Category: Cardiovascular Disease

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Dapagliflozin Shows Benefits for Patients with MASH

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Results support the potential for dapagliflozin to benefit these patients

Human liver. Credit: NIH

The sodium glucose cotransporter 2 (SGLT-2) inhibitor drug dapagliflozin, widely used to treat type 2 diabetes, also shows improvements for patients with progressive liver disease, according to results of a clinical trial in China published by The BMJ.

The results show that treatment with dapagliflozin improved metabolic dysfunction-associated steatohepatitis (MASH) – a condition where excess fat accumulates in the liver, leading to inflammation – and liver fibrosis compared with placebo.

MASH affects more than 5% of adults, more than 30% of individuals with diabetes or obesity, and can progress to cirrhosis in up to 25% of individuals.

Several studies have reported that SGLT-2 inhibitors can improve liver fat content, liver enzymes, and liver stiffness, but no trial has been carried out among patients with MASH.

To address this, researchers enrolled 154 adults (average age 35; 85% men) diagnosed with MASH after a liver biopsy at six medical centres in China from November 2018 to March 2023.

Almost half (45%) had type 2 diabetes, and almost all had liver fibrosis (33% stage 1, 45% stage 2, 19% stage 3).

After an initial screening biopsy, participants were randomly assigned to receive 10 mg of dapagliflozin or matching placebo once daily for 48 weeks and attended health education sessions twice a year.

Various factors including body weight, blood pressure, blood glucose, liver enzymes, physical activity, diet, insulin, and lipids were also assessed at enrollment and throughout the trial.

MASH improvement was defined as a decrease of at least 2 points in non-alcoholic fatty liver disease activity score (NAS) or a NAS of 3 points or less.

After an end of study biopsy at week 48, 53% (41 of 78) participants in the dapagliflozin group showed improvement in MASH without worsening of fibrosis (defined as no increase in fibrosis stage) compared with 30% (23 of 76) in the placebo group.

Resolution of MASH without worsening of fibrosis occurred in 23% (18 of 78) participants in the dapagliflozin group compared with 8% (6 of 76) in the placebo group.

Fibrosis improvement without worsening of MASH was also reported in 45% (35 of 78) participants in the dapagliflozin group compared with 20% (15 of 76) in the placebo group.

The percentage of participants who discontinued treatment because of adverse events was 1% (1 of 78) in the dapagliflozin group and 3% (2 of 76) in the placebo group.

The researchers acknowledge that the trial was conducted in a Chinese population, which limits its broader generalisability, and that female and older patients were under-represented. But they point out that results were consistent after further analyses, suggesting they are robust.

As such, they conclude: “Our findings indicate that dapagliflozin may affect key aspects of MASH by improving both steatohepatitis and fibrosis.” Large scale and long term trials are needed to further confirm these effects, they add.

The coming years are expected to be particularly exciting in the field of pharmacological treatment for MASH, say researchers from Argentina in a linked editorial.

As more drugs become available, therapeutic decisions will likely become increasingly tailored to individual patient profiles, they write. “Ideally, such treatments should provide cardiovascular benefit, have an established safety profile, and be accessible to broad and diverse patient populations,” they conclude.

Source: BMJ Group

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New Gene Variants Significantly Increase the Risk of Blood Clots

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Thrombophilia. Credit: Scientific Animations CC4.0.

Though blood clots can form in both arteries and veins, the reasons behind them differ, as do the consequences and the chances of preventing blood clots. In Sweden, almost half of all cases of venous thrombosis have a genetic explanation. A team of researchers from Lund University in Sweden has now discovered three gene variants that increase the risk of blood clots in the leg by up to 180%.

There is a difference between arterial and venous blood clots. Blood clots in the arteries form when plaque in calcified vessels bursts and the body perceives it as an injury. This activates the platelets, which clump together and form a clot. In the worst case, it can lead to a stroke or heart attack. A venous thrombus, on the other hand, usually forms in the leg when the blood stagnates for too long. This can activate the body’s coagulation system, allowing the clotting system to be activated and the blood to clot, blocking blood flow. If the clot breaks loose and travels with the blood to the lungs, it can lead to pulmonary embolism, a life-threatening condition.

