Clinician Reviews

A small increase in new cases brought COVID-19’s latest losing streak to an end at 4 weeks, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

After the 57% decline in cases seen during those 4 weeks of September, new cases rose by 3.7% during the week of Sept. 30 to Oct. 6. The 40,656 new cases reported bring the U.S. cumulative count of child COVID-19 cases to over 14.8 million since the pandemic began, which represents 18.4% of all cases, the AAP and CHA said in their weekly report based on state-level data.

The increase in new cases was not reflected in emergency department visits or hospital admissions, which both continued sustained declines that started in August. In the week from Sept. 27 to Oct. 4, the 7-day averages for ED visits with diagnosed COVID were down by 21.5% (age 0-11), 27.3% (12-15), and 18.2% (16-17), the Centers for Disease Control and Prevention said, while the most recent 7-day average for new admissions – 127 per day for Oct. 2-8 – among children aged 0-17 years with confirmed COVID was down from 161 per day the previous week, a drop of over 21%.

The state-level data that are currently available (several states are no longer reporting) show Alaska (25.5%) and Vermont (25.4%) have the highest proportions of cumulative cases in children, and Florida (12.3%) and Utah (13.5%) have the lowest. Rhode Island has the highest rate of COVID-19 per 100,000 children at 40,427, while Missouri has the lowest at 14,252. The national average is 19,687 per 100,000, the AAP and CHA reported.
 

Taking a look at vaccination

Vaccinations were up slightly in children aged 12-17 years, as 20,000 initial doses were given during the week of Sept. 29 to Oct. 5, compared with 17,000 and 18,000 the previous 2 weeks. Initial vaccinations in younger children, however, continued declines dating back to August, the AAP said in its weekly vaccination trends report.

The District of Columbia and Massachusetts have the most highly vaccinated groups of 12- to 17-year-olds, as 100% and 95%, respectively, have received initial doses, while Wyoming (39%) and Idaho (42%) have the lowest. D.C. (73%) and Vermont (68%) have the highest proportions of vaccinated 5- to 11-year-olds, and Alabama (17%) and Mississippi (18%) have the lowest. For children under age 5 years, those in D.C. (33%) and Vermont (26%) are the most likely to have received an initial COVID vaccination, while Alabama, Louisiana, and Mississippi share national-low rates of 2%, the AAP said its report, which is based on CDC data.

When all states and territories are combined, 71% of children aged 12-17 have received at least one dose of vaccine, as have 38.6% of all children 5-11 years old and 6.7% of those under age 5. Almost 61% of the nation’s 16- to 17-year-olds have been fully vaccinated, along with 31.5% of those aged 5-11 and 2.4% of children younger than 5 years, the CDC said on its COVID Data Tracker.

About 42 million children – 58% of the population under the age of 18 years – have not received any vaccine yet, the AAP noted. Meanwhile, CDC data indicate that 36 children died of COVID in the last week, with pediatric deaths now totaling 1,781 over the course of the pandemic.

A small increase in new cases brought COVID-19’s latest losing streak to an end at 4 weeks, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

After the 57% decline in cases seen during those 4 weeks of September, new cases rose by 3.7% during the week of Sept. 30 to Oct. 6. The 40,656 new cases reported bring the U.S. cumulative count of child COVID-19 cases to over 14.8 million since the pandemic began, which represents 18.4% of all cases, the AAP and CHA said in their weekly report based on state-level data.

The increase in new cases was not reflected in emergency department visits or hospital admissions, which both continued sustained declines that started in August. In the week from Sept. 27 to Oct. 4, the 7-day averages for ED visits with diagnosed COVID were down by 21.5% (age 0-11), 27.3% (12-15), and 18.2% (16-17), the Centers for Disease Control and Prevention said, while the most recent 7-day average for new admissions – 127 per day for Oct. 2-8 – among children aged 0-17 years with confirmed COVID was down from 161 per day the previous week, a drop of over 21%.

The state-level data that are currently available (several states are no longer reporting) show Alaska (25.5%) and Vermont (25.4%) have the highest proportions of cumulative cases in children, and Florida (12.3%) and Utah (13.5%) have the lowest. Rhode Island has the highest rate of COVID-19 per 100,000 children at 40,427, while Missouri has the lowest at 14,252. The national average is 19,687 per 100,000, the AAP and CHA reported.
 

Taking a look at vaccination

Vaccinations were up slightly in children aged 12-17 years, as 20,000 initial doses were given during the week of Sept. 29 to Oct. 5, compared with 17,000 and 18,000 the previous 2 weeks. Initial vaccinations in younger children, however, continued declines dating back to August, the AAP said in its weekly vaccination trends report.

The District of Columbia and Massachusetts have the most highly vaccinated groups of 12- to 17-year-olds, as 100% and 95%, respectively, have received initial doses, while Wyoming (39%) and Idaho (42%) have the lowest. D.C. (73%) and Vermont (68%) have the highest proportions of vaccinated 5- to 11-year-olds, and Alabama (17%) and Mississippi (18%) have the lowest. For children under age 5 years, those in D.C. (33%) and Vermont (26%) are the most likely to have received an initial COVID vaccination, while Alabama, Louisiana, and Mississippi share national-low rates of 2%, the AAP said its report, which is based on CDC data.

When all states and territories are combined, 71% of children aged 12-17 have received at least one dose of vaccine, as have 38.6% of all children 5-11 years old and 6.7% of those under age 5. Almost 61% of the nation’s 16- to 17-year-olds have been fully vaccinated, along with 31.5% of those aged 5-11 and 2.4% of children younger than 5 years, the CDC said on its COVID Data Tracker.

About 42 million children – 58% of the population under the age of 18 years – have not received any vaccine yet, the AAP noted. Meanwhile, CDC data indicate that 36 children died of COVID in the last week, with pediatric deaths now totaling 1,781 over the course of the pandemic.

A small increase in new cases brought COVID-19’s latest losing streak to an end at 4 weeks, based on data from the American Academy of Pediatrics and the Children’s Hospital Association.

After the 57% decline in cases seen during those 4 weeks of September, new cases rose by 3.7% during the week of Sept. 30 to Oct. 6. The 40,656 new cases reported bring the U.S. cumulative count of child COVID-19 cases to over 14.8 million since the pandemic began, which represents 18.4% of all cases, the AAP and CHA said in their weekly report based on state-level data.

The increase in new cases was not reflected in emergency department visits or hospital admissions, which both continued sustained declines that started in August. In the week from Sept. 27 to Oct. 4, the 7-day averages for ED visits with diagnosed COVID were down by 21.5% (age 0-11), 27.3% (12-15), and 18.2% (16-17), the Centers for Disease Control and Prevention said, while the most recent 7-day average for new admissions – 127 per day for Oct. 2-8 – among children aged 0-17 years with confirmed COVID was down from 161 per day the previous week, a drop of over 21%.

The state-level data that are currently available (several states are no longer reporting) show Alaska (25.5%) and Vermont (25.4%) have the highest proportions of cumulative cases in children, and Florida (12.3%) and Utah (13.5%) have the lowest. Rhode Island has the highest rate of COVID-19 per 100,000 children at 40,427, while Missouri has the lowest at 14,252. The national average is 19,687 per 100,000, the AAP and CHA reported.
 

Taking a look at vaccination

Vaccinations were up slightly in children aged 12-17 years, as 20,000 initial doses were given during the week of Sept. 29 to Oct. 5, compared with 17,000 and 18,000 the previous 2 weeks. Initial vaccinations in younger children, however, continued declines dating back to August, the AAP said in its weekly vaccination trends report.

The District of Columbia and Massachusetts have the most highly vaccinated groups of 12- to 17-year-olds, as 100% and 95%, respectively, have received initial doses, while Wyoming (39%) and Idaho (42%) have the lowest. D.C. (73%) and Vermont (68%) have the highest proportions of vaccinated 5- to 11-year-olds, and Alabama (17%) and Mississippi (18%) have the lowest. For children under age 5 years, those in D.C. (33%) and Vermont (26%) are the most likely to have received an initial COVID vaccination, while Alabama, Louisiana, and Mississippi share national-low rates of 2%, the AAP said its report, which is based on CDC data.

When all states and territories are combined, 71% of children aged 12-17 have received at least one dose of vaccine, as have 38.6% of all children 5-11 years old and 6.7% of those under age 5. Almost 61% of the nation’s 16- to 17-year-olds have been fully vaccinated, along with 31.5% of those aged 5-11 and 2.4% of children younger than 5 years, the CDC said on its COVID Data Tracker.

About 42 million children – 58% of the population under the age of 18 years – have not received any vaccine yet, the AAP noted. Meanwhile, CDC data indicate that 36 children died of COVID in the last week, with pediatric deaths now totaling 1,781 over the course of the pandemic.

Pregnant or postpartum women with disabilities are at relatively high risk of experiencing violence, often from the people closest to them, new research suggests.

The researchers set out to measure risk of interpersonal violence, which the World Health Organization defines as “the intentional use of physical force or power against an individual by an intimate partner, family member, or other community member.”

Hilary K. Brown, PhD, with the department of health & society, University of Toronto, led the study published online in Obstetrics and Gynecology.

Large, population-based dataset

The population study included people 15-49 years old with births in Ontario from 2004 to 2019. They included 147,414 people with physical disabilities; 47,459 people with intellectual disabilities; 2,557 with developmental disabilities; and 9,598 with multiple disabilities.

The control group was 1,594,441 million people without disabilities.

The outcome measured was “any emergency department visit, hospital admission, or death related to physical, sexual, or psychological violence between fertilization and 365 days post partum.”

Researchers found that the adjusted relative risk of interpersonal violence for those with disabilities, compared with those with no disabilities was 1.40 (95% confidence interval, 1.31-1.50) in those with physical disabilities; 2.39 (95% CI, 1.98-2.88) in those with intellectual or developmental disabilities; and 1.96 (95% CI, 1.66-2.30) in those with multiple disabilities.
 

History of violence means higher risk

Those with a history of interpersonal violence and a disability were at particularly high risk for perinatal violence.

The authors note that pregnancy is a high-risk period for interpersonal violence for all women, particularly by an intimate partner.

“More than 30% of intimate partner violence begins during pregnancy, and preexisting violence tends to escalate perinatally,” they write.

The authors cite previous research that found women with disabilities experience higher rates of abuse overall and by an intimate partner – two to four times rates reported by those without disabilities.
 

Opportunities for provider intervention

Since the period surrounding pregnancy is a time of increased contact with medical providers and resources, there may be opportunities for identifying abuse and providing interventions.

Those might include better screening, access to violence-related information and services, and education of health care professionals to support people with disabilities. For example, “Tools used for violence screening perinatally do not include items about forms of violence that are unique to individuals with disabilities, such as refusal to assist with activities of daily living.”

The authors add: “[G]iven that the strongest risk factor for interpersonal violence in the perinatal period, particularly in those with disabilities, was a prepregnancy history of interpersonal violence, our findings suggest that more could be done before pregnancy to offer screening and support at the index encounter.”
 

Violence can lead to adverse outcomes

Implications are important as the violence can result in barriers to care and adverse perinatal outcomes.

