A new thesis by Karolinska Institutet student Tessa Schillemans has found that exposure persistent environmental pollutants did not increase biomarkers of cardiovascular disease risk – rather, exposure reduced them, raising further questions on their complex interactions with the environment and within the human body.
What is the thesis about? The thesis is about a group of environmental pollutants called per- and polyfluoroalkyl substances (PFAS), also called “forever-chemicals”. Since we all are exposed and their chemical structure resembles that of fatty acids, we wanted to investigate whether exposure to PFAS associated with increased risk of cardiovascular disease. Additionally, we also explored if we could gain insight in potential underlying molecular pathways by linking PFAS exposure to biological molecules in the blood.
Can you tell us about some interesting results? We found no evidence that PFAS was linked to increased risk of cardiovascular disease in the general population. If anything, rather the opposite – which also deserves careful consideration. We did observe associations with higher cholesterol, lower triglycerides and with lipid metabolism intermediates, which all point towards potential perturbations in lipid metabolism.
What further research is needed in the area? It is essential to fully understand any adverse consequences that PFAS may have, since they are omnipresent and persistent. Thus, epidemiological studies involving other outcomes and vulnerable subgroups (such as pregnant women and children) should also be performed, as disturbances in lipid metabolism could impact other physiological processes. For a deeper mechanistic understanding, integration of data from different biological systems (genome, epigenome, transcriptome, proteome, metabolome) in human and experimental settings would be optimal. Additionally, since humans are exposed to many different chemicals simultaneously and these could interact with each other, there is a need for studies that investigate multiple exposures at the same time (exposome studies).
Bempedoic acid, a new cholesterol-lowering drug, has the potential to be an effective substitute for patients who can’t tolerate statins. Bempedoic acid is an ATP citrate lyase inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events. Its effects on cardiovascular outcomes were uncertain, so researchers used a double-blind, randomised, placebo-controlled trial to determine outcomes on a variety of cardiovascular measures in statins-intolerant patients.
The study, published in the New England Journal of Medicine, recruited patients aged 18–85 years at increased cardiovascular risk and unable or unwilling to take statins due to adverse effects. Patients were first tested with placebo over a 4-week run-in period, and were not randomised if they experience unacceptable adverse effects or if adherence was less than 80%. The 13 970 patients who successfully completed run-in were randomised to receive bempedoic acid 180mg orally per day or matching placebo.
The mean LDL cholesterol level at baseline was 139.0mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2mg/dL; the observed difference in the percent reductions was 21.1 percentage points in favour of bempedoic acid.
Compared to placebo, risk of fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause after significantly were lower by 13%, after a median of 40.6 months of follow-up. The risk of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction was 15% lower with bempedoic acid than with placebo, and the risks of fatal or nonfatal myocardial infarction and coronary revascularisation were 23% lower and 19% lower, respectively.
The researchers noted that the LDL-cholesterol lowering effects were similar in magnitude and predicted reduction in cardiovascular risks to that observed with statins. In addition, bempedoic acid did not increase glycated haemoglobin levels or the incidence of new-onset diabetes, unlike statins. Due to the demonstrated benefits, those taking placebo were offered the chance to transition to taking bempedoic acid.
A trial limitation was that it only included patients with statins intolerance, and who therefore had higher LDL cholesterol levels at baseline.
Being overweight in childhood and in early adulthood are discrete risk factors for blood clots (thrombi) later in life, according to a study using school health care and military service records, according to a study published in the Journal of Internal Medicine.
The association between obesity and blood clots is already established. However, to date it has been unclear how much influence a raised BMI in childhood and puberty exerts. Thrombi usually arise in the legs, often starting in a blood vessel in the calf. Swelling, pain and redness are common symptoms. Though easily treated if caught early, they can result pulmonary embolism may be life-threatening.
The present study comprises 37 672 men in Sweden, born between 1945 and 1961. It is based on information about height, weight, and BMI from the men’s records, first from school health care services (at the age of 8 years) and, second, from medical examinations on enrolment in the Armed Services (at age 20), along with register data on any blood clots up to age 62 on average.
Distinctly elevated thrombus risk
The results showed that BMI at both ages 8 and 20, independently of each other, can be linked to venous blood clots. These may occur in, for example, the leg (deep vein thrombosis, DVT) or the lung (pulmonary embolism).
In adulthood, two groups were found to be at a significantly increased risk of venous thrombi. The first was individuals who had been overweight both as children and as young adults, while the second was composed of those whose weight in childhood was normal and who became overweight only in early adulthood.
