Doctors have demonstrated a new type of CT scan that lights up tiny nodules in the adrenal glands which give rise to hypertension in about 5% of hypertensive patients. enabling hypertension to be cured by their removal. The nodules are discovered in about 5% of hypertensive patients.
Published in The Journal of Hypertension, this work solves a 60-year problem of how to detect the hormone-producing nodules without a difficult and failure-prone catheter study that is available in only a few hospitals. The research also found that, when combined with a urine test, the scan detects a group of patients who come off all their blood pressure medicines after treatment.
The study, led by doctors at Queen Mary University of London and Barts Hospital, and Cambridge University Hospital, involved 128 participants for whom hypertension was found to be caused by aldosterone. The scan found that in two thirds of patients with elevated aldosterone secretion, this is coming from a benign nodule in just one of the adrenal glands, which can then be safely removed. The scan uses a very short-acting dose of metomidate, a radioactive dye that sticks only to the aldosterone-producing nodule.
The scan was as accurate as the old catheter test, but quick, painless and technically successful in every patient. Until now, the catheter test was unable to predict which patients would be completely cured of hypertension by surgical removal of the gland. By contrast, the combination of a ‘hot nodule’ on the scan and urine steroid test detected 18 of the 24 patients who achieved a normal blood pressure off all their drugs.
Professor Morris Brown, co-senior author of the study and Professor of Endocrine Hypertension at Queen Mary University of London, said: “These aldosterone-producing nodules are very small and easily overlooked on a regular CT scan. When they glow for a few minutes after our injection, they are revealed as the obvious cause of hypertension, which can often then be cured. Until now, 99% are never diagnosed because of the difficulty and unavailability of tests. Hopefully this is about to change.”
In most people with hypertension, the cause is unknown, and the condition requires life-long treatment by drugs. Previous research by the group at Queen Mary University discovered that in 5–10% of people with hypertension the cause is a gene mutation in the adrenal glands, which results in excessive amounts of the steroid hormone, aldosterone, being produced. Aldosterone causes salt retention, driving up blood pressure. Patients with excessive aldosterone levels in the blood are resistant to treatment with standard antihypertensives, and at increased risk of cardiovascular disease.
Research published in the journal Molecular Psychiatry suggest that clonidine, a 50-year-old blood pressure drug, could provide immediate treatment to the significant number of people emerging from the current pandemic with PTSD, as well as from longer-established causes like wars and other violence.
Clonidine is commonly used as a hypertension medication and for ADHD. It’s also already been studied in PTSD because clonidine works on adrenergic receptors in the brain, likely best known for their role in “fight or flight,” a heightened state of response that helps keep us safe.
These receptors are thought to be activated in PTSD and to have a role in consolidating a traumatic memory. Clonidine’s sister drug guanfacine, which also activates these receptors, also has been studied in PTSD. Conflicting results from the clinical trials have clonidine, which has shown promise in PTSD, put aside along with guanfacine, which has not.
Laboratory evidence shows that while the two drugs bind to the same receptors, they do different things there, says Qin Wang, MD, PhD, neuropharmacologist and founding director of the Program for Alzheimer’s Therapeutics Discovery at MCG.
Large-scale clinical trials of clonidine in PTSD are warranted, the scientists write. Their studies also indicate that other new therapies could be identified by looking at the impact on activation of a key protein called cofilin by existing drugs.
The new studies looked in genetically modified mice as well as neurons that came from human stem cells, which have the capacity to make many cell types.
In the hippocampus, they found that a novel axis on an adrenergic receptor called ɑ2A is essential to maintaining fear memories which associate a place or situation, like the site of a horrific car accident, with fear or other distressing emotions that are hallmarks of PTSD.
In this axis, they found the protein spinophilin interacts with cofilin, which is known to control protrusions on the synapses of neurons called dendritic spines, where memories are consolidated and stored.
A single neuron can have hundreds of these spines which change shape based on brain activity and whose changing impacts the strength of the synapse, the juncture between two neurons where they swap information.
“Normally whenever there is a stimulation, good or bad, in order to memorize it, you have to go through a process in which the spines store the information and get bigger,” Wang says, morphing from a slender profile to a more mushroom-like shape.
