Category: Cardiovascular Disease

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In Severe Stroke, Mechanical Clot Removal Leads to Improved Outcomes

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A clot within a blood vessel interrupting blood flow to the brain.
Copyright American Heart Association

Ischaemic stroke patients previously considered unlikely to survive without severe disability may regain far more function if the blood clots are mechanically removed in addition to standard medical therapy, according to preliminary late-breaking research presented today at the American Stroke Association’s International Stroke Conference 2022.

In 2018, the American Heart Association’s stroke treatment guidelines were updated to recommend endovascular therapy (mechanical clot removal) for select stroke patients to improve the odds of functional recovery. This new study in Japan is the first randomised, controlled trial to demonstrate the effectiveness of endovascular therapy in patients with severe strokes involving clots in one or more large brain arteries, causing a large blood flow interruption in the brain. This approach had worked for patients with fewer areas of the brain disrupted, however, clinical experience was mixed for patients with more severe strokes.

Infarction area, or core area, estimates the volume of brain affected and describes the blockage location as seen on a brain CT. A lower number translates to a stroke affecting more core areas of the brain: 8-10=small core, 6-7=moderate core and 0-5=large core. Current US stroke guidelines recommend endovascular therapy for core areas 6-9. This study examined blockages that scored as 3-5. Strokes with blockages measuring 0-2 core areas are considered too severe and highly unlikely the patient would return to ambulatory independence.

“I have often encountered a dramatic improvement in a patient just after the mechanical clot removal procedure, even when the infarction area was large. Yet, patients sometimes also experienced severe haemorrhagic transformation [a life-threatening complication that occurs when blood from outside the brain crosses the blood-brain barrier and worsens stroke outcome] after the artery was reopened. So, in Japan, our stroke physicians are always cautious about endovascular therapy when the infarction area is large,” said Professor Shinichi Yoshimura, lead author of the study.

This randomised study included 203 stroke patients (average age of 76 years; 44% women). Most (71%) were examined and had MRI or a CT scan of the brain within 6 hours after stroke symptoms were first noticed, when patients are generally considered eligible for endovascular therapy. The other patients were seen between 6-24 hours after symptoms were noticed, and additional imaging showed areas of the brain that might benefit from prompt treatment.

On imaging, all patients were found to have clots blocking a large cerebral artery – either the internal carotid artery, the proximal middle cerebral artery or both. The strokes were rated as severe (median 22 on the National Institutes of Health (NIH) Stroke Scale,) and involved disrupted blood flow to large areas of the brain (about 7 out of 10 regions).

After imaging, the patients were randomly selected to receive either standard medical care for stroke (intravenous fluids, controlling blood pressure and other risk factors, and thrombolytics for lower bleeding risk patients) or standard medical care plus endovascular therapy performed within an hour after imaging to mechanically remove the clots. Due to bleeding concerns, intravenous thrombolytics were sparingly administered to select patients in a similar proportion in both treatment groups (27 of those who received endovascular therapy and 29 who received standard care).

Comparing the 100 patients who received endovascular therapy with 102 on standard therapy alone, the analysis found:

  • Patients who received endovascular therapy were 2.43 times more likely (31% vs 13%) to be able to walk unassisted and to have a residual disability rated as none to moderate 90 days later.
  • After 90 days, more of the patients (14% vs. 6.9%) who received endovascular therapy were considered functionally independent, meaning they were either able to carry out all their pre-stroke activities or to have a slight disability that did not require daily assistance.
  • At 48 hours after treatment, more of the patients (31% vs. 8.8%) who received endovascular therapy had major early neurological improvement.

“Our findings confirm that anyone who suffers from stroke should be transferred to a medical facility capable of endovascular therapy as soon as possible. The benefit of endovascular therapy is not limited by the severity or region of a stroke. These patients may have the chance to more fully recover from stroke and go back to their previous lives and activity levels,” said Professor Takeshi Morimoto, senior author of the study.