“Venous thrombosis is in fact one of the most common causes of death in the world. It is a common disease that has always been somewhat overshadowed by arterial blood clots,” says Bengt Zöller, a specialist in general medicine at Skåne University Hospital and professor of general medicine at Lund University.

In Sweden, more than 10 000 people suffer from venous thromboembolism each year and that number appears to be increasing. Several factors are contributing to this increase. One of the strongest risk factors is age, and as the number of older people in Sweden grows, the number of clots is also increasing. Ten per cent of 80-year-olds experience a blood clot at some point. The risk also increases if you are overweight or tall.

“The muscles control the blood flow in the veins and the legs become like columns of fluid where the force of gravity is strong. Too much sedentary and inactive behaviour, then, is harmful. Only the valves of the veins prevent backflow and if these are damaged, the risk of blood clots can increase. Therefore, tall people are more prone to blood clots, as their larger veins provide less blood flow, combined with the fact that blood must travel a greater distance back to the heart.”

Because the heart pumps blood out into the arteries, there is much higher blood pressure in the arteries than in the veins, which can contribute to atherosclerosis. High blood pressure, high levels of blood lipids and smoking are all risk factors for atherosclerosis of the arteries. But because the veins are a low-pressure system, the vessels do not become atherosclerotic. Therefore, neither high blood pressure nor blood lipids are associated with venous clots and smoking is considered only a weak to moderate risk factor. Being overweight, on the other hand, is a very significant culprit. Obesity has a negative impact on venous circulation, especially when combined with the fact that overweight people are often less active. Some clotting factors are also affected by obesity.

“In terms of diet, there are fewer studies, but ultra-processed foods have been associated with a slightly increased risk of blood clots, and plant-based, healthy foods with a reduced risk. In our studies, we have also seen that commercial fishermen have a lower risk, which may be due to a higher omega-3 content in their diet.”

There are also specific situations in which the risk of venous blood clots is particularly high. The risk of blood clots increases when blood flow is reduced, such as when travelling by air for long periods of time or when lying in bed for several days. Surgery or inflammation that damages the vessel wall can also lead to an increased tendency to clot. Particularly during pregnancy, blood clotting factors increase and levels of some protective proteins may decrease.

“In these risk situations, prophylaxis in the form of blood thinners may be particularly important if other risk factors are also present.”

Other risk factors are the genetic variants that affect different parts of the blood’s clotting ability. In Sweden, we have a high prevalence of APC (activated protein C) resistance due to an inherited mutation in the gene for coagulation factor V, called Factor V Leiden. About 10 per cent of Swedes have this mutation, which is considered the most common coagulation mutation among Indo-Europeans.

“Evolutionarily, bleeding less has been an advantage, but in our modern, sedentary society, APC resistance is becoming a risk factor.”

Bengt Zöller and his fellow researchers have now identified the strongest genetic risk factor since Factor V Leiden was discovered. They used data from the population-based Malmö Kost Cancer study, involving 30,000 Malmö residents. By selecting 27 genes previously associated with clotting disorders, they found three variants that, when taken together, were as significant a risk factor for venous blood clots as Factor V Leiden: ABO, F8, and VWF each increased the risk of venous blood clots by 10 to 30 percent.

“And the more of these variants a person has – the higher the risk. An individual with five of these gene variants has a 180 per cent higher risk of venous thrombosis. Unlike Factor V Leiden, which is only found in Indo-Europeans, these three different mutations are found in between five and fifty per cent of various populations around the globe.”

As these genetic variants are present in all populations, the next step is to investigate how the number of risk genes affects the duration of treatment with anticoagulants after a blood clot.

“I think tailoring treatment based on risk assessment will become increasingly important,” concludes Bengt Zöller.

