Tag: myocardial infarction

New Findings on Cardiovascular Risk, Menopause and Migraines Ease Concerns

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Research suggesting a link between migraines and menopause symptoms and cardiovascular disease has gotten a lot of attention. But a pair of new studies in the journal Menopause suggest that most women experiencing these symptoms can rest easier, especially if they don’t have both migraines and long-term hot flashes and night sweats.

Instead, they should focus on tackling the other factors that can raise their cardiovascular risk by getting more sleep, exercise and healthy foods, quitting tobacco, and minding their blood pressure, blood sugar, cholesterol and weight.

For women who have experienced both migraines and hot flashes or night sweats over many years, one of the new studies does suggest an extra level of cardiovascular risk.

That makes heart disease and stroke prevention even more important in this group, says study leader Catherine Kim, MD, MPH, of the University of Michigan.

And for women currently in their 20s and 30s who experience migraines, the new research suggests that they might be heading for a higher risk of long-term menopause-related symptoms when they get older.

Long-term study yields important insights

Kim and her colleagues at Michigan Medicine, U-M’s academic medical centre, published the new pair of studies based on an in-depth analysis of data from a long-term study of more than 1900 women who volunteered to have regular physical exams and blood tests, and to take yearly health surveys, when they were in their late teens to early 30s.

Those women, now in their 50s and 60s, have provided researchers with a priceless view of what factors shape health in the years leading up to menopause and beyond, through their continued participation in the CARDIA study.

“The anxiety and dread that women with migraines and menopausal symptoms feel about cardiovascular risk is real – but these findings suggest that focusing on prevention, and correcting unhealthy habits and risk factors, could help most women,” said Kim, who is an associate professor of internal medicine at U-M and a primary care physician.

“For the subgroup with both migraines and early persistent hot flashes and night sweats, and for those currently experiencing migraines in their early adulthood, these findings point to an added need to control risks, and address symptoms early,” she adds.

Just over 30% of the middle-aged women in the study reported they had persistent hot flashes and night sweats, which together are called vasomotor symptoms or VMS because they relate to changes in the diameter of blood vessels.

Of them, 23% had reported also having migraines. This was the only group for whom Kim and her colleagues found extra risk of stroke, heart attack or other cardiovascular events that couldn’t be explained by other risk factors that have long been known to be linked to cardiovascular problems.

In addition to those with persistent vasomotor symptoms starting in their 40s or before, 43% of the women in the study had minimal levels of such symptoms in their 50s, and 27% experienced an increase in VMS over time into their 50s and early 60s.

The latter two groups had no excess cardiovascular risk once their other risk factors were taken into account, whether or not they had migraines.

Use of hormone-based birth control and estrogen to address medical issues did not affect this risk.

Controlling destiny

In the study of data from the same women in their earlier stages of life, the researchers found that the biggest factors in predicting which ones would go on to have persistent hot flashes and night sweats were having migraines, having depression, and smoking cigarettes, as well as being Black or having less than a high school education.

“These two studies, taken together, underscore that not all women have the same experiences as they grow older, and that many can control the risk factors that might raise their chances of heart disease and stroke later in life,” said Kim.

“In other words, women can do a lot to control their destiny when it comes to both menopause symptoms and cardiovascular diseases.”

She notes that the American Heart Association calls these risk factors the “Essential 8” and offers guides for what women, men and even children and teens can do to address them.

Evolving knowledge and treatment

The long-term study that the two new findings come from was specifically designed to look at cardiovascular risks when it launched in the mid-1980s. CARDIA stands for Coronary Artery Risk Development in Young Adults.

Back in the 80s, knowledge about the biology of blood vessels, down to the cellular and molecular level, was nowhere near where it is today. Both vasomotor symptoms in menopause and migraines have to do with blood vessel contraction and dilation.

But decades of research has shown the microscopic impacts on blood vessels of years of smoking, poor sleep, poor eating habits and lack of activity, as well as a person’s genetic inheritance, life experiences and hormonal history.

Newer injectable migraine medications called calcitonin gene-related peptide (CGRP) antagonists have reached the market in recent years. Using monoclonal antibodies, they target a key receptor on the surface of blood vessel cells to prevent migraines and cluster headaches. But they are expensive and not covered by insurance for all people with migraines.

While the new study is based on data from years before these medications became available, Kim said she recommends them to her patients with persistent migraines, as well as working with them to understand what triggers their migraines and how to use other medications including pain relievers and antiseizure medications to prevent them.

