Blood Lipoprotein(a) measurements are genetically determined. Lifestyle, physical activity or dietary habits do not change its levels. Epidemiologically, Lp(a) has been found to be an independent risk factor for poor ASCVD outcomes. Lp(a) is a promoter of atherosclerosis, thrombosis and aortic valve stenosis.

In this meta-analysis of 7 statin-outcome randomized clinical trials, authors showed that baseline and on-statin treatment Lp(a) levels correlated positively and linearly with ASCVD events: the higher the Lp(a) measurements, the higher the cardiovascular outcomes.

Development of specific drug therapies in reducing Lp(a) are need. These therapies would then be tested in outcome driven ASCVD clinical trials.

Also see:

Lipoprotein(a)

Lipids

ASCVD

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

HRs were almost identical after further adjustment for previous CVD, DM, SMK, sBP, LDLc, and HDLc.

The association of on-statin Lp(a) with CVD risk was stronger than for on-placebo Lp(a) (interaction p=0.01) and was more pronounced at younger ages (interaction p=0·008) without effect-modification by any other patient-level or study-level characteristics.

Interpretation

In this individual-patient data meta-analysis of statin-treated patients, ELEVATED baseline and on-statin Lp(a) showed an independent approximately linear relation with CVD risk. This study provides a rationale for testing the Lp(a) lowering hypothesis in CVD outcomes trials.

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

Respective HRs for on-statin lipoprotein(a) were:

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

HRs were almost identical after further adjustment for previous CVD, DM, SMK, sBP, LDLc, and HDLc.

Interpretation

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).

For baseline Lp(a), HRs adjusted for age and sex ( vs <15 mg/dL) were:

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

Respective HRs for on-statin lipoprotein(a) were:

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

HRs were almost identical after further adjustment for previous CVD, DM, SMK, sBP, LDLc, and HDLc.