A study published in The Lancet Healthy Longevity shows that brain metabolism, detected with advanced imaging techniques, declines more sharply in middle-aged people with a sustained high cardiovascular risk over 5 years
Cardiovascular disease and dementia frequently occur together in elderly people. Nevertheless, few longitudinal studies have examined how atherosclerosis and its associated risk factors affect brain health from middle age. Now, a new study by scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid provides new data on this relationship; the results confirm the importance of controlling traditional cardiovascular risk factors, such as hypertension, cholesterol, diabetes, smoking, and a sedentary lifestyle, not only to preserve cardiovascular health, but also to prevent Alzheimer’s disease and other dementias.
The CNIC study shows that atherosclerosis (accumulation of fatty deposits in the arteries) and its associated risk factors, in addition to being the main cause of cardiovascular disease, are also implicated in the cerebral alterations typically found in Alzheimer’s disease, the most frequent cause of dementia.
According to study author Dr Valentín Fuster, CNIC General Director, the new findings are important because they open up the possibility of treating a modifiable disorder, ie cardiovascular disease, to prevent the development a presently untreatable disease – dementia. “The sooner we act to control cardiovascular risk factors, the better it is for our brain health,” said Dr. Fuster.
“Everybody knows that a healthy lifestyle and controlling cardiovascular risk factors are important for preventing a heart attack,” continued Dr Fuster. “Nevertheless, the additional information linking the same risk factors to a decline in brain health could further increase awareness of the need to acquire healthy habits from the earliest life stages.”
In 2021, CNIC scientists discovered that the presence of cardiovascular risk factors and subclinical (presymptomatic) atherosclerosis in the carotid arteries (the arteries that supply the brain) was associated with lower glucose metabolism in the brains of apparently healthy 50-year-old participants in the PESA-CNIC-Santander study. Glucose metabolism in the brain is considered an indicator of brain health.
The PESA-CNIC-Santander study directed by Dr Fuster is a prospective study that includes more than 4000 asymptomatic middle-aged participants who have been exhaustively assessed for the presence and progression of subclinical atherosclerosis since 2010.
Dr Fuster’s team, led by Drs Marta Cortés Canteli and Juan Domingo Gispert, have continued to monitor the cerebral health of these participants over 5 years. Their research shows that individuals who maintained a high cardiovascular risk throughout this period had a more pronounced reduction in cerebral glucose metabolism, detected using imaging techniques such as positron emission tomography (PET).
“In participants with a sustained high cardiovascular risk, the decline in cerebral metabolism was three times greater than in participants who maintained a low cardiovascular risk,” commented Catarina Tristão-Pereira, first author on the study and INPhINIT fellow.
Glucose is the main energy source for neurons and other brain cells. “If there is a sustained decline in cerebral glucose consumption over several years, this may limit the brain ability to withstand neurodegenerative or cerebrovascular diseases in the future,” explained Dr Gispert, an expert in neuroimaging at the CNIC and Barcelonaβeta Research Center.
Through a collaboration with Drs Henrik Zetterberg and Kaj Blennow, world experts in the identification of new blood biomarkers at the University of Gothenburg in Sweden, the CNIC team discovered that the individuals showing this metabolic decline already show signs of neuronal injury. “This is a particularly important finding because neuronal death is irreversible”, said Dr. Cortés Canteli, a neuroscientist at the CNIC and a Miguel Servet fellow at the Fundación Jiménez Díaz Health Research Institute.
The CNIC team also discovered that the progression of subclinical atherosclerosis in the carotid arteries over five years is linked to a metabolic decline in brain regions vulnerable to Alzheimer’s disease, in addition to the effect of cardiovascular risk factors. “These results provide yet another demonstration that the detection of subclinical atherosclerosis with imaging techniques provides highly relevant information,” said Dr Fuster, who is the principal investigator on the PESA study. “The interaction between the brain and the heart is a fascinating topic, and with this study we have seen that this relationship begins much earlier than was thought.”
The scientists conclude that, “carotid screening has great potential to identify individuals at risk of cerebral alterations and cognitive decline in the future.” In the published article they write, “this work could have important implications for clinical practice since it supports the implementation of primary cardiovascular prevention strategies early in life as a valuable approach for a healthy cerebral longevity.”