Jeanne L. Alhusen, PhD, CRNP, RN, University of Virginia Medical Center professor of nursing and associate dean for research, was not part of this research but wrote a paper earlier this year on the subject and had similar conclusions.

She said before this study by Brown et al., “our understanding of the risk of violence by disability type throughout the perinatal period, on a population-based level, was quite limited.”

With the size of this dataset, she said, this paper provides critical information for health care providers. It extends physicians’ ability to examine risk of violence by disability type as well as these patients’ risk of experiencing different types of violence.

She pointed out that the Pregnancy Risk Assessment Monitoring System (PRAMS) recently incorporated a disability supplement that allows better understanding of pregnancy risks in people with disabilities.

“It will be critical that U.S. states continue to incorporate the disability questions into their PRAMS administration [because] without that information, persons with disabilities will continue to experience unconscionable inequities,” she said.
 

Barriers to equitable care

Dr. Alhusen added that people with disabilities experience significant barriers in accessing equitable care – both at the provider and the system level.

She said it is critical that we recognize and address the sexual and reproductive health needs of all persons with disability. “This includes screening every person for violence and [ensuring] the tools we utilize are accessible and include items specific to disability-related abuse. In our qualitative studies, we have heard from pregnant persons that they were never screened or that they were screened with their abusive partner sitting next to them.”
 

Screening questions to ask

The American College of Obstetricians and Gynecologists provides examples of screening questions that are specific to people with disabilities such as asking if a partner has ever prevented the individual from using an assistive device (for example, a wheelchair, cane, or respirator) or refused to help with an important personal need, such as taking medication or getting out of bed.

“For many reasons, people with disabilities are less likely to disclose violence, and health care professionals are less likely to ask them about it,” said coauthor of the current study, Yona Lunsky, PhD, clinician-scientist, Centre for Addiction and Mental Health, Toronto, in a statement. Based on the findings, she said, she hopes clinicians will see the need to develop disability-informed screening tools to capture abuse and identify the appropriate resources for this population before, during, and after pregnancy.

Coauthor Dr. Natasha Saunders receives an honorarium from the BMJ Group (Archives of Diseases in Childhood). Coauthor Dr. Simone N. Vigod receives royalties from UpToDate for authorship of materials related to depression and pregnancy. The other authors did not report any potential conflicts of interest. Dr. Alhusen reported no relevant financial relationships.

Pregnant or postpartum women with disabilities are at relatively high risk of experiencing violence, often from the people closest to them, new research suggests.

The researchers set out to measure risk of interpersonal violence, which the World Health Organization defines as “the intentional use of physical force or power against an individual by an intimate partner, family member, or other community member.”

Hilary K. Brown, PhD, with the department of health & society, University of Toronto, led the study published online in Obstetrics and Gynecology.

Large, population-based dataset

The population study included people 15-49 years old with births in Ontario from 2004 to 2019. They included 147,414 people with physical disabilities; 47,459 people with intellectual disabilities; 2,557 with developmental disabilities; and 9,598 with multiple disabilities.

The control group was 1,594,441 million people without disabilities.

The outcome measured was “any emergency department visit, hospital admission, or death related to physical, sexual, or psychological violence between fertilization and 365 days post partum.”

Researchers found that the adjusted relative risk of interpersonal violence for those with disabilities, compared with those with no disabilities was 1.40 (95% confidence interval, 1.31-1.50) in those with physical disabilities; 2.39 (95% CI, 1.98-2.88) in those with intellectual or developmental disabilities; and 1.96 (95% CI, 1.66-2.30) in those with multiple disabilities.
 

History of violence means higher risk

Those with a history of interpersonal violence and a disability were at particularly high risk for perinatal violence.

The authors note that pregnancy is a high-risk period for interpersonal violence for all women, particularly by an intimate partner.

“More than 30% of intimate partner violence begins during pregnancy, and preexisting violence tends to escalate perinatally,” they write.

The authors cite previous research that found women with disabilities experience higher rates of abuse overall and by an intimate partner – two to four times rates reported by those without disabilities.
 

Opportunities for provider intervention

Since the period surrounding pregnancy is a time of increased contact with medical providers and resources, there may be opportunities for identifying abuse and providing interventions.

Those might include better screening, access to violence-related information and services, and education of health care professionals to support people with disabilities. For example, “Tools used for violence screening perinatally do not include items about forms of violence that are unique to individuals with disabilities, such as refusal to assist with activities of daily living.”

The authors add: “[G]iven that the strongest risk factor for interpersonal violence in the perinatal period, particularly in those with disabilities, was a prepregnancy history of interpersonal violence, our findings suggest that more could be done before pregnancy to offer screening and support at the index encounter.”
 

Violence can lead to adverse outcomes

Implications are important as the violence can result in barriers to care and adverse perinatal outcomes.

Jeanne L. Alhusen, PhD, CRNP, RN, University of Virginia Medical Center professor of nursing and associate dean for research, was not part of this research but wrote a paper earlier this year on the subject and had similar conclusions.

She said before this study by Brown et al., “our understanding of the risk of violence by disability type throughout the perinatal period, on a population-based level, was quite limited.”

With the size of this dataset, she said, this paper provides critical information for health care providers. It extends physicians’ ability to examine risk of violence by disability type as well as these patients’ risk of experiencing different types of violence.

She pointed out that the Pregnancy Risk Assessment Monitoring System (PRAMS) recently incorporated a disability supplement that allows better understanding of pregnancy risks in people with disabilities.

“It will be critical that U.S. states continue to incorporate the disability questions into their PRAMS administration [because] without that information, persons with disabilities will continue to experience unconscionable inequities,” she said.
 

Barriers to equitable care

Dr. Alhusen added that people with disabilities experience significant barriers in accessing equitable care – both at the provider and the system level.

She said it is critical that we recognize and address the sexual and reproductive health needs of all persons with disability. “This includes screening every person for violence and [ensuring] the tools we utilize are accessible and include items specific to disability-related abuse. In our qualitative studies, we have heard from pregnant persons that they were never screened or that they were screened with their abusive partner sitting next to them.”
 

Screening questions to ask

The American College of Obstetricians and Gynecologists provides examples of screening questions that are specific to people with disabilities such as asking if a partner has ever prevented the individual from using an assistive device (for example, a wheelchair, cane, or respirator) or refused to help with an important personal need, such as taking medication or getting out of bed.

“For many reasons, people with disabilities are less likely to disclose violence, and health care professionals are less likely to ask them about it,” said coauthor of the current study, Yona Lunsky, PhD, clinician-scientist, Centre for Addiction and Mental Health, Toronto, in a statement. Based on the findings, she said, she hopes clinicians will see the need to develop disability-informed screening tools to capture abuse and identify the appropriate resources for this population before, during, and after pregnancy.

Coauthor Dr. Natasha Saunders receives an honorarium from the BMJ Group (Archives of Diseases in Childhood). Coauthor Dr. Simone N. Vigod receives royalties from UpToDate for authorship of materials related to depression and pregnancy. The other authors did not report any potential conflicts of interest. Dr. Alhusen reported no relevant financial relationships.

Pregnant or postpartum women with disabilities are at relatively high risk of experiencing violence, often from the people closest to them, new research suggests.

The researchers set out to measure risk of interpersonal violence, which the World Health Organization defines as “the intentional use of physical force or power against an individual by an intimate partner, family member, or other community member.”

Hilary K. Brown, PhD, with the department of health & society, University of Toronto, led the study published online in Obstetrics and Gynecology.

Large, population-based dataset

The population study included people 15-49 years old with births in Ontario from 2004 to 2019. They included 147,414 people with physical disabilities; 47,459 people with intellectual disabilities; 2,557 with developmental disabilities; and 9,598 with multiple disabilities.

The control group was 1,594,441 million people without disabilities.

The outcome measured was “any emergency department visit, hospital admission, or death related to physical, sexual, or psychological violence between fertilization and 365 days post partum.”

Researchers found that the adjusted relative risk of interpersonal violence for those with disabilities, compared with those with no disabilities was 1.40 (95% confidence interval, 1.31-1.50) in those with physical disabilities; 2.39 (95% CI, 1.98-2.88) in those with intellectual or developmental disabilities; and 1.96 (95% CI, 1.66-2.30) in those with multiple disabilities.
 

History of violence means higher risk

Those with a history of interpersonal violence and a disability were at particularly high risk for perinatal violence.

The authors note that pregnancy is a high-risk period for interpersonal violence for all women, particularly by an intimate partner.

“More than 30% of intimate partner violence begins during pregnancy, and preexisting violence tends to escalate perinatally,” they write.

The authors cite previous research that found women with disabilities experience higher rates of abuse overall and by an intimate partner – two to four times rates reported by those without disabilities.
 

Opportunities for provider intervention

Since the period surrounding pregnancy is a time of increased contact with medical providers and resources, there may be opportunities for identifying abuse and providing interventions.

Those might include better screening, access to violence-related information and services, and education of health care professionals to support people with disabilities. For example, “Tools used for violence screening perinatally do not include items about forms of violence that are unique to individuals with disabilities, such as refusal to assist with activities of daily living.”

The authors add: “[G]iven that the strongest risk factor for interpersonal violence in the perinatal period, particularly in those with disabilities, was a prepregnancy history of interpersonal violence, our findings suggest that more could be done before pregnancy to offer screening and support at the index encounter.”
 

Violence can lead to adverse outcomes

Implications are important as the violence can result in barriers to care and adverse perinatal outcomes.

Jeanne L. Alhusen, PhD, CRNP, RN, University of Virginia Medical Center professor of nursing and associate dean for research, was not part of this research but wrote a paper earlier this year on the subject and had similar conclusions.

She said before this study by Brown et al., “our understanding of the risk of violence by disability type throughout the perinatal period, on a population-based level, was quite limited.”

With the size of this dataset, she said, this paper provides critical information for health care providers. It extends physicians’ ability to examine risk of violence by disability type as well as these patients’ risk of experiencing different types of violence.

She pointed out that the Pregnancy Risk Assessment Monitoring System (PRAMS) recently incorporated a disability supplement that allows better understanding of pregnancy risks in people with disabilities.

“It will be critical that U.S. states continue to incorporate the disability questions into their PRAMS administration [because] without that information, persons with disabilities will continue to experience unconscionable inequities,” she said.
 

Barriers to equitable care

Dr. Alhusen added that people with disabilities experience significant barriers in accessing equitable care – both at the provider and the system level.

She said it is critical that we recognize and address the sexual and reproductive health needs of all persons with disability. “This includes screening every person for violence and [ensuring] the tools we utilize are accessible and include items specific to disability-related abuse. In our qualitative studies, we have heard from pregnant persons that they were never screened or that they were screened with their abusive partner sitting next to them.”
 

Screening questions to ask

The American College of Obstetricians and Gynecologists provides examples of screening questions that are specific to people with disabilities such as asking if a partner has ever prevented the individual from using an assistive device (for example, a wheelchair, cane, or respirator) or refused to help with an important personal need, such as taking medication or getting out of bed.