Several outcomes were compared to evaluate the safety of adding endovascular therapy to medical treatment, with researchers reporting:

  • Within 48 hours, scans revealed that more of the patients who received endovascular therapy had experienced some bleeding within the brain (with or without symptoms), 58% vs. 31%, respectively.
  • However, the number of patients who experienced other adverse outcomes was similar in the two treatment groups. The adverse events included brain bleeding within 48 hours that caused a worsening of neurological status (4 points or greater worsening on the NIH Stroke Scale); the need for surgery to relieve pressure on the brain in the first week; death within 90 days; or the recurrence of ischaemic stroke within 90 days.

“The finding of more intracranial bleeding in the patients who received endovascular therapy is very important. However, there were haemorrhages with symptoms and some that caused no symptoms. The haemorrhages with no symptoms were detected on imaging conducted for this study in the endovascular treatment group, not in the standard practice group. Symptomatic intracranial haemorrhage still occurred more commonly among patients in the endovascular group, however, it was not a statistically significant difference from the standard care group,” Morimoto said.

Due to different treatment protocols in Japan, where there is less use of intravenous thrombolysis than in the US and other western countries, and where more strokes are imaged with MRI than CT, this study’s results may over- or underestimate the effectiveness of endovascular therapy.

The researchers are currently performing sub-analyses to help identify factors that might signal which patients are more likely to have a greater return of function after the treatment. “In addition, tools, devices or rehabilitation methods that could potentially improve the likelihood for similar patients to recover with less disability should be investigated,” Morimoto said.

Source: American Heart Association

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Micronutrients Could Replenish Mitochondria in Cardiac Cells

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There is convincing evidence that micronutrients, such as iron, selenium, zinc, copper, and coenzyme Q10, can impact the function of cardiac cells’ energy-producing mitochondria to contribute to heart failure according to a review published in the Journal of Internal Medicine.

Research has established a relationship between poor cardiac performance and metabolic perturbations, including deficits in substrate uptake and utilisation, reduction in mitochondrial oxidative phosphorylation and excessive reactive oxygen species production. Together, these disturbances result in depletion of cardiac adenosine triphosphate (ATP) and loss of cardiac energy. Delivering more energy substrates such as fatty acids to the mitochondria will be worthless if the mitochondria can’t turn them into fuel. 

Micronutrients are required to efficiently convert macronutrients to ATP. However, studies have shown that up to 50% of patients with heart failure have deficiencies in one or more micronutrients. “Micronutrient deficiency has a high impact on mitochondrial energy production and should be considered an additional factor in the heart failure equation,” the authors argued. Their findings suggest that micronutrient supplementation could represent an effective treatment for heart failure.

“Micronutrient deficiency has a high impact on mitochondrial energy production and should be considered an additional factor in the heart failure equation, moving our view of the failing heart away from ‘an engine out of fuel’ to ‘a defective engine on a path to self-destruction’,” said co–lead author Nils Bomer, PhD, of the University Medical Center Groningen, in The Netherlands.

An accompanying editorial suggests a large trial to see if there is indeed a clinical benefit.

Source: Wiley

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Intensive Hypertension Treatment may Prevent Strokes in Older Adults

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More intensive hypertension treatment could help prevent or delay strokes in older adults, according to an analysis of results from randomised clinical trials published in the Journal of the American Geriatrics Society.

The researchers initially screened 22 trials for inclusion. Nine trials involving 38 779 adults with an average age ranging from 66 to 84 years were included in the analysis, with follow-up times ranging from 2.0 to 5.8 years.

On average, the researchers found that it took 1.7 years to prevent 1 stroke for 200 older persons treated with more intensive hypertension treatment.

For older adults with baseline systolic blood pressures below 150 mmHg, the time to benefit from more intensive hypertension treatment was longer than 1.7 years; for older adults with baseline systolic blood pressure above 190 mmHg, the time to benefit was shorter than 1.7 years.

