Medical bulletin 13/ March/ 2024

In a study, published in the Journal Nature Cardiovascular Research, researchers from Karolinska Institute in Sweden revealed that immune cells in the liver react to high cholesterol levels and eat up excess cholesterol that can otherwise cause damage to arteries and that the response to the onset of atherosclerosis begins in the liver.

Cholesterol is a type of fat that is essential for many functions in the body, such as making hormones and cell membranes. However, too much cholesterol in the blood can be harmful, as it can stick to the walls of the arteries and form plaques that narrow or block the blood flow. This results in atherosclerotic cardiovascular disease, the primary underlying cause of heart attacks and strokes, and the leading cause of death worldwide.

In the study, researchers tried to understand how different tissues in the body react to high levels of LDL, also called ‘bad cholesterol’, in the blood. To test this, they created a system where they could quickly increase the cholesterol in the blood of mice.

“Essentially, we wanted to detonate a cholesterol bomb and see what happened next. We found that the liver responded almost immediately and removed some of the excess cholesterol,” said Stephen Malin, lead author of the study and principal researcher at the Department of Medicine, Solna, Karolinska Institute.

However, it wasn’t the typical liver cells that responded, but a type of immune cell called Kupffer cells that are known for recognising foreign or harmful substances and eating them up.

“We were surprised to see that the liver seems to be the first line of defence against excess cholesterol and that the Kupffer cells were the ones doing the job. This shows that the liver immune system is an active player in regulating cholesterol levels, and suggests that atherosclerosis is a systemic disease that affects multiple organs and not just the arteries.” Said Malin.

“Our next step is to look at how other organs respond to excess cholesterol, and how they interact with the liver and the blood vessels in atherosclerosis. This could help us develop more holistic and effective strategies to combat this common and deadly disease.”

Reference: Giada Di Nunzio, Sanna Hellberg, Yuyang Zhang, Osman Ahmed, Jiawen Wang, Xueming Zhang, Hanna M. Björck, Veronika Chizh, Ruby Schipper, Hanna Aulin, Roy Francis, Linn Fagerberg, Anton Gisterå, Jari Metso, Valentina Manfé, Anders Franco-Cereceda, Per Eriksson, Matti Jauhiainen, Carolina E. Hagberg, Peder S. Olofsson & Stephen G. Malin; Journal: Nature Cardiovascular Research; DOI: 10.1038/s44161-024-00448-6

90% of symptomatic individuals not diagnosed with TB may also harbor tuberculosis bacteria

A study published in the Journal Proceedings of the National Academy of Sciences revealed that mycobacterium tuberculosis (Mtb), the bacteria that causes a tuberculosis infection, is present in the exhaled breath of 90% of those presenting with suspected tuberculosis and also includes those who were negative on conventional sputum testing and not diagnosed with TB.

Tuberculosis remains a significant global health concern with approximately 10 million people worldwide suffering from it, according to the World Health Organization (WHO). Mycobacterium tuberculosis, the bacterium responsible for tuberculosis (TB), enters the body through inhalation and primarily affects the lungs. Once inhaled, the bacteria can evade the immune system. The bacterium spreads through the air when an infected individual coughs or sneezes, making it highly contagious and can affect other organs besides the lungs, leading to extrapulmonary TB.

“If someone carries Mtb in their respiratory tract, this may also mean they can spread it. Therefore, since these results suggest a much broader range of people transmitting TB than previously recognised, there are significant implications for public health interventions designed to interrupt transmission.” said Ben Patterson, external Ph.D. candidate at Amsterdam UMC and the Amsterdam Institute for Global Health and Development.

In the study, participants were evaluated for TB diagnosis. Aerosol samples were collected in a dedicated TB aerobiology lab. These samples, gathered from all participants, detected Mtb in 90% of patients, even those initially testing negative for tuberculosis via sputum analysis. Sampling was repeated at three intervals over six months for each participant.

Researchers found that the presence of Mtb decreased in those on treatment as well, surprisingly, as those not on treatment over the time period. Nevertheless, 20% of all participants continued to test positively for Mtb in aerosol after six months. The findings suggested that the transmission could continue over a period longer than previously thought.

"Together, our results indicate how complex tuberculosis is, and perhaps also why it is so difficult to eliminate tuberculosis in endemic areas. Even when public health agencies work, according to the current guidelines, effectively against symptomatic TB cases. In this sense, a revaluation of our practices is necessary,” said Frank Cobelens, professor of Global Health at Amsterdam UMC and senior fellow at the AIGHD.

Reference: Journal: Proceedings of the National Academy of Sciences

Analysis highlights health effects of calcium and vitamin D supplements in postmenopausal women

A study published in the Journal Annals of Internal Medicine revealed that the use of calcium and vitamin D supplements among postmenopausal women was associated with decreased risk for cancer mortality, but increased risk for cardiovascular disease (CVD) mortality.

Calcium and vitamin D supplements consumption can potentially lead to cardiovascular mortality by altering calcium metabolism and vascular calcification, increasing the risk of cardiovascular events such as heart attacks and strokes in postmenopausal women.

Researchers from the University of Arizona conducted a WHI trial of CaD supplement versus placebo to evaluate long-term health outcomes among postmenopausal women. The researchers looked for incidence of cancer, disease-specific and all-cause mortality, CVD, and hip fracture by randomization assignment. Analyses also were stratified on personal supplement use.

They found that for women who were randomly assigned to take CaD supplements had a 7% lower risk of dying from cancer over a period of about 22 years compared to those taking placebo. However, there was also a 6% higher risk of dying from CVD among those who took the supplements. The study didn't find any significant overall effect on other measures, including all-cause mortality.

The study also noted that cancer incidence seemed to depend on whether the women were already taking supplements before the study began and that the CVD mortality was higher among those taking the supplements.

The findings suggested that Calcium and vitamin D supplements seemed to reduce cancer mortality and increase CVD mortality after more than 20 years of follow-up among postmenopausal women, with no effect on all-cause mortality.

Reference: Cynthia A. Thomson, PhD, RD, Aaron K. Aragaki, MS, Ross L. Prentice, PhD, Marcia L. Stefanick, PhD, JoAnn E. Manson, MD, MPH, DrPH, Jean Wactawski-Wende, PhD, Nelson B. Watts, MD, Linda Van Horn, PhD, RD, James M. Shikany, DrPH, Thomas E. Rohan, MBBS, PhD, DHSc, Dorothy S. Lane, MD, MPH, Robert A. Wild, MD, PhD, MPH, Rogelio Robles-Morales, MD, Aladdin H. Shadyab, PhD, MPH, Nazmus Saquib, MBBS, MPH, PhD, MBA, and Jane Cauley, DrPH; Journal: Annals of Internal Medicine; DOI: 10.7326/M23-2598