Every year, researchers gain a deeper understanding of the pathways that lead to cardiovascular disease and how to better prevent and treat heart disease and stroke.
In 2023, investigators made important strides toward improving and extending the lives of people affected by these conditions, along with potentially lowering the burden of disease with therapies and strategies that hold promise for prevention.
Particularly noteworthy were advances in technology to restore blood flow to blocked and narrowed arteries, potentially preventing death and disability for a wide range of patients, including those with severe illness.
As the leading funder of heart- and stroke-related research outside the U.S. government, the American Heart Association compiles an annual overview of significant scientific advances in the fight against cardiovascular disease, which claims more than 850,000 lives in the U.S. each year and is the leading cause of death and disability worldwide. Here are some of the most significant developments from 2023.
New drug suppresses key protein needed for development of hypertension
Hypertension affects nearly half of all U.S. adults, many of whom don’t even know they have it. Left untreated, it greatly increases the risk for having a heart attack, stroke and other serious health problems. It also can cut life expectancy by up to five years.
Blood pressure is considered too high if it is persistently 130/80 mmHg or greater. Despite advances in medications that should be able to control hypertension in most people, fewer than 25% of those being treated keep blood pressure levels within the target range.
And the consequences are getting worse.
Mortality due to high blood pressure has risen more than 30% since the 1990s. Multiple factors may play a role, and researchers are looking for new approaches. One strategy is to thwart the development of hypertension by interfering in the mechanisms that produce it.
Angiotensinogen, a protein secreted by the liver, is believed to play a key role in increasing blood pressure. Prior research shows the more angiotensinogen produced, the higher the blood pressure measurement. Zilebesiran is an investigational drug that decreases production of angiotensinogen.
This phase I study looked at whether Zilebesiran was safe and effective for 107 people 65 and older with high blood pressure. The multi-center investigation was divided into three parts. In the first part, participants were randomly assigned to a single injection of the drug ranging from 10 to 800 milligrams or placebo. In the second, they were given a single 800-mg dose while eating low- or high-salt diets. In the third, they were given the 800-mg dose and a second medication, Irbesartan.
Over eight weeks, people who received doses of 200 mg or more of Zilebesiran saw reductions in their blood pressure measurements. The higher the dose, the greater the reduction. The reductions lasted through 24 weeks of treatment. A high-salt diet reduced the drug’s effectiveness, while the addition of Irbesartan (an established oral therapy to treat hypertension) enhanced its effectiveness. The injections caused mild reactions in most people at the site of the injection.
Not only does the suppression of angiotensinogen hold promise for more effectively reducing hypertension for extended periods of time after injection, there is growing excitement over the possibility it also might be therapeutic for kidney and heart disease. The results are also highly significant because only a single dose was needed, which could improve access to care and adherence to long-term drug regimens.
Thrombectomy could offer greater independence to even the most severe stroke patients
Endovascular thrombectomy is a minimally invasive surgical procedure to remove a blood clot from a blocked artery in the brain that has caused a stroke. The procedure, which can restore blood flow and prevent further brain damage and disability, has become standard treatment for some people who have medium-sized strokes. But it’s been unclear whether people with larger, more severe strokes might benefit. Though they account for up to one-fourth of all stroke patients, this group has largely been left out of clinical trials.
A study of stroke patients in Japan had previously suggested endovascular thrombectomy might benefit this group. But it was unclear whether the results would be applicable to other populations. Last year, three additional studies – two in the New England Journal of Medicine (NEJM) and one in the Lancet – provided evidence thrombectomy was superior to standard medical treatment for large-stroke patients in China, North America, Europe, Australia and New Zealand. All three trials were halted early when they quickly showed a shift from worse to better outcomes after the thrombectomy.
In one NEJM study, researchers compared the safety and effectiveness of endovascular thrombectomy with medical management within 24 hours of a severe stroke to medical management alone. The analysis included 456 stroke patients treated at 46 hospitals in China. Patients had severe strokes caused by blood clots in the large vessels of the brain. Over three months of follow-up, those who received thrombectomies were significantly more functionally independent. However, they also experienced more brain bleeds.
Another NEJM study found endovascular thrombectomy within 24 hours of a stroke superior to standard medical care in 352 people from North America, Europe, Australia and New Zealand who had large, severe strokes. The group receiving thrombectomies experienced fewer disabilities and the patients were more functionally independent over three months of follow-up. In this trial, the incidence of intracranial hemorrhage (bleeding in the brain) and death was similar for both groups. But 18% of those undergoing thrombectomy surgery had complications associated with the surgical procedure.
The Lancet study likewise showed people treated with endovascular thrombectomy and standard medical treatment retained better functional independence and were less likely to die than those who received standard medical treatment alone. The research included 253 patients treated at 40 hospitals in Europe and one in Canada.