“For many reasons, people with disabilities are less likely to disclose violence, and health care professionals are less likely to ask them about it,” said coauthor of the current study, Yona Lunsky, PhD, clinician-scientist, Centre for Addiction and Mental Health, Toronto, in a statement. Based on the findings, she said, she hopes clinicians will see the need to develop disability-informed screening tools to capture abuse and identify the appropriate resources for this population before, during, and after pregnancy.

Coauthor Dr. Natasha Saunders receives an honorarium from the BMJ Group (Archives of Diseases in Childhood). Coauthor Dr. Simone N. Vigod receives royalties from UpToDate for authorship of materials related to depression and pregnancy. The other authors did not report any potential conflicts of interest. Dr. Alhusen reported no relevant financial relationships.

A 13-YEAR-OLD GIRL presented to the clinic with a 1-year history of a slow-growing mass on the third toe of her right foot. As a soccer player, she experienced associated pain when kicking the ball or when wearing tight-fitting shoes. The lesion was otherwise asymptomatic. She denied any overt trauma to the area and indicated that the mass had enlarged over the previous year.

On exam, there was a nontender 8 × 8-mm firm nodule underneath the nail with associated nail dystrophy (FIGURE 1). The toe had full mobility, sensation was intact, and capillary refill time was < 2 seconds.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Subungual exostosis

A plain radiograph of the patient’s foot showed continuity with the bony cortex and medullary space, confirming the diagnosis of subungual exostosis (FIGURE 2).¹ An exostosis, or osteochondroma, is a form of benign bone tumor in which trabecular bone overgrows its normal border in a nodular pattern. When this occurs under the nail bed, it is called subungual exostosis.² Exostosis represents 10% to 15% of all benign bone tumors, making it the most common benign bone tumor.³ Generally, the age of occurrence is 10 to 15 years.³

Repetitive trauma can be a culprit. Up to 8% of exostoses occur in the foot, with the most commonly affected area being the distal medial portion of the big toe.^3,4 Repetitive trauma and infection are potential risk factors.^3,4 The affected toe may be painful, but that is not always the case.⁴ Typically, lesions are solitary; however, multiple lesions can occur.⁴

Most pediatric foot lesions are benign and involve soft tissue

Benign soft-tissue masses make up the overwhelming majority of pediatric foot lesions, accounting for 61% to 87% of all foot lesions.³ Malignancies such as chondrosarcoma can occur and can be difficult to diagnose. Rapid growth, family history, size > 5 cm, heterogenous appearance on magnetic resonance imaging, and poorly defined margins are a few characteristics that should increase suspicion for possible malignancy.⁵

The definitive treatment for subungual exostosis is surgical excision, preferably once the patient has reached skeletal maturity.

The differential diagnosis for a growth on the toe similar to the one our patient had would include pyogenic granuloma, acral fibromyxoma, periungual fibroma, and verruca vulgaris.

Pyogenic granulomas are benign vascular lesions that occur in patients of all ages. They tend to be dome-shaped and flesh-toned to violaceous red, and they are usually found on the head, neck, and extremities—­especially fingers.⁶ They are associated with trauma and are classically tender with a propensity to bleed.⁶

Acral fibromyxoma is a benign, slow-growing, predominately painless, firm mass with an affinity for the great toe; the affected area includes the nail in 50% of cases.⁷ A radiograph may show bony erosion or scalloping due to mass effect; however, there will be no continuity with the bony matrix. (Such continuity would suggest exostosis.)

Periungual fibromas are benign soft-tissue masses, which are pink to red and firm, and emerge from underneath the nails, potentially resulting in dystrophy.⁸ They can bleed and cause pain, and are strongly associated with tuberous sclerosis.⁵

Continue to: Verruca vulgaris

Verruca vulgaris, the common wart, can also manifest in the subungual region as a firm, generally painless mass. It is the most common neoplasm of the hand and fingers.⁶ Tiny black dots that correspond to thrombosed capillaries are key to identifying this lesion.

Surgical excision when patient reaches maturity

The definitive treatment for subungual exostosis is surgical excision, preferably once the patient has reached skeletal maturity. Surgery at this point is associated with decreased recurrence rates.^3,4 That said, excision may need to be performed sooner if the lesion is painful and leading to deformity.³

Our patient’s persistent pain prompted us to recommend surgical excision. She underwent a third digit exostectomy, which she tolerated without any issues. The patient was fitted with a postoperative shoe that she wore until her 2-week follow-up appointment, when her sutures were removed. The patient’s activity level progressed as tolerated. She regained full function and returned to playing soccer, without any pain, 3 months after her surgery.

A 13-YEAR-OLD GIRL presented to the clinic with a 1-year history of a slow-growing mass on the third toe of her right foot. As a soccer player, she experienced associated pain when kicking the ball or when wearing tight-fitting shoes. The lesion was otherwise asymptomatic. She denied any overt trauma to the area and indicated that the mass had enlarged over the previous year.

On exam, there was a nontender 8 × 8-mm firm nodule underneath the nail with associated nail dystrophy (FIGURE 1). The toe had full mobility, sensation was intact, and capillary refill time was < 2 seconds.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Subungual exostosis

A plain radiograph of the patient’s foot showed continuity with the bony cortex and medullary space, confirming the diagnosis of subungual exostosis (FIGURE 2).¹ An exostosis, or osteochondroma, is a form of benign bone tumor in which trabecular bone overgrows its normal border in a nodular pattern. When this occurs under the nail bed, it is called subungual exostosis.² Exostosis represents 10% to 15% of all benign bone tumors, making it the most common benign bone tumor.³ Generally, the age of occurrence is 10 to 15 years.³

Repetitive trauma can be a culprit. Up to 8% of exostoses occur in the foot, with the most commonly affected area being the distal medial portion of the big toe.^3,4 Repetitive trauma and infection are potential risk factors.^3,4 The affected toe may be painful, but that is not always the case.⁴ Typically, lesions are solitary; however, multiple lesions can occur.⁴

Most pediatric foot lesions are benign and involve soft tissue

Benign soft-tissue masses make up the overwhelming majority of pediatric foot lesions, accounting for 61% to 87% of all foot lesions.³ Malignancies such as chondrosarcoma can occur and can be difficult to diagnose. Rapid growth, family history, size > 5 cm, heterogenous appearance on magnetic resonance imaging, and poorly defined margins are a few characteristics that should increase suspicion for possible malignancy.⁵

The definitive treatment for subungual exostosis is surgical excision, preferably once the patient has reached skeletal maturity.

The differential diagnosis for a growth on the toe similar to the one our patient had would include pyogenic granuloma, acral fibromyxoma, periungual fibroma, and verruca vulgaris.

Pyogenic granulomas are benign vascular lesions that occur in patients of all ages. They tend to be dome-shaped and flesh-toned to violaceous red, and they are usually found on the head, neck, and extremities—­especially fingers.⁶ They are associated with trauma and are classically tender with a propensity to bleed.⁶

Acral fibromyxoma is a benign, slow-growing, predominately painless, firm mass with an affinity for the great toe; the affected area includes the nail in 50% of cases.⁷ A radiograph may show bony erosion or scalloping due to mass effect; however, there will be no continuity with the bony matrix. (Such continuity would suggest exostosis.)

Periungual fibromas are benign soft-tissue masses, which are pink to red and firm, and emerge from underneath the nails, potentially resulting in dystrophy.⁸ They can bleed and cause pain, and are strongly associated with tuberous sclerosis.⁵

Continue to: Verruca vulgaris

Verruca vulgaris, the common wart, can also manifest in the subungual region as a firm, generally painless mass. It is the most common neoplasm of the hand and fingers.⁶ Tiny black dots that correspond to thrombosed capillaries are key to identifying this lesion.

Surgical excision when patient reaches maturity

The definitive treatment for subungual exostosis is surgical excision, preferably once the patient has reached skeletal maturity. Surgery at this point is associated with decreased recurrence rates.^3,4 That said, excision may need to be performed sooner if the lesion is painful and leading to deformity.³

Our patient’s persistent pain prompted us to recommend surgical excision. She underwent a third digit exostectomy, which she tolerated without any issues. The patient was fitted with a postoperative shoe that she wore until her 2-week follow-up appointment, when her sutures were removed. The patient’s activity level progressed as tolerated. She regained full function and returned to playing soccer, without any pain, 3 months after her surgery.

A 13-YEAR-OLD GIRL presented to the clinic with a 1-year history of a slow-growing mass on the third toe of her right foot. As a soccer player, she experienced associated pain when kicking the ball or when wearing tight-fitting shoes. The lesion was otherwise asymptomatic. She denied any overt trauma to the area and indicated that the mass had enlarged over the previous year.

On exam, there was a nontender 8 × 8-mm firm nodule underneath the nail with associated nail dystrophy (FIGURE 1). The toe had full mobility, sensation was intact, and capillary refill time was < 2 seconds.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

 

 

Diagnosis: Subungual exostosis

A plain radiograph of the patient’s foot showed continuity with the bony cortex and medullary space, confirming the diagnosis of subungual exostosis (FIGURE 2).¹ An exostosis, or osteochondroma, is a form of benign bone tumor in which trabecular bone overgrows its normal border in a nodular pattern. When this occurs under the nail bed, it is called subungual exostosis.² Exostosis represents 10% to 15% of all benign bone tumors, making it the most common benign bone tumor.³ Generally, the age of occurrence is 10 to 15 years.³

Repetitive trauma can be a culprit. Up to 8% of exostoses occur in the foot, with the most commonly affected area being the distal medial portion of the big toe.^3,4 Repetitive trauma and infection are potential risk factors.^3,4 The affected toe may be painful, but that is not always the case.⁴ Typically, lesions are solitary; however, multiple lesions can occur.⁴

Most pediatric foot lesions are benign and involve soft tissue

Benign soft-tissue masses make up the overwhelming majority of pediatric foot lesions, accounting for 61% to 87% of all foot lesions.³ Malignancies such as chondrosarcoma can occur and can be difficult to diagnose. Rapid growth, family history, size > 5 cm, heterogenous appearance on magnetic resonance imaging, and poorly defined margins are a few characteristics that should increase suspicion for possible malignancy.⁵

The definitive treatment for subungual exostosis is surgical excision, preferably once the patient has reached skeletal maturity.

The differential diagnosis for a growth on the toe similar to the one our patient had would include pyogenic granuloma, acral fibromyxoma, periungual fibroma, and verruca vulgaris.

Pyogenic granulomas are benign vascular lesions that occur in patients of all ages. They tend to be dome-shaped and flesh-toned to violaceous red, and they are usually found on the head, neck, and extremities—­especially fingers.⁶ They are associated with trauma and are classically tender with a propensity to bleed.⁶

Acral fibromyxoma is a benign, slow-growing, predominately painless, firm mass with an affinity for the great toe; the affected area includes the nail in 50% of cases.⁷ A radiograph may show bony erosion or scalloping due to mass effect; however, there will be no continuity with the bony matrix. (Such continuity would suggest exostosis.)

