Cost-Effectiveness Model of Use of Genetic Testing as an Aid in Assessing the Likely Benefit of Aspirin Therapy for Primary Prevention of Cardiovascular Disease

Shiffman, Dov; Slawsky, K; Fusfeld, Lauren; Devlin, James J.; Goss, Thomas F.

doi:10.1016/j.clinthera.2012.04.004

Cited by 13 publications

(10 citation statements)

References 16 publications

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“…7 The variants have been reported to be associated with small apo(a) alleles in whites, 7 and it had been suggested that they could be used as surrogate markers to identify small apo(a) isoforms associated with high Lp(a) and increased risk. 17 However, 35.2% of the clinically recognized, highly selected Pro(a)LiFe patients with a small apo(a) phenotype would not be tagged by either of these SNPs, which suggests that these 2 SNPs would classify 35.2% of patients incorrectly to be at low Lp(a)-associated risk. A similar finding has been reported for the general German population in which 47% of the individuals carrying a small apo(a) isoform would not be identified by these 2 SNPs.…”

Section: Discussionmentioning

confidence: 99%

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

Roeseler

Julius

Heigl

et al. 2016

ATVB

187

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Objective— Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. Approach and Results— This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene ( LPA ) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter ( P <0.0001); 95.3% of patients expressed at least 1 small apo(a) isoform. Small apo(a) isoform (35.2%) carrying phenotypes were not tagged by single-nucleotide polymorphisms rs10455872 or rs3798220. Conclusions— Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

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Section: Discussionmentioning

confidence: 99%

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

Roeseler

Julius

Heigl

et al. 2016

ATVB

187

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“…Shiffman et al 28 have proposed genetic testing to improve aspirin usage for primary prevention. Their model starts with the assumption that using aspirin for individuals with a Ն10% Framingham risk score for CVD is beneficial, a position not supported by the literature.…”

Section: Discussionmentioning

confidence: 99%

Effects of Changing Guidelines on Prescribing Aspirin for Primary Prevention of Cardiovascular Events

Hissett

Folks

Coombs

et al. 2014

The Journal of the American Board of Family Medicine

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Objective: The use of low-dose aspirin for primary prevention of cardiovascular events in patients at elevated risk for cardiovascular disease (CVD) is increasingly being questioned. Aspirin may not benefit this population and may increase the risk of major bleeding events. Data support aspirin use in patients with known CVD.Methods: This is a secondary analysis of de-identified electronic health record (

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“…The question of whether the results of such association studies in one population (i.e., Europeans) are valid for other ethnic groups has recently been addressed for the nonsynonymous SNP, rs3798220 (201). This SNP has been promoted by commercial laboratories for CHD risk screening, as it tags high risk LPA alleles in Europeans, claiming that it was a cost-efficient way to assess the risk potential of LPA and provide guidance on the benefit of aspirin therapy for prevention of CVD (227). The variant allele of r33798220 is found at low frequencies in African Americans and Europeans, while at much higher frequencies in Asian populations and with highest frequencies in admixed Americans (Mexicans, Columbians, Puerto Ricans, and Peruvians), but it is absent in autochthonous Africans (199,201).…”

Section: New Phenotypic Associations Of Lp(a)mentioning

confidence: 99%

Structure, function, and genetics of lipoprotein (a)

Schmidt

Noureen

Kronenberg

et al. 2016

Journal of Lipid Research

445

346

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between apoB-100 of the LDL moiety and one of the kringle domains in apo(a) (4,5,(14)(15)(16). The assembly of Lp(a) is believed to occur at the hepatocyte cell membrane surface (17), but other scenarios have also been proposed [reviewed in (18, 19)].Lp(a) was originally described as a dichotomous (Lp+, Lp) genetic trait (20), but it soon became evident that it is quantitative rather than qualitative in nature (21-23). Lp(a) plasma concentrations are highly heritable (24-28). The major locus controlling the Lp(a) concentrations is the LPA gene (MIM 152200; ENSG00000198670) on the reverse strand of chromosome 6q27 (29-31), which encodes the apo(a) component of Lp(a) (25,26,(32)(33)(34). Close LPA orthologs are found in all apes and in Old World monkeys. INTRA-AND INTER-POPULATION DIFFERENCES INLp ( INTRODUCTION TO THE LIPOPROTEIN (a) TRAITHuman lipoprotein (a) [Lp(a)] is a macromolecular complex in plasma that was first described in 1963 by the Norwegian physician Kåre Berg (1). Ever since its discovery, this enigmatic particle has intrigued basic researchers and clinicians due to its unknown physiological function and its association with atherosclerotic diseases, in particular coronary heart disease (CHD) [reviewed in (2)]. Lp(a) is composed of one molecule of a LDL-particle containing apoB-100 and one molecule of a large highly polymorphic glycoprotein named apo(a) (3-6). A characteristic feature of apo(a) is the presence of loop-like structures called kringles (7,8). Kringle domains are triple loop structures stabilized by three internal disulfide bonds and are also present in other coagulation factors, such as plasminogen (PLG), prothrombin, urokinase, and tissue-type PLG activators (9-12). In contrast to PLG, the linker domain between kringles is glycosylated in apo(a). The apo(a) is synthesized by the liver (13). The two components of Lp(a) are covalently linked together by a disulfide bond

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Cost-Effectiveness Model of Use of Genetic Testing as an Aid in Assessing the Likely Benefit of Aspirin Therapy for Primary Prevention of Cardiovascular Disease

Cited by 13 publications

References 16 publications

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

Lipoprotein Apheresis for Lipoprotein(a)-Associated Cardiovascular Disease

Effects of Changing Guidelines on Prescribing Aspirin for Primary Prevention of Cardiovascular Events

Structure, function, and genetics of lipoprotein (a)

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