Martine Paquette1, Sophie Bernard2, George Thanassoulis3, Alexis Baass4. 1. Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Québec, Canada. 2. Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Québec, Canada; Division of Endocrinology, Department of Medicine, Université de Montreal, Québec, Canada. 3. Preventive and Genomic Cardiology, Divisions of Cardiology and Clinical Epidemiology, McGill University Health Center and Research Institute, Québec, Canada. 4. Lipids, Nutrition and Cardiovascular Prevention Clinic of the Montreal Clinical Research Institute, Québec, Canada; Division of Experimental Medicine, Department of Medicine, McGill University, Québec, Canada; Division of Medical Biochemistry, Department of Medicine, McGill University, Québec, Canada. Electronic address: alexis.baass@ircm.qc.ca.
Abstract
BACKGROUND: In recent years, lipoprotein (a) (Lp(a)) has been recognized as an important risk factor for cardiovascular disease (CVD). A variant in the LPA gene, rs10455872, has been associated with higher concentrations of Lp(a), as well as an increased risk of CVD in the general population. OBJECTIVE: The objective of the present study is to compare the predictive value of an LPA variant, rs10455872, as well as Lp(a) concentration on the prevalence of CVD and on the age of the first CVD event in a cohort of genetically confirmed heterozygous patients with familial hypercholesterolemia (FH). METHODS: Lp(a) total particle mass was measured by an enzyme-linked immunoassay kit. The rs10455872 genotype has been obtained via an exome chip genotyping method. RESULTS: The cohort comprised 88 carriers and 580 noncarriers of the rs10455872. The Lp(a) concentration (g/L) was significantly higher in carriers than in noncarriers (0.41 [0.33-0.60] vs 0.12 [0.05-0.27], respectively, P < .0001). There was a significant association between rs10455872 and prevalent CVD in a model corrected for classical CVD risk factors (odds ratio 1.97, 95% confidence interval 1.05-3.68, P = .04). There was a significant association between rs10455872 and the age of the first CVD event in a model corrected for all cardiovascular risk factors including Lp(a) levels (39.7 vs 43.9 years in carriers vs noncarriers, respectively, P = .02). CONCLUSION: Our results suggest that the LPA variant rs10455872 is a good predictor of premature CVD risk in FH. This also suggest that targeting Lp(a) in FH subjects could be associated with further reduction in CVD risk.
BACKGROUND: In recent years, lipoprotein (a) (Lp(a)) has been recognized as an important risk factor for cardiovascular disease (CVD). A variant in the LPA gene, rs10455872, has been associated with higher concentrations of Lp(a), as well as an increased risk of CVD in the general population. OBJECTIVE: The objective of the present study is to compare the predictive value of an LPA variant, rs10455872, as well as Lp(a) concentration on the prevalence of CVD and on the age of the first CVD event in a cohort of genetically confirmed heterozygous patients with familial hypercholesterolemia (FH). METHODS:Lp(a) total particle mass was measured by an enzyme-linked immunoassay kit. The rs10455872 genotype has been obtained via an exome chip genotyping method. RESULTS: The cohort comprised 88 carriers and 580 noncarriers of the rs10455872. The Lp(a) concentration (g/L) was significantly higher in carriers than in noncarriers (0.41 [0.33-0.60] vs 0.12 [0.05-0.27], respectively, P < .0001). There was a significant association between rs10455872 and prevalent CVD in a model corrected for classical CVD risk factors (odds ratio 1.97, 95% confidence interval 1.05-3.68, P = .04). There was a significant association between rs10455872 and the age of the first CVD event in a model corrected for all cardiovascular risk factors including Lp(a) levels (39.7 vs 43.9 years in carriers vs noncarriers, respectively, P = .02). CONCLUSION: Our results suggest that the LPA variant rs10455872 is a good predictor of premature CVD risk in FH. This also suggest that targeting Lp(a) in FH subjects could be associated with further reduction in CVD risk.
Authors: Daniel I Swerdlow; David A Rider; Arash Yavari; Marie Wikström Lindholm; Giles V Campion; Steven E Nissen Journal: Cardiovasc Res Date: 2022-03-25 Impact factor: 10.787