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6th June 2022
The post-myocardial infarction (post-MI) mortality risk has been found to be significantly lower among those who are classed as overweight or obese yet much higher for those with a body mass index (BMI) below the ideal range. This was the conclusion of a systematic review and meta-analysis by an international team led by researchers from Aberdeen University, Scotland, UK.
Body mass index (BMI) is a measure of nutritional status in adults and defined as a person’s weight in kilograms divided by the square of the person’s height in metres (kg/m2). Based on the BMI, individuals are deemed to be of normal weight when their BMI is being 18.5 and 24.9. According to the World Health Organization, individuals with a BMI > 25 are classed as overweight, and obese when their BMI is equal to or > 30). According to the American Heart Association, the presence of obesity leads to the development of cardiovascular disease and mortality, independently of other cardiovascular risk factors. However, there is increasing evidence that patients with an elevated BMI may have better outcomes if they develop cardiovascular or renal disease, which is referred to as the “obesity paradox”. Despite this, meta-analyses support a J-shaped relationship between mortality and BMI in patients with coronary artery disease, i.e., the risk is highest for underweight and overweight individuals and lowest for those with a normal BMI.
Nevertheless, whether this same J-shaped relationship holds for post-MI mortality is unknown and was subject of the present meta-analysis. The researchers looked for studies in adults with a previous myocardial infarction where the BMI had been measured and which reported on outcomes such as all-cause mortality, recurrence of an adverse cardiovascular event or hospital re-admission. Hazard ratios (HRs) were used to assess the risk of mortality and the normal BMI (18.5 – 24.9) was used as the reference range for comparative purposes.
Post-MI mortality and BMI
A total of 27 articles with 308,430 participants and with follow-up periods ranging from 6 months to 17 years were included in the analysis.
Among individuals who were classed as overweight (BMI 25 – 29.9) compared to those of normal BMI and based on 8 studies, there as a 15% lower risk of post-MI mortality (HR = 0.85, 95% CI 0.76 – 0.94, p = 0.002). In 14 studies that reported on odds ratios (ORs) rather than hazard ratios, there was also a reduced mortality risk (OR = 0.72, 95% CI 0.64 – 0.81, p < 0.0001).
Among obese patients (BMI > 30) the HR was 0.86 (95% CI 0.81 – 0.91, p < 0.0001) and for morbidly obese patients, although the HR was reduced, it was not statistically significant (HR = 0.89, 95% CI 0.78 – 1.01, p = 0.08).
In contrast, among those with a BMI < 18.5, there was a 42% higher risk of post-MI mortality (HR = 1.42, 95% CI 1.25 – 1.62, p < 0.0001) and again, where studies reported odds ratios, this was also significantly increased (OR = 2.48, 95% CI 1.77 – 3.47, p < 0.0001).
There were no significant effects when comparing the risk of hospital re-admission for those who were overweight, obese and underweight.
The authors concluded that individuals who have a BMI less than the normal range are at a significantly higher risk of post-MI mortality. They called for future studies to examine the prognostic utility of other markers of nutritional status in MI to better identify those at a higher risk of poor clinical outcomes.
De Paola L et al. Body Mass Index and Mortality, Recurrence and Readmission after Myocardial Infarction: Systematic Review and Meta-Analysis J Clin Med 2022
13th April 2022
COVID-19 vaccinated cancer patients have been found to be at a higher risk of breakthrough infections and which are associated with a substantial risk of hospitalisation and mortality. This was the conclusion of a retrospective cohort study of electronic health records by a team from the Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Ohio, US.
Patients with cancer have been found to be at a significantly increased risk for COVID-19 infection and worse outcomes though fortunately, COVID-19 vaccination has been shown to be associated with lower infection rates in cancer patients. However, despite vaccination, the occurrence of breakthrough infections has also been reported and this appears to be correlated with neutralising antibody titers during the peri-infection period. While COVID-19 vaccinated cancer patients are also potentially likely to experience breakthrough infections, there is a lack of data on the extent to which such breakthrough infections occur among those with cancer and how, or if, this might be influenced by the different cancer sites.
