After a 30-year study, American researchers have suggested that inflammation could be a key factor in explaining why some women experience heart attacks and strokes – despite having none of the usual risk factors, reports The Independent.
Many women who have major cardiovascular events, like heart attacks and strokes, often do not present with what are thought to be typical risk factors like high blood pressure, high cholesterol, diabetes, or a history of smoking.
The latest insight comes from researchers presenting at the recent European Society of Cardiology (ESC) meeting in Madrid.
Published in the European Heart Journal, the three-decade study tracked 12 530 initially healthy women who lacked these traditional risk factors.
They had started the study with elevated levels of an inflammation marker called C-reactive protein, or CRP, as measured by a high-sensitivity test; 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 compared with women with lower CRP.
High levels on the high sensitivity test were defined as greater than three milligrams per litre of blood.
An observational study like this one can’t prove that inflammation caused the cardiovascular events. It is well known, however, that over time, even low levels of inflammation can promote the growth of plaques in arteries, loosen those plaques and trigger the blood clots that are the primary causes of heart attacks and strokes.
“Our data clearly show that apparently healthy women who are inflamed are at substantial lifetime risk,” said study leader Dr Paul Ridker of Mass General Brigham’s Heart and Vascular Institute.
“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,” he said.
Looking back at data from earlier randomised trials, his team also found that statin drugs can cut the risk of heart attack and stroke by more than one-third for women with inflammation who don’t have the usual cardiovascular risk factors.
While those with inflammation should aggressively initiate lifestyle and behavioural preventive efforts, statin therapy could also play an important role in helping reduce risk among these individuals, Ridker noted.
Study details
C-reactive protein and cardiovascular risk among women with no standard modifiable risk factors: evaluating the ‘SMuRF-less but inflamed’
Paul Ridker, Gemma Figtree, M Vinayaga Moorthy, Samia Mora, Julie Buring.
Published in the European Heart Journal on 29 August 2025.
Abstract
Background and Aims
Interventions in preventive cardiology traditionally focus on four standard modifiable cardiovascular risk factors (SMuRFs): hypertension, dyslipidaemia, diabetes mellitus, and smoking. Yet, a substantial proportion of incident cardiovascular events accrues for individuals with none of these factors, particularly among women for whom cardiovascular disease remains under-detected and under-treated. The utility of the inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) was evaluated to detect cardiovascular risk in SMuRF-less women participating in the prospective NIH-funded Women’s Health Study.
Methods
High-sensitivity C-reactive protein was measured at baseline among 12 530 initially healthy American women with no standard modifiable risk factors who were followed over 30 years for first major adverse cardiovascular events (myocardial infarction, coronary revascularization, ischaemic stroke, or cardiovascular death). Hazard ratios (HRs) and 95% confidence intervals (95% CI) for incident coronary heart disease (CHD), ischaemic stroke, and total cardiovascular events were calculated across quintiles of hsCRP, along with 30-year cumulative incidence curves. Hazard ratios were also computed according to common clinical thresholds of hsCRP, according to standard deviation change in hsCRP, and as a continuous variable in penalised spline regression models.
Results
During 30-year follow-up, 973 first major cardiovascular events accrued. Median baseline hsCRP was significantly higher among SMuRF-less women who subsequently suffered a cardiovascular event when compared with those who did not (median hsCRP 2.22 vs 1.50 mg/L, P < .0001). In age-adjusted analyses, the HRs for the primary endpoint of incident CHD from lowest (referent) to highest levels of hsCRP at study entry were 1.0 (referent), 1.24, 1.41, 1.57, and 2.23 (P-trend < .0001) such that CHD risk over 30 years increased 21% for each increasing quintile of hsCRP (age-adjusted HR 1.21, 95% CI 1.13–1.29, P < .0001). Corresponding HRs for the top vs bottom quintile of hsCRP were 1.69 (95% CI 1.16–2.47) for ischaemic stroke and 1.74 (95% CI 1.42–2.14) for total cardiovascular disease events. Using common clinical hsCRP thresholds, SMuRF-less women with hsCRP > 3 mg/L had a 77% higher risk of CHD events, a 39% higher risk of ischaemic stroke events, and a 52% higher risk of total cardiovascular disease events when compared with those with hsCRP < 1 mg/L. Spline analyses demonstrated linear association with risk across the spectrum of hsCRP values. Hazards were moderately attenuated after additional adjustment for body mass index and estimated glomerular filtration rate [covariate-adjusted CHD HR 1.86 (95% CI 1.35–2.58, P = .0002) for comparison of the top vs bottom quintile of hsCRP and 1.52 (95% CI 1.20–1.92, P = .0006) for comparison of those with hsCRP > 3 mg/L to those < 1 mg/L].
Conclusions
Over a 30-year horizon, cardiovascular events commonly occur among ‘SMuRF-less but inflamed’ women who are otherwise missed by current screening algorithms, a clinically important observation given recent trial data demonstrating that statin therapy reduces risk by 38% among such individuals.
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