Lipoprotein(a) Interactions With Low-Density Lipoprotein Cholesterol and Other Cardiovascular Risk Factors in Premature Acute Coronary Syndrome (ACS).
Current recommendations for lipoprotein(a) (Lp[a]) focus on the control of other risk factors, including lowering low-density lipoprotein cholesterol (LDL-C), with little evidence to support this approach. Identifying interactions between Lp(a) and other risk factors could identify individuals at increased risk for Lp(a)-mediated disease.



We used a case-only study design and included 939 participants (median age=49 years, interquartile range 46-53, women=33.1%) from the GENdEr and Sex determInantS of cardiovascular disease: from bench to beyond-Premature Acute Coronary Syndrome (GENESIS-PRAXY) study, a multicenter prospective cohort study of premature acute coronary syndrome. There was a higher prevalence of elevated Lp(a) levels (>50 mg/dL; 80th percentile) in PRAXY participants as compared to the general population (31% versus 20%; P<0.001). Lp(a) was strongly associated with LDL-C (adjusted β 0.17; P<0.001). Individuals with high Lp(a) were more likely to have LDL-C >2.5 mmol/L, indicating a synergistic interaction (adjusted odds ratio 1.51; 95% CI 1.08-2.09; P=0.015). The interaction with high Lp(a) was stronger at increasing LDL-C levels (LDL-C >3.5, adjusted odds ratio 1.87; LDL-C >4.5, adjusted odds ratio 2.72). In a polytomous logistic model comparing mutually exclusive LDL-C categories, the interaction with high Lp(a) became attenuated at LDL-C ≤3.5 mmol/L (odds ratio 1.16; 95% CI 0.80-1.68, P=0.447). Other risk factors were not associated with high Lp(a).



In young acute coronary syndrome patients, high Lp(a) is more prevalent than in the general population and is strongly associated with high LDL-C, suggesting that Lp(a) confers greater risk for acute coronary syndrome when LDL-C is elevated. Individuals with high Lp(a) and LDL-C >3.5 mmol/L may warrant aggressive LDL-C lowering.
Department of Medicine, McGill University, Montreal, Quebec, Canada Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Quebec, Canada.
Mehdi
M
Afshar
Department of Medicine, McGill University, Montreal, Quebec, Canada Department of Clinical Epidemiology, McGill University Health Center, Montreal, Quebec, Canada.
Louise
L
Pilote
Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Quebec, Canada.
Line
L
Dufresne
Department of Medicine, McGill University, Montreal, Quebec, Canada Department of Human Genetics, McGill University, Montreal, Quebec, Canada Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Quebec, Canada.
James C
JC
Engert
Department of Medicine, McGill University, Montreal, Quebec, Canada Preventive and Genomic Cardiology, McGill University Health Center and Research Institute, Montreal, Quebec, Canada Department of Clinical Epidemiology, McGill University Health Center, Montreal, Quebec, Canada george.thanassoulis@mcgill.ca.
George
G
Thanassoulis
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood*; D004562:Electrocardiography; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D015995:Prevalence; D011446:Prospective Studies; D011792:Quebec / Q000453:epidemiology; D012307:Risk Factors; D012737:Sex Factors; D013557:Switzerland / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
D015415:Biomarkers; D008078:Cholesterol, LDL; D017270:Lipoprotein(a)
acute coronary syndrome; atherosclerosis; lipids and lipoproteins; lipoprotein(a); prevention; risk factor