Lipoprotein(a): a promising marker for residual cardiovascular risk assessment.
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ABSTRACT:
SUBMITTER: Cai A
PROVIDER: S-EPMC3819768 | biostudies-literature | 2013
REPOSITORIES: biostudies-literature
Publications
Lipoprotein(a): a promising marker for residual cardiovascular risk assessment.
Cai Anping A Li Liwen L Zhang Ying Y Mo Yujin Y Mai Weiyi W Zhou Yingling Y
Disease markers 20131022 5
Atherosclerotic cardiovascular diseases (CVD) are still the leading cause of morbidity and mortality worldwide, although optimal medical therapy has been prescribed for primary and secondary preventions. Residual cardiovascular risk for some population groups is still considerably high although target low density lipoprotein-cholesterol (LDL-C) level has been achieved. During the past few decades, compelling pieces of evidence from clinical trials and meta-analyses consistently illustrate that l ...[more]
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Project description:BackgroundCurrent guidelines target low-density lipoprotein cholesterol (LDL-C) concentrations to reduce atherosclerotic cardiovascular disease (ASCVD) risk, and yet clinical trials demonstrate persistent residual ASCVD risk despite aggressive LDL-C lowering.ContentNon-LDL-C lipid parameters, most notably triglycerides, triglyceride-rich lipoproteins (TGRLs), and lipoprotein(a), and C-reactive protein as a measure of inflammation are increasingly recognized as associated with residual risk after LDL-C lowering. Eicosapentaenoic acid in statin-treated patients with high triglycerides reduced both triglycerides and ASCVD events. Reducing TGRLs is believed to have beneficial effects on inflammation and atherosclerosis. High lipoprotein(a) concentrations increase ASCVD risk even in individuals with LDL-C < 70 mg/dL. Although statins do not generally lower lipoprotein(a), proprotein convertase subtilisin/kexin type 9 inhibitors reduce lipoprotein(a) and cardiovascular outcomes, and newer approaches are in development. Persistent increases in C-reactive protein after intensive lipid therapy have been consistently associated with increased risk for ASCVD events.SummaryWe review the evidence that biochemical assays to measure TGRLs, lipoprotein(a), and C-reactive protein are associated with residual risk in patients treated to low concentrations of LDL-C. Growing evidence supports a causal role for TGRLs, lipoprotein(a), and inflammation in ASCVD; novel therapies that target TGRLs, lipoprotein(a), and inflammation are in development to reduce residual ASCVD risk.
| S-EPMC7793228 | biostudies-literature
Project description: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.
| S-EPMC7376542 | biostudies-literature
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.
| S-EPMC5586287 | biostudies-literature
Project description:BackgroundCardiovascular disease risk increases when lipoprotein metabolism is dysfunctional. We have developed a computational model able to derive indicators of lipoprotein production, lipolysis, and uptake processes from a single lipoprotein profile measurement. This is the first study to investigate whether lipoprotein metabolism indicators can improve cardiovascular risk prediction and therapy management.Methods and resultsWe calculated lipoprotein metabolism indicators for 1981 subjects (145 cases, 1836 controls) from the Framingham Heart Study offspring cohort in which NMR lipoprotein profiles were measured. We applied a statistical learning algorithm using a support vector machine to select conventional risk factors and lipoprotein metabolism indicators that contributed to predicting risk for general cardiovascular disease. Risk prediction was quantified by the change in the Area-Under-the-ROC-Curve (?AUC) and by risk reclassification (Net Reclassification Improvement (NRI) and Integrated Discrimination Improvement (IDI)). Two VLDL lipoprotein metabolism indicators (VLDLE and VLDLH) improved cardiovascular risk prediction. We added these indicators to a multivariate model with the best performing conventional risk markers. Our method significantly improved both CVD prediction and risk reclassification.ConclusionsTwo calculated VLDL metabolism indicators significantly improved cardiovascular risk prediction. These indicators may help to reduce prescription of unnecessary cholesterol-lowering medication, reducing costs and possible side-effects. For clinical application, further validation is required.
