Tag: antihypertensives

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Long-term Blood Pressure Control from Bariatric Surgery is Most Effective

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Compared to antihypertensives alone, bariatric surgery is more effective in controlling hypertension rates in people with obesity and uncontrolled hypertension, according to a study published in the Journal of the American College of Cardiology. People who underwent bariatric surgery had lower BMI and were on fewer medications after five years while maintaining normal blood pressure levels than those who only used antihypertensive medications.

“In clinical practice, obesity is an overlooked condition. As a consequence, there is a frequent failure in approaching obesity as a crucial step for mitigating the risk of important cardiovascular risk factors including hypertension,” said Carlos Aurelio Schiavon, MD, FACS, lead author of the study and a surgeon specialising in bariatric surgery at Heart Hospital (hcor) and BP Hospital in Sao Paulo.

Researchers in this study looked at the impact of treating obesity to lower hypertension. While new weight loss drugs exist, long-term adherence to medication can be challenging.

This study looks at bariatric surgery as a better long-term solution to control obesity and, as a result, hypertension.

The GATEWAY trial included 100 people (76% of whom were female) who had a body mass index (BMI) of around 36.9kg/m2. All participants had hypertension and were using at least two medications. People with previous cardiovascular events and poorly controlled Type 2 diabetes were excluded.

Subjects were assigned to either Roux-en-Y gastric bypass with medical therapy or medial therapy alone and the primary outcome was reduction of at least 30% antihypertensive medications while maintaining blood pressure levels less than 140/90mmHg at five years.

At five years, BMI was 28.01kg/m2 for those who received bariatric surgery and 36.40kg/m2 for those on medical therapy alone.

People who had bariatric surgery had an 80.7% reduction in the number of medications they were taking compared to a 13.7% reduction in those only using medical therapy.

Hypertension remission, defined as controlled blood pressure without medications, was 46.9% in those who underwent bariatric surgery compared to 2.4% in those on medical therapy alone.

“Our results underscore the importance of approaching obesity in reducing hypertension rates,” Schiavon said.

Limitations of the study include that it was a single-center, open-label study with a small sample size and there was loss of follow up in some patients.

In an accompanying editorial comment, Michael Hall, MD, MSc, professor and chair of the Department of Medicine at the University of Mississippi Medical Center, said the study provides important long-term data on the benefits of gastric bypass on weight loss and blood pressure control, but questions remain.

“Further studies assessing the threshold for bariatric surgery in people with obesity, optimal timing of bariatric surgery in obese people with cardiometabolic diseases, type of bariatric surgery and comparative studies of obesity pharmacotherapies and bariatric surgery are needed to clarify the optimal treatment pathways for this common and growing disease,” he said.

Source: American College of Cardiology

Categories : Cardiovascular DiseaseTags :

Genetic Risks for ACE Inhibitor-induced Angioedema Identified

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Angioedema is a rare but potentially life-threatening adverse reaction to ACE inhibitors. In a joint analysis of eight European study collectives, researchers for the first time conducted a genome-wide association study (GWAS) with more than 1000 affected individuals, identifying a total of three risk loci in the genome. These included a new locus that had not previously been associated with the risk of ACE inhibitor-induced angioedema. The results of the study have now been published in the Journal of Allergy and Clinical Immunology.

Angiotensin-converting enzyme (ACE) inhibitors are effective antihypertensive drugs. They block the formation of the hormone angiotensin II, which plays a central role in the development of hypertension.

On the other hand, these drugs increase the concentration of the vasoactive signalling substance bradykinin. Among other things, this can lead to acute swelling of the skin or mucous membranes.

Such swellings are generally not life-threatening – but if they affect the tongue, throat or larynx, angioedema can be life-threatening for the patient due to the potential risk of suffocation.

Research to date suggests that susceptibility to such drug-induced angioedema is influenced by hereditary as well as lifestyle and environmental factors. This led researchers from the University Hospital Bonn (UKB), the University of Bonn and the Federal Institute for Drugs and Medical Devices (BfArM) to investigate potential genetic involvement.

