Despite clinicians recommending that many patients with diabetes take statins, nearly one in five opt to delay treatment. In a new study, researchers from Mass General Brigham found that patients who started statin therapy right away reduced the rate of heart attack and stroke by one third compared to those who chose to delay taking the medication. The results, which can help guide decision-making conversations between clinicians and their patients, are published in the Journal of the American Heart Association.
“I see patients with diabetes on a regular basis, and I recommend statin therapy to everyone who is eligible,” said senior author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “Some people refuse because they want to first try lifestyle interventions or other drugs. But other interventions are not as effective at lowering cholesterol as starting statin therapy as soon as possible. Time is of the essence for your heart and brain health.”
Heart attacks and strokes remain the leading cause of complications and mortality for patients with diabetes. Statin therapy reduces risk of these cardiovascular events by preventing plaque buildup in the blood vessels.
The researchers used an artificial intelligence method called Natural Language Processing to gather data from the electronic health records of 7239 patients at Mass General Brigham who ultimately started statin therapy during the nearly 20-year study period. The median patient age was 55, with 51% being women, 57% white, and a median HbA1c of 6.9.
Nearly one-fifth (17.7%) of the patients in the study declined statin therapy when it was first recommended by their clinicians, then later accepted the therapy (after a median of 1.5 years) upon repeated recommendation by their clinician. Of those who delayed, 8.5% had a heart attack or stroke. But for patients who started statins immediately, the rate of those cardiovascular events was just 6.4%.
“Clinicians should recognize the increased cardiovascular risk associated with delaying statin therapy for patients with diabetes and use this information to guide shared decision-making conversations with their patients,” said Turchin.
People with a certain heart valve abnormality, mitral annular disjunction, are at increased risk of severe heart rhythm disorders, even after successful valve surgery. This is according to a new study from Karolinska Institutet and Karolinska University Hospital in Sweden published in the European Heart Journal. The condition is more common in women and younger patients with valve disorder and can, in the worst case, lead to sudden cardiac arrest.
Mitral annular disjunction, MAD, is a heart abnormality in which the mitral valve attachment ‘slides’. In recent years, the condition has been linked to an increased risk of severe cardiac arrhythmias. Until now, it has not been known whether the risk of arrhythmias disappears if MAD is surgically corrected.
MAD is often associated with a heart disease called mitral valve prolapse, which affects 2.5% of the population and causes one of the heart’s valves to leak. This can lead to blood being pumped backwards in the heart, causing heart failure and arrhythmias. The disease can cause symptoms such as shortness of breath and palpitations.
Followed patients after surgery
In the current study, researchers at Karolinska Institutet investigated the risk of cardiac arrhythmias in 599 patients with mitral valve prolapse who underwent heart surgery at Karolinska University Hospital between 2010 and 2022. Sixteen percent of the patients also had the cardiac abnormality MAD.
“We have been able to show that people with MAD have a significantly higher risk of suffering from ventricular arrhythmias, a dangerous type of heart rhythm disorder that in the worst case can lead to cardiac arrest in a subset of patients,” says Bahira Shahim, associate professor at the Department of Medicine, Solna, Karolinska Institutet and cardiologist at Karolinska University Hospital
People with MAD were more likely to be female and were on average eight years younger than those without MAD. They also had more extensive mitral valve disease. Although the surgery was successful in correcting MAD, these patients had more than three times the risk of ventricular arrhythmias during five years of follow-up compared to patients without preoperative MAD.
“Our results show that it is important to closely monitor patients with this condition, even after a successful operation,” says Bahira Shahim.
Investigating new hypotheses
The study has led to new hypotheses that the researchers are now investigating further. One hypothesis is that MAD causes permanent changes in the heart muscle over time. Another is that MAD is a sign of an underlying heart muscle disease. The researchers are now continuing to study scarring in the heart using MRI (magnetic resonance imaging) and analyse tissue samples from the heart muscle.
