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Common drug may protect hearts from damage caused by breast cancer chemotherapy

Anthracyclines and trastuzumab are effective therapies for many women with breast cancer. However, increased risk of cardiotoxicity has limited their use, and damage can be severe enough to lead to heart failure.

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New research from UHN’s Peter Munk Cardiac Centre (PMCC) shows statins, commonly prescribed to lower cholesterol and reduce the risk of heart disease and stroke, may also protect the heart from damaging side-effects of early breast cancer treatment.

Published Jan. 6, 2021 in the Journal of the American Heart Association, an observational study found women already taking statins and treated with either anthracyclines or trastuzumab were half as likely to be hospitalized or visit an Emergency Department for heart failure within five years after chemotherapy.

“Our job is to protect the heart and ensure it has the greatest fighting chance to get through chemotherapy,” says Dr. Husam Abdel-Qadir, lead author of the paper and a cardiologist at the PMCC and Women’s College Hospital. He notes prior observational studies have reported measures of heart strength in statin-treated women after chemotherapy, but only focused on a single centre.

Anthracyclines and trastuzumab are effective therapies for many women with breast cancer. However, increased risk of cardiotoxicity has limited their use, and damage can be severe enough to lead to heart failure.

Using several health databases in Ontario, researchers reviewed the occurrence of heart failure in women aged 66 and older who received trastuzumab or anthracyclines for newly diagnosed early breast cancer between 2007 and 2017.

In the 666 pairs of women treated with anthracyclines, those taking statins were 55 per cent less likely to be treated at the hospital for heart failure. In the 390 pairs of women treated with trastuzumab, those taking statins were 54 per cent less likely, which suggested a protective trend but did not meet statistical significance.

Oxidative stress is believed to be one of the mechanisms in which cancer treatment eventually leads to damage of the heart muscle. It is defined as the imbalance of free radicals, compounds which can harm your body if levels are too high, and antioxidants, molecules that fight free radicals.

In addition to lowering cholesterol, statins may also protect the body against the effects of oxidative stress. If statins can stop this imbalance, they may decrease the likelihood the heart sustains damage due to cancer treatment.

“In order to know whether it’s a true cause and effect relationship, we need to do a proper randomized control trial,” says Dr. Abdel-Qadir, who is also part of the Ted Rogers Centre for Heart Research (TRCHR) Cardiotoxicity Prevention Program. “For the time being, if a woman is supposed to be starting treatment for breast cancer and already has an established indication to be on a statin, there’s now additional motivation to start it or stay on it.”

As for next steps, Dr. Dinesh Thavendiranathan, cardiologist at the PMCC, lead of the TRCHR Cardiotoxicity Prevention Program and senior author on the study is currently recruiting for the SPARE-HF randomized control trial, which will assess whether pre-treatment with statins before anthracycline-chemotherapy can prevent cardiotoxicity in high-risk patients.

“It’s part of the larger principles we try and apply within the TRCHR Cardiotoxicity Program, which is ideally you shouldn’t change the cancer treatment, you let the oncologist pick the best treatment for the patient,” says Dr. Abdel-Qadir. “We try to reduce the risks that come with it. Our vision is that patients should be able to get the best cancer treatment while reducing concerns for the heart as much as possible.”

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More sleep boosts teens’ ability to cope with pandemic

Changes to daily routines triggered by lockdowns allowed teenagers to follow their biological impulse to wake up and sleep later, reducing daytime sleepiness.

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While poor sleep was linked to higher levels of stress during the COVID-19 pandemic, more teens actually obtained the recommended amount of sleep compared to pre-pandemic sleep patterns, according to a new study from McGill University. Changes to daily routines triggered by lockdowns allowed teenagers to follow their biological impulse to wake up and sleep later, reducing daytime sleepiness.

The study, published in Child and Adolescent Psychiatry and Mental Health, explores pre‑pandemic sleep behavior and stress during the COVID-19 pandemic. According to the researchers, encouraging better sleeping habits could help reduce teens’ stress and improve their ability to cope in times of crisis.

“The pandemic has shown that delaying school start times could help and should be implemented by schools interested in supporting the mental health of their students,” says lead author Reut Gruber, a Full Professor in the Department of Psychiatry at McGill University.

