Plasma Lipoprotein(a) Concentration Predicts Future Coronary and Cardiovascular Events in Patients With Stable Coronary Heart Disease

Nestel, Paul J.; Barnes, Elizabeth H; Tonkin, Andrew; Simes, John; Fournier, Marion; White, Harvey D.; Colquhoun, David; Blankenberg, Stefan; Sullivan, David

doi:10.1161/atvbaha.113.302479

Cited by 121 publications

(74 citation statements)

References 39 publications

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“…Three recent studies have linked high Lp(a) to increased residual cardiovascular risk, despite optimal LDL-C reduction. [28][29][30] This supports our finding of high Lp(a) being associated with residual vascular risk after the first-ever ischemic stroke independent of other risk factors, such as LDL-C.…”

Section: Discussionsupporting

confidence: 85%

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke

Lange

Nave

Liman

et al. 2017

Stroke

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Background and Purpose— The association of elevated lipoprotein(a) (Lp(a)) levels and the incidence of cardiovascular disease, especially coronary heart disease and ischemic stroke, is well established. However, evidence on the association between Lp(a) levels and residual vascular risk in stroke survivors is lacking. We aimed to elucidate the risk for recurrent cardiovascular and cerebrovascular events in the patients with first-ever ischemic stroke with elevated Lp(a). Methods— All patients with acute ischemic stroke who participated in the prospective Berlin C&S study (Cream & Sugar) between January 2009 and August 2014 with available 12-month follow-up data and stored blood samples were eligible for inclusion. Lp(a) levels were determined in serum samples using an isoform-insensitive nephelometry assay. We assessed the risk for the composite vascular end point of ischemic stroke, transient ischemic attack, myocardial infarction, nonelective coronary revascularization, and cardiovascular death with elevated Lp(a) defined as >30 mg/dL using Cox regression analyses. Results— Of 465 C&S study participants, 250 patients were included into this substudy with a median National Institutes of Health Stroke Scale score of 2 (1–4). Twenty-six patients (10%) experienced a recurrent vascular event during follow-up. Among patients with normal Lp(a) levels, 11 of 157 subjects (7%) experienced an event at a median time of 161 days (interquartile range, 19–196 days), whereas in patients with elevated Lp(a) levels, 15 of 93 subjects (16%) experienced an event at a median time of 48 days (interquartile range, 9–194 days; P =0.026). The risk for a recurrent event was significantly higher in patients with elevated Lp(a) levels after adjustment for potential confounders (hazard ratio, 2.60; 95% confidence interval, 1.19–5.67; P =0.016). Conclusions— Elevated Lp(a) levels are associated with a higher risk for combined vascular event recurrence in patients with acute, first-ever ischemic stroke. This finding should be validated in larger, multicenter trials. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01378468.

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Section: Discussionsupporting

confidence: 85%

Lipoprotein(a) Levels and Recurrent Vascular Events After First Ischemic Stroke

Lange

Nave

Liman

et al. 2017

Stroke

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“…12,16,17 Lp(a) has been implicated in both atherogenesis and thrombosis. [18][19][20][21][22][23][24][25] Our study also demonstrated that the plasma Lp(a) levels were significantly elevated according to the quartiles of the Gensini scores in CAD patients. The alleles of 2 SNPs in the LPA gene, rs10455872 and rs3798220, have been shown to be associated with high plasma levels of Lp(a) and CAD in Europeans.…”

Section: Discussionsupporting

confidence: 71%

Functional Variant in the SLC22A3-LPAL2-LPA Gene Cluster Contributes to the Severity of Coronary Artery Disease

Wang¹,

Chen²,

Zeng³

et al. 2016

ATVB

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Objective— Recent genome-wide association studies have identified that genetic variants in the SLC22A3-LPAL2-LPA gene cluster influence plasma lipoprotein(a) [Lp(a)] concentration. However, the association between this gene cluster and the severity of coronary artery disease (CAD), especially the potential underlying mechanism, remains unclear. The purpose of this study was to investigate the association between variation in the SLC22A3-LPAL2-LPA gene cluster and CAD. Approach and Results— We performed 2-stage case–control studies in a Chinese Han population. The variant genotypes were examined for their association with both Lp(a) level and severity of CAD. Putative mechanisms were also evaluated. One single nucleotide polymorphism, rs3088442, in the SLC22A3-LPAL2-LPA gene cluster was significantly associated with both plasma Lp(a) levels and CAD severity. The gene dosage of the risk allele at rs3088442 indicated a robust association with left main trunk disease ( P =0.046), number of vascular lesions ( P =4.5×10 –3 ), and Gensini scores ( P =0.012) in patients with CAD. Reporter gene analysis indicated that the rs3088442 G allele might suppress miR-147a binding to the 3′ untranslated region of SLC22A3 , resulting in altered SLC22A3 and LPA gene expression ( P =0.015 and 9.2×10 –6 , respectively), possibly explaining the increased plasma Lp(a) levels and risk of CAD. Conclusions— The genotype of rs3088442 within the SLC22A3-LPAL2-LPA gene cluster may contribute to regulation of plasma Lp(a) levels and possibly to the severity of CAD in a Chinese Han population.

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“…This threshold was based on prevalence of Lp(a) values in the general population and not necessarily based on when risk of Lp(a) begins. Epidemiological and genetic studies suggest the risk thresholds start at 25-30 mg/dl in primary care populations ( 1,14,20 ), but >50 mg/dl in secondary prevention populations that have been treated with several secondary prevention measures such as aspirin, clopidogrel, statins, and antihypertensive medications ( 22,23 ). Our fi ndings suggest that the thresholds for determining what is a high level and who is at risk should be reported as assay-specifi c thresholds until assays from all manufacturers are sufficiently standardized and each assay provides the same absolute values for a given plasma sample.…”

Section: Resultsmentioning

confidence: 99%