It differed from the other two in the type of imaging used to select patients for inclusion. Rather than using advanced imaging techniques to determine stroke size and severity – which would limit their ability to generalize findings to other populations – the researchers in this study used non-contrast CT scans, the type of brain scans more typically used in clinical practice.
Taken together, the trials suggest even patients who experience the most severe strokes may benefit from a treatment that offers a chance for greater independence and fewer disabilities.
Advances in imaging help guide stent placement in people with complex coronary lesions
Percutaneous coronary intervention, or PCI, is a non-surgical procedure used to place a stent in blood vessels in the heart that have become blocked or too narrow due to plaque buildup along the artery walls. But sometimes, placing a stent can be challenging because of where the plaque build-up, or lesion, is located. For example, it might be in a place where the artery branches, making it hard to reach, or too close to the aorta, the heart’s main blood vessel. PCI doesn’t always work well for these people or for people with diabetes, who instead might need surgery to restore blood flow to and from their hearts.
At first, PCI was only used for people with simple coronary artery disease. But advances in the types of imaging used to guide stent selection and placement have led to improvements in long-term outcomes for patients treated with PCI, allowing cardiologists to use the procedure on people with more complex heart problems. Three New England Journal of Medicine studies and one published in the American Heart Association journal Circulation looked at ways to improve the way stents work in these higher-risk patients. The studies compared the safety and effectiveness of different types of imaging used to guide the placement of stents.
Angiography is a type of X-ray used to look inside blood vessels after a special dye is injected into the blood to make it easier to see problems — typically called a cardiac catheterization. It is the most commonly used method for guiding the placement of stents in people with complex, coronary artery lesions. But it doesn’t provide a detailed look at the plaque or how well stents are working once they’ve been placed.
Intravascular imaging allows cardiologists to see more details of what’s inside the artery, such as features of the plaque and the artery walls, but is less frequently used. There are two kinds: intravascular ultrasonography, which uses sound waves to see inside blood vessels, and optical coherence tomography. Optical coherence tomography, or OCT, uses light waves to look more closely at plaque in the arteries. It provides high-resolution images that help physicians determine the right stent size to use and where and how to place it.
The ILUMIEN IV study compared OCT-guided PCI to angiography-guided PCI in 2,487 people with diabetes or high-risk coronary lesions at 80 sites in 18 countries. OCT guidance resulted in a larger minimum stent area – the area opened up so blood could flow more freely – and appeared to be safe. Both methods were equally effective at preventing death, heart attacks or the need for further revascularization over two years of follow-up.
The OCTOBER trial compared these two methods for placing stents in 1,201 people in 38 centers in Europe who had complex coronary artery bifurcation lesions – plaque build-up in areas where arteries branch that are difficult to see. Over two years of follow-up, people who had OCT-guided PCI had fewer adverse major cardiac events and deaths than those whose stents were placed using angiography guidance. There was a similar rate of complications for both groups.
A third NEJM study – RENOVATE-COMPLEX-PCI – compared intravascular imaging-guided PCI (either ultrasonography or OCT) to angiography-guided PCI for 1,639 patients in South Korea with complex coronary artery lesions. Over two years of follow-up, people treated with either type of intravascular imaging-guided PCI experienced fewer heart-related deaths, heart attacks or need for further revascularization than those whose PCI was guided by angiography. Complication rates were similar for both groups.
The OCTIVUS randomized, clinical trial, published in Circulation, compared the safety and effectiveness of the two types of intravascular image guidance in 2,008 patients with significant coronary artery lesions and found both were equally safe and effective.
Together, these studies illustrate the complexity of coronary artery disease and the promise of more advanced guidance technologies for tailoring treatment to improve patient outcomes.
Could anticoagulant drugs be given sooner to AFib patients following a stroke?
People with atrial fibrillation, also known as AFib, experience rapid and irregular heartbeats in the upper chamber of the heart. This can slow blood flow, causing blood to collect in the heart, where it forms clots that may travel to the brain and cause a stroke.
People with AFib may be treated with Direct-Acting Oral Anticoagulants (DOAC) – quick-acting blood thinners that help to prevent strokes from occurring. But how soon to begin this medication after a stroke in a person with AFib was unclear. Doing so too early could increase the risk of brain bleeds, while doing so later could raise the risk of having a second stroke.
Under current clinical practice, treatment is typically delayed at least a few days. European guidelines suggest waiting three days after a minor stroke, six days after a moderate stroke and 12 days after a severe stroke while the American Heart Association/American Stroke Association guidelines suggest waiting more than two weeks in some high-risk patients.
A new study, published in the New England Journal of Medicine, suggested treatment with DOACs might safely begin much sooner.