For the present study, the US team turned to the TriNetX database which contains de-identified information on 90 million patients in the US. The team looked for vaccinated patients with one of 12 different cancers including pancreatic, liver, lung, colorectal, skin and thyroid and compared the level of breakthrough infections with a group of vaccinated, patients without any of the specified cancers. Data on age, sex, race and co-morbidities were collected for all patients and adjusted for in the analysis. The researchers examined the monthly incidence of breakthrough infections between December 2020 and November 2021 as well as the risk of hospitalisation and death among those infected.
COVID-19 vaccinated cancer patients and breakthrough infections
A total of 45,253 vaccinated cancer patients with a mean age of 68.7 years (53.5% female) were included in the analysis and matched with 591,212 vaccinated, non-cancer patients.
The cumulative risk of a breakthrough infection during the period of study among vaccinated COVID-19 cancer patients, was 13.6% which was higher than vaccinated, non-cancer patients, (Hazard ratio, HR = 1.24, 95% CI 1.19 – 1.29). Among the different cancer sites, the highest risk was for patients with pancreatic cancer (24.7%), followed by liver (22.8%), lung (20.4%) and colorectal (17.5%). The only cancer not associated with a significant increased risk for a breakthrough infection was thyroid (HR = 1.07, 95% CI 0.88 – 1.30) although the increased risk among patients with skin cancer was of borderline significance (HR = 1.17, 95% CI 0.99 – 1.38).
The risk of hospitalisation among cancer patients with breakthrough infections was much higher than matched, non-cancer patients (31.6% vs 3.9%, HR = 13.48). In addition, mortality risks were also significantly elevated (HR = 6.76, 95% CI 4.97 – 9.20).
The authors concluded that their results emphasised the need for those with cancer to maintain mitigation practices, especially given the emergence of COVID-19 variants for which vaccination might not provide full protection.
Wang W et al. Breakthrough SARS-CoV-2 Infections, Hospitalizations, and Mortality in Vaccinated Patients With Cancer in the US Between December 2020 and November 2021 JAMA Oncol 2022
29th March 2022
Individuals who become infected with the Omicron COVID-19 variant experience less severe outcomes such as hospitalisation and death compared to those with the Delta variant according to the results of a large study by a multi-disciplinary group of UK researchers.
The Omicron COVID-19 variant has produced a surge of infections and been found to be associated with high transmission among household contacts, particularly among those who lived with index patients who were not vaccinated or who did not take measures to reduce the risk of transmission to household contacts. Nevertheless, despite a higher level of transmissibility, studies have also suggested that the Omicron variant is associated with substantial severity of illness in comparison to the Delta variant.
With an increasing number of individuals now fully vaccinated against COVID-19, the purpose of the present study was to offer a more detailed understanding of the overall impact of both less severe outcomes and greater immunity on rates of hospitalisation and mortality during the Omicron wave. The UK team obtained individual-level data on confirmed cases of COVID-19 infection in England between November 2021 and 9 January 2022 and linked these to vaccination status, hospital attendance and admission as well as deaths. During the period of study genomic sequencing was performed for some of the infections which enabled the team to distinguish between the two variants. For the study, a hospital admission was defined as a stay of at least one or more days. The analysis was stratified by age, vaccination status and adjusted for sex, deprivation index and evidence of prior infection.
Omicron caused less severe outcomes
During the period of study there were 4,135,347 confirmed cases of COVID-19, of which 1,526,702 (37%) had information on the infecting variant and consisted of 448,843 Delta and 1,067,859 Omicron cases.
The adjusted hazard ratio (HR) for attendance at hospital, but not necessarily admission, was lower for Omicron than Delta (HR = 0.56, 95% CI 0.54 – 0.58). In addition, compared to Delta, the risk of hospital admission among those infected with Omicron was 59% lower (HR = 0.41, 95% CI 0.39 – 0.43) and the risk of death within 28 days was 69% lower (HR = 0.31, 95% CI 0.26 – 0.37).
When stratified by age, there was no difference between the two variants among those 10 years of age and younger (HR = 1.10, 95% CI 0.85 – 1.42). However, there was a significant difference and reduction among those at least 80 years of age (HR = 0.47, 95% CI 0.40 – 0.56).
