AHA names top heart disease and stroke research advances of 2020
Humanity's most urgent public health problem at the end of 2020 was just a tiny blip on the world's radar as the year got started.
The emergence of the COVID-19 pandemic would require a massive research effort — stat — to understand the disease's effects on the body and in diverse populations.
By midyear, a COVID-19 registry — a data-gathering framework that drew on the American Heart Association's Get With the Guidelines hospital quality-improvement program — was yielding early insights into which populations are most likely to be hospitalized and which are most vulnerable to severe illness.
But COVID-19 is only one area where important research advances were made in 2020. Heart disease and stroke remain the world's top killers.
As a leading funder of heart- and stroke-related research, the AHA annually compiles a recap of pivotal scientific studies. Here are some of 2020's key developments.
A unique therapy could transform how hypertrophic cardiomyopathy (HCM) is treated
About 1 in every 500 people has HCM, in which the heart muscle thickens and can stiffen, making it harder for the heart to pump blood. Most people with the condition have obstructive HCM, in which blood flow from the left ventricle to the aorta is impeded. These patients are at risk for life-threatening arrhythmias as well.
Current medicines often don't work, don't target specific characteristics of the condition, or aren't well tolerated by patients.
A phase 3 study, EXPLORER-HCM, tested a first-in-class HCM medicine, mavacamten — which targets cells involved in the heart muscle's ability to contract — in patients with symptomatic, obstructive HCM. The study, involving 68 heart clinics in 13 countries, found that among 251 patients, those who received the drug rather than a placebo were more likely to show improvements in measurements of cardiac function, exercise performance, NYHA functional class, symptoms and health status.
The benefit of mavacamten over placebo was apparent regardless of patient age, gender, body mass index, use of beta blockers and baseline measurements of health and well-being, the research team reported in The Lancet.
More treatment isn't necessarily better treatment in coronary heart disease
When the coronary arteries become progressively narrowed, blood flow to the heart is inadequate, a clinical situation known as coronary ischemia. Until recently, doctors lacked clarity on how best to treat moderate or severe ischemia, in terms of timing and extent of therapy, in patients with stable coronary disease.
But a massive international trial explored whether early, aggressive care involving coronary angiography to visualize reduced blood flow to the heart, plus bypass surgery or coronary intervention to improve blood flow when needed, could prevent more heart problems and heart-related deaths than could initial treatment with medicines alone.
The trial, known as ISCHEMIA, encompassed more than 5,000 patients in 37 countries. Half the patients were assigned to the aggressive care, and half started with a medicines-only approach. Patients in both groups were about as likely to have any of the measured outcomes, which included heart attack; hospitalization for unstable angina, heart failure or after cardiac arrest; and death from cardiovascular causes.
A related trial, ISCHEMIA-CKD, addressed coronary ischemia treatment in patients with chronic kidney disease, which affects roughly 14% of Americans. More than two-thirds of people 66 and older with chronic renal disease have cardiovascular disease. Forty percent have heart disease caused by plaque buildup in the arteries.
In the trial, among 777 patients with severe loss of kidney function — defined in as an estimated glomerular filtration rate below 30 ml/min/1.73m2 — and moderate or severe ischemia, those treated more aggressively had about the same risk of dying or having heart attacks as those treated just with medicines. Also, the more aggressive approach was linked to more than triple the risk of stroke.
Both studies appeared in the New England Journal of Medicine.
New findings may reshape the first line in the treatment of atrial fibrillation
Two studies described in the New England Journal of Medicine suggested that more active treatment strategies within a year of diagnosis can moderate the grave health consequences of atrial fibrillation, an irregular heartbeat originating in the atrium of the heart.
One international trial, EAST-AFNET 4, involved nearly 2,800 patients with cardiovascular disease and recently diagnosed AFib. Half received usual care and symptom management.
But those whose early treatment included restoring the heart to a normal rhythm were 21% less likely to have a stroke; be hospitalized with heart attack, related conditions or worsening heart failure; or die from heart disease. Rhythm control therapy included use of antiarrhythmic drugs and ablation, which scars heart tissue to disrupt electrical signals and correct the rhythm.
The second study, called EARLY-AF and described at the AHA's virtual Scientific Sessions 2020, involved 300 patients with symptomatic but untreated AFib. Initial treatment with catheter balloon cryoablation, which freezes damaged heart cells, was more effective than antiarrhythmic drugs in preventing future AFib-related problems.
America has a growing hypertension problem
While overall prevalence of hypertension has crept up to 46% in recent years, recent studies highlight the threat of high blood pressure in pregnancies, a broader struggle to control the condition and gaps in scientists' understanding of its underpinnings.
In a nationwide study published in the Journal of the American College of Cardiology, researchers calculated that women's rates of pre-pregnancy hypertension had nearly doubled from 2007 to 2018 in both urban and rural women, affecting more than 77,000 births and potentially fueling U.S. maternal mortality rates, among the highest in developed nations. Hypertension is a key risk factor for cardiovascular disease, which is the leading cause of pregnancy-related death.
