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Aortic valve stenosis (AVS), the most common form of valve disease in the western world, afflicts more than 1 million individuals in North America and the burden of AVS is high and is expected to double within the next 50 years. Medical therapy to prevent development or reduce progression of AVS is currently not available and the only effective treatment for AVS is aortic valve replacement, for which costs have been estimated up to 120,000$. Recently, we and others have identified rs10455872 at the LPA locus as a susceptibility single nucleotide polymorphism (SNP) for aortic valve calcification (AVC) and AVS [5,6] and rs10455872 is associated with elevated plasma lipoprotein (Lp)(a) levels. Lp(a) is a LDL-like particle consisting of hepatically synthesized apolipoprotein B-100 that is noncovalently bound to the plasminogen-like glycoprotein apolipoprotein(a). Lp(a) promotes atherosclerotic stenosis, and possibly thrombosis, and has been hypothesized to contribute to wound healing, each of which could explain an association with AVS. Lp(a) is relatively refractory to both lifestyle and drug intervention, with only nicotinic acid and monoclonal antibody inhibition of the proprotein convertase subtilisin/kexin type 9 that have showed reductions in Lp(a) levels. However, the evidence that patients with AVS could be characterized by high Lp(a) levels is scarce. Glader et al. showed that plasma levels of Lp(a) were almost 1.5-fold higher in 101 patients with AVS compared to matched controls, although this relationship did not reach statistical significance. Subsequent studies have also reported an association between elevated plasma Lp(a) levels and higher prevalence of AVS. More specifically, Kamstrup and colleagues reported that elevated Lp(a) levels and corresponding genotypes were associated with increased risk of AVS in the general population with levels >90 mg/dL predicting a threefold increased risk. We have measured Lp(a) and oxidized phospholipids plasma levels in 220 patients with mild-to-moderate calcific AVS enrolled in the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial. Results of this study suggest that high Lp(a) and oxidized phospholipids both predict calcific AVS progression, especially in younger patients with calcific AVS. We also found that statin therapy considerably increased both Lp(a) and oxidized phospholipids levels. Whether the fact that statins increase these risk factors for calcific AVS might explain at least to a certain extent why statins failed to promote calcific AVS regression or stabilization in at least four trials, including ASTRONOMER.
Familial hypercholesterolemia (FH) is an autosomal codominant single-gene disorder caused by mutations in the LDL receptor gene that disrupt normal clearance of LDL. Phenotypic features characteristic of the disease's heterozygous form are 2- to 3-fold raise in plasma LDL-cholesterol concentrations, tendinous xanthomatosis and premature atherosclerotic coronary artery disease. High Lp(a) levels have been shown to explain residual cardiovascular disease risk in FH. Recent studies have demonstrated that FH heterozygotes have elevated AVC compared with non-FH subjects and that Lp(a) levels were positively correlated with AVC in asymptomatic FH heterozygotes . Vongpromek et al. demonstrated that plasma Lp(a) concentration is a independent risk factor for AVC in a cohort of 129 asymptomatic heterozygous FH patients aged between 40 and 69 years. In this study, AVC was significantly associated with plasma Lp(a) level, age, body mass index, blood pressure, duration of statin use, cholesterol-year score and coronary artery calcification (CAC) score.
Observational Model: Case Control, Time Perspective: Cross-Sectional
Heterozygous Familial Hypercholesterolemia
Institute of Nutrition and Functional Foods (INAF)
Not yet recruiting
Published on BioPortfolio: 2016-11-30T15:45:14-0500
The purpose of this study is to determine if implitapide, used in conjunction with other lipid-lowering therapies, is safe and effective when compared to placebo in lowering low-density li...
The purpose of the study is to assess the safety and efficacy of fluvastatin in children diagnosed with heterozygous familial hypercholesterolemia
A Phase 2 study of patients with HeFH
This is a randomized, double-blind, placebo-controlled, parallel-group, multi-national study alirocumab (REGN727/ SAR236553) in patients with Heterozygous Familial Hypercholesterolemia (he...
To evaluate the efficacy and safety of dosing with mipomersen for 26 weeks in subjects with heterozygous familial hypercholesterolemia (HeFH) and coronary artery disease (CAD) on lipid-low...
The role of plasma cholesterol in impairing arterial function and elasticity remains unclear. We evaluated arterial stiffness, measured locally in the common carotid artery by high-resolution echo-tra...
Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were recently approved for lowering low-density lipoprotein cholesterol in heterozygous familial hypercholesterolemia (FH) or atheroscl...
Familial hypercholesterolemia (FH) is the most common and serious monogenic disorder of lipid metabolism, causing premature coronary heart disease (CHD) due to accelerated atherosclerosis from birth, ...
To evaluate the effectiveness of criteria based on child-parent assessment in predicting familial hypercholesterolemia (FH)-causative mutations in unselected children with hypercholesterolemia.
A group of HEREDITARY AUTOINFLAMMATION DISEASES, characterized by recurrent fever, abdominal pain, headache, rash, PLEURISY; and ARTHRITIS. ORCHITIS; benign MENINGITIS; and AMYLOIDOSIS may also occur. Homozygous or compound heterozygous mutations in marenostrin gene result in autosomal recessive transmission; simple heterozygous, autosomal dominant form of the disease.
The condition of being heterozygous for hemoglobin S.
Diseases in which there is a familial pattern of AMYLOIDOSIS.
A familial disorder marked by AMYLOID deposits in the walls of small and medium sized blood vessels of CEREBRAL CORTEX and MENINGES.
A condition with abnormally high levels of CHOLESTEROL in the blood. It is defined as a cholesterol value exceeding the 95th percentile for the population.