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13th January 2023
A high respiratory SOFA (Sequential Organ Failure Assessment) score combined in a predictive model with the total body surface area burned (TBSA), was the best predictor of mortality risk in patients with severe burns and inhalation injury, according to a study by Chinese researchers.
Patients with severe burns and inhalation injury are at an increased risk of infection, longer hospital stays and death. In fact, the presence of smoke inhalation injury with a cutaneous burn significantly increases morbidity and mortality.
Assessment of burns can be undertaken using the Baux score, which is the summation of the patient’s age and the percentage of total body surface area (%TBSA) burned and is often quoted as the estimated percentage risk of death.
However, a revised Baux score includes inhalation injury and is simple enough for mental calculation.
The respiratory SOFA score is based on the PaO2/FiO2 (PF) ratio and ranges from 0 to 4 points, where higher scores indicate worsening respiratory dysfunction.
The PF ratio has also been shown to be highly correlated with smoke inhalation injury in burned children.
Despite this, to date, there is a lack of data on the value of the respiratory SOFA score in the prognosis of severe burn patients with inhalation injury.
For the present study, the Chinese team speculated that the respiratory SOFA score might be an important prognostic factor in such patients and undertook a retrospective analysis to determine the relevance of the score in the survival of severe burn patients with inhalation injury.
The study included adult burn patients with inhalation injury and where the burn area was greater than 20%. Multivariate Cox’s regression analysis was used to identify significant predictors of death and the sensitivity, specificity, and accuracy of the area under the ROC curve calculated.
The retrospective analysis included 118 patients with a mean age of 45.9 years (23.7% female) and of whom, 74.6% had experienced a flame burn, with a mean TBSA of 56.4%.
Univariate analysis revealed that both a large-area TBSA and a respiratory SOFA score of 3 – 4, increased the risk of death. In fact, TBSA (Hazard ratio, HR = 2.38, 95% CI 1.49 –3.79, p < 0.001) and the respiratory SOFA score (HR = 3.12, 95% CI 1.90 – 5.19, p < 0.001) were both independently associated with a shorter time to death.
In ROC curve analysis, a model incorporating TBSA and the respiratory SOFA score had an area under the curve, AUC, of 0.96 compared to the revised Baux score model (AUC = 0.93) for prediction of mortality and this difference was non-significant (p = 0.18).
In addition, the TBSA and the respiratory SOFA score model had a sensitivity of 0.95 and a specificity of 0.85.
The authors concluded that combining the TBSA and the respiratory SOFA score, improves the predictive level for patients with inhalation burns.
Citation
Ji Q et al. Survival and analysis of prognostic factors for severe burn patients with inhalation injury: based on the respiratory SOFA score. BMC Emerg Med 2023.
Three screening-based predictive tools for COVID-19 used within an emergency department (ED) have been shown to be inferior to a polymerase chain reaction (PCR) test according to the results of a study by US researchers.
During the early phase of the COVID-19 pandemic, diagnostic testing was not always readily available. Consequently, there was a need for clinical decision-making methods to identify patients most likely to be infected with the virus. Some such methods were developed and one study using a risk score for COVID-19 diagnosis, achieved an area under the receiver operating characteristic curve of 0.85 in a validation dataset, prompting the authors to suggest that it could be used as a supplemental tool to assist in the clinical decision to quarantine patients admitted to hospital from the emergency room. Nevertheless, while there are several available methods, no studies have compared the performance of different methods to predict the likelihood that a patient presenting to an ED has COVID-19.
In the current study, the US team retrospectively assessed three screening-based methods to determine which was better at detecting those who ultimately tested positive for COVID-19. The three methods were a nursing triage screen (NTS), an ED review of systems (ROS) performed by physicians and physician assistants and a standardised COVID-19 probability assessment (PA) by an ED attending (i.e., consultant) physician. The study included all patients aged 18 years or older who were admitted to hospital from the ED and who had a PCR confirmed positive COVID-19 infection. The NTS for example, involved asking about the presence of symptoms including fever, chills, weakness, severe headache, anosmia, dysgeusia, conjunctival injection, sore throat, cough, shortness of breath (SOB), abdominal pain, vomiting, diarrhoea, bruising or bleeding, myalgia, arthralgia and rash. Similarly, the ED review of ROS asked about symptoms, whereas after the initial ROS (but before the COVID-19 test result was available), the attending physician would classify the patient as high, moderate, low or no probability of having COVID-19. The sensitivity, specificity and positive predictive value (PPV) and negative predictive value (NPV) were calculated for each method. and regression analysis used to assessed each tool’s performance.
