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High lipoprotein(a) levels may raise familial hypercholesterolemia risk
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Adults with high levels of lipoprotein(a) are more likely to have clinical familial hypercholesterolemia and an increased risk for myocardial infarction, according to recent study findings.
“Of all clinical diagnoses of familial hypercholesterolemia, 25% is due to high lipoprotein(a) concentrations,” Borge G. Nordestgaard, MD, DMSc, clinical professor and chief physician at University of Copenhagen and Copenhagen University Hospital, Denmark, told Endocrine Today. “All patients with familial hypercholesterolemia should have lipoprotein(a) measured, and if elevated, treatment should target not only LDL but also lipoprotein(a).”
Borge G. Nordestgaard
In a prospective cohort study, Nordestgaard, Anne Langsted, MD, of the department of clinical biochemistry at Herlev and Gentofte Hospital in Copenhagen, and colleagues analyzed data from 46,200 Danish adults from the Copenhagen General Population Study who had lipoprotein(a) measurements and were genotyped for common familial hypercholesterolemia mutations. All participants completed a self-administered questionnaire, underwent a physical exam and provided blood samples during a single hospital visit. Individuals receiving cholesterol-lowering drugs had their concentrations of LDL and total cholesterol multiplied by 1.43, corresponding to an estimated 30% reduction in LDL from the treatment.
In lipoprotein(a) cholesterol-adjusted analyses, total cholesterol and LDL were adjusted for the lipoprotein(a) cholesterol content by subtracting 30% of the individuals’ lipoprotein(a) total mass before total and LDL cholesterol were used for diagnosis of clinical familial hypercholesterolemia.
Researchers used Cox proportional hazard regression analysis to calculate HRs for MI.
Using unadjusted LDL, mean lipoprotein(a) concentrations were 23 mg/dL in individuals unlikely to have familial hypercholesterolemia, 32 mg/dL in those with possible familial hypercholesterolemia and 35 mg/dL in those with probable or definite familial hypercholesterolemia (P < .0001 for trend); corresponding values were 24 mg/dL, 22 mg/dL and 21 mg/dL, respectively, when adjusting LDL for lipoprotein(a) cholesterol content (P = .46 for trend).
Researchers found that 25% of all participants diagnosed with clinical familial hypercholesterolemia had high lipoprotein(a) cholesterol; LPA risk genotypes also were more frequent in clinical familial hypercholesterolemia, whereas lipoprotein(a) concentrations were similar in those with and without familial hypercholesterolemia mutations.
Using Dutch Lipid Clinic Network criteria, the HRs for MI compared with individuals unlikely to have familial hypercholesterolemia and lipoprotein(a) concentration of 50 mg/dL or less were 1.4 (95% CI, 1.1-1.7) in those unlikely to have familial hypercholesterolemia and lipoprotein(a) concentrations of more than 50 mg/dL, 3.2 (95% CI, 2.5-4.1) in those with possible, probable or definite familial hypercholesterolemia and lipoprotein(a) concentration of 50 mg/dL or less, and 5.3 (95% CI, 3.6-7.6) in those with possible, probable or definite familial hypercholesterolemia and lipoprotein(a) concentration of more than 50 mg/dL. Results were similar when researchers used Simon-Broome or Make Early Diagnosis to Prevent Early Death (MEDPED) criteria.
“Although it could be argued that this finding is not surprising, the fact that high lipoprotein(a) concentration has a potentially causal association with clinical familial hypercholesterolemia has not, to our knowledge, previously been recognized or shown,” the researchers wrote. “Of all the individuals in this study with clinical familial hypercholesterolemia, a quarter obtained the diagnosis because of high lipoprotein(a) concentrations, and high lipoprotein(a) in addition to high LDL cholesterol increased the already high risk of [MI] in clinical familial hypercholesterolemia.” – by Regina Schaffer
For more information:
Borge G. Nordestgaard, MD, DMSc, can be reached at the department of clinical biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark; email: Boerge.Nordestgaard@regionh.dk.
Disclosure: The Danish Heart Association and IMK General Fund in Copenhagen funded this study. Nordestgaard reports receiving lecture or consultancy honoraria from Aegerion, Amgen, AstraZeneca, B. Braun, Denka Seiken, Dezima, Fresenius, Ionis Pharmaceuticals, Kaneca, Lilly, Merck, Omthera, Pfizer, Regeneron and Sanofi. Please see the full study for the other researchers’ relevant financial disclosures.
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