Elevated Stress Hormones Linked to Higher Risk of High Blood Pressure and Heart Events

Adults with normal blood pressure and high levels of stress hormones were more likely to develop high blood pressure and experience cardiovascular events compared to those who had lower stress hormone levels, according to new research published today in Hypertension, an American Heart Association journal.

Studies have shown that cumulative exposure to daily stressors and exposure to traumatic stress can increase cardiovascular disease risk. A growing body of research refers to the mind-heart-body connection, which suggests a person’s mind can positively or negatively affect cardiovascular health, cardiovascular risk factors and risk for cardiovascular disease events, as well as cardiovascular prognosis over time.

“The stress hormones norepinephrine, epinephrine, dopamine and cortisol can increase with stress from life events, work, relationships, finances and more. And we confirmed that stress is a key factor contributing to the risk of hypertension and cardiovascular events,” said study author Kosuke Inoue, M.D., Ph.D., assistant professor of social epidemiology at Kyoto University in Kyoto, Japan. Inoue also is affiliated with the department of epidemiology at the Fielding School of Public Health at the University of California, Los Angeles.

“Previous research focused on the relationship between stress hormone levels and hypertension or cardiovascular events in patients with existing hypertension. However, studies looking at adults without hypertension were lacking,” Inoue said. “It is important to examine the impact of stress on adults in the general population because it provides new information about whether routine measurement of stress hormones needs to be considered to prevent hypertension and CVD events.”

Study subjects were part of the MESA Stress 1 study, a substudy of the Multi-Ethnic Study of Atherosclerosis (MESA), a large study of atherosclerosis risk factors among more than 6,000 men and women from six U.S. communities. As part of MESA exams 3 and 4 (conducted between July 2004 and October 2006), white, Black and Hispanic participants with normal blood pressure from the New York and Los Angeles sites were invited to participate in the substudy MESA Stress 1. In this substudy, researchers analyzed levels of norepinephrine, epinephrine, dopamine and cortisol – hormones that respond to stress levels. Hormone levels were measured in a 12-hour overnight urine test. The substudy included 412 adults ages 48 to 87 years. About half were female, 54% were Hispanic, 22% were Black and 24% were white.

Participants were followed for three more visits (between September 2005 and June 2018) for development of hypertension and cardiovascular events such as chest pain, the need for an artery-opening procedure, or having a heart attack or stroke.

Norepinephrine, epinephrine and dopamine are molecules known as catecholamines that maintain stability throughout the autonomic nervous system—the system that regulates involuntary body functions such as heart rate, blood pressure and breathing. Cortisol is a steroid hormone released when one experiences stress and is regulated by the hypothalamic-pituitary-adrenal axis, which modulates stress response.

“Although all of these hormones are produced in the adrenal gland, they have different roles and mechanisms to influence the cardiovascular system, so it is important to study their relationship with hypertension and cardiovascular events, individually,” Inoue said.

Their analysis of the relationship between stress hormones and development of atherosclerosis found:

  • Over a median of 6.5-year follow-up period, every time the levels of the four stress hormones doubled was associated with a 21-31% increase in the risk of developing hypertension.
  • During a median of 11.2-years of follow-up, there was a 90% increased risk of cardiovascular events with each doubling of cortisol levels. There was no association between cardiovascular events and catecholamines.

“It is challenging to study psychosocial stress since it is personal, and its impact varies for each individual. In this research, we used a noninvasive measure — a single urine test — to determine whether such stress might help identify people in need of additional screening to prevent hypertension and possibly cardiovascular events,” Inoue said.

“The next key research question is whether and in which populations increased testing of stress hormones could be helpful. Currently, these hormones are measured only when hypertension with an underlying cause or other related diseases are suspected. However, if additional screening could help prevent hypertension and cardiovascular events, we may want to measure these hormone levels more frequently.”

A limitation of the study is that it did not include people who had hypertension at the study’s start, which would have resulted in a larger study population. Another limitation is that researchers measured stress hormones via a urine test only, and no other tests for stress hormone measurement were used.

Source: American Heart Association

Does Testosterone Influence Success? Not Much, Research Suggests

It is already known that in men testosterone is linked with socioeconomic position, such as income or educational qualifications. Researchers from the University of Bristol’s Population Health Sciences (PHS) and MRC Integrated Epidemiology Unit (IEU) wanted to find out whether this is because testosterone actually affects socioeconomic position, as opposed to socioeconomic circumstances affecting testosterone, or health affecting both. The findings are published in Science Advances.

To isolate effects of testosterone itself, the research team applied an approach called Mendelian randomization in a sample of 306,248 UK adults from UK Biobank. They explored testosterone’s influence on socioeconomic position, including income, employment status, neighbourhood-level deprivation, and educational qualifications; on health, including self-rated health and BMI, and on risk-taking behaviour.

Dr Amanda Hughes, Senior Research Associate in Epidemiology in Bristol Medical School: Population Health Sciences (PHS), said: “There’s a widespread belief that a person’s testosterone can affect where they end up in life. Our results suggest that, despite a lot of mythology surrounding testosterone, its social implications may have been over-stated.”