Moreover, being overweight in both childhood and young adulthood was found to raise the risk of arterial thrombi – clots resulting from constricted blood vessels with fatty deposits and inflammation. Since there were few cases of arterial blood clots in the study, however, further studies are needed to confirm these findings. All comparisons in the study were made with the control group, whose weight was normal at both 8 and 20 years of age.
Overweight in puberty an important factor
The first and corresponding author of the study is Lina Lilja, a doctoral student at Sahlgrenska Academy, University of Gothenburg, and paediatrician. At the time of the study, she worked at the Kungshöjd paediatric clinic in Gothenburg. Today, she is a senior physician in child health care in Region Västra Götaland.
“Our study shows that both overweight in childhood and overweight in young adulthood increase the risk of venous blood clots later in life. The latter, overweight when the men were young adults, proved to be a more influential factor than overweight when they were children,” Lilja notes.
The study includes data from the BMI Epidemiology Study (BEST) in Gothenburg, a population study, and from Swedish national registers.
Regular physical activity can improve young adolescents’ mental health and help with behavioural difficulties, suggests research published in Mental Health and Physical Activity. Investigators found that engaging in regular moderate to vigorous physical activity at age 11 was associated with better mental health between the ages of 11 and 13.
Physical activity was also associated with reduced hyperactivity and behavioural problems, such as loss of temper, fighting with other children, lying, and stealing, in young people.
Researchers from the Universities of Edinburgh, Strathclyde, Bristol, and Georgia in the United States explored data from the Children of the 90s study (also known as the Avon Longitudinal Study of Parents and Children; ALSPAC). They looked at the levels of physical activity of 4755 11-year-olds which was measured using devices.
The devices recorded levels of moderate physical activity, typically defined as brisk walking or cycling, as well as vigorous activity which boosts heart rate and breathing, such as aerobic dancing, jogging or swimming.
The young people and their parents reported on their levels of depressive symptoms from age 11 and at age 13 years. Participants’ parents and teachers were also quizzed about the young people’s general behaviour and emotional difficulties.
In analysing the impact of moderate to vigorous exercise on the young people’s mental health and behaviour, the team also considered factors such as age, sex and socio-economic status.
They found that higher levels of moderate or intense physical activity had a small but detectable association with decreases in depressive symptoms and emotional difficulties.
Regular exercise had a small but detectable association with reduced behavioural problems, even after controlling for other possible influences, the study found.
The findings suggest regular moderate and intense physical activity may have a small protective influence on mental health in early adolescence, researchers say.
Dr Josie Booth, of the University of Edinburgh’s Moray House School of Education and Sport, said: “This study adds to the increasing evidence base about how important physical activity is for all aspects of young people’s development – it can help them feel better, and do better at school. Supporting young people to lead healthy active lives should be prioritised.”
Researchers say the study is the first to offer such a comprehensive approach to examining mental health and exercise in young people.
Professor John Reilly, at the University of Strathclyde, said: “While it might seem obvious that physical activity improves mental health the evidence for such a benefit in children and young people has been scarce, so the study findings are important. The findings are also important because levels of moderate-to-vigorous intensity activity globally are so low in pre-teens globally – less than a third achieve the 60 minutes per day recommended by the WHO and UK Health Departments.”
The study is a long-term health-research project that enrolled more than 14 000 pregnant women in 1991 and 1992.
Children of the 90s has been following the health and development of the parents and their children in detail and is currently recruiting the children and the siblings of the original children into the study. It receives core funding from the Medical Research Council, the Wellcome Trust and the University of Bristol.
Scientific evidence that supports vaping as an additional approach to tackle smoking-related morbidity and mortality is fast growing. The time is ripe for decisionmakers to embrace tobacco harm reduction and to steer away from precautionary principle-based tobacco control policies. This is according to Dr Riccardo Polosa, Founder of the Centre of Excellence for the Acceleration of Harm Reduction (CoEHAR) and Professor of Internal Medicine of the University of Catania, Italy.
Towards the end of 2022, the South African Tobacco Products and Electronic Delivery Systems Control Bill was officially introduced into parliament by the Minister of Health. Now, in the coming months, it will be discussed and possibly amended by a portfolio committee.