She also notes that the paper on future risk of persistent hot flashes and night sweats echoes the recent trend of using antidepressant medications to try to ease these menopause effects.

Kim also says that evidence has grown about the importance of healthy sleep habits for reducing hot flashes, as well the short-term use of oestradiol-based hormone therapy patches, which have not been shown to have a link to cardiovascular risk. And, she notes that research has not shown any over-the-counter supplement or herbal remedy to be effective, and that these are far less regulated than medications.

Source: Michigan Medicine – University of Michigan

Semaglutide Cuts CVD Events by 20% in People with Obesity or Overweight but not Diabetes

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In a large, international clinical trial, people with obesity or overweight but not diabetes taking semaglutide for more than three years had a 20% lower risk of cardiovascular disease outcomes and lost an average of 9.4% of their body weight.

Semaglutide, a GLP-1 medication primarily prescribed for people with Type 2 diabetes, is also FDA-approved for weight loss in people with obesity.

These results were shared in a late-breaking science presentation at the American Heart Association’s Scientific Sessions 2023 and the full manuscript was also published in The New England Journal of Medicine.

“This news is very encouraging for people with overweight or obesity because no treatment specifically directed at the management of obesity and overweight in people without Type 1 or Type 2 diabetes has been tested in a randomised trial and been shown to influence cardiovascular outcomes,” said lead study author A. Michael Lincoff, MD.

While prior research has confirmed the benefits of semaglutide in managing blood sugar, decreasing cardiovascular disease events and reducing weight in people with Type 2 diabetes, this study specifically investigated the potential impact of semaglutide on cardiovascular disease in people with overweight or obesity and cardiovascular disease who did not have either Type 1 or Type 2 diabetes.

In this randomised, controlled, double-blind trial, participants were assigned to take either 2.4mg of semaglutide (the FDA-approved semaglutide dose for weight management) or a placebo once a week, which is higher than the FDA-approved semaglutide dose limit for Type 2 diabetes of 2.0mg/week. Each person in the study used a ‘pen’ to inject the medicine or placebo into a skin fold in their stomach, thigh or upper arm each week on the same day, and the dose started at 0.24mg and gradually increased every four weeks up to 2.4mg, and mean follow-up for all participants was 40 months.

In addition to taking either semaglutide or placebo for the trial, all participants also received standard of care treatment for cardiovascular disease, such as cholesterol modifying medications, antiplatelet therapies, beta blockers or other treatments. The authors note that heart disease diagnoses varied among the participants, therefore, treatment was adjusted to meet each individual’s diagnosis and needs, as well as the treatment guidelines in their country of residence.

The study, which ran from October 2018 through June 2023, indicated the following:

  • There was a 20% reduction in the risk of heart attacks, strokes or death due to cardiovascular disease in the participants who took semaglutide, compared to the participants in the placebo group.
  • In the semaglutide group, the participants’ body weight was reduced, on average, by 9.4% compared to a reduction of 0.9% among the adults in the placebo group.
  • There were no new safety concerns found in the study, which researchers note is encouraging since the SELECT trial is the largest and longest (4.5 years) trial of semaglutide in adults without Type 1 or Type 2 diabetes.
  • The number of serious adverse events was lower in the semaglutide group. Previous studies of medications of the GLP-1 receptor agonist class have shown an association with gallbladder disorders, and in SELECT, there was a slightly higher rate of gallbladder disorders in the semaglutide vs placebo group (2.8% vs 2.3%, respectively).
  • Semaglutide was stopped more frequently than placebo for gastrointestinal intolerance, a known side effect of this class of medications; however, there was no higher rate of serious gastrointestinal events.
  • The researchers noted that this medication did not lead to an increased rate of pancreatitis, which has been a concern with prior medications of this type.
  • Of note, other weight-loss medications that are not GLP-1 receptor agonists have been associated with increased risks of psychiatric disorders or cancer; these risks were not elevated with semaglutide in the SELECT trial.

“It’s been estimated that within about ten years, over half of the world’s population will have overweight or obesity,” said Dr Lincoff. “And while GLP-1 medications are frequently prescribed for patients with vascular disease and Type 2 diabetes, there is a significant number of people who do not have Type 1 or Type 2 diabetes but do have vascular disease and overweight or obesity for whom these medications are often not available due to access to care issues, insurance coverage or other factors. This population may now potentially benefit from semaglutide, and importantly, our results indicate the magnitude of cardiovascular risk reduction with semaglutide among people without Type 1 or Type 2 diabetes is the same as what we have seen in people with Type 2 diabetes. Our findings expand the opportunity to treat patients who have overweight or obesity and existing heart disease without Type 1 or Type 2 diabetes, and we have a chance to significantly reduce their risk of a secondary cardiovascular event including death.”

