Tag: Mortality

Climate change predicted to spike cardiovascular deaths in China
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A new study published in the journal eBioMedicine aims to predict the extent to which climate change may impact the risk of cardiovascular disease (CVD) mortality in China.

Study: Projecting heat-related cardiovascular mortality burden attributable to human-induced climate change in China. Image Credit: Piyaset / Shutterstock.com

Climate change and CVD

Current estimates indicate that about 19 million people die each year due to CVD, five million of whom reside in China. Furthermore, CVD causes over 390 million disability-adjusted life years (DALYs) globally.

Due to climate change, the global temperature at the earth’s surface has risen by 1.15 °C above that in the pre-industrial era. Previous studies have reported an adverse impact of climate change on overall mortality that is dependent on age, sex, and cause of death, as well as deaths due to CVD.

Heat affects the cardiovascular system in multiple ways, including the excretion of salt and water as sweat, higher cholesterol levels, and hemodynamic strain. Moreover, climate change-related heat can increase the risk of atherosclerotic thrombosis of the heart and brain vessels and, as a result, the rate of strokes and heart attacks.

About the study

The present study attempted to predict CVD mortality associated with climate change in a Chinese setting. Current temperatures were measured at 161 disease surveillance points (DSPs).

These projections were based on the Coupled Model Intercomparison Project Phase 6 (CMIP6), which is under the World Climate Research Programme (WCRP). WCRP examines natural climate change and the combined scenario with both natural and anthropogenic impacts on the climate.

A total of 22 General Climate Models (GCMs) were used to determine projected temperatures from 2010 to 2100 in both human-induced and natural scenarios. Human-induced scenarios were calculated based on the difference between the combined and natural impacts.

Recognizing that economic and social change is closely related to climate change, the Intergovernmental Panel on Climate Change (IPCC) has presented a series of integrated scenarios that combine both shared socioeconomic pathways (SSPs) and climate representative concentration pathways (RCPs).

Study findings

The mean annual temperature at the DSPs varied from 12.6 to 28.4 °C, during which time about 330,000 CVD deaths occurred.

Under natural conditions, the summer temperatures in China would not significantly change. Similarly, in this scenario, the proportion of CVD deaths related to heat would decline by 0.5% in the 2090s as compared to 2010 death rates due to CVD.

Conversely, summer temperatures increased by 5-6 °C with the combined scenarios, depending on the region. The predicted CVD mortality fraction in the 2090s rose from 10% to 30%, depending on the modeled scenario.

The death rate among CVD patients followed a J-shaped curve beyond a critical minimum temperature. The most significant increase relative to baseline temperature was in the South and East of China.

The proportion of heat-related deaths due to CVD with human-induced climate change continued to rise during each decade from about 31% in the 2010s to an estimated 70-90% in the 2090s under different scenarios.

Individuals who were considered to be most vulnerable to heat-related CVD mortality included those living in rural areas, those with lower education levels, stroke patients, females, older adults, and those residing in Southern and Eastern China. Importantly, individuals with lower levels of education are more likely to work outdoor jobs, have unequal access to healthcare, and be diagnosed with chronic diseases.

Conclusions

“This study provides evidence that human activities will amplify future heat-related cardiovascular mortality burden.”

Anthropogenic climate change resulting in CVD deaths could account for as much as 90% of excess mortality due to excessive heat by 2090. Simultaneously, the CVD burden associated with natural climate change may not change significantly. Nevertheless, the study findings emphasize the importance of limiting carbon emissions to prevent further global warming ultimately.

“Active adaptation and mitigation measures towards future warming could yield substantial health benefits for the patients with CVD.”

Future studies are needed to identify populations and groups at the greatest risk of climate-related health effects and the different types of risk that may be associated with global climate change. These data will assist in implementing integrated and sensitive public health policies to ultimately reach environmental targets.
Journal reference:

Zhu, Q., Zhou, M., Sakhvidi, M. J. Z., et al. (2024). Projecting heat-related cardiovascular mortality burden attributable to human-induced climate change in China. eBioMedicine. doi:10.1016/j.ebiom.2024.105119.
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April 22, 2024
Rising trend in atrial fibrillation risk over 20 years heightens concern for related heart and stroke complications
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In a recent Danish population-based cohort study published in the British Medical Journal, researchers analyzed the changes in lifetime risks of atrial fibrillation (AF) and complications. They compared the data between two periods, 2000-2010 and 2011-2022. They found that the lifetime risk of AF increased over the study period, and individuals with AF showed significant risks of heart failure (HF) and stroke over their lifetime.

Study: Temporal trends in lifetime risks of atrial fibrillation and its complications between 2000 and 2022: Danish, nationwide, population based cohort study. Image Credit: Magic mine / Shutterstock

Background

AF poses a growing health concern globally, with a substantial projected increase in affected populations. While improvements in mortality rates have been observed, AF remains linked to increased risks of stroke, HF, and myocardial infarction (MI). Understanding and effectively assessing AF risk, including its long-term complications, are crucial for prevention efforts. Residual lifetime risk, a measure capturing cumulative disease risk over the remaining lifespan, offers valuable insights for public health initiatives and patient education. Despite previous studies on AF lifetime risk, data on temporal trends and comprehensive complication risks are lacking. Monitoring changes in AF burden is vital for evaluating management strategies and prevention efforts, especially amid evolving stroke prevention therapies. In the present investigation involving the Danish population, researchers aimed to assess the lifetime risk of AF and its associated complications and to analyze their temporal trends spanning from 2000 to 2022.

