Silent coronary disease ‘SMuRFs’ the new unmet need: Prof Figtree

Risk factors

By Mardi Chapman

20 Jun 2022

The substantial and growing proportion of patients who develop STEMI in the absence of standard modifiable cardiovascular risk factors (SMuRFs) is proving a challenge for the cardiac community.

As previously reported in the limbic, patients with STEMI in the absence of SMuRFs have poorer outcomes – increased in-hospital and 30-day all-cause and cardiovascular mortality – which warrants a concerted effort at identifying the underlying pathophysiologic mechanisms at play.

In a new study led by Professor Gemma Figtree, individual patient-level data from 10 randomised STEMI with confirmed CAD trials was interrogated for new clues.

In the cohort of 2,862 patients, 18.3% were SMuRF-less and 81.7% had at least one SMuRF of dyslipidaemia, hypertension, diabetes mellitus or smoking.

The study, published in JACC: Cardiovascular Interventions, found SMuRF-less patients had higher rates of TIMI 0/1 flow pre-PCI compared with SMuRF-positive patients (72% vs 64%, P = 0.0007).

“This association between TIMI flow and SMuRF-less status remained significant after adjusting for age, sex, and LAD versus non-LAD as the culprit lesion (P = 0.011).”

Imaging found no significant association between SMuRF-less status and infarct size, MVO, or LVEF assessed at a median of 4 days post-PCI.

Unlike the SWEDEHEART registry study, SMuRF-less patients in the current study had similar 30-day and 1-year rates of mortality, reinfarction, and hospitalisation for heart failure.

“These discrepancies are likely caused by selection bias as well as greater adherence to guideline-recommended therapies, including those for secondary prevention, within randomised trials compared with what occurs in the “real world,” the study authors said.

They added that medications including statins, ACE inhibitors/ARBs and beta blockers were therefore still important in patients without SMuRFs.

“The substantial proportion of patients who develop STEMI despite no previously diagnosed SMuRF warrants further investigation of potential mechanisms to help guide strategies for both primary and secondary prevention in this patient population,” they wrote.

Beyond traditional risk factors

Professor Figtree told the limbic that primary care had done a creditable job preventing heart attacks in people with traditional risk factors.

“But what it’s doing is highlighting the fact that now a quarter of our patients actually are having heart attacks without a single risk factor that would have flagged them as at risk with their GP.”

“Whilst we have not won the battle at a community level to help people maximise their lifestyle opportunities and really address the modifiable risk factors we know about, we shouldn’t be blaming the patient every time someone has a heart attack because it’s not always their fault. It’s not always their lifestyle. There are huge amounts of the biology that are missing in all of this.”

Professor Figtree, from the Kolling Research Institute at the University of Sydney, emphasised that patients without traditional risk factors still benefited from medications such as statins.

She said there was strong data that people who have a heart attack in the setting of a lower cholesterol receive just as good a benefit from statins, if not more.

“Using the big cholesterol trials data, they actually say that the relative risk reduction with statins in a secondary prevention setting is actually greater in people with a low Framingham risk score that developed atherosclerosis.”

“What’s really interesting here is the susceptibility of the individual’s blood vessels to getting atherosclerosis and coronary disease is actually heightened in these individuals against a lower risk factor burden, or at least the lower burden of risk factors we understand about.”

“We can address the unmet need… there’s this whole population of people sitting in our community with silent coronary disease, that we’re not picking up with traditional risk factors, that could benefit massively from getting the same preventative management that would actually completely halt progression of their disease.”

“The holy grail of all of this is ultimately finding a marker …We’re actually trying to pick up the earliest coronary disease and give effective treatment to people to completely abolish the risk.”

A Comment article in the journal said the study’s findings underline the need for “new prediction models to estimate the risk of fatal and non-fatal CV events including additional clinical variables and biomarkers”.

“The inclusion of plasma biomarkers such as natriuretic peptides, high-sensitivity troponins, and high-sensitivity C-reactive protein is reported to improve the prediction of coronary artery disease in subjects without baseline CV disease, and the measurement of their levels could represent a first step toward a more thorough approach in both primary and secondary CV prevention,” it said.

“In the next years, the development of novel technologies with the purpose to achieve the spreading of integrated panels of genes, biomarkers, and proteins may contribute to further refine CV risk assessment.”

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