With this Bill lumping Electronic Nicotine Delivery Systems (ENDS, i.e. e-cigarettes and vapes) in the same category as smoking, Kurt Yeo, co-founder of consumer advocacy group Vaping Saved My Life (VSML), explains that it is essential for those involved in this process to consider the mounting scientific evidence demonstrating that vaping is far less harmful than tobacco smoking and is an effective way to support smokers seeking less risky alternatives and/or wanting to quit.
Dr Colin Mendelsohn is an Australian academic, researcher and clinician, who has helped smokers quit for over 30 years, says that vaping nicotine is a more effective quitting aid than nicotine replacement products such as patches and gums and is the most popular aid for quitting or reducing smoking globally. “It has the potential to save the lives of hundreds of thousands of South African smokers and prevent untold disease and suffering.”
He adds that vaping has been estimated to cause no more than 5% of the harm from smoking. “While the long-term effects have not yet been established, e-cigarettes are certain to be far less harmful than smoking. Vaping carries only a small fraction of the risk of tobacco smoking and is an effective quitting aid or long-term safer substitute for smoking. Vaping should be easily accessible to help adult smokers to quit deadly cigarettes.”
Dr Polosa highlights that decisionmakers and the public should also beware of many flawed articles scientific and fake news that are propagating ‘findings’ of potential harms, thus feeding the counter-narrative that e-cigarettes are ‘not as safe as promoted’. “Proliferation of poor-quality science and fake news need to be actively contrasted by good quality science and by correct information/education.”
The proof is in the numbers
“Countries which have supported vaping such as the United Kingdom and New Zealand have had accelerated declines in smoking rates,” explains Dr Mendelsohn. “For example, in New Zealand the national adult smoking rate fell by an unprecedented 33% in the two years between 2020 and 2022 after vaping was legalised.”
Illustrating this point further, Dr Polosa says that according to the same national surveys used for reporting smoking prevalence to the World Health Organization (WHO), these countries show faster declines in smoking prevalence compared with neighbouring countries with lower uptake of these alternatives. “In Sweden and Norway, eradication of smoking is now almost a reality with a daily smoking prevalence among Norwegian and Swedish youth close to zero (1% and 3%, respectively). Widespread diffusion of e-cigarettes in New Zealand and the United States is also contributing to the historical acceleration in the downward trend in daily prevalence of smoking among young people (1.3% and 1.9%, respectively).”
Regulation is essential, but the proposed Bill is deeply flawed
When it comes to regulation, Dr Polosa asserts that vaping and smoking are completely different animals. “Smoking kills. Vaping does not.”
Therefore, to regulate vaping in the same way as smoking does not make any sense, says Dr Polosa. “Doing so denies smokers access to much lower risk products. Rather, the South African government should table a risk-proportionate approach where the main regulatory levers are applied differentially.”
“This means that the most stringent and restrictive regulation would be applied to the most harmful products: tobacco cigarettes. Regulation of the smoke-free alternatives would focus on consumer protection (i.e., benefits to the consumer) and control of uptake by adolescents in a way that does not cause significant harm to adult smokers. This would meet the demands of people who cannot or do not wish to quit completely, but with much less cancer, cardiovascular and respiratory disease as a result,” Dr Polosa explains.
Dr Mendelsohn agrees and says that the preferred regulatory model is for nicotine liquids for vaping to be sold as adult consumer products from licensed premises, with strict age verification, like cigarettes and alcohol. “Regulation of e-cigarettes should be proportionate to risk and a light touch approach is more appropriate. A balanced regulatory model is needed which allows adult smokers easy access to regulated vaping products while restricting access to underage users. The current proposals will restrict adult smokers’ access to an effective quitting aid which can save lives and prevent smoking-related illness.”
“A precautionary approach to prevent the use of much less harmful smoke-free products is unjustified in the face of the massive burden of smoked tobacco products, which are widely available. This principle requires policymakers to compare the risks of introducing a product with the risks of delaying its introduction. In the case of vaping, the relatively small risks of harm will be outweighed by the far more substantial harms from delaying access to current smokers,” Dr Mendelsohn explains.
He points out that harsh restrictions on the sale and marketing of electronic cigarettes will have negative unintended consequences and will lead to black market sales of unregulated products to both adults and children. “The public health goal should be to encourage smokers who are unable to quit to switch to vaping, a far safer alternative.”
Yeo concludes by saying: “With the Bill aiming to reduce the incidence of tobacco-related illness, disability and death, regulations should be drawn up based on all available research and case studies to ensure South Africa’s smokers are truly helped.”