Periungual fibromas are benign soft-tissue masses, which are pink to red and firm, and emerge from underneath the nails, potentially resulting in dystrophy.⁸ They can bleed and cause pain, and are strongly associated with tuberous sclerosis.⁵

Continue to: Verruca vulgaris

Verruca vulgaris, the common wart, can also manifest in the subungual region as a firm, generally painless mass. It is the most common neoplasm of the hand and fingers.⁶ Tiny black dots that correspond to thrombosed capillaries are key to identifying this lesion.

Surgical excision when patient reaches maturity

The definitive treatment for subungual exostosis is surgical excision, preferably once the patient has reached skeletal maturity. Surgery at this point is associated with decreased recurrence rates.^3,4 That said, excision may need to be performed sooner if the lesion is painful and leading to deformity.³

Our patient’s persistent pain prompted us to recommend surgical excision. She underwent a third digit exostectomy, which she tolerated without any issues. The patient was fitted with a postoperative shoe that she wore until her 2-week follow-up appointment, when her sutures were removed. The patient’s activity level progressed as tolerated. She regained full function and returned to playing soccer, without any pain, 3 months after her surgery.

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

A version of this article first appeared on Medscape.com.

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

A version of this article first appeared on Medscape.com.

Google the word “dopamine” and you will learn that its nicknames are the “happy hormone” and the “pleasure molecule” and that it is among the most important chemicals in our brains. With The Guardian branding it “the Kim Kardashian of neurotransmitters,” dopamine has become a true pop-science darling – people across the globe have attempted to boost their mood with dopamine fasts and dopamine dressing.

A century ago, however, newly discovered dopamine was seen as an uninspiring chemical, nothing more than a precursor of noradrenaline. It took several stubborn and hardworking scientists to change that view.
 

Levodopa: An indifferent precursor

When Casimir Funk, PhD, a Polish biochemist and the discoverer of vitamins, first synthesized the dopamine precursor levodopa in 1911, he had no idea how important the molecule would prove to be in pharmacology and neurobiology. Nor did Markus Guggenheim, PhD, a Swiss biochemist, who isolated levodopa in 1913 from the seeds of a broad bean, Vicia faba. Dr. Guggenheim administered 1 g of levodopa to a rabbit, with no apparent negative consequences. He then prepared a larger dose (2.5 g) and tested it on himself. “Ten minutes after taking it, I felt very nauseous, I had to vomit twice,” he wrote in his paper. In the body, levodopa is converted into dopamine, which may act as an emetic – an effect Dr. Guggenheim didn’t understand. He simply abandoned his human study, erroneously concluding, on the basis of his animal research, that levodopa is “pharmacologically fairly indifferent.”

Around the same time, several scientists across Europe successfully synthesized dopamine, but those discoveries were shelved without much fanfare. For the next 3 decades, dopamine and levodopa were pushed into academic obscurity. Just before World War II, a group of German scientists showed that levodopa is metabolized to dopamine in the body, while another German researcher, Hermann Blaschko, MD, discovered that dopamine is an intermediary in the synthesis of noradrenaline. Even these findings, however, were not immediately accepted.

The dopamine story picked up pace in the post-war years with the observation that the hormone was present in various tissues and body fluids, although nowhere as abundantly as in the central nervous system. Intrigued, Dr. Blaschko, who (after escaping Nazi Germany, changing his name to Hugh, and starting work at Oxford [England] University) hypothesized that dopamine couldn’t be an unremarkable precursor of noradrenaline – it had to have some physiologic functions of its own. He asked his postdoctoral fellow, Oheh Hornykiewicz, MD, to test a few ideas. Dr. Hornykiewicz soon confirmed that dopamine lowered blood pressure in guinea pigs, proving that dopamine indeed had physiologic activity that was independent of other catecholamines.
 

Reserpine and rabbit ears

While Dr. Blaschko and Dr. Hornykiewicz were puzzling over dopamine’s physiologic role in the body, across the ocean at the National Heart Institute in Maryland, pharmacologist Bernard Brodie, PhD and colleagues were laying the groundwork for the discovery of dopamine’s starring role in the brain.

Spoiler alert: Dr. Brodie’s work showed that a new psychiatric drug known as reserpine was capable of fully depleting the brain’s stores of serotonin and – of greatest significance, as it turned out – mimicking the neuromuscular symptoms typical of Parkinson’s disease. The connection to dopamine would be made by new lab colleague Arvid Carlsson, MD, PhD, who would go on to win a Nobel Prize.

Derived from Rauwolfia serpentina (a plant that for centuries has been used in India for the treatment of mental illness, insomnia, and snake bites), reserpine was introduced in the West as a treatment for schizophrenia.

It worked marvels. In 1954, the press lauded the “dramatic” and seemingly “incredible”: results in treating “hopelessly insane patients.” Reserpine had a downside, however. Reports soon changed in tone regarding the drug’s severe side effects, including headaches, dizziness, vomiting, and, far more disturbingly, symptoms mimicking Parkinson’s disease, from muscular rigidity to tremors.

Dr. Brodie observed that, when reserpine was injected, animals became completely immobile. Serotonin nearly vanished from their brains, but bizarrely, drugs that spur serotonin production did not reverse the rabbits’ immobility.

Dr. Carlsson realized that other catecholamines must be involved in reserpine’s side effects, and he began to search for the culprits. He moved back to his native Sweden and ordered a spectrophotofluorimeter. In one of his experiments, Carlsson injected a pair of rabbits with reserpine, which caused the animals to become catatonic with flattened ears. After the researchers injected the animals with levodopa, within 15 minutes, the rabbits were hopping around, ears proudly vertical. “We were just as excited as the rabbits,” Dr. Carlsson later recalled in a 2016 interview. Dr. Carlsson realized that, because there was no noradrenaline in the rabbits’ brains, dopamine depletion must have been directly responsible for producing reserpine’s motor inhibitory effects.
 

Skeptics are silenced

In 1960, however, the medical community was not yet ready to accept that dopamine was anything but a boring intermediate between levodopa and noradrenaline. At a prestigious London symposium, Dr. Carlsson and his two colleagues presented their hypothesis that dopamine may be a neurotransmitter, thus implicating it in Parkinson’s disease. They were met with harsh criticism. Some of the experts said levodopa was nothing more than a poison. Dr. Carlsson later recalled facing “a profound and nearly unanimous skepticism regarding our points of view.”

That would soon change. Dr. Hornykiewicz, the biochemist who had earlier discovered dopamine’s BP-lowering effects, tested Dr. Carlsson’s ideas using the postmortem brains of Parkinson’s disease patients. It appeared Dr. Carlsson was right: Unlike in healthy brains, the striatum of patients with Parkinson’s disease contained almost no dopamine whatsoever. Beginning in 1961, in collaboration with neurologist Walther Birkmayer, MD, Hornykiewicz injected levodopa into 20 patients with Parkinson’s disease and observed a “miraculous” (albeit temporary) amelioration of rigidity, motionlessness, and speechlessness.

By the late 1960s, levodopa and dopamine were making headlines. A 1969 New York Times article described similar stunning improvements in patients with Parkinson’s disease who were treated with levodopa. A patient who had arrived at a hospital unable to speak, with hands clenched and rigid expression, was suddenly able to stride into his doctor’s office and even jog around. “I might say I’m a human being,” he told reporters. Although the treatment was expensive – equivalent to $210 in 2022 – physicians were deluged with requests for “dopa.” To this day, levodopa remains a gold standard in the treatment of Parkinson’s disease.
 

Still misunderstood

The history of dopamine, however, is not only about Parkinson’s disease but extends to the treatment of schizophrenia and addiction. When in the1940s a French military surgeon started giving a new antihistamine drug, promethazine, to prevent shock in soldiers undergoing surgery, he noticed a bizarre side effect: the soldiers would become euphoric yet oddly calm at the same time.

After the drug was modified by adding a chlorine atom and renamed chlorpromazine, it fast became a go-to treatment for psychosis. At the time, no one made the connection to dopamine. Contemporary doctors believed that it calmed people by lowering body temperature (common treatments for mental illness back in the day included swaddling patients in cold, wet sheets). Yet just like reserpine, chlorpromazine produced range of nasty side effects that closely mimicked Parkinson’s disease. This led a Dutch pharmacologist, Jacques van Rossum, to hypothesize that dopamine receptor blockade could explain chlorpromazine’s antipsychotic effects – an idea that remains widely accepted today.

In the 1970s, dopamine was linked with addiction through research on rodents, and this novel idea caught people’s imagination over the coming decades. A story on dopamine titled, “How We Get Addicted,” made the cover of Time in 1997.

Yet as the dopamine/addiction connection became widespread, it also became oversimplified. According to a 2015 article in Nature Reviews Neuroscience, a wave of low-quality research followed – nonreplicated, insufficient – which led the authors to conclude that we are “addicted to the dopamine theory of addiction.” Just about every pleasure under the sun was being attributed to dopamine, from eating delicious foods and playing computer games to sex, music, and hot showers. As recent science shows, however, dopamine is not simply about pleasure – it’s about reward prediction, response to stress, memory, learning, and even the functioning of the immune system. Since its first synthesis in the early 20th century, dopamine has often been misunderstood and oversimplified – and it seems the story is repeating itself now.

In one of his final interviews, Dr. Carlsson, who passed away in 2018 at the age of 95, warned about playing around with dopamine and, in particular, prescribing drugs that have an inhibitory action on this neurotransmitter. “Dopamine is involved in everything that happens in our brains – all its important functions,” he said.

We should be careful how we handle such a delicate and still little-known system.

A version of this article first appeared on Medscape.com.

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

A version of this article first appeared on Medscape.com.

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

A version of this article first appeared on Medscape.com.

Whatever the mechanism of benefit from dapagliflozin (Farxiga) in patients with heart failure (HF) – and potentially also other sodium-glucose cotransporter 2 (SGLT2) inhibitors – its blood pressure lowering effects aren’t likely to contribute much.

Indeed, at least in patients with HF and non-reduced ejection fractions, dapagliflozin has only a modest BP-lowering effect and cuts cardiovascular (CV) risk regardless of baseline pressure or change in systolic BP, suggests a secondary analysis from the large placebo-controlled DELIVER trial.

Systolic BP fell over 1 month by just under 2 mmHg, on average, in trial patients with either mildly reduced or preserved ejection fraction (HFmrEF or HFpEF, respectively) assigned to take dapagliflozin versus placebo.

The effect was achieved without increasing the risk for adverse events from dapagliflozin, even among patients with the lowest baseline systolic pressures. Adverse outcomes overall, however, were more common at the lowest systolic BP level than at higher pressures, researchers reported.

They say the findings should help alleviate long-standing concerns that initiating SGLT2 inhibitors, with their recognized diuretic effects, might present a hazard in patients with HF and low systolic BP.

“It is a consistent theme in heart failure trials that the blood pressure–lowering effect of SGLT2 inhibitors is more modest than it is in non–heart-failure populations,” Senthil Selvaraj, MD, Duke University, Durham, N.C., told this news organization.

Changes to antihypertensive drug therapy throughout the trial, which presumably enhanced BP responses and “might occur more frequently in the placebo group,” Dr. Selvaraj said, “might explain why the blood pressure effect is a little bit more modest in this population.”

Dr. Selvaraj presented the analysis at the Annual Scientific Meeting of the Heart Failure Society of America, held in National Harbor, Md., and is lead author on its same-day publication in JACC: Heart Failure.

