Four behaviours explain a majority of the socioeconomic disparities observed in the disease
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Lower socioeconomic status is associated with higher rates of death from coronary artery disease compared to higher socioeconomic status, and more than half of the disparities can be explained by four unhealthy behaviours. Dr Yachen Zhu of the Alcohol Research Group, US, and Dr Charlotte Probst of the Centre for Addiction and Mental Health, Canada, report these findings in a new study published September 17th in the open-access journal PLOS Medicine.
Coronary artery disease, also known as coronary heart disease or ischaemic heart disease, occurs when the arteries supplying the heart cannot deliver enough oxygen-rich blood due to plaque buildup, and is a major cause of death in the US. The condition poses a greater risk to people with lower socioeconomic status, but previous studies have reported conflicting results on whether certain unhealthy behaviours, like smoking, are primarily responsible for the observed disparities in deaths from the disease.
In the new study, researchers used data from 524 035 people aged 25 years and older whose mortality statuses were recorded in the National Death Index and who answered the National Health Interview Survey on demographics and health behaviours. The team used education as the primary indicator for socioeconomic status, and investigated four behavioural risk factors: smoking, alcohol use, physical inactivity and BMI. The four factors together explained 74% of the differences in mortality risk from coronary artery disease in men belonging to different socioeconomic levels and 61% in women.
The researchers conclude that their results highlight the need for effective public health policies and interventions that address each of these behaviours – both separately and together – because unhealthy behaviours often cluster among individuals from low socioeconomic backgrounds. They urge public health campaigns to raise awareness about heart health with messaging and outreach efforts customised for male and female audiences. The authors add, “These efforts are crucial to reducing the socioeconomic disparities in deaths from coronary artery disease in the US.”
Coronary artery disease and major depression may be genetically linked via inflammatory pathways to an increased risk for cardiomyopathy, a degenerative heart muscle disease, researchers at Vanderbilt University Medical Center and Massachusetts General Hospital have found.
Their report, published in Nature Mental Health, suggests that drugs prescribed for coronary artery disease and depression, when used in combination, potentially may reduce inflammation and prevent the development of cardiomyopathy.
“This work suggests that chronic low-level inflammation may be a significant contributor to both depression and cardiovascular disease,” said the paper’s corresponding author, Lea Davis, PhD, associate professor of Medicine in the Division of Genetic Medicine and Vanderbilt Genetics Institute.
The connection between depression and other serious health conditions is well known. As many as 44% of patients with coronary artery disease (CAD), the most common form of cardiovascular disease, also have a diagnosis of major depression. Yet the biological relationship between the two conditions remains poorly understood.
A possible connection is inflammation. Changes in the levels of inflammatory markers have been observed in both conditions, suggesting that there may be a common biological pathway linking neuroinflammation in depression with atherosclerotic inflammation in CAD.
In the current study, the researchers used a technique called transcriptome-wide association scans to map single nucleotide polymorphisms (genetic variations) involved in regulating the expression of genes associated with both CAD and depression.
The technique identified 185 genes that were significantly associated with both depression and CAD, and which were “enriched” for biological roles in inflammation and cardiomyopathy.
This suggests that predisposition to both depression and CAD, which the researchers called (major) depressive CAD, or (m)dCAD, may further predispose individuals to cardiomyopathy.
However, when the researchers scanned large electronic health record databases at VUMC, Mass General, and the National Institutes of Health’s All of Us Research Program, they found the actual incidence of cardiomyopathy in patients with the enriched genes for (m)dCAD was lower than in patients with CAD alone.
One possible explanation is that medications prescribed for CAD and depression, such as statins and antidepressants, may prevent development of cardiomyopathy by reducing inflammation, the researchers concluded.
“More research is needed to investigate optimal treatment mechanisms,” Davis added, “but at a minimum this work suggests that patient heart and brain health should be considered together when developing management plans to treat depression or cardiovascular disease.”
Withdrawing aspirin one month after percutaneous coronary intervention (PCI) in high-risk heart patients and keeping them on ticagrelor alone safely improves outcomes and reduces major bleeding by more than half when compared to patients taking aspirin and ticagrelor combined (also known as dual antiplatelet therapy or DAPT), which is the current standard of care.