Among the study limitations were including adults with prior cardiovascular disease, thereby not investigating primary prevention of cardiovascular disease (people with no history of a heart attack, stroke and/or peripheral artery disease). In addition, 28% of the study participants were female, which is not proportionate to the number of women with cardiovascular disease and overweight or obesity in the general population.

Additional analyses will include identifying the mediators of the cardiovascular benefit to determine to what extent the results were driven by reduction of metabolically unhealthy body fat, positive impacts on inflammation or blood sugar, direct effects of the medication itself on plaque build-up in the arteries, or a combination of one or more variables.

Source: American Heart Association

First Myocardial Damage-based Classification of Heart Attack is Released

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Heart attacks, or acute myocardial infarction (MI), are one of the leading causes of death worldwide. The newly released Canadian Cardiovascular Society Classification of Acute Myocardial Infarction (CCS-AMI) appearing in the Canadian Journal of Cardiology, published by Elsevier, presents a four-stage classification of heart attack based on heart muscle damage. This work by a group of noted experts has the potential to stratify risk more accurately in heart attack patients and lays the groundwork for development of new, injury-stage-specific and tissue pathology-based therapies.

Lead author Andreas Kumar, MD, MSc, Northern Ontario School of Medicine University, explains: “MI remains a leading cause of morbidity and mortality. Existing tools classify MIs using a patient’s clinical presentation and/or the cause of the heart attack, as well as ECG findings. Although these tools are very helpful to guide treatment, they do not consider details of the underlying tissue damage caused by the heart attack. This expert consensus, based on decades of data, is the first classification system of its kind ever released in Canada and internationally. It offers a more differentiated definition of heart attacks and improves our understanding of acute atherothrombotic MI. On a tissue level, not all heart attacks are the same; the new CCS-AMI classification paves the way for development of more refined therapies for MI, which could ultimately result in better patient clinical care and improved survival rates.”

The CCS-AMI classification describes damage to the heart muscle following an MI in four sequential and progressively severe stages. Each stage reflects progression of tissue pathology of myocardial ischemia and reperfusion injury from the previous stage. It is based on a strong body of evidence about the effect an MI has on the heart muscle.

As damage to the heart increases through each progressive CCS-AMI stage, patients have dramatically increased risk of complications such as arrhythmia, heart failure, and death. Appropriate therapy can potentially stop injury from progressing and halt the damage at an earlier stage.

  • Stage 1: Aborted MI (no/minimal myocardial necrosis). No or minimal damage to the heart muscle. In the best case the entire area of myocardium at risk may be salvaged.
  • Stage 2: MI with significant cardiomyocyte necrosis, but without microvascular injury. Damage to the heart muscle and no injury to small blood vessels in the heart. Revascularisation therapy will result in restoration of normal coronary flow.
  • Stage 3: MI with cardiomyocyte necrosis and microvascular dysfunction leading to microvascular obstruction (ie, “no-reflow”). Damage to the heart muscle and blockage of small blood vessels in the heart. The major adverse cardiac event rate is increased 2- to 4-fold at long-term follow-up.
  • Stage 4: MI with cardiomyocyte and microvascular necrosis leading to reperfusion hemorrhage. Damage to the heart muscle, blockage and rupture of small blood vessels resulting in bleeding into the heart muscle. This is a more severe form of microvascular injury, and the most severe form of ischemia-reperfusion injury. It is associated with a further increase in adverse cardiac event rate of 2- to 6-fold at long-term follow-up.

Dr Kumar concludes: “The new classification will help differentiate heart attacks according to the stage of tissue damage and allow healthcare providers to estimate a patient’s risk more precisely for arrhythmia, heart failure, and death. The CCS-AMI is ultimately expected to lead to better care, better recovery, and better survival rates for heart attack patients.”

In an accompanying editorial, Prakriti Gaba, MD, Brigham and Women’s Hospital, Harvard Medical School, and Deepak L. Bhatt, MD, MPH, Mount Sinai Heart, Icahn School of Medicine at Mount Sinai, comment: “Kumar et al. present a novel and intriguing four-tiered classification scheme of patients with acute MI. This allows unique utilisation of prognostic pathologic features to help distinguish between high and low risk acute MI patients. Greater access to cardiovascular magnetic resonance would be needed to implement this new clinical approach broadly, however, for research on emerging diagnostic and therapeutic strategies, it could be implemented immediately.”

