Prognostic impact of microvascular dysfunction and systemic inflammation in women with chronic heart failure

Background Microvascular dysfunction and systemic inflammation are increasingly recognized as key contributors to chronic heart failure (CHF), particularly in women, who often present with preserved ejection fraction and cardiometabolic comorbidities. However, their combined prognostic significance remains insufficiently defined. This study evaluated the association between microvascular dysfunction, inflammatory biomarkers, and clinical outcomes in women with CHF. Material and methods A prospective cohort study included 350 women with stable CHF (mean age 63.4 ± 10.7 years; 52% HFpEF, 31% HFmrEF, 17% HFrEF). Patients underwent echocardiography, 6-minute walk test (6MWT), and assessment of coronary microvascular function using coronary flow reserve (CFR) measured by Doppler echocardiography. Systemic inflammation was evaluated using high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and neutrophil-to-lymphocyte ratio (NLR). Microvascular dysfunction was defined as CFR <2.0. The primary endpoint was cardiovascular death or heart failure hospitalization during a median 20-month follow-up. Multivariable Cox regression, Kaplan–Meier analysis, and ROC curves were performed. Results Microvascular dysfunction was present in 162 patients (46.3%) and was associated with higher inflammatory markers (hs-CRP: 5.1 ± 2.3 vs 3.4 ± 1.8 mg/L; IL-6: 6.8 ± 2.5 vs 4.9 ± 2.1 pg/mL; NLR: 3.9 ± 1.6 vs 2.8 ± 1.2; all p < 0.001). CFR correlated inversely with IL-6 (r = −0.42, p < 0.001) and hs-CRP (r = −0.37, p < 0.001). During follow-up, the primary endpoint occurred in 104 patients (29.7%), with higher event rates in those with impaired CFR (41% vs 20%, log-rank p < 0.001). After adjustment for age, ejection fraction, NT-proBNP, diabetes, and renal function, independent predictors included CFR <2.0 (HR 1.92, 95% CI 1.32–2.79, p < 0.001), IL-6 (HR 1.36, p = 0.001), hs-CRP (HR 1.28, p = 0.006), and 6MWT distance (HR 0.81 per 50 m, p = 0.004). NT-proBNP showed weaker predictive value (HR 1.18, p = 0.04). A combined model integrating CFR and inflammatory biomarkers demonstrated superior prognostic discrimination compared with NT-proBNP alone (AUC 0.84 vs 0.71, p = 0.002), with significant net reclassification improvement (NRI 0.29, p = 0.01). Conclusions Microvascular dysfunction is common in women with CHF and closely linked to systemic inflammation. The combined assessment of coronary microvascular function and inflammatory biomarkers independently predicts adverse outcomes and improves risk stratification beyond conventional markers. These findings highlight the importance of the inflammation–microvascular axis in heart failure pathophysiology in women and support targeted therapeutic strategies.