First, the team identified genetic variants linked to higher testosterone levels and then investigated how these variants were related to the outcomes. A person’s genetic code is determined before birth, and generally does not change during their lifetime (there are rare exceptions, such as changes that occur with cancer). This makes it very unlikely that these variants are affected by socioeconomic circumstances, health, or other environmental factors during a person’s lifetime. Consequently, any association of an outcome with variants linked to testosterone would strongly suggest an influence of testosterone on the outcome.

Similar to previous studies the research found that men with higher testosterone had higher household income, lived in less deprived areas, and were more likely to have a university degree and a skilled job. In women, higher testosterone was linked to lower socioeconomic position, including lower household income, living in a more deprived area, and lower chance of having a university degree. Consistent with previous evidence, higher testosterone was associated with better health for men and poorer health for women, and greater risk-taking behaviour for men.

In contrast, there was little evidence that the testosterone-linked genetic variants were associated with any outcome for men or women. The research team concluded that there is little evidence that testosterone meaningfully affected socioeconomic position, health, or risk-taking in men or women. The study suggests that – despite the mythology surrounding testosterone – it might be much less important than previously claimed.

Results for women were less precise than results for men, so the influence of testosterone in women could be studied in more detail in the future using larger samples.

Dr Hughes added: “Higher testosterone in men has previously been linked to various kinds of social success. A study of male executives found that testosterone was higher for those who had more subordinates. A study of male financial traders found that higher testosterone correlated with greater daily profits. Other studies have reported that testosterone is higher for more highly educated men, and among self-employed men, suggesting a link with entrepreneurship.

“Such research has supported the widespread idea that testosterone can influence success by affecting behaviour. There is evidence from experiments that testosterone can make a person more assertive or more likely to take risks – traits which can be rewarded in the labour market, for instance during wage negotiations. But there are other explanations. For example, a link between higher testosterone and success might simply reflect an influence of good health on both. Alternatively, socioeconomic circumstances could affect testosterone levels. A person’s perception of their own success could influence testosterone: in studies of sports matches, testosterone has been found to rise in the winner compared to the loser.”

Source: University of Bristol

Close Monitoring for Heart Risk Needed if Breast, Prostate Cancer Treatment Includes Hormones

The hormonal therapies used to treat many breast and prostate cancers raise the risk of a heart attack and stroke, and patients should be monitored regularly and receive treatment to reduce risk and detect problems as they occur, according to a new American Heart Association scientific statement, published today in the Association’s journal Circulation: Genomic and Precision Medicine.

“The statement provides data on the risks of each type of hormonal therapy so clinicians can use it as a guide to help manage cardiovascular risks during cancer treatment,” said Tochi M. Okwuosa, D.O., FAHA, chair of the scientific statement writing group, an associate professor of medicine and cardiology and director of Cardio-Oncology Services at Rush University Medical Center in Chicago.

Hormone-dependent cancers, such as prostate and breast cancer, are the most common cancers in the United States and worldwide not including skin cancers. As improvements in treatment – including increased use of hormonal therapies – allow people with these cancers to live longer, cardiovascular disease has emerged as a leading cause of illness and death in these patients.

Hormonal treatments for breast cancer include selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs). SERMs block estrogen receptors in cancer cells so the hormone can’t spur tumor growth, while letting estrogen act normally in other tissues such as bone and liver tissue; examples of SERMs include tamoxifen and raloxifene. Aromatase inhibitors lower the amount of estrogen produced in post-menopausal women and include exemestane, anastrozole and letrozole. Endocrine treatments for prostate cancer, called androgen deprivation therapy, include some medications that decrease production of testosterone by their action on the brain and others that block testosterone receptors found in prostate cells and some prostate cancer cells.

The writing group reviewed existing evidence from observational studies and randomized controlled trials and found that:

  • Tamoxifen increases the risk of blood clots, while aromatase inhibitors increase the risk of heart attack and stroke more than tamoxifen. For breast cancer patients who require more than one type of hormonal therapy because of developed resistance to the initial medication, , there is an improvement in cancer outcomes. However, treatment with multiple hormones is associated with higher rates of cardiovascular conditions such as high blood pressure, abnormal heart rhythms and blood clots.
  • Androgen deprivation therapy (to reduce testosterone) for prostate cancer increases cholesterol and triglyceride levels, adds body fat while decreasing muscle and impairs the body’s ability to process glucose (which may result in type 2 diabetes). These metabolic changes are associated with a greater risk of heart attacks, strokes, heart failure and cardiovascular death.
  • The longer people receive hormonal therapy, the greater the increased risk of cardiovascular problems. Further research is required to better define the risks associated with duration of treatment.
  • The hormonal therapy-associated increase in CVD risk was highest in people who already had heart disease or those who had two or more cardiovascular risk factors – such as high blood pressure, obesity, high cholesterol, smoking or a family history of heart disease or stroke – when they began treatment.

“A team-based approach to patient care that includes the oncology team, cardiologist, primary care clinician, dietician, endocrinologist and other health care professionals as appropriate is needed to work with each patient to manage and reduce the increased risk of heart disease and strokes associated with hormonal therapy in breast and prostate cancer treatment,” Okwuosa said.

