Ederer S, Dahlem K, et al. Terry’s nails: a window to systemic diseases. Am J Med 2011;124:603-604. https://www.ncbi.nlm.nih.gov/pubmed/21683827 
3. Holzberg M, Walker HK. Terry’s nails: revised definitions and new correlations. Lancet 1984;1(8382):896-99. https://www.ncbi.nlm.nih.gov/pubmed/6143196 
4. Pitukweerakul S, Pilla S. Terry’s nails and Lindsay’s nails: Two nail abnormalities in chronic systemic diseases. J Gen Intern Med 31;970.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4945547/ 
5. Gagnon AL, Desai T. Dermatological diseases in patients with chronic kidney disease 2013;2:104-109.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3891143/

Figure 1. Terry’s nails in a patient with end-stage liver disease

Figure 2. Lindsay’s nails in a patient with chronic kidney disease

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What is the significance of Terry’s or Lindsay’s nails in my hospitalized patient?