Screening-based prediction and COVID-19 positivity
A total of 748 patients with mean age of 57.5 years (56.8% male) were included in the analysis. Overall, 21.3% of patients tested positive for COVID-19 following a PCR test.
The attending physician had the highest sensitivity (0.62, 95% CI 0.53 – 0.71), followed by the ED ROS (0.53, 95% CI 0.43 – 0.62) and the least sensitive was the NTS (0.46, 95% CI 0.37 – 0.56). Specificity values were also highest for the attending physician (0.76) though this was similar to the NTS (0.71) and lowest for the ED ROS (0.62). Nevertheless, all three methods had a low positive predictive value, ranging from 26% (ED ROS) to 40% (attending physician).
The authors concluded that none of the three screening-based tools was accurate enough to replace a COVID-19 PCR test, adding that hospitals should not rely symptom screening to identify infected patients and recommended universal COVID-19 testing prior to all admissions.
Citation
Dilorenzo MA et al. Performance of three screening tools to predict COVID-19 positivity in emergency department patients. Emerg Med J 2023
A brain-derived tau biomarker which can be easily measured in blood samples, represents an important step in the specific identification of Alzheimer’s disease-type neuro-degeneration according to a study by an international research group.
Biomarkers for the identification of Alzheimer’s disease (AD) are based on the A/T/N” system where ‘A’ refers to the value of a β-amyloid biomarker, ‘T’ the value of a tau biomarker and ‘N’, biomarkers of neuro-degeneration or neuronal injury. To date, at least two of these markers are satisfactory. For example, plasma β-amyloid marker measurement (A), accurately determines amyloid positron emission tomography status in cognitively normal research participants.
In addition, blood-based tau markers (T) could be used as a simple, accessible, and scalable test for screening and diagnosis of Alzheimer’s disease. Nevertheless, neuro-degeneration (N) markers such as plasma neurofilament light chain (NfL), which measures axonal injury, showed no discriminatory power for AD compared to other neurological diseases.
Rather than focusing on developing a more specific ‘N’, researchers recognised that since tau measurements can be contaminated by peripherally generated (i.e., from liver, kidney or heart), it might be better to focus to identifying a specific brain-derived tau. In the present study, researchers created an anti-tau antibody which was designed to selectively bind with only brain-derived tau and which would hopefully be specific for patients with Alzheimer’s disease. The team then set out to validate the biomarker in five independent cohorts, including autopsy samples.
Brain-derived tau and Alzheimer’s disease
Using paired cerebrospinal fluid (CSF) and serum samples from AD patients and controls, there was a strong correlation (Spearman’s rho = 0.85, p < 0.0001) between the brain-derived (BD) tau levels in serum and CSF samples. In contrast, serum and total tau measurements were no significantly correlated (Spearman’s rho = 0.23, p = 0.3364). In addition, plasma brain-derived tau accurately distinguished autopsy-confirmed Alzheimer’s disease from other neurodegenerative diseases, with an area under the curve (AUC) value of 86.4%.
Furthermore, using samples from patients in two memory clinic cohorts, serum brain-derived tau differentiated Alzheimer’s disease from a range of other neurodegenerative disorders (AUC = 99.6%). In another cohort, BD-tau levels were significantly increased in AD patient serum and CSF samples compared to controls (p < 0.0001). Finally, BD-tau levels were inversely correlated with clinical dementia rating global scores (Spearman’s rho = -0.30, p = 0.0352).
Taken together, the authors wrote ‘across cohorts, plasma/serum brain-derived tau was associated with CSF and plasma AT(N) biomarkers and cognitive function. Brain-derived tau is a new blood-based biomarker that outperforms plasma total-tau and, unlike neurofilament light, shows specificity to Alzheimer’s disease-type neuro-degeneration.’
They concluded that the brain-derived tau demonstrates potential to complete the AT(N) scheme in blood, and will be useful to evaluate Alzheimer’s disease-dependent neurodegenerative processes for clinical and research purposes.