In their discussion, the researchers noted the risks of aggressive hypertension treatment, including hypotension, syncope and falls. However, they noted that emerging evidence shows that the increase in fall risk is transient.

“While the 2017 American College of Cardiology/American Heart Association guidelines recommend individual risk discussions about hypertension treatment for primary prevention in older adults, there is a critical gap in data about how long a patient needs to receive blood pressure treatment before they will benefit – or the blood pressure treatment’s time to benefit,” said lead author Vanessa S. Ho, MS, of California Northstate University College of Medicine. “A treatment’s time to benefit is an especially important consideration for patients with a limited life expectancy who may experience immediate burdens or harms from any additional medication.”

Source: Wiley

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American Heart Association’s In-hospital Stroke Evaluation and Treatment Recommendations

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Image copyright American Heart Association

Despite the fact that hospitalised patients are in a monitored environment, stroke evaluation and treatment are often delayed compared to patients arriving with a stroke at the emergency department, contributing to higher rates of morbidity and mortality for in-hospital stroke. 

This is according to an American Heart Association scientific statement published in Stroke. This scientific statement was discussed at the Association’s International Stroke Conference in New Orleans. An American Heart Association scientific statement is an expert analysis of current research and may inform future clinical practice guidelines. This follows on from a previous 2019 update on recommendations systems of care to improve patient outcomes in stroke.

The statement outlines five elements for the development of hospital systems of care and targeted quality improvement to reduce delays and optimise treatment to improve outcomes for patients who experience an in-hospital stroke. In-hospital stroke is a stroke that occurs during a hospitalisation for another diagnosis and affects between 35 000 and 75 000 hospitalised patients annually in the United States.

The five core elements of the statement are:

  • training all hospital staff on stroke signs, symptoms and activation protocols for in-hospital stroke alerts;
  • creating rapid response teams with dedicated stroke training and immediate access to neurologic expertise;
  • standardising the evaluation of potential in-hospital stroke patients with physical assessment and imaging;
  • eliminating and addressing potential treatment barriers including interfacility transfer to advanced stroke treatment; and
  • establishing an in-hospital stroke quality oversight program delivering data-driven performance feedback and driving targeted quality improvement efforts.

The statement encourages institutions to develop a plan for in-patient stroke response teams that includes education, quality review and specified oversight.

The statement was developed by the writing committee on behalf of the American Heart Association’s Stroke Council; the Council on Arteriosclerosis, Thrombosis and Vascular Biology; the Council on Cardiovascular and Stroke Nursing; the Council on Clinical Cardiology; and the Council on Lifestyle and Cardiometabolic Health. The diverse committee included experts in nursing, neurology, internal medicine, neurocritical care, neurosurgery and neurointerventional radiology. The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists, and the American Association of Neurological Surgeons/Congress of Neurological Surgeons Cerebrovascular Section affirms the educational benefit of this statement.

American Heart Association scientific statements promote greater awareness about cardiovascular diseases and stroke issues and help facilitate informed health care decisions. Scientific statements outline what is currently known about a topic, and what areas need additional research. While scientific statements inform the development of guidelines, they do not make treatment recommendations. American Heart Association guidelines provide the Association’s official clinical practice recommendations.

Source: American Heart Association

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Hypertension Warning for Long-term Paracetamol Use

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BP cuff for home monitoring, Source: Pixabay

Long-term paracetamol use could increase the risk of heart disease and strokes in people with high blood pressure, according to a randomised clinical trial by the University of Edinburgh.

Researchers recommend that patients with a long term prescription, usually for chronic pain, should rather choose the lowest effective dose for the shortest possible time.

The study, which appears in Circulation, is the first large randomised clinical trial to address the question of paracetamol’s effect on cardiovascular disease, and complements earlier work in observational studies.

Paracetamol was often suggested as a safer alternative to non-steroidal anti-inflammatory drugs (NSAIDs), which are known to increase blood pressure and risk of heart disease.

