Category: Cardiovascular Disease

In Diabetes, Oestrogen Protects Against Cardiomyopathy

Source: Pixabay CC0

Oestrogen may protect diabetes patients from cardiomyopathy, according to research published in Circulation: Heart Failure. The study showed that severe insulin resistance in the heart causes cardiomyopathy and death in male mice, but also showed that oestrogen protected female mice.

“Cardiovascular disease is the major cause of morbidity and mortality for diabetic patients,” explained Shaodong Guo, PhD, primary investigator for the study at Texas A&M.

“Previous studies have shown that while there’s a lower instance of both cardiovascular disease and Type 2 diabetes in premenopausal women than in their age-matched male counterparts, these incidences rise sharply after female menopause,” Prof Guo said.

This indicates that the ovaries and ovarian hormones, such as oestrogen, may protect from Type 2 diabetes and cardiovascular diseases, he said.

The study investigated the role of ovaries and oestrogen in cardiac function and energy metabolism with mice who had the the cardiac insulin receptor substrate, IRS, modified or suppressed to mimic cardiac insulin resistance.

“Our previous studies reported that impaired cardiac insulin signalling with loss of insulin receptor substrate IRS1 and IRS2 genes leads to death of male mice,” he said. “In this study, we wanted to know how the removal of the ovaries might affect cardiomyopathy in female mice and also what other impacts the loss of insulin receptors might have on energy metabolism and mitochondrial function.” 

Insulin resistance and signaling

About 90–95% of patients with Type 2 diabetes suffer from insulin resistance, a risk factor for heart failure. In healthy tissue, insulin binds to insulin receptors, activating a network of intracellular signalling pathways. Disruptions in these signalling pathways have been linked to mitochondrial dysfunction, cardiomyopathy, and impaired glucose and fatty acid metabolism, among other health issues.

In this study, mice lacking IRS developed dilated cardiomyopathy, and analysis showed lowered activity of genes important for mitochondrial function and energy metabolism.

“Type 2 diabetes patients and insulin-resistant patients exhibit mitochondrial dysfunction,” Prof Guo explained.

The study fills in some blanks in understanding the role of insulin and estrogen signaling in mitochondrial function.

Study findings

Guo said there were four important findings from the study:

  • All female mice that lacked insulin receptor substrates survived for more than a year.
  • Female mice without insulin receptor substrates were less likely to experience severe cardiac dysfunction and death if they had ovaries. If the mice also lacked ovaries but received oestrogen, it prolonged their lifespans. Doses of oestrogen also protected IRS-altered male mice from heart dysfunction. 

Guo said oestrogen also prevents cardiomyopathy induced by loss of cardiac insulin receptor substrates.

“And removal of the ovaries leads to the death of female cardiac IRS1 and IRS2 double genes knockout mice if there is no reintroduction of oestrogen,” he said.

Loss of IRS1 and IRS2 genes in heart tissue disrupts cardiac energy metabolism, gene activity involved in mitochondrial function, and whole-body energy metabolism. However, oestrogen partially reverses these effects.

Oestrogen is important for healthy cellular signalling pathways and promotes mitochondrial function.

Prof Guo said the study shows that oestrogen enhances cardiac function, promotes energy metabolism, prevents cardiomyopathy and prolongs survival in both male and ovariectomy female mice lacking the insulin receptor substrates.  

“This study provides evidence for the gender difference for the incidence of cardiovascular disease and implies that oestrogen replacement therapy is feasible for the treatment of diabetic cardiomyopathy through enhancement of mitochondrial function and energy metabolism,” he said. “It also reveals some of the signalling pathways that may be potential therapeutic targets for the prevention or treatment of cardiovascular diseases in patients with Type 2 diabetes.” 

Guo also noted that diet could also play a role with oestrogens in foods.

“The study implies that food-derived oestrogens or phytoestrogens may play similar roles to oestrogen, as observed in mice,” he said. “This may help us reshape our knowledge of nutrient and food sciences related to plant hormones that can modulate chronic metabolic diseases such as Type 2 diabetes and associated cardiovascular complications.”

Source: Texas A&M University

RAAS Inhibitors Reduce Risk of Intracranial Aneurysm Rupture

Credit: American Heart Association

The risk of intracranial aneurysm rupture was lower in people taking renin-angiotensin-aldosterone system (RAAS) inhibitors for hypertension, according to the findings of a Chinese study published in Hypertension.

A database with more than 3000 people with these aneurysms in 2016–2021, rupture rates reached 23.4% in RAAS inhibitor users and 76.6% in non-users.