Citation
Gonzalez-Ortis F et al. Brain-derived tau: a novel blood-based biomarker for Alzheimer’s disease-type neurodegeneration. Brain 2022.
12th January 2023
Early prophylactic emollient use (EU) among high-risk infants, prevents the development of atopic eczema (AE) and emollient emulsions are likely to be the most effective, according to the findings of a network meta-analysis by Chinese researchers.
Atopic eczema is a chronic, inflammatory disorder of the skin and which affects between 0.9% and 22.5% of children aged 6 to 7. It is characterised by a persistent skin dryness, erythema and pruritus, leading to an impaired in quality of life. While the precise cause remains to be determined, a feature of the disease is a defective epidermal barrier that enables greater water loss through the skin leading to dryness.
However, this can be remedied to a large extent through EU, which alleviates the clinical symptoms and reduces the need for anti-inflammatory agents such as topical corticosteroids. In recent years, it has been suggested that early emollient use to high-risk infants, i.e., those with a family history of the disease or other atopic conditions such as asthma or hay fever, might prevent the subsequent development of AE.
The evidence to support this is equivocal, with one meta-analysis finding that use of emollients made no difference, whereas another concluded that prophylactic emollient use, initiated in early infancy may prevent AE, especially in high-risk populations and when used continuously. A further consideration and which might account for the observed discrepancies in the meta-analyses, is the type of emollient used. In fact, there is some data to show that different emollient creams have different effects on the skin and only certain types have the ability to improve the skin’s barrier and protect against irritants that trigger eczema.
With some uncertainty over whether early EU could prevent the development of AE, in the present study, the Chinese researchers undertook a network meta-analysis to address both whether the early application of emollients in infancy could prevent the later development of AE and which types of emollients were most effective. They used the surface under the cumulative ranking area curve (SUCRA) which to rank the different types of emollients, which could be either emulsions, creams or mixed formulations (e.g., creams, gels) and where a higher SUCRA value indicated a greater preventive efficacy.
Early emollient use and the development of atopic eczema
A total of 11 trials with 3,483 subjects were included in the network meta-analysis. Overall, the results showed that the development of AE was significantly lower after early emollient application (Risk Ratio, RR = 0.75, 95% CI 0.57 – 0.99, p = 0.001). In addition, this risk was also significantly lower, when the analysis was restricted to high-risk infants (RR = 0.64, 95% CI 0.47 – 0.88).
When examining the different types of emollients, the SUCRA values were highest for emollient emulsions, with values of 82.6% for all populations and 78.0% for high-risk populations.
The authors concluded that the early application of emollients is an effective strategy for preventing AE development in high-risk infants and that an emollient emulsion may be the optimal type of formulation.
Citation
Liang J et al. Systematic review and network meta-analysis of different types of emollient for the prevention of atopic dermatitis in infants. J Eur Acad Dermatol Venereol 2022
11th January 2023
Pfizer has reported that its candidate gene therapy, fidanacogene elaparvovec, is effective in reducing the annualised bleeding rate (ABR) of total bleeds compared to a prophylaxis regimen with Factor IX (FIX) administered as part of usual care.
Haemophilia B is a rare, X-linked inherited bleeding disorders caused by mutations in the F9 gene, which results in missing or reduced production/function of clotting factor IX (FIX). The prevalence of haemophilia B is one in 40,000 live males although female carriers may also show some signs of bleeding.
An absence or reduced level of of FIX can result in spontaneous bleeding into the joints, muscles or brain causing serious complications. Currently, the mainstay of treatment for haemophilia B involves replacement of factor IX although adeno-associated viral (AAV)-based gene therapy is one of the most emerging treatment approaches. Fidanacogene elaparvovec is a novel, investigational vector that contains a bio-engineered AAV capsid (i.e. protein shell) and a high-activity human coagulation FIX gene.
The aim of such gene therapy is that once treated, individuals are able to produce FIX rather than having to regularly receive exogenous FIX. In a Phase 1/2a study, 15 adult haemophilia B patients were infused with 5 x 1011 vg/kg of fidanacogene elaparvovec and followed for at least one year. The study examined the ABR prior to and 52 weeks after the infusion. The results showed that the mean ABR during the first 52 weeks following fidanacogene elaparvovec infusion was 0.4 ± 1.1 compared to 8.9 ± 14.0 in the 52 weeks preceding infusion (p<0.001) and in fact, 12 patients reported zero bleeds in the 52 weeks post-infusion.