Researchers randomly assigned 2,013 people with AFib from 103 stroke centers in Europe, the Middle East and Asia to receive early anti-coagulation treatment (within 48 hours of a minor or moderate stroke and on day six or seven following a major stroke) or later anti-coagulation treatment (on day three or four following a minor stroke, day six or seven following a moderate stroke and on day 12, 13 or 14 following a major stroke).
How researchers measured stroke severity differed from previous investigations. The standard practice is to use a score based on the location and size of an infarct, or dead tissue in the brain caused by the loss of blood supply. In this trial, researchers used CT or MRI scans to measure the size of infarcts. They concluded that this method allowed them to better identify people who could benefit from earlier use of DOACs.
While outcomes between the two groups were not substantially different, overall, the findings showed earlier treatment resulted in a lower risk for recurrent strokes and slightly lower risk for bleeding outside the brain in the month following a stroke, even in those who had major strokes. The incidence of bleeding inside the brain was low in both groups. The trial was not designed to test whether earlier treatment was better than later treatment, but to help health care providers estimate possible outcomes.
Diabetes drugs may offer heart protections to people who don’t have diabetes
Obesity rates in the U.S. have tripled over the last 50 years, contributing to the increase in a wide range of health problems, including type 2 diabetes and cardiovascular disease. This has led to the development of medications to manage weight and lower blood glucose levels.
Glucose-lowering drugs have been shown to reduce major cardiovascular events and outcomes for people with diabetes, who are at high risk for heart attack, stroke, heart failure and cardiovascular-related death. A review paper in Circulation summarized how this class of drugs has changed the landscape for people with type 2 diabetes, offering heart-health protection regardless of how well glucose levels are being controlled.
A growing body of research suggests these drugs may also improve heart health in obese people who don’t have diabetes.
Two studies suggested semaglutide, a medication approved for long-term weight management, could help obese people lower their risk for heart problems and reduce heart failure-related symptoms.
Heart failure with preserved ejection fraction (HFpEF) happens when the heart muscle becomes thick and stiff and can’t pump out enough blood to meet the body’s needs. This condition has been increasing in prevalence, often accompanied by symptoms such as shortness of breath, fatigue and decreased tolerance for exercise, especially in people who are obese. But no therapies have been approved to treat this group of patients.
A paper in the New England Journal of Medicine suggests semaglutide can improve quality of life for patients with heart failure. Among 529 patients given once-weekly injections of semaglutide or placebo for one year, semaglutide led to greater reductions in heart failure-related symptoms, greater improvements in the ability to exercise and greater weight loss.
Semaglutide had already been shown to lower the risk for heart problems in people with diabetes. Researchers investigated whether it might also benefit overweight and obese people who didn’t have diabetes but who did have cardiovascular disease. Among 17,604 people 45 and older, they found the drug superior to placebo in reducing cardiovascular-related death, nonfatal heart attacks and nonfatal strokes.
While these developments are certainly promising, an editorial in the New England Journal of Medicine warns the high cost of these medications may make them inaccessible to many who need them and should not deter public health efforts to fight the root causes of the nation’s obesity epidemic.
A deeper look into what may be driving disparities in cardiovascular death rates
Cardiovascular disease is the world’s leading killer, but research shows it affects some people more than others. For example, Black adults and people in rural areas have disproportionate rates of heart disease and are more likely to die from it.
A growing body of research highlights how social determinants of health (SDOH) play a role in these disparities. These social factors can include where a person lives, access to health care, transportation, healthy foods and safe places to stay physically active. The stress of structural racism and other types of discrimination can also play a role, as can whether they live in low-income neighborhoods or have clean air or water.
A longitudinal analysis in the Journal of the American Heart Association used federal SDOH data, coupled with county-level cardiovascular disease mortality data, to analyze which factors were most strongly linked to heart-related death rates. They noted that while county-level cardiovascular death rates were declining in the decade studied, they remained higher in rural counties and in counties with a higher percentage of Black residents. Cardiovascular death rates were most strongly linked to income status, along with access to healthy foods and housing, suggesting that addressing these issues could save lives.
Another way race affects cardiovascular mortality has to do with how likely people are to receive help when they need it, such as when someone experiences sudden cardiac arrest outside a hospital setting.
People who experience an out-of-hospital cardiac arrest – when the heart suddenly stops – are nearly twice as likely to survive if a bystander performs CPR while they wait for emergency medical personnel to arrive. But as few as 35% of people who need this help ever get it – and new research in the NEJM shows rates are even lower for Black and Hispanic people. The disparity exists whether the cardiac arrest is witnessed at home or out in public, regardless of the racial or ethnic make-up or income level of people in the neighborhood where it occurs.
While CPR training is less common in Black communities than in white communities, implicit biases also appear to play a role. As noted in a related editorial, efforts to improve bystander CPR rates may be complicated “by a legacy of structural racism that has left many of our communities segregated and with inequitable social determinants of sudden cardiac death.”