Source: Elsevier

Red Blood Cells Exposed to Oxygen Deficiency Protect against Myocardial Infarction

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Red blood cells exposed to oxygen deficiency protect against myocardial infarction, according to a new study published in the Journal of Clinical Investigation. This study, conducted at Karolinska Institutet in collaboration with Karolinska University Hospital, also shows that that protection can be enhanced by a diet containing nitrate-rich vegetables, such as arugula and other green leafy vegetables.

“This effect was also shown in a clinical study in patients with high blood pressure who were randomly assigned to eat nitrate-rich vegetables or a diet low in nitrates,” says John Pernow, Professor of Cardiology at the Department of Medicine, Karolinska Institutet in Solna and senior physician at Karolinska University Hospital, and the study’s corresponding author together with Jon Lundberg, professor at the Department of Physiology and Pharmacology, Karolinska Institutet.

Part of the study was conducted through experiments with red blood cells from mice that were added to a myocardial infarction model with hearts from mice. Before the experiment, the red blood cells were exposed to low oxygen pressure, while nitrate was added to the drinking water.

In a clinical study, red blood cells were collected from patients with high blood pressure who were randomly assigned a nitrate-rich diet with green leafy vegetables or a diet with nitrate-poor vegetables. These red blood cells were given to the corresponding myocardial infarction model with hearts from rats.

“The results show both that the red blood cells convey protection against injury in the heart in the event of low oxygen levels, and how that protection can be enhanced through a simple dietary advice. This may be of great importance for patients at risk of myocardial infarction,” says the study’s first author Jiangning Yang, a researcher at the Department of Medicine, Solna, Karolinska Institutet.

The next step in the research is to develop additional drugs that can activate the protective signalling mechanism in red blood cells to provide protection to the body’s tissues and cells in the event of oxygen deficiency.

“In addition, we need to map how the blood cells transmit their protective signal to the heart muscle cells,” says John Pernow.

Source: Karolinska Institutet

European COVID Lockdowns Cost Heart Attack Patients up to Two Years of Life

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Patients who had heart attacks during the first COVID lockdown in the UK and Spain are predicted to live 1.5 and 2 years less, respectively, than their pre-COVID counterparts. That’s the finding of a study just published in European Heart Journal – Quality of Care and Clinical Outcomes.

“Restrictions to treatment of life-threatening conditions have immediate and long-term negative consequences for individuals and society as a whole,” said study author Professor William Wijns of the Lambe Institute for Translational Medicine, University of Galway, Ireland. “Back-up plans must be in place so that emergency services can be retained even during natural or health catastrophes.”

Research has shown that during the first wave of the pandemic, about 40% fewer heart attack patients went to hospital as governments told people to stay at home, fear of catching the virus, and the stopping of some routine emergency care. Compared to receiving timely treatment, heart attack patients who stayed at home were more than twice as likely to die, while those who delayed going to the hospital were nearly twice as likely to have serious complications that could have been avoided.

Heart attacks require urgent treatment with stents (called percutaneous coronary intervention or PCI) to open the blocked artery and restore blood flow. Delays, and the resulting lack of oxygen, lead to irreversible damage of the heart muscle and can cause heart failure or other complications. When a large amount of heart tissue is damaged, potentially fatal cardiac arrest results.

This study estimated the long-term clinical and economic implications of reduced heart attack treatment during the pandemic in the UK and Spain. The researchers compared the predicted life expectancy of patients who had a heart attack during the first lockdown with those who had a heart attack at the same time in the previous year. The study focused on ST-elevation myocardial infarction (STEMI), where a coronary artery is completely blocked. The researchers also compared the cost of STEMIs during lockdown with the equivalent period the year before.

A model was developed to estimate long-term survival, quality of life and costs related to STEMI. The UK analysis compared the period 23 March (when lockdown began) to 22 April 2020 with the equivalent time in 2019. The Spanish analysis compared March 2019 with March 2020 (lockdown began on 14 March 2020). Survival projections considered age, hospitalisation status and time to treatment using published data for each country. For example, using published data, it was estimated that 77% of STEMI patients in the UK were hospitalised prior to the pandemic compared with 44% during lockdown. The equivalent rates for Spain were 74% and 57%. The researchers also compared how many years in perfect health were lost for patients with a STEMI before versus during the pandemic.

