Residual atherosclerotic risk in older patients with atherosclerotic cardiovascular disease: where inflammation meets lipoprotein(a)

Abstract Background Inflammation and hyperlipidaemia contribute with similar magnitude to the risk of future atherothrombotic events. However, the relative importance of high-sensitivity CRP (hsCRP) and lipoprotein(a) (Lp[a]) as determinants of risk of major adverse cardiovascular events (MACE) are not well defined among patients aged 75 years or older with established atherosclerotic cardiovascular disease (ASCVD). Methods The present study prospectively enrolled 2,333 patients aged 75 years or older diagnosed with ASCVD with measurement of hsCRP and Lp(a) at Fuwai Hospital. The primary endpoint was MACE, defined as a composite of all-cause death, myocardial infarction (MI), stroke or ischaemia-driven coronary revascularisation. Results The median follow-up time was 3.0 years (interquartile range [IQR]: 2.5–3.2 years). hsCRP was significantly associated with an increased risk of MACE (adjusted hazard ratio [aHR]: 1.05, 95% confidence interval [CI]: 1.03–1.08 per 1 mg/l increment, P < 0.001; highest versus lowest quartile: aHR: 1.70 [1.22–2.38]), whereas there was no significant association between Lp(a) and MACE risk (aHR: 1.02 [0.98–1.06] per 10 mg/dl increment, P = 0.341; highest versus lowest quartile: aHR: 1.06 [0.77–1.47]). Risks of MACE were significantly higher in participants with hsCRP ≥2 mg/l than in those with hsCRP <2 mg/l, irrespective of Lp(a) strata (aHR: 1.41 [1.12–1.79]; P = 0.004). Concomitant elevation of hsCRP (≥2 mg/l) and Lp(a) (≥30 mg/dl) was associated with the greatest risk of MACE (aHR, 1.54 [1.13–2.12]; P = 0.007). Conclusions Inflammation assessed by hsCRP predicted risk of future cardiovascular events more strongly than Lp(a) in patients aged 75 years or older with established ASCVD. These results provided real-world evidence on older patients potentially benefit by targeted anti-inflammatory strategies for secondary ASCVD prevention.