RAAS inhibitor use was associated with a significantly reduced risk of intracranial aneurysm rupture (odds ratio [OR] 0.490), and this applied to angiotensin-converting enzyme (ACE) inhibitors (OR 0.559) and angiotensin receptor blockers (ARBs) alike (OR 0.414).

The RAAS inhibitors’ effect persisted across subgroups by age, sex, BMI, control of hypertension, monotherapy and combination therapy, and location and size of intracranial aneurysms.

The researchers pointed out the safety and affordability of RAAS inhibitors, and suggested that a randomised trial be conducted to confirm whether these medications protect against aneurysm rupture.

Hypertension is known to to increases the risk of intracranial aneurysm rupture, the cause of most subarachnoid haemorrhage strokes.

The authors note that there is evidence suggesting RAAS activation is involved in the pathogenesis of intracranial aneurysms.

“In hypertension, the RAAS has wide-ranging effects on blood pressure regulation through sodium retention, pressure natriuresis, salt sensitivity, vasoconstriction, endothelial dysfunction, and vascular injury. Given these facts, in addition to the directly increasing hemodynamic stresses, activation of the RAAS by systemic hypertension can cause vascular inflammation, injury, and remodeling and thereby contribute to the process of intracranial aneurysm rupture,” they explained.

How inhibiting RAAS would prevent aneurysm rupture was unclear, the authors noted, which could be investigated in a future study.

For this retrospective study, the authors reviewed the records of 3044 adults (mean age 61, 36.6% men) patients across 20 Chinese academic medical centres.

Patients were on blood pressure medications and had an intracranial aneurysm, and split between those whose aneurysms had ruptured (n = 1238) or had not ruptured (n = 1806) by the time of analysis. Aneurysms could be treated by clipping, coiling, and/or conservative treatment.

A secondary analysis matched 541 RAAS inhibitor users with an equal number of non-users, revealing that 17.7% of ruptured aneurysms would be prevented if all patients took RAAS inhibitors.

Besides RAAS inhibitor non-use, other independent predictors of rupture included female sex, passive smoking, uncontrolled or unmonitored hypertension, hyperlipidaemia, and aneurysmal location outside the internal carotid artery.

“Our study importantly extends previous studies of blood pressure control, treating hyperlipidemia and diabetes aggressively, and avoiding passive smoking as second [prevention] for these patients,” the authors wrote.

Limitations include possible confounding variables, as well as key clinical variables, such as blood pressure measurements and duration and dose of RAAS inhibitor therapy not being included in the database.

Source: MedPage Today

Deep Nerve Stimulation Controls Blood Pressure

Blood pressure cuff
BP cuff for home monitoring. Source: Pixabay

A study published in Frontiers in Neuroscience demonstrated that blood pressure and renal sympathetic nerve activity (RSNA) can be controlled by bioelectronic treatment. RSNA is often increased in hypertension and renal disease.

Using a custom-wired electrode, Professor Mario Romero-Ortega previously reported that deep peroneal nerve stimulation (DPNS) elicits an acute reduction in blood pressure. The current study, advances that work, focusing on his development of a small implantable wireless neural stimulation system and exploration of different stimulation parameters to achieve a maximum lowered response.

Prof Romero-Ortega integrated a nerve stimulation circuit less than a millimetre in size, with a novel nerve attachment microchannel electrode that can be implanted into small nerves, while enabling external power and DPNS modulation control.

Using this implantable device, his team demonstrated that systolic blood pressure can be lowered 10% in one hour and 16% two hours after nerve stimulation.

“Our results indicate that DPNS consistently induces an immediate and reproducible arterial depressor effect in response to electrical stimulation of the deep peroneal nerve,” reported Prof Romero-Ortega.

While pharmacological treatments are effective, blood pressure remains uncontrolled in 50–60% of resistant hypertensive subjects. Unfortunately, despite the use of multiple antihypertensive drugs in combination, blood pressure remains poorly controlled in 50–60% of the hypertensive population and approximately 12–18% of them develop resistant hypertension, defined as blood pressure greater than 140/90 mmHg despite the use of antihypertensive drugs.

“In this study, DPNS induced an initial increase in RSNA during the first 2–3 seconds, followed by a reduction in renal activity and mean arterial pressure, despite the increase in heart rate,” said Prof Romero-Ortega. “The observed activation of the RSNA during the DPNS was not expected since its activity is associated with hypertension.”