The BENEGENE-2 study was a single arm trial, designed to evaluate the efficacy and safety of fidanacogene elaparvovec in adult male participants with moderately severe to severe haemophilia B (defined by a Factor IX circulating activity of 2% or less). The primary outcome was the ABR for total bleeds from week 12 to month 15 post-infusion. In the trial, 45 eligible participants completed at least six months of routine exogenous FIX prophylaxis therapy during the study lead-in before receiving a single intravenous dose of fidanacogene elaparvovec (5e11 vg/kg).
Fidanacogene elaparvovec and annualised bleeding rate
The mean ABR for all bleeds was 1.3 for the 12 months from week 12 to month 15 compared to an ABR of 4.43 during the lead-in six months pre-treatment period, giving in a 71% reduction in ABR (p<0.0001) after a single dose of fidanacogene elaparvovec.
For secondary endpoints, there was a 78% reduction in treated ABR (p=0.0001) and a 92% reduction in the annualised infusion rate (p<0.0001). The mean FIX activity was 27% after 15 months and 25% at 24 months and the mean steady-state FIX concentration was significantly higher than the pre-specified threshold of 5% (p<0.0001).
Fidanacogene elaparvovec has been granted breakthrough regenerative medicines advance therapy (RMAT) and orphan drug designations from the US Food and Drug Administration, as well as PRIority MEdicines (PRIME) and orphan drug designation from the European Medicines Agency.
Molnupiravir treatment in vaccinated, high-risk patients infected with COVID-19, failed to reduce both the rate of hospitalisation and death compared to usual care according to the results of a large, randomised trial by members of the PANORAMIC Trial collaborative group.
It is possible that the early treatment of COVID-19 infected patients with anti-viral agents, might prevent deterioration, speed up recovery and reduce the need for hospital admission. One such anti-viral is molnupiravir (EIDD-2801) and which was originally shown to be a potentially effective clinical candidate with high potential for monotherapy of seasonal and pandemic influenza virus infections.
Nevertheless, early molnupiravir treatment in patients infected with COVID-19 and at least one risk factor for severe illness, was subsequently shown to reduce the risk of hospitalisation or death in unvaccinated adults. But with millions of individuals now vaccinated against COVID-19, it remains uncertain whether molnupiravir treatment is still an effective option in such patients.
There is some evidence that molnupiravir has antiviral activity in vaccinated and unvaccinated individuals infected with a broad range of SARS-CoV-2 variants, although this is not conclusive. As a result, in the present study, researchers set out to establish the effectiveness of molnupiravir in vaccinated, high-risk, community patients at reducing hospital admission or death.
The study included community (i.e., non-hospitalised) patients aged 50 years and older, or 18 years and older with relevant comorbidities and who had COVID-19 symptoms within the previous 5 days, together with a positive PCR or rapid antigen test within the past 7 days. Eligible participants were randomly assigned (1:1) to receive molnupiravir 800 mg twice daily for 5 days plus usual care or usual care alone. The primary outcome was set as all-cause hospitalisation or death within 28 days of randomisation.
Molnupiravir treatment and adverse COVID-19 outcomes
A total of 25,783 individuals with a mean age of 56·6 years (58.5% female) were randomised to molnupiravir (12, 821) or usual care. Additionally, 69% of the whole cohort had comorbidities and 94% had received at least three doses of a COVID-19 vaccine.
Hospitalisations or deaths were recorded in 1% of both groups (adjusted odds ratio, aOR = 1·06, 95% CI 0·81 – 1·41, p = 0.33). Moreover, in subgroup analyses, there were no significant differences when assessed on several factors including the presence/absence of co-morbidities, age (< 65 vs > 65), or among those who were immunocompromised.
Despite no difference in the primary outcome, molnupiravir treatment was associated with a reduction in the median time from randomisation to first recovery (hazard ratio, HR = 1·36, 95% CI 1·32 – 1·40).