A newly published study from the University of Waterloo suggests that increasing the ratio of dietary potassium to sodium intake may be more effective for lowering blood pressure than simply reducing sodium intake.
“Usually, when we have high blood pressure, we are advised to eat less salt,” said Dr Anita Layton, professor at the University of Waterloo. “Our research suggests that adding more potassium-rich foods to your diet, such as bananas or broccoli, might have a greater positive impact on your blood pressure than just cutting sodium.”
Potassium and sodium are both electrolytes – substances that help the body send electrical signals to contract muscles, affect the amount of water in your body and perform other essential functions.
“Early humans ate lots of fruits and vegetables, and as a result, our body’s regulatory systems may have evolved to work best with a high potassium, low sodium diet,” said Melissa Stadt, a PhD candidate in Waterloo’s Department of Applied Mathematics and the lead author of the study.
“Today, western diets tend to be much higher in sodium and lower in potassium. That may explain why high blood pressure is found mainly in industrialised societies, not in isolated societies.”
While previous research found that increasing potassium intake can help control blood pressure, the researchers developed a mathematical model that successfully identifies how the ratio of potassium to sodium impacts the body.
The model also identifies how sex differences affect the relationship between potassium and blood pressure. The study found that men develop high blood pressure more easily than pre-menopausal women, but men are also more likely to respond positively to an increased ratio of potassium to sodium.
The researchers emphasise that mathematical models like the one used in this study allow these kinds of experiments to identify how different factors impact the body quickly, cheaply, and ethically.
Deciding whether to start hormone therapy during the menopause transition, the life phase that’s the bookend to puberty and when a woman’s menstrual cycle stops, is a hotly debated topic. While hormone therapy is recommended to manage bothersome symptoms like hot flashes and night sweats, Matthew Nudy, assistant professor of medicine at the Penn State College of Medicine, said there’s confusion about the long-term effects of hormone therapy, especially on cardiovascular health.
However, long-term use of oestrogen-based hormone therapies may have beneficial effects on heart health, according to a new study led by Nudy. A multi-institutional team analysed data from hormone therapy clinical trials that were part of the Women’s Health Initiative (WHI), a long-term national study focused on menopausal women, and found that oestrogen-based hormone therapy improved biomarkers associated with cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attack and stroke.
“The pendulum has been swinging back and forth as to whether hormone therapy is safe for menopausal women, especially from a cardiovascular disease perspective,” Nudy said. “More recently, we’re recognising that hormone therapy is safe in younger menopausal women within 10 years of menopause onset, who are generally healthy and who have no known cardiovascular disease.”
The hormonal changes that accompany menopause come with an increased risk of cardiovascular disease. The decline in the oestrogen can lead to changes in cholesterol, blood pressure and plaque buildup in blood vessels, which increase the risk of heart attack and stroke.
The research team was interested in understanding the long-term effect of hormone therapy on cardiovascular biomarkers, which hasn’t been evaluated over an extended period of time. Prior research in the field primarily looked at short-term effects.
Here, the team analysed biomarkers associated with cardiovascular health over a six-year period from a subset of women who had participated in an oral hormone therapy clinical trial that was part of the WHI. Post-menopausal participants aged 50 to 79 were randomly assigned to one of two groups, an oestrogen-only group and an oestrogen plus progesterone group. They provided blood samples at baseline and at the one-, three- and six-years marks. In total, they analysed samples from 2696 women, approximately 10% of the total trial participants.
The research team found that hormone therapy had a beneficial effect on most biomarkers in both the oestrogen-only and the oestrogen-plus-progesterone groups over time. Levels of LDL cholesterol, the so-called “bad” cholesterol, were reduced by approximately 11% while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% and 7% for the oestrogen-only and oestrogen-and-progesterone groups, respectively.
However, triglycerides and coagulation factors, proteins in the blood that help form blood clots, increased.
The decrease in lipoprotein(a) concentration was more pronounced among participants with American Indian or Alaska Native ancestry or Asian or Pacific Islander ancestry, by 41% and 38%, respectively. The reason why was unclear, Nudy said.
