Elevated lipoprotein(a), hypertension and renal insufficiency as predictors of coronary artery disease in patients with genetically confirmed heterozygous familial hypercholesterolemia.
BACKGROUND
Familial hypercholesterolemia (FH) is characterized by elevated LDL-cholesterol and increased risk of premature coronary artery disease (CAD). Lipoprotein(a) [Lp(a)] increases CAD in FH, although the independence of this association relative to other CAD risk factors remains unclear. In this study, we examined the association between Lp(a) and other cardiovascular risk factors and prevalent CAD in patients with FH.


METHODS
A cross-sectional study of 390 patients with genetically confirmed FH were studied. Clinical and biochemical parameters of FH patients with and without CAD were compared.


RESULTS
FH patients with CAD were older and more often male and had a higher prevalence of hypertension, smoking, diabetes, obesity, reduced eGFR, and elevated plasma Lp(a) and pre-treatment LDL-cholesterol and triglyceride (or low HDL-cholesterol) than FH patients without CAD (P<0.05 for all). In univariate analyses, age, male gender, smoking, hypertension, reduced eGFR, diabetes, obesity, plasma creatinine, Lp(a) and pretreatment LDL-cholesterol, triglycerides and HDL-cholesterol levels were significant predictors of CAD in the FH patients (P<0.05 for all). Elevated LDL-cholesterol, raised Lp(a), hypertension and reduced eGFR remained significant independent predictors of CAD (P<0.05 for all) in FH after adjusting for other modifiable risk factors.


CONCLUSIONS
Elevated Lp(a), hypertension and renal insufficiency are independent risk factors beyond elevated pretreatment LDL-cholesterol which predict CAD in patients with FH. In spite of the cross-sectional design of our study, we propose the need for identifying and managing these abnormalities to reduce excess CAD risk in FH patients. However, this proposal remains to be formally tested in a prospective study.
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia.
Dick C
DC
Chan
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia.
Jing
J
Pang
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Australia; School of Pathology and Laboratory Medicine, University of University of Western Australia, Perth, Australia.
Amanda J
AJ
Hooper
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Australia; Lipid Disorders Clinic, Cardiometabolic Service, Royal Perth Hospital, Perth, Australia.
John R
JR
Burnett
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia; Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Australia; Lipid Disorders Clinic, Cardiometabolic Service, Royal Perth Hospital, Perth, Australia; Department of Clinical Biochemistry, St. John of God Pathology, Osborne Park, Australia.
Damon A
DA
Bell
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia; Lipid Disorders Clinic, Cardiometabolic Service, Royal Perth Hospital, Perth, Australia.
Timothy R
TR
Bates
Department of Clinical Biochemistry, PathWest Laboratory Medicine, Royal Perth Hospital, Perth, Australia; School of Surgery, University of University of Western Australia, Perth, Australia.
Frank M
FM
van Bockxmeer
School of Medicine and Pharmacology, University of Western Australlia, Perth, Australia; Lipid Disorders Clinic, Cardiometabolic Service, Royal Perth Hospital, Perth, Australia. Electronic address: gerald.watts@uwa.edu.au.
Gerald F
GF
Watts
D000328:Adult; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology*; D003430:Cross-Sectional Studies; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D005820:Genetic Testing / Q000379:methods*; D005919:Glomerular Filtration Rate; D006579:Heterozygote; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000097:blood / Q000150:complications / Q000235:genetics*; D006973:Hypertension / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015995:Prevalence; D051437:Renal Insufficiency / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D014904:Western Australia / Q000453:epidemiology
D017270:Lipoprotein(a); D004247:DNA
Cardiovascular disease; Familial hypercholesterolemia; Risk factors