The analysis predicted that patients who had a STEMI during the first UK lockdown would lose an average of 1.55 years of life compared to patients presenting with a STEMI before the pandemic. In addition, while alive, those with a STEMI during lockdown were predicted to lose approximately one year and two months of life in perfect health. The equivalent figures for Spain were 2.03 years of life lost and around one year and seven months of life in perfect health lost.

The cost analysis focused on initial hospitalisation and treatment, follow-up treatment, management of heart failure and productivity loss in patients unable to return to work. For example, the cost applied to a STEMI admission with PCI was £2837 in the UK and €8780 in Spain. Heart failure costs were estimated at £6086 in year one and £3882 in all subsequent years for the UK. The equivalent figures for Spain were €3815 (year one) and €2930 (each subsequent year).

Professor Wijns said: “The findings illustrate the repercussions of delayed or missed care. Patients and societies will pay the price of reduced heart attack treatment during just one month of lockdown for years to come. Health services need a list of lifesaving therapies that should always be delivered, and resilient healthcare systems must be established that can switch to emergency plans without delay. Public awareness campaigns should emphasise the benefits of timely care, even during a pandemic or other crisis.”

Source: European Society of Cardiology

Strong Legs Reduce Risk of Heart Failure after Heart Attack

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People with strong legs are less likely to develop heart failure after a heart attack, according to new research. Myocardial infarction is the most common cause of heart failure, with around 6–9% of heart attack patients going on to develop the condition. Previous research has shown that having strong quadriceps is associated with a lower risk of death in patients with coronary artery disease.

Presented at Heart Failure 2023, a scientific congress of the European Society of Cardiology (ESC), this study tested the hypothesis that leg strength is associated with a lower risk of developing heart failure after acute myocardial infarction. The study included 932 patients hospitalised in 2007 to 2020 with acute myocardial infarction who did not have heart failure prior to the admission and did not develop heart failure complications during their hospital stay. The median age was 66 years and 753 participants (81%) were men.

Maximal quadriceps strength was measured as an indicator of leg strength. Patients sat on a chair and contracted the quadriceps muscles as hard as possible for five seconds. A handheld dynamometer attached to the ankle recorded the maximum value in kg. The measurement was performed on each leg and the researchers used the average of both values. Strength was expressed relative to body weight, meaning that quadriceps strength in kg was divided by body weight in kg and multiplied by 100 for a % body weight value. Patients were classified as ‘high’ or ‘low’ strength according to whether their value was above or below the median for their se

The median value for women was 33% body weight and the median value for men was 52% body weight. A total of 451 patients had low quadriceps strength and 481 had high strength. During an average follow-up of 4.5 years, 67 patients (7.2%) developed heart failure. The incidence of heart failure was 10.2 per 1000 person-years in patients with high quadriceps strength and 22.9 per 1000 person-years in those with low strength.

The researchers analysed the association between quadriceps strength (low vs. high) and the risk of developing heart failure. The analysis was adjusted for factors known to be associated with the development of heart failure after myocardial infarction including age, sex, body mass index, prior myocardial infarction or angina pectoris, diabetes, atrial fibrillation, chronic obstructive pulmonary disease, peripheral arterial disease and kidney function. Compared with low quadriceps strength, a high strength level was associated with a 41% lower risk of developing heart failure (hazard ratio [HR]: 0.59; 95% confidence interval [CI] 0.35–1.00; p=0.048).

The investigators also analysed the association between quadriceps strength as a continuous variable and the risk of developing heart failure. Each 5% body weight increment in quadriceps strength was associated with an 11% lower likelihood of heart failure (HR 0.89; 95% CI 0.81–0.98; p=0.014).

Study author Mr. Kensuke Ueno, a physical therapist at the Kitasato University Graduate School of Medical Sciences, Sagamihara, Japan said: “Quadriceps strength is easy and simple to measure accurately in clinical practice. Our study indicates that quadriceps strength could help to identify patients at a higher risk of developing heart failure after myocardial infarction who could then receive more intense surveillance. The findings need to be replicated in other studies, but they do suggest that strength training involving the quadriceps muscles should be recommended for patients who have experienced a heart attack to prevent heart failure.”

Source: European Society of Cardiology

Women Have Double the Mortality Risk After Heart Attack

The risk of dying after a heart attack is more than twice as high for women than it is for men, according to research presented at Heart Failure 2023, held by the European Society of Cardiology (ESC).