Reducing stress by promoting more sleep

During the pandemic, the wake-up and sleep time of teens shifted by about two hours later. Many teens also slept longer and had less of a need to catch up on lost sleep during the weekend.

The elimination of the morning commute, a delayed school start time, and cancellation of extracurricular activities allowed teens to follow their ‘delayed biological rhythm’ – or natural tendency to wake up and go to bed later, the researchers explain.

These changes meant that teens had more ‘useable hours’ during the weekdays to complete their homework and didn’t have to sacrifice sleep to fulfill their obligations during the week. Similar findings have been reported in multiple countries around the world during the COVID-19 pandemic.

Less sleep linked to higher levels of stress

The researchers found a connection between the amount of sleep teenagers were getting before the pandemic and their level of perceived stress during the pandemic.

“Shorter sleep duration and higher level of arousal at bedtime were linked to higher levels of stress, whereas longer sleep and lower level of arousal at bedtime was linked to reduced stress,” says Gruber, who is also the Director of the Attention, Behavior and Sleep Laboratory at the Douglas Research Centre.

“The tendency of teens not getting enough sleep was already a global concern prior to the COVID-19 pandemic. Now more than ever it’s critical we tackle the problem,” says co-author Sujata Saha, a Principal at Heritage Regional High School of the Riverside School Board. “Across the world the pandemic has increased levels of uncertainty and psychological stress. It’s projected that today’s elevated mental health challenges will continue well beyond the pandemic itself.”

“Not sleeping enough and being overly stimulated before bedtime are poor habits that are modifiable. We can target these behaviors with preventative measures to reduce teens’ stress in the face of overwhelming situations like to COVID-19 pandemic,” says Gruber.

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Eye conditions linked to heightened risk of dementia

Vision impairment can be one of the first signs of dementia, and reduced stimulation of visual sensory pathways is believed to accelerate its progression.

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Age-related macular degeneration, cataract and diabetes-related eye disease are linked to an increased risk of dementia, suggests research published online in the British Journal of Ophthalmology.

Vision impairment can be one of the first signs of dementia, and reduced stimulation of visual sensory pathways is believed to accelerate its progression.

Some small studies have suggested there may be a link between ophthalmic conditions that cause vision impairment – age-related macular degeneration, cataract, diabetes-related eye disease and glaucoma – and cognitive impairment. The incidence of these ophthalmic conditions increases with age, as does the incidence of systematic conditions such as diabetes, high blood pressure, heart disease, depression and stroke, which are accepted risk factors for dementia.

It is therefore unclear whether these ophthalmic conditions are associated with a higher incidence of dementia independently of these systematic conditions, so to investigate, the authors analysed data on 12,364 adults aged 55-73 years enrolled in the UK Biobank study. 

The participants were assessed between 2006 and 2010 at baseline and followed up until early 2021. During the 1,263,513 person-years of follow-up 2,304 cases of dementia were recorded.

Analysis of these data showed that age-related macular degeneration, cataract and diabetes-related eye disease, but not glaucoma, were independently associated with increased risk of dementia from any cause.

Compared with people who did not have ophthalmic conditions at the start of the study, the risk of dementia was 26% higher in those with age-related macular degeneration, 11% higher in those with cataract, and 61% higher in those with diabetes-related eye disease.

While glaucoma was not associated with increased risk of Alzheimer’s disease, it was associated with a higher risk of vascular dementia.

At the start of the study, participants were asked whether they had ever experienced heart attack, angina, stroke, high blood pressure or diabetes, and were assessed for depression. Diabetes, heart disease, stroke and depression were all associated with increased risk of dementia.

Having one of these conditions (a systemic condition) as well as an ophthalmic condition increased the risk of dementia further, and the risk was greatest when diabetes-related eye disease occurred alongside a systemic condition. Larger relative risk for dementia was observed among individuals with more ophthalmic conditions.

This is an observational study, and as such, can’t establish cause, and the authors also highlight several potential limitations, mostly related to data capture. They point out that ophthalmic conditions were defined based on self-reported and inpatient record data which was likely to underestimate their prevalence, that medical records and death registers may not have captured all cases of dementia, and that some dementia documented during follow-up may have occurred before eye diseases.

