The potential impact of residual inflammation and elevated Lipoprotein (a) levels in long-term cardiovascular patients' survival

Background Many patients with cardiovascular disease will remain at elevated 10-year risk, even with optimal treatment. Novel risk stratification approaches may be used to identify high-risk patients who can benefit from new interventions. High lipoprotein (a) [Lp(a)] and high-sensitivity C-reactive protein (hsCRP) may synergistically influence the long-term survival of these patients. Aim Investigate whether the synergistic impact of residual inflammation, evaluated by hsCRP, together with elevated Lp(a) levels, influences the long-term survival of cardiovascular patients. Methods We evaluated a cohort of 1,719 cardiovascular patients (mean age 53.3±7.8 years, 78.8% male) from our Research Unit dataset, discharged from the Cardiology Department between 2000 and 2018, with a long follow-up period of average 7.3±6.0 years. All relevant biochemical variables, including Lp(a) and hsCRP, were measured. Traditional and clinical risk factors were also determined. Afterwards, four groups were created according to Lp(a) and hsCRP levels above or below the median values: Group 1: Lp(a)≤13.48 mg/dL & hsCRP≤0.21 mg/dL, Group 2: Lp(a)≤13.48 mg/dL & hsCRP>0.21 mg/dL, Group 3: Lp(a)>13.48 mg/dL & hsCRP≤0.21 mg/dL, and Group 4: Lp(a)>13.48 mg/dL & hsCRP>0.21 mg/dL. Cox regression analysis and Kaplan-Meier survival analysis were employed to determine the combined effects of Lp(a) and hsCRP on the risk of all-cause cardiovascular events. Results Over an extended follow-up, patients experienced 696 cardiovascular events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, heart failure, transient ischemic attack, and stroke). The multivariate Cox regression analysis revealed that in the adjusted Group 4, the combination of Lp(a) and hsCRP exhibited a significant association with cardiovascular events (Group 4 versus Group 1: HR=1.248, 95% CI=1.002–1.554, p=0.048; Group 4 versus other groups: HR=1.256, 95% CI=1.077–1.464, p=0.004). Conclusion High levels of Lp(a) and hsCRP, synergistically, increase the risk of cardiovascular events over a long follow-up period, highlighting the importance of these two concurrent biochemical markers in the prognosis and management of these patients. Patients with low levels of these markers lose protection after fifteen years.