The findings “reinforce the clinical benefits of SGLT2 inhibitors in patients with heart failure across the full spectrum of ejection fractions and large range of systolic blood pressures,” said Gregg C. Fonarow, MD, University of California, Los Angeles Medical Center, who was not part of the DELIVER analysis.

The study’s greater adjusted risks for CV and all-cause mortality risks at the lowest baseline systolic pressures “parallels a series of observational analyses from registries, including OPTIMIZE-HF,” Dr. Fonarow observed.

A version of this article first appeared on Medscape.com.

Dermoscopy revealed a uniform, sharply demarcated, slightly scaly lesion on a background of occasional scale and solar-damaged skin. This appearance, paired with the absence of abnormal blood vessels or suspicious, irregular pigmentation, pointed to a diagnosis of benign lichenoid keratosis also known as lichenoid keratosis (LK) or lichen planus-like keratosis. (It’s worth noting that in some cases, a dermoscopic evaluation will reveal blue-grey dots rather than the uniform, velvety brown pigmentation that was seen here.)

LK is a benign reactive inflammatory lesion that usually manifests as a solitary lesion in middle age. LKs can be found on the trunk or lower extremities. As the alternative name “lichen planus-like keratosis” implies, the lesions can be purple, polygonal, raised, and have stria. The etiology is unknown but thought to be a reaction to a lentigo or another lesion, resulting in an inflammatory infiltrate.¹

If dermoscopic evaluation of the lesion is unclear, biopsy is warranted. Maor et al¹ reported the pathology results of 263 consecutive patients with a histologic diagnosis of LK. Of those cases, 47% were clinically thought to be basal cell carcinoma (BCC) and 18% were submitted with a diagnosis of seborrheic keratosis.¹ The high rate of concern for BCC and not listing a diagnosis of LK may have been the result of clinicians doing biopsies on the atypical lesions and clinically following the typical banal lesions.

At the patient’s request, he was given a written list of the diagnoses of his various skin lesions and advised that his LK was benign and did not require treatment. He was advised to continue coming in for serial skin examinations and report any concerning lesions in the interim.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.

Dermoscopy revealed a uniform, sharply demarcated, slightly scaly lesion on a background of occasional scale and solar-damaged skin. This appearance, paired with the absence of abnormal blood vessels or suspicious, irregular pigmentation, pointed to a diagnosis of benign lichenoid keratosis also known as lichenoid keratosis (LK) or lichen planus-like keratosis. (It’s worth noting that in some cases, a dermoscopic evaluation will reveal blue-grey dots rather than the uniform, velvety brown pigmentation that was seen here.)

LK is a benign reactive inflammatory lesion that usually manifests as a solitary lesion in middle age. LKs can be found on the trunk or lower extremities. As the alternative name “lichen planus-like keratosis” implies, the lesions can be purple, polygonal, raised, and have stria. The etiology is unknown but thought to be a reaction to a lentigo or another lesion, resulting in an inflammatory infiltrate.¹

If dermoscopic evaluation of the lesion is unclear, biopsy is warranted. Maor et al¹ reported the pathology results of 263 consecutive patients with a histologic diagnosis of LK. Of those cases, 47% were clinically thought to be basal cell carcinoma (BCC) and 18% were submitted with a diagnosis of seborrheic keratosis.¹ The high rate of concern for BCC and not listing a diagnosis of LK may have been the result of clinicians doing biopsies on the atypical lesions and clinically following the typical banal lesions.

At the patient’s request, he was given a written list of the diagnoses of his various skin lesions and advised that his LK was benign and did not require treatment. He was advised to continue coming in for serial skin examinations and report any concerning lesions in the interim.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.

Dermoscopy revealed a uniform, sharply demarcated, slightly scaly lesion on a background of occasional scale and solar-damaged skin. This appearance, paired with the absence of abnormal blood vessels or suspicious, irregular pigmentation, pointed to a diagnosis of benign lichenoid keratosis also known as lichenoid keratosis (LK) or lichen planus-like keratosis. (It’s worth noting that in some cases, a dermoscopic evaluation will reveal blue-grey dots rather than the uniform, velvety brown pigmentation that was seen here.)

LK is a benign reactive inflammatory lesion that usually manifests as a solitary lesion in middle age. LKs can be found on the trunk or lower extremities. As the alternative name “lichen planus-like keratosis” implies, the lesions can be purple, polygonal, raised, and have stria. The etiology is unknown but thought to be a reaction to a lentigo or another lesion, resulting in an inflammatory infiltrate.¹

If dermoscopic evaluation of the lesion is unclear, biopsy is warranted. Maor et al¹ reported the pathology results of 263 consecutive patients with a histologic diagnosis of LK. Of those cases, 47% were clinically thought to be basal cell carcinoma (BCC) and 18% were submitted with a diagnosis of seborrheic keratosis.¹ The high rate of concern for BCC and not listing a diagnosis of LK may have been the result of clinicians doing biopsies on the atypical lesions and clinically following the typical banal lesions.

At the patient’s request, he was given a written list of the diagnoses of his various skin lesions and advised that his LK was benign and did not require treatment. He was advised to continue coming in for serial skin examinations and report any concerning lesions in the interim.

‌

Image and text courtesy of Daniel Stulberg, MD, FAAFP, Professor and Chair, Department of Family and Community Medicine, Western Michigan University Homer Stryker MD School of Medicine, Kalamazoo.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Weight loss after bariatric surgery was linked with visceral fat reduction as well as reduced blood pressure, fasting glucose, and left ventricular remodeling, based an imaging study in 213 patients.

“We found that ventricular function measured by strain imaging improved in both the left and right sides of the heart, but function measured in the traditional method using endocardial motion [in other words, ejection fraction] actually worsened,” senior investigator Barry A. Borlaug, MD, said in an interview.

Although previous studies have shown positive effects of weight loss on the heart after bariatric surgery, most have been short term and have not specifically examined the effects of visceral fat reduction, wrote the investigators.

“We are in the middle of an increasing epidemic of obesity worldwide, but particularly in the United States, where it is currently projected that one in two adults will be obese by 2030,” added Dr. Borlaug of Mayo Clinic, Rochester, Minn. “Heart failure with preserved ejection fraction (HFpEF) is growing in tandem, and numerous recent studies have shown that obesity is one of the strongest risk factors for developing HFpEF, and that the severity of HFpEF is intimately linked to excess body fat. This suggests that therapies to reduce body fat could improve the cardiac abnormalities that cause HFpEF, which was our focus in this study,” he explained.

In the study, published in the Journal of the American College of Cardiology, the researchers reviewed echocardiography data from 213 obese patients before and more than 180 days after bariatric surgery. They also measured abdominal visceral adipose tissue (VAT) of 52 patients via computed tomography. The average age of the patients was 54 years, the average body mass index was 45 kg/m², and 67% were women. Comorbidities included hypertension, diabetes, dyslipidemia, and obstructive sleep apnea.

The primary outcome was changes in cardiac structure and function.

After a median follow-up of 5.3 years, patients overall averaged a 23% reduction in body weight and a 22% reduction in BMI. In the 52 patients with abdominal scans, the VAT area decreased by 30% overall. Changes in left ventricular mass were significantly correlated to changes in the VAT.

Epicardial adipose thickness decreased by 14% overall. Left and right ventricular longitudinal strains improved at follow-up, but left atrial strain deteriorated, the researchers noted.

Although the mechanism of action remains unclear, the results suggest that left ventricular remodeling was associated with visceral adiposity rather than subcutaneous fat, the researchers wrote.

They also found that right ventricular strain was negatively correlated with VAT, but not with body weight or BMI.

“These findings suggest that weight loss, particularly reduction in visceral adiposity, benefits [right ventricular] structure and function in a manner akin to that observed in the [left ventricle],” the researchers noted.

Some surprises and limitations

Dr. Borlaug said he found some, but not all, of the results surprising. “Earlier studies had shown evidence for benefit from weight loss on cardiac structure and function, but had been limited by smaller sample sizes, shorter durations of evaluation, and variable methods used,” he said in an interview.

The findings that strain imaging showed both left and right ventricular function improved while EF declined “shows some of the problems with using EF, as it is affected by chamber size and geometry. We have previously shown that patients with HFpEF display an increase in fat around the heart, and this affects cardiac function and interaction between the left and right sides of the heart, so we expected to see that this fat depot would be reduced, and this was indeed the case,” Dr. Borlaug added.

In the current study, “visceral fat was most strongly tied to the heart remodeling in obesity, and changes in visceral fat were most strongly tied to improvements in cardiac structure following weight loss,” Dr. Borlaug told this news organization. “This further supports this concept that excess visceral fat plays a key role in HFpEF, especially in the abdomen and around the heart,” he said.

However, “The biggest surprise was the discordant effects in the left atrium,” Dr. Borlaug said. “Left atrial remodeling and dysfunction play a crucial role in HFpEF as well, and we expected that this would improve following weight loss, but in fact we observed that left atrial function deteriorated, and other indicators of atrial myopathy worsened, including higher estimates of left atrial pressures and increased prevalence of atrial fibrillation,” he said.

This difference emphasizes that weight loss may not address all abnormalities that lead to HFpEF, although a key limitation of the current study was the lack of a control group of patients with the same degree of obesity and no weight-loss intervention, and the deterioration in left atrial function might have been even greater in the absence of weight loss, Dr. Borlaug added.
 

Larger numbers support effects

Previous research shows that structural heart changes associated with obesity can be reversed through weight loss, but the current study fills a gap by providing long-term data in a larger sample than previously studied, wrote Paul Heidenreich, MD, of Stanford (Calif.) University in an accompanying editorial).

“There has been uncertainty regarding the prolonged effect of weight loss on cardiac function; this study was larger than many prior studies and provided a longer follow-up,” Dr. Heidenreich said in an interview.

“One unusual finding was that, while weight loss led to left ventricle reverse remodeling (reduction in wall thickness), the same effect was not seen for the left atrium; the left atrial size continued to increase,” he said. “I would have expected the left atrial changes to mirror the changes in the left ventricle,” he noted.

The findings support the greater cardiac risk of visceral vs. subcutaneous adipose tissue, and although body mass index will retain prognostic value, measures of central obesity are more likely predictors of cardiac structural changes and events and should be reported in clinical studies, Dr. Heidenreich wrote.

However, “We need a better understanding of the factors that influence left atrial remodeling and reverse remodeling,” Dr. Heidenreich told this news organization. “While left ventricular compliance and pressure play a role, there are other factors that need to be elucidated,” he said.

 

Studies in progress may inform practice

The current data call for further study to test novel treatments to facilitate weight loss in patients with HFpEF and those at risk for HFpEF, and some of these studies with medicines are underway, Dr. Borlaug said in the interview.

“Until such studies are completed, we will not truly understand the effects of weight loss on the heart, but the present data certainly provide strong support that patients who have obesity and HFpEF or are at risk for HFpEF should try to lose weight through lifestyle interventions,” he said. 