“The mushroom spine is very important for your memory formation,” says corresponding author Wang. For these mushroom shapes to happen, levels of cofilin must be significantly reduced in the synapse where the spines reside. That is where clonidine comes in.
The scientists found clonidine interferes with cofilin’s exit by encouraging it to interact with the receptor which consequently interferes with the dendritic spine’s ability to resume a mushroom shape and retain the memory. Guanfacine, on the other hand, had no effect on this key player cofilin.
The findings help clarify the disparate results in the clinical trials of these two similar drugs, Wang says. In fact, when mice got both drugs, the guanfacine appeared to lessen the impact of clonidine in the essential step of reconsolidating – and so sustaining – a traumatic memory, indicating their polar-opposite impact at least on this biological function, Wang says.
There was also living evidence. In their studies that mimicked how PTSD happens, mice were given a mild shock then treated with clonidine right after they were returned to the place where they received the shock and should be recalling what happened earlier. Clonidine-treated mice had a significantly reduced response, like freezing in their tracks, compared to untreated mice when brought back to the scene. In fact, their response was more like the mice who were never shocked. Guanfacine had no effect on freezing behaviour.
Obviously, Wang says, they cannot know for certain how much the mice remember of what previously happened, but clearly those treated with clonidine did not have the same overt reaction as untreated mice or those receiving guanfacine.
“The interpretation is that they don’t have as strong a memory,” she says, noting that the goal is not to erase memories like those of wartime, rather diminish their disruption in a soldier’s life.
When a memory is recalled, like when you return to an intersection where you were involved in a horrific car wreck, the synapses that hold the memory of what happened there become temporarily unstable, or labile, before the memory restabilises, or reconsolidates. This natural dynamic provides an opportunity to intervene in reconsolidation and so at least diminish the strength of a bad memory, Wang says. Clonidine appears to be one way to do that.
Adrenergic drugs like clonidine bind to receptors in the central nervous system to reduce blood levels of the stress hormones you produce like epinephrine (adrenaline) and norepinephrine, which do things like increase blood pressure and heart rate.
Studies like one that came out 15 years ago, which only looked at guanfacine, indicated it was of no benefit in PTSD. But then in 2021, a retrospective look at a cohort of 79 veterans with PTSD treated with clonidine, for example, indicated 72% experienced improvement and 49% were much improved or very much improved with minimal side effects.
Previous basic science studies also have indicated that manipulating the adrenergic receptor can impact fear memory formation and memory, but how has remained unknown.
PTSD has emerged as a major neuropsychiatric component of the COVID-19 pandemic, affecting about 30% of survivors, a similar percentage of the health care workers who care for them and an estimated 20% of the total population, Wang says, which means the impact on human health and health care systems could be “profound.”
Psychotherapy is generally considered the most effective treatment for PTSD, and some medications, like antidepressants, can also be used, but there are limited drug options, with only two approved specifically for the condition, she says. The lack of approved drugs has led to off-label uses of drugs like clonidine.
Cofilin is a key element in helping muscle cells and other cell types contract as well as the flexibility of the cytoskeleton of the dendritic spine. A single neuron can have thousands of dendritic spines which change shape based on brain activity and whose changing shape impacts the strength of the synapse.
Young people with Type 1 diabetes (T1D) who took bromocriptine, a medication used to treat Parkinson’s disease and Type 2 diabetes, had lower blood pressure and less stiff arteries after one month of treatment compared to taking placebo, according to a small study published today in Hypertension.
Hypertension and stiff arteries contribute to the development of heart disease, for which those with T1D are at higher risk. Those diagnosed with T1D as children have even higher risks for heart disease than people diagnosed in adulthood. Therefore, researchers are interested in ways to slow down the onset of vascular disease in children with T1D.
“We know that abnormalities in the large vessels around the heart, the aorta and its primary branches, begin to develop in early childhood in people with Type 1 diabetes,” said lead study author Michal Schäfer, PhD, a researcher and fourth-year medical student at the University of Colorado School of Medicine. “We found that bromocriptine has the potential to slow down the development of those abnormalities and decrease the risk for cardiovascular disease in this population.”