“However, the understanding of the underlying biological processes, ie the pathophysiology, and thus the individual risk assessment is still limited. The identification of the responsible genes will provide completely new insights here,” says Prof Markus Nöthen at the University of Bonn.

Which biological processes play a role in ACE inhibitor-induced angioedema?

Based on data from eight European study collectives, the team from Bonn, together with cooperation partners, conducted the first GWAS with more than 1000 patients with ACE inhibitor-induced angioedema.

They identified a total of three loci in the genome that are associated with the risk of ACE inhibitor-induced angioedema.

“While two of the loci have already been described in previous studies, our study was the first to demonstrate a significant association for a new locus on chromosome 20,” explains corresponding author Prof.

Andreas Forstner from the Institute of Human Genetics at the UKB and the University of Bonn and at the Institute of Neuroscience and Medicine (INM-1) at the Research Center Jülich.

“Through further bioinformatic analyses, we were able to identify several candidate genes at the three risk loci indicating that genetic changes in the bradykinin, coagulation and fibrinolysis signalling play a role in the development of this type of angioedema,” adds first author Carina Mathey, doctoral student at the Institute of Human Genetics at the UKB and the University of Bonn.

Source: Universitatsklinikum Bonn

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Intensive BP Target of Under 120mmHg Yields even Better Outcomes

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An intensive three-year intervention to lower systolic blood pressure (BP) to less than 120mmHg was more effective at preventing death, heart attack, stroke and other cardiovascular events in adults at high risk for cardiovascular disease, compared to the standard treatment target of under 140mmHg, according to late-breaking science presented at the American Heart Association’s Scientific Sessions 2023.

“Our study provides evidence to support targeting systolic blood pressure to less than 120mmHg in hypertensive patients with high cardiovascular risk and normal or mild-reduced kidney function, regardless of their diabetes status (Type 1, Type 2 or none) or history of stroke,” said lead study author Jing Li, MD, PhD, director of the department of preventive medicine at the National Center for Cardiovascular Diseases in Beijing, China.

The researchers conducted a multi-centre, randomised controlled trial to evaluate the effects of an intensive blood pressure-lowering strategy on the incidence of major cardiovascular events, including heart attack, stroke, cardiovascular death, revascularisation, or hospitalisation or emergency room visit for heart failure, in participants with increased cardiovascular risk.

Participants in the ESPRIT trial were randomised to receive intensive antihypertensive treatment with a systolic BP target of less than 120mmHg (using higher doses and multiple classes of drugs) or standard treatment, with a target measurement of under 140mmHg over a three-year period. Safety was assessed between treatment groups by comparing serious adverse events among participants.

The researchers found that after two years, participants in the intensive treatment group had significantly better outcomes than those receiving standard care. Compared with the standard treatment, the intensive treatment strategy prevented:

  • 12% of heart attacks, stroke, revascularisation procedures, death from cardiovascular causes and hospitalisation or emergency room visit for heart failure;
  • 39% of deaths from cardiovascular causes; and
  • 21% of deaths from any cause.
  • There was no significant difference in serious adverse events of hypotension, electrolyte abnormality, fall resulting in an injury, acute kidney injury or renal failure.

Syncope, or fainting, was one of the serious adverse events used to evaluate safety. Syncope occurred at a rate of 0.4% per year in the intensive group and 0.1% in the standard group. This means that for every 1000 patients receiving the intensive treatment for 3 years, 3 patients would experience a serious adverse event of syncope, while 14 major vascular events and 8 deaths would be further prevented, Li noted.

“These results provide evidence that intensive hypertension treatment focused on achieving systolic blood pressure of less than 120mmHg is beneficial and safe for individuals with high blood pressure and increased cardiovascular risk factors,” Li said. “Implementing this intensive treatment strategy for high-risk adults has the potential to save more lives and reduce the public health burden of heart disease worldwide.”