“Although we still don’t know what impact this decline in cerebral metabolism has on cognitive function, the detection of neuronal injury in these individuals shows that the earlier we start to control cardiovascular risk factors, the better it will be for our brain,” concluded Dr Cortés Canteli.
In apparent resistant hypertension (aRH), more medication and medical management is needed than for normal hypertension. Novel research published in Hypertension found that aRH prevalence was lower in a real-world sample than previously reported, but still relatively frequent – affecting nearly 1 in 10 hypertensive patients. The researchers stressed the need for clinicians to be on the lookout for the condition.
In their analysis, the Cedars-Sinai investigators also learned that patients with well-managed aRH were more likely to be treated with mineralocorticoid receptor antagonist (MRA). These MRA treatments were used in 34% of patients with controlled aRH, but only 11% of patients with uncontrolled aRH.
“Apparent resistant hypertension is more common than many would anticipate,” said Joseph Ebinger, MD, assistant professor of Cardiology in the Smidt Heart Institute and corresponding author of the study. “We also learned that within this high-risk population, there are large differences in how providers treat high blood pressure, exemplifying a need to standardise care.”
Study findings were based on a unique design, which used clinically generated data from the electronic health records of three large, geographically diverse healthcare organisations. Of the 2 420 468 patients analysed in the study, 55% were hypertensive. Of these hypertension patients, 8.5%, or 113 992 individuals, met criteria for aRH.
According to Ebinger, treating aRH can be just as tricky as diagnosing it.
In fact, the “apparent” in apparent resistant hypertension stems from the fact that before diagnosis, medical professionals must first rule out other potential reasons for a patient’s blood pressure to be high.
These reasons might include medication non-adherence, inappropriate medication selection, or white coat hypertension from measurement in the doctor’s office.
“Large amounts of data tell us that patients with aRH, compared to those with non-resistant forms of hypertension, are at greatest risk for adverse cardiovascular events,” said Ebinger, director of Clinical Analytics in the Smidt Heart Institute. “Identifying these patients and possible causes for their elevated blood pressure is increasingly important.”
The takeaway, Ebinger says, is awareness – for both medical professionals and patients. He says providers should be mindful that if it’s taking four or more antihypertensive medications to control a patient’s blood pressure, they should consider evaluation for alternative causes of hypertension, or refer patients to a specialist.
Similarly, patients should press their healthcare providers to help them navigate the complex disease, including talking about strategies for remembering to take their medication and addressing possible treatment side effects.
Women ages 45 years and older taking oral oestrogen pills were more likely to develop hypertension than those using transdermal or vaginal formulations, according to new research published in Hypertension.
Hormone therapy may be prescribed to relieve symptoms of menopause, in gender-affirming care and in contraception. Previous studies have found that some hormone therapies may reduce cardiovascular disease risk in menopausal women under 60 years of age or for whom it has been fewer than 10 years since menopause. The authors of this study noted that while hypertension is a modifiable risk factor for cardiovascular disease, the potential effects of different types of hormone therapy on blood pressure in menopausal women remain uncertain.
“We know oestrogens ingested orally are metabolised through the liver, and this is associated with an increase in factors that can lead to higher blood pressure,” said lead study author Cindy Kalenga, an MD/PhD-candidate at the University of Calgary.
“We know that post-menopausal women have increased risk of high blood pressure when compared to pre-menopausal women, furthermore, previous studies have shown that specific types of hormone therapy have been associated with higher rates of heart disease,” Kalenga said. “We chose to dive deeper into factors associated with hormone therapy, such as the route of administration (oral vs non-oral) and type of oestrogen, and how they may affect blood pressure.”
This study involved a large group of over 112 000 women, ages 45 years and older, who filled at least two consecutive prescriptions (a six-month cycle) for oestrogen-only hormone therapy, as identified from health administrative data in Alberta, Canada between 2008 and 2019. The main outcome of high blood pressure (hypertension) was identified via health records.
First, researchers investigated the relationship between route of oestrogen-only hormone therapy administration and risk of developing high blood pressure at least one year after starting the treatment. The 3 different routes of hormone therapy administration were oral (by mouth), transdermal and vaginal application. Additionally, researchers evaluated the formulation of oestrogen used and the risk of developing high blood pressure. For this study, the researchers reviewed medical records of individuals taking oestrogen-only hormone therapy. The two most common forms of oestrogen used by study participants were oestradiol – a synthetic form of oestrogen closest to the naturally produced form – and conjugated equine oestrogen, an animal-derived form of oestrogen and the oldest type of oestrogen therapy.