The multidisciplinary team conducted this study to examine the impact of bromocriptine on blood pressure and aortic stiffness compared with a placebo in adolescents with Type 1 diabetes. Bromocriptine is in a class of medications called dopamine receptor agonists. It increases levels of dopamine, a chemical in the brain, which leads to an increase in the body’s responsiveness to insulin, called insulin sensitivity. Bromocriptine has been FDA-approved since 2009 to treat adults with Type 2 diabetes due to its effect on insulin sensitivity.
The study included 34 participants (13 male, 21 female) aged 12 to 21 years who had been diagnosed with Type 1 diabetes for at least a year, and their HbA1c was 12% or less. An HbA1c level of 6.5% or higher indicates diabetes. They were randomly divided into two groups of 17, with one group receiving bromocriptine quick-release therapy and the other receiving a placebo once daily. The study was conducted in two phases. Participants took the first treatment or placebo for 4 weeks in phase 1, then had no treatment for a 4-week “wash-out” period, followed by phase 2 with 4 weeks on the opposite treatment. In this “crossover” design, each participant served as their own control for comparison.
Blood pressure and aortic stiffness were measured at the start of the study and at the end of each phase. Aortic stiffness was determined by assessing the large arteries with cardiovascular magnetic resonance imaging (MRI) and a measurement of the velocity of the blood pressure pulse called pulse wave velocity.
The study found:
Compared to placebo, blood pressure was significantly decreased with bromocriptine. On average, bromocriptine therapy resulted in a systolic blood pressure decrease of 5 mm Hg and a diastolic blood pressure decrease of 2 mm Hg at the end of 4 weeks of treatment.
Aortic stiffness was also reduced with bromocriptine therapy. The improvement in aortic stiffness was most pronounced in the ascending aorta with a lowered pulse wave velocity of about 0.4 meters/second, and an increase in distensibility, or elasticity, of 8%. In the thoraco-abdominal aorta, bromocriptine was associated with a lowered pulse wave velocity of about 0.2 meters/second, with a 5% increase in distensibility.
“A stiff aorta predisposes a patient to other health issues, such as organ dysfunction or atherosclerosis and higher stress or strain on cardiac muscle,” Schäfer said. “We were able to take it a notch further and show, using more sophisticated metrics, that these central large arteries are impaired, and impairment among adolescents and young adults with Type 1 diabetes may be decelerated with this drug.”
The study’s small size is a limitation. However, the researchers note that further research into bromocriptine’s impact on vascular health in a greater number of people with Type 1 diabetes is warranted; they are planning larger trials.
A global study of over 28 000 people has provided the strongest evidence to date that lowering blood pressure in later life can cut the risk of dementia. The study, which included five randomised controlled trials, was published in the European Heart Journal, and constitutes the highest grade of evidence for this preventative association.
Dr Ruth Peters, Program Lead for Dementia in The George Institute’s Global Brain Health Initiative, said that with no significant dementia treatment breakthroughs being made, reducing the risk of developing the disease would be a welcome step forward.
“Given population ageing and the substantial costs of caring for people with dementia, even a small reduction could have considerable global impact,” she said.
“Our study suggests that using readily available treatments to lower blood pressure is currently one of our ‘best bets’ to tackle this insidious disease.”
Dementia is fast becoming a global epidemic, currently affecting an estimated 50 million people worldwide. This number is projected to triple by 2050 mainly from ageing populations.
Current estimates put the cost at US$20–$40 000 per person with the condition each year.
Dr Peters explained that while many trials have looked at the health benefits of lowering blood pressure, few included dementia outcomes and even fewer were placebo-controlled.
“Most trials were stopped early because of the significant impact of blood pressure lowering on cardiovascular events, which tend to occur earlier than signs of dementia,” she said.
To examine the relationship between blood pressure and dementia more closely, researchers analysed five double-blind placebo-controlled randomised trials that used different blood pressure lowering treatments and followed patients until the development of dementia. A total of 28 008 individuals with an average age of 69 and a history of hypertension from 20 countries were included. Across these studies, the mid-range of follow up was just over four years.