Source: University of Houston

New SGLT-2 Inhibitors Could Reduce Heart Failure Risk in Diabetes

Diabetes - person measures blood glucose
Photo by Photomix Company from Pexels

A study published in Annals of Internal Medicine has suggested that the new SGLT-2 inhibitors may be viable as a first-line treatment in patients with type 2 diabetes, with reduced odds of hospitalisation for heart failure compared to those receiving metformin.

In cardiovascular outcome trials among adults with type 2 diabetes (T2D), sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have shown therapeutic promise, including reduced risk of hospitalisation for heart failure compared to placebo. However, SGLT-2i have mainly been evaluated as a second-line treatment – metformin is generally given as a first-line, antidiabetic treatment.

In this new study, researchers from the Brigham and Women’s Hospital compared cardiovascular outcomes among adults with T2D who initiated first-line treatment with either metformin or SGLT-2i. For the study, 8613 patients receiving SGLT-2i were matched to 17 226 patients receiving metformin.

The researchers reported that that patients receiving SGLT-2i showed a similar risk for myocardial infarction, stroke, and all-cause mortality, and a lower risk for hospitalisation for heart failure compared with patients who received metformin. The risk for adverse events was similar except for an increased risk for genital infections compared with those receiving metformin.

“Our results suggest that SGLT-2i may be considered as first-line treatment for patients with T2D and cardiovascular disease or who are at increased risk for cardiovascular events,” said lead author HoJin Shin, BPharm, PhD, of the Division of Pharmacoepidemiology and Pharmacoeconomics. “However, more evidence from randomised clinical trials or observational studies will help us to identify patients who would benefit most from using SGLT-2i as first-line type 2 diabetes treatment.”

Source: EurekAlert!

An Egg a Day Keeps the Cardiologist Away

Photo by Annie Spratt on Unsplash

Research published in eLife has shown how moderate egg consumption can increase the amount of heart-healthy metabolites in the blood. The findings suggest that eating up to one egg per day may help lower the risk of developing cardiovascular disease.

A rich source of dietary cholesterol, eggs also contain a variety of essential nutrients. Eggs have long had a bad rap when it comes to cardiovascular health, with conflicting evidence as to whether egg consumption is beneficial or harmful to heart health. A large study in China showed that those who ate one egg a day had a lower cardiovascular disease risk than those who ate eggs occasionally. To explore this, researchers carried out a population-based study exploring how egg consumption affects markers of cardiovascular health in the blood.

“Few studies have looked at the role that plasma cholesterol metabolism plays in the association between egg consumption and the risk of cardiovascular diseases, so we wanted to help address this gap,” explained first author Lang Pan, MSc at the Department of Epidemiology and Biostatistics, Peking University, Beijing, China.

Pan and the team selected 4778 participants from the China Kadoorie Biobank, 3401 of whom had a cardiovascular disease and 1377 did not. Measuring 225 metabolites in plasma samples taken from the participants’ blood, they identified 24 that were associated with self-reported levels of egg consumption.

Their analyses showed that individuals who ate a moderate amount of eggs had higher levels of a protein in their blood called apolipoprotein A1- a building-block of high-density lipoprotein (HDL). These individuals especially had more large, protective HDL molecules in their blood.

The researchers further identified 14 metabolites linked to heart disease, and participants who ate fewer eggs had lower levels of beneficial metabolites and higher levels of harmful ones in their blood, compared to regular egg eaters.

“Together, our results provide a potential explanation for how eating a moderate amount of eggs can help protect against heart disease,” says author Canqing Yu, Associate Professor at the Department of Epidemiology and Biostatistics, Peking University. “More studies are needed to verify the causal roles that lipid metabolites play in the association between egg consumption and the risk of cardiovascular disease.”

“This study may also have implications for Chinese national dietary guidelines,” adds senior author Liming Li, Boya Distinguished Professor at the Department of Epidemiology and Biostatistics, Peking University. “Current health guidelines in China suggest eating one egg a day, but data indicate that the average consumption is lower than this. Our work highlights the need for more strategies to encourage moderate egg consumption among the population, to help lower the overall risk of cardiovascular disease.”

Source: eLife

Gut Bacteria can Reduce Effectiveness of Antihypertensive Drugs

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

Study Sheds Light on Cardiac Repair after MI

Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Immune response and the lymphatic system are central to cardiac repair after a heart attack, according to a study published in the Journal of Clinical Investigation. These insights into the basic mechanisms of cardiac repair pave the way towards the development of new treatments to preserve heart function.