These are the results from the ULTIMATE-DAPT study announced during a late-breaking trial presentation at the American College of Cardiology Scientific Sessions on Sunday, April 7, and published in The Lancet.
This is the first and only trial to test high-risk patients with recent or threatened heart attack (acute coronary artery syndromes, or ACS) taking ticagrelor with a placebo starting one month after PCI, and compare them with ACS patients taking ticagrelor with aspirin over the same period. The significant findings could change the current guidelines for standard of care worldwide.
“Our study has demonstrated that withdrawing aspirin in patients with recent ACS one month after PCI is beneficial by reducing major and minor bleeding through one year by more than 50 percent. Moreover, there was no increase in adverse ischaemic events, meaning continuing aspirin was causing harm without providing any benefit,” says Gregg W. Stone, MD, the study co-chair of ULTIMATE-DAPT, who presented the trial results.
“It is my belief that it’s time to change the guidelines and standard clinical practice such that we no longer treat most ACS patients with dual antiplatelet therapy beyond one month after a successful PCI procedure. Treating these high-risk patients with a single potent platelet inhibitor such as ticagrelor will improve prognosis,” adds Dr Stone.
The study analysed 3400 patients with ACS at 58 centres in four countries between August 2019 and October 2022. All of the patients had undergone PCI, a non-surgical procedure in which interventional cardiologists use a catheter to place stents in the blocked coronary arteries to restore blood flow. The patients were stable one month after PCI and were on ticagrelor and aspirin. Researchers randomised the patients after one month, withdrawing aspirin in 1700 patients and putting them on ticagrelor and a placebo, while leaving the other 1700 patients on ticagrelor and aspirin. All patients were evaluated between 1 and 12 months after the procedure.
During the study period, 35 patients in the ticagrelor-placebo group had a major or minor bleeding event, compared to 78 patients in the ticagrelor-aspirin group, meaning that the incidence of overall bleeding incidents was reduced by 55 percent by withdrawing aspirin. The study also analysed major adverse cardiac and cerebrovascular events including death, heart attack, stroke, bypass graft surgery, or repeat PCI. These events occurred in 61 patients in the ticagrelor-placebo group compared to 63 patients in the ticagrelor-aspirin group, and were not statistically significant – further demonstrating that removing aspirin did no harm and improved outcomes.
“It was previously believed that discontinuing dual antiplatelet therapy within one year after PCI in patients with ACS would increase the risk of heart attack and other ischaemic complications, but the present study shows that is not the case, with contemporary drug-eluting stents now used in all PCI procedures. Discontinuing aspirin in patients with a recent or threatened heart attack who are stable one month after PCI is safe and, by decreasing serious bleeding, improves outcomes,” Dr Stone adds. “This study extends the results of prior work that showed similar results but without the quality of using a placebo, which eliminates bias from the study.”
Researchers have developed a new catheter-based device that combines two powerful optical techniques to image atherosclerotic plaques that can build up inside the heart’s coronary arteries. By providing new details about plaque, the device could help clinicians and researchers improve treatments for preventing heart attacks and strokes.
“Atherosclerosis, leading to heart attacks and strokes, is the number one cause of death in Western societies – exceeding all combined cancer types – and, therefore, a major public health issue,” said research team member leader Laura Marcu from University of California, Davis. “Better clinical management made possible by advanced intravascular imaging tools will benefit patients by providing more accurate information to help cardiologists tailor treatment or by supporting the development of new therapies.”
In the Optica Publishing Group journal Biomedical Optics Express, researchers describe their new flexible device, which combines fluorescence lifetime imaging (FLIM) and polarisation-sensitive optical coherence tomography (PSOCT) to capture rich information about the composition, morphology and microstructure of atherosclerotic plaques. The work was a collaborative project with Brett Bouma and Martin Villiger, experts in OCT from the Wellman Center for Photomedicine at Massachusetts General Hospital.