“We found there was a significant effect of treatment in lowering the odds of dementia associated with a sustained reduction in blood pressure in this older population,” said Dr Peters.
“Our results imply a broadly linear relationship between blood pressure reduction and lower risk of dementia, regardless of which type of treatment was used.”
Researchers hope the results will help in designing public health measures to slow the advance of dementia as well as informing treatment, where there may be hesitancy in how far to lower blood pressure in older age.
“Our study provides the highest grade of available evidence to show that blood pressure lowering treatment over several years reduces the risk of dementia, and we did not see any evidence of harm,” said Dr Peters.
“But what we still don’t know is whether additional blood pressure lowering in people who already have it well-controlled or starting treatment earlier in life would reduce the long-term risk of dementia,” she added.
Only 48% of people age 50 to 80 taking blood pressure medications or have a health condition affected by hypertension regularly check their blood pressure at home or other places, found a new study published in JAMA Network Open.
A somewhat higher number (62%) say a health care provider encouraged them to perform such checks. Poll respondents whose providers had recommended they check their blood pressure at home were three and a half times more likely to do so than those who didn’t recall getting such a recommendation.
The findings underscore the importance of exploring the reasons why at-risk patients aren’t checking their blood pressure, and why providers aren’t recommending they check — as well as finding ways to prompt more people with these health conditions to check their blood pressure regularly. This could play an important role in helping patients live longer and maintain heart and brain health, the study’s authors say.
Past research has shown that regular home monitoring can help with blood pressure control, and that better control can mean reduced risk of death; of cardiovascular events including strokes and heart attacks; and of cognitive impairment and dementia.
A team from Michigan Medicine, the University of Michigan’s academic medical centre, conducted the research. The data come from the National Poll on Healthy Aging and build on a report issued last year.
The poll, based at the U-M Institute for Healthcare Policy and Innovation and supported by Michigan Medicine and AARP, asked adults aged 50 to 80 about their chronic health conditions, blood pressure monitoring outside of clinic settings, and interactions with health providers about blood pressure. Study authors Mellanie V. Springer, M.D., M.S., of the Michigan Medicine Department of Neurology, and Deborah Levine, M.D., M.P.H., of the Department of Internal Medicine, worked with the NPHA team to develop the poll questions and analyze the findings.
The data in the new paper come from the 1,247 respondents who said they were either taking a medication to control their blood pressure or had a chronic health condition that requires blood pressure control — specifically, a history of stroke, coronary heart disease, congestive heart failure, diabetes, chronic kidney disease or hypertension.
Of them, 55% said they own a blood pressure monitor, though some said they don’t ever use it. Among those who do use it, there was wide variation in how often they checked their pressure — and only about half said they share their readings with a health provider. But those who own a monitor were more than 10 times more likely to check their blood pressure outside of health care settings than those who don’t own one.
The authors note that blood pressure monitoring is associated with lower blood pressure and is cost-effective. They say that the results suggest that protocols should be developed to educate patients about the importance of self blood pressure monitoring and sharing readings with clinicians.
A new study published in the Journal of the American Geriatrics Society suggests that experiencing financial exploitation, fraudulent schemes, and scams may raise a person’s blood pressure, especially in later life. A key difference in the findings was that fraud victimisation was linked with elevated blood pressure in men, but not in women.
Instead of focusing on subjective measures of health after fraud vicitimisation, this study included objective measures of physical health, specifically, systolic and diastolic blood pressure, pulse pressure, and mean arterial pressure. Chronic elevation of these measures are known to contribute to end organ damage including stroke, cardiovascular disease morbidity, and mortality.
The study participants consisted of 1200 older adults from the Rush Memory and Aging Project. During up to 11 years of annual observations, participants were asked about fraud victimisation and underwent serial blood pressure measurements.
In men, blood pressure elevations were observed after they had been the victims of fraud. Those elevations, compounded over time, could indicate future poor health. The rise in blood pressure persisted for years after the fraud had taken place, especially in old age.
“These findings show that fraud victimisation has important public health consequences and underscore the need for efforts to prevent exploitation,” said lead author Melissa Lamar, PhD, of Rush University Medical Center.