More evidence links healthy eating patterns to lower death risks
Researchers have long known that a healthy diet plays a critical role in good health. That’s why the American Heart Association included an overall healthy eating pattern as one of the key components in Life’s Essential 8 ™, its blueprint for how to maintain good heart and brain health.
The USDA publishes dietary guidelines to encourage people to follow healthy eating patterns, based on the latest nutrition science. A study in JAMA Internal Medicine analyzed whether adherence to the Dietary Guidelines for Americans could be linked to a lower risk of death. They analyzed data for 75,230 women in the Nurses’ Health Study and 44,085 men in the Health Professionals Follow-Up Study and found a strong link between adherence to a variety of healthy eating patterns aligned with these guidelines and a lower death risk. The link was consistent across racial and ethnic groups, suggesting the guidelines could be adapted to individual food traditions and preferences.
These findings from such a large cohort provide further support for the American Heart Association’s Food is Medicine initiative, which encourages health care systems to help patients access and consume healthy foods based on scientific evidence that a healthy diet can help prevent, manage and treat chronic illness.
Exploring the link between cardiovascular, kidney disease and metabolic syndrome
Evidence has been building of a deep interconnection between obesity, chronic kidney disease, diabetes and cardiovascular disease, leading to what’s become known as the cardiovascular-kidney-metabolic (CKM) syndrome. CKM syndrome includes people at risk for cardiovascular disease and those who already have it, including people with heart failure, AFib, coronary heart disease, stroke and peripheral artery disease.
Poor CKM health has been linked to premature death and disability, making it a public health priority. The increase in prevalence of CKM syndrome and the growing body of research surrounding it has led to the publication of an American Heart Association Scientific Statement and Presidential Advisory, along with the creation of a new heart disease risk calculator that takes CKM health measures into account.
The Scientific Statement summarizes what’s known about CKM health and how it may be prevented and managed. It also highlights gaps in the science, screening, prevention and management of CKM that should be addressed. The Presidential Advisory provides guidance on the definition, prevention and treatment of the syndrome across diverse clinical and community settings.
The American Heart Association PREVENT risk calculator estimates the 10- and 30-year risks for heart attacks, stroke and heart failure for people 30 and older. It is the first risk calculator to combine measures of cardiovascular, kidney and metabolic health to estimate future cardiovascular risk. And it can take into account social determinants of health that lead to disparities.
While CKM syndrome adds to the high burden of chronic illness in the U.S., there are likewise numerous therapies and strategies with the potential for improving the lives of those affected.
Expanding treatment options for people with limb-threatening PAD
Peripheral arterial disease occurs when arteries carrying blood between the heart and limbs become narrow or blocked, and it is associated with an increases in the risk of having a heart attack or stroke as people get older. It happens when plaque builds up in the arteries and though it can develop in any blood vessel, it most often affects the arms and legs. An aging population, coupled with the growing prevalence of diabetes, has led to an increase in peripheral arterial disease, or PAD, in recent years.
Chronic limb-threatening ischemia is an advanced form of PAD. People who have this condition need treatment to restore blood flow to the limbs, a process known as revascularization, to lower the risk of amputation and death. Bypass surgery is one way to do this. Endovascular therapy is a less invasive method that involves inserting a catheter into the vein. The catheter can be used to push a balloon through the artery, pressing plaque up against the walls in a process called angioplasty. Or the catheter can be used to insert a stent that holds the artery open, allowing blood to flow more freely.
Two randomized studies compared the safety and effectiveness of endovascular therapies to surgical bypass in people with severe PAD.
BASIL-2 compared the effectiveness of a vein bypass to angioplasty in 345 men and women with severe ischemia of the leg at 41 vascular surgery centers in the United Kingdom, Sweden and Denmark. People who received the endovascular treatment had greater amputation-free survival, a finding based on the larger number of deaths in the surgery group. But an accompanying editorial in the Lancet noted these results may have been skewed by the COVID-19 pandemic. Patients were still being seen at the start of the pandemic, which may have limited the number of follow-up visits and boosted the death rate.
The BEST-CLI study, published in the New England Journal of Medicine, compared bypass surgery to endovascular therapy in two groups of patients: one with a greater saphenous vein (the large vein that runs the length of the lower leg) that was suitable for surgery and another group that needed an alternative type of bypass. The study included 1,830 patients from 150 sites in the U.S., Canada, Finland, Italy and New Zealand. Among patients with a greater saphenous vein that was suitable, surgery was the better option, resulting in fewer amputations and deaths. But there were no significant differences in outcomes among the other groups.
These results, while inconclusive, suggest the choice of intervention should be based on shared decision making among interventional cardiologists, vascular surgeons and the patient.