About the study

Data were gathered from national registries, including the Danish National Patient Registry for hospital stays and outpatient contacts, the Civil Registration System for demographics and vital status, and the Danish National Prescription Registry for medication information. The study included 3,574,903 Danish individuals without AF at or after the age of 45 between 2000 and 2022. About 51.7% of the participants were women. Those aged 95 years or older were excluded. Follow-up ended at incident AF, death, age 95 years, emigration, or period end. Primary analysis used 45 years as the index age, with secondary analyses for ages 55, 65, and 75 or older. Incident AF was identified from hospital diagnoses.

A total of 362,721 individuals were followed up upon newly diagnosed AF (46.4% females). Complications, including HF, stroke, MI, or systemic embolism, were recorded post-diagnosis. Exclusions comprised pre-existing complications and events within seven days of diagnosis. The diagnosis followed strict International Classification of Diseases 10 (ICD-10) criteria with high predictive values. Analyses were conducted for index ages 45, 55, 65, and 75 years.

Study populations were characterized by assessing medical history along with family income and educational attainment. The statistical methods included the use of the Aalen-Johansen estimator for cumulative incidence, pseudo-value regression, propensity score adjustment using logistic regression, stabilized inverse propensity weighting, and subgroup analyses with interaction testing.

Results and discussion

Age distributions were found to remain consistent across the periods, while hypertension, dyslipidemia, and diabetes prevalence rose over time, whereas HF and MI prevalence reduced.

The lifetime risk of AF at the age of 45 between 2000-2022 was 27.7%, with higher risk observed among men, those with a history of certain cardiovascular conditions, and individuals with higher socioeconomic status. From 2000-2010 to 2011-2022, there was an absolute increase in lifetime risk from 24.2% to 30.9%. This trend persisted across all subgroups, with slightly higher increases among men, individuals with HF or stroke history, and those without dyslipidemia. At ages 55, 65, and 75, the lifetime risk also showed an upward trajectory, with absolute increases between the two periods.

Among individuals diagnosed with AF, HF was the most common complication, with a lifetime risk of 41.2%, followed by stroke (21.4%), MI (11.5%), and diagnosed systemic embolism (1.8%). Men generally faced higher risks of HF and MI compared to women, while women had a higher risk of stroke post-AF. History of certain cardiovascular conditions significantly increased the risk of HF post-AF. Over time, a slight decrease in the lifetime risks of stroke (-2.5%) and MI (-3.9%) was observed.

The study reports the temporal patterns in lifetime risks associated with AF and its subsequent complications for the first time. However, the study is limited by its potential underestimation of incident events due to a lack of differentiation between AF and atrial flutter and the absence of data on lifestyle factors and causes of death, among others.

Conclusion

The present Denmark-wide study reveals a concerning trend: the lifetime risk of AF has increased from one in four to one in three over the past two decades. HF emerged as the most common complication following AF, with a lifetime risk twice that of stroke. While there were slight improvements in the lifetime risks of stroke, ischemic stroke, and MI after AF, the rates remained high. These findings highlight the urgent need for effective strategies to prevent HF and stroke in patients with AF.
Journal reference:

Temporal trends in lifetime risks of atrial fibrillation and its complications between 2000 and 2022: Danish, nationwide, population-based cohort study. Vinter N. et al., British Medical Journal, 385:e077209 (2024), DOI: doi:10.1136/bmj-2023-077209, https://www.bmj.com/content/385/bmj-2023-077209
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April 22, 2024
Aging affects immune response and virus dynamics in COVID-19 patients, study finds

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In a recent study published in the journal Science Translational Medicine, researchers investigated the impact of aging on immune response, viral dynamics, and nasal microbiome in 1031 hospitalized coronavirus disease 2019 (COVID-19) patients, using advanced profiling techniques to understand age-related differences in disease severity and immune function.

Study: Host-microbe multiomic profiling reveals age-dependent immune dysregulation associated with COVID-19 immunopathology. Image Credit: Corona Borealis Studio / Shutterstock

Background

Age is a significant risk factor for severe COVID-19 outcomes, with older adults facing drastically higher risks of complications and mortality than younger individuals. Despite high vaccination rates, older adults are still profoundly vulnerable. Aging correlates with elevated levels of inflammatory cytokines, like interleukin-6 (IL-6), which are critical markers of COVID-19 severity, hinting at a link between aging and disease pathophysiology. Studies show that aging dampens both innate and adaptive immune responses, including reduced type I interferon (IFN) production. Additionally, older adults show enhanced inflammatory responses and impaired immune signaling when infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Further research is needed to fully understand the complex interactions between aging, immune response variations, and COVID-19 severity to improve treatment strategies and outcomes for older populations.

About the study

The present study utilized data from 1,031 participants enrolled in the IMmunoPhenotyping Assessment in a COVID-19 Cohort (IMPACC) observational cohort, which involved 20 hospitals across 15 medical centers in the United States from May 5, 2020, to March 19, 2021. It involved hospitalized individuals with reverse transcription polymerase chain reaction (rt-PCR) confirmed SARS-CoV-2 infections, displaying typical COVID-19 symptoms. Blood and respiratory tract samples were collected within 72 hours of hospitalization, following a standardized protocol across participating institutions. Ethical approval was granted under the public health surveillance exception, with participant consent for follow-up involvement and data usage.

Statistical analysis was performed using R software. Initial assessments were done within 72 hours of hospital admission, followed by longitudinal evaluations at subsequent visits. Data analysis applied various statistical methods depending on the data type and required adjustments for factors like age, sex, and baseline disease severity. For longitudinal studies, age groups were divided into quintiles and analyzed for changes in viral abundance and immune response, employing linear and generalized additive models to account for the observed non-linear patterns. All p-values were adjusted using the Benjamini-Hochberg method, considering results statistically significant at p < 0.05.

