Abstract
Background
There is strong evidence linking high lipoprotein(a) (Lp(a)) to development of incident cardiovascular disease (CVD), but it is not clear whether Lp(a) is associated with risk of recurrent CVD events in individuals from the general population with preexisting CVD. This is of importance as the first drugs specifically aimed at lowering Lp(a) are currently in development, and these would likely be used primarily in individuals with established CVD for secondary prevention of recurrent CVD events.
Purpose
We tested the hypothesis that high concentrations of Lp(a) are associated with high risk of recurrent CVD in individuals from the general population with preexisting CVD.
Methods
From the Copenhagen General Population Study (CGPS) (2003–2015) of 58,527 individuals with measurements of Lp(a) at baseline, 2,527 aged 20–79 with a history of CVD were studied. The primary endpoint was major adverse cardiovascular event (MACE). We also studied 1,115 individuals with CVD at baseline from the Copenhagen City Heart Study (CCHS) (1991–1994) and the Copenhagen Ischemic Heart Disease Study (CIHDS) (1991–1993).
Results
During a median follow-up of 5 years (range: 0–13, 13,974 person-years), 493 individuals (20%) experienced a MACE in the CGPS. MACE incidence rates per 1,000 person-years were 29 (95% CI: 25–34) for individuals with Lp(a) <10mg/dL (<18nmol/L), 35 (30–41) for 10–49mg/dL (18–104nmol/L), 42 (34–51) for 50–99mg/dL (105–213nmol/L), and 54 (42–70) for ≥100mg/dL (≥214nmol/L) (see Figure). Compared to individuals with Lp(a) <10mg/dL (<18nmol/L), the MACE incidence rate ratios were 1.21 (0.98–1.50) for 10–49mg/dL (18–104nmol/L), 1.43 (1.12–1.82) for 50–99mg/dL (105–213nmol/L), and 1.85 (1.38–2.49) for ≥100mg/dL (≥214nmol/L). Independent confirmation was obtained in individuals from the CCHS and CIHDS with MACE incidence rates per 1,000 person-years of 94 (95 CI: 84–106) for individuals with Lp(a) <10mg/dL (<18nmol/L), 115 (103–129) for 10–49mg/dL (18–104nmol/L), 134 (115–156) for 50–99mg/dL (105–213nmol/L), and 140 (116–169) for ≥100mg/dL (≥214nmol/L).
Conclusion
High concentrations of Lp(a) are associated with high risk of recurrent CVD in individuals from the general population with preexisting CVD. This points to a possible unmet need for secondary prevention in individuals with increased Lp(a), and such individuals could be a target group for upcoming randomized cardiovascular outcome trials.
Acknowledgement/Funding
The Novo Nordisk Foundation, Herlev and Gentofte Hospital, Chief Physician Johan Boserup and Lise Boserup's Fund
Lipoprotein(a) and mortality—a high risk relationship