In the latest study, 110 patients with a history of high blood pressure were prescribed one gram of paracetamol four times a day – a routinely prescribed dose in patients with chronic pain – or a matched placebo for two weeks. All patients received both treatments, with the order randomised and blinded. The paracetamol group saw a significant increase in blood pressure, compared to the placebo group.

This rise was similar to that seen with NSAIDs, and could be expected to increase the risk of heart disease or stroke by around 20%. The findings should lead to a review of long-term paracetamol prescriptions to patients, said the researchers, especially to those with hypertension and an increased risk of heart disease or stroke.

Lead Investigator Dr. Iain MacIntyre said: “This is not about short-term use of paracetamol for headaches or fever, which is, of course, fine—but it does indicate a newly discovered risk for people who take it regularly over the longer term, usually for chronic pain.”

Principal Investigator Professor David Webb said: “We would recommend that clinicians start with a low dose of paracetamol, and increase the dose in stages, going no higher than needed to control pain. Given the substantial rises in blood pressure seen in some of our patients, there may be a benefit for clinicians to keep a closer eye on blood pressure in people with high blood pressure who newly start paracetamol for chronic pain.”

Professor Sir Nilesh Samani, Medical Director at the British Heart Foundation, who funded the study, said: “This research shows how quickly regular use of paracetamol can increase blood pressure in people with hypertension who are already at increased risk of heart attacks and strokes. It emphasises why doctors and patients should regularly review whether there is an ongoing need to take any medication, even something that may seem relatively harmless like paracetamol, and always weigh up the benefits and risks. However, if you take paracetamol occasionally to manage an isolated headache or very short bouts of pain, these research findings should not cause unnecessary concern.”

Source: University of Edinburgh

Categories : Cardiovascular Disease Metabolic DisordersTags :

GLP-1: The Missing Link of Diabetes and Hypertension

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An international team of researchers has finally cracked the puzzle of why so many patients with hypertension also have diabetes. Their discovery has shown that glucagon-like peptide-1 (GLP-1) couples the body’s control of blood glucose and blood pressure.

Senior Author Professor Julian Paton at the University of Auckland, said: “We’ve known for a long time that hypertension and diabetes are inextricably linked and have finally discovered the reason, which will now inform new treatment strategies.”

The study is published online in Circulation Research.

It has long been known that GLP-1 is released from the wall of the gut after eating and acts to stimulate insulin from the pancreas to control blood sugar levels.  However, the researchers found that GLP-1 also stimulates the carotid body, a chemoreceptor located in the neck.

Researchers used RNA sequencing to read all the messages of the expressed genes in the carotid body in rats with and without high blood pressure. This led to the finding that the receptor that senses GLP-1 is located in the carotid body, but less so in hypertensive rats.

David Murphy, Professor of Experimental Medicine from Bristol Medical School: Translational Health Sciences (THS) and senior author, explained: “Locating the link required genetic profiling and multiple steps of validation.  We never expected to see GLP-1 come up on the radar, so this is very exciting and opens many new opportunities.”

Professor Paton added: “The carotid body is the convergent point where GLP-1 acts to control both blood sugar and blood pressure simultaneously; this is coordinated by the nervous system which is instructed by the carotid body.”

Even when on medication, many patients with hypertension and/or diabetes are at high risk of life-threatening cardiovascular disease. This is because most medications only treat symptoms and not causes of high blood pressure and high sugar.

Professor Rod Jackson, an epidemiologist from the University of Auckland, said: “We’ve known that blood pressure is notoriously difficult to control in patients with high blood sugar, so these findings are really important because by giving GLP-1 we might be able to reduce both sugar and pressure together, and these two factors are major contributors to cardiovascular risk.”

Lead author Audrys Pauža, PhD student in the Bristol Medical School, added: “The prevalence of diabetes and hypertension is increasing throughout the world, and there is an urgent need to address this.

“Drugs targeting the GLP-1 receptor are already approved for use in humans and widely used to treat diabetes. Besides helping to lower blood sugar these drugs also reduce blood pressure, however, the mechanism of this effect wasn’t well understood.