More surprising to the research team, they said, levels of lipoprotein(a), a type of cholesterol molecule, decreased 15% and 20% in the oestrogen-only and the oestrogen-plus-progesterone groups, respectively. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, concentrations of lipoprotein(a) are thought to be determined primarily by genetics, Nudy explained. Patients with a high lipoprotein(a) concentration have an increased risk of heart attack and stroke, especially at a younger age. There’s also an increased risk of aortic stenosis, where calcium builds up on a heart valve.
“As a cardiologist, this finding is the most interesting aspect of this research,” Nudy said. “Currently, there are no medications approved by the Food and Drug Administration (FDA) to lower lipoprotein(a). Here, we essentially found that oral hormone therapy significantly reduced lipoprotein(a) concentrations over the long-term.”
Nudy noted that the oestrogen therapy the women received in the clinical trial was conjugated equine oestrogens, a commonly prescribed form of oral oestrogen therapy. Before being absorbed by the body, oral hormone therapy is processed in the liver, through a process called first-pass metabolism. That process could increase inflammatory markers, which may explain the rise in triglycerides and coagulation factors.
“There are now other common formulations of oestrogen hormone therapy like transdermal oestrogen, which is administered through the skin,” Nudy said. “Newer studies have found that transdermal oestrogen doesn’t increase triglycerides, coagulation factors or inflammatory markers.”
For those considering menopause hormone therapy, Nudy recommended undergoing a cardiovascular disease risk assessment, even if the person hasn’t had a previous heart attack or stroke or hasn’t been diagnosed with cardiovascular disease. It will give health care providers more information when considering the best option to treat menopause symptoms.
“Currently, hormone therapy is not FDA-approved to reduce the risk of coronary artery disease or stroke,” Nudy said.
Right side heart failure. Credit: Scientific Animations CC4.0
People with type 2 diabetes (DM2) are at increased risk of developing heart failure due to the presence of prominent risk factors (hypertension, obesity, coronary heart disease, etc).
Now, a study published in the journal Cellular and Molecular Life Sciences has identified a new factor linked to the development of pathological hypertrophy. The results of the study suggest that increasing the activity of the GADD45A protein could be a promising therapeutic strategy to slow the progression of this clinical condition.
A factor with a prominent role in cardiac function
The GADD45A (growth arrest and DNA damage inducible 45A) protein is a multifunctional factor associated with stress signalling and cell damage. In this study, the team assessed the role of GADD45A in cardiac function using animal models and human cardiac cells.
The main mechanisms involved in pathological hypertrophy include inflammatory processes, fibrosis, mitochondrial dysfunction, dysregulation of calcium-handling proteins, metabolic alterations, cardiomyocyte hypertrophy and cell death. Fibrosis and inflammation are key factors in the progression of this pathological cardiac hypertrophy and subsequent heart failure.
“Fibrosis, in particular, correlates directly with the development of the disease and with adverse clinical outcomes, and has a major impact on the clinical condition of the patient”, says study leader Professor Manuel Vázquez-Carrera.
The results reveal that the lack of GADD45A factor in mice triggers cardiac fibrosis, inflammation and apoptosis. These changes correlate with hyperactivation of the proinflammatory and profibrotic transcription factors AP-1 (activator protein-1), NF-κB (nuclear factor-κB) and STAT3 (signal transducer and activator of transcription 3).
According to the findings, deletion of GADD45A also caused substantial cardiac hypertrophy that negatively affected cardiac morphology and function in mice lacking this protein. Furthermore, overexpression of GADD45A in human AC16 cardiomyocytes partially prevented the inflammatory and fibrotic response induced by tumour necrosis factor-alpha (TNF-α).
“Taken together, the data presented in this study highlight an important role for GADD45A protein in the heart, as it may prevent inflammation, fibrosis and apoptosis and thus preserve cardiac function”, says Associate Professor Xavier Palomer, who also led the study.