“Women of all ages who experience a myocardial infarction are at particularly high risk of a poor prognosis,” said study author Dr Mariana Martinho of Hospital Garcia de Orta. “These women need regular monitoring after their heart event, with strict control of blood pressure, cholesterol levels and diabetes, and referral to cardiac rehabilitation. Smoking levels are rising in young women and this should be tackled, along with promoting physical activity and healthy living.”

Previous studies have found that women with ST-elevation myocardial infarction (STEMI) have a worse prognosis during their hospital stay compared to men, and that this may be due to their older age, increased numbers of other conditions, and less use of stents (percutaneous coronary intervention; PCI) to open blocked arteries. This study compared short- and long-term outcomes after STEMI in women and men, and examined whether any sex differences were apparent in both premenopausal (55 years and under) and postmenopausal (over 55) women.

This was a retrospective observational study which enrolled consecutive patients admitted with STEMI and treated with PCI within 48 hours of symptom onset between 2010 and 2015. Adverse outcomes were defined as 30-day all-cause mortality, five-year all-cause mortality and five-year major adverse cardiovascular events (MACE; a composite of all-cause death, reinfarction, hospitalisation for heart failure and ischaemic stroke).

The study included 884 patients. The average age was 62 years and 27% were women. Women were older than men (average age 67 vs 60 years) and had higher rates of high blood pressure, diabetes and prior stroke. Men were more likely to be smokers and have coronary artery disease. The interval between symptoms and treatment with PCI did not differ between women and men overall, but women aged 55 and below had a significantly longer treatment delay after arriving at the hospital than their male peers (95 vs 80 minutes).

The researchers compared the risk of adverse outcomes between women and men after adjusting for factors that could influence the relationship including diabetes, high cholesterol, hypertension, coronary artery disease, heart failure, chronic kidney disease, peripheral artery disease, stroke and family history of coronary artery disease. At 30 days, 11.8% of women had died compared to 4.6% of men, for a hazard ratio (HR) of 2.76. At five years, nearly one-third of women (32.1%) had died versus 16.9% of men (HR 2.33). More than one-third of women (34.2%) experienced MACE within five years compared with 19.8% of men (HR 2.10).

Dr Martinho said: “Women had a two to three times higher likelihood of adverse outcomes than men in the short- and long-term even after adjusting for other conditions and despite receiving PCI within the same timeframe as men.”

The researchers conducted a further analysis in which they matched men and women according to risk factors for cardiovascular disease including hypertension, diabetes, high cholesterol and smoking. Adverse outcomes were then compared between matched men and women aged 55 years and under, and between matched men and women over 55 years old.

There were 435 patients in the matched analysis. In matched patients over 55 years of age, all adverse outcomes measured were more common in women than men. Some 11.3% of women died within 30 days compared with 3.0% of men, for an HR of 3.85. At five years, one-third of women (32.9%) had died compared with 15.8% of men (HR 2.35) and more than one-third of women (34.1%) had experienced MACE compared with 17.6% of men (HR 2.15). In matched patients aged 55 years and below, one in five women (20.0%) experienced MACE within five years compared to 5.8% of men (HR 3.91), while there were no differences between women and men in all-cause mortality at 30 days or five years.

Dr Martinho said: “Postmenopausal women had worse short- and long-term outcomes after myocardial infarction than men of similar age. Premenopausal women had similar short-term mortality but a poorer prognosis in the long-term compared with their male counterparts. While our study did not examine the reasons for these differences, atypical symptoms of myocardial infarction in women and genetic predisposition may play a role. We did not find any differences in the use of medications to lower blood pressure or lipid levels between women and men.”

She concluded: “The findings are another reminder of the need for greater awareness of the risks of heart disease in women. More research is required to understand why there is gender disparity in prognosis after myocardial infarction so that steps can be taken to close the gap in outcomes.”

Source: European Society of Cardiology

Atherosclerosis is a Greater Heart Attack Risk for Women

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Postmenopausal women with atherosclerosis are at higher risk of heart attacks than men of similar age, according to research presented at EACVI 2023, a scientific congress of the European Society of Cardiology (ESC), and published in European Heart Journal – Cardiovascular Imaging. Researchers used imaging techniques to examine the arteries of nearly 25 000 patients and followed them for heart attacks and death.

