Archive for category: News

India: A recent case study published in Annals of Internal Medicine: Clinical Cases reports the case of classical dystonia in a young girl who presented with reduced systolic left ventricular function, had cardiac surgery, and was prescribed sacubitril/valsartan combination for reversal of heart remodelling.

A range of reproductive factors, including age when periods first start and an early menopause, are all linked to a heightened risk of COPD-the umbrella term for progressive lung conditions that cause breathing difficulties-finds research published online in the journal Thorax.

Miscarriage, stillbirth, infertility, and having 3 or more children are also associated with a heightened risk of COPD, which includes emphysema and chronic bronchitis, the findings show.

Recent evidence indicates substantial gender differences in susceptibility to, and severity of, COPD, note the researchers. Women seem to develop severe COPD at younger ages than men. And while smoking is a major risk factor, non-smokers with COPD are more likely to be women, they add.

Previously published studies looking at the potential influence of female hormones on COPD risk have been hampered by methodological flaws, note the researchers. To try and get round these issues, they drew on the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events (InterLACE) consortium.

This is a collection of 27 observational studies, pooling individual level data from more than 850,000 women in 12 countries.

For the purposes of the current study, the researchers included three groups of women (283,070; average age 54) with data on reproductive factors and COPD: the Australian Longitudinal Study on Women’s Health 1946–51 (ALSWH-mid); the UK Biobank; and the Swedish Women’s Lifestyle and Health Study (WLH).

In the ALSWH-mid and UK Biobank groups, women were tracked until the end of December 2019. Women in WLH were tracked up to the end of 2010.

Information on reproductive factors was collected at study entry or at subsequent data collection points, along with potentially influential factors: birth year (before or after 1950), ethnicity, educational level, duration of smoking, asthma (never and ever), and weight (BMI).

COPD was retrospectively and prospectively identified through self-report and medical records, which included prescriptions, hospital admissions, emergency care visits, and death registry data.

The women’s health was monitored for an average of 11 years. During this time, 10,737 (4%) women developed COPD at an average age of 63.

Women with COPD were more likely to be older when recruited to their studies, to have fewer than 10 years of formal education, to be obese, to have smoked for at least 10 years, and to have asthma–all risk factors for the condition. Some 53, 205 (16%) women were excluded because of missing data.

Several reproductive factors were associated with the risk of COPD, including age when periods first started; number of children; a history of infertility, miscarriage or stillbirth, especially multiple miscarriages or stillbirths; and age at menopause.

A U-shaped pattern emerged for the age at which periods first started. Those who began menstruating before or at the age of 11 were 17% more likely to develop COPD than those who did so at the age of 13; after the age of 16, the risk was 24% higher.

Women with children were at higher risk of COPD than childless women. Compared with having 2 children, more than 3 was associated with a 34% higher risk, while women with one child were at 18% higher risk.

Women who experienced infertility also had a 13% higher risk of COPD than women who were fertile.

And among those who had ever been pregnant, a history of miscarriage was associated with a 15% higher risk of COPD, with the risk rising in tandem with the number of miscarriages: 28% higher for 2; and 36% higher for 3 or more.

Similarly, stillbirth was associated with a 42% overall higher risk of COPD, with the risk rising in tandem with the number of stillbirths.

Menopause before the age of 40 was associated with a 69% higher risk, compared with those experiencing it naturally at the age of 50-51, while the risk was 21% lower for those who went through it at or after the age of 54.

This is an observational study, so can’t establish cause, and the researchers acknowledge various limitations to their findings, including potentially influential factors.

For example, they had no detailed information on hormonal contraception and HRT use, and data on parental history of COPD, childhood respiratory infections, secondhand smoking or occupational exposures, weren’t available for all 3 of the groups.

But by way of an explanation for their findings, they suggest that the female hormone oestrogen is likely to have a key role in COPD risk in women, because of its various effects on the lung.

“The overall effect of oestrogen might differ depending on the timing,” they suggest. “In the early or middle reproductive stage, long or higher accumulated exposure to oestrogen would be detrimental to the lung, leading to a higher risk of COPD among women with early menarche or multiple live births.

“In the later stage, oestrogen may be protective, since earlier age at menopause or [ovary removal] (indicates shorter exposure to oestrogen) were associated with a higher risk of COPD.”

Other factors, including autoimmune disease, such as type 1 diabetes, and social and environmental factors, such as air pollution, underweight, and socioeconomic deprivation, might also be influential, they add.

Reference:

Liang C, Chung H, Dobson A, et alFemale reproductive histories and the risk of chronic obstructive pulmonary diseaseThorax Published Online First: 13 February 2024. doi: 10.1136/thorax-2023-220388.

University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The findings were published in Nature Metabolism today.

The study, which combined small human trials with experiments in mice and cells in a Petri dish, showed that consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk. Furthermore, the scientists showed that one amino acid-leucine-seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis, or stiff, hardened arteries.

“Our study shows that dialing up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, M.D., Ph.D., professor of cardiology at Pitt. “Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks.”

According to a survey of an average American diet over the last decade, Americans generally consume a lot of protein, mostly from animal sources. Further, nearly a quarter of the population receives over 22% of all daily calories from protein alone.

That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Razani. But his and other groups have shown that overreliance on protein may not be such a good thing for long-term health.

Following their 2020 research, in which Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice, his next study in collaboration with Bettina Mittendorfer, Ph.D., a metabolism expert at the University of Missouri, Columbia, delved deeper into the potential mechanism and its relevance to the human body.

To arrive at the answer, Razani’s laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of experiments across various models – from cells to mice to humans.

“We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said. “For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis.”

Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation following ingestion of protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.

Their work showed that consuming more than 22% of daily dietary calories through protein can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a “graveyard” of those cells inside the vessel walls and worsening of atherosclerotic plaques overtime. Interestingly, the analysis of circulating amino acids showed that leucine – an amino acid enriched in animal-derived foods like beef, eggs and milk – is primarily responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.”

Razani is careful to note that many questions remain to be answered, mainly: What happens when a person consumes between 15% of daily calories from protein as recommended by the USDA and 22% of daily calories from protein, and if there is a ‘sweet spot’ for maximizing the benefits of protein – such as muscle gain – while avoiding kick-starting a molecular cascade of damaging events leading to cardiovascular disease.

The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.

“Perhaps blindly increasing protein load is wrong,” Razani said. “Instead, it’s important to look at the diet as a whole and suggest balanced meals that won’t inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders.”

Razani also notes that these findings suggest differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health. “The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.

Reference:

Zhang, X., Kapoor, D., Jeong, SJ. et al. Identification of a leucine-mediated threshold effect governing macrophage mTOR signalling and cardiovascular risk. Nat Metab 6, 359–377 (2024). https://doi.org/10.1038/s42255-024-00984-2.