This paper expands our knowledge of the action mechanisms of GADD45A in the body. To date, previous studies have identified the role as a tumour suppressor in cancer development, as well as its involvement in the regulation of catabolic and anabolic metabolic pathways and in the prevention of inflammation, fibrosis and oxidative stress in some tissues and organs. Finally, some studies have indicated that the modulation of GADD45A could be a suitable therapeutic strategy to prevent obesity and diabetes.
A new study in the European Heart Journal shows that people who develop type 1 diabetes in adulthood have an increased risk of cardiovascular disease and death, and that those diagnosed later in life do not have a better prognosis than those diagnosed earlier. The study, conducted by researchers at Karolinska Institutet, points to modifiable factors – smoking, poor glucose control and obesity – as the main risk factors.
Type 1 diabetes used to be called childhood diabetes but can start at any time during life – a situation for which there is limited research. The researchers behind the current study wanted to investigate the risk of cardiovascular disease and death in this group, particularly for those diagnosed after the age of 40.
The registry-based study identified 10 184 people diagnosed with type 1 diabetes in adulthood between 2001 and 2020 and compared them to 509 172 matched people in the control group.
The study shows that these people with adult-onset type 1 diabetes had a higher risk of cardiovascular disease and death from all causes, including cancer and infections, compared to the control group.
“The main reasons for the poor prognosis are smoking, overweight/obesity and poor glucose control. We found that they were less likely to use assistive devices, such as insulin pumps,” says first author Yuxia Wei, postdoctoral fellow at the Institute of Environmental Medicine, Karolinska Institutet.
The prognosis can be improved
The results emphasise the seriousness of type 1 diabetes, even when it starts later in life, the researchers say. But the prognosis can improved by avoiding smoking and obesity, especially for those diagnosed later in life.
The researchers plan to continue investigating adult-onset type 1 diabetes, including risk factors for developing the disease and the prognosis of other outcomes, such as microvascular complications. Optimal treatment in adult-onset type 1 diabetes, including the effect of pump use and other advanced technologies, also needs to be explored.
Researchers from the University of Tokyo have found a way to observe clotting activity in blood as it happens – without needing invasive procedures. Using a new type of microscope and artificial intelligence (AI), their study shows how platelet clumping can be tracked in patients with coronary artery disease (CAD), opening the door to safer, more personalised treatment.
“Platelets play a crucial role in heart disease, especially in CAD, because they are directly involved in forming blood clots,” explained Dr Kazutoshi Hirose, an assistant professor at the University of Tokyo Hospital and lead author of the study in Nature Communications. “To prevent dangerous clots, patients with CAD are often treated with antiplatelet drugs. However, it’s still challenging to accurately evaluate how well these drugs are working in each individual, which makes monitoring platelet activity an important goal for both doctors and researchers.”
That challenge pushed Hirose and his collaborators to develop a new system for monitoring platelets in motion, using a high-speed optical device and artificial intelligence.
“We used an advanced device called a frequency-division multiplexed (FDM) microscope, which works like a super high-speed camera that takes sharp pictures of blood cells in flow,” said co-author Yuqi Zhou, an assistant professor of chemistry at the University of Tokyo . “Just like traffic cameras capture every car on the road, our microscope captures thousands of images of blood cells in motion every second. We then use artificial intelligence to analyse those images. The AI can tell whether it’s looking at a single platelet (like one car), a clump of platelets (like a traffic jam), or even a white blood cell tagging along (like a police car caught in the jam).”
The research team applied this technique to blood samples from over 200 patients. Their images revealed that patients with acute coronary syndrome had more platelet aggregates than those with chronic symptoms – supporting the idea that this technology can track clotting risk in real time.
“Part of my scientific curiosity comes from the recent advances in high-speed imaging and artificial intelligence, which have opened up new ways to observe and analyse blood cells in motion,” said Keisuke Goda, a professor of chemistry at the University of Tokyo who led the research team. “AI can ‘see’ patterns beyond what the human eye can detect.”