The analysis found:
Women taking oral oestrogen therapy had a 14% higher risk of developing high blood pressure compared to those using transdermal oestrogen and a 19% higher risk of developing high blood pressure compared to those using vaginal oestrogen creams or suppositories. After accounting for age, a stronger association was seen among women younger than 70 years of age compared to women older than 70.
Compared to estradiol, conjugated equine estrogen was associated with an 8% increased risk of developing high blood pressure.
Taking oestrogen for a longer period of time or taking a higher dose was associated with greater risk of high blood pressure, the authors noted. According to Kalenga, the study’s findings suggest that if menopausal woman take hormone therapy, there are different types of oestrogen that may have lower cardiovascular risks.
“These may include low-dose, non-oral oestrogen – like oestradiol, in transdermal or vaginal forms – for the shortest possible time period, based on individual symptoms and the risk–benefit ratio, Kalenga said. “These may also be associated with the lowest risk of hypertension. Of course, this must be balanced with the important benefits of hormone therapy, which include treatment of common menopausal symptoms.”
The average age of natural menopause among women worldwide is about 50 years of age. Current evidence supports that initiating menopausal hormone therapy in the early stages may have cardiovascular benefits, though not in the late stages of menopause, according to the American Heart Association’s 2020 Statement on Menopause Transition and Cardiovascular Disease Risk: Implications for Timing of Early Prevention. Previous studies have found that menopausal hormone therapy may help relieve symptoms of menopause, including hot flashes, night sweats, mood changes or sleep disturbances.
Limitations included being based only on medical records, not including women younger than the age of 45 and not collecting data about hysterectomies or menopausal status (which was inferred by taking oestrogen after 45).
The authors will be conducting more research investigating combined oestrogen and progestin, as well as progestin-only formulations of hormone therapy and their impact on heart and kidney diseases.
Engineers have developed a simple, low-cost clip that uses a smartphone’s camera and flash to monitor blood pressure at the user’s fingertip. The clip works with a custom smartphone app and currently costs about $0.80 to make. The researchers estimate that the cost could be as low as $0.10 apiece when manufactured at scale. The technology was described in the journal Scientific Reports.
Researchers say it could help make regular blood pressure monitoring easy, affordable and accessible to people in resource-poor communities. It could benefit older adults and pregnant women, for example, in managing conditions such as hypertension.
“We’ve created an inexpensive solution to lower the barrier to blood pressure monitoring,” said study first author Yinan (Tom) Xuan, an electrical and computer engineering PhD student at University of California San Diego.
“Because of their low cost, these clips could be handed out to anyone who needs them but cannot go to a clinic regularly,” said study senior author Edward Wang, a professor of electrical and computer engineering at UC San Diego and director of the Digital Health Lab. “A blood pressure monitoring clip could be given to you at your checkup, much like how you get a pack of floss and toothbrush at your dental visit.”
Another key advantage of the clip is that it does not need to be calibrated to a cuff.
“This is what distinguishes our device from other blood pressure monitors,” said Wang. Other cuffless systems being developed for smartwatches and smartphones, he explained, require obtaining a separate set of measurements with a cuff so that their models can be tuned to fit these measurements.
“Our is a calibration-free system, meaning you can just use our device without touching another blood pressure monitor to get a trustworthy blood pressure reading.”
To measure blood pressure, the user simply presses on the clip with a fingertip. A custom smartphone app guides the user on how hard and long to press during the measurement.
The clip is a 3D-printed plastic attachment that fits over a smartphone’s camera and flash. It features an optical design similar to that of a pinhole camera. When the user presses on the clip, the smartphone’s flash lights up the fingertip. That light is then projected through a pinhole-sized channel to the camera as an image of a red circle. A spring inside the clip allows the user to press with different levels of force. The harder the user presses, the bigger the red circle appears on the camera.