Study results

The study involved analyzing blood and nasal swab specimens from 1,031 vaccine-naïve adults hospitalized with COVID-19. These participants were part of the IMPACC cohort, sourced from 20 hospitals across the United States. They were categorized into five age quintiles, ranging from 18 to 96 years, with each group comprising between 187 and 223 individuals. Samples were collected at the time of hospital admission and during up to five follow-up visits. The distribution of ages showed that older individuals were often more severely affected by the disease, evident in both the initial severity of symptoms and the outcomes, including mortality.

At the initial hospital visit, typically within 72 hours of admission, a range of diagnostic assays was conducted. These included transcriptional profiling of peripheral blood mononuclear cells (PBMCs) and nasal swabs, serum inflammatory protein profiling, whole blood mass cytometry (CyTOF), nasal metatranscriptomics, and SARS-CoV-2 antibody (Ab) assays. A significant finding from these initial tests was that older adults displayed higher viral loads and experienced delayed viral clearance compared to younger patients. Moreover, age-related differences in immune cell populations were noted, with older adults showing higher proportions of various monocyte subtypes and activated T cells but lower levels of naïve T and B cells.

The study’s longitudinal analysis revealed that these differences persisted over time, affecting viral load dynamics, antibody titers, and immune response. Specifically, the eldest participants not only retained high levels of the virus longer but also showed more significant fluctuations in antibody levels over time. Additionally, immune cell analysis by CyTOF highlighted that with advancing age, certain immune cell types, including different monocyte classes and differentiated natural killer cells, increased, suggesting shifts in immune system composition and function with age.

Changes in cytokine and chemokine levels measured in the participants’ serum further underscored the impact of aging on the immune response. Older individuals showed elevated levels of inflammatory markers at hospital admission, which were linked to more severe disease outcomes.

Moreover, the analysis extended to the nasal microbiome and upper respiratory gene expression, revealing age-associated changes in the microbial composition and host gene activity. Changes in Toll-like receptor signaling and other immune pathways were evident, suggesting that older adults experience different immune modulations, possibly influencing their susceptibility to severe outcomes.

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April 19, 2024
Study shows antipsychotic drugs increase health risks in dementia patients
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In a recent British Medical Journal study, researchers assess the adverse effects associated with the use of antipsychotic drugs in people with dementia.

Study: Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. Image Credit: Fahroni / Shutterstock.com

The role of antipsychotics in dementia management

Individuals diagnosed with dementia undergo functional disability and progressive cognitive decline. Some common psychological and behavioral symptoms of dementia include anxiety, depression, apathy, aggression, delirium, irritability, and psychosis.

To manage psychological and behavioral symptoms of dementia, patients are commonly treated with antipsychotics. The United Kingdom National Institute for Health and Care Excellence currently recommends the use of antipsychotics only when non-drug interventions are ineffective in alleviating behavioral and psychological symptoms of dementia. However, there has been an increase in antipsychotic use during the recent coronavirus disease 2019 (COVID-19) pandemic, which has been attributed to lockdown measures and the unavailability of non-pharmaceutical treatments.

In the U.K., risperidone and haloperidol are the only antipsychotics that have received approval for the treatment of behavioral or psychological symptoms of dementia. In 2003, the United States Food and Drug Administration (FDA) highlighted the risks, such as stroke, transient ischaemic attack, and mortality, associated with the use of risperidone in older adults with dementia.

Based on multiple study reports, regulatory guidelines have been formulated in the U.K., U.S., and Europe to reduce inappropriate prescriptions of antipsychotic drugs for the treatment of behavioral and psychological symptoms of dementia. To date, few studies have provided evidence of the association between antipsychotic drug prescriptions in older adults with dementia and risks of multiple diseases, such as myocardial infarction, venous thromboembolism, ventricular arrhythmia, and acute kidney injury.

About the study

The current study investigated the risk of adverse outcomes associated with antipsychotics in a large cohort of adults with dementia. Some adverse outcomes considered in this study were venous thromboembolism, stroke, heart failure, ventricular arrhythmia, fracture, myocardial infarction, pneumonia, and acute kidney injury.

Over 98% of the U.K. population is registered with National Health Service (NHS) primary care general practice. All relevant data were collected from the electronic health records held at the Clinical Practice Research Datalink (CPRD), which is associated with over 2,000 general practices. CPRD comprises the Aurum and GOLD databases, which can be considered as broadly representative of the U.K. population.

Individuals above 50 years of age and diagnosed with dementia were recruited. Importantly, none of the study participants were under antipsychotic intervention one year before their diagnosis.

The researchers utilized a matched cohort design, in which each patient who used antipsychotics after their initial dementia diagnosis was matched using the incidence density sampling method. This method considered up to 15 randomly selected patients who were diagnosed with dementia on the same date but were not prescribed antipsychotic drugs.

Antipsychotics increase the risk of adverse effects in dementia patients

Across the two cohorts, the mean age of the participants was 82.1 years. A total of 35,339 participants were prescribed an antipsychotic during the study period.

The mean number of days between the first diagnosis of dementia and the date of a first antipsychotic prescription was 693.8 and 576.6 days for Aurum and GOLD, respectively. The most commonly prescribed antipsychotics were risperidone, haloperidol, olanzapine, and quetiapine.

The current population-based study revealed that adults with dementia prescribed antipsychotics are at a greater risk of venous thromboembolism, myocardial infarction, stroke, heart failure, pneumonia, fracture, and acute kidney injury than non-users. This observation was based on analyzing 173,910 adults with dementia selected from both databases.

The increased risk of adverse outcomes was most prevalent among current and recent users of antipsychotic drugs. After 90 days of antipsychotic use, the risk of venous thromboembolism, pneumonia, acute kidney injury, and stroke was higher than non-users. However, antipsychotic drugs did not impact the risk of ventricular arrhythmia, appendicitis, and cholecystitis.