Polycystic ovary syndrome (PCOS) is the most common hormonal disorder in reproductive-age women. In a study published in Acta Obstetricia et Gynecologica Scandinavica, women with PCOS were more likely to also have migraine, hypertension, tendinitis, osteoarthritis, and endometriosis. Affected women were also using medications more often and reported their own health to be poorer than women without PCOS.
Few studies have systematically assessed the overall comorbidity in women with PCOS, which should be of greater importance given the high costs of PCOS-related comorbidity. For example, PCOS-related type 2 diabetes alone has been estimated to carry an annual cost of $310 million in the UK and $1.77 billion in the USA. The syndrome often remains underdiagnosed despite being so common, and therefore is less represented in national databases, making it harder to assess comorbidities.
The present study included 246 women with PCOS symptoms or diagnoses and 1573 controls who were surveyed during their late reproductive years at age 46.
“PCOS is often labelled as a reproductive concern; however, in most cases this is well managed with fertility treatments. Our study underscores the need for health professionals to acknowledge the risk for several comorbidities and increased health burden related to this common syndrome,” said senior author professor Terhi T. Piltonen, MD, PhD, of the University of Oulu, in Finland. “Women should also be aware of this risk, and they should be supported by early diagnosis and treatment.”
The risk of intracranial aneurysm rupture was lower in people taking renin-angiotensin-aldosterone system (RAAS) inhibitors for hypertension, according to the findings of a Chinese study published in Hypertension.
A database with more than 3000 people with these aneurysms in 2016–2021, rupture rates reached 23.4% in RAAS inhibitor users and 76.6% in non-users.
RAAS inhibitor use was associated with a significantly reduced risk of intracranial aneurysm rupture (odds ratio [OR] 0.490), and this applied to angiotensin-converting enzyme (ACE) inhibitors (OR 0.559) and angiotensin receptor blockers (ARBs) alike (OR 0.414).
The RAAS inhibitors’ effect persisted across subgroups by age, sex, BMI, control of hypertension, monotherapy and combination therapy, and location and size of intracranial aneurysms.
The researchers pointed out the safety and affordability of RAAS inhibitors, and suggested that a randomised trial be conducted to confirm whether these medications protect against aneurysm rupture.
Hypertension is known to to increases the risk of intracranial aneurysm rupture, the cause of most subarachnoid haemorrhage strokes.
The authors note that there is evidence suggesting RAAS activation is involved in the pathogenesis of intracranial aneurysms.
“In hypertension, the RAAS has wide-ranging effects on blood pressure regulation through sodium retention, pressure natriuresis, salt sensitivity, vasoconstriction, endothelial dysfunction, and vascular injury. Given these facts, in addition to the directly increasing hemodynamic stresses, activation of the RAAS by systemic hypertension can cause vascular inflammation, injury, and remodeling and thereby contribute to the process of intracranial aneurysm rupture,” they explained.
How inhibiting RAAS would prevent aneurysm rupture was unclear, the authors noted, which could be investigated in a future study.
For this retrospective study, the authors reviewed the records of 3044 adults (mean age 61, 36.6% men) patients across 20 Chinese academic medical centres.
Patients were on blood pressure medications and had an intracranial aneurysm, and split between those whose aneurysms had ruptured (n = 1238) or had not ruptured (n = 1806) by the time of analysis. Aneurysms could be treated by clipping, coiling, and/or conservative treatment.
A secondary analysis matched 541 RAAS inhibitor users with an equal number of non-users, revealing that 17.7% of ruptured aneurysms would be prevented if all patients took RAAS inhibitors.
Besides RAAS inhibitor non-use, other independent predictors of rupture included female sex, passive smoking, uncontrolled or unmonitored hypertension, hyperlipidaemia, and aneurysmal location outside the internal carotid artery.
“Our study importantly extends previous studies of blood pressure control, treating hyperlipidemia and diabetes aggressively, and avoiding passive smoking as second [prevention] for these patients,” the authors wrote.
Limitations include possible confounding variables, as well as key clinical variables, such as blood pressure measurements and duration and dose of RAAS inhibitor therapy not being included in the database.