The authors concluded that in a highly vaccinated population at high risk of complications from COVID-19, the avoidance of hospitalisation and death was primarily achieved via extensive vaccination. They added that the benefits of molnupiravir in terms of a faster recovery time need to be considered in the context of several other relevant factors including the prevailing disease, burden on health-care services, drug-acquisition cost, social circumstances, cost-effectiveness, and opportunity costs.
Citation
Butler CC et al. Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial. Lancet 2022.
10th January 2023
The anti-viral agent favipiravir reduces the recovery time in hospitalised patients with COVID-19 but only for those under 60 years of age, according to the findings of a randomised, controlled trial by the PIONEER group.
Intravenous remdesivir was the first effective antiviral agent in adults hospitalised with COVID-19 and shown to be superior to placebo in shortening the time to recovery in adults. Moreover, other anti-viral agents such as oral molnupiravir and nirmatrelvir plus ritonavir have all been shown to be effective at reducing COVID-19 disease progression.
Favipiravir is another anti-viral agent that selectively and potently inhibits the RNA-dependent RNA polymerase of RNA viruses and has demonstrated in vitro activity against COVID-19. In addition, favipiravir has demonstrated an antiviral effect against COVID-19 in a small animal model study though the authors suggested that clinical studies were needed to assess the efficacy in humans.
Consequently, in the present study, researchers conducted an open-label, randomised, phase 3 controlled study of favipiravir plus standard care versus standard care alone.
The PIONEER Trial recruited adults admitted to hospital for suspected or confirmed COVID-19 and then randomised participants 1:1 to receive oral favipiravir (1800 mg twice daily orally on day 1, followed by 800 mg twice daily from day 2 to day 10) and standard care or standard care alone. In the trial, standard care evolved as per local guidelines, with systemic corticosteroids, remdesivir, and tocilizumab used by the clinical teams as necessary. Individuals were followed for 28 days and assessed on a seven category ordinal scale, ranging from 1 (not hospitalised with resumption of normal activities) through to 7 (death). The primary outcome was the time from randomisation to recovery which was censored at 28 days.
Favipiravir and COVID-19 outcomes
A total of 502 patients with a mean age of 58.9 years (61% male) were randomised to favipiravir (251) or standard care alone.
Overall, there was no significant difference between those assigned to favipiravir and standard care, relative to those who received standard care alone in the time to recovery (Hazard ratio, HR = 1.06, 95% CI 0.89 – 1.27, p = 0.52). However, in a post-hoc analysis, it was found that patients younger than 60 years who received favipiravir, showed a faster rate of recovery compared to standard care alone (HR = 1·35, 95% CI 1.06 – 1.72, p = 0.01). Despite this age-related benefit on recovery time, the researchers found that there were no aged-related mortality effects.
There were also no significant between-group difference with respect to serious adverse events (p = 0·87).
The authors concluded that whilst there was no overall benefit from favipiravir, there was a benefit in terms of the time to recovery, in patients younger than 60 years. They added that the indiscriminate use of favipiravir globally should be cautioned and called fir further studies of antiviral agents in COVID-19.
Citation
Shah PL et al. Favipiravir in patients hospitalised with COVID-19 (PIONEER trial): a multicentre, open-label, phase 3, randomised controlled trial of early intervention versus standard care. Lancet Resp Med 2022
9th January 2023
An analysis by US researchers suggests that only some of the post COVID-19 condition symptoms can be uniquely attributed to infection with the virus when compared to the post-infection symptoms induced by other, common viral infections.
Post COVID-19 condition which is also commonly referred to as long COVID, is defined as the continuation or development of new symptoms 3 months after the initial COVID-19 infection, with these symptoms lasting for at least 2 months with no other explanation. Although there are a number of specific symptoms that have been recognised, the more common ones have included fatigue, cough, chest tightness, breathlessness, palpitations and myalgia. Nevertheless, it is also known that other viral infections can result in lasting symptoms and myalgic encephalomyelitis or post-viral fatigue syndrome is a common disorder, in which patient complain of exhaustion, fatigue, muscle aches and pains, and invariable psychiatric symptoms such as emotional lability, poor memory/concentration, and depression. Thus it is necessary to have a better understanding of the risks associated with the development of specific symptoms to enable a more accurate characterisation of post COVID-19 condition.