The study results were published in Research and Practice in Thrombosis and Haemostasis.

Source: Lund University

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Cardiologist “Gags” Carte Blanche

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By Tania Broughton

Photo by Bill Oxford on Unsplash

A Durban-based cardiologist has secured a “gagging order” against Carte Blanche, stopping it from broadcasting a programme in which patients accuse him of medical malpractice for inserting stents unnecessarily.

Dr Ntando Peaceman Duze was given multiple opportunities for more than a week to respond to the allegations raised by his patients, which were corroborated by independent experts. But instead of responding, he launched an urgent application in the Kwazulu-Natal High Court in Pietermaritzburg on Friday.

He gave Carte Blanche only one day’s notice of the application.

Carte Blanche opposed it, arguing that Duze wanted to “bury these allegations for as long as possible if not indefinitely”, and that he was seeking an “unlawful prior restraint on freedom of speech and media”.

But Acting Judge Mpumelelo Sibisi granted an interim interdict, stopping the broadcast scheduled for Sunday 8 June.

Judge Sibisi said Duze needed to be given an opportunity to file a replying affidavit and that Carte Blanche had put a “gun to his head” to answer the questions posed to him. The judge said it would be appropriate to interdict the broadcast until the matter could be properly ventilated.

He set the return date for 13 June. But unless the matter is given a special allocation, it may not be argued and finalised on that day.

Cardiologists accused of defamation

Duze, who runs his practice from Life Westville Hospital, initially cited two other cardiologists in his application, seeking orders that they must desist from making “slanderous, insulting and defamatory remarks” about him.

He put this down to professional jealousy because their patients had moved over to his practice.

He alleged that the two cardiologists had instigated complaints laid by about seven of his patients against him with the Health Professionals Council of South Africa (HPCSA). He claimed that such was the professional jealousy, that he had been a victim of “witchcraft”, with chicken bones and red [Hindu] strings being left in the operating theatre.

He said the cardiologists had told his patients that “I had opened up their blood vessels” [an apparent reference to stent surgery], when it was unnecessary to do so.

Duze said the complaints to the HPCSA were “baseless”.

The cardiologists opposed the application.

Then on Friday, Duze’s legal team withdrew the claim against the cardiologists, and tendered to pay their legal costs. The lawyers gave no explanation for this. But it came in the wake of Carte Blanche, in its affidavit, saying they had not interviewed the cardiologists. Instead they had interviewed Duze’s aggrieved patients on camera and done follow-up investigations, including obtaining independent medical corroboration based on the patients’ medical records.

Gag order

Duze, in his application, said at any given time he had an average of 50 patients at the hospital, all with heart conditions. He had never before been reported to the HPCSA and, if the allegations against him continued and were made public on Carte Blanche, it would severely harm his reputation, “and may even lead to my financial demise”.

“Carte Blanche launched their own investigation and wants to broadcast a programme about this on Sunday 8 June, which I want to prevent, because it will be filled with untruths and defamation,” he said.

He said Carte Blanche had approached him for comment, and asked 14 specific questions, which he was not prepared to answer because the issue was “sub judice”.

“Once the [HPCSA] has completed its investigation, I will no doubt be willing to be interviewed and explain everything, because I will no doubt be cleared of these false allegations,” he said.

In her opposing affidavit, Carte Blanche producer Mart-Marie Faure said the application was an “abuse of process”.

“It is unsustainable on the facts and law and constitutes an impermissible attempt to obtain a pre-publication interdict in circumstances where no case has been made out for one and such an extreme order is not justified,” she said.

“The complaints, which form the subject matter of the inset entitled ‘Dr Stent’, were initiated by his patients, who had all, they allege, been subjected to unnecessary surgical procedures.

“Independent medical professionals who have been interviewed or consulted all confirm that the applicant [Duze] undertook unnecessary surgery that has had adverse consequences for his patients.