“We found that macrophages, or immune cells that rush to the heart after a heart attack to ‘eat’ damaged or dead tissue, also induce vascular endothelial growth factor C (VEGFC) that triggers the formation of new lymphatic vessels and promotes healing,” said co-senior author Edward Thorp, PhD, from the Heart Center at Lurie Children’s and Associate Professor of Pathology and Pediatrics at Northwestern University Feinberg School of Medicine. “Our challenge now is to find a way either to administer VEGFC or to coax these macrophages to induce more VEGFC, in order to speed the heart repair process.”

People who suffer a heart attack are at high risk for heart failure, even with the advances in medications to reduce mortality. This occurs in part because some macrophages that arrive at the site of damage are proinflammatory and do not induce VEGFC.

“It is a Dr. Jekyll and Mr. Hyde scenario, with ‘good’ macrophages that induce VEGFC and the ‘bad’ ones that don’t. We need to prevent the ‘bad’ macrophages from causing further damage,” said co-senior author Guillermo Oliver, PhD, Director of Feinberg Cardiovascular and Renal Research Institute – Center for Vascular and Developmental Biology, and Professor of Medicine at Northwestern University Feinberg School of Medicine. “We are working to understand more about the progression to heart failure after a heart attack, in order to intervene early and reset the course to cardiac repair.”

Source: DICardiology

Empagliflozin Could Reduce Blood Vessel Dysfunction from Ageing

Red blood cells
Source: Pixabay

Empagliflozin, normally used to reduce blood sugar levels in adults with Type 2 diabetes, may also decrease blood vessel dysfunction associated with ageing such as arteriosclerosis, according to a new study published in the journal GeroScience.

First, the researchers studied the role ageing plays in human blood vessel function and stiffness. Then they evaluated how treatment with the sodium glucose co-transporter 2 (SGLT2) inhibitor empagliflozin improved blood vessel function and reduced arterial stiffness in aged male mice.

“Cardiovascular disease is the main cause of death in older adults in the US,” explained Camila Manrique-Acevedo, MD, associate professor of medicine. “Weight loss, physical activity, antihypertensive therapy and lipid-lowering drugs have shown variable effectiveness at improving blood vessel function and reducing arterial stiffness. But additional approaches are needed to improve vascular health in older adults.”

The study first compared blood vessel function and stiffness in 18 healthy human patients, average age 25, with 18 patients, average age 61. They found the older patients had impaired endothelial function and increased aortic stiffness when compared to the younger patients.

“Our findings in young and older adults confirm previous clinical data demonstrating the impact of aging on blood vessel function and arterial stiffness,” Associate Prof Manrique-Acevedo said. “Importantly, we were able to replicate this data in a rodent model.”

To investigate the effects of empagliflozin on vascular ageing, researchers fed empagliflozin to 72-week-old mice in their diet, while their control group received standard food. After six weeks, researchers discovered the mice given empagliflozin experienced improved blood vessel function, reduced arterial stiffness and other vascular benefits.

“To our knowledge, this is the first study to examine the potential role of SGLT2 inhibition in reversing vascular ageing,” Associate Prof Manrique-Acevedo said. “And our findings highlight the need for further clinical investigations to determine the potential role of SGLT2 inhibition as a therapeutic tool to delay or reverse vascular ageing in humans.”

Source: University of Missouri

The American Heart Association’s New Intracerebral Haemorrhage Guideline

Credit: American Heart Association

A new guideline published in the journal Stroke reveal that home treatments or preventive therapies used to manage intracerebral haemorrhages (ICH) are not as effective as previously believed.

The guideline from the  American Heart Association/American Stroke Association includes recommendations on surgical techniques, individual activity levels after an ICH, and additional education and training for at-home caregivers. It reflects advances in the intracerebral haemorrhage field since the last guideline on ICH management was published in May 2015.

“Advances have been made in an array of fields related to ICH, including the organisation of regional health care systems, reversal of the negative effects of blood thinners, minimally invasive surgical procedures and the underlying disease in small blood vessels,” said Steven M. Greenberg, M.D., Ph.D., FAHA, chair of the guideline writing group.

Updates to Standard Care Practices

The new guideline suggests that many techniques widely considered “standard care” are unnecessary. For example, wearing compression socks or stockings to prevent deep vein thrombosis after ICH was not found to be effective. Instead, use of intermittent pneumatic compression may be helpful if started on the same day of an ICH diagnosis.

“This is an area where we still have a lot of exploration to do. It is unclear whether even specialised compression devices reduce the risks of deep vein thrombosis or improve the overall health of people with a brain bleed. Even more research is needed on how new blood clot prevention medications may help, especially within the first 24 to 48 hours of the first symptoms,” said Dr Greenberg.