Whether the cardiac changes seen in the current study would be different with nonsurgical weight loss remains a key question because many obese patients are reluctant to undergo bariatric surgery, Dr. Borlaug said. “We cannot assess whether the effects would differ with nonsurgical weight loss, and this requires further study,” he added.

As for additional research, “Randomized, controlled trials of weight-loss interventions, with appropriate controls and comprehensive assessments of cardiac structure, function, and hemodynamics will be most informative,” said Dr. Borlaug. “Larger trials powered to evaluate cardiovascular outcomes such as heart failure hospitalization or cardiovascular death also are critically important to better understand the role of weight loss to treat and prevent HFpEF, the ultimate form of obesity-related heart disease,” he emphasized.

The study was supported in part by grants to lead author Dr. Hidemi Sorimachi of the Mayo Clinic from the Uehara Memorial Foundation, Japan, and to corresponding author Dr. Borlaug from the National Institutes of Health. Dr. Borlaug also disclosed previous grants from National Institutes of Health/National Heart, Lung, and Blood Institute, AstraZeneca, Corvia, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr. Heidenreich had no financial disclosures.

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Exposure to air pollution not only raises stroke risk, but it is also tied to poor post-stroke outcomes, including death. Results of a UK biobank study show high levels of air pollution were associated with an increased risk of transition from health to a first stroke and subsequent progression to cardiovascular (CV) events and death.

“These results indicate that understanding and reducing the effects of air pollutants on different transition stages in stroke will be beneficial in managing people’s health and preventing the occurrence and progression of stroke,” study investigator Hualiang Lin, PhD, of Sun Yat-sen University School of Public Health, Guangzhou, China, said in a news release.

The study was published online  in the journal Neurology.
 

A way to stop stroke progression?

The researchers assessed air pollution exposure in 318,752 people (mean age, 56) from the UK biobank database. None had a history of stroke or heart disease at the start of the study. Annual concentrations of air pollution near where people lived were estimated through land-use regressions.

During an average follow-up of 12 years, 5,967 people had a stroke, 2,985 developed post-stroke CVD, and 1,020 died.

After adjusting for confounding factors, every 5 µg/m³ increase in exposure to fine particulate matter (PM_2.5) was associated with a 24% increase in transition from healthy to first stroke (hazard ratio, 1.24; 95% confidence interval, 1.10-1.40) and a 30% increase in transition from being healthy to dying (HR, 1.30; 95% CI, 1.21-1.40).

PM_2.5 is less than 2.5 microns in diameter and includes fly ash from coal combustion. The World Health Organization recommends that annual PM_2.5 exposure should not exceed 5 µg/m³.

Those who had a stroke during the study had an average exposure of 10.03 µg/m³ of PM_2.5, compared with 9.97 µg/m³ for those who did not have a stroke.

The air pollutants nitrogen oxide and nitrogen dioxide were also associated with an increased risk of stroke and death, but the associations were weaker.

“More research is needed, but it’s possible that decreasing exposure to heavy levels of air pollution could play a role in reducing the progression of stroke,” Dr. Lin said.

“People can reduce their exposure by staying indoors on heavy pollution days, reducing their outdoor exercise, wearing masks to filter out particulate matter, and using air purifiers,” Dr. Lin added.

Public policy implications

Reached for comment, Steffen E. Petersen, MD, MPH, professor of cardiovascular medicine, Barts Health NHS Trust, London, said the study “elegantly confirms the increased risk of stroke due to air pollution in the UK Biobank population study but interestingly suggests that the impact of air pollution may continue to adversely impact cardiovascular health even after the stroke occurred.”

“This is further evidence to inform policymakers to tackle air pollution and get levels below the recommended levels,” Dr. Petersen said.

“On a personal level, everyone, including stroke patients, may wish to consider personal measures to reduce exposure to air pollution, such as avoiding walking along polluted streets and rather take a less polluted route away from the main roads,” Dr. Petersen added.

The study had no targeted funding. Dr. Lin and Dr. Petersen report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A weighted blanket of approximately 12% body weight used at bedtime prompted the release of higher concentrations of melatonin, as measured in the saliva, compared with a lighter blanket of only about 2.4% of body weight.

This suggests that weighted blankets may help promote sleep in patients suffering from insomnia, according to the results from the small, in-laboratory crossover study.

“Melatonin is produced by the pineal gland and plays an essential role in sleep timing,” lead author Elisa Meth, PhD student, Uppsala University, Sweden, and colleagues observe.

“Using a weighted blanket increased melatonin concentration in saliva by about 30%,” Ms. Meth added in a statement.

“Future studies should investigate whether the stimulatory effect on melatonin secretion remains when using a weighted blanket over more extended periods,” the researchers observe, and caution that “it is also unclear whether the observed increase in melatonin is therapeutically relevant.”

The study was published online in the Journal of Sleep Research.

Weighted blankets are commercially available at least in some countries in Scandinavia and Germany, as examples, and in general, they are sold for therapeutic purposes. And at least one study found that weighted blankets were an effective and safe intervention for insomnia in patients with major depressive disorder, bipolar disorder, generalized anxiety disorder, and attention deficit hyperactivity disorder and led to improvements in daytime symptoms and levels of activity.
 

Study done in healthy volunteers

The study involved a total of 26 healthy volunteers, 15 men and 11 women, none of whom had any sleep issues. “The day before the first testing session, the participants visited the laboratory for an adaptation night,” the authors observe. There were two experimental test nights, one in which the weighted blanket was used and the second during which the lighter blanket was used.

On the test nights, lights were dimmed between 9 PM and 11 PM and participants used a weighted blanket covering the extremities, abdomen, and chest 1 hour before and during 8 hours of sleep. As the authors explain, the filling of the weighted blanket consisted of honed glass pearls, combined with polyester wadding, which corresponded to 12.2% of participants’ body weight.

“Saliva was collected every 20 minutes between 22:00 and 23:00,” Ms. Meth and colleagues note. Participants’ subjective sleepiness was also assessed every 20 minutes using the Karolinska Sleepiness Scale both before the hour that lights were turned off and the next morning.

“Sleep duration in each experimental night was recorded with the OURA ring,” investigators explain.

The OURA ring is a commercial multisensor wearable device that measures physiological variables indicative of sleep. Investigators focused on total sleep duration as the primary outcome measure.

On average, salivary melatonin concentrations rose by about 5.8 pg/mL between 10 PM and 11 PM (P < .001), but the average increase in salivary melatonin concentrations was greater under weighted blanket conditions at 6.6 pg/mL, compared with 5.0 pg/mL during the lighter blanket session (P = .011).

Oxytocin in turn rose by about 315 pg/mL initially, but this rise was only transient, and over time, no significant difference in oxytocin levels was observed between the two blanket conditions. There were also no differences in cortisol levels or the activity of the sympathetic nervous system between the weighted and light blanket sessions.

Importantly, as well, no significant differences were seen in the level of sleepiness between participants when either blanket was used nor was there a significant difference in total sleep duration.

“Our study cannot identify the underlying mechanism for the observed stimulatory effects of the weighted blanket on melatonin,” the investigators caution.

However, one explanation could be that the pressure exerted by the weighted blanket activates cutaneous sensory afferent nerves, carrying information to the brain. The region where the sensory information is delivered stimulates oxytocinergic neurons that can promote calm and well-being and decrease fear, stress, and pain. In addition, these neurons also connect to the pineal gland to influence the release of melatonin, the authors explain.
 

Melatonin often viewed in the wrong context

Senior author Christian Benedict, PhD, associate professor of pharmacology, Uppsala University, Sweden, explained that some people think of melatonin in the wrong context.

In point of fact, “it’s not a sleep-promoting hormone. It prepares your body and brain for the biological night ... [and] sleep coincides with the biological night, but it’s not like you take melatonin and you have a very nice uninterrupted slumber – this is not true,” he told this news organization.

He also noted that certain groups respond to melatonin better than others. For example, children with attention deficit hyperactivity disorder may have some benefit from melatonin supplements, as may the elderly who can no longer produce sufficient amounts of melatonin and for whom supplements may help promote the timing of sleep.

However, the bottom line is that, even in those who do respond to melatonin supplements, they likely do so through a placebo effect that meta-analyses have shown plays a powerful role in promoting sleep. 

Dr. Benedict also stressed that just because the body makes melatonin, itself, does not mean that melatonin supplements are necessarily “safe.”

“We know melatonin has some impact on puberty – it may delay the onset of puberty – and we know that it can also impair blood glucose, so when people are eating and have a lot of melatonin on board, the melatonin will tell the pancreas to turn off insulin production, which can give rise to hyperglycemia,” he said.

However, Dr. Benedict cautioned that weighted blankets don’t come cheap. A quick Google search brings up examples that cost upwards of $350. “MDs can say try one if you can afford these blankets, but perhaps people can use several less costly blankets,” he said. “But I definitely think if there are cheap options, why not?” he concluded.

Dr. Benedict has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A weighted blanket of approximately 12% body weight used at bedtime prompted the release of higher concentrations of melatonin, as measured in the saliva, compared with a lighter blanket of only about 2.4% of body weight.

This suggests that weighted blankets may help promote sleep in patients suffering from insomnia, according to the results from the small, in-laboratory crossover study.

“Melatonin is produced by the pineal gland and plays an essential role in sleep timing,” lead author Elisa Meth, PhD student, Uppsala University, Sweden, and colleagues observe.

“Using a weighted blanket increased melatonin concentration in saliva by about 30%,” Ms. Meth added in a statement.

“Future studies should investigate whether the stimulatory effect on melatonin secretion remains when using a weighted blanket over more extended periods,” the researchers observe, and caution that “it is also unclear whether the observed increase in melatonin is therapeutically relevant.”

The study was published online in the Journal of Sleep Research.

Weighted blankets are commercially available at least in some countries in Scandinavia and Germany, as examples, and in general, they are sold for therapeutic purposes. And at least one study found that weighted blankets were an effective and safe intervention for insomnia in patients with major depressive disorder, bipolar disorder, generalized anxiety disorder, and attention deficit hyperactivity disorder and led to improvements in daytime symptoms and levels of activity.
 

Study done in healthy volunteers

The study involved a total of 26 healthy volunteers, 15 men and 11 women, none of whom had any sleep issues. “The day before the first testing session, the participants visited the laboratory for an adaptation night,” the authors observe. There were two experimental test nights, one in which the weighted blanket was used and the second during which the lighter blanket was used.

On the test nights, lights were dimmed between 9 PM and 11 PM and participants used a weighted blanket covering the extremities, abdomen, and chest 1 hour before and during 8 hours of sleep. As the authors explain, the filling of the weighted blanket consisted of honed glass pearls, combined with polyester wadding, which corresponded to 12.2% of participants’ body weight.

“Saliva was collected every 20 minutes between 22:00 and 23:00,” Ms. Meth and colleagues note. Participants’ subjective sleepiness was also assessed every 20 minutes using the Karolinska Sleepiness Scale both before the hour that lights were turned off and the next morning.

“Sleep duration in each experimental night was recorded with the OURA ring,” investigators explain.

The OURA ring is a commercial multisensor wearable device that measures physiological variables indicative of sleep. Investigators focused on total sleep duration as the primary outcome measure.

