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Lipoprotein(a) Is an Independent Risk Factor for Cardiovascular Disease in Heterozygous Familial Hypercholesterolemia

¹ St. Paul’s Hospital Lipid Clinic and the University of British Columbia Department of Pathology and Laboratory Medicine, Vancouver, BC, Canada.
² The Centre for Health Evaluations and Outcomes Sciences, St. Paul’s Hospital, Vancouver BC, Canada.

^aAddress correspondence to this author at: Department of Pathology and Laboratory Medicine, University of British Columbia, Room B180, 1081 Burrard St., Vancouver, BC, V6Z 1Y6, Canada. Fax 604-806-8590; e-mail dtholmes{at}interchange.ubc.ca.

Background: The role of lipoprotein(a) [Lp(a)] as a predictor of cardiovascular disease (CVD) in patients with heterozygous familial hypercholesterolemia (HFH) is unclear. We sought to examine the utility of this lipoprotein as a predictor of CVD outcomes in the HFH population at our lipid clinic.

Methods: This was a retrospective analysis of clinical and laboratory data from a large multiethnic cohort of HFH patients at a single, large lipid clinic in Vancouver, Canada. Three hundred and eighty-eight patients were diagnosed with possible, probable, or definite HFH by strict clinical diagnostic criteria. Multivariate Cox regression analysis was used to study the relationship between several established CVD risk factors, Lp(a), and the age of first hard CVD event.

Results: An Lp(a) concentration of 800 units/L (560 mg/L) or higher was a significant independent risk factor for CVD outcomes [hazard ratio (HR) = 2.59; 95% confidence interval (CI), 1.53–4.39; P <0.001]. Other significant risk factors were male sex [HR = 3.19 (1.79–5.69); P <0.001] and ratio of total to HDL-cholesterol [1.18 (1.07–1.30); P = 0.001]. A previous history of smoking or hypertension each produced HRs consistent with increased CVD risk [HR = 1.55 (0.92–2.61) and 1.57 (0.90–2.74), respectively], but neither reached statistical significance (both P = 0.10). LDL-cholesterol was not an independent predictor of CVD risk [HR = 0.85 (0.0.71–1.01); P = 0.07], nor was survival affected by the subcategory of HFH diagnosis (i.e., possible vs probable vs definite HFH).

Conclusion: Lp(a) is an independent predictor of CVD risk in a multiethnic HFH population.

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