Medical Bulletin 04/August/2025

"Cardiorespiratory fitness is a potent predictor of all-cause and cardiovascular mortality risk across a range of populations, including obesity, diabetes and heart failure," said Angadi, a cardiovascular exercise physiologist with UVA's Department of Kinesiology. "In a recent study by our group that examined mortality outcomes from almost 400,000 individuals across the world, we found that CRF was far superior to overweight or obesity status for predicting the risk of death. In fact, once CRF was factored in, body weight failed to predict the risk of mortality. This is why it's so important to understand the effects of this new class of drugs on it."

The authors recommend integrating exercise programs and proper nutrition alongside GLP-1 therapy to mitigate muscle loss and improve long-term outcomes. Until more solutions are available, the researchers stress the importance of patient-provider discussions on nutrition, physical activity, and regular screenings for malnutrition and muscle loss risk.

Reference: Zhenqi Liu, Nathan R Weeldreyer, Siddhartha S Angadi. Incretin Receptor Agonism, Fat-free Mass, and Cardiorespiratory Fitness: A Narrative Review. The Journal of Clinical Endocrinology & Metabolism, 2025; DOI: 10.1210/clinem/dgaf335

High-Potency Statins Found Most Effective in Lowering Bad Cholesterol: Study

New research published in Trends in Cardiovascular Medicine emphasizes the importance of aggressively lowering LDL cholesterol with high-dose statins to prevent and treat cardiovascular disease. In an invited editorial, experts from Florida Atlantic University’s Schmidt College of Medicine argue that potent statins like rosuvastatin and atorvastatin should be used as first-line pharmacologic therapies, alongside lifestyle interventions, to significantly reduce heart attack and stroke risks.

LDL, or low-density lipoprotein cholesterol, commonly known as "bad" cholesterol, is a major contributor to clogged arteries and cardiovascular events. Researchers analyzed a comprehensive body of randomized trial data and concluded that high-potency statins have the “strongest and most consistent body of evidence” for both prevention and treatment—across genders and age groups.

The authors, including senior author Dr. Charles H. Hennekens, highlighted the importance of starting treatment with maximum statin doses and reducing only if necessary. “Practicing cardiologists may wish to consider that all adjunctive drug therapies to therapeutic lifestyle changes should be added only after achieving maximal doses of statins,” said Hennekens.

While statins remain central, the editorial also underscores the continued value of lifestyle changes such as quitting smoking, maintaining a healthy weight, managing blood pressure, increasing physical activity, and limiting alcohol intake. However, many high-risk individuals remain underdiagnosed and undertreated.

The authors offered cautious support for adjunctive therapies like ezetimibe and evolocumab, noting these may benefit only select high-risk patients who don't reach LDL goals with statins alone. Similarly, they acknowledged mixed findings around omega-3 fatty acids, with icosapent ethyl being the only formulation to show significant benefit in modern trials such as REDUCE-IT.

In conclusion, the researchers advocate a prevention-first approach.

Reference: John Dunn, Charles H. Hennekens. Low density lipoprotein (LDL) and beyond in the treatment and prevention of cardiovascular disease. Trends in Cardiovascular Medicine, 2025; DOI: 10.1016/j.tcm.2025.07.005

How COVID-19 May Awaken Dormant Breast Cancer Cells?

A new study published in the journal Nature reveals that respiratory viruses such as COVID-19 and influenza can awaken dormant breast cancer cells in the lungs, potentially leading to cancer recurrence years after initial treatment.

Cancer recurrence remains a looming concern for survivors, even after remission. Researchers from Albert Einstein College of Medicine and Utrecht University investigated the impact of viral infections on dormant breast cancer cells—also known as disseminated cancer cells (DCCs)—in mice. These DCCs migrate from the primary tumor to distant organs like the lungs and remain inactive for years. But the study found that respiratory viruses can act as a trigger, reactivating these cells and leading to rapid tumor formation.

In the experiment, mice that had dormant breast cancer cells in their lungs were exposed to either SARS-CoV-2 or influenza. Within just two weeks, the previously resting cells had begun to proliferate, forming visible tumors. Scientists found that inflammation caused by viral infection played a key role. When the immune system fights off infections, it releases signaling proteins to coordinate its response. One of these proteins, interleukin-6, was identified as a major driver behind the reactivation of dormant cancer cells.

To test whether this finding held true in humans, researchers analyzed breast cancer patient databases. They discovered that survivors who contracted respiratory infections had a significantly increased risk of lung metastases within the first year post-infection. These findings align with early pandemic data showing a spike in cancer deaths and metastatic disease among survivors who had contracted COVID-19.

This research highlights the importance of monitoring cancer survivors more closely following respiratory illnesses, especially in the first year after infection.

Reference: Chia, S.B., Johnson, B.J., Hu, J. et al. Respiratory viral infections awaken metastatic breast cancer cells in lungs. Nature (2025). https://doi.org/10.1038/s41586-025-09332-0