Lipoprotein(a) and ultrasonographically determined early atherosclerotic changes in the carotid and femoral artery

Abstract

Summary. Recent studies suggest that high lipoprotein(a) [Lp(a)] plasma levels are associated with symptomatic ischemic cardiovascular disease. We examined whether Lp(a) plasma levels are associated with early atherosclerotic vessel wall changes in a group of asymptomatic subjects. In a group of 142 asymptomatic men, the intima-media thickness (IMT) in the common carotid artery, the carotid bifurcation and the common femoral artery was determined by B-mode ultrasonography. In addition to Lp(a) Several hypotheses have been put forward concerning the etiological role of Lp(a) in cardiovascular disease, based on the specific structure of Lp(a). Lipoprotein(a) consists of an LDLlike particle that is disulfide-linked to an apolipoprotein(a). LDL levels are major independent risk factors for atherosclerosis, and DNA sequence analysis has shown that a part of apolipoprotein(a) resembles plasminogen [9]. It has been hypothesized that because of this, high levels of Lp(a) might interfere with the fibrinolytic process, leading to a prothrombotic state [10]. This could be enhanced by the ability of Lp(a) to activate PAI-1 (plasminogen activator inhibitor-1) and inactivate t-PA (tissue-type plasminogen activator) and TFPI (tissue factor pathway inhibitor) [11][12][13]. Furthermore, Lp(a) might directly contribute to the atherogenic process by decreasing the break-up of mural thrombi which subsequently may be incorporated in atherosclerotic plaques. Finally, according to recent studies, high Lp(a) levels decrease tissue growth factor-b activation, resulting in proliferation and migration of smooth muscle cells into the intimal layer of the arterial wall [14,15]. This process is considered to be one of the earliest stages in the atherosclerotic process.To study the role of Lp(a) in the atherosclerotic process, a number of research groups have investigated whether high Lp(a) levels are associated with symptomatic and premature atherosclerosis in the carotid artery as assessed by ultrasound [16][17][18][19][20][21][22][23][24][25]. The results of these studies are, however, contradictory.In this study, we examined the effect of Lp(a) on premature atherosclerotic vessel wall changes by ultrasound measurement. Contrary to previous studies, we also included the femoral artery, as risk factors may differ in their effects on various arteries. We measured Lp(a) levels and intima-media thickness in a group of asymptomatic population controls. Major cardiovascular risk factors were assessed to examine the atherogenic effect of Lp(a) in addition to the conventional risk factors. Materials and methods Study designWe included 142 asymptomatic male volunteers who were randomly selected from the archives of the Leiden Anticoagulation Clinic (108 individuals) and asymptomatic friends (34 individuals) of patients who received anticoagulant treatment. All the individuals from the Leiden Anticoagulation Clinic received temporarily prophylactic anticoagulant treatment because of an orthopedic condition such as orthopedic surgery and fractures.

Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology

“…This would then cause a thickening of aortic valve leaflets and the arterial intima. However, as mentioned above, there is no human evidence to support that high Lp(a) concentrations promote early atherosclerosis (160,(208)(209)(210)(211)(212)(213), at least in the form of increased intima-media thickness.…”

“…In contrast, high Lp(a) concentrations or LPA risk alleles have not been associated with early atherosclerosis measured as modest intima-media thickening in carotid or femoral arteries (160,(208)(209)(210)(211)(212)(213); however, there is controversy as to whether such intima-media thickness represents atherosclerosis per se. For example, in the Young Finns Study, including 939 men and 1,141 women, data from observational and Mendelian randomization analyses provided no support for early atherogenic effects of high Lp(a) concentrations (211).…”

Lipoprotein(a) Genetic Variants Associated With Coronary and Peripheral Vascular Disease but Not With Stroke Risk in the Heart Protection Study

“…6 Furthermore, previous studies examining the associations of Lp(a) concentrations with carotid artery intima-media thickness and flow-mediated arterial dilation failed to demonstrate significant associations. [7][8][9][10][11][12][13] Understanding the effects of Lp(a) at different arterial sites may be informative about the mechanisms by which Lp(a) causes vascular disease and have relevance for potential therapies to lower Lp(a) levels for the prevention of atherothrombotic disease.…”

Relationship between Lipoprotein(a), Metabolic Syndrome, and Carotid Atherosclerosis in Older Japanese People

“…The plasma/serum Lp(a) level is considered an independent risk factor for atherosclerotic events such as cardiovascular and cerebrovascular disease [1] , while conflicting data exists [2,3] . Positive associations between Lp(a) and carotid artery intima-media thickness (CIMT), a well-established surrogate index of coronary/cerebral atherosclerosis, have reported in some [4,5] but not all [6][7][8] studies.…”