“With further testing and development, our device could be used for longitudinal studies where intravascular imaging is obtained from the same patients at different timepoints, providing a picture of plaque evolution or response to therapeutic interventions,” said Julien Bec, first author of the paper. “This will be very valuable to better understand disease evolution, evaluate the efficacy of new drugs and treatments and guide stenting procedures used to restore normal blood flow.”
Gaining an unprecedented view
Most of what scientists know about how atherosclerosis forms and develops over time comes from histopathology studies of postmortem coronary specimens. Although the development of imaging systems such as intravascular ultrasound and intravascular OCT has made it possible to study plaques in living patients, there is still a need for improved methods and tools to investigate and characterise atherosclerosis.
To address this need, the researchers embarked on a multi-year research project to develop and validate multispectral FLIM as an intravascular imaging modality. FLIM can provide insights into features such as the composition of the extracellular matrix, the presence of inflammation and the degree of calcification inside an artery. In earlier work, they combined FLIM with intravascular ultrasound, and in this new work they combined it with PSOCT. PSOCT provides high-resolution morphological information along with birefringence and depolarisation measurements. When used together, FLIM and PSOCT provide an unprecedented amount of information on plaque morphology, microstructure and biochemical composition.
“Birefringence provides information about the plaque collagen, a key structural protein that helps with lesion stabilization, and depolarisation is related to lipid content that contributes to plaque destabilization,” said Bec. “Holistically, this hybrid approach can provide the most detailed picture of plaque characteristics of all intravascular imaging modalities reported to date.”
Getting two imaging modalities into one device
The development of multimodal intravascular imaging systems compatible with coronary catheterisation is technologically challenging. It requires flexible catheters < 1mm diameter that can operate in vessels with sharp twists and turns. A high imaging speed of around 100 frames/second is also necessary to limit cardiac motion artefacts and ensure proper imaging inside an artery.
To integrate FLIM and PSOCT into a single device without compromising the performance of either imaging modality, the researchers used optical components previously developed by Marcu’s lab and other research groups. Key to achieving high PSOCT performance was a newly designed rotary collimator with high light throughput and a high return loss, ie the ratio of power reflected back toward the light source compared to the power incident on the device. The catheter system they developed has similar dimensions and flexibility as the intravascular imaging devices that are currently in clinical use.
After testing the new system with artificial tissue to demonstrate basic functionality on well characterized samples, the researchers also showed that it could be used to measure properties of a healthy coronary artery removed from a pig. Finally, in vivo testing in swine hearts demonstrated that the hybrid catheter system’s performance was sufficient to support work toward clinical validation. These tests all showed that the FLIM-PSOCT catheter system could simultaneously acquire co-registered FLIM data over four distinct spectral bands and PSOCT backscattered intensity, birefringence and depolarization information.
Next, the researchers plan to use the intravascular imaging system to image plaques in ex vivo human coronary arteries. By comparing the optical signals acquired using the system with plaque characteristics identified by expert pathologists, they can better understand which features can be identified by FLIM-PSOCT and use this to develop prediction models. They also plan to move forward with testing in support of clinical validation of the system in patients.
University of Virginia Health researchers probing the causes of coronary artery disease have identified why blood vessel lining, which usually secure plaques to stop them drifting, sometimes instead contribute to plaque buildup. The discovery, published in Circulation: Genomic and Precision Medicine, provides new targets for scientists looking for better ways to treat and prevent the disease.
“Smooth muscle cells that make up the bulk of our blood vessels play important roles in coronary artery disease. They undergo pathological transformations as the disease develops inside our arteries,” said researcher Mete Civelek, of the University of Virginia School of Medicine’s Center for Public Health Genomics and the Department of Biomedical Engineering.
“Our results point to a previously underappreciated role for metabolic pathways during this pathological transformation,” he said.
Civelek and his team wanted to unravel a longstanding mystery about the behaviour of smooth muscle cells during plaque formation. These cells, which line blood vessels, protect the body during plaque formation by building stabilising caps over the plaque that prevent the lesions from breaking loose and causing strokes.
But sometimes smooth muscle cells begin to accelerate the plaque development and spur the progression of the disease, scientists believe.