The smartphone app extracts two main pieces of information from the red circle. By looking at the size of the circle, the app can measure the amount of pressure that the user’s fingertip applies. And by looking at the brightness of the circle, the app can measure the volume of blood going in and out of the fingertip. An algorithm converts this information into systolic and diastolic blood pressure readings.
The researchers tested the clip on 24 volunteers from the UC San Diego Medical Center. Results were comparable to those taken by a blood pressure cuff.
“Using a standard blood pressure cuff can be awkward to put on correctly, and this solution has the potential to make it easier for older adults to self-monitor blood pressure,” said study co-author and medical collaborator Alison Moore, chief of the Division of Geriatrics in the Department of Medicine at UC San Diego School of Medicine.
While the team has only proven the solution on a single smartphone model, the clip’s current design theoretically should work on other phone models, said Xuan.
Next steps include making the technology more user friendly, especially for older adults; testing its accuracy across different skin tones; and creating a more universal design.
While HIV and tuberculosis (TB) rates in South Africa are slowly declining, indications are that rates of non-communicable diseases (NCDs) like hypertension and diabetes are on the rise. One response to this shift is to bring some of the strategies used in combatting HIV to NCDs.
Hypertension, more commonly known as high blood pressure, has been described as a “silent killer” because there are often no symptoms associated with having it. Hypertension is when someone’s blood pressure is consistently higher than normal, which can lead to a host of complications, including stroke, heart attack, and kidney disease. Someone’s risk of developing hypertension is influenced by a number of things, including lifestyle, genetics, age, and family history as well as conditions like diabetes. (Spotlight previously reported on the state of hypertension in South Africa.)
90-60-50
For much of the last decade, UNAIDS’s 90-90-90 targets have been central to how governments have kept track of their HIV responses. The first 90 measured the success of testing programmes, the second 90 measured the success of efforts to get people on to treatment, and the third 90 provided information on how well people are doing once on treatment.
South Africa’s National Strategic Plan (NSP) for the prevention and control of NCDs (2022-2027) sets out similar targets for hypertension and diabetes. As with HIV, the three hypertension indicators will paint a picture of how South Africa is doing on testing, getting people onto treatment, and finally how well people are doing once on treatment.
The hypertension targets are as follows:
90% of people over 18 will know whether they have raised blood pressure.
60% of people with raised blood pressure will receive interventions.
50% of people receiving interventions for hypertension will have controlled blood pressure levels.
Implementation will be key
Local experts interviewed by Spotlight agree that the NSP is a step in the right direction but are clear that much more will be needed.
Professor Brian Rayner, Emeritus Professor in the Division of Nephrology and Hypertension at the University of Cape Town, says he finds the NSP lacking in practical details of how the targets will be achieved. “I’d love for the government to have the plan for how they can achieve this and not another document actually… they need to actually say how are we going do this,” he says.
Professor Angela Woodiwiss of the School of Physiology at the University of the Witwatersrand, and member of the board of the Southern African Hypertension Society has similar concerns. She says the objectives and deliverables in the NSP are sound, but it is short on details when it comes to implementation.
Ways to address this, according to Woodiwiss, is to include “examples of cost-effective practical approaches such as the establishment of cardiovascular screening centres at all district clinics where measurements of blood pressure are done; monthly screening drives at community centres over weekends to increase accessibility to those that work during the week; [and] awareness campaigns at shopping centres”. Another suggestion is for awareness and education campaigns on hypertension to be conducted on media platforms like TV and radio.
“In order to reduce the burden of disease, this target needs to be raised. I would therefore suggest 90-80-70 as the proportions,” she adds.
Professor Andre Kengne, the director of NCD research at the South African Medical Research Council, who was also part of the planning committee for this version of the NSP, says the plan is only a starting point. “The plan says that these [NSP targets] are the entry point, so it’s going to be a catalyst,” he says. “That’s why we just need to start somewhere and then improve on that and again, I think that’s exactly the approach that the plan is taking, This is let’s start small but with the aim of actually progressing.”
Screening: 90% of people over 18 will know whether they have raised blood pressure
A major challenge with NCDs such as hypertension and diabetes is that we don’t have very good epidemiological data in South Africa. Experts referred Spotlight to data from two sources.