“This has nothing to do with jealous colleagues. The complaints are driven by his patients who allege serious medical malpractice with the most grave medical consequences.”

Faure said she had engaged with Duze and his attorneys for nine days in an attempt to secure answers to her questions “to no avail”.

“Carte Blanche was contacted by patients who claimed they were operated on unnecessarily. They consulted with other medical professionals who have said the insertion of stents was unnecessary. And in fact had caused heart disease when none was previously present.

“They will be required to take blood thinning and other medication for the rest of their lives.

“The HPCSA confirmed it received five complaints against the applicant.

“Life Healthcare has confirmed that it received information regarding allegations against the applicant from the HPCSA and has initiated an investigation.”

Faure said the complaints were not sub judice and that the explanation the doctor would advance to justify his conduct in that investigation would no doubt be the same he would give on camera or in a written response.

“If media houses were required to await the finalisation of proceedings before any professional or regulatory body, the public would be deprived of timely, relevant information on matters of pressing concern,” she said.

“This is antithetical to the very purpose of a free press.

“The patients’ accounts are based on their personal experiences and have been corroborated by independent experts. In every such story the person in respect of whom the investigation is conducted is unhappy. The remedy is to tell their side of the story, which the applicant has been repeatedly offered – not to gag the media.”

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Read the original article.

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Extensive Study Refutes the Notion that Statins Have Antidepressant Effect

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Photo by Towfiqu Barbhuiya on Unsplash

Lipid-lowering medicines, known as statins, are prescribed in cases of high cholesterol levels, to reduce the risk of atherosclerosis, heart attack and stroke. The results of some small studies suggest that statins could also have an antidepressive effect. Researchers from Charité – Universitätsmedizin Berlin have now conducted an extensive study to investigate this claim. However, they could not verify that statins cause any additional antidepressive effects. As a result, the researchers suggest following the general guidelines and prescribing statins to help lower cholesterol, but not to manage depression. The study has now been published in JAMA Psychiatry.

Cholesterol-lowering drugs are the most commonly prescribed medicines globally. They have anti-inflammatory effects and lower the production of cholesterol in the liver, which in turn reduces the risk of developing cardiovascular diseases. In the past, numerous small studies have suggested that statins may also have antidepressive effects, alongside these more common properties. “If statins really did have this antidepressive effect, we could kill two birds with one stone,” says study leader Prof Christian Otte, Director of the Department of Psychiatry and Neurosciences on the Charité Campus Benjamin Franklin. “Depression and adiposity, or obesity, are among the most common medical conditions globally. And they actually often appear together: Those who are obese are at a higher risk of depression. In turn, those with depression are at a higher risk of obesity.” Obese patients often have higher cholesterol levels, so statins are administered to reduce the risk of cardiovascular diseases. But could they also alleviate depression?

An extensive, controlled study

Led by Christian Otte, the research team conducted a comprehensive study to investigate the potential antidepressive effects of statins that have been suggested. A total of 161 patients took part in the study, all of whom suffered from both depression and obesity. During the 12-week study, all participants were treated with a standard antidepressant (Escitalopram). Half of the participants also received a cholesterol-lowering drug (Simvastatin), while the other half were given a placebo. It was decided at random who would receive statins and who would be given the placebo – the recipients of each were unknown to both the medical team and the participants. This ensured a randomized and double-blind study that would produce reliable results. “This method should show us whether we can observe a stronger antidepressive effect among participants treated with statins, compared to those in the placebo group,” explains co-lead author Dr. Woo Ri Chae, Charité BIH Clinician Scientist at the Department of Psychiatry and Neurosciences.

The researchers used established clinical interviews and self-completed questionnaires to record the severity of depression in the patients at the beginning and end of the study. Blood samples were taken from the participants to determine their blood lipid levels and level of the C-reactive protein (CRP), which are known indicators of inflammatory processes in the body. “People with obesity and/or depression commonly exhibit slightly raised inflammatory markers in the blood. For some of those affected, this can actually be the cause of depression,” explains Christian Otte. “And this is precisely where we began with our hypothesis on the potential antidepressive effect of statins: If administering statins leads to an improvement in inflammatory markers, could this also possibly be accompanied by an antidepressive effect for some of the study participants?”