Civelek’s new discovery helps explain why. Noah Perry, a doctoral student on Civelek’s team, analysed smooth muscle cells collected from 151 heart transplant donors and used a sophisticated approach to identify genes responsible for the smooth muscle cells’ behaviour.
After initially identifying 86 groups of genes, the researchers focused in on 18 groups that could explain the mysterious behaviour. Their analysis suggested that the smooth muscle cells’ shift might stem from problems with how the cells use nitrogen and glycogen.
The researchers identified a particular sugar, mannose, that may be contributing to the problems, potentially even triggering them. But determining that, the scientists say, will require more research.
“The metabolic shift in the cells as they transition to a disease state can point to points of intervention and therapy,” said Perry, of UVA’s Department of Biomedical Engineering, the lead author of the study.
By better understanding what triggers the smooth muscle cells to become harmful, Civelek says, doctors may be able to develop ways to prevent that from happening. That could open the door to new ways to treat and prevent coronary artery disease.
“Coronary artery disease is still the leading cause of death worldwide,” Civelek said. “Although cholesterol-lowering therapies and blood pressure control have been very effective tools to prevent deaths from heart attacks, we still need more targets to reduce the suffering of patients and their families from this devastating disease.”
A clinical trial found that cardiac computed tomography (CT) offers similar diagnostic accuracy to catheterisation – the current standard diagnostic test for intermediate-risk patients – in people with suspected coronary artery disease, as well as being associated with a lower risk of complications. The trial’s findings were published in the New England Journal of Medicine.
The current standard diagnostic test for coronary artery disease (CAD) is coronary angiography (often along with cardiac catheterisation). This minimally invasive procedure uses dye marker visible on X-ray imaging to detect arterial narrowing. Any narrowing detected in this manner can be treated during the procedure itself using stents, which prop open the newly widened blood vessels. More than 3.5 million of these procedures are carried out in European catheterisation laboratories every year, and more are carried out every year. Approximately two million of these do not involve immediate treatment in the cath lab. In these cases, the procedure is able to rule out narrowed or blocked coronary arteries.
The main question addressed by the DISCHARGE Trial Group was whether the low-risk, non-invasive coronary CT method can provide a safe alternative to catheterization in certain patients with suspected CAD. In order to test the effectiveness of both of these diagnostic imaging techniques in patients with stable chest pain, the project followed more than 3500 patients for a duration of four years. Patients were randomised to either computed tomography or cardiac catheterisation. If their initial evaluation ruled out obstructive coronary artery disease, participants were discharged back to their referring physician for further treatment – a step which gave the trial its name: DISCHARGE. Patients who were diagnosed as having the disease were managed in accordance with European guidelines at the time of the study.
Discussing the long-term results, trial leader Professor Dr Marc Dewey said: “The trial confirmed that a CT-based management is safe in patients with stable (ie, non-acute) chest pain and suspected coronary artery disease.”
Evaluation of safety was based on the incidence of major cardiovascular events over a period of up to four years. He added: “Among the patients referred for cardiac catheterisation and included in this trial, the risk of major adverse cardiovascular events was found to be similar in both the CT and catheterisation groups, occurring in 2.1% and 3.0% of patients, respectively. The incidence of major procedure-related complications was found to be four-times lower in patients managed with an initial CT strategy.”
Other outcome measures were included in the DISCHARGE trial, such as improvements in chest pain and quality of life over the course of the trial. This new strategy could help relieve pressure on health care systems by helping to reduce the volume of catheterisation procedures. Prof Dewey said: “Now that CT has been standardised and quality-tested as part of the DISCHARGE trial, this method could be made more widely available as part of the routine clinical care of people with intermediate CAD risk.”
As a next step, the trial’s method for estimating a person’s clinical risk of having coronary artery disease will need to be further evaluated to determine whether it can improve referral and indication for CT in routine clinical care. Health economics are an important component in making decisions about reimbursement in health care systems. As mentioned in the discussion of the publication, further methodologically very rigorous cost-effectiveness analyses of CT and cardiac catheterisation are necessary and will be conducted by the DISCHARGE Trial Group.