On average, salivary melatonin concentrations rose by about 5.8 pg/mL between 10 PM and 11 PM (P < .001), but the average increase in salivary melatonin concentrations was greater under weighted blanket conditions at 6.6 pg/mL, compared with 5.0 pg/mL during the lighter blanket session (P = .011).

Oxytocin in turn rose by about 315 pg/mL initially, but this rise was only transient, and over time, no significant difference in oxytocin levels was observed between the two blanket conditions. There were also no differences in cortisol levels or the activity of the sympathetic nervous system between the weighted and light blanket sessions.

Importantly, as well, no significant differences were seen in the level of sleepiness between participants when either blanket was used nor was there a significant difference in total sleep duration.

“Our study cannot identify the underlying mechanism for the observed stimulatory effects of the weighted blanket on melatonin,” the investigators caution.

However, one explanation could be that the pressure exerted by the weighted blanket activates cutaneous sensory afferent nerves, carrying information to the brain. The region where the sensory information is delivered stimulates oxytocinergic neurons that can promote calm and well-being and decrease fear, stress, and pain. In addition, these neurons also connect to the pineal gland to influence the release of melatonin, the authors explain.
 

Melatonin often viewed in the wrong context

Senior author Christian Benedict, PhD, associate professor of pharmacology, Uppsala University, Sweden, explained that some people think of melatonin in the wrong context.

In point of fact, “it’s not a sleep-promoting hormone. It prepares your body and brain for the biological night ... [and] sleep coincides with the biological night, but it’s not like you take melatonin and you have a very nice uninterrupted slumber – this is not true,” he told this news organization.

He also noted that certain groups respond to melatonin better than others. For example, children with attention deficit hyperactivity disorder may have some benefit from melatonin supplements, as may the elderly who can no longer produce sufficient amounts of melatonin and for whom supplements may help promote the timing of sleep.

However, the bottom line is that, even in those who do respond to melatonin supplements, they likely do so through a placebo effect that meta-analyses have shown plays a powerful role in promoting sleep. 

Dr. Benedict also stressed that just because the body makes melatonin, itself, does not mean that melatonin supplements are necessarily “safe.”

“We know melatonin has some impact on puberty – it may delay the onset of puberty – and we know that it can also impair blood glucose, so when people are eating and have a lot of melatonin on board, the melatonin will tell the pancreas to turn off insulin production, which can give rise to hyperglycemia,” he said.

However, Dr. Benedict cautioned that weighted blankets don’t come cheap. A quick Google search brings up examples that cost upwards of $350. “MDs can say try one if you can afford these blankets, but perhaps people can use several less costly blankets,” he said. “But I definitely think if there are cheap options, why not?” he concluded.

Dr. Benedict has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

A weighted blanket of approximately 12% body weight used at bedtime prompted the release of higher concentrations of melatonin, as measured in the saliva, compared with a lighter blanket of only about 2.4% of body weight.

This suggests that weighted blankets may help promote sleep in patients suffering from insomnia, according to the results from the small, in-laboratory crossover study.

“Melatonin is produced by the pineal gland and plays an essential role in sleep timing,” lead author Elisa Meth, PhD student, Uppsala University, Sweden, and colleagues observe.

“Using a weighted blanket increased melatonin concentration in saliva by about 30%,” Ms. Meth added in a statement.

“Future studies should investigate whether the stimulatory effect on melatonin secretion remains when using a weighted blanket over more extended periods,” the researchers observe, and caution that “it is also unclear whether the observed increase in melatonin is therapeutically relevant.”

The study was published online in the Journal of Sleep Research.

Weighted blankets are commercially available at least in some countries in Scandinavia and Germany, as examples, and in general, they are sold for therapeutic purposes. And at least one study found that weighted blankets were an effective and safe intervention for insomnia in patients with major depressive disorder, bipolar disorder, generalized anxiety disorder, and attention deficit hyperactivity disorder and led to improvements in daytime symptoms and levels of activity.
 

Study done in healthy volunteers

The study involved a total of 26 healthy volunteers, 15 men and 11 women, none of whom had any sleep issues. “The day before the first testing session, the participants visited the laboratory for an adaptation night,” the authors observe. There were two experimental test nights, one in which the weighted blanket was used and the second during which the lighter blanket was used.

On the test nights, lights were dimmed between 9 PM and 11 PM and participants used a weighted blanket covering the extremities, abdomen, and chest 1 hour before and during 8 hours of sleep. As the authors explain, the filling of the weighted blanket consisted of honed glass pearls, combined with polyester wadding, which corresponded to 12.2% of participants’ body weight.

“Saliva was collected every 20 minutes between 22:00 and 23:00,” Ms. Meth and colleagues note. Participants’ subjective sleepiness was also assessed every 20 minutes using the Karolinska Sleepiness Scale both before the hour that lights were turned off and the next morning.

“Sleep duration in each experimental night was recorded with the OURA ring,” investigators explain.

The OURA ring is a commercial multisensor wearable device that measures physiological variables indicative of sleep. Investigators focused on total sleep duration as the primary outcome measure.

On average, salivary melatonin concentrations rose by about 5.8 pg/mL between 10 PM and 11 PM (P < .001), but the average increase in salivary melatonin concentrations was greater under weighted blanket conditions at 6.6 pg/mL, compared with 5.0 pg/mL during the lighter blanket session (P = .011).

Oxytocin in turn rose by about 315 pg/mL initially, but this rise was only transient, and over time, no significant difference in oxytocin levels was observed between the two blanket conditions. There were also no differences in cortisol levels or the activity of the sympathetic nervous system between the weighted and light blanket sessions.

Importantly, as well, no significant differences were seen in the level of sleepiness between participants when either blanket was used nor was there a significant difference in total sleep duration.

“Our study cannot identify the underlying mechanism for the observed stimulatory effects of the weighted blanket on melatonin,” the investigators caution.

However, one explanation could be that the pressure exerted by the weighted blanket activates cutaneous sensory afferent nerves, carrying information to the brain. The region where the sensory information is delivered stimulates oxytocinergic neurons that can promote calm and well-being and decrease fear, stress, and pain. In addition, these neurons also connect to the pineal gland to influence the release of melatonin, the authors explain.
 

Melatonin often viewed in the wrong context

Senior author Christian Benedict, PhD, associate professor of pharmacology, Uppsala University, Sweden, explained that some people think of melatonin in the wrong context.

In point of fact, “it’s not a sleep-promoting hormone. It prepares your body and brain for the biological night ... [and] sleep coincides with the biological night, but it’s not like you take melatonin and you have a very nice uninterrupted slumber – this is not true,” he told this news organization.

He also noted that certain groups respond to melatonin better than others. For example, children with attention deficit hyperactivity disorder may have some benefit from melatonin supplements, as may the elderly who can no longer produce sufficient amounts of melatonin and for whom supplements may help promote the timing of sleep.

However, the bottom line is that, even in those who do respond to melatonin supplements, they likely do so through a placebo effect that meta-analyses have shown plays a powerful role in promoting sleep. 

Dr. Benedict also stressed that just because the body makes melatonin, itself, does not mean that melatonin supplements are necessarily “safe.”

“We know melatonin has some impact on puberty – it may delay the onset of puberty – and we know that it can also impair blood glucose, so when people are eating and have a lot of melatonin on board, the melatonin will tell the pancreas to turn off insulin production, which can give rise to hyperglycemia,” he said.

However, Dr. Benedict cautioned that weighted blankets don’t come cheap. A quick Google search brings up examples that cost upwards of $350. “MDs can say try one if you can afford these blankets, but perhaps people can use several less costly blankets,” he said. “But I definitely think if there are cheap options, why not?” he concluded.

Dr. Benedict has reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Older adults who take part in regular weight lifting – either with or without moderate to vigorous aerobic activity – show significant reductions in all-cause and cardiovascular disease (CVD) mortality, with the strongest effects observed when the two types of exercise are combined, new research shows.

“The novel finding from our study is that weight lifting is independently associated with lower all-cause and CVD-specific mortality, regardless of aerobic activity,” first author Jessica Gorzelitz, PhD, said in an interview.

Wavebreakmedia/Getty Images

“What’s less surprising – but consistent and nonetheless noteworthy – is that weight lifting in combination with aerobic exercise provides the lowest...risk for mortality in older adults,” added Dr. Gorzelitz, an assistant professor of health promotion in the department of health and human physiology at the University of Iowa, Iowa City.

Those who undertook weight lifting and aerobic exercise in combination had around a 40% lower risk of death than those who reported no moderate to vigorous aerobic activity or weight lifting. The findings were recently published online in the British Journal of Sports Medicine.

Physical activity guidelines generally recommend regular moderate to vigorous aerobic physical activity, in addition to at least 2 days per week of muscle-strengthening exercise for all major muscle groups for adults to improve health and boost longevity.

However, few observational studies have examined the association between muscle strengthening and mortality, and even fewer have looked specifically at the benefits of weight lifting, Dr. Gorzelitz said.
 

Benefit of weight lifting stronger in women than men

To investigate, Dr. Gorzelitz and coauthors evaluated data on participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which, initiated in 1993, and involved adults aged 55-74 at 10 U.S. cancer centers.

Thirteen years into the trial, in 2006, participants completed follow-up questionnaires that included an assessment of weight lifting (not included in a baseline survey).

Among 99,713 participants involved in the current analysis, the mean age at the time of the follow-up questionnaire was 71.3 years. Participants had a mean body mass index of 27.8 kg/m² and 52.6% were women.

Only about a quarter of adults (23%) reported any weight lifting activity within the previous 12 months, with fewer, at 16%, reporting regular weight lifting of between one and six times per week.

Participants’ physical aerobic activity was also assessed. Physical activity guidelines (2018) recommend at least 150-300 minutes per week of moderate-intensity aerobic physical activity or 75-150 minutes per week of vigorous intensity aerobic activity or an equal combination of the two. Overall, 23.6% of participants reported activity that met the guideline for moderate to vigorous physical activity, and 8% exceeded it.

Over a median follow-up of about 9 years, 28,477 deaths occurred.

Those reporting weight lifting had a 9% lower risk of combined all-cause mortality and CVD mortality, after adjustment for any moderate to vigorous physical activity (each hazard ratio, 0.91).

Adults who met aerobic activity recommendations but did not weight lift had a 32% lower risk of all-cause mortality (HR, 0.68), while those who also reported weight lifting 1-2 times per week in addition to the aerobic activity had as much as a 41% lower risk of death (HR, 0.59), compared with adults reporting no moderate to vigorous aerobic activity or weight lifting.

The benefit of weight lifting in terms of cancer mortality was only observed without adjustment for moderate to vigorous physical activity, and was therefore considered null, which Dr. Gorzelitz said was somewhat surprising. “We will examine this association further because there could still be a signal there,” she said, noting other studies have shown that muscle strengthening activity is associated with lower cancer-specific mortality.

Of note, the benefit of weight lifting appeared stronger in women versus men, Dr. Gorzelitz said.
 

What are the mechanisms?

Underscoring that the results show only associations and not causation, Dr. Gorzelitz speculated that mechanisms behind a mortality benefit could include known favorable physiological changes of weight lifting.