One of the most important findings was that a simple blood drawn from the arm – rather than from the heart’s arteries – provided nearly the same information.
“Typically, if doctors want to understand what’s happening in the arteries, especially the coronary arteries, they need to do invasive procedures, like inserting a catheter through the wrist or groin to collect blood,” said Hirose. “What we found is that just taking a regular blood sample from a vein in the arm can still provide meaningful information about platelet activity in the arteries. That’s exciting because it makes the process much easier, safer and more convenient.”
The long-term hope is that this technology will help doctors better personalise heart disease treatment.
“Just like some people need more or less of a painkiller depending on their body, we found that people respond differently to antiplatelet drugs. In fact, some patients are affected by recurrent thrombosis and others are suffering from recurrences of bleeding events even on the same antiplatelet medications,” said Hirose. “Our technology can help doctors see how each individual’s platelets are behaving in real time. That means treatments could be adjusted to better match each person’s needs.”
“Our study shows that even something as small as a blood cell can tell a big story about your health,” Zhou added.
People who sit or remain sedentary for more than 14 hours a day, on average, may have a higher risk of a cardiovascular event or death in the year after treatment at a hospital for symptoms of a heart attack such as chest pain, according to new research published today in the American Heart Association’s peer-reviewed scientific journal Circulation: Cardiovascular Quality and Outcomes.
Previous research from the study authors found that people who had experienced a heart attack were spending up to 12 to 13 hours each day being sedentary, defined as any awake activity that involved little-to-no physical movement. In this study, the researchers used a wrist accelerometer to track the amount of time each participant spent moving or being sedentary for a median of 30 days after discharge from a hospital’s emergency department.
Wrist accelerometers measure the acceleration of motion in three directions: forwards and backwards, side-to-side, and up and down. These measurements allowed the researchers to infer the intensity of a participant’s physical activity, and they provide more accurate measurements of the participants’ time spent moving, rather than asking participants to remember. Some examples of moderate intensity physical activities are brisk walking, water aerobics, dancing, playing doubles tennis or gardening, and examples of vigorous-intensity activities are running, lap swimming, heavy yardwork such as continuous digging or hoeing, playing singles tennis or jumping rope.
”Current treatment guidelines after a cardiac event focus mainly on encouraging patients to exercise regularly,” said study lead author Keith Diaz, Ph.D., the Florence Irving Associate Professor of Behavioral Medicine at Columbia University Medical Center in New York City, a certified exercise physiologist and a volunteer member of the American Heart Association’s Physical Activity Science Committee. “In our study, we explored whether sedentary time itself may contribute to cardiovascular risk.”
Researchers followed more than 600 adults, ages 21 to 96, treated for a heart attack or chest pain in the emergency department at a single hospital system in New York City. Participants wore a wrist accelerometer for a median of 30 consecutive days after hospital discharge to measure the amount of time they spent sitting or being inactive each day. Additional cardiac events and deaths were evaluated one year after hospital discharge via phone surveys with patients, electronic health records and the Social Security Death Index. The study was focused on understanding the risk of sedentary behavior and identifying modifiable risk factors that may improve long-term outcomes in this high-risk group.
The analysis found:
Compared to participants in the group with the highest physical activity level, those in the group with the lowest activity level had a 2.58 times higher risk of having another heart problem or dying within the next year.
Replacing 30 minutes of sedentary time with 30 minutes of moderate to vigorous physical activity, daily, reduced the risk of adverse cardiovascular events or death by 61%; replacing the sedentary time with light-intensity physical activity reduced risk by 50%; and replacing the sedentary time with 30 minutes of sleep lowered risk by 14%.
According to accelerometer data, participants in the most physically active group had average daily physical activity measures of 143.8 minutes of light physical activity; 25 minutes of moderate-to-vigorous physical activity; 11.7 hours spent sedentary; and 8.4 hours of sleep.
Participants in the least physically active group had daily averages of 82.2 minutes each day of light physical activity; 2.7 minutes of moderate-to-vigorous physical activity; 15.6 hours spent sedentary; and 6.6 hours of sleep.