Study details and background:

  • The ESPRIT trial included 11,255 adults in China. Participants had a baseline systolic blood pressure measurement of 130–180mmHg and either established cardiovascular disease or at least two major risk factors for cardiovascular disease.
  • Participants were an average age of 64.6 years; 41.3% women and 58.7% men.
  • Approximately 27% of the study participants had a history of stroke; approximately 29% had previous coronary heart disease; and approximately 39% had diabetes, Type 1 or Type 2.
  • The trial’s primary outcome was a composite outcome of heart attack, coronary or non-coronary revascularisation, hospitalisation/emergency room visit for heart failure, stroke or CV death. Secondary outcomes included CV outcomes, kidney outcomes and cognitive outcomes.

Study limitations included that the cardiovascular benefits of the intensive intervention emerged after two years, while the intervention only lasted three years, meaning the relatively short study period may underestimate the benefits, Li said. In addition, the study was conducted in China and therefore, the results may not be generalisable to people in other racial and ethnic groups or living in other countries. However, Li also noted that the results were consistent with similar studies in people of other racial and ethnic groups.

Future work will involve examining the longer-term effects of the intensive intervention strategy over the follow-up period.

Source: American Heart Association

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Cold Weather may Make Blood Pressure Control More Challenging

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Blood pressure among patients diagnosed with hypertension appeared to slightly increase and rates of systolic blood pressure being controlled during an outpatient visit appeared to slightly decrease during winter months, according to a new study presented at the American Heart Association’s Hypertension Scientific Sessions 2023.

Previous research has found that blood pressure varies with the seasons of the year, most of which is systolic blood pressure. The study authors sought to understand whether blood pressure control, defined in this study as less than 140/90mmHg among patients with hypertension, varied by season.

“Despite the smaller degree of systolic blood pressure variation in comparison to previous studies on seasonality in blood pressure, we were surprised to observe a large degree of change in blood pressure control between winter and summer months,” said lead study author Robert B. Barrett, a software engineer at the American Medical Association in Greenville, South Carolina. “Individuals with hypertension or values near the range of hypertension may benefit from periodic blood pressure monitoring and improvements in physical activity and nutritional patterns during winter months to offset adverse effects from seasonal blood pressure changes.”

The researchers reviewed electronic health records for 60 676 adults treated for hypertension between July 2018 and June 2023 at six health care centres. Each participant remained on their originally prescribed classes of antihypertensive drugs throughout the review period. The centres ranged from small health centres or clinics to large academic medical centres. Seasonal blood pressure readings were analysed to assess variations in blood pressure control during the northern hemisphere’s winter vs summer months (December through February vs June through August, respectively) as part of an American Medical Association-supported, quality-improvement program for clinicians and health care centres. Study participants were an average age of 62 years old; 52.3% identified as white race; 59.7% identified as female.

The analysis of the health records found that, on average, participants’ systolic blood pressure increased by up to 1.7mmHg in the winter months compared to the summer months. In addition, they found that blood pressure control rates decreased by up to 5% during the winter months.

Future directions for investigation might include analysing the frequency of heart disease and deaths during each season, the authors noted.

The study’s limitations include that the electronic health records did not capture a complete health history for each participant and that information collected for each patient was retrieved only from the institution where they were treated.

Source: American Heart Association

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Treatment-resistant Hypertension Affects 1 in 10 Hypertensive Patients

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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.

Source: Cedars-Sinai Medical Center

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Some Antihypertensives might Boost the Effectiveness of Cancer Immunotherapy

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A study reported in the latest issue of Nature has shown that some molecules previously used to treat hypertension might also help the immune system to better target cancer cells. The researchers believe that these findings could eventually be applied to significantly improve the effectiveness and applicability of cancer immunotherapy.