In the present study, the US researchers focused on the identification of the persistent symptoms that could be used to define post COVID-19 condition. They made use of information held in the Cerner Real-World Data, which is large US database that receives input from 122 centres across the US. The researchers looked at a wide range of symptoms and which developed 30 days after an acute infection with either COVID-19 and the common cold, influenza and viral pneumonia. These latter three infections were combined to create a viral respiratory infection (VRI) group and de-identified participants were included if they had at least 365 days of data following their acute infection. In addition, a third cohort which included individuals who did not have any recorded infection with COVID-19 or a VRI were included as controls. Comparisons were then made for COVID-19 vs VRI, COVID-19 vs non-infected controls and VRI vs non-infected controls.
Post COVID-19 condition and subsequent significant diagnoses
A total of 17,487 COVID-19 patients were propensity matched with VRI patients and 15,694 individuals were propensity matched with non-infected controls.
When compared to non-infected controls, COVID-19 infection was a significant and positive predictor, for a diagnosis of palpitations (odds ratio, OR = 1.32, 95% CI 1.17 – 1.49), hair loss (OR = 1.32), fatigue (OR = 1.13), chest pain (OR = 1.10), dyspnoea (OR = 1.09), joint pain (OR = 1.08) and obesity (OR = 1.08). Moreover, the odds ratios were also significantly elevated for these conditions when compared to the VRI group.
However, there were notable differences for some recognised post COVID-19 condition symptoms. For example, there was no difference between COVID-19 and the VRI group for anxiety/depression, myalgia, insomnia and anosmia. While there was a significantly elevated risk of cognitive impairment when comparing COVID-19 and the VRI group, there was no difference between COVID-19 and non-infected controls.
The authors concluded n how infection with COVID-19 was not more significantly associated with an increased risk of some recognised post COVID-19 conditions compared to other common viral infections.
Citation
Baskett WI et al. COVID-Specific Long-Term Sequelae in Comparison to Common Viral Respiratory Infections: An Analysis of 17,487 Infected Adult Patients. Open Forum Infect 2022
Combining a patient’s coronary artery calcium score and their cystatin C level provides an incremental risk assessment of major adverse cardiac and cerebrovascular events (MACCEs) and all-cause death, in patients symptomatic with chest pain according to the findings of a study by Chinese researchers.
The World Health Organisation describes how cardiovascular diseases are the leading cause of global deaths, with an estimated 17.9 million lives lost each year. Consequently, risk stratification tools are required to inform on the subsequent management decisions for patients. One such measure to assist in cardiovascular disease risk stratification is the coronary artery calcium (CAC) score, which is a highly specific feature of coronary atherosclerosis. In fact, the extent of CAC has been shown to accurately predicts 15-year mortality in a large cohort of asymptomatic patients. Another potentially useful marker is Cystatin C (Cys-C) which is cysteine protease inhibitor produced at a constant rate by all nucleated cells and used as a sensitive marker of renal function. Moreover, Cys-C has been found to be a strong predictor of the risk of death and cardiovascular events in elderly patients.
Given the potential and independent value of these markers for predicting the risk of a cardiovascular event, the Chinese researchers wondered if there was an association between baseline CAC scores and Cys-C levels and both MACCEs and all-cause death in symptomatic, chest pain patients. They included all individuals presenting with symptomatic chest pain suggestive of CHD and who were referred for cardiac computed tomography (CT) by their cardiologists, which enabled assessment of the coronary artery calcium score. Based on the CT findings, patients were classified into two groups: those with CAC scores < 100 or CAC scores ≥ 100. Blood samples were taken to measure Cys-C levels and risk stratification of CAC score and Cys-C level were as follows: low risk (CAC score < 100 or Cys-C < 0.995 mg/L. and high risk (CAC score ≥ 100 or Cys-C ≥ 0.995 mg/L).
Coronary artery calcium and cysteine C levels and MACCEs
A total of 7140 participants with a median age of 63 years (64.9% male) were included and followed for a median of 1,106 days. During the period of follow-up, 305 MACCEs and 191 all-cause death events were observed.
A higher incidence of MACCEs were independently associated with CAC scores ≥ 100 (hazard ratio, HR = 1.46, 95% CI 1.15 – 1.85, p = 0.002) and where Cys-C levels were ≥ 0.995 mg/L (HR = 1.57, 95% CI 1.24 – 2.00, p < 0.001).
