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.”
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.”
A new study published this month in the journal Hypertension has shown gut bacteria can reduce the effectiveness of certain antihypertensive drugs. The researchprovides 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.”
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.”
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.”
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.
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.”
Vascular endothelial cells use a vast network of connections to control all cardiovascular functions, and failures in this network contribute to the risk of developing cardiovascular disease, according to a new study published in PNAS.
It has long been known that the development of these conditions begins with changes in the vascular endothelial cells lining the body’s blood vessels. But why and how changes in endothelial cell function occur is not entirely clear.
Research has revealed that these cells communicate with each other using a sophisticated system. Failures in this communication system may be the first step in the development of cardiovascular disease.
The endothelium, which forms the thin inner layer of cells in blood vessels, regulates blood flow, blood pressure, blood clotting, inflammation and response to disease. On a continual basis, it processes the vast amounts of information held in the composition of blood, and chemicals in the area around each blood vessel to keep the cardiovascular system working properly.
The study identified clusters of cells in the endothelium that are specialised to particular functions and they operate in ‘cliques’. Between cliques, numerous interlinked connections act to convey information, with a high density of connections to protect the system against communication failures. The system bypasses neighbouring cells by use of shortcuts to transmit information quickly over distance.
The endothelial communication network design is in fact remarkably similar to the communication operations of the internet and it is effective for local blood vessel control and global efficiency in determining overall cardiovascular activity. The design is robust, so that communication systems to control cardiovascular activity will not fail even when there is extensive damage.
The findings also indicate that changes in the organisation of communication, rather than behaviour and function of individual cells, may underlie disease.
The researchers addressed the nature of the communication network by using single-cell calcium ion imaging across thousands of endothelial cells in intact blood vessels and applying mathematical network (graph) theory.
Professor John McCarron at Strathclude University said: “Cells in the endothelium are a major target for the control of cardiovascular disease and are often treated as being a uniform population of cells. Our findings show the cells are not uniform but specialised to particular types of function.
“There is a well-organised, rapid and robust communication system that shares information so that co-ordinated responses occur. The communication system offers new targets for therapy development and insights into why developing treatments has proven so difficult.”
Cutting down daily sedentary time can have a positive effect on the risk factors of cardiovascular disease and type 2 diabetes in as little as three months, according to a study published in the Journal of Science and Medicine in Sport. The study findings suggest that simply one hour less sitting daily and increasing light physical activity can help in the prevention of these diseases.
Regular exercise is well known to be beneficial in weight management and prevention of chronic diseases. However, many adults do not meet the weekly recommendation of 2.5 hours of moderate-intensity exercise, and the majority of the day is typically spent sitting.
In an intervention study, researchers investigated whether health benefits can be achieved by reducing daily sedentary time during a three-month intervention period. The research participants were sedentary and physically inactive working-age adults with an increased risk of type 2 diabetes and cardiovascular diseases.
The researchers compared two groups: the intervention group was guided to reduce their sitting time by one hour per day by increasing standing and light-intensity physical activity, while the control group was instructed to maintain their usual habits and sedentary lifestyle.
“What makes our research design unique is that sedentary time and physical activity of both groups were measured with accelerometers throughout the entire three-month period, whereas in earlier studies activity has typically been measured only for a few days at the beginning and end of the study period. This makes it possible to receive more information on the actual behaviour changes over a longer time period,” explained Doctoral Candidate Taru Garthwaite from the University of Turku in Finland.
The intervention group reduced sedentary time by 50 minutes per day on average, mainly by increasing the amount of light- and moderate-intensity physical activity. Over the three-month period, the researchers observed benefits in health outcomes related to blood sugar regulation, insulin sensitivity and liver health in the intervention group.
“It is an encouraging thought that health benefits can be achieved by reducing the time spent sitting and increasing the amount of even light-intensity physical activity. For many, this may be an easier starting point than increasing actual exercise,” said Garthwaite.
People who do not meet the weekly physical activity recommendations atre the most likely to benefit the most from replacing sedentary time with light physical activity. However, reducing sedentary time is probably not enough in itself to prevent diseases if the person has several risk factors of diabetes and cardiovascular diseases.
Garthwaite stressed the encouraging nature of the findings: “Reducing the time spent sitting might still slow down the development of these diseases, but greater benefits can of course be gained by increasing the amount or intensity of physical activity in addition to sitting less.”
The researchers next aim to study how changes in daily activity and sedentary time affect energy metabolism and body composition in addition to the risk factors of diabetes and cardiovascular diseases over a six-month study period.
The US Preventive Services Task Force (USPSTF) has issued a recommendation statement on the use of aspirin in the prevention of cardiovascular disease (CVD). The recommendation shifts the use of aspirin to an earlier window, and making it an individualised decision for people in their 40s to 50s with a > 10% 10-year CVD risk.
The previous recommendation from 2016had called for low-dose aspirin for people in their 50s with a > 10% 10-year CVD risk and individualised decisions for those in their 60s with similar risk. The update comes after new evidence emergedin a number of randomised controlled trials.
For the update, which appears in JAMA Network, a systematic review was conducted on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD. The effect of aspirin use on colorectal cancer incidence and mortality was also investigated in primary CVD prevention populations, as well as the harms (particularly bleeding) associated with aspirin use.
The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults aged 40–59 years with a 10% or greater 10-year CVD risk has a small net benefit, and starting low-dose aspirin use for CVD prevention should be an individual decision for them. Those not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older.
Aspirin’s mechanism of action in CVD protection is well known. Aspirin at low doses is an irreversible cyclooxygenase 1 (COX-1) enzyme inhibitor, and at higher doses, it also inhibits COX-2. By inhibiting platelet function through COX-1, aspirin reduces atherothrombosis risk, and has been used widely for the prevention of CVD events, particularly for secondary prevention. However the COX-1 is also involved with protection of the gastrointestinal mucosa, and inhibition of it can promote gastrointestinal bleeding. The mechanism for the possible antineoplastic effects of aspirin is not as well understood.
Older age is one of the strongest risk factors for CVD, and men have a higher overall CVD disease burden and tend to experience CVD events earlier in life. Race and ethnicity affects CVD burden, with Black persons having the highest prevalence of CVD.
Similar CVD benefits appear for a low aspirin dose (≤ 100mg/d) and for all doses that have been studied in CVD prevention trials (50 to 500mg/d). A pragmatic approach would be to use 81 mg/d, which is the most commonly prescribed dose in the US.
Because CVD risk estimation is imprecise and imperfect at the individual level, the USPSTF suggests using these risk estimates as a starting point to discuss with appropriate candidates their desire for daily aspirin use. The benefits of initiating aspirin use are greater for individuals at higher risk for CVD events (eg, those with > 15% or > 20% 10-year CVD risk).
In addition to age and estimated level of CVD risk, decisions about initiating aspirin use should be based on shared decision-making between clinicians and patients about the potential benefits and harms, based on the relative values the patient places on these (reduced CVD risk vs increased bleeding and stroke risk).
Annual bleeding events in individuals without risk factors for increased bleeding (eg, history of gastrointestinal bleeding risk, history of peptic ulcer disease, or use of nonsteroidal anti-inflammatory drugs or corticosteroids) are rare, but risk for bleeding increases modestly with advancing age. For persons who have initiated aspirin use, the net benefits continue to accrue over time in the absence of a bleeding event. However, benefits shrink with advancing age because of increased bleeding risk, with modelling data suggesting stopping aspirin use around age 75.