Traditional antidepressants remain the gold standard

At the beginning of the study, the participants ranged from moderately to severely depressed. Over the course of the 12-week study, the depression symptoms in all patients showed clear improvement – there was, however, no difference between those who received statins and those in the placebo group. “Administering the cholesterol-lowering drug improved blood lipid levels, as expected, and the inflammatory marker CRP also displayed a marked reduction,” says Woo Ri Chae. “So, unfortunately, this does not point to an additional antidepressive effect.” Christian Otte adds: “When it comes to treating depression, statins therefore have no additional benefit. To our present knowledge, traditional antidepressants remain the gold standard.” According to current guidelines, statins should be prescribed to reduce the risk of atherosclerosis and cardiovascular diseases. The researchers recommend that the same should naturally also apply for patients suffering from depression.

In further studies, Christian Otte’s team will conduct a more thorough analysis of the blood samples taken as part of this research on a cellular and molecular level, to reveal potential differences and correlations. The researchers are also continuing to work at full speed on improved strategies for treating patients with depression who also suffer from other conditions.

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Combination Therapy can Prolong Life in Severe Heart Disease

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Human heart. Credit: Scientific Animations CC4.0

Aortic valve narrowing (aortic stenosis) with concomitant cardiac amyloidosis is a severe heart disease of old age that is associated with a high risk of death. Until now, treatment has consisted of valve replacement, while the deposits in the heart muscle, known as amyloidosis, often remain untreated. An international research consortium led by MedUni Vienna and University College London has shown for the first time that combined treatment consisting of heart valve replacement and specific drug therapy offers a significant survival advantage for patients. The study results have been published in the European Heart Journal.

As part of the study conducted by the research team led by Christian Nitsche (MedUni Vienna) and Thomas Treibel (University College London), data from 226 patients with aortic stenosis and concomitant cardiac amyloidosis from ten countries were examined. Aortic stenosis is a narrowing of the heart valve that directs blood from the left ventricle into the bloodstream. In cardiac amyloidosis, misfolded proteins are deposited in the heart muscle. Both diseases occur in older people and often together. Until now, it was unclear whether treating amyloidosis in addition to valve surgery would benefit patients.

The analysis now published showed that both aortic valve replacement and treatment with the drug tafamidis for amyloidosis were associated with a significantly lower risk of death. The survival benefit was highest in patients who received both forms of treatment. “Our results even show that patients with both conditions who received valve replacement and specific amyloidosis therapy had similar long-term survival rates to people with aortic stenosis without amyloidosis,” emphasises study leader Christian Nitsche.

Targeted tests necessary

Both aortic stenosis and cardiac amyloidosis impair the heart’s pumping function and can lead to death if left untreated. Targeted therapy can slow the progression of amyloidosis, while valve replacement treats the mechanical stress caused by the narrowed heart valve. Around ten percent of patients with aortic stenosis also have amyloidosis, but this is often not diagnosed in everyday clinical practice. “Our findings also suggest that patients with severe aortic valve stenosis should be screened for amyloidosis so that we can offer them targeted life-prolonging treatment options,” emphasises Christian Nitsche.

Source: Medical University of Vienna

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Whether It’s Smoking or Edibles, Marijuana Is Bad for the Heart

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Photo by Crystalweed Cannabis on Unsplash

A new study led by UC San Francisco researchers finds that chronic cannabis use, whether it’s smoked or consumed in edible form, is associated with significant cardiovascular risks.

The report, published in JAMA Cardiology, found that people who regularly used marijuana in either form had reduced blood vessel function that was comparable to tobacco smokers. Vascular function in those who used cannabis by either means was reduced roughly by half compared to those who did not use it.

