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Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting.


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.

SUBMITTER: Verbeek R 

PROVIDER: S-EPMC6287703 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Cardiovascular disease risk associated with elevated lipoprotein(a) attenuates at low low-density lipoprotein cholesterol levels in a primary prevention setting.

Verbeek Rutger R   Hoogeveen Renate M RM   Langsted Anne A   Stiekema Lotte C A LCA   Verweij Simone L SL   Hovingh G Kees GK   Wareham Nicholas J NJ   Khaw Kay-Tee KT   Boekholdt S Matthijs SM   Nordestgaard Børge G BG   Stroes Erik S G ESG  

European heart journal 20180701 27


<h4>Aims</h4>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.<h4>Methods and results</h4>In 16 654 individuals from the EPIC-Norfolk prospective population study, and in 9448 individuals from the Cope  ...[more]

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