Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
Independence of Lipoprotein(a) and LDL Cholesterol-Mediated Cardiovascular Risk
TAKE-HOME MESSAGE
- This meta-analysis sought to clarify the association of lipoprotein(a) [LP(a)] and low-density lipoprotein cholesterol (LDL-C) with the risk of developing atherosclerotic cardiovascular disease (ASCVD). LP(a) and LDL-C were independently and additively associated with the risk of developing ASCVD, with the risk remaining elevated among individuals with elevated LP(a) levels despite using statin therapy to achieve the lowest quartile of LDL-C level. Conversely, the highest risk of developing ASCVD was observed among individuals with the highest LP(a) and LDL-C levels.
- These findings suggest that LDL-C and LP(a) are independent risk factors for developing ASCVD, and control of elevated LDL-C levels with statins may reduce but not eliminate the risk posed by high LP(a) levels.
abstract
This abstract is available on the publisher's site.
Access this abstract nowBACKGROUND
Low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, the relationship between Lp(a) level, LDL-C level, and ASCVD risk at different thresholds is not well defined.
METHODS
A participant-level meta-analysis of 27 658 participants enrolled in 6 placebo-controlled statin trials was performed to assess the association of LDL-C and Lp(a) levels with risk of fatal or nonfatal coronary heart disease events, stroke, or any coronary or carotid revascularization (ASCVD). The multivariable-adjusted association between baseline Lp(a) level and ASCVD risk was modeled continuously using generalized additive models, and the association between baseline LDL-C level and ASCVD risk by baseline Lp(a) level by Cox proportional hazards models with random effects. The joint association between Lp(a) level and statin-achieved LDL-C level with ASCVD risk was evaluated using Cox proportional hazards models.
RESULTS
Compared with an Lp(a) level of 5 mg/dL, increasing levels of Lp(a) were log-linearly associated with ASCVD risk in statin- and placebo-treated patients. Among statin-treated individuals, those with Lp(a) level >50 mg/dL (≈125 nmol/L) had increased risk across all quartiles of achieved LDL-C level and absolute change in LDL-C level. Even among those with the lowest quartile of achieved LDL-C level (3.1-77.0 mg/dL), those with Lp(a) level >50 mg/dL had greater ASCVD risk (hazard ratio, 1.38 [95% CI, 1.06-1.79]) than those with Lp(a) level ≤50 mg/dL. The greatest risk was observed with both Lp(a) level >50 mg/dL and LDL-C level in the fourth quartile (hazard ratio, 1.90 [95% CI, 1.46-2.48]).
CONCLUSIONS
These findings demonstrate the independent and additive nature of Lp(a) and LDL-C levels for ASCVD risk, and that LDL-C lowering does not fully offset Lp(a)-mediated risk.
Additional Info
Disclosure statements are available on the authors' profiles:
Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol-Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis
Circulation 2024 Nov 04;[EPub Ahead of Print], HS Bhatia, S Wandel, P Willeit, A Lesogor, K Bailey, PM Ridker, P Nestel, J Simes, A Tonkin, GG Schwartz, H Colhoun, C Wanner, S TsimikasFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
It is well established that LDL-C and lipoprotein(a) (Lp[a]) are independently associated with atherosclerotic cardiovascular disease (ASCVD). However, in contrast to the growing number of LDL-C–lowering therapies, there are currently no medical therapies available specifically targeting Lp(a). Several targeted therapies are currently in advanced clinical trials, offering hope for new options in the coming years. Elevated Lp(a) levels are highly prevalent and associated with several cardiovascular diseases, highlighting the need for management strategies for this large patient population at risk, particularly while we await novel therapies.
In the present study, a participant-level meta-analysis of six randomized placebo-controlled trials of statin therapy was conducted to evaluate the independent association of Lp(a) and LDL-C with ASCVD risk and whether lowering of LDL-C levels with statin therapy mitigates the risk conferred by elevated Lp(a) levels. Among 27,658 patients, baseline Lp(a) and LDL-C levels were independently associated with ASCVD risk, with no significant interaction observed. In patients assigned to statin therapy, the combined effect of achieved LDL-C levels and elevated Lp(a) (≥50 mg/dL) was assessed. Patients with elevated Lp(a) levels remained at increased risk (HR, 1.38; 95% CI, 1.06–1.79) even with the lowest on-treatment LDL-C levels (3.1–77.0 mg/dL). Conversely, risk was highest (HR, 1.90; 95% CI, 1.46–2.48) among patients with elevated Lp(a) and the highest on-treatment LDL-C levels (>140.8 mg/dL). Among patients with elevated Lp(a), observed event rates were generally lower with lower achieved LDL-C levels. Consistent results were seen in analyses evaluating absolute LDL-C level change, LDL-C thresholds of 100 or 55 mg/dL, and median follow-up LDL-C levels.
The take-home message is that Lp(a) and LDL-C levels are independently associated with and additively contribute to cardiovascular risk. While LDL-C lowering reduces overall risk in patients with elevated Lp(a), it does not fully offset the associated risk, underscoring the need to address both factors for optimal cardiovascular risk reduction.