Decreased vascular function is associated with a greater risk of heart attack, hypertension, and other cardiovascular conditions.

The researchers recruited 55 people between October 2021 and August 2024 who were outwardly healthy and either regularly smoked marijuana or consumed edibles containing tetrahydrocannabinol (THC), the primary psychoactive compound found in cannabis.

The participants, none of whom used any form of nicotine, consumed cannabis at least three times a week for at least a year. Smokers averaged 10 years of chronic use, and those who took edibles averaged five years.

Along with decreased vascular function, marijuana smokers had changes in their blood serum that were harmful to endothelial cells, which form the inner lining of all blood and lymphatic vessels. Those who took edibles containing THC, however, did not display these changes in blood serum.

It’s unclear how THC damages blood vessels. But the researchers said it must be happening in a way that does not involve those changes to blood serum.

These results suggest smoking marijuana negatively affects vascular function for different reasons than ingesting THC does, according to first author Leila Mohammadi, MD, PhD, and senior author Matthew L. Springer, PhD.

Source: University of California – San Francisco

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Timely Initiation of Statins in Diabetes Shown to Dramatically Reduce Cardiovascular Risk

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Despite clinicians recommending that many patients with diabetes take statins, nearly one in five opt to delay treatment. In a new study, researchers from Mass General Brigham found that patients who started statin therapy right away reduced the rate of heart attack and stroke by one third compared to those who chose to delay taking the medication. The results, which can help guide decision-making conversations between clinicians and their patients, are published in the Journal of the American Heart Association.

“I see patients with diabetes on a regular basis, and I recommend statin therapy to everyone who is eligible,” said senior author Alexander Turchin, MD, MS, of the Division of Endocrinology at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system. “Some people refuse because they want to first try lifestyle interventions or other drugs. But other interventions are not as effective at lowering cholesterol as starting statin therapy as soon as possible. Time is of the essence for your heart and brain health.”

Heart attacks and strokes remain the leading cause of complications and mortality for patients with diabetes. Statin therapy reduces risk of these cardiovascular events by preventing plaque buildup in the blood vessels.

The researchers used an artificial intelligence method called Natural Language Processing to gather data from the electronic health records of 7239 patients at Mass General Brigham who ultimately started statin therapy during the nearly 20-year study period. The median patient age was 55, with 51% being women, 57% white, and a median HbA1c of 6.9.

Nearly one-fifth (17.7%) of the patients in the study declined statin therapy when it was first recommended by their clinicians, then later accepted the therapy (after a median of 1.5 years) upon repeated recommendation by their clinician. Of those who delayed, 8.5% had a heart attack or stroke. But for patients who started statins immediately, the rate of those cardiovascular events was just 6.4%.

“Clinicians should recognize the increased cardiovascular risk associated with delaying statin therapy for patients with diabetes and use this information to guide shared decision-making conversations with their patients,” said Turchin.

Source: Mass General Brigham

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Heart Valve Abnormality is Associated with Malignant Arrhythmias

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Source: CC0

People with a certain heart valve abnormality, mitral annular disjunction, are at increased risk of severe heart rhythm disorders, even after successful valve surgery. This is according to a new study from Karolinska Institutet and Karolinska University Hospital in Sweden published in the European Heart Journal. The condition is more common in women and younger patients with valve disorder and can, in the worst case, lead to sudden cardiac arrest.

Mitral annular disjunction, MAD, is a heart abnormality in which the mitral valve attachment ‘slides’. In recent years, the condition has been linked to an increased risk of severe cardiac arrhythmias. Until now, it has not been known whether the risk of arrhythmias disappears if MAD is surgically corrected.

MAD is often associated with a heart disease called mitral valve prolapse, which affects 2.5% of the population and causes one of the heart’s valves to leak. This can lead to blood being pumped backwards in the heart, causing heart failure and arrhythmias. The disease can cause symptoms such as shortness of breath and palpitations.