Participants in the group between most and least physically active had daily averages of 109.2 minutes of light intensity physical activity; 11.4 minutes of moderate-to-vigorous intensity physical activity; 13.5 hours spent sedentary and 7.8 hours of sleep.
“We were surprised that replacing sedentary time with sleep also lowered risk. Sleep is a restorative behavior that helps the body and mind recover, which is especially important after a serious health event like a heart attack,” Diaz said. “Our study indicates that one doesn’t have to start running marathons after a cardiovascular event to see benefits. Sitting less and moving or sleeping a little more can make a real difference. More physical activity and more sleep are healthier than sitting, so we hope these findings support health professionals to move toward a more holistic, flexible and individualized approach for physical activity in patients after a heart attack or chest pain.”
Physical activity and sleep are both key components of the American Heart Association’s Life’s Essential 8, a list of health behaviours and factors that support optimal cardiovascular health. Poor sleep is a known risk factor for cardiovascular disease, which claims more lives each year in the U.S. than all forms of cancer and chronic lower respiratory disease combined, according to the American Heart Association’s 2025 Statistical Update. In addition to sleep duration, a recent scientific statement from the Association highlighted the importance of sleep continuity, sleep timing, sleep satisfaction, sleep regularity, sleep-related daytime functioning and sleep architecture in cardiometabolic health.
The study had several limitations, including that the definition of sedentary behaviour was based only on the intensity level of physical movement, meaning that the study may have overestimated the time participants spent in sedentary behaviour. Additionally, there was no information about participants’ income and characteristics of the neighbourhoods where they live, which limits the study’s ability to account for social and environmental factors, including participants’ risk of one-year cardiac events and deaths. Also, hospital discharge information about whether patients were sent home, referred to rehabilitation or referred to other care centres such as skilled nursing facilities were not collected. This limited the study’s ability to fully assess whether the patients’ settings had an impact on their recovery.
A new study led by researchers at Tulane University suggests that people with hypertension can significantly reduce, and possibly eliminate, their increased risk of premature death by controlling several key health risk factors at once.
The study, appearing in Precision Clinical Medicine, tracked more than 70 000 people with hypertension and over 224 000 without it, using data from the UK Biobank. Researchers followed participants for nearly 14 years to understand how managing these risk factors affected early mortality, defined as dying before age 80.
The eight health risk factors evaluated in the study include: blood pressure, body mass index, waist circumference, LDL “bad” cholesterol, blood sugar, kidney function, smoking status and physical activity. Notably, researchers found that hypertensive patients who had addressed at least four of these risk factors had no greater risk of an early death than those without hypertension.
“Our study shows that controlling blood pressure is not the only way to treat hypertensive patients, because high blood pressure can affect these other factors,” said corresponding author Dr Lu Qi, professor of epidemiology at Tulane University. “By addressing the individual risk factors, we can help prevent early death for those with hypertension.”
Hypertension, defined as a blood pressure of 130mmHg or higher, is the leading preventable risk factor for premature death worldwide.
The study found that addressing each additional risk factor was associated with a 13% lower risk of early death, 12% lower risk of early death due to cancer and 21% lower risk of death due to cardiovascular disease, the leading cause of premature death globally.
“Optimal risk control” – having 7 or more of the risk factors addressed – was linked to 40% less risk of early death, 39% less risk of early death due to cancer and 53% less risk of early death due to cardiovascular disease.
“To our knowledge, this is the first study to explore the association between controlling joint risk factors and premature mortality in patients with hypertension,” Qi said. “Importantly, we found that any hypertension-related excess risk of an early death could be entirely eliminated by addressing these risk factors.”
Only 7% of hypertensive participants in the study had seven or more risk factors under control, highlighting a major opportunity for prevention. Researchers say the findings underscore the importance of personalised, multifaceted care – not just prescribing medication for blood pressure, but addressing a broader range of health behaviours and conditions.
