Coronary Artery Disease Risk of Familial Hypercholesterolemia Genetic Variants Independent of Clinically Observed Longitudinal Cholesterol Exposure.
Circ Genom Precis Med
; 15(2): e003501, 2022 04.
Article
em En
| MEDLINE
| ID: mdl-35143253
ABSTRACT
BACKGROUND:
Familial hypercholesterolemia (FH) genetic variants confer risk for coronary artery disease independent of LDL-C (low-density lipoprotein cholesterol) when considering a single measurement. In real clinical settings, longitudinal LDL-C data are often available through the electronic health record. It is unknown whether genetic testing for FH variants provides additional risk-stratifying information once longitudinal LDL-C is considered.METHODS:
We used the extensive electronic health record data available through the Million Veteran Program to conduct a nested case-control study. The primary outcome was coronary artery disease, derived from electronic health record codes for acute myocardial infarction and coronary revascularization. Incidence density sampling was used to match case/control exposure windows, defined by the date of the first LDL-C measurement to the date of the first coronary artery disease code of the index case. Adjustments for the first, maximum, or mean LDL-C were analyzed. FH variants in LDLR, APOB, and PCSK9 (Proprotein convertase subtilisin/kexin type 9) were assessed by custom genotype array.RESULTS:
In a cohort of 23 091 predominantly prevalent cases at enrollment and 230 910 matched controls, FH variant carriers had an increased risk for coronary artery disease (odds ratio [OR], 1.53 [95% CI, 1.24-1.89]). Adjusting for mean LDL-C led to the greatest attenuation of the risk estimate, but significant risk remained (odds ratio, 1.33 [95% CI, 1.08-1.64]). The degree of attenuation was not affected by the number and the spread of LDL-C measures available.CONCLUSIONS:
The risk associated with carrying an FH variant cannot be fully captured by the LDL-C data available in the electronic health record, even when considering multiple LDL-C measurements spanning more than a decade.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença da Artéria Coronariana
/
Hiperlipoproteinemia Tipo II
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Circ Genom Precis Med
Ano de publicação:
2022
Tipo de documento:
Article