Kengne says that based on data collected by the NCD Risk Factor Collaboration, a global network of health scientists that provide data on NCDs, which he is part of, about 40% of adult men and about 42% of adult women in South Africa had hypertension in 2019. Only about 38.5% of men with hypertension were diagnosed at the time and 61.5% of women.
Woodiwiss cites data collected through ‘May Measure Month’ (MMM) South Africa, of where she is a principal investigator. MMM is a global campaign run by the International Society of Hypertension to raise awareness. She cites data collected from screenings conducted from 2017 to 2022.
“The proportion of hypertensive adults aware that they have hypertension ranged from 42.5 to 56.7%,” she says.
When looking at the South African population as a whole, Woodiwiss calculates that this means that only around 13.6 to 19.6% of all people over the age of 18 are aware of whether they have hypertension or not. “We, therefore, have a long way to go in order to achieve the target of 90% of all adults being aware of whether they have raised blood pressure or not,” she adds.
Whichever of the two data sources you look at, South Africa seems to fall well short of the 90% target.
To improve the country’s performance on this measure, experts interviewed by Spotlight agree that there needs to be greater awareness of hypertension (including the importance of checking your blood pressure regularly) and better opportunities for screening.
“There will be no other way of actually improving the numbers without screening people,” Kengne says.
“The current screening approach is essentially hospital-based, and it’s not even yet comprehensive. Meaning only those in contact with the health system are likely, for a proportion, to get their blood pressure measured and then eventually diagnosed with hypertension,” he explains. “The first focus is really to optimise that hospital-based screening, to make sure that everything is in place to measure the blood pressure of whoever gets in contact with the health system.”
Ultimately, Kengne suggests what is needed is to implement community-based approaches to blood pressure screening. One way to do this would be to couple HIV community screening efforts with hypertension screening. As well as to empower community healthcare workers to check blood pressure when doing household visits and then refer people with elevated blood pressure to clinics if needed.
“There need to be national awareness campaigns on TV and radio. These campaigns can be used to encourage individuals to have their blood pressure measured at free screening sites such as community centres, shopping malls, and university campuses as is done as part of the May Measure Month campaign,” Woodiwiss suggests. She adds that a celebrity ambassador would be a great asset for such campaigns.
Treatment: 60% of people with raised blood pressure will receive interventions
“About 85% of those [men] who are diagnosed [with hypertension] are on treatment. And in women it’s about 86%,” Kengne says.
He adds that this is where the NSP targets are maybe not as ambitious as they could be because when you look at the data in the context of everyone who has hypertension (not just those with diagnosed hypertension), only 33% of men and 53% of women are on treatment.
In Woodiwiss’s data, the proportion of hypertensive adults who were receiving medication for hypertension ranged from 36.1 to 49.2%.
Either way, both data sources suggest that one of the biggest challenges to getting people onto treatment is actually diagnosing them in the first place. There is a question, however, whether the health system will be able to cope with the increased treatment load should diagnosis improve.
Kengne suggests that facilities, specifically public health sector facilities, may not be able to cope with the increased demand. “We’re going to need to prepare the health system to cope with the high demand for hypertension care subsequent to increased screening,” he says.
He thinks task-shifting may be part of the solution. Task-shifting was critical to the scaling up of South Africa’s HIV treatment programme, for example, by allowing qualifying nurses to prescribe antiretroviral treatment. Similarly, more healthcare workers, including community healthcare workers, nurses, and field workers can be trained to screen for and treat hypertension.
Woodiwiss stresses the importance of education and awareness when it comes to treatment.
“To facilitate the participation of individuals in the management of their blood pressure, education, and awareness are paramount… An important aspect is to empower individuals to be part of the management of their blood pressure; to re-enforce that hypertension is a chronic problem that requires daily management; and to dispel any notions of stigmatisation due to having high blood pressure,” she says.
Another important practical step would be to reduce the pill burden on hypertension patients in the public sector, according to Rayner. While medication is relatively cheap in this sector, there has not been a move towards combining multiple blood pressure drugs into a single pill, which would make patient adherence easier.
He adds that the process of prescribing blood pressure medication in the private sector needs to be simplified. In line with the idea of task-shifting, Rayner suggests allowing nurses to prescribe medication for straightforward hypertension cases in the public sector as a cost-effective way of treating hypertension.
