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Maintaining weight loss with regular exercise rather than the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide, a drug used to treat type 2 diabetes and obesity, seems to reduce atherosclerosis development in adults with obesity-a leading underlying cause of cardiovascular disease.

The study of adults with obesity but not diabetes is by researchers from the University of Copenhagen, Denmark, and is presented at this year’s Annual Meeting of The European Association for the Study of Diabetes (EASD), Vienna (15-19 Sept).

Our findings reveal that regular exercise is crucial to helping people living with obesity get the full cardiovascular benefits after a substantial weight loss.”

Dr. Rasmus Sandsdal, Study Lead Author, University of Copenhagen, Denmark

Cardiovascular disease is the leading cause of death worldwide and often originates in atherosclerosis, a chronic condition in which inflammation and fat deposits cause arteries to harden and narrow. Over time, plaques can rupture, causing serious complications such as heart attacks and strokes.

Obesity causes chronic low-grade inflammation, which can lead to endothelial dysfunction (a condition in which the blood vessels become unable to contract and relax adequately and the development of atherosclerosis.

Both exercise and GLP-1RAs have been shown to reduce the obesity-associated risk of cardiovascular events like heart failure and heart attacks, but little is known about their impact on the development of atherosclerosis during weight loss maintenance.

To explore this further, Danish researchers conducted a randomised placebo-controlled trial involving 215 adults (aged 18-65 years; 63% female) living with obesity (BMI 32-43 kg/m²) who did not have diabetes or other serious chronic disease at the start of the trial.

Initially, participants were asked to adhere to a low-calorie diet of 800 kcal per day (Cambridge Weight Plan) for 8 weeks. The 195 participants who had lost at least 5% of their body weight (average reduction in body weight of 12%/13.1 kg) were randomly assigned for 1 year to one of four weight maintenance strategies: moderate-to-vigorous-intensity exercise 150 min/week plus placebo; treatment with liraglutide (3.0 mg per day); combination of exercise 150 min/week and liraglutide; or placebo.

Blood levels of inflammatory biomarkers interleukin-6 [IL-6] and interferon-γ [IFN-γ] and biomarkers of endothelial function (intercellular adhesion molecule [ICAM-1], vascular adhesion molecule [VCAM-1], and tissue plasminogen activator [tPA]) were measured at the start of the low-calorie diet, the start of the weight maintenance period, and after one year. Participants also had an ultrasound of the carotid artery to measure intima-media thickness [cIMT].

After the 1-year weight maintenance period, both exercising participants and those undergoing liraglutide treatment maintained weight loss.

Nevertheless, the study found that participants who followed an exercise programme (with or without treatment with liraglutide) had lower levels of inflammatory biomarkers compared with non-exercising participants (with an average IL-6 level 21% lower and an IFN-γ level 27% lower).

Exercising also had a favourable impact on biomarkers of endothelial function (with an average 6% drop in VCAM-1, an 8% drop in ICAM-1, and a 12% decrease in tPA) compared to non-exercising participants, and reduced carotid artery thickness (average -0.024 mm).

Interestingly, no differences were noted in inflammatory or endothelial function biomarkers or carotid artery thickness between participants treated with liraglutide and those not taking the drug.

“Regular exercise seems to confer a protective effect against the development of atherosclerosis in people trying to maintain weight loss. Since both exercise and GLP-1RA treatment were successful at keeping weight off, it seems that exercise plays an important role in mitigating cardiovascular risk factors in a weight-independent manner,” said Dr Sandsdal.

Exercise benefits health in numerous ways, including improving body composition and increasing cardiorespiratory fitness. These benefits collectively contribute to improved cardiometabolic health.

“The most important message from our findings is that, for those trying to maintain weight loss, exercise is crucial in improving long-term health,” said corresponding author Professor Signe Sørensen Torekov from the University of Copenhagen. “Given the substantial societal and economic costs of obesity-related cardiovascular disease, these findings underscore regular exercise as a critical component of weight management and heart health.”

The study had some limitations, including the small sample size and that performing the structured exercise program outside the support of this trial, in free living conditions, might reduce individual adherence. The researchers note that future research should investigate the combined effects of adherent exercise and newer GLP-1RAs for treatment periods longer than one year.

A new machine learning model developed by The George Institute for Global Health can successfully predict heart disease risk in women by analyzing mammograms. The findings were published today in Heart, the official journal of the British Cardiovascular Society.

Developed in collaboration with the University of New South Wales and University of Sydney, this is the first deep learning algorithm based on only mammographic features and age to predict major cardiac events with comparable accuracy to traditional cardiovascular risk calculators.

Associate Professor Clare Arnott, Global Director of the Cardiovascular Program at The George Institute said that new ways to identify women at risk of cardiovascular disease (CVD) were needed, given that many women are not accessing or being offered CV risk screening in the community.

“It’s a common misconception that CVD predominantly affects men, resulting in underdiagnosis and undertreatment of the condition in women. By integrating CV risk screening with breast screening through the use of mammograms – something many women already engage with at a stage in life when their cardiovascular risk increases – we can identify and potentially prevent two major causes of illness and death at the same time.”

The model was designed and validated using routine mammograms from over 49,000 women in metropolitan and rural areas of Victoria, Australia, linked to individual hospital and death records. Researchers then compared the model to traditional models that require multiple data points based on known CV risk factors such as blood pressure and cholesterol.

“We found that our model performed just as well without the need for extensive clinical and medical data,” said A/Prof Arnott.

Previous research to date has focused on certain mammographic features such as breast arterial calcification (BAC), which has been found to be associated with cardiovascular risk in some populations. Relying on BAC alone, however, has limitations. For example, BAC is less accurate at predicting CVD risk in older women.

