Acute MI Patients Without Standard CVD Risk Factors at Higher Risk of Death

Patients without standard modifiable cardiovascular risk factors (SMuRFs) who present with acute MI are at an increased risk of dying when compared with those who present with at least one risk factor, according to an analysis published recently in the Journal of the American Heart Association.

Overall, the mortality risk was two to three times higher in acute MI patients without modifiable CVD risk factors, such as high cholesterol or blood pressure, an event rate investigators believe may be driven by lower use of guideline-directed medical therapy (GDMT).

“Especially when it’s a younger patient, those without standard modifiable cardiovascular risk factors are much less likely to get the standard of care for acute coronary syndrome,” senior investigator Arman Qamar, MD, MPH (NorthShore University Health System, Evanston, IL), told TCTMD. “That might be expected—young patient, no risk factors—and that might lead to delays [in treatment]. The challenge is how to address that.” 

Qamar said that while the majority of patients who present with acute MI have at least one standard modifiable cardiovascular risk factor, most physicians, at least anecdotally, have encountered so-called SMuRF-less patients—people in seemingly good health if judged by traditional risk factors. “These patients are quite surprising when you see them,” he said.

The prevalence of patients without SMuRFs is variable, with registry studies suggesting it ranges anywhere from 5% to 25%. In the YOUNG-MI registry, for example, 17% of patients younger than 50 years who presented with an acute MI lacked traditional risk factors. Data from an Australian registry showed an increasing trend in STEMI patients without traditional risk factors, with the proportion rising from 14% in 1999 to 23% in 2017. Australian researchers have shown previously that these SMuRF-less patients with STEMI are at a higher risk of early and late mortality.

Much of the variance in prevalence is likely explained by how risk factors are captured in the various registries, said Qamar.

False Reassurances With Zero Risk Factors

Using data from the Atherosclerosis Risk in Communities (ARIC) study, which includes four geographically diverse regions of the US, researchers led by Zainali Chunawala, MBBS (UT Southwestern Medical Center, Dallas, TX), identified 20,569 patients hospitalized for acute MI between 2000 and 2014. Of these, 3.6% did not smoke and had no history of hypertension, hypercholesterolemia, or diabetes. Hypertension and diabetes were classified based on a diagnosis in the medical history, while hypercholesterolemia was defined by the use of lipid-lowering therapies.

Patients without standard modifiable risk factors were more likely to be female and white, although the mean age of those with and without SMuRFs was 60 years old. Those without risk factors were less likely to present with chest pain and STEMI but were more likely to present with ventricular fibrillation. They were also less likely to have a prior MI, stroke, revascularization, or history of kidney disease.

Those who presented without any risk factors were less likely to receive aspirin, antiplatelet therapy, or beta-blockers during the hospitalization and were less likely to undergo invasive angiography or coronary revascularization compared with patients with at least one risk factor.

At 28 days, patients without SMuRFs had a significantly higher rate of all-cause mortality compared with those with at least one risk factor (16% vs 6%; P < 0.0001). At 1 year, the death rate was also significantly higher in those who presented without risk factors (24% vs 13%; P = 0.0006). After adjusting for age, race, sex, year of admission, geographic region, and other variables, acute MI patients without risk factors had a higher likelihood of death at 28 days (OR 3.23; 95% CI 1.78-5.88) and 1 year (HR 2.09; 95% CI 1.29-3.37).

Over time, the risk of death at 28 days increased significantly among those who lacked risk factors (up from 7% in 2000-2004 to 27% in 2010-2014) but declined for those who presented with traditional risk factors. One-year mortality rates also increased over time for those presenting without risk factors but the change was more gradual and did not reach statistical significance.

The higher risk of death in SMuRF-less patients with acute MI might be attributable to delays in GDMT during the hospitalization, said Qamar. However, he pointed that patients without risk factors have likely flown under the radar of their primary care physicians and not received any type of risk mitigation.

“For patients with traditional risk factors, they get put on statins, blood pressure-lowering medications, or aspirin,” said Qamar. “They are told they have risk factors and that they should be exercising and doing all the right things. They might have good behaviors, disease-modifying behaviors, integrated into their life before they come in with acute MI. The problem with people without conventional risk factors is that they may be getting a false reassurance.”     

Current clinical guidelines do not recommend screening with coronary artery calcium or CT angiography in patients with low risk scores, the researchers point out in their paper, but these new findings may “warrant a greater emphasis on modifying existing imaging guidelines to include patients at low overall risk.”

Lots of Underrecognized Risk Factors

To TCTMD, Qamar stressed that while high blood pressure, high LDL-cholesterol level, diabetes, and smoking are important CVD risk factors, there’s accumulating evidence highlighting the role of emerging or novel risk factors.

For example, lipoprotein(a) is now recognized as an important predictor of risk, with several Lp(a)-lowering drugs now in development, among them pelacarsen (Ionis Pharmaceuticals/Novartis). Increased inflammation, as measured by high-sensitivity C-reactive protein (CRP) and other biomarkers, is also a risk factor for cardiovascular disease. Clonal hematopoiesis of indeterminate potential (CHIP), which is less well-known than Lp(a) and CRP, has also been shown to be associated with increased CVD risk beyond atherosclerosis. CHIP is a novel risk factor that captures age-related clonal expansion of blood stem cells with leukemia-associated mutations. In addition, various polygenic risk scores have been developed to capture the risk associated with known genetic variants across the genome.

Moreover, there are other factors, such as air pollution, stress, sleep duration, and substance abuse, that have been shown to be associated with heightened CVD risk.

“Some of these risk factors are underappreciated,” said Qamar. “What we knew in 1990 was good, but we have to remember that in the last several decades the field has changed.” Still, he is optimistic cardiology is moving into the future with CVD risk prediction and is hopeful that advances in artificial intelligence will help physicians digest the wealth of data to identify the seemingly healthy patients who may be at risk.