Another study, encompassing two decades and over 18,000 people, found that after improving from 2000 to 2008 and then leveling off, the proportion of all Americans with controlled hypertension appears to have declined by 2018 — leaving more patients with uncontrolled blood pressure at risk for cardiovascular, kidney, vision and other health problems.
In this study about 44% of U.S. adults with hypertension had the condition controlled in 2017-18, investigators reported in the Journal of the American Medical Association. Rates of control among Black, Hispanic and Asian populations lagged behind those of whites.
A third, foundational study suggests that a rarely diagnosed condition called primary aldosteronism — a disorder involving increased secretion of a hormone called aldosterone that can elevate blood pressure — is greatly underrecognized.
The study, published in the Annals of Internal Medicine, tested over 1,000 patients at four U.S. academic medical centers. Not only was primary aldosteronism more prevalent than expected, but researchers found a "continuum" of aldosterone overproduction that paralleled increasing hypertension severity among people with normal blood pressure, untreated stage 1 and 2 hypertension, and treated, resistant hypertension. This suggests a potential role of aldosterone in high blood pressure that has no apparent cause.
Sometimes a diabetes drug isn't just a diabetes drug
That appears to be the case with a class of medicines called SGLT2 inhibitors, which are used to treat Type 2 diabetes but also can reduce serious renal problems and heart failure hospitalizations.
Studies in 2020 highlighted these benefits of kidney function preservation and reduction in heart failure hospital visits regardless of whether participants had Type 2 diabetes, suggesting the drugs could change the landscape in treating patients without diabetes with those conditions.
One trial, DAPA-CKD, was halted early because the results clearly showed improvement among the chronic kidney disease patients on the SGLT2 inhibitor dapagliflozin, compared with placebo. The 4,304 participants, about one-third of whom did not have diabetes, were followed for a median period of 2.4 years.
Among the people given the placebo, 14.5% experienced a steep, sustained decline in kidney function, end-stage kidney disease or death from kidney or cardiovascular causes. That compared with just 9.2% of the patients given dapagliflozin, scientists wrote in the New England Journal of Medicine.
A second article in the same journal issue describes similar success with the SGLT2 inhibitor empagliflozin in patients with heart failure.
Over 3,700 people received empagliflozin or a placebo on top of usual heart failure care for a median period of 16 months. About 1 in 4 patients in the placebo group were hospitalized for worsening heart failure or died of cardiovascular illness, compared with only 1 in 5 participants receiving the drug.
Findings from two other trials, presented at Scientific Sessions and published in the New England Journal of Medicine, showed benefits of another SGLT2 inhibitor, sotagliflozin.
The SCORED trial found the drug reduces the risk of hospitalization and urgent visits for heart failure as well as death from heart attack or stroke among patients with Type 2 diabetes and chronic kidney disease. In that study, involving over 10,000 people, those receiving sotagliflozin had a 26% lower risk of death from cardiovascular causes or hospitalization/urgent care for heart failure.
The second study, SOLOIST-WHF, reported a decrease of 33% in those three outcomes combined. The research included more than 1,200 patients with Type 2 diabetes and recently worsening heart failure that required hospitalization.
Groundbreaking therapies aim to tame troublesome cholesterol levels
Three such therapies were described in the New England Journal of Medicine.
One uses RNA interference, a cutting-edge approach that deploys molecules called small interfering RNAs (siRNA) to switch gene expression on and off. In a pair of trials known as ORION-10 and ORION-11, an siRNA called inclisiran on average halved participants' elevated blood levels of LDL, the so-called bad cholesterol. LDL levels in a placebo group rose slightly.
Together the studies involved nearly 3,200 patients, most of whom had cardiovascular disease due to plaque buildup in the arteries.
Another study focused on high levels of an LDL variant called lipoprotein(a), known as Lp(a), which has been linked to cardiovascular illness including heart attack, aortic stenosis and stroke. Trying to lower them has been a challenge: Lp(a) concentrations are largely set by genetics and unaffected by lifestyle.
But researchers showed that Lp(a) could be reduced therapeutically. In an international study, investigators at 30 sites tested different doses of AKCEA-APO(a)-LRx, a type of treatment called an antisense oligonucleotide, against a placebo.
Nearly 300 patients with heart disease and high Lp(a) received the therapy for six to 12 months. The higher the level of the therapy given, the more patients' average Lp(a) dropped.
Researchers also are logging progress in treating a rare, deadly condition called homozygous familial hypercholesterolemia (HoFH). A genetic defect inherited from both parents results in extremely high, unmanageable levels of LDL, resulting in heart disease at a young age.
In the ELIPSE HoFH trial, an international research team described how LDL levels plummeted 47% over 24 weeks — from an average of 260 to about 135 ml/dL— among 43 people receiving the biologic therapy evinacumab, a monoclonal antibody.