As compared to the use of risperidone, haloperidol was significantly associated with an increased risk of pneumonia, fracture, and acute kidney injury. Although the adverse effects of haloperidol were higher than quetiapine, no significant differences were observed between risperidone and quetiapine for the risk of fracture, heart failure, and myocardial infarction. The risk of pneumonia, stroke, acute kidney injury, and venous thromboembolism was lower for quetiapine as compared to risperidone.

Conclusions

The current study highlights how antipsychotic drugs affect older adults with dementia. The use of these drugs was associated with many serious adverse outcomes, such as stroke, acute kidney injury, pneumonia, venous thromboembolism, heart failure, and myocardial infarction.

In the future, these risks must be considered, along with cerebrovascular events and mortality, while making regulatory decisions about the use of antipsychotic drugs for the treatment of dementia in older adults.
Journal reference:

Mok, L. H. P., Carr, M. J., Guthrie, B., et al. (2024) Multiple adverse outcomes associated with antipsychotic use in people with dementia: population based matched cohort study. BMJ. doi:10.1136/bmj.2023.076268
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April 19, 2024
Discovery of new vascular cell type may pave way for novel strategies to treat cardiovascular diseases

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Cardiovascular diseases, including stroke and myocardial infarction, are the world’s leading causes of mortality, accounting for over 18 million deaths a year. A team of KIT researchers has now identified a new cell type in blood vessels responsible for vascular growth. This discovery may allow for novel therapeutic strategies to treat ischemic cardiovascular diseases, i.e. diseases that are caused by reduced or absent blood flow. Nature Communications (DOI: 10.1038/s41467-024-47434-x)

In our body, a large network of blood vessels distributes blood across our organs and thereby ensures that the active cells are supplied with sufficient oxygen and nutrients to function and to maintain heart beat and brain activities for example. Occlusion of blood vessels and compromising oxygen delivery may cause neuronal or cardiac cell death culminating in stroke or heart attack. Revascularization , i. e. restoring vascular perfusion and promoting tissue regeneration, requires functional blood vessels, but how to effectively revascularize organs still is an unsolved clinical question.

Since each organ fulfills a different physiological function, vascular branching patterns differ across organs. It has long been a mystery how such unique, so-called organo-typical vascular structures develop.

From a therapeutic point of view, it is believed that understanding the organ-specific molecular control of vascular growth and patterning could open the doors for developing personalized medicine strategies to combat cardiovascular and neurodegenerative diseases and cancer.

Pioneer cells move inside the vessel walls

Scientists of the KIT led by Professor Ferdinand le Noble, Head of the Department of Cell and Developmental Biology and Director of the Zoological Institute of KIT, now discovered that one crucial element contributing to organ-dependent variability in vascular branching involves the activation of a novel vascular cell type they coined endothelial L-tip cell or pioneer cell. Pioneer cells reside inside the inner layer that lines the blood vasculature, the so-called endothelium.

Using high-end imaging techniques, the scientists found that pioneer cells move inside the vessel wall. Once they come into contact with specific signals produced by cells in the surrounding organ, pioneer cells start to make new blood vessels. To elucidate which cells produce such signals and how these signals are sensed to promote pioneer cell differentiation, the scientists used a recently developed technique called single cell sequencing.

Molecular cocktail encodes the time and place of blood vessel formation

Dr. Laetitia Preau, first author of the paper, explains: “Single cell sequencing combines detailed RNA sequencing of individual cells with bio-informatic analyses and allows precise identification of cell subtypes and the molecules these cells produce for cell-to-cell communication. Using this technique, we discovered that the vascular patterning is encoded by a distinct set of molecules that can only be sensed by a subset of endothelial cells to promote vessel growth.”

The cells in the tissue produce an organ-specific set of molecules that encode the instruction how to make a new blood vessel at that particular place and time. Once the prospective pioneer cell senses and unravels this specific tissue-derived molecular code, it will initiate the vascular growth process.

Foundations for new therapeutic approaches

It turned out that several organ-specific vascular growth code molecules are drug-targetable, i.e. react to externally added chemicals.

To explore the therapeutic avenues, we are collaborating with chemists, tissue engineers, and artificial intelligence (AI) specialists at the 3ROCKIT platform of the Health Technologies Center established recently at Karlsruhe Institute of Technology (KITHealthTech). We hope to identify novel smart molecules to target the vascular growth process that may benefit patients suffering from ischemic cardiovascular diseases, such myocardial infarction and stroke, as well as from certain forms of cancer.”

Professor Ferdinand le Noble

The study was financed by the German Research Foundation (DFG) and carried out by KIT in cooperation with the German Center for Cardiovascular Research (DZHK) at its partners sites in Heidelberg and Munich and the Max Planck Institute for Molecular Biomedicine in Münster.

Source:

Karlsruhe Institute of Technology

Journal reference:

Préau, L., et al. (2024). Parenchymal cues define Vegfa-driven venous angiogenesis by activating a sprouting competent venous endothelial subtype. Nature Communications. doi.org/10.1038/s41467-024-47434-x.

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April 18, 2024
Lifetime risk of atrial fibrillation rises to nearly 31% in recent decade
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Atrial fibrillation (AF) is a common arrhythmia or cardiac rhythm disorder. It is associated with significant mortality risk and also a higher risk of multiple complications. As such, understanding the risk of AF in the population is necessary.

A new study published online in the BMJ explores the risk of both AF and its complications in a Danish national cohort, beginning from the age of 45 years. The results underline the risk for preventive strategies to reduce the burden of AF on public health.

Study: Temporal trends in lifetime risks of atrial fibrillation and its complications between 2000 and 2022: Danish, nationwide, population based cohort study. Image Credit: Orawan Pattarawimonchai/Shutterstock.com

AF risk and complications

About 16 million and 18 million people are predicted to develop AF by 2050 in the USA and Europe, respectively. In this condition, the atria, or heart chambers that receive the venous blood, begin to show irregular twitches rather than a coordinated pumping contraction.