For both of the variants, prior infection offered protected against death in those who were vaccinated (HR = 0.47) and unvaccinated (HR = 0.18). Interestingly, among those who were vaccinated, prior infection appeared to offer no additional protection against infection (HR = 0.96, 95% CI 0.88 – 1.04), which was in contrast to those who were unvaccinated but had a previous infection (HR = 0.55, 95% CI 0.48 – 0.63).
The authors concluded that the less severe outcomes observed for Omicron were largely driven by a less severe variant and increased immunity due to vaccination.
Nyberg T et al. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study Lancet 2022
10th March 2022
A higher sodium intake from the use of soluble paracetamol tablets has been found to increase the risk of both cardiovascular disease (CVD) and mortality in patients, irrespective of their hypertensive status. This was the conclusion of a study by researchers from the Department of Orthopaedics, Xiangya Hospital, Changsha, China.
It has been known for some time that a higher sodium intake increases blood pressure and is therefore a risk factor for cardiovascular disease. Furthermore, an increased intake of the mineral has also been linked to an additional 1.65 million deaths from cardiovascular causes above a reference level intake of 2.0 g per day. In addition, studies suggest that in comparison to a moderate intake of sodium, higher intakes are associated with an increased risk of cardiovascular events and death among those with hypertensive but not form normotensive patients.
While lowering intake of sodium is known to be associated with a reduced risk of stroke and fatal coronary heart disease in adults, it would be unethical to examine the impact of a greater intake on CVD and mortality risk, given the benefits of reducing intake. While dietary sodium is a major source of intake, sodium is also contained within several medicines, in particular, soluble paracetamol. For the present study, the Chinese team compared the risks of incident CVD and all-cause mortality associated with the intake of sodium-containing soluble paracetamol (acetaminophen) compared to intake of non-sodium containing formulations according to patient’s hypertension status.
The team turned to the Health Improvement Network which is an electronic medical record database in the UK containing anonymised data for approximately 17 million patients as their source of information. They extracted data for two separate cohorts. The first included patients aged 60 – 90 years of age and with a diagnosis of hypertension and prescribed either a sodium and non-containing paracetamol formulation. The second cohort was similar although this time included patients without a diagnosis of hypertension. Socio-demographic data including gender, age, body mass index and various lifestyle factors were recorded and used as covariates in their analysis. The primary outcomes of interest were incident CVD which included myocardial infarction, stroke and heart failure, and all-cause mortality.
Sodium intake and CVD/mortality outcomes
For the first cohort, a total of 151,398 individuals with a mean age of 78.3 years (65.8% female) and a history of hypertension were included and of whom, 4532 were given a sodium-containing paracetamol. These were matched with a total of 147,299 without hypertension and a mean age of 71.4 (63.3% female), of whom 5,351 were given a sodium-containing paracetamol formulation.
Among those with hypertension, there were 122 cases of CVD among those given the mineral and 3051 cases among the non-sodium group over a median follow-up period of 0.89 and 0,93 years respectively. This gave a 59% higher risk of incident CVD among those taking a sodium-containing paracetamol formulation (Hazard ratio, HR = 1.59, 95% CI 1.32 – 1.92). Furthermore, the risk of all-cause mortality was more than double (HR = 2.05, 95% CI 1.92 – 2.19).
Among those given a sodium-containing paracetamol formulation but without hypertension, there was a 45% increased risk of CVD (HR = 1.45, 95% CI 1.18 – 1.79) and a 87% increased mortality risk (HR = 1.87, 95% CI 1.74 – 2.00).
Commenting on these results, the authors noted that sodium-containing drugs are an important but often overlooked source of the mineral. They concluded that individuals should avoid unnecessary excessive sodium intake through sodium-containing paracetamol use.
Zeng C et al. Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension Eur Heart J 2022
14th February 2022
Rates of re-hospitalisation and mortality among people who were originally admitted to hospital with an acute COVID-19 infection, appear to be much higher than those hospitalised with other conditions. This was the key finding from an analysis of information in the OPENSAFELY database by researchers at the Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, United Kingdom.