“This research revealed that these drugs may actually work on the carotid bodies to enact their anti-hypertensive effect. Leading from this work, we are already planning translational studies in humans to bring this discovery into practice so that patients most at risk can receive the best treatment available.”

The research has also revealed many novel targets for ongoing functional studies that the team hope will lead to studies in human hypertensive and diabetic patients.

Source: University of Bristol

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Uncovering the Mechanical Basis for Abdominal Aortic Aneurysm

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A new study reveals the mechanical basis underlying abdominal aortic aneurysm (AAA), a complex and life-threatening vascular disease with high incidence worldwide.

Known as the ‘silent killer’, most AAAs are asymptomatic, often undetected until rupture, and involve a poorly understood set of mechanical and biochemical events. Studies have shown that AAA is associated with both vascular inflammation and increased stiffness. That the latter happens with ageing partly explains why AAA is almost only ever seen in people over 65.

Evidence suggests that abnormal acclimation of vascular smooth muscle cells (VSMC) to biomechanical disturbances, such as increased circumferential stress in hypertension, can lead to the development of AAA. However, not much is known about the molecular drivers of altered mechanobiological behaviors of VSMC. Understanding these might provide promising targetable signals that could repress AAA progression and limit rupture incidents.

Now, researchers have demonstrated mechanobiological changes in VSMC and identified a key ion channel that is involved in the development of AAA. In a new study, in Nature Communications, they describe how VSMC gradually adopts a solid-like state by upregulating cytoskeleton crosslinker, α-actinin2, which powers the mechanosensitive ion channel Piezo1.

“Our team applied biomechanical engineering to study aneurysm pathology,” explained study leader Professor Weiqiang Chen. “In contrast to the extensive study of aorta wall properties, we explored how a cell’s mechanical sensitivity, or ‘mechanosensation’ to mechanical stimuli presents an innovative perspective in revealing disease pathogenesis and progression mechanisms.”

Measuring misshapen VSMC with a novel ultrasound tweezers system and a single-cell RNA sequencing technique, the researchers identified Piezo1, which critically regulates VSMC mechanical sensitivity. Inhibiting Piezo1 in mice prevented them from developing AAA, by relieving pathological vascular remodeling. The researchers concluded that deviations of mechanosensation behaviours of VSMC is detrimental for AAA, and Piezo1 could be responsible for mechanically fatigued aorta in AAA. This could lead to new mechano-medical approaches to treating this devastating cardiovascular disease.

Source: EurekAlert!

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Having Better Conversations about Post-stroke Prognosis

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Though conversations with stroke survivors and their loved ones about possible lasting impairment can be traumatic, they might also be therapeutic, according to research from The University of Queensland, published in the American Journal of Speech-Language Pathology.

PhD candidate Bonnie Cheng from UQ’s School of Health and Rehabilitation Sciences said that prognosis conversations can trigger mixed emotions of hope and grief, so knowing  how people would prefer for them to happen is important.

“When stroke is encountered for the first time, it’s hard to know what’s important and relevant to ask about, especially during that time of crisis immediately after such a serious health event,” Ms Cheng said.

“During this time, there’s also an immense sense of gratitude for the survival of their loved one that seems to stop significant others from asking for more information.

“Conversations about prognosis and lasting impairments, like speech difficulties, need to be an ongoing dialogue between health professionals, the patient, and their support network.

“It’s important for these conversations to be based on a mutual understanding of what improvements are personally meaningful to the patient and their significant others.”

Aphasia is a common condition after a stroke, diagnosed in one-in-three people after a stroke.

The researchers interviewed people who identified as a significant other of someone with aphasia between three and 12 months after stroke, including spouses, close friends, adult children and parents of someone with aphasia.

“In the interviews, we talked in-depth about their experience of finding out about the prognosis for aphasia, the impact these experiences had on them, and how they would want to get information about prognosis in a perfect world,” Ms Cheng said.

