Lipoprotein(a), or Lp(a), levels are primarily determined by genetics, and unlike many other cardiovascular risk factors, they remain unaffected by lifestyle changes, physical activity, or diet. Numerous epidemiological studies have identified Lp(a) as an independent risk factor for adverse atherosclerotic cardiovascular disease (ASCVD) outcomes. Elevated Lp(a) levels contribute to atherosclerosis, thrombosis, and aortic valve stenosis, further increasing the risk of cardiovascular events.
In a meta-analysis of seven randomized clinical trials evaluating statin treatment and outcomes, the authors demonstrated a clear positive correlation between Lp(a) levels—both at baseline and during statin therapy—and ASCVD events. The analysis showed that higher Lp(a) levels were directly associated with an increased risk of cardiovascular complications, reinforcing Lp(a)’s role as a potent predictor of heart disease outcomes.
Given the strong association between elevated Lp(a) and poor cardiovascular prognosis, there is an urgent need for the development of targeted therapies that can specifically reduce Lp(a) levels. These novel treatments could then be tested in outcome-driven clinical trials, aiming to reduce the incidence of ASCVD in patients with elevated Lp(a), offering hope for improved management of this significant risk factor.
The Lancet, Meta-analysis, October 2018
Background
Elevated lipoprotein(a) is a genetic risk factor for cardiovascular disease in general population studies. However, its contribution to risk for cardiovascular events in patients with established cardiovascular disease or on statin therapy is uncertain.
Methods
Patient-level data from seven randomised, placebo-controlled, statin outcomes trials were collated and harmonised to calculate hazard ratios (HRs) for cardiovascular events, defined as fatal or non-fatal CHD, stroke, or revascularization procedures.
HRs for cardiovascular events were estimated within each trial across predefined Lp(a) groups (15-30 mg/dL, 30-50 mg/dL, and ≥50 mg/dL, VS. <15 mg/dL) before pooling estimates using multivariate random-effects meta-analysis.
Findings
Analyses included data for 29,069 patients with repeat Lp(a) measurements (mean age 62, 28% women; 5,751 events during 95,576 person-years at risk).
Initiation of statin therapy reduced LDLc (by 39% mean change, without a significant change in Lp(a).
Associations of baseline and on-statin treatment Lp(a) with CVD risk were approximately linear, with:
- 0.94 (0.81–1.10) for 15-30 mg/dL
- 1.06 (0.94–1.21) for 30-50 mg/dL
- 1.43 (1.15–1.76) for >50 mg/dL
- 1.04 (95% CI 0.91–1.18) for 15-30 mg/dL
- 1.11 (95% CI 1.00–1.22) for 30-50 mg/dL
- 1.31 (95% CI 1.08–1.58) for >50 mg/dL
- Increased CVD risk at Lp(a) values of ≥30 mg/dL for baseline Lp(a).
- Increased CVD risk at Lp(a) values of ≥50 mg/dL for on-statin Lp(a).