This prevents the efficient movement of blood through the atria into the ventricles, the main pumping chambers.

The complications of AF include stroke, heart failure, and heart attacks, though the overall and specific AF-related mortality risk has gone down over time. Primary and secondary prevention is, therefore, essential in protecting AF patients.

This motivated the present study, which seeks to establish the lifetime risk of AF in a large Danish cohort. Two periods were chosen to capture any change in risk over time.

Residual lifetime risk of a disease is the measure of the total risk that a given individual who does not have the disease at a specified age will develop it during the rest of the lifespan.

It helps educate the public about health risks and encourages compliance with healthy lifestyle recommendations. Not much is known about the long-term risk of several complications.

Though patients with AF are typically warned about their risk for stroke, all the long-term sequelae require more study, especially to identify how these risks have changed since the introduction of new stroke-prevention protocols for AF.

About the study cohort

The cohort included all Danes aged at least 45 years but less than 95 years who had never had an episode of AF. Those who developed AF from that point onwards were followed up for five complications arising from the diagnosis.

These included heart failure, any stroke, ischaemic stroke, myocardial infarction, and systemic embolism.

AF risk

There were over 3.5 million individuals without a history of AF at the age of 45 years or above. In this group, there was a rising prevalence of hypertension, diabetes, dyslipidemia, and stroke over the study periods among both the baseline population and those who developed AF after the study began.

AF was newly diagnosed in over 360,000 individuals with a similar age spectrum at the time of diagnosis in both periods. The lifetime risk of AF at 45 years was ~28% over the two decades of the study.

The same pattern was observed at the later index ages, viz., 55, 65, and 75 years. The risk at each age was 28%, 27%, and 24%, respectively.

Risk factors for AF included male sex, a history of hypertension, heart failure, heart attacks, other heart conditions, and dyslipidemia. Those with higher educational status and household income were also at greater risk.

Patients with stroke, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD) were more likely to die early compared to others, thus accounting for a significantly lower risk of AF over their lifespan.

Comparing the first decade to the second, they observed a 6.7% increased lifetime risk of AF from 45 years onwards, from 24% to 31%. This was unchanged after compensating for confounding factors. Similar increases were observed, by 6.5%, 6.3%, and 5.6%, at the later ages, respectively.

AF complications

The study shows a high lifetime risk of post-AF complications. While heart failure was the most common, affecting 41% of AF patients over their lifespan, stroke occurred in 21% of the patients. Heart attacks affected 12% of the patients.

Men had a higher risk, with 44% of them likely to develop AF complications, vs 35% of women with AF. The post-AF stroke risk was somewhat lower in men, affecting 21% of them vs 22.6% of women.

The risk of all AF complications except for all strokes was higher among hypertensive individuals.

Heart failure was much more likely among those who had a history of heart attacks, cardiomyopathy, or valvular heart disease, with the difference being as large as 22% to 45% compared to those without such conditions.

However, the lifetime risk of heart failure did not change over the study periods. Marginal decreases were observed in the risk of stroke (by 2.5%), ischemic stroke (~5%), and heart attacks (~4%).

When stratified by health condition, patients with hypertension or dyslipidemia had a reduced risk of post-AF heart failure over this period by 10% and 5%, respectively.

The heart attack risk among those with dyslipidemia went down by 11% vs 4% for those with normal lipid levels. These findings may be attributable to better medical care for such conditions. The risk of such complications decreases with age.

Conclusions

The study shows an increased lifetime risk for new AF over time, from one in four to one in three, over the two study periods. The most frequent complication was heart failure, affecting two out of five patients over the lifespan.

People with hypertension or dyslipidemia showed reduced lifetime risk of heart failure, however, compared with the general cohort, which showed no change in risk.

This is twice as high as the risk of post-AF stroke and four times greater than the risk of heart attack. This underlines the need for secondary prevention of heart failure in this group.

The results corroborate previous studies on the incidence of AF at various ages. The study demonstrates, for the first time, a rising risk of AF.

This may be due to better diagnostic methods and a lower threshold of suspicion, with improved clinical practice coupled with higher life expectancy. However, the increasing prevalence of risk factors like hypertension and diabetes must also be kept in mind.

By providing estimates of the lifetime risk of AF and its complications, the study could be important in helping to develop more efficient preventive strategies and policies.

For instance, stroke risk is managed by anticoagulants in Denmark, with compliance above 85%. The persistently high risk of stroke indicates the need for additional steps.

“As atrial fibrillation is a common arrhythmia, a lower incidence of complications may reduce the future economic costs in healthcare.”
Journal reference:

Vinter, N., Cordsen, P., Johnsen, S. P., et al. (2024) Temporal trends in lifetime risks of atrial fibrillation and its complications between 2000 and 2022: Danish, nationwide, population based cohort study. BMJ. doi: http://dx.doi.org/10.1136/bmj-2023-077209.
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April 17, 2024
Sugary beverages linked to higher risk of atrial fibrillation

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In a recent study published in the European Journal of Clinical Nutrition, researchers used Mendelian randomization (MR) to explore the associations between the intake of pure fruit juices (PFJ) and sugar-sweetened beverages (SSBs) with cardiovascular disease (CVD).

Study: Association between sugar-sweetened beverages and pure fruit juice with risk of six cardiovascular diseases: a Mendelian randomization study. Image Credit: Andrii Zastrozhnov/Shutterstock.com

Background

Cardiovascular illnesses are a major worldwide health problem, with risk factors including high body mass index (BMI), alcohol use, and smoking habits.

SSBs and PFJ are associated with CVD; however, the causative relationship is uncertain. SSBs may be an elastic dietary target for lowering the CVD risk among females; however, PFJ may be a primary predictor.