“What we found was significant others need to be included in prognosis conversations so that they too can be informed and supported, alongside the patient.

“The prognosis of aphasia is a sensitive issue to address because it often involves having to adjust to long-term difficulties and changes.

“Recovery needs to be looked at holistically in terms of everyday activities that affect the individual, rather than just scores on a language impairment test.

“Even though we can’t yet ‘cure’ aphasia, this research brings us one step closer to talking about recovery in a way that’s as informative and as compassionate as possible, so that people living with aphasia can be supported to live successfully with the condition.”

Source: University of Queensland

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US Sees Surge in Hypertension Hospitalisations

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The number of people hospitalised for a hypertensive crisis in the US more than doubled from 2002 to 2014, according to researchers from Cedars-Sinai Medical Center. Possible causes included socioeconomic factors such as reduced access to healthcare.

A hypertensive crisis is an acute, marked elevation in blood pressure that is associated with signs of target-organ damage. This increase in hypertensive crises happened at a time when some studies reported overall progress in blood pressure control and a decline in related cardiovascular events in the US. The findings are published in the Journal of the American Heart Association.

“Although more people have been able to manage their blood pressure over the last few years, we’re not seeing this improvement translate into fewer hospitalisations for hypertensive crisis,” said first author Joseph E. Ebinger, MD, a clinical cardiologist and director of clinical analytics at the Smidt Heart Institute

Dr Ebinger said there could be a number of explanations for the incrrease. More people may be unable to afford hypertension medications or are taking inadequate doses of these drugs. Socioeconomic factors may also make it difficult for people to avoid unhealthy behaviours that can contribute to hypertension, such as smoking, as well as having limited access to health care and other concerns.

“We need more research to understand why this is happening and how clinicians can help patients stay out of the hospital,” Dr Ebinger said.

For their study, the investigators used data from the National Inpatient Sample, which is a publicly available database. The data include a subset of all hospitalisations across the US, providing a picture of nationwide trends. They found that annual hospitalisations for hypertensive crises more than doubled over a 13-year period. Hospitalisations related to hypertensive crises accounted for 0.17% of all admissions for men in 2002 but 0.39% in 2014, and represented 0.16% of all admissions for women in 2002 but 0.34% in 2014.

The mortality risk for hypertensive crisis, however, did decrease slightly overall during the studied time period. Women died at the same rate as men, even though they had fewer health issues than men who also were hospitalised for a hypertensive crisis.

“These findings raise the question: Are there sex-specific biologic mechanisms that place women at greater risk for dying during a hypertensive crisis?” said senior study author Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the Department of Cardiology at the Smidt Heart Institute. “By understanding these processes, we could prevent more deaths among women,” she added.

Source: Cedars-Sinai Medical Center

Categories : Ageing Cardiovascular DiseaseTags :

Reduced Heart Failure Risk in Postmenopausal Women Who Walk Faster

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A study of postmenopausal women, published in the Journal of the American Geriatrics Society, found that those who reported a faster walking pace had a lower risk of developing heart failure. 

Among 25 183 women aged 50 to 79 years, there were 1455 cases of hospitalisation for heart failure during a median follow-up of 16.9 years. Compared with women who walked at a casual pace, those who walked at an average pace or fast pace had 27% and 34% lower risks of heart failure, respectively.

Fast walking for less than 1 hour per week was associated with the same risk reduction of heart failure as average or casual walking for more than 2 hours per week.

“This study confirms other studies demonstrating the importance of walking speed on mortality and other cardiovascular outcomes,” said senior author Charles B. Eaton, MD, MS, of the Warren Alpert Medical School of Brown University. “Given that limited time for exercise is frequently given as a barrier to regular physical activity, walking faster but for less time might provide similar health benefits as the recommended 150 minutes per week of moderate physical activity.”

Further study is warranted to determine whether interventions to increase the walking pace in older adults will reduce heart failure risk and whether fast pace will compensate for the short duration of walking.

Source: Wiley