Control: 50% of people receiving interventions are controlled
About 43% of men in South Africa with hypertension and who are on treatment have controlled blood pressure compared to 54.6% of women, according to Kengne. “Now taken as a proportion of all those with hypertension, I mean our target of 50% controlled will narrow down to about 27% of all people with hypertension [being controlled],” he says. “Using that as the estimate among men currently only 14% of all those with hypertension are controlled and among women, 29% are controlled.”
Data from Woodiwiss suggested that “the proportion of treated individuals with controlled blood pressure ranges from 49.6 to 57.5%.”
For this target then, the country isn’t too far off the 50% target.
But Kengne stresses that blood pressure control is not straightforward. “Diagnosing, it’s not that difficult. Starting treatment it’s not difficult, but actually treating to target it’s a challenge and a number of factors can come into play. Some factors [are] linked to people with hypertension [and] some linked to healthcare providers and the health system,” he says.
For patients, issues like adherence to treatment can be difficult. He suggests using mobile technology, like text messages, to remind patients to take their medication. As well as reducing the pill burden by investing in combination medications.
From the healthcare provider side, Kengne says there needs to be monitoring of patients so that changes to the treatment plan can be made if needed so that the patient can achieve blood pressure control.
“Improving the proportion of treated individuals who have controlled blood pressure requires ongoing monitoring and regular blood pressure checks. As the vast majority of South Africans cannot afford home blood pressure monitors, easy access to blood pressure checks at community clinics, pharmacies, etc. should be provided country-wide,” Woodiwiss says. “It would be ideal if companies could all have corporate wellness days for employees.”
Results from a clinical trial published in the Journal of Internal Medicine reveal several health benefits of moderate salt restriction in patients on standard medical treatment for primary aldosteronism/ These included lowered blood pressure and reduced depressive symptoms.
Primary aldosteronism – when adrenal glands produce excess aldosterone – is a common cause of secondary hypertension. The combination of aldosterone excess and high dietary salt intake leaves affected patients with a higher risk of cardiovascular disease than patients with hypertension from other causes. Mineralocorticoid antagonists are the main treatment of primary aldosteronism, but these medications do not completely normalise patients’ elevated cardiovascular risk.
Because elevated aldosterone and high dietary salt intake have detrimental effects on patients’ health, investigators wanted to find out whether salt restriction might benefit patients. In the non-randomised single-arm Salt CONNtrol trial that included 41 patients, moderate salt restriction reduced blood pressure and depressive symptoms without detectable adverse effects.
“The study shows that a moderate dietary salt restriction is feasible, when combined with a dedicated smartphone app for continuous motivation, and has a strong antihypertensive effect in patients with primary aldosteronism,” said corresponding author Christian Adolf, MD, of Ludwig Maximilian University of Munich, in Germany. “Our findings will help to improve care for patients with primary aldosteronism and, likely, also for subgroups of patients with essential hypertension.”
A device that uses ultrasound to calm overactive nerves in the kidneys may be able to help some people get their blood pressure under control, according to successful test results published in JAMA Cardiology.
Led by researchers at Columbia University and Université de Paris, the study has found that the device consistently reduced daytime ambulatory blood pressure by an average of 8.5 points among middle-aged people with hypertension.
Lifestyle changes, such as cutting salt intake or losing weight, along with medications are often prescribed to lower blood pressure in patients with hypertension. Yet about one-third of hypertensive patients have resistant hypertension.
“Many patients in our clinical practice are just like the patients in our study, with uncontrolled blood pressure in the 150s despite some efforts,” says Ajay Kirtane, MD, professor of medicine at Columbia University Vagelos College of Physicians and Surgeons and co-leader of the study.
Leaving blood pressure uncontrolled for too long can lead to heart failure, strokes, heart attacks, and irreversible kidney damage.
“Renal ultrasound could be offered to patients who are unable to get their blood pressure under control after trying lifestyle changes and drug therapy, before these events occur,” says Kirtane, who is also an interventional cardiologist and director of cardiac catheterisation laboratories at NewYork-Presbyterian/Columbia University Irving Medical Center.
The study tested the device, which is used in an outpatient procedure called ultrasound renal denervation. The device is still investigational and has not yet been approved by the FDA for use outside of clinical trials.