“The study suggests that a given burden of atherosclerosis is riskier in postmenopausal women than it is in men of that age,” said study author Dr Sophie van Rosendael of Leiden University Medical Centre. “Since atherosclerotic plaque burden is emerging as a target to decide the intensity of therapy to prevent heart attacks, the findings may impact treatment. Our results indicate that after menopause, women may need a higher dose of statins or the addition of another lipid-lowering drug. More studies are needed to confirm these findings.”

While young women do have heart attacks, in general, women develop atherosclerosis (narrowing of arteries due to plaque buildup) later in life than men and have heart attacks at an older age than men, in part because of the protective effect of oestrogen. This study examined whether the prognostic importance of atherosclerotic plaques are the same for women and men at different ages as this could be important for selecting treatments to prevent heart attacks.

The study included 24 950 patients referred for coronary computed tomography angiography (CCTA) and enrolled in the CONFIRM registry, which was conducted in six countries in North America, Europe, and Asia. CCTA is used to obtain 3D images of the arteries in the heart.

Total atherosclerotic burden was rated using the Leiden CCTA score, which incorporates the following items for each coronary segment: plaque presence (yes/no), composition (calcified, noncalcified or mixed), location, and severity of narrowing, for a final value of 0 to 42. Patients were divided into three categories previously found to predict the risk myocardial infarction: low atherosclerotic burden (0 to 5), medium (6 to 20) and high (over 20). In addition, obstructive coronary artery disease was defined as 50% narrowing or more.

The primary outcome was the difference in Leiden CCTA score between women and men of similar age. The investigators also analysed sex differences in the rates of major adverse cardiovascular events (MACE), which included all-cause death and myocardial infarction, after adjusting for age and cardiovascular risk factors (hypertension, high cholesterol, diabetes, current smoking and family history of coronary artery disease).

A total of 11 678 women (average age 58.5 years) and 13 272 men (average age 55.6 years) were followed for 3.7 years. Regarding the primary outcome, the study showed an approximately 12 year delay in the onset of coronary atherosclerosis in women: the median Leiden CCTA risk score was above zero at age 64 to 68 years in women versus 52 to 56 years in men (p<0.001). In addition, the overall plaque burden as quantified by the Leiden CCTA score was significantly lower in women, who had more non-obstructive disease.

Dr. van Rosendael said: “The results confirm the previously reported delay in the start of atherosclerosis in women. We also found that women are more likely to have non-obstructive disease. It was formerly thought that only obstructive atherosclerosis caused myocardial infarction but we now know that non-obstructive disease is also risky.”
The burden of atherosclerosis was equally predictive of MACE in premenopausal women (aged under 55 years) and men of the same age group. However, in postmenopausal women (age 55 years and older), the risk of MACE was higher than men for a given score. In postmenopausal women, compared to those with a low burden, those with a medium and high burden had 2.21-fold and 6.11-fold higher risks of MACE. While in men aged 55 years and older, compared to those with a low burden, those with a medium and high burden had 1.57-fold and 2.25-fold greater risks of MACE.

Dr van Rosendael said: “In this study, the elevated risk for women versus men was especially observed in postmenopausal women with the highest Leiden CCTA score. This could be partly because the inner diameter of coronary arteries is smaller in women, meaning that the same amount of plaque could have a larger impact on blood flow. Our findings link the known acceleration of atherosclerosis development after menopause with a significant increase in relative risk for women compared to men, despite a similar burden of atherosclerotic disease. This may have implications for the intensity of medical treatment.”

Source: European Society of Cardiology

Time to Rethink Beta Blockers as Secondary Prevention for Heart Attack Survivors?

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Secondary prevention after a heart attack, where beta blockers are used over the long term to curb the risk of further heart attacks or death, doesn’t seem to be warranted in patients who don’t have heart failure, suggests a large study published in the journal Heart.

The researchers found no difference in these risks between patients taking beta blockers more than a year after their heart attack and those not on these drugs.

Beta blockers are mostly used to manage abnormal heart rhythms, as well as angina and high blood pressure. They are routinely prescribed after a heart attack as secondary prevention to lower the risk of recurrence and other cardiovascular complications.

But it’s not clear if these drugs are warranted in patients who don’t have heart failure, or a potentially fatal complication of heart attack known as left ventricular systolic dysfunction (LVSD) beyond the first year.

Most of the current evidence is based on the results of clinical trials that predate major changes to the routine care of heart attack patients, explain the researchers.

The researchers drew on 43 618 adults who had had a heart attack between 2005 and 2016 that required hospital treatment, and whose details had been entered into the national Swedish register for coronary heart disease (SWEDEHEART).

