High Lp(a) confers greater risk for early ACS when LDL-C is elevatedAfshar M et al., J Am Heart Assoc. 2016
Lipoprotein(a) Interactions With Low-Density Lipoprotein Cholesterol and Other Cardiovascular Risk Factors in Premature Acute Coronary Syndrome (ACS)
Afshar M, Pilote L, Dufresne L, et al.
J Am Heart Assoc. 2016; published online ahead of print
BackgroundIncreased Lp(a) is a common genetic dyslipidemia that has been associated with CVD risk [1-3], however there are finite therapeutic options for the management of elevated Lp(a) . There is limited evidence that supports the recommended control of other risk factors, like LDL-C, in case of elevated Lp(a) .
It is hypothesised that the identification of interactions between Lp(a) and other CV risk factors could identify individuals at increased risk for Lp(a)-mediated disease, and help develop strategies to attenuate the risk conferred by high Lp(a) levels. .
In this case-only design study, it was evaluated whether high Lp(a) interacts with LDL-C levels and other ACS risk factors in 939 participants of the GENESIS-PRAXY (GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary Syndrome) study. A case-only design study can identify interactions between genes and the environment, when genetic and environmental exposure are not associated in the general population [6,7]. Lp(a) is under strong genetic regulation and was not influenced by most CV risk factors, including LDL-c in the general population [8-11].
- There was a higher prevalence of elevated Lp(a) levels (>50 mg/dL; 80th percentile) in GENESIS-PRAXY participants compared with the general population (31% versus 20%; P<0.001)
- Lp(a) was strongly associated with LDL-C (adjusted β: 0.17; P<0.001)
- In logistic regression analysis, individuals with high Lp(a) >50 mg/dL were more likely to have LDL-C >2.5 mmol/L, indicating a synergistic interaction: unadjusted OR: 1.53; 95% CI: 1.11–2.11; P=0.009, adjusted OR: 1.51; 95% CI: 1.08–2.09; P=0.015
- In sensitivity analyses, the interaction with high Lp(a) was stronger at increasing LDL-C levels. The adjusted odds ratio increased: from 1.51 (95% CI: 1.08–2.09; P=0.015) at LDL-C >2.5 mmol/L to 2.72 (95% CI: 1.67–4.42; P<0.001) at LDL-C >4.5 mmol/L
- The interaction with high Lp(a) became attenuated at LDL-C ≤3.5 mmol/L in a polytomous logistic model. As compared to LDL-C <2.5 mmol/L, adjusted Lp(a) interaction odds ratios across LDL-C groups were for LDL-C 2.5-3.5 mmol/L: 1.16 (95%CI: 0.80–1.68; P=0.447), for LDL-C 3.5-4.5 mmol/L: 1.66 (95%CI: 1.11–2.51; P=0.015) and for LDL-C >4.5 mmol/L: 3.31 (95% CI: 1.93–5.67; P<0.001).
- Other risk factors were not associated with high Lp(a)
ConclusionIn young ACS patients, high Lp(a) is more prevalent than in the general population and is strongly associated with high LDL-C. These findings suggest that Lp(a) confers a greater risk for ACS when LDL-C is elevated. LDL-C lowering therapy in individuals with high Lp(a) and LDL-C >3.5 mmol/L may yield meaningful reductions of premature CV risk.
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