However, several investigations have found no direct link between SSBs and CVD. PFJ use can increase important nutrient intake; however, one should limit intake due to the high free sugar and energy content.

The health consequences of PFJ consumption are inconsistent, and dietary advice differs among nations. The link between PFJ use and CVD mortality is unclear.

About the study

The present study researchers investigated whether SSB and PFJ consumption increased CVD risk.

The researchers assessed genetically estimated causal relationships between sugar-sweetened beverages, pure fruit juices [obtained from genome-wide association studies (GWAS) of European individuals], and six CVDs [hypertension, angina pectoris, atrial fibrillation (AF), coronary atherosclerosis (CA), acute myocardial infarction (AMI), and heart failure (HF)] using mendelian randomization.

The team obtained dietary intake data from the United Kingdom Biobank based on the Oxford WebQ 24-hour diet recall questionnaires filled out by 85,852 individuals. GWAS data on atrial fibrillation included 3,818 cases, with 333,381 control individuals. Angina data included 10,083 patients and 452,927 disease-free individuals.

AMI data included 3,927 patients and 333,272 control individuals. Coronary atherosclerosis data included 14,334 patients with 346,860 controls. Heart failure GWAS data included 1,405 patients with 359,789 control individuals. GWAS data on hypertension included 54,358 patients with 408,652 controls.

The researchers used the inverse variance weighted (IVW) approach for analysis, supplemented by the Cochran Q test, weighted median, MR Egger regressions, MR pleiotropy, Bonferroni corrections, and funnel plots.

To ensure that the primary analysis findings were robust, they calculated F-values as complementary tests to establish looser cut-offs for exposing the instrumental variables (IVs) and selected IVs by detecting single nucleotide polymorphisms (SNPs) strongly associated with PFJ and SSBs.

They determined odds ratios (OR) for the associations between SSB, PFJ intake, and CVD.

Results and discussion

The MR analysis showed genetically causal positive associations between sugar-sweetened beverages and atrial fibrillation (OR, 1.02) and negative associations between pure fruit juice and angina pectoris (OR, 0.97).

However, there were no causal relationships between SSB and PFJ intake and other cardiovascular disease risks. Supplementary MR methods yielded similar results.

The leave-one-out analysis showed that individual SNP removal did not alter the causal associations, indicating that the primary findings were reliable and robust.

SSB and PFJ intakes have distinct substance compositions, which can raise the chance of developing AF while decreasing the risk of angina. SSBs contain dietary additives such as sodium citrate, which may increase the risk of AF over time.

Excessive intake of SSBs can activate an inflammatory response, resulting in higher levels of circulating inflammatory markers such as interleukin-6 (IL-6), C-reactive protein (CRP), and tumor necrosis factor receptors 1 and 2 (TNF-r1, r2). Higher IL-6 levels are associated with an increase in AF burden and mortality.

PFJ, on the other hand, has high levels of polyphenols, some of which have anti-inflammatory properties. Pomegranate juice can lower inflammatory indicators such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and IL-6 due to its high concentration of hydrolyzable tannins.

PFJ’s anti-inflammatory properties may lower angina incidence by blocking platelet aggregation and preventing coronary plaque development.

Conclusions

The study findings revealed a positive relationship between sugar-sweetened beverages and atrial fibrillation, whereas pure fruit juice had a negative link with angina.

The findings should help us better understand the impact of long-term SSB/PFJ intake on cardiovascular disease (CVD) and recommend dietary choices for people who are at risk. Patients with AF should limit their SSB consumption to prevent potential pathogenic hazards, whereas individuals may incorporate PFJ into their diet as a protective factor against angina.

However, further clinical and fundamental research is required to confirm these findings. Future research should concentrate on non-European ancestry groups and study data on various types of SSBs/PFJ and consumption rates to better understand their impact on CVD.

Further research is needed to improve the understanding of their protective and pathogenic characteristics and assess their potential utility in clinical CVD prevention and therapy.

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April 17, 2024
Persistent measles importations challenge U.S. elimination efforts

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A recent Centers for Disease Control and Protection (CDC) report published in the Morbidity and Mortality Weekly Report (MMWR) assessed the status of measles elimination in the United States (U.S.) and reported on the recent increase in cases by analyzing surveillance data from January 2020 to March 2024.

Study: Measles — United States, January 1, 2020–March 28, 2024. Image Credit: sulit.photos/Shutterstock.com

Background

Measles, a highly contagious viral illness, was considered eliminated in the U.S. in 2000 due to high coverage with the measles, mumps, and rubella (MMR) vaccine.

Despite this, the elimination status faced challenges in 2019 following significant outbreaks in under-vaccinated communities in New York, contributing to a notable rise in cases.

Further research is needed to address gaps in vaccine coverage and enhance surveillance systems to prevent future outbreaks and sustain measles elimination.

About the study

Confirmed measles cases are reported to the Centers for Disease Control and Prevention (CDC) by state health departments through the National Notifiable Disease Surveillance System and directly via email or telephone to the National Center for Immunization and Respiratory Diseases.

The Council of State and Territorial Epidemiologists classifies measles cases. Cases are deemed import-associated if they originate internationally, are epidemiologically linked to an imported case, or show viral genetic evidence of an imported measles genotype.

Conversely, cases without an epidemiologic or virologic connection to an imported source are categorized as having an unknown origin.

For analytical purposes, unique sequences are identified as those varying by at least one nucleotide in the N-450 sequence, following the World Health Organization’s (WHO)’s recommendations for describing sequence variants.

Patients who were unvaccinated yet eligible for vaccination were identified based on the criteria set by the Advisory Committee on Immunization Practices.

A surveillance system is considered effective if at least 80% of cases meet three criteria: classification as import-associated, comprehensive reporting on key surveillance indicators, and confirmation through laboratory testing.

