Epidemiology
Elevated Lp(a) risk fades when LDL cholesterol is below 2.5 mmol/L, an EPIC-Norfolk and Copenhagen City Heart Study analysis (Eur Heart J 2018)
Original title: Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting
Researchers led by Verbeek, Hoogeveen and colleagues at Amsterdam UMC tested whether elevated Lp(a) cardiovascular risk is attenuated at low LDL cholesterol, using 16,654 participants from the EPIC-Norfolk prospective population study and 9,448 from the Copenhagen City Heart Study. Individuals were categorised by Lp(a) (80th cohort percentile cutoff) and Lp(a)-corrected LDL cholesterol (cutoffs 2.5, 3.5, 4.5 and 5.5 mmol/L). In both cohorts, individuals with Lp(a) at or above the 80th percentile had increased cardiovascular disease risk compared with those below it, for LDL cholesterol levels of 2.5 mmol/L or higher, but this excess risk attenuated when LDL cholesterol was below 2.5 mmol/L, though no formal interaction between LDL cholesterol and Lp(a) was found in either cohort. The findings show Lp(a) and LDL cholesterol are independently associated with cardiovascular risk, but the risk from elevated Lp(a) attenuates at LDL cholesterol below 2.5 mmol/L in a primary prevention setting.
Original abstract
Aims: Lipoprotein(a) (Lp(a)) elevation is a causal risk factor for cardiovascular disease (CVD). It has however been suggested that elevated Lp(a) causes CVD mainly in individuals with high low-density lipoprotein cholesterol (LDL-C) levels. We hypothesized that the risk associated with high Lp(a) levels would largely be attenuated at low LDL-C levels.
Methods And Results: In 16 654 individuals from the EPIC-Norfolk prospective population study, and in 9448 individuals from the Copenhagen City Heart Study (CCHS) parallel statistical analyses were performed. Individuals were categorized according to their Lp(a) and LDL-C levels. Cut-offs were set at the 80th cohort percentile for Lp(a). Low-density lipoprotein cholesterol cut-offs were set at 2.5, 3.5, 4.5, and 5.5 mmol/L. Low-density lipoprotein cholesterol levels in the primary analyses were corrected for Lp(a)-derived LDL-C (LDL-Ccorr). Multivariable-adjusted hazard ratios were calculated for each category. The category with LDL-Ccorr <2.5 mmol/L and Lp(a) <80th cohort percentile was used as reference category. In the EPIC-Norfolk and CCHS cohorts, individuals with an Lp(a) ≥80th percentile were at increased CVD risk compared with those with Lp(a) <80th percentile for any LDL-Ccorr levels ≥2.5 mmol/L. In contrast, for LDL-Ccorr <2.5 mmol/L, the risk associated with elevated Lp(a) attenuated. However, there was no interaction between LDL-Ccorr and Lp(a) levels on CVD risk in either cohort.
Conclusion: Lipoprotein(a) and LDL-C are independently associated with CVD risk. At LDL-C levels below <2.5 mmol/L, the risk associated with elevated Lp(a) attenuates in a primary prevention setting.
Dutch researchepidemiologyrisk prediction
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.