Serum lipoprotein(a) in patients heterozygous for familial hypercholesterolemia, their relatives, and unrelated control populations.

Abstract

Serum lipoprotein(a) (Lp[a]) levels were significantly higher in 89 patients with heterozygous familial hypercholesterolemia (FH) (geometric mean, 22.7 mg/dl) than in 109 normocholesterolemic controls (10.0 mg/dl, p<0.05) and 40 controls (9.1 mg/dl, /?<0.05) with similarly elevated low density lipoprotein cholesterol levels due to other primary hypercholesterolemias. To provide further evidence that the increased serum Lp(a) concentration was due to inheritance of the FH gene, 24 unaffected first-degree relatives were compared with their FH probands. Serum Lp(a) in affected individuals was significantly greater than in unaffected relatives (geometric means, 26.5 versus 13.7 mg/dl, respectively; p<0.05). Family membership exerted an effect on serum Lp(a) concentrations, indicating that other genetic influences were also operating, as is known to be the case in general populations. Serum Lp(a) in 30 of the FH patients, who had coronary heart disease, was not significantly different from 30 age-and sex-matched controls with FH but without coronary heart disease (geometric means, 23.6 versus 24.7 mg/dl, respectively). FH is associated with an increase in serum Lp(a). Elevated serum Lp(a) concentrations should probably now be regarded as a component of the clinical syndrome of FH. However, within our FH population Lp(a) did not distinguish those with clinically overt coronary heart disease from those without the disease. (Arteriosclerosis and Thrombosis 1991;ll:940-946)

Lipoprotein [a] is cleared from the plasma primarily by the liver in a process mediated by apolipoprotein [a]

“…Although some in vitro studies support this proposal (11-13), others do not (42)(43)(44). In addition, several studies have reported that individuals with familial hypercholesterolemia, in which there is a genetic absence of functional LDLRs, have increased plasma Lp[a] levels, suggesting a role for the LDLR and the liver in the plasma clearance of Lp[a] (10,14,15 [a] was ‫%9ف‬ less and hepatic uptake was reduced by ‫%02ف‬ during 24 h. On the other hand, for LDL, the FCR was reduced by ‫%05ف‬ and the hepatic uptake was less than half that for wild-type mice. Thus, it is possible that in wild-type mice the LDLR may make a minor contribution to the hepatic uptake of Lp [a] but that its role is much more limited than it is in the uptake of LDL.…”

“…These include the LDL receptor (LDLR) (10)(11)(12)(13)(14)(15), megalin/gp330 (16), the LDL receptor-related protein (LRP) (17), and the VLDL receptor (18). The latter two receptors can mediate binding to lipoproteins through apoE.…”

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

“…Some early studies, whether they found a correlation between Lp(a) concentration and CVD (3)(4)(5)(6) or not (8,9,12,13 ), had smaller sample sizes ranging from 24 (3 ) to 98 (13 ) individuals.…”

Lipoprotein(a) levels in relation to diabetic complications in patients with non‐insuIin‐dependent diabetes

“…Elevated Lp(a) levels may distinguish those patients with familial hypercholesterolaemia and clinically overt coronary heart disease from those without the disease [36,40], although it may also be regarded as a part of the clinical syndrome of familial hypercholesterolaemia [41]. Dietary treatments, such as a vegetation diet [42], have failed to lower serum Lp(a) concentrations in non-diabetic subjects.…”