“If people are weight lifting [to a degree] to reap strength benefits, we generally see improvement in body composition, including reductions in fat and improvements in lean tissue, and we know that those changes are associated with mortality, so it could be that the weight lifting is driving the strength or body composition,” she said.

The full body response involved in weight lifting could also play a key role, she noted.

With weight lifting, “the muscles have to redirect more blood flow, the heart is pumping harder, the lungs breathe more and when the muscles are worked in that fashion, there could be other system-wide adaptations,” she said.

Furthermore, social aspects could play a role, Dr. Gorzelitz observed.

“Unlike muscle strengthening [activities] that can be done in the home setting, weight lifting typically has to be done in recreational facilities or other community centers, and considering that this is an older adult population, that social interaction could be very key for preventing isolation.”

Important limitations include that the study did not determine the nature of the weight lifting, including the duration of the weight lifting sessions or type of weight, which could feasibly range from small hand-held weights to heavier weight lifting.

The study also couldn’t show how long participants had engaged in weight lifting in terms of months or years, hence, the duration needed to see a mortality benefit was not established.

Nevertheless, the study’s finding that the group with the lowest benefits was the one reporting no aerobic or weight lifting exercise underscores the benefits of even small amounts of exercise.

“I think it’s really important to promote the importance of adding muscle strengthening, but also of any physical activity,” Dr. Gorzelitz said. “Start small, but something is better than nothing.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Older adults who take part in regular weight lifting – either with or without moderate to vigorous aerobic activity – show significant reductions in all-cause and cardiovascular disease (CVD) mortality, with the strongest effects observed when the two types of exercise are combined, new research shows.

“The novel finding from our study is that weight lifting is independently associated with lower all-cause and CVD-specific mortality, regardless of aerobic activity,” first author Jessica Gorzelitz, PhD, said in an interview.

Wavebreakmedia/Getty Images

“What’s less surprising – but consistent and nonetheless noteworthy – is that weight lifting in combination with aerobic exercise provides the lowest...risk for mortality in older adults,” added Dr. Gorzelitz, an assistant professor of health promotion in the department of health and human physiology at the University of Iowa, Iowa City.

Those who undertook weight lifting and aerobic exercise in combination had around a 40% lower risk of death than those who reported no moderate to vigorous aerobic activity or weight lifting. The findings were recently published online in the British Journal of Sports Medicine.

Physical activity guidelines generally recommend regular moderate to vigorous aerobic physical activity, in addition to at least 2 days per week of muscle-strengthening exercise for all major muscle groups for adults to improve health and boost longevity.

However, few observational studies have examined the association between muscle strengthening and mortality, and even fewer have looked specifically at the benefits of weight lifting, Dr. Gorzelitz said.
 

Benefit of weight lifting stronger in women than men

To investigate, Dr. Gorzelitz and coauthors evaluated data on participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which, initiated in 1993, and involved adults aged 55-74 at 10 U.S. cancer centers.

Thirteen years into the trial, in 2006, participants completed follow-up questionnaires that included an assessment of weight lifting (not included in a baseline survey).

Among 99,713 participants involved in the current analysis, the mean age at the time of the follow-up questionnaire was 71.3 years. Participants had a mean body mass index of 27.8 kg/m² and 52.6% were women.

Only about a quarter of adults (23%) reported any weight lifting activity within the previous 12 months, with fewer, at 16%, reporting regular weight lifting of between one and six times per week.

Participants’ physical aerobic activity was also assessed. Physical activity guidelines (2018) recommend at least 150-300 minutes per week of moderate-intensity aerobic physical activity or 75-150 minutes per week of vigorous intensity aerobic activity or an equal combination of the two. Overall, 23.6% of participants reported activity that met the guideline for moderate to vigorous physical activity, and 8% exceeded it.

Over a median follow-up of about 9 years, 28,477 deaths occurred.

Those reporting weight lifting had a 9% lower risk of combined all-cause mortality and CVD mortality, after adjustment for any moderate to vigorous physical activity (each hazard ratio, 0.91).

Adults who met aerobic activity recommendations but did not weight lift had a 32% lower risk of all-cause mortality (HR, 0.68), while those who also reported weight lifting 1-2 times per week in addition to the aerobic activity had as much as a 41% lower risk of death (HR, 0.59), compared with adults reporting no moderate to vigorous aerobic activity or weight lifting.

The benefit of weight lifting in terms of cancer mortality was only observed without adjustment for moderate to vigorous physical activity, and was therefore considered null, which Dr. Gorzelitz said was somewhat surprising. “We will examine this association further because there could still be a signal there,” she said, noting other studies have shown that muscle strengthening activity is associated with lower cancer-specific mortality.

Of note, the benefit of weight lifting appeared stronger in women versus men, Dr. Gorzelitz said.
 

What are the mechanisms?

Underscoring that the results show only associations and not causation, Dr. Gorzelitz speculated that mechanisms behind a mortality benefit could include known favorable physiological changes of weight lifting.

“If people are weight lifting [to a degree] to reap strength benefits, we generally see improvement in body composition, including reductions in fat and improvements in lean tissue, and we know that those changes are associated with mortality, so it could be that the weight lifting is driving the strength or body composition,” she said.

The full body response involved in weight lifting could also play a key role, she noted.

With weight lifting, “the muscles have to redirect more blood flow, the heart is pumping harder, the lungs breathe more and when the muscles are worked in that fashion, there could be other system-wide adaptations,” she said.

Furthermore, social aspects could play a role, Dr. Gorzelitz observed.

“Unlike muscle strengthening [activities] that can be done in the home setting, weight lifting typically has to be done in recreational facilities or other community centers, and considering that this is an older adult population, that social interaction could be very key for preventing isolation.”

Important limitations include that the study did not determine the nature of the weight lifting, including the duration of the weight lifting sessions or type of weight, which could feasibly range from small hand-held weights to heavier weight lifting.

The study also couldn’t show how long participants had engaged in weight lifting in terms of months or years, hence, the duration needed to see a mortality benefit was not established.

Nevertheless, the study’s finding that the group with the lowest benefits was the one reporting no aerobic or weight lifting exercise underscores the benefits of even small amounts of exercise.

“I think it’s really important to promote the importance of adding muscle strengthening, but also of any physical activity,” Dr. Gorzelitz said. “Start small, but something is better than nothing.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Older adults who take part in regular weight lifting – either with or without moderate to vigorous aerobic activity – show significant reductions in all-cause and cardiovascular disease (CVD) mortality, with the strongest effects observed when the two types of exercise are combined, new research shows.

“The novel finding from our study is that weight lifting is independently associated with lower all-cause and CVD-specific mortality, regardless of aerobic activity,” first author Jessica Gorzelitz, PhD, said in an interview.

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“What’s less surprising – but consistent and nonetheless noteworthy – is that weight lifting in combination with aerobic exercise provides the lowest...risk for mortality in older adults,” added Dr. Gorzelitz, an assistant professor of health promotion in the department of health and human physiology at the University of Iowa, Iowa City.

Those who undertook weight lifting and aerobic exercise in combination had around a 40% lower risk of death than those who reported no moderate to vigorous aerobic activity or weight lifting. The findings were recently published online in the British Journal of Sports Medicine.

Physical activity guidelines generally recommend regular moderate to vigorous aerobic physical activity, in addition to at least 2 days per week of muscle-strengthening exercise for all major muscle groups for adults to improve health and boost longevity.

However, few observational studies have examined the association between muscle strengthening and mortality, and even fewer have looked specifically at the benefits of weight lifting, Dr. Gorzelitz said.
 

Benefit of weight lifting stronger in women than men

To investigate, Dr. Gorzelitz and coauthors evaluated data on participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which, initiated in 1993, and involved adults aged 55-74 at 10 U.S. cancer centers.

Thirteen years into the trial, in 2006, participants completed follow-up questionnaires that included an assessment of weight lifting (not included in a baseline survey).

Among 99,713 participants involved in the current analysis, the mean age at the time of the follow-up questionnaire was 71.3 years. Participants had a mean body mass index of 27.8 kg/m² and 52.6% were women.

Only about a quarter of adults (23%) reported any weight lifting activity within the previous 12 months, with fewer, at 16%, reporting regular weight lifting of between one and six times per week.

Participants’ physical aerobic activity was also assessed. Physical activity guidelines (2018) recommend at least 150-300 minutes per week of moderate-intensity aerobic physical activity or 75-150 minutes per week of vigorous intensity aerobic activity or an equal combination of the two. Overall, 23.6% of participants reported activity that met the guideline for moderate to vigorous physical activity, and 8% exceeded it.

Over a median follow-up of about 9 years, 28,477 deaths occurred.

Those reporting weight lifting had a 9% lower risk of combined all-cause mortality and CVD mortality, after adjustment for any moderate to vigorous physical activity (each hazard ratio, 0.91).

Adults who met aerobic activity recommendations but did not weight lift had a 32% lower risk of all-cause mortality (HR, 0.68), while those who also reported weight lifting 1-2 times per week in addition to the aerobic activity had as much as a 41% lower risk of death (HR, 0.59), compared with adults reporting no moderate to vigorous aerobic activity or weight lifting.

The benefit of weight lifting in terms of cancer mortality was only observed without adjustment for moderate to vigorous physical activity, and was therefore considered null, which Dr. Gorzelitz said was somewhat surprising. “We will examine this association further because there could still be a signal there,” she said, noting other studies have shown that muscle strengthening activity is associated with lower cancer-specific mortality.

Of note, the benefit of weight lifting appeared stronger in women versus men, Dr. Gorzelitz said.
 

What are the mechanisms?

Underscoring that the results show only associations and not causation, Dr. Gorzelitz speculated that mechanisms behind a mortality benefit could include known favorable physiological changes of weight lifting.

“If people are weight lifting [to a degree] to reap strength benefits, we generally see improvement in body composition, including reductions in fat and improvements in lean tissue, and we know that those changes are associated with mortality, so it could be that the weight lifting is driving the strength or body composition,” she said.

The full body response involved in weight lifting could also play a key role, she noted.

With weight lifting, “the muscles have to redirect more blood flow, the heart is pumping harder, the lungs breathe more and when the muscles are worked in that fashion, there could be other system-wide adaptations,” she said.

Furthermore, social aspects could play a role, Dr. Gorzelitz observed.

“Unlike muscle strengthening [activities] that can be done in the home setting, weight lifting typically has to be done in recreational facilities or other community centers, and considering that this is an older adult population, that social interaction could be very key for preventing isolation.”

Important limitations include that the study did not determine the nature of the weight lifting, including the duration of the weight lifting sessions or type of weight, which could feasibly range from small hand-held weights to heavier weight lifting.

The study also couldn’t show how long participants had engaged in weight lifting in terms of months or years, hence, the duration needed to see a mortality benefit was not established.

Nevertheless, the study’s finding that the group with the lowest benefits was the one reporting no aerobic or weight lifting exercise underscores the benefits of even small amounts of exercise.

“I think it’s really important to promote the importance of adding muscle strengthening, but also of any physical activity,” Dr. Gorzelitz said. “Start small, but something is better than nothing.”

The authors reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.