Additionally, measles cases are categorized into chains of transmission based on known epidemiologic links. These include isolated cases, two-case chains involving two linked cases, and outbreaks consisting of three or more linked cases.

The analysis of two-case chains and outbreaks also involves assessing the potential for missed cases by examining the time intervals between the onset of measles rashes, with intervals exceeding one maximum incubation period suggesting possible unreported cases.

Study results

From January 1, 2020, to March 28, 2024, the CDC was notified of 338 confirmed measles cases across 30 jurisdictions. A noticeable portion of these cases, particularly 12 of 13 reported before the COVID-19 mitigation measures began in March 2020, marked the early stages of this period.

In the following years, 2021 and 2022 witnessed 170 reported cases, 78% of which were linked to distinct outbreaks. Notably, 47 of the 49 cases in 2021 were among Afghan evacuees at U.S. military bases during Operation Allies Welcome, and 86 of the 121 cases in 2022 stemmed from an outbreak in Central Ohio.

By 2023, 48% of the 58 cases reported were associated with four outbreaks. As of late March 2024, 97 cases had been reported for the year, signifying a significant increase over previous first-quarter averages.

The median age of the affected individuals was three years, ranging from newborns to 64 years old, with 58% of the cases occurring in the 16 months to 19 years age group.

A significant majority, 91% of patients, were either unvaccinated or had an unknown vaccination status, and of these, 84% were eligible for vaccination.

Hospitalization data showed that 46% of the patients were hospitalized, primarily children under five years old, with 92% being unvaccinated or of unknown vaccination status. There were no reported deaths due to measles.

Regarding the origin of the cases, 96% were linked to importation. A detailed breakdown reveals that the majority of the 326 import-related cases involved U.S. residents eligible yet unvaccinated or of unknown vaccination status.

The most frequent origins of these imported cases were from the Eastern Mediterranean and African WHO regions. However, the first quarter of 2024 saw increased European and Southeast Asian cases.

Surveillance quality was notably high, with nearly all cases (98%) including comprehensive data on key indicators. Timeliness of reporting showed that 58% of cases were reported to health departments on or before the day of rash onset.

Laboratory confirmations were achieved in 93% of cases, with a large majority verified through real-time reverse transcription-polymerase chain reaction (rRT-PCR) testing and successful genotyping of most specimens, identifying predominant measles genotypes B3 and D8.

Transmission patterns were categorized into 92 chains, with the majority being isolated cases. However, 20 chains qualified as outbreaks involving three or more cases, and the typical outbreak lasted 20 days, highlighting the rapid transmission potential of measles.

Notably, none of the two-case chains or larger outbreaks experienced a gap exceeding the maximum incubation period.

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April 16, 2024
Study shows potential for universal flu vaccine with broad antibody response
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A recent study published in the journal Nature Communications observed antibody breadth and effector functions as important immune correlates that can be used to develop universal influenza vaccines. This vaccine could be effective against all influenza virus strains, even those having pandemic potential.

Study: Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children. Image Credit: Africa Studio / Shutterstock

Background

Children are particularly vulnerable to influenza viruses that cause seasonal epidemics and sporadic pandemics. Seasonal influenza epidemics not only lead to an upsurge in hospital admissions but also increase mortality rates in older adults with comorbidities. Many studies have shown that seasonal influenza vaccines provide limited protection against influenza viruses that have the potential to cause a pandemic. However, the 2009 H1N1 pandemic (pH1N1) revealed the effectiveness of seasonal vaccines in protecting children and older adults from the infection. This protection could be due to cross-reactive antibody responses.

Compared to children, adults possess additional immune correlates, such as T-cell responses and non-neutralizing antibody functions. This is the reason why children require higher concentrations of HAI antibodies for an equivalent amount of immune protection from the infection. To design a next-generation vaccine, it is important to identify immune correlates of protection. In the context of pH1N1 infection, HA-stem-specific antibodies play a crucial role in providing protection, which is mediated by the Fc Receptor (FcR) function.

Some antibodies that can cross-react between pandemic, seasonal, and avian influenza viruses could reduce the severity of influenza virus infection. In this context, serum antibodies, particularly IgG, can facilitate effector functions, such as directing immune cells to kill infected cells, engulfing infected cells via antibody-dependent phagocytosis (ADCP), and promoting antibody-dependent cellular cytotoxicity (ADCC). These functions are mediated by Fc gamma receptors (FcγR) 3a and FcγR2a.

Mechanistically, FcγR 3a and FcγR2a employ macrophages and natural killer (NK) cells to remove viruses-infected cells. Cross-reaction of ADCC antibodies has been associated with targeting conserved antigenic sites of influenza virus hemagglutinin (HA), the Nucleoprotein (NP), and Matrix 1 (M1).

About the Study

The current study identified several gaps in research regarding antibody effector functions. For instance, few studies have assessed the vaccine-induced ADCC changes, longitudinal durability of vaccine-induced antibody FcR binding and isotype changes, and the alterations in HA-specific antibody responses with vaccination and infection. The currently performed randomized placebo control trial (RCT) investigated the influenza-specific antibody breadth and function of seasonal (S1) H1N1 vaccination and pH1N1 infection.

The antibody features, particularly HAI titer, from seasonal vaccination that could have helped in reducing or delaying contraction of pH1N1 were assessed using selected archived samples. These samples were collected from NCT00792051, a randomized placebo-controlled trial and its follow-up study that used school children between 6 and 17 years old.

A subset of children who received any influenza vaccination in Year 1 (V1) or not (placebo-V0) was selected for secondary analyses, which helped determine the effectiveness of vaccination against pH1N1 infection.

Study Findings

The current study indicated that non-neutralizing antibodies are highly cross-reactive between different influenza strains and subtypes, which could play an important role in reducing the incidence and severity of infection.