There are currently no definitive guidelines for monitoring and managing hormonal therapy-related heart risks. The statement calls for clinicians to be alert for worsening heart problems in those with prior heart disease or risk factors, and to recognize that even those without pre-existing heart problems are at higher risk because of their exposure to hormonal therapies.

“For patients who have two or more cardiovascular risk factors, it is likely that referral to a cardiologist would be appropriate prior to beginning hormone treatment. For patients already receiving hormonal therapies, a discussion with the oncology team can help to determine if a cardiology referral is recommended,” Okwuosa said.

The statement also calls for additional research in several areas, including:

  • Further evaluation of racial and ethnic disparities among breast and prostate cancer patients who have received hormone therapy. In the few studies that exist, racial and ethnic differences detected may be related to health inequities and other factors, and these are important areas to address.
  • Heart disease and stroke outcomes and risks should be added as primary endpoints in randomized trials of hormonal therapies.
  • Studies of specific hormonal medications are needed since each one may have different heart risks even if they work in the same way to treat breast or prostate cancer.

Source: American Heart Association

Gut Hormone Blocks Brain Cell Formation and is Linked to Parkinson’s Dementia

A gut hormone, ghrelin, is a key regulator of new nerve cells in the adult brain, a Swansea-led research team has discovered. It could help pave the way for new drugs to treat dementia in patients with Parkinson’s Disease.

Blood-borne factors such as hormones regulate the process of brain cell formation – known as neurogenesis – and cognition in adult mammals.

The research team focused on the gut hormone acyl-ghrelin (AG), which is known to promote brain cell formation. A structure change to the hormone results in two distinct forms: AG and unacylated-ghrelin (UAG).

The team, led by Dr Jeff Davies of Swansea University Medical School, studied both AG and UAG to examine their respective influences over brain cell formation.

This research is relevant to Parkinson’s as a large proportion of those with the disease experience dementia, which is linked to a loss of new nerve cells in the brain. This loss leads to a reduction in nerve cell connectivity, which plays a vital role in regulating memory function.

The team’s key overall findings were:

  • the UAG form of ghrelin reduces nerve cell formation and impairs memory
  • Individuals diagnosed with Parkinson’s disease dementia have a reduced AG:UAG ratio in their blood

Dr Jeff Davies of Swansea University Medical School, lead researcher, said:

“Our work highlights the crucial role of ghrelin as a regulator of new nerve cells in the adult brain, and the damaging effect of the UAG form specifically.

This hormone represents an important target for new drug research, which could lead ultimately to better treatment for people with Parkinson’s.

Our findings show that the AG:UAG ratio could also serve as a biomarker, allowing earlier identification of dementia in people with Parkinson’s disease.”

The team included collaborators from Newcastle University (UK) and Monash University (Australia). They examined the role of AG and UAG in the brain, and also compared blood collected from Parkinson’s disease patients diagnosed with dementia with cognitively intact PD patients and a control group.

They found:

  • Higher levels of UAG, using both pharmacological and genetic methods, reduced hippocampal neurogenesis and brain plasticity.
  • AG helped reverse spatial memory impairments
  • UAG blocks the process of brain cell formation prompted by AG
  • The Parkinson’s patients with dementia were the only one of the three patient groups examined to show a reduced AG:UAG ratio in their blood.

The research was published in Cell Reports Medicine.

Source: Swansea University

‘Love Hormone’ Could Hold Key to Treating COVID

The so-called love hormone, oxytocin, may be worth investigating as a treatment for COVID-19, a new study suggests.

One of the most serious complications of infection with the new coronavirus is a “cytokine storm,” in which the body attacks its own tissues.

There are currently no U.S. Food and Drug Administration-approved treatments for COVID-19, which means that “repurposing existing drugs that can act on the adaptive immune response and prevent the cytokine storm in early phases of the disease is a priority,” according to the researchers.

Previous research suggests that oxytocin — a hormone that’s produced in the brain and is involved in reproduction and childbirth — reduces inflammation.

In this new study, researcher Ali Imami, a graduate research assistant at the University of Toledo in Ohio, and colleagues used a U.S. National Institutes of Health database to analyze characteristics of genes treated with drugs closely related to oxytocin.

The investigators found that one drug in particular, carbetocin, has similar characteristics (called a signature) to genes with reduced expression of the inflammatory markers that trigger cytokine storm in COVID-19 patients.

Carbetocin’s signature suggests that the drug may trigger activation of immune cells called T-cells that play an important role in immune response. In addition, carbetocin’s signature is also similar to that of lopinavir, an antiretroviral medication under study as a treatment for COVID-19.

All of these factors indicate that oxytocin may have potential as a targeted treatment for cytokine storms in COVID-19 patients, the researchers said in a news release from the American Physiological Society.

“Understanding the mechanisms by which oxytocin or the oxytocin system can be a new immune target is crucial,” the authors concluded in their report, which was published online recently in the journal Physiological Genomics.

However, they added that “safety and efficacy of intravenous oxytocin in hospitalized patients with COVID-19 remains to be assessed.”

Source: HealthDay