| Summary: | Abstract Aim Current study was to evaluate relationship between baseline serum lipoprotein (a) [Lp(a)] level and prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and to explore whether the relationship would be modified by baseline high‐sensitivity C‐reactive protein (Hs‐CRP) level. Methods and results This is an observational prospective study. HFrEF patients from outpatient clinic were consecutively recruited (n = 362). Based on Lp(a) cutoff (30 mg/dL), patients were divided into normal and high Lp(a) groups; and based on Hs‐CRP cutoff (3 mg/dL), patients were divided into low‐degree and high‐degree groups. The 1 year rate of HF rehospitalization was similar between these two groups (22.7% vs. 24.1%, P = 0.18), while the 1 year rate of cardiovascular mortality was higher in Lp(a) ≥ 30 mg/dL versus Lp(a) < 30 mg/dL groups (20.3% vs. 13.3%, P = 0.009), as was composite endpoint (44.4% vs. 36.0%, P < 0.001). After adjusting for covariates, elevated Lp(a) level remained associated with a higher risk of cardiovascular mortality [hazard ratio (HR) 1.22 and 95% confidence interval (CI) 1.04–1.64, P = 0.02] and composite endpoint (HR 1.38 and 95% CI 1.16–2.01, P = 0.006). In Hs‐CRP ≥ 3 mg/dL group, elevated Lp(a) level was associated with HF rehospitalization, cardiovascular mortality, and composite endpoint, which was not observed in Hs‐CRP < 3 mg/dL group. The association was greater for cardiovascular mortality (P‐interaction = 0.04) and composite endpoint (P‐interaction = 0.02) in Hs‐CRP ≥ 3 mg/dL versus Hs‐CRP < 3 mg/dL groups. Conclusion Elevated Lp(a) level is associated with higher risk of cardiovascular mortality in HFrEF patients, which might be due to enhanced systemic inflammation.
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