Detecting antibody functions other than HAI is vital to developing next-generation vaccines. This study identified the serological correlates that play an important role in protecting children from pandemic infection. In 2009, when schools were closed for two months, H1N1 transmission was low. However, soon after schools reopened in September 2009, more than 50% of the students were infected within a few months. A very low community uptake of the monovalent pH1N1 vaccine has been documented.

The half-life of different antibody subclasses alters significantly. The current study observed that seasonal vaccination enhances Fc effector functions of pH1N1 specific NP, HA, and neuraminidase (NA) antibodies. However, their function was short-term as it waned off within one year of vaccination. A greater antibody decline was observed in unvaccinated children.

Seasonal vaccination did not boost FcR effector functions to other seasonal-specific antibody responses. Unvaccinated, uninfected children also exhibited increased FcR-mediated effector functions of pandemic-specific NA, HA, and NP antibodies. These children displayed a higher antibody level of NK cell function. pH1 antibodies against H3-HA responses were associated with cross-reactive avian H5-specific IgG, FcγR2a, and FcγR3a responses. This finding implies that cross-reactive responses are less focused and are not trained by seasonal virus exposure of other groups.

Considering the experimental results, vaccination and prior infection are not associated with the lack of infection in unvaccinated, uninfected children or susceptibility of V1S1 children. More research is required to understand the host factors leading to these outcomes.

Results also indicated that group 2 H3 HA-specific IgG3 antibodies are negative predictors of infection. However, seasonal H1 and pH1-IgG3 antibodies before infection were positively associated and, therefore, protected against infection.

Conclusions

This study shows how universal influenza vaccines, effective against seasonal to pandemic viruses, can be developed. Antibody breadth and FcR effector functions are two important immune correlates that could be exploited to develop this vaccine.
Journal reference:

Jia, J. Z. et al. (2024) Influenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children. Nature Communications. 15(1), 1-15. DOI: 10.1038/s41467-024-47590-0, https://www.nature.com/articles/s41467-024-47590-0
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April 16, 2024
Genetic predisposition for muscle strength linked to longer lifespan and lower disease risk

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A study conducted at the Faculty of Sport and Health Sciences at the University of Jyväskylä, Finland, showed that a genetic predisposition for higher muscle strength predicts a longer lifespan and a lower risk for developing common diseases. This is the most comprehensive international study to date on hereditary muscle strength and its relationship to morbidity. The genome and health data of more than 340,000 Finns was used in the research.

Muscle strength, especially hand grip strength, can indicate an individual’s physiological resources to protect against age-related diseases and disabilities, as well as their ability to cope with them. Age-related loss of muscle strength is individual and influenced not only by lifestyle but also by genetics.

The study revealed that individuals with a genetic predisposition for higher muscle strength have a slightly lower risk for common noncommunicable diseases and premature mortality. However, it did not predict better survival after acute adverse health events compared to the time before illness onset.

It seems that a genetic predisposition for higher muscle strength reflects more on an individual’s intrinsic ability to resist and protect oneself against pathological changes that occur during aging than the ability to recover or completely bounce back after severe adversity.”

Päivi Herranen, doctoral researcher from the Faculty of Sport and Health Sciences

The research utilized a unique study population

Muscle strength is a multifactorial trait influenced by lifestyle and environmental factors but also by numerous genetic variants, each with a very small effect on muscle strength. In this study, the genetic predisposition for muscle strength was defined by constructing a polygenic score for muscle strength, which summarizes the effects of hundreds of thousands of genetic variants into a single score. The polygenic score makes it possible to compare participants with an exceptionally high or low genetic predisposition for muscle strength, and to investigate associations with inherited muscle strength and other phenotypes, in this case, common diseases.

“In this study, we were able to utilize both genetic information and health outcomes from over 340,000 Finnish men and women,” Herranen explains.

“To our knowledge, this is the first study to investigate the association between a genetic predisposition for muscle strength and various diseases on this scale.”

Further research on the effects of lifestyles is still needed

Information about the genetic predisposition for muscle strength could be used alongside traditional risk assessment in identifying individuals who are at particularly high risk of common diseases and health adversities. However, further research on the topic is still needed.

“Based on these results, we cannot say how lifestyle factors, such as physical activity, modify an individual’s intrinsic ability to resist diseases and whether their impact on health differs among individuals due to genetics,” Herranen notes.

The study utilized the internationally unique FinnGen dataset, compiled through the collaboration of Finnish biobanks. The dataset consisted of 342,443 Finns who had given their consent and provided a biobank sample. The participants were aged 40 to 108 years, and 53% of them were women. The diagnoses selected for the study were based on the leading causes of death and the most significant noncommunicable diseases in Finland. Selected diagnoses included the most common cardiometabolic and pulmonary diseases, musculoskeletal and connective tissue diseases, falls and fractures, mental health and cognitive disorders, cancers, as well as overall mortality and mortality from cardiovascular diseases.

The study is the second publication of Päivi Herranen’s doctoral thesis, which investigates how genetics and environmental factors affect biological aging, particularly the weakening of muscle strength and functional capacity with age. The research is part of the GenActive project, funded by the Research Council of Finland and the Juho Vainio and Päivikki and Sakari Sohlberg foundations. The project is led by Assistant Professor and Academy Research Fellow Elina Sillanpää. The research was conducted in collaboration with the Gerontology Research Center (GEREC), the Institute for Molecular Medicine Finland (FIMM), and the FinnGen research project.

Source:

University of Jyväskylä

Journal reference:

Herranen, P., et al. (2024). Genome-Wide Polygenic Score for Muscle Strength Predicts Risk for Common Diseases and Lifespan: A Prospective Cohort Study. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences. doi.org/10.1093/gerona/glae064.

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April 13, 2024