During the early stages of the COVID-19 pandemic, although many patients were initially managed in an outpatient settings, one study found that 15% of cases required hospitalisation and 4% died within a month of first symptoms. The introduction of COVID-19 vaccines have been effective at preventing symptomatic and asymptomatic SARS-CoV-2 infections and COVID-19-related hospitalisations. Nevertheless, there is little currently known about the subsequent outcomes for those patients who were initially hospitalised because of COVID-19, although where such data does exist, it appears that patients are still at risk of future adverse outcomes. For example, in one US study it was found that beyond the first 30 days of illness, people with COVID-19 exhibit a higher risk of death and use of health resources. Similarly, a UK-based study concluded that individuals discharged from hospital after COVID-19 had increased rates of multi-organ dysfunction compared with the expected risk in the general population.
For the present study, the UK team decided to examine the incidence of subsequent re-hospitalisation and death in those initially admitted to hospital with COVID-19 in comparison to both the general population and those who were hospitalised prior to the pandemic, with influenza. They used the OPENSAFELY platform which provides information from primary care practices and linked patient information with other databases providing data on hospitalisations and mortality. Their main outcomes of interest were re-hospitalisation or death and all-cause mortality. The team used used regression models which were adjusted for a number of covariates such as age, sex, ethnicity, obesity and other co-morbidities.
Re-hospitalisation and mortality after acute COVID-19
The analysis included 24,673 individuals discharged from hospital after a COVID-19 hospitalisation and who were matched with 123,362 controls and 16,058 patients who had been hospitalised and discharged due to influenza. COVID-19 patients had a median age of 66 years (55.7% male) which was slightly younger than the median age of those hospitalised due to influenza (69 years).
The overall risk of re-hospitalisation was higher in the discharged COVID-19 group compared to the general population (adjusted hazard ratio, aHR = 2.22, 95% CI 2.14 – 2.30, p < 0.001). However, the risk of re-hospitalisation was lower than the influenza group (aHR = 0.95, 95% CI 0.91 – 0.98, p = 0.004).
All-cause mortality was higher in the COVID-19 discharged group than in the general population (aHR = 4.82, 95% CI 4.48 – 5.19, p < 0.001) and for the influenza group (aHR = 1.74, 95% 1.61 – 1.88, p < 0.001).
When examining the reported cause of death, 24.7% of deaths had COVID-19 listed as the cause although in comparison, less than 5 deaths were reportedly due to influenza.
The authors concluded that among patients who survived hospitalisation after an acute infection with COVID-19, there was a substantially higher risk of subsequent re-hospitalisation and death over the next 10 months. They suggested that these findings highlighted a need for services to support and closely monitor people following discharge from hospital.
Bhaskaran K et al. Overall and cause-specific hospitalisation and death after COVID-19 hospitalisation in England: A cohort study using linked primary care, secondary care, and death registration data in the OpenSAFELY platform. PLos Med 2022
7th October 2021
In systemic inflammatory conditions such as sepsis, low serum albumin levels are associated with an increased risk of death in patients with severe disease. However, whether serum albumin (SA) levels can used predictively to identify those at risk of both severe disease and mortality in COVID-19 remains unclear. This was the question addressed in a retrospective study by a team from the Emergency Department, Alto Adige, Italy. The team considered consecutive patients with COVID-19 seen at the emergency department (ED) of three hospitals during March to April 2020. Serum albumin levels were added to the panel of blood samples routinely performed on those with suspected COVID-19 upon arrival at the ED. The primary outcome of the study was the presence of severe COVID-19 infection. In addition, the team explored 30-day mortality after the initial ED assessment as a secondary outcome. The researchers categorised SA levels upon ED admission as < 3 g/dL, 3 – 3.49 g/dL and greater than 3.5 g/dL.
There were 296 patients with COVID-19 for whom the overall mean SA value was 3.7 g/dL. Serum albumin levels were higher for patients aged under 75 years of age (3.9 vs 3.4, under 75 years vs over 75 years, p < 0.001) although there were no gender differences. Most patients (59.8%) had SA levels above 3.5 g/dL with only 10.1% having levels below 3 g/dL. Nearly two thirds (63.2%) of patients had severe COVID-19 infection and 18.2% of all patients died within 30 days of their arrival at the ED.
