IHD , without RIsk Factors( SMuRF-Less )but Inflamed: Is Inflammation the Missing Link in Women’s Heart Disease?
Is Inflammation the Missing Link in Women’s Heart Disease?
Source: Medscape Medical News
Date: January 8, 2026
Key Points
• Major burden in women:
• Despite this, women represent <40% of participants in cardiovascular clinical trials.
• The SMuRF-less paradox:
• Many women experience acute myocardial infarction (AMI) without standard modifiable risk factors (SMuRFs) such as hypertension, diabetes, dyslipidemia, or smoking.
• SMuRF-less women have been shown to have up to threefold higher AMI mortality compared with men who have at least one traditional risk factor.
• Inflammation as the missing risk factor:
• New data presented at the European Society of Cardiology Congress and published in The European Heart Journal highlight high-sensitivity C-reactive protein (hsCRP) as a key predictor of risk.
• In 12,530 initially healthy women followed for 30 years, hsCRP >3 mg/L was associated with:
• 77% higher risk of coronary heart disease
• 52% higher risk of cardiovascular events
• 39% higher risk of stroke
• These associations persisted after adjustment for BMI and kidney function.
• HsCRP predicted first cardiovascular events more strongly than LDL-C or lipoprotein(a) in this population.
• From risk marker to treatment target:
• Reanalysis of the JUPITER trial showed that SMuRF-less but inflamed patients (hsCRP >2 mg/L) treated with rosuvastatin had a 38% reduction in major cardiovascular events compared with placebo.
• Clinical implications:
• Inflammation should be considered an independent cardiovascular risk factor, particularly in women.
• Measuring hsCRP may help refine risk assessment when traditional scores appear reassuring.
• Earlier statin therapy may be reasonable in SMuRF-less patients with elevated inflammation, even before overt disease develops.
• Expert perspective:
• Inflammatory states such as pregnancy complications, autoimmune and rheumatologic diseases may act as risk enhancers in women.
• When traditional risk factors fail to explain events, clinicians are urged to “look beyond cholesterol” toward inflammation.
Bottom Line:
For many women, cardiovascular risk may be driven less by classic factors and more by chronic vascular inflammation, positioning hsCRP as both a critical risk marker and a potential therapeutic guide.