Our model is the first to use a range of features from mammographic images combined simply with age – a key advantage of this approach being that it doesn’t require additional history taking or medical record data, making it less resource intensive to implement, but still highly accurate.”

Clare Arnott, Global Director, Cardiovascular Program, The George Institute

Globally, cardiovascular disease is the leading cause of mortality in women, amounting to around 9 million deaths annually, or approximately one third of all deaths in women. Despite the high burden of disease, multiple studies internationally have shown that cardiovascular disease symptoms and risk factors are under-considered in women, leading to fewer diagnostic tests, specialist referrals and prescriptions in women compared to men.

Conversely, mammography-based screening programs have engaged women very effectively in some countries, with more than 67% of women in the United States and the United Kingdom participating in screening mammography.

Dr Jennifer Barraclough, Research Fellow at The George Institute, said that leveraging an existing risk screening process already widely utilized by women, means this model could serve as a cardiovascular risk prediction tool for women in diverse communities across Australia and around the world. 

“We hope this technology will one day provide greater, and more equitable access to screening in rural areas, as many women already benefit from mobile mammography units free of charge,” she said.

“We have shown the potential of this innovative new screening tool, so we now look forward to testing the model in additional, diverse, populations and understanding potential barriers to its implementation.”

A bout of the common bladder infection, cystitis, may signal the presence of urogenital cancers-which affect parts of the body involved in reproduction and excretion-in middle aged adults, suggests research published in the open access journal BMJ Public Health. 

The risks seem to be especially high within 3 months of infection, suggesting that acute cystitis might be a useful clinical marker for urogenital cancer, say the researchers. Men seem to be at greater risk than women, the findings indicate.

The lifetime prevalence of a urinary tract infection (UTI) is 50–60% in women and 13–14% in men. With the exception of a spike in young women, incidence rates of UTIs increase with age in both men and women, note the researchers.

Previously published research has shown that a bout of cystitis might be linked to an increased risk of urogenital cancers, but only a few such studies have been published and they didn’t include data from primary care facilities, which is where most cases of acute cystitis are diagnosed, they explain.

To try and plug this knowledge gap, the researchers mined several comprehensive national population and health registers and primary healthcare data sources, containing individual-level information on all people living in Sweden from 1997 to the end of 2018.

Data were available for 1,668,371 (47%) men and 1,889,211 (53%) women during this period, of whom 605,557 (17%) people were diagnosed with acute cystitis for the first time. 

Most of these diagnoses (91%) were made in primary care facilities and most cases were in women (71%; 427,821). 

During an average monitoring period of 15 years, a total of 257,026 (just over 7%) people were diagnosed with urogenital cancer, most of whom were men (77.5%; 199,144).

The average age at cancer diagnosis was 73, with prostate cancer the most common cancer type (62%), followed by bladder cancer (16.5%), and endometrial (lining of the womb) cancer (10%).

Cystitis preceded a cancer diagnosis in 24,137 people–almost 9.5% of all those diagnosed with cancer during the study period. Their average age at diagnosis was 76: prostate cancer was the most common diagnosis (39.5%), followed by bladder (32%), and endometrial (14%) cancer. 

The risks of a urogenital cancer diagnosis were heightened across all age groups among those who had had a bout of cystitis, and peaked within 3 months of infection, especially for prostate and bladder cancers, but persisted over several years for most cancers. 

For prostate cancer, the risk, measured as a standardized incidence ratio (SIR) within 3 months of infection was 7 times higher in those who had had the infection than it was in those who hadn’t. 

This corresponds to an excess cancer rate of nearly 551 per 10, 000 person-years–a unit of measurement that combines the number of people and the time during which they were observed. For example, 10,000 patients monitored for 1 year or 1000 patients monitored for 10 years.

Similarly, the risk of bladder cancer was 3.5 times higher in men and more than 3 times higher in women who had had cystitis than it was in those who didn’t have the infection during the monitoring period. This corresponds to an excess rate of around 40 and nearly 8 more cancer cases, respectively, than would be expected per /10,000 person-years.

For gynecologic cancers, the SIRs within 3 months of infection were between 4 and 8 times higher among women who had had cystitis. 

Overall, the risk of urogenital cancer was nearly 34 times higher in men and 30 times higher in women, within 3 months of infection, corresponding to nearly 484 and 96 excess cancer rates/10,000 person-years, respectively.

While the risks fell as time went on, they persisted throughout all the follow-up periods for both sexes. For example, 3–12 months after infection, the excess cancer rates/10,000 person-years were more than 79 in men and more than 19 in women. And after 5 years, these were around 9 in men and 2.5 in women.

In general, men who had had cystitis seemed to be at higher risk of urogenital cancer than women: for example, their risk of bladder cancer was twice as high for those in their 50s, 57% higher for those in their 60s, and 23% higher for those in their 70s.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. And the researchers acknowledge that they lacked microbiological confirmation of cystitis infection or information on potentially influential factors, such smoking and underlying conditions, including obesity and undiagnosed diabetes.

But they say: “The present study adds to the accumulating evidence of infections as markers of increased cancer risk. For clinicians, the findings indicate that acute cystitis could be a clinical marker for urogenital cancer (at least when no other cause is obvious), and particularly for occult urogenital cancer, as the risks for cancers were highest within 3 months of cystitis diagnosis.” 

They add: “It is plausible that urogenital cancer, and perhaps even pre-cancerous changes in the urogenital organs, might increase the risk of cystitis because of compromised urinary tract and host defence.”