Use of anti-seizure medicines or anti-depressants after ICH is also updated; neither of these classes of medications helps a person’s overall health unless a seizure or depression is already present, therefore, they are not advised for most people. Anti-seizure medication did not contribute to improvements in functionality or long-term seizure control, and the use of anti-depressants increased the chance of bone fractures.

The guideline writing group also addresses previously standard in-hospital therapies. They suggest administering steroids to prevent complications from a bleeding stroke is ineffective and highlight that platelet transfusions, unless used during an emergency surgery, may worsen the stroke survivor’s condition.

Surgical Intervention

Some research suggests procedures with a less invasive approach are less likely to damage brain tissue while removing the fluid build-up.

“The evidence is now reasonably strong that minimally invasive surgery may improve the likelihood that a patient will survive following a moderate or large ICH,” says Greenberg. “It is less clear, however, whether this or any other kind of surgical procedure improves the chances of survival and recovery from ICH, which are our ultimate goals.”

Recovery and Rehabilitation

Stroke rehabilitation includes several strategies to help restore the individual’s quality of life, and the guideline reinforces the importance of having a multi-disciplinary team to develop a plan for recovery. Research suggests a person with a mild or moderate ICH may begin activities like stretching, dressing, bathing and other normal daily tasks 24–48 hours after the stroke to improve survival rate and recovery time; however, moving too much or too intensely within 24 hours is linked to an increased risk of death within 14 days after an ICH.

Home Caregivers

The guideline also recommends education, practical support and training for family members so they may be involved and knowledgeable about what to expect during rehabilitation.

Other Highlights

The guideline suggests there may be an opportunity to prevent ICH in some people by using MRI which can image small blood vessel damage. In addition, major risk factors for small vessel damage are high blood pressure, Type 2 diabetes and older age. Blood thinners remain an important topic since the use of these medications may increase complications and death from a bleeding stroke. Updated guidance is provided for immediate reversal of the newer blood thinners like apixaban, rivaroxaban, edoxaban and dabigatran, as well as older medications like warfarin or heparin.

Renewed emphasis is placed on the complexities of a do-not-attempt-resuscitation (DNAR) status versus the decision to limit other medical and surgical interventions. The writing group highlights the need to educate medical professionals, stroke survivors and/or the individual’s caregiver about the differences. The guideline recommends the severity of a hemorrhage, as measured by the standard scales, not be used as the sole basis for determining life-saving treatments.

Source: American Heart Association

Mental Health Conditions Disrupt Blood Pressure and Heart Rate

Photo by Alex Green on Pexels

A new study published in BioMedical Engineering has revealed that mental health is closely aligned to blood pressure and heart rate variations. The researchers found that mental illness could cause widely fluctuating blood pressure, which can lead to cardiovascular disease and organ damage.

University of South Australia researcher Dr Renly Lim and colleagues said there is clear evidence that mental illness interferes with the body’s autonomic functions, including blood pressure, heart rate, temperature and breathing.

“We reviewed 12 studies on people with anxiety, depression and panic disorders and found that, regardless of age, mental said is significantly associated with greater blood pressure variations during the day,” Dr Lim says.

“We also found that for people who are mentally ill, their heart rate does not adapt to external stressors as it should.

“Contrary to what many people think, a healthy heart is not one that beats like a metronome. Instead, it should adjust to withstand environmental and psychological challenges. A constantly changing heart rate is actually a sign of good health.”

Reduced heart rate variation (HRV) is common in people with mental illness and indicates that the body’s stress response is poor, exacerbating the negative effects of chronic stress.

Unlike normally consistent heart rates, HRV is more complex and is the time between two heartbeats, which should change according to external stressors.

“What we aim for is not a constantly changing heart rate but a high heart rate variation. This is achieved through a healthy diet, exercise, low stress and good mental health.”

Low HRV occurs during ‘fight-or-flight’ mode, or in those who are easily stressed and is common in people with chronic diseases, including cardiovascular and mental health problems.

While large blood pressure variations (BPV) during the day are not ideal, at night the systolic pressure should dip by between 10–20% to allow the heart to rest. People with mental health issues were found to have an insufficient BP drop at night, dropping less than 10%.

The reduced dipping can be caused by many factors, including autonomic dysfunction, poor quality of sleep and disrupted circadian rhythms that regulate the sleep-wake cycle.

“The takeout from this study is that we need to pay more attention to the physical impacts of mental illness,” Dr Lim said.

“It is a major global burden, affecting between 11–18 per cent (one billion) of people worldwide. Since mental illness can contribute to the deterioration of heart and blood pressure regulation, early therapeutic intervention is essential.”

Source: University of South Australia