Many observational studies have shown that people who exercise more and have good cardiorespiratory fitness early in life are at lower risk of premature death from causes such as cancer and cardiovascular disease. But a new study published in the European Journal of Preventive Cardiology suggests that the association between physical fitness and a reduced risk of mortality may be misleading.
“We found that people with high fitness levels in late adolescence had a lower risk of dying prematurely, for example from cardiovascular disease, compared to those with low fitness levels. But when we looked at their risk of dying in random accidents, we found an almost similarly strong association. This suggests that people with high and low fitness levels may differ in other important ways, which is something that previous studies have not fully taken into account,” says Marcel Ballin, associated researcher in epidemiology and lead author of the study.
Conscription data from over 1 million men
In the study, the researchers leveraged data from 1.1 million Swedish men who were conscripted for military service between the years 1972 and 1995. The men, who were on average 18 years old at the time of conscription, were divided into five groups based on their fitness level at the time. They were then followed until their 60s or until they died. With access to the National Cause of Death Register, the researchers were able to see their cause of death. They subsequently used different methods to study the association between fitness level in late adolescence and premature death.
The researchers started with a traditional analysis of mortality from cardiovascular disease, cancer and from all causes, as in previous observational studies. They adjusted their statistical models for factors such as BMI, age at conscription, year of conscription, and parents’ income and education level. The results showed that the group with the highest fitness level had a 58% lower risk of dying from cardiovascular disease, a 31% lower risk of dying from cancer, and a 53% lower risk of dying from all causes, compared with the group with the lowest fitness level.
Very similar risk of dying in random accidents
Next, the researchers examined how fitness was associated with the risk of dying in random accidents such as car accidents, drownings and homicides. They chose random accidents because they assumed that there ought to be no association between the men’s fitness in late adolescence and the risk of dying in random accidents. This method is called negative control outcome analysis and involves testing the validity of your results for a primary outcome by comparing them with an outcome where no association ought to be found. If, however, an association is found, it may indicate that the groups studied are not actually comparable, and that the study suffers from what is typically referred to as confounding. The researchers found that men with the highest fitness levels had a 53% lower risk of dying in random accidents. Yet, it is unlikely that the men’s fitness would have such a big effect on their risk of dying in random accidents.
These results were also confirmed when the researchers used the sibling comparison design. Using this method, the researchers compared the risk of premature death between siblings with different fitness levels to control for all the factors that the siblings share such as behaviours, environmental factors, and some genetic factors.
“It surprised us that the association with accidental mortality reflected the other associations, even after we controlled for all the factors that siblings share. This underlines how strong the assumptions are that you make in observational studies, since it appears to be very difficult to create comparable groups. The consequences may be that you overestimate the magnitudes of the effects you find,” says Marcel Ballin.
Picture confirmed in other studies
The study is one of the largest of its kind in which researchers used negative control outcomes to investigate whether the associations between fitness and mortality are in fact valid. The results in this study are also supported by other research.
“That the effects of good cardiorespiratory fitness may be overstated might sound controversial to some, but the fact is that if you look at the results from studies others than traditional observational studies, a more nuanced picture does emerge. A number of twin studies for example have found similar results. Some genetic studies also suggest that there are genes that affect both the propensity to be physically active or have a good fitness level, and the risk of developing diseases such as cardiovascular disease.”
Important to base interventions on correct estimates
Marcel Ballin also argues that there are many different reasons for promoting physical activity. However, large-scale interventions or policy changes intended to apply to the entire population must be based on reliable estimates – otherwise there is a risk of expecting effects that have in fact been overestimated.
“Our results should not be interpreted as if physical activity and exercise are ineffective or that you should not try to promote it. But to create a more nuanced understanding of how big the effects of fitness actually are on different outcomes, we need to use several different methods. If we just ask the question in the same way, we will always get the same answer. It’s only when we get the same answer to a question that we have asked in slightly different ways that we can be sure that the findings are accurate,” says Marcel Ballin.
