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Lipoprotein (a): An Update on a Marker of Residual Risk and Associated Clinical Manifestations.

ABSTRACT: Lipoprotein (a) [Lp(a)] is a low-density, cholesterol-containing lipoprotein that differs from other low-density lipoproteins due to the presence of apolipoprotein(a) bound to its surface apolipoprotein B100. Multiple epidemiologic studies, including Mendelian Randomization studies, have demonstrated that increasing Lp(a) levels are associated with increased risk of heart disease, including atherosclerotic cardiovascular disease and calcific aortic stenosis. The risk associated with elevations in Lp(a) appears to be independent of other lipid markers. While the current treatment options for elevated Lp(a) are limited, promising new therapies are under development, leading to renewed interest in Lp(a). This review provides an overview of the biology and epidemiology of Lp(a), available outcome studies, and insights into future therapies.

SUBMITTER: Shah NP

PROVIDER: S-EPMC7376542 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Lipoprotein (a): An Update on a Marker of Residual Risk and Associated Clinical Manifestations.

Shah Nishant P NP Pajidipati Neha J NJ McGarrah Robert W RW Navar Ann Marie AM Vemulapalli Sreekanth S Blazing Michael A MA Shah Svati H SH Hernandez Adrian F AF Patel Manesh R MR

The American journal of cardiology 20200407

Lipoprotein (a) [Lp(a)] is a low-density, cholesterol-containing lipoprotein that differs from other low-density lipoproteins due to the presence of apolipoprotein(a) bound to its surface apolipoprotein B100. Multiple epidemiologic studies, including Mendelian Randomization studies, have demonstrated that increasing Lp(a) levels are associated with increased risk of heart disease, including atherosclerotic cardiovascular disease and calcific aortic stenosis. The risk associated with elevations i ...[more]

PMID: 32336532

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Project description:Levels of LDL (low-density lipoprotein) cholesterol in the population are declining, and increasing attention is being focused on residual lipid-related pathways of atherosclerotic cardiovascular disease risk beyond LDL cholesterol. Among individuals with low (<130 mg/dL) LDL cholesterol, we undertook detailed profiling of circulating atherogenic lipoproteins in relation to incident cardiovascular disease in 2 populations. We performed proton nuclear magnetic resonance spectroscopy to quantify concentrations of LDL and VLDL (very low-density lipoprotein) particle subclasses in 11 984 JUPITER trial participants (NCT00239681). Adjusted Cox models examined cardiovascular disease risk associated with lipoprotein measures according to treatment allocation. Risk (adjusted hazard ratio [95%CI] per SD increment) among placebo-allocated participants was associated with total LDL particles (1.19 [1.02, 1.38]) and total VLDL particles (1.21 [1.04, 1.41]), as well as apolipoprotein B, non-high-density lipoprotein cholesterol, and triglycerides, but not LDL-c. Rosuvastatin reduced LDL measures but had variable effects on triglyceride and VLDL measures. On-statin levels of the smallest VLDL particle subclass were associated with a 68% per-SD (adjusted hazard ratio 1.68 [1.28, 2.22]) increase in residual risk-this risk was related to VLDL cholesterol and not triglyceride or larger VLDL particles. There was evidence that residual risk prediction during statin therapy could be significantly improved through the inclusion of key VLDL measures (Harrell C-index 0.780 versus 0.712; P<0.0001). In an independent, prospective cohort of 4721 individuals referred for cardiac catheterization (CATHGEN), similar patterns of lipoprotein-related risk were observed. Atherogenic lipoprotein particle concentrations were associated with cardiovascular disease risk when LDL cholesterol was low. VLDL lipoproteins, particularly the smallest remnant subclass, may represent unused targets for risk prediction and potential therapeutic intervention for reducing residual risk. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Project description:BackgroundChemically measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL measures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy.Methods and resultsIn Justification for the Use of statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10 886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/d or placebo. Levels were examined with first CVD (n=234). HDL-P correlated better with apoA-I (Spearman r=0.69, P<0.0001) than with HDL-C (r=0.55, P<0.0001). Rosuvastatin lowered low-density lipoprotein cholesterol (49%) and raised HDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%), and HDL size (1.2%); all P<0.0001. Among placebo-allocated individuals, on-treatment HDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor-adjusted hazard ratio and 95% confidence interval per 1 standard deviation: 0.79 [0.63-0.98], 0.75 [0.62-0.92], and 0.81 [0.67-0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57-0.93, P=0.01) than HDL-C (0.82, 0.63-1.08, P=0.16) or apoA-I (0.86, 0.67-1.10, P=0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53-0.97, P=0.03) after additionally adjusting for HDL-C. In risk factor-adjusted models, HDL size showed no significant association with CVD.ConclusionsIn the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT00239681.

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Project description:BACKGROUND:In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil). METHODOLOGY:The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002-2009), the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. PRINCIPAL FINDINGS:Model 1 (period 2002-2009; 111 deaths from VL and 777 cured patients) included the variables present in both SINAN versions, whereas Model 2 (period 2007-2009; 49 deaths from VL and 327 cured patients) included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3-6.4), Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2-4.8) and age ?60 years (OR 2.5; 95%CI 1.5-4.3). In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2-10.3), other associated infections (OR 3.2; 95%CI 1.3-7.8), jaundice (OR 10.1; 95%CI 3.7-27.2) and age ?60 years (OR 3.1; 95%CI 1.4-7.1). The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2). The predictive performance of which was evaluated by sensitivity (71.4%), specificity (73.7%), positive and negative predictive values (28.9% and 94.5%) and area under the receiver operating characteristic curve (75.6%). CONCLUSIONS:Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower mortality.

Dataset Information

Lipoprotein (a): An Update on a Marker of Residual Risk and Associated Clinical Manifestations.

Publications

Lipoprotein (a): An Update on a Marker of Residual Risk and Associated Clinical Manifestations.

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