Nevertheless, they conclude: “Age-related macular degeneration, cataract and diabetes-related eye disease but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.”

They add: “Newly developed hypertension, diabetes, stroke, heart disease and depression mediated the association between cataract/ diabetes-related eye disease and dementia.”

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Exposure to traffic noise linked to higher dementia risk

Reducing noise is a public health priority, say experts.

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Exposure to noise from traffic on roads and railways over a long period is associated with a higher risk of developing dementia, especially Alzheimer’s disease, suggests a study from Denmark published in The BMJ

The researchers estimate that as many as 1,216 out of the 8,475 cases of dementia registered in Denmark in 2017 could be attributed to these noise exposures, indicating a great potential for dementia prevention through reduction in traffic related noise. 

Worldwide, the number of people with dementia is expected to exceed 130 million by 2050, making it a costly and growing global health crisis. Besides well established risk factors, such as cardiovascular diseases and unhealthy lifestyle, environmental exposures may also play a role in the development of dementia.

Transportation noise is considered the second worst environmental risk factor for public health in Europe after air pollution, and around a fifth of the European population is exposed to transportation noise above the recommended level of 55 dB (decibels).

Studies have consistently linked transportation noise to various diseases and health conditions, such as coronary heart disease, obesity, and diabetes. There is, however, little research on transportation noise and dementia and findings are inconsistent.

To address this, researchers investigated the association between long term residential exposure to road traffic and railway noise and risk of dementia among two million adults aged over 60 and living in Denmark between 2004 and 2017. 

The researchers estimated road traffic and railway noise at the most and least exposed sides (or façades) of all residential addresses in Denmark. 

They then analysed national health registers to identify cases of all-cause dementia and different types of dementia (Alzheimer’s disease, vascular dementia, and Parkinson’s disease related dementia) over an average of 8.5 years.

They found 103,500 new cases of dementia during the study period.

After taking account of potentially influential factors related to residents and their neighbourhoods, the researchers found that a 10-year average exposure to road traffic and railway noise at the most and least exposed sides of buildings was associated with a higher risk of all-cause dementia.

These associations showed a general pattern of higher risk with higher noise exposure, but with a levelling off or even small declines in risk at higher noise levels.

Further analysis by type of dementia showed both road traffic and railway noise were associated with a higher risk of Alzheimer’s disease – up to 27% higher for exposure to road traffic noise of 55 dB and up to 24% higher for exposure to railway noise of 50 dB compared with less than 40 dB.

However, only road traffic noise was associated with an increased risk of vascular dementia, and not railway noise.

Possible explanations for an effect of noise on health include release of stress hormones and sleep disturbance, leading to a type of coronary artery disease, changes in the immune system and inflammation – all of which are seen as early events in the onset of dementia and Alzheimer’s disease.

This is an observational study so can’t establish cause, and the authors point to some limitations such as a lack of information about lifestyle habits, which can play a part in a person’s risk of developing dementia, and a lack of information on factors such as sound insulation in homes that might affect personal exposure to noise.

However, the study’s strengths included its large size, long follow-up time, and high quality assessment of noise exposure from two different transportation sources.

As such, the authors conclude: “If these findings are confirmed in future studies, they might have a large effect on the estimation of the burden of disease and healthcare costs attributed to transportation noise. Expanding our knowledge on the harmful effects of noise on health is essential for setting priorities and implementing effective policies and public health strategies focused on the prevention and control of diseases, including dementia.”

This large and comprehensive study has substantial strengths, but does not present the full picture of possible harm to the ageing brain associated with long term exposure to noise, for example from airports, industrial activities, or occupational exposure, say US researchers in a linked editorial.

Noise might also affect the risk of other chronic disorders such as high blood pressure, through which noise contributes indirectly to dementia risk, they add. 

The widespread and substantial exposures to noise worldwide, the severity of associated health consequences, and the limited tools available for people to protect themselves, strongly support the WHO’s argument that “noise pollution is not only an environmental nuisance but also a threat to public health,” they write.

“Reducing noise through transportation and land use programs or building codes should become a public health priority,” they conclude.

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