In their analysis, the authors calculated that SA levels < 3.5 g/dL was an independent risk factor for both severe infection (adjusted odds ratio, aOR = 2.92, 95% CI 1.51 – 5.66) and 30-day mortality (aOR – 2.62, 95% CI 1.13 – 6.1).
In their conclusion, the authors stated that their preliminary data suggested that “serum albumin level in the ED may play a role in the assessment of the severity of SARS-CoV-2 infection and the risk of death at 30 days.” They also called for more prospective evaluations to confirm whether albumin levels was an important prognostic factor in patients with COVID-19.
14th September 2021
An analysis of all COVID-19-related deaths in England between the 2nd of January and July 2021, has been published by the Office for National Statistics (ONS). The data include a breakdown of all recorded deaths analysed by vaccination status. Clearly, a certain number of both infections and deaths among those who have been vaccinated, referred to as breakthrough infections, are likely to occur simply because the COVID-19 vaccines have been administered to many millions of people and none can be considered as 100 per cent effective.
The risk of becoming infected with COVID-19 is, according to the ONS infection survey, highest within the first 21 days after receipt of the primer vaccine dose. The bulletin from the ONS examines deaths in relation to vaccination status and uses age-standardised mortality rates, which adjusts for differences in the population age distribution.
There were a total of 640 deaths in those who had received two COVID-19 vaccines; 182 within 21 days of their second vaccine dose and 458, 21 days after their second dose. Together, both groups represent 1.2% of all COVID-19 related deaths although only 0.8% (458/51,281) of all deaths occurred 21 days after the second vaccine dose. In other words, less than 1% of all COVID-19 related deaths occurred in those who were fully vaccinated. However, it is worth noting that the more infectious delta variant only became the dominant strain, according to the ONS, since the end of May 2021 and hopefully future bulletins will report upon any associated mortality changes.
In cases where the date of infection was known, among those who had received two vaccinations, 47.5% became infected 14 or more days after the second dose, leading to 256 deaths.
Characteristics of individuals with breakthrough deaths
Among the 256 deaths occurring 14 or more days after infection, linked data, which provides demographic and clinical information was available for 252 individuals. The information showed that the average age of death among these fully vaccinated individuals was 84 years. Nearly two-thirds (61.1%) were male and 76.6% were described as clinically vulnerable and 13.1% of deaths occurred among immunocompromised patients.
The latest set of ONS data clearly shows that COVID-19 related deaths are significantly reduced due to vaccination but also serves as a reminder that deaths will still occur, especially among the clinically vulnerable and immunocompromised, highlighting the need for booster doses.
27th July 2021
Patients hospitalised with COVID-19 experience a wide range of organ system complications including cardiac problems such as arrhythmias and myocarditis. Due to its widespread availability and potential for bedside use, echocardiographic information captured through transthoracic echocardiography (TTE), has become recognised as the preferred first-line imaging modality for patients with either known or suspected cardiac problems. Nevertheless, advice from the European Association of Cardiovascular Imaging (EACVI) is that cardiac imaging should only be performed where appropriate and only if it is likely to substantially change patient management or be lifesaving. Whether echocardiographic data can help with risk stratification in patients hospitalised with COVID-19 has been poorly explored. Thus, a team from the Department of Medicine and Surgery, University of Salerno, Italy, sought to determine whether echocardiographic parameters were associated with in-hospital mortality among those with COVID-19. They undertook a retrospective observational study among consecutive patients admitted to hospital with confirmed COVID-19 infection at seven Italian centres between March and April 2020. All patients underwent TTE within 48 hours of admission and the need for TTE was confirmed as being clinically appropriate by a consultant cardiologist. All patient demographics (age, gender, weight and height) clinical (i.e., co-morbidities, current therapies), laboratory and echocardiographic data were collected and stored electronically. Echocardiographic data included an evaluation of left ventricular end-diastolic (LVEDV) and end-systolic volumes (LVESV). Left ventricular function was assessed by determination of left ventricular ejection fraction (LVEF) and the parameter used to assess global right ventricular function was tricuspid annular plane systolic excursion (TAPSE). The clinical course of patients was also recorded including the proportion who developed acute respiratory distress syndrome (ARDS).