Followed patients after surgery

In the current study, researchers at Karolinska Institutet investigated the risk of cardiac arrhythmias in 599 patients with mitral valve prolapse who underwent heart surgery at Karolinska University Hospital between 2010 and 2022. Sixteen percent of the patients also had the cardiac abnormality MAD.

“We have been able to show that people with MAD have a significantly higher risk of suffering from ventricular arrhythmias, a dangerous type of heart rhythm disorder that in the worst case can lead to cardiac arrest in a subset of patients,” says Bahira Shahim, associate professor at the Department of Medicine, Solna, Karolinska Institutet and cardiologist at Karolinska University Hospital

People with MAD were more likely to be female and were on average eight years younger than those without MAD. They also had more extensive mitral valve disease. Although the surgery was successful in correcting MAD, these patients had more than three times the risk of ventricular arrhythmias during five years of follow-up compared to patients without preoperative MAD.

“Our results show that it is important to closely monitor patients with this condition, even after a successful operation,” says Bahira Shahim.

Investigating new hypotheses

The study has led to new hypotheses that the researchers are now investigating further. One hypothesis is that MAD causes permanent changes in the heart muscle over time. Another is that MAD is a sign of an underlying heart muscle disease. The researchers are now continuing to study scarring in the heart using MRI (magnetic resonance imaging) and analyse tissue samples from the heart muscle.

Source: Karolinska Institutet

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Potassium is Also Important for Lowering Blood Pressure

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Credit: Pixabay CC0

A newly published study from the University of Waterloo suggests that increasing the ratio of dietary potassium to sodium intake may be more effective for lowering blood pressure than simply reducing sodium intake.

“Usually, when we have high blood pressure, we are advised to eat less salt,” said Dr Anita Layton, professor at the University of Waterloo. “Our research suggests that adding more potassium-rich foods to your diet, such as bananas or broccoli, might have a greater positive impact on your blood pressure than just cutting sodium.”

Potassium and sodium are both electrolytes – substances that help the body send electrical signals to contract muscles, affect the amount of water in your body and perform other essential functions.

“Early humans ate lots of fruits and vegetables, and as a result, our body’s regulatory systems may have evolved to work best with a high potassium, low sodium diet,” said Melissa Stadt, a PhD candidate in Waterloo’s Department of Applied Mathematics and the lead author of the study.

“Today, western diets tend to be much higher in sodium and lower in potassium. That may explain why high blood pressure is found mainly in industrialised societies, not in isolated societies.”

While previous research found that increasing potassium intake can help control blood pressure, the researchers developed a mathematical model that successfully identifies how the ratio of potassium to sodium impacts the body.

The model also identifies how sex differences affect the relationship between potassium and blood pressure. The study found that men develop high blood pressure more easily than pre-menopausal women, but men are also more likely to respond positively to an increased ratio of potassium to sodium.

The researchers emphasise that mathematical models like the one used in this study allow these kinds of experiments to identify how different factors impact the body quickly, cheaply, and ethically.

The study was recently published in the American Journal of Physiology-Renal Physiology.

Source: University of Waterloo

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Does Hormone Therapy Improve Heart Health in Menopausal Women?

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Deciding whether to start hormone therapy during the menopause transition, the life phase that’s the bookend to puberty and when a woman’s menstrual cycle stops, is a hotly debated topic. While hormone therapy is recommended to manage bothersome symptoms like hot flashes and night sweats, Matthew Nudy, assistant professor of medicine at the Penn State College of Medicine, said there’s confusion about the long-term effects of hormone therapy, especially on cardiovascular health.

However, long-term use of oestrogen-based hormone therapies may have beneficial effects on heart health, according to a new study led by Nudy. A multi-institutional team analysed data from hormone therapy clinical trials that were part of the Women’s Health Initiative (WHI), a long-term national study focused on menopausal women, and found that oestrogen-based hormone therapy improved biomarkers associated with cardiovascular health over time. In particular, the study suggests that hormone therapy may lower levels of lipoprotein(a), a genetic risk factor associated with a higher risk of heart attack and stroke.