A study published in Frontiers in Neuroscience demonstrated that blood pressure and renal sympathetic nerve activity (RSNA) can be controlled by bioelectronic treatment. RSNA is often increased in hypertension and renal disease.
Using a custom-wired electrode, Professor Mario Romero-Ortega previously reported that deep peroneal nerve stimulation (DPNS) elicits an acute reduction in blood pressure. The current study, advances that work, focusing on his development of a small implantable wireless neural stimulation system and exploration of different stimulation parameters to achieve a maximum lowered response.
Prof Romero-Ortega integrated a nerve stimulation circuit less than a millimetre in size, with a novel nerve attachment microchannel electrode that can be implanted into small nerves, while enabling external power and DPNS modulation control.
Using this implantable device, his team demonstrated that systolic blood pressure can be lowered 10% in one hour and 16% two hours after nerve stimulation.
“Our results indicate that DPNS consistently induces an immediate and reproducible arterial depressor effect in response to electrical stimulation of the deep peroneal nerve,” reported Prof Romero-Ortega.
While pharmacological treatments are effective, blood pressure remains uncontrolled in 50–60% of resistant hypertensive subjects. Unfortunately, despite the use of multiple antihypertensive drugs in combination, blood pressure remains poorly controlled in 50–60% of the hypertensive population and approximately 12–18% of them develop resistant hypertension, defined as blood pressure greater than 140/90 mmHg despite the use of antihypertensive drugs.
“In this study, DPNS induced an initial increase in RSNA during the first 2–3 seconds, followed by a reduction in renal activity and mean arterial pressure, despite the increase in heart rate,” said Prof Romero-Ortega. “The observed activation of the RSNA during the DPNS was not expected since its activity is associated with hypertension.”
A new study published this month in the journal Hypertension has shown gut bacteria can reduce the effectiveness of certain antihypertensive drugs. The researchprovides the first clues into why some people not respond well to medication.
Among those with hypertension, an estimated 20% have resistant hypertension, where their blood pressure remains high despite aggressive treatment.
“The only thing doctors can really do in these patients is adding or switching medications and increasing the dose with the hope they can find something that works,” said Dr Tao Yang, an assistant professor at University of Toledo and the study’s first and lead author. “Until now, we haven’t had any clear indication what the mechanism is for resistant hypertension. Our research could provide a first step toward identifying new ways to effectively overcome treatment-resistant hypertension.”
Recent research has focused on the link between blood pressure and the gut microbiome. That work has helped to unravel potential causes of hypertension beyond diet and exercise. However, Dr Yang’s research is the first to examine the impact of gut bacteria on blood pressure medication itself.
In the study, UToledo scientists compared the effectiveness of the antihypertensive drug quinapril in rats with normal gut bacteria against those with gut microbiota depleted by high doses of antibiotics.
Researchers found a clear difference between the two, with animals that were given antibiotics first responding much better to quinapril.
Analysis of the gut bacteria composition in the animals identified the bacteria Coprococcus as the culprit. Laboratory experiments proved that Coprococcus comes, a dominant bacteria species in this genus, can break down quinapril and ramipril, resulting in the compromised blood pressure-lowering effects.
While the study was confined to animal models and lab experiments, researchers did find at least one intriguing case study that seems to support the notion that this could be applicable to humans.
That 2015 report, published in the International Journal of Cardiology, described a woman with a long history of treatment-resistant hypertension whose blood pressure was controlled without any antihypertensive medication for the two weeks she was taking antibiotics for a post-surgical infection. Her blood pressure was able to be controlled with only one medication for six months after stopping antibiotics, before again becoming treatment-resistant.
“This is just one report and more research is needed. However, this suggests that gut bacteria can play a very real and very important role in regulating the efficacy of blood pressure medication,” Dr Yang said.
The research group intends to further explore the interaction between additional blood pressure medications and other common types of gut bacteria.
Though long-term use of antibiotics isn’t a realistic strategy for addressing treatment-resistant hypertension, Dr Yang said it should be possible for someone to alter their microbiota through probiotics, prebiotics and changes in diet.
“The ultimate goal of my research is to identify ways we can specifically target the bacteria in an individual’s gut to improve drug efficacy,” he said. “This has the potential to benefit a lot of people.”