Stroke prevention studies highlight diverse tactics
One approach targets carotid stenosis, a plaque buildup inside arteries in the neck that is a major cause of stroke.
Carotid stenosis often is treated with direct surgery on the affected carotid artery. The new study, dubbed ROADSTER 2, was conducted at 43 sites in nearly 700 patients who weren't surgery candidates.
Doctors tested a minimally invasive procedure called transcarotid artery revascularization (TCAR). In TCAR, a sheath is placed in the carotid artery through a small neck incision. Blood flow is temporarily reversed to ensure breakaway plaque isn't carried to the brain. The vessel is opened with a balloon catheter, and a stent is placed to improve blood flow.
Just 1.7% of patients whose care followed the study protocol had a stroke or heart attack or died within 30 days of the procedure, researchers reported in the American Stroke Association/American Heart Association journal Stroke. The results compare favorably with data from studies of open surgery and another minimally invasive procedure, which accesses the carotid through the femoral artery, the scientists said.
Another study, nicknamed THALES and published in the New England Journal of Medicine, examined how effectively aspirin, plus another drug that inhibits blood clotting, might prevent future strokes in patients who'd just had a mini-stroke (TIA) or a mild to moderate ischemic stroke.
In about 11,000 patients receiving aspirin alone or the drug ticagrelor plus aspirin, the combination treatment was linked to a 17% lower risk of death or any type of stroke within 30 days.
People who've had a recent ischemic stroke or mini-stroke and have plaque buildup affecting blood flow to the brain or heart might also benefit from lower target levels for LDL, another study in the New England Journal of Medicine reported.
Researchers in France and South Korea followed 2,860 patients on cholesterol-lowering therapy with a statin, ezetimibe or both, for a median period of 3.5 years. Patients with a target LDL level below 70 mg/dL had a 22% lower risk than those with a target range of 90-110 of having a major cardiovascular event such as an ischemic stroke, heart attack or death from cardiovascular causes.
There are many steps to take toward better health
Two recent studies highlight the potential benefit of high daily step counts.
In one, involving 4,840 people, taking 8,000 steps a day was associated with half the odds of dying over an average 10 years of follow-up, compared with 4,000 steps a day. But more vigorous or intense stepping didn't seem to affect death risk.
The research, published in the New England Journal of Medicine, involved U.S. adults 40 and older who wore an accelerometer for up to seven days — on average, more than 14 hours a day.
The other study, published in the AHA journal Circulation Research, deployed smartwatches to overcome the challenge of accurately tracking physical activity for long periods.
Researchers focused on about 900 people as part of the expansive Framingham Heart Study. For every 1,000 daily steps a watch tracked, the participant's predicted cardiovascular risk for the next decade was 0.18% lower. The effect was smaller in women (0.13%) than in men (0.28%) and disappeared in women when BMI was taken into account.
Science is just beginning to shed light on COVID-19's mysteries
One key question has been whether ACE inhibitors and ARBs, two types of drugs for high blood pressure and heart failure, might leave patients more vulnerable to the virus — or, alternately, might help protect them from its ravages.
There are rationales for both possibilities. But analyses of over 1,100 COVID-19 patients with hypertension hospitalized in China found lower rates of death from any cause among those receiving ACEI/ARB drugs than those given other blood pressure drugs in the hospital and in those not given hypertension medications. The results, published in Circulation Research, appeared early in the pandemic, helping clinicians worldwide in managing their patients.
Meanwhile, the AHA's COVID-19 Cardiovascular Disease Registry is answering other vital questions.
In a study of patients at 88 hospitals in the registry, researchers found Hispanic and Black patients had a disproportionately high risk of landing in the hospital with COVID-19. Hispanics accounted for one-third of hospitalized COVID-19 patients but just 9% of the population in neighborhoods nearby. One-fourth of the patients were Black, compared with fewer than 11% of residents nearby.
Another study found that obesity posed a higher risk of complications and death in COVID-19 patients, regardless of age. Those with severe obesity — a BMI of 40 or higher — had over double the risk of being put on a ventilator and a 26% higher risk of in-hospital death compared with normal-weight patients.
Both registry studies were presented at the virtual Scientific Sessions and published in the AHA journal Circulation.
Finally, don't forget the flu
It's hard on the heart.
In a study of over 80,000 U.S. patients hospitalized in 2010-18 with lab-confirmed influenza, almost 12% had an acute cardiac event, such as acute heart failure, heart attack or a hypertensive crisis, before discharge.
Among those patients, 31% required intensive care and 7% died, researchers wrote in the Annals of Internal Medicine, noting that the findings emphasize the importance of increasing flu vaccination rates.
At Scientific Sessions and in the Journal of the American Medical Association, describing a study of 5,000 North American patients with heart disease, researchers reported that a high-dose, trivalent flu vaccine was no more effective over three flu seasons than the standard-dose vaccine in lowering risk of death or hospitalization due to heart- or lung-related illnesses.
