Medical Bulletin 08/ June/ 2024

In an analysis of more than 50 years of health data, women who were overweight or obesity at age 14 or 31 were more likely to have an ischemic (clot-caused) stroke before age 55, according to research published in Stroke, the peer-reviewed scientific journal of the American Stroke Association.

According to the American Heart Association, an ischemic stroke occurs when a vessel supplying blood to the brain is obstructed. Ischemic stroke is the most common type of stroke and accounts for about 87% of all strokes.

The study suggested that women with overweight at age 14 were associated with later clot caused stroke risk despite having lost weight by age 31. Also, women with overweight at age 31 were associated with later clot caused stroke risk despite having been normal weight at age 14. An increased risk of clot caused stroke was not found in men who were overweight at ages 14 or 31. However, men with obesity at age 31 had a higher risk of bleeding stroke compared to women with obesity at age 31.

The study analysed the association between weight at different ages and the risk of stroke before age 55 by reviewing long-term data from a birth cohort. Researchers used the body mass index (BMI), a ratio of weight to height, to determine if those who were overweight or obese at age 14 or age 31 had a different risk of early stroke compared to peers who were not overweight or obese at these ages.

Assessing the impact of periods of excess weight on stroke risk, the researchers found:

1. Women affected by obesity at age 14 were 87% more likely to have an early clot-caused stroke or mini-stroke, while those with obesity at age 31 were 167% more likely to have a stroke compared to those at appropriate weight. Similar associations were not found among men.

2. Women with obesity at age 31 had almost 3 ½ times increased risk of bleeding stroke, and men with obesity at age 31 had more than 5 ½ times increased risk of bleeding stroke.

3. BMI measurements earlier in childhood or later in adulthood did not appear to affect the results.

“Our findings suggest that being overweight may have long-term health effects even if the excess weight is temporary. Healthcare professionals should pay attention to overweight and obesity in young people and work with them to develop healthier eating patterns and physical activity. However, conversations with teens and young adults about weight should be approached in a non-judgmental and non-stigmatizing manner,” said lead study author Ursula Mikkola.

Reference: Ursula Mikkola, Ina Rissanen, Milja Kivelä, Harri Rusanen, et al.; Overweight in Adolescence and Young Adulthood in Association With Adult Cerebrovascular Disease: The NFBC1966 Study; Stroke; https://doi.org/10.1161/STROKEAHA.123.045444

A study conducted by the University of Oklahoma and published in the journal CANCER found that both obesity and metabolic syndrome – a cluster of conditions like high blood pressure and high blood sugar – increase the risk of breast cancer, but in differing ways for different subtypes of the cancer.

Breast cancer is one of the most prevalent cancers globally, significantly affecting women. It is the most common cancer among women, with millions of new cases diagnosed each year. According to the World Health Organization (WHO), breast cancer accounts for approximately 24.5% of all cancer cases in women, making it a leading cause of cancer-related deaths.

In the study, a total of 68,132 postmenopausal women without prior breast cancer and with normal mammograms were enrolled in the Women’s Health Initiative randomized clinical trials. The study population consisted of 63,330 women with an entry metabolic syndrome score. At the start, body mass index (BMI) was determined, and the metabolic syndrome score included the following criteria: (1) high waist circumference (≥88 cm), (2) high blood pressure (systolic ≥130 mm Hg and/or diastolic ≥85 mm Hg, or a history of hypertension), (3) a history of high cholesterol, and (4) a history of diabetes. The study outcomes included breast cancer incidence, breast cancer mortality, deaths following breast cancer, and results categorized by hormone receptor status.

The results showed that:

1. Metabolic syndrome is significantly associated with 53% more deaths after breast cancer and a 44% higher breast cancer mortality (the proportion of a population that dies).

2. Metabolic syndrome is also associated with poor prognosis in two specific types of breast cancer: estrogen receptor (ER)-positive and progesterone receptor (PR)-negative.

ER-positive breast cancer occurs when high levels of estrogen in the breast cancer cells help the cancer grow and spread. PR-negative breast cancer means the cancer has no hormone receptors and therefore does not respond to hormone therapy. It also tends to grow faster than hormone-positive cancers.

3. Obesity status is significantly associated with more total breast cancers and more deaths after breast cancer, with higher mortality only in women with severe obesity.

4. Obesity status is also associated with good prognosis in ER-positive and PR-positive cancers. Both can be treated with hormone therapy and tend to grow more slowly than those that are hormone receptor-negative.

“The study showed that obesity and metabolic syndrome independently affect breast cancer risk, each influencing various subtypes differently and impacting diagnosis and mortality. It emphasized the importance of prevention, highlighting the need to address both metabolic syndrome and weight. Metabolic syndrome, which includes high blood pressure, high blood sugar, excess waist fat, and abnormal cholesterol or triglycerides, also raises the risk for cardiovascular disease and diabetes,” said Robert Wild, co-author of the study.

Reference: Chlebowski RT, Aragaki AK, Pan K, et al. Breast cancer incidence and mortality by metabolic syndrome and obesity: The Women’s Health Initiative. Cancer. 2024; 1-10. doi:10.1002/cncr.35318

The Endocrine Society's annual meeting revealed guidelines on Vitamin D for disease prevention, emphasizing the restriction of vitamin D supplementation beyond the daily recommended intake to certain high-risk groups. Additionally, the guidelines advise against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals.

The guidelines were published in the Journal of Clinical Endocrinology and Metabolism.

A team of clinical experts, along with experts in guideline methodology and systematic literature review, identified and ranked 14 clinically relevant questions regarding the use of vitamin D and 25(OH)D testing to reduce disease risk. They prioritized randomized placebo-controlled trials in general populations (without a specific indication for vitamin D treatment or 25[OH]D testing), assessing the impacts of vitamin D supplementation across all age groups. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology was employed to evaluate evidence certainty and inform recommendations.

The guidelines advised that people who may benefit from vitamin D supplementation include:

1. Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections

2. Pregnant people to lower the risk for maternal and fetal or neonatal complications

3. Adults older than 75 years to lower the risk for mortality

4. Adults with prediabetes to lower the risk for type 2 diabetes

The guidelines also recommended daily (rather than intermittent) vitamin D supplementation at doses higher than those suggested by the National Academy of Medicine (NAM) in 2011: 600 IU/day for individuals aged 1-70 years and 800 IU/day for those over 70 years.

Based on the absence of supportive clinical trial evidence, the guidelines suggested against routine 25(OH)D testing in the absence of established indications. Further research is needed to determine optimal 25(OH)D levels for specific health benefits.

“The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those]. New data have been released regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients,” said the authors.

Reference: Marie B Demay, Anastassios G Pittas, Daniel D Bikle, Dima L Diab, Mairead E Kiely, Marise Lazaretti-Castro, Paul Lips, Deborah M Mitchell, M Hassan Murad, Shelley Powers, Sudhaker D Rao, Robert Scragg, John A Tayek, Amy M Valent, Judith M E Walsh, Christopher R McCartney, Vitamin D for the Prevention of Disease: An Endocrine Society Clinical Practice Guideline, The Journal of Clinical Endocrinology & Metabolism, 2024;, dgae290, https://doi.org/10.1210/clinem/dgae290