Kidney nerves and hypertension
Hypertension in middle age is thought to be caused in part by overactive nerves in the kidneys, which trigger water and sodium retention and release hormones that can raise blood pressure. (In older people, hypertension often occurs as blood vessels stiffen). Antihypertensive drugs work in different ways to lower blood pressure, by dilating blood vessels, removing excess fluid, or blocking hormones that raise blood pressure. But none target the renal nerves directly.
Ultrasound therapy calms overactive nerves in the renal artery, disrupting signals that lead to hypertension. The therapy is delivered to the nerves via a thin catheter that is inserted into a vein in the leg or wrist and threaded to the kidney.
Study results
The new study pooled data from three randomised trials encompassing more than 500 middle-aged patients with varying degrees of hypertension and medication use.
Twice as many patients who received the ultrasound therapy reached their target daytime blood pressure (less than 135/85 mmHg) compared to patients in the sham groups.
“The result was almost identical across the different study groups, which definitively shows that the device can lower blood pressure in a broad range of patients,” Kirtane says.
The procedure was well-tolerated, and most patients were discharged from the hospital the same day. According to Kirtane, improvements in blood pressure were seen as soon as one month after the procedure.
The treatment will be evaluated by the FDA in the coming months.
Bottom line for patients with resistant hypertension
The investigators expect the treatment could be offered as an adjunct to medication therapy and lifestyle changes for patients with uncontrolled hypertension.
“Once the device is available, we envision recommending it to patients who have tried other therapies first. The hope is that by controlling blood pressure, we might be able to prevent kidney damage and other effects of uncontrolled blood pressure,” Kirtane adds.
Hypertension and diabetes are known risk factors for stroke, but now a new study shows that the amount of risk may decrease as people age. The study is published in Neurology.
“High blood pressure and diabetes are two important risk factors for stroke that can be managed by medication, decreasing a person’s risk,” said study author George Howard, DrPH, of the University of Alabama at Birmingham School of Public Health. “Our findings show that their association with stroke risk may be substantially less at older ages, yet other risk factors do not change with age. These differences in risk factors imply that determining whether a person is at high risk for stroke may differ depending on their age.”
The study involved 28 235 people who had never had a stroke and were followed for 11 years. Risk factors included hypertension, diabetes, smoking, atrial fibrillation, heart disease and left ventricular hypertrophy. Because of the well-known higher stroke risk in Black people (comprising 41% of participants), race was also considered as part of the assessed risk factors, Howard added.
Researchers followed up with participants every six months, confirming strokes by reviewing medical records.
During the study, there were 1405 strokes over 276 074 person-years. Participants were divided into three age groups. The age ranges for those groups varied slightly depending on the data being analysed by researchers. In general, the younger group included participants ages 45–69, the middle group included people in their late 60s to 70s and the older group included people 74 and older.
Researchers found that people with diabetes in the younger age group were approximately twice as likely to have a stroke as people of similar age who did not have diabetes, while people with diabetes in the older age group had an approximately 30% higher risk of having a stroke than people of similar older age who did not have diabetes.
Researchers also found that people with high blood pressure in the younger age group had an 80% higher risk of having stroke than people of similar age without high blood pressure while that risk went down to 50% for people with high blood pressure in the older age group compared to people of similar age without high blood pressure.
With race/ethnicity as a risk factor, Black participants in the younger age group compared to White participants in that group, a difference which decreased in the older age group. For stroke risk factors such as smoking, atrial fibrillation and left ventricular hypertrophy, researchers did not find an age-related change in risk.
“It is important to note that our results do not suggest that treatment of high blood pressure and diabetes becomes unimportant in older age,” said Howard. “Such treatments are still very important for a person’s health. But it also may be wise for doctors to focus on managing risk factors such as atrial fibrillation, smoking and left ventricular hypertrophy as people age.”
Howard also noted that even where the impact of risk factors decreases with age, the total number of people with strokes at older ages may still be larger since overall risk of stroke increases with age. For example, in the younger age group for hypertension, researchers estimate that about 2.0% of normotensive people had a stroke, compared to 3.6% of hypertensive people. In the older age group, about 6.2% of normotensive people had a stroke, compared to 9.3% of hypertensive people.
A limitation of the research was that participants’ risk factors were assessed only once at the start of the study, and it’s possible they may have changed over time.
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.
