LDL-C and lipoprotein(a) levels independently and additively associated with ASCVD risk: Study

The results of a recent study that was published in the journal of Circulation, suggest that low-density lipoprotein cholesterol (LDL-C) and lipoprotein(a) (Lp[a]) levels are independent and additive for atherosclerotic cardiovascular disease (ASCVD) risk, and lowering LDL-C does not completely counteract Lp(a)-mediated risk.

Lp(a), which is mostly genetically driven, has been demonstrated to be an independent predictor of calcific aortic stenosis and ASCVD risk. Numerous genetic studies have demonstrated a link between elevated Lp(a) and cardiovascular disease, and several treatments are being developed to reduce and treat it. According to US standards, Lp(a) is regarded as a "risk enhancer," a surrogate that can assist certain patients in making treatment decisions. Some guidelines, including those from the European Atherosclerosis Society and the National Lipid Association, suggest being more aggressive with LDL reduction to counter the risk associated with high Lp(a) in the absence of effective medications.

To evaluate the relationship between LDL-C and Lp(a) levels and the risk of stroke, coronary heart disease events, or any coronary or carotid revascularization, a participant-level meta-analysis of 27,658 patients included in six placebo-controlled statin trials was conducted. Generalized additive models were used to continuously model the multivariable-adjusted relationship between baseline Lp(a) level and ASCVD risk, and Cox proportional hazards models with random effects were used to model the relationship between baseline LDL-C level and ASCVD risk by baseline Lp(a) level. Cox proportional hazards models were used to assess the combined relationship between ASCVD risk and Lp(a) level and statin-achieved LDL-C level.

In patients receiving statins and placebos, rising Lp(a) levels were log-linearly linked to an increased risk of ASCVD when compared to a level of 5 mg/dL. All quartiles of the attained LDL-C level and the absolute change in LDL-C level were associated with increased risk among statin-treated people whose Lp(a) level was more than 50 mg/dL (≈125 nmol/L).

The risk of ASCVD was higher for the ones with Lp(a) levels >50 mg/dL than for the ones with Lp(a) levels ≤50 mg/dL, even among the individuals with the lowest quartile of attained LDL-C levels (3.1–77.0 mg/dL). LDL-C levels in the fourth quartile and Lp(a) levels greater than 50 mg/dL were associated with the highest risk. Overall, greater levels of lipoprotein (a) are linked to a greater risk of cardiovascular disease events in individuals with low LDL cholesterol, including the ones who have very significant absolute reductions with statin medication.

Source:

Bhatia, H. S., Wandel, S., Willeit, P., Lesogor, A., Bailey, K., Ridker, P. M., Nestel, P., Simes, J., Tonkin, A., Schwartz, G. G., Colhoun, H., Wanner, C., & Tsimikas, S. (2024). Independence of Lipoprotein(a) and Low-Density Lipoprotein Cholesterol–Mediated Cardiovascular Risk: A Participant-Level Meta-Analysis. In Circulation. Ovid Technologies (Wolters Kluwer Health). https://doi.org/10.1161/circulationaha.124.069556