Impact of markedly elevated serum lipoprotein(a) levels (> or = 100 mg/dL) on the risk of coronary heart disease

Abstract

The serum lipoprotein(a) [Lp(a)] concentration is under genetic control, and most humans have values lower than 30 mg/dL. Subjects with markedly elevated serum Lp(a) concentrations, that is, > or =100 mg/dL, are rarely encountered, and these subjects have not yet been fully characterized from the clinical point of view. In the present investigation, we studied a total of 223 subjects, comprising 123 males and 100 females, with serum Lp(a) values of more than 100 mg/dL. Many of these subjects had a variety of underlying diseases, including metabolic disorders, renal diseases, and hypertension. We focused our attention on the patients with metabolic disorders, namely, familial hypercholesterolemia (FH), primary non-FH hypercholesterolemia (HC), and type 2 diabetes mellitus (DM), and conducted a comparative study of the patients of these 3 disease groups with the corresponding disease controls with serum Lp(a) levels of less than 30 mg/dL, a presumed high normal value. The frequency of markedly elevated serum Lp(a) levels in the general population has not been reported previously. We determined the frequencies in a consecutive series of patients at our Diabetes and Lipid Outpatient Clinic; the results revealed that the frequencies were 6.4% (8/125), 2.6% (6/232), and 0.9% (3/352) in patients with FH, HC, and type 2 DM, respectively. In an attempt to further demonstrate the impact of markedly elevated serum Lp(a) concentrations on the risk of coronary heart disease (CHD), we compared the prevalence of CHD among the study subjects with that among the corresponding disease controls. The results revealed a significantly higher CHD prevalence in the study subjects of all the 3 groups as compared with that in the corresponding disease controls: the odds ratios of a markedly elevated serum Lp(a) level were 5.429 (95% confidence interval [CI], 1.353-21.782), 8.243 (95% CI, 2.793-24.327), and 5.981 (95% CI, 2.530-14.139) for FH, HC, and type 2 DM, respectively. In the present study, we examined some characteristics of this rare population of subjects with markedly elevated serum Lp(a) levels and demonstrated a very high prevalence of CHD among these patients with FH, HC, and type 2 DM, strongly suggesting the significance of Lp(a) as a risk factor for CHD.