“Immunotherapy today can effectively fight only 30% to 40% of cancers,” said Benoît Van den Eynde, at the Ludwig Institute for Cancer Research, co-director of the de Duve Institute and professor of Tumour Immunology at the University of Oxford. “Many cancers are resistant, largely because their T lymphocytes are not reactive enough. We discovered that drugs once used to treat hypertension could have a very interesting effect in combating these forms of immunotherapy-resistant cancers.”

T lymphocytes are active components in the immune system, recognising and destroying cells that appear foreign. Cancer cells, however, are not foreign and are therefore often not recognised and attacked by T lymphocytes. But about thirty years ago, Thierry Boon and his colleagues at the former Brussels Branch of the Ludwig Institute for Cancer Research at the de Duve Institute discovered specific markers on the surface of cancer cells – tumour antigens – that can be recognised by T cells that then destroy the cancerous cells.

This work paved the way for cancer immunotherapy, a treatment approach that helps T cells destroy cancerous cells. Thanks to T cells’ specificity and memory of tumour antigens, immunotherapy makes it possible to treat advanced cancers with some success. It is now used worldwide. However, such therapies are not equally effective in all patients or against all types of cancer.

In the current study, a team led by Jingjing Zhu in Van den Eynde’s laboratory shows that anti-hypertensive drug-molecules known as α2-adrenergic receptor (α2AR) agonists also influence the behaviour of macrophages. While doing that job, macrophages also alert T cells of any abnormalities they encounter, presenting suspicious antigens to the cells to trigger a possible immune response.

Zhu, Van den Eynde and colleagues discovered that alongside their known hypotensive and anaesthetic effects, α2AR agonists can also stimulate macrophages in their role as sentinels, making T cells more reactive and more effective at rejecting cancer cells. The effect extended, most notably, to cancer models that are resistant to standard immunotherapy. This suggests the new approach could boost the efficacy of clinical immunotherapy, even for the many types of cancer that are largely unresponsive to such interventions.

These findings also present a rationale for the development of new molecules that might be used in combination with immunotherapy to improve its efficacy.

“One could imagine using existing blood pressure-lowering drugs,” said Van den Eynde. “But that would be quite risky, owing to the undesired effects and the toxicity of these drugs at the necessary doses. Another approach would be to develop new molecules that would act in the same way on macrophages but would not have the unwanted toxic effects. We have already made significant progress in this direction.”

Source: Ludwig Cancer Research

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Novel Antihypertensive Flounders in Early Trial Phase

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BP cuff for home monitoring, Source: Pixabay

A phase II trial with the novel antihypertensive baxdrostat did not replicate the impressive results in a similar trial for the drug in treatment-resistant hypertension, failing to improve on placebo effect.

Deepak Bhatt, MD, MPH, of Mount Sinai Heart in New York City, presented the disappointing findings at the American College of Cardiology (ACC) annual meeting, but noted that the findings were not a complete write-off for the drug, hampered as the trial was by poor patient adherence and the confounding effect of other antihypertensives.

For baxdrostat, seated systolic blood pressure was lowered by 16.0–19.8mmHg across the doses tested, compared to 16.6mmHg for placebo, a nonsignificant difference. Diastolic blood pressure drops showed a similar pattern, even slightly favouring placebo.

HALO included 249 participants with a mean seated systolic blood pressure of 140–180 mmHg at baseline despite treatment with a stable regimen of an ACE inhibitor or one of those drugs plus a thiazide diuretic or a calcium channel blocker. They were randomised to placebo or a 0.5-, 1.0-, or 2.0-mg dose of baxdrostat for 8 weeks.

In the prior phase II BrighHTN trial, baxdrostat reduced systolic blood pressure by 11 and 8.1 mm Hg more than placebo in the two higher dose groups.

The drug, which is in a new class of highly selective aldosterone synthase inhibitors, did decrease serum aldosterone and increase plasma renin activity as expected compared with placebo in HALO.

A post hoc analysis to understand why the trial failed despite high pill-count based adherence showed that 36% of the baxdrostat patients in the highest, 2-mg dose group (20 of 54) were actually not adherent, based on plasma levels < 1% of expected.