A total of 1401 patients were hospitalised with COVID-19 and of whom, 226 (16.1%) underwent echocardiographic testing with TTE. Among this smaller cohort, the mean age was 68.9 years (62.4% male) and the majority (61.1%) had hypertension. In addition, 36 and 13 patients had previously undergone percutaneous coronary interventions and coronary artery bypass grafting respectively. Overall, 68 patients within this cohort died in hospital among whom, ARDS was more common (83.3% vs 31%, p <0.001). In those who died in hospital, there was a lower mean LVEF (47.6% vs 55.5%, death vs survivors, p < 0.001) and a lower TAPSE (17.5 vs 21.7, p < 0.001). Using regression analysis and after adjustment for various factors, amongst patients who experienced in-hospital mortality, reduced LVEF was independently associated with in-hospital mortality (relative risk, RR = 0.93, 95% CI 0.89–0.97, p < 0.001), as was reduced TAPSE (RR = 0.80, 95% CI 0.72–0.88) and the development of ARDS (RR = 3.05).
In discussing these findings, the authors highlighted how the risk of mortality was increased among patients with ARDS and the echocardiographic parameters TAPSE < 17 and an LVEF <50%. They suggested that TTE was useful for risk stratification in COVID-19 patients but recognised the limitation of not having TTE data prior to hospitalisation. The authors concluded that while their study has suggested an important relationship between echocardiographic parameters and in-hospital mortality, further studies were necessary to confirm these findings.
Silverio A et al. Clinical conditions and echocardiographic parameters associated with mortality in COVID-19. Eur J Clin Invest 2021
28th May 2021
Infection with COVID-19 has been found to be associated with raised levels of systemic inflammatory markers such as C-reactive protein (CRP), interleukin-6 (IL-6) and other cytokines. In addition, data have revealed how engagement of protein platforms (inflammasomes) and in particular, the nucleotide binding domain-like pyrin domain 3 (NLRP3) inflammasome, is strongly associated with disease severity.
The anti-inflammatory gout drug, colchicine, is known to inhibit the NLRP3 inflammasome and may therefore be of value in the treatment of patients hospitalised with COVID-19. The randomised evaluation of COVID-19 therapy (RECOVERY) trial aims to evaluate a number of therapeutic options for the management of hospitalised patients infected with COVID-19. The RECOVERY group have investigated several different treatments and recently examined the use of colchicine. For the present trial, patients were randomised 1:1 to usual care or usual care plus colchicine at a dose of 1mg after randomisation, followed by 500mcg 12 hours later and then 500mcg twice daily (orally or via nasogastric tube) for 10 days or until discharged from hospital. However, although patients were randomised, this was an open label trial, hence both treating clinicians and patients were not masked to treatment allocation although the study steering group and investigated were masked to outcome data during the trial. The primary outcome was all-cause mortality and assessed at 28 days post-randomisation. Secondary outcomes included time to hospital discharge and the need for invasive mechanical ventilation.
A total of 5610 patients with a mean age of 63.4 years (31% female) and of predominately (77%) White ethnicity, were randomised to colchicine and 5730 to usual care. The median duration of treatment with colchicine was 6 days and use of all other treatments was similar between the two groups. The proportion of patients allocated to colchicine who achieved the primary outcome was not different to placebo (21%) and the median time to hospital discharge was 10 days and again, similar between the two groups. Moreover, an equal number of patients progressed to invasive mechanical ventilation (70%).
In discussing these findings, the authors commented on how the use of colchicine had no impact on mortality, duration of hospitalisation or the need for mechanical ventilation. Additionally, this effect was evidence across all ages, ethnic groups and irrespective of symptom duration prior to randomisation. They also speculated that the anti-inflammatory properties of colchicine were either inadequate or did not sufficiently target the pathways induced by COVID-19 and concluded that the drug was of no benefit to those hospitalised with COVID-19.
RECOVERY Collaborative Group. Colchicine in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. MedRxiv 2021