When categorised as high risk (i.e., CAC score ≥ 100 or Cys-C ≥ 0.995 mg/L), patients also had a significantly increased risk of MACCEs (HR = 2.33, 95% CI 1.64 – 3.29, p < 0.001). In addition, this high risk pattern was also associated with a significantly greater risk of all-cause mortality (HR = 2.85, 95% CI 1.79 – 4.55, p < 0.001). In fact, even in patients with CAC scores of < 100 but a Cys-C ≥ 0.995 mg/L, there was an increased risk of MACCEs (HR = 1.76, p = 0.003) and all-cause mortality (HR = 2.02, p = .007).
The authors concluded that the combined stratification of CAC score and Cys-C showed an incremental risk of MACCEs and all-cause death thus reflecting complementary prognostic value of these measures.
Citation
Luo F et al. Coronary artery calcium and cystatin C for risk stratification of MACCEs and all-cause death in symptomatic patients. Clin Cardiol 2022
Infection with herpes zoster is associated with a higher long‐term risk of a major cardiovascular event such as a stroke and the development of coronary heart disease, according to an analysis of three large, prospective studies by researchers from Harvard Medical School, Boston, US.
Herpes zoster (HZ) occurs after reactivation of the varicella-zoster virus which is both persistent and clinically dormant, within spinal ganglia or cranial sensory nerves following an initial infection with varicella. In fact, HZ strikes millions of older adults annually worldwide and disables a substantial number of them via post-herpetic neuralgia. Moreover, in recent years, emerging evidence suggests that HZ infection leads to 1.3 to 4-fold increased risk of cerebrovascular events with a higher risk among adults under 40 years of age and within one year after an HZ episode. However, what remains unclear, is the long‐term association between HZ infection and the risk of adverse cardiovascular events or cardiovascular disease.
In the present study, US researchers investigated the longitudinal association of herpes zoster (or ‘shingles’) and the risk of stroke or coronary heart disease (CHD) among participants in 3 large US cohorts; the NHS (Nurses’ Health Study), NHS II (Nurses’ Health Study II), and HPFS (Health Professionals Follow-Up Study). Within the three cohorts, participants were asked to self-report about clinician‐diagnosed shingles and the year of diagnosis. The primary exposure for the study was categorised according to time (in years) since the participant’s HZ event and those with no history of HZ served as the reference group. The researchers then categorised the time since HZ as never, 1 to 4 years since infection, 5 to 8 years, 9 to 12 years and ≥13 years. In their analysis, adjustment were made for several factors that could potentially be related to HZ and stroke or CHD, including age, race, smoking history, body mass index, waist circumference etc.
Herpes zoster infection and cardiovascular events
The study included data on 79,658 women in the NHS, 93,932 in the NHS II and 31,440 men in the HPFS (2004-2016), without prior stroke or CHD. During >2 million person-years of follow-up, 3603 incident stroke and 8620 incident CHD cases were documented.
In a pooled analyses and compared to those without a history of HZ infection, the multivariable-adjusted hazard ratio (HR) for stroke was non-significant for those with 1 to 4 years since HZ infection (HR = 1.05, 95% CI 0.88 – 1.25). However, the associations became significant as the duration from infection increased. For example, among those with 5 to 8 years since HZ, the hazard ratio was 1.38 (95% CI 1.10 – 1.74) and 1.28 (95% CI 1.03 – 1.59) among those with for 9 to 12 years since HZ. Interestingly, the association became non-significant among those with ≥13 years since HZ (HR = 1.19, 95% CI 0.90 – 1.56).
When considering CHD, the corresponding multivariable-adjusted hazard ratios were similar, e.g. 1.25 (95% CI 1.07 – 1.46) for 9 to 12 years and, as with stroke, the risk of CHD became non-significant after ≥13 years (HR = 1.00, 95% CI 0.83 – 1.21).
The authors concluded that herpes zoster is associated with a higher long-term risk of a major cardiovascular event, underscoring the importance of prevention of infection.
Citation
Curhan SG et al. Herpes Zoster and Long-Term Risk of Cardiovascular Disease. J Am Heart Assoc. 2022
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