None of these patients had heart failure or LVSD: 34 253 of them were prescribed beta blockers and were still on these drugs 1 year after hospital discharge; 9365 hadn’t been prescribed these drugs. Their average age was 64 and around 1 in 4 were women.

The researchers wanted to find out if there were any differences between the two groups in terms of deaths from any cause and rates of further heart attacks, revascularisation, or hospitalisation for heart failure.

The real time data showed that long term treatment with beta blockers wasn’t associated with improved cardiovascular outcomes during an average monitoring period of 4.5 years.

Some 6475 (19%) of those on beta blockers, and 2028 (22%) of those who weren’t, died from any cause, or had another heart attack, or required unscheduled revascularisation, or were admitted to hospital for heart failure.

After accounting for potentially influential factors, including demographics and relevant co-existing conditions, no significant difference was seen in rates of these events between the two groups.

As an observational study, it can’t establish cause. Additionally, despite being the largest study of its kind to date, the findings should be viewed in the context of certain limitations, acknowledge the researchers.

Patients weren’t randomised to treatment; only certain cardiovascular outcomes were included; there was no indication of how consistently patients took their drugs; nor any information on their health related quality of life.

And there were some differences between the two groups in respect of factors known to influence the risk of poor cardiovascular outcomes.

But, the researchers point out, beta blockers are associated with several side effects such as depression and fatigue, and it’s now time to reassess the value of long term treatment with these drugs in heart attack patients who don’t have heart failure or LVSD, they suggest.

In a linked editorial, Professor Ralph Stewart and Dr Tom Evans write: “Despite strong evidence that long-term beta-blockers can improve outcomes after [heart attack], it has been uncertain whether this benefit applies to lower risk patients who are taking other evidence-based therapies and who have a [normal functioning heart].”

They point out: “Recommendations on the duration of beta blocker therapy are variable or absent because this question was not specifically evaluated in clinical trials. Most patients take daily medications for many years after a [heart attack] because they believe they are beneficial.”

And they conclude: “[This] study raises an important question directly relevant to the quality of care –do patients with a normal [functioning heart] benefit from long term beta-blocker therapy after [heart attack]? To answer this question, more evidence from large randomised clinical trials is needed.”

Source: EurekAlert!

Bempedoic Acid Could be a Viable Alternative to Statins

Photo by Towfiqu Barbhuiya on Unsplash

Bempedoic acid, a new cholesterol-lowering drug, has the potential to be an effective substitute for patients who can’t tolerate statins. Bempedoic acid is an ATP citrate lyase inhibitor that reduces low-density lipoprotein (LDL) cholesterol levels and is associated with a low incidence of muscle-related adverse events. Its effects on cardiovascular outcomes were uncertain, so researchers used a double-blind, randomised, placebo-controlled trial to determine outcomes on a variety of cardiovascular measures in statins-intolerant patients.

The study, published in the New England Journal of Medicine, recruited patients aged 18–85 years at increased cardiovascular risk and unable or unwilling to take statins due to adverse effects. Patients were first tested with placebo over a 4-week run-in period, and were not randomised if they experience unacceptable adverse effects or if adherence was less than 80%. The 13 970 patients who successfully completed run-in were randomised to receive bempedoic acid 180mg orally per day or matching placebo. 

The mean LDL cholesterol level at baseline was 139.0mg/dL in both groups, and after 6 months, the reduction in the level was greater with bempedoic acid than with placebo by 29.2mg/dL; the observed difference in the percent reductions was 21.1 percentage points in favour of bempedoic acid.

Compared to placebo, risk of fatal or nonfatal stroke, death from cardiovascular causes, and death from any cause after significantly were lower by 13%, after a median of 40.6 months of follow-up. The risk of death from cardiovascular causes, nonfatal stroke, or nonfatal myocardial infarction was 15% lower with bempedoic acid than with placebo, and the risks of fatal or nonfatal myocardial infarction and coronary revascularisation were 23% lower and 19% lower, respectively.

The researchers noted that the LDL-cholesterol lowering effects were similar in magnitude and predicted reduction in cardiovascular risks to that observed with statins. In addition, bempedoic acid did not increase glycated haemoglobin levels or the incidence of new-onset diabetes, unlike statins. Due to the demonstrated benefits, those taking placebo were offered the chance to transition to taking bempedoic acid.

A trial limitation was that it only included patients with statins intolerance, and who therefore had higher LDL cholesterol levels at baseline.