Inflammation may explain why women with no standard modifiable risk factors have heart attacks and strokes: ESC Study

Cardiologists have long known that up to half of all heart attacks and strokes occur among apparently healthy individuals who do not smoke and do not have high blood pressure, high cholesterol, or diabetes, the “standard modifiable risk factors” which doctors often call “SMuRFs.” How to identify risk among the “SMuRF-Less” has been an elusive goal in preventive cardiology, particularly in women who are often under-diagnosed and under-treated. A new study by Mass General Brigham researchers that leverages data from the Women’s Health Study has found hsCRP-a marker of inflammation-can help identify women who are at risk but are missed by current screening algorithms. Results are presented at a late-breaking clinical science session at the European Society of Cardiology Congress (ESC) and simultaneously published in The European Heart Journal.

“Women who suffer from heart attacks and strokes yet have no standard modifiable risk factors are not identified by the risk equations doctors use in daily practice,” said Paul Ridker, MD, MPH, a preventive cardiologist at Mass General Brigham’s Heart and Vascular Institute. “Yet our data clearly show that apparently healthy women who are inflamed are at substantial lifetime risk. We should be identifying these women in their 40s, at a time when they can initiate preventive care, not wait for the disease to establish itself in their 70s when it is often too late to make a real difference.”

As part of the federally funded study, researchers studied 12,530 initially healthy women with no standard modifiable risk factors who had the inflammatory biomarker hsCRP measured at study entry and who were then followed over 30 years. Despite the lack of traditional risks, women who were inflamed as defined by hsCRP levels > 3 mg/L had a 77% increased lifetime risk of coronary heart disease, a 39% increased lifetime risk of stroke, and a 52% increased lifetime risk of any major cardiovascular event.

Additionally, researchers released a new analysis of randomized trial data showing that “SMuRF-Less but Inflamed” patients can reduce their risk of heart attack and stroke by 38% using statin therapy.

“While those with inflammation should aggressively initiate lifestyle and behavioral preventive efforts, statin therapy could also play an important role in helping reduce risk among these individuals,” said Ridker.

Reference:

Paul M Ridker, Gemma A Figtree, M Vinayaga Moorthy, Samia Mora, Julie E Buring, C-reactive protein and cardiovascular risk among women with no standard modifiable risk factors: evaluating the ‘SMuRF-less but inflamed’, European Heart Journal, 2025;, ehaf658, https://doi.org/10.1093/eurheartj/ehaf658