Their findings were published in the journal Obstetrics & Gynecology.

“The pendulum has been swinging back and forth as to whether hormone therapy is safe for menopausal women, especially from a cardiovascular disease perspective,” Nudy said. “More recently, we’re recognising that hormone therapy is safe in younger menopausal women within 10 years of menopause onset, who are generally healthy and who have no known cardiovascular disease.”

The hormonal changes that accompany menopause come with an increased risk of cardiovascular disease. The decline in the oestrogen can lead to changes in cholesterol, blood pressure and plaque buildup in blood vessels, which increase the risk of heart attack and stroke.

The research team was interested in understanding the long-term effect of hormone therapy on cardiovascular biomarkers, which hasn’t been evaluated over an extended period of time. Prior research in the field primarily looked at short-term effects.

Here, the team analysed biomarkers associated with cardiovascular health over a six-year period from a subset of women who had participated in an oral hormone therapy clinical trial that was part of the WHI. Post-menopausal participants aged 50 to 79 were randomly assigned to one of two groups, an oestrogen-only group and an oestrogen plus progesterone group. They provided blood samples at baseline and at the one-, three- and six-years marks. In total, they analysed samples from 2696 women, approximately 10% of the total trial participants.

The research team found that hormone therapy had a beneficial effect on most biomarkers in both the oestrogen-only and the oestrogen-plus-progesterone groups over time. Levels of LDL cholesterol, the so-called “bad” cholesterol, were reduced by approximately 11% while total cholesterol and insulin resistance decreased in both groups. HDL cholesterol, the so-called “good” cholesterol, increased by 13% and 7% for the oestrogen-only and oestrogen-and-progesterone groups, respectively.

However, triglycerides and coagulation factors, proteins in the blood that help form blood clots, increased.

The decrease in lipoprotein(a) concentration was more pronounced among participants with American Indian or Alaska Native ancestry or Asian or Pacific Islander ancestry, by 41% and 38%, respectively. The reason why was unclear, Nudy said.

More surprising to the research team, they said, levels of lipoprotein(a), a type of cholesterol molecule, decreased 15% and 20% in the oestrogen-only and the oestrogen-plus-progesterone groups, respectively. Unlike other types of cholesterol, which can be influenced by lifestyle and health factors such as diet and smoking, concentrations of lipoprotein(a) are thought to be determined primarily by genetics, Nudy explained. Patients with a high lipoprotein(a) concentration have an increased risk of heart attack and stroke, especially at a younger age. There’s also an increased risk of aortic stenosis, where calcium builds up on a heart valve.

“As a cardiologist, this finding is the most interesting aspect of this research,” Nudy said. “Currently, there are no medications approved by the Food and Drug Administration (FDA) to lower lipoprotein(a). Here, we essentially found that oral hormone therapy significantly reduced lipoprotein(a) concentrations over the long-term.”

Nudy noted that the oestrogen therapy the women received in the clinical trial was conjugated equine oestrogens, a commonly prescribed form of oral oestrogen therapy. Before being absorbed by the body, oral hormone therapy is processed in the liver, through a process called first-pass metabolism. That process could increase inflammatory markers, which may explain the rise in triglycerides and coagulation factors.

“There are now other common formulations of oestrogen hormone therapy like transdermal oestrogen, which is administered through the skin,” Nudy said. “Newer studies have found that transdermal oestrogen doesn’t increase triglycerides, coagulation factors or inflammatory markers.”

For those considering menopause hormone therapy, Nudy recommended undergoing a cardiovascular disease risk assessment, even if the person hasn’t had a previous heart attack or stroke or hasn’t been diagnosed with cardiovascular disease. It will give health care providers more information when considering the best option to treat menopause symptoms.

“Currently, hormone therapy is not FDA-approved to reduce the risk of coronary artery disease or stroke,” Nudy said. 

Source: Penn State