ACC session moderator Kim Eagle, MD, of the University of Michigan in Ann Arbor wondered if the patients were flushing their pills, and Bhatt replied that these were clustered at a few sites, highlighting issues of site selection and providing patient support.

The adherence problem does not explain away the placebo effect, Eagle told MedPage Today. “The placebo effect may well be that by enrolling in a trial, the patient is also taking their other meds for hypertension. Recall that the patients were already supposed to be taking several antihypertensives.”

Nevertheless, he called it compelling that, in “patients who were taking the larger dose and who had evidence of adherence by blood levels, the drug clearly seems to work.”

Source: MedPage Today

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Common Hypertension Drug Extends Lifespan in Animal Studies

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Researchers have found that, in animal studies, the hypertension drug rilmenidine can extend lifespan and slow ageing. Published in Aging Cell, the findings show that animals treated with rilmenidine at young and older ages increases lifespan and improves health markers by mimicking the effects of caloric restriction.

They also demonstrate that the healthspan and lifespan benefits of rilmenidine treatment in the roundworm C. elegans are mediated by the I1-imidazoline receptor nish-1, identifying this receptor as a potential longevity target.

With side-effects being rare and non-severe, unlike other drugs previously studied for this purpose by the researchers, the widely-prescribed antihypertensive has potential for future translatability.

A caloric restriction diet has thus far proved to be the most robust anti-ageing intervention, promoting longevity across species. However, studies of caloric restriction in humans have had mixed results and side effects, meaning finding medications like rilmenidine that can mimic the benefits of caloric restriction is the most reasonable anti-ageing strategy.

Professor João Pedro Magalhães, who led the research whilst at the University of Liverpool and is now based at the University of Birmingham, said: “With a global ageing population, the benefits of delaying ageing, even if slightly, are immense. Repurposing drugs capable of extending lifespan and healthspan has a huge untapped potential in translational geroscience. For the first time, we have been able to show in animals that rilmenidine can increase lifespan. We are now keen to explore if rilmenidine may have other clinical applications.”

Source: University of Liverpool. 

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A Trend of Prescribing Oral Minoxidil Off-label for Baldness

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The New York Times reports that low oral doses of the cheap antihypertensive drug minoxidil – a key ingredient in many hair-loss treatments such as Rogaine – is now being widely used as an off-label prescription for male and female hair loss.

Since the accidental discovery of minoxidil’s topical efficacy in treating hair loss in the 1980s, it had became a staple in `Rogaine for male and female patients. However, applying the foam or lotion onto scalps is time-consuming and uncomfortable for many – as well as expensive.

There is not much in the way of clinical evidence as to its efficacy. A 2019 study in the Journal of the American Academy of Dermatology is so far the only randomised open study to compare 1mg oral minoxidil against 5% topical minoxidil for hair loss in female patients.

The oral minoxidil was not inferior to the topical version, and indeed trend analysis suggested it might be more effective.

According to the Times, the off-label designation might scare off some, but such drugs are widely used in practice.

Dermatologist Robert Swerlick, of the Emory University School of Medicine, noted that “most things we [dermatologists] do are off-label because there is nothing on-label.”

Brett King, a Yale School of Medicine dermatologist, told the Times that it would likely stay off-label because there wasn’t a financial incentive for Big Pharma to invest in proper trials.

“Oral minoxidil costs pennies a day,” King told the Times. “There is no incentive to spend tens of millions of dollars to test it in a clinical trial. That study truly is never, ever going to be done.”

Until researchers have the motivation and funding to conduct randomised controlled trials into low-dose oral minoxidil as a baldness treatment, the situation is likely to remain unchanged even if it is growing in popularity with certain dermatologists.

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Gut Bacteria can Reduce Effectiveness of Antihypertensive Drugs

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A new study published this month in the journal Hypertension has shown gut bacteria can reduce the effectiveness of certain antihypertensive drugs. The research provides 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.”

Source: University of Toledo