| S-EPMC3965475 | biostudies-literature
Project description:BACKGROUND:Although lipoprotein(a) [Lp(a)] is associated with incident cardiovascular disease (CVD), its contribution to prediction remains controversial. OBJECTIVES:This study examined the association and clinical utility of Lp(a) with incident CVD in women. METHODS:A turbidimetric assay assessed Lp(a) in 3 cohorts of women (the WHS [Women's Health Study] [N = 24,558], a case-cohort sample from the WHI [Women's Health Initiative] Observational Study [n = 1,815 cases, subcohort n = 1,989], and the JUPITER [Justification for Use of Statins in Prevention] trial [n = 2,569]) and in men from JUPITER (n = 5,161). A WHS derivation sample (n = 16,400) determined the form of association with incident CVD. This was tested in WHS validation data (n = 8,158) and the other study samples. Models including traditional CV risk factors but with and without Lp(a) were compared using risk reclassification. RESULTS:In the WHS, there was a curvilinear association, with increased CVD risk among those with Lp(a) >50 mg/dl, but only among women with total cholesterol (TC) >220 mg/dl. In the WHS test sample, there was a small but significant change in the C-statistic (0.790 to 0.797; p = 0.035) but no improvement in measures of reclassification. This pattern was replicated among women in the WHI and JUPITER trial. In contrast, there was a strong association of Lp(a) with CVD among men with low TC levels in JUPITER. CONCLUSIONS:In 3 cohorts of women, Lp(a) was associated with CVD only among those with high TC, and improvement in prediction was minimal. These data have implications for Lp(a) in clinical practice among women and for trials of Lp(a)-lowering agents.
| S-EPMC6277983 | biostudies-literature
Project description:AimsThe aims of the study were, first, to critically evaluate lipoprotein(a) [Lp(a)] as a cardiovascular risk factor and, second, to advise on screening for elevated plasma Lp(a), on desirable levels, and on therapeutic strategies.Methods and resultsThe robust and specific association between elevated Lp(a) levels and increased cardiovascular disease (CVD)/coronary heart disease (CHD) risk, together with recent genetic findings, indicates that elevated Lp(a), like elevated LDL-cholesterol, is causally related to premature CVD/CHD. The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels. Mechanistically, elevated Lp(a) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a) resembles both plasminogen and plasmin but has no fibrinolytic activity, or may accelerate atherosclerosis because, like LDL, the Lp(a) particle is cholesterol-rich, or both. We advise that Lp(a) be measured once, using an isoform-insensitive assay, in subjects at intermediate or high CVD/CHD risk with premature CVD, familial hypercholesterolaemia, a family history of premature CVD and/or elevated Lp(a), recurrent CVD despite statin treatment, ≥3% 10-year risk of fatal CVD according to European guidelines, and/or ≥10% 10-year risk of fatal + non-fatal CHD according to US guidelines. As a secondary priority after LDL-cholesterol reduction, we recommend a desirable level for Lp(a) <80th percentile (less than ∼50 mg/dL). Treatment should primarily be niacin 1-3 g/day, as a meta-analysis of randomized, controlled intervention trials demonstrates reduced CVD by niacin treatment. In extreme cases, LDL-apheresis is efficacious in removing Lp(a).ConclusionWe recommend screening for elevated Lp(a) in those at intermediate or high CVD/CHD risk, a desirable level <50 mg/dL as a function of global cardiovascular risk, and use of niacin for Lp(a) and CVD/CHD risk reduction.
| S-EPMC3295201 | biostudies-literature
Project description:BackgroundHypertensive individuals on blood pressure (BP)-lowering treatment with BP in the normal or high-normal range have higher cardiovascular risk than untreated persons with usual BP in the same range. This residual risk (relative and absolute) is not well quantified and may be attributable in part to the higher burden of subclinical disease in treated individuals.Methods and resultsWe assigned 3024 Framingham Offspring Cohort participants to 5 categories based on systolic BP (SBP) and diastolic BP (DBP) and use of BP-lowering treatment: (1) untreated SBP/DBP <120/80 mm Hg; (2) untreated SBP/DB ?120/80 to <140/90 mm Hg; (3) treated SBP/DBP <140/90 mm Hg; (4) untreated SBP/DBP ?140/90 mm Hg; and (5) treated SBP/DBP ?140/90 mm Hg. A composite subclinical disease score was constructed, including information on left ventricular hypertrophy, systolic dysfunction, carotid ultrasound abnormality, peripheral artery disease, and microalbuminuria. The prevalence of subclinical disease rose across BP groups, as did the event rates for incident cardiovascular disease (449 events, median follow-up of 11 years; group 1, 0.65 event per 100 person-years; group 5, 3.20 events per 100 person-years; P<0.0001 for trend). On multivariable adjustment, treated hypertensives in groups 3 and 5 had 50% (95% CI 13% to 99%) and 28% (95% CI -6% to 73%) higher hazards, respectively, of developing cardiovascular disease compared with their untreated counterparts with similar levels of BP (groups 1 and 2 and group 4, respectively). The increased risk of cardiovascular disease in treated hypertensives was attributable in part to greater subclinical disease burden.ConclusionsTreated hypertensives have higher subclinical cardiovascular disease burden, which partly explains their higher cardiovascular disease risk compared with untreated persons with similar BP levels.
| S-EPMC4845218 | biostudies-literature
Project description:Background Conventional "low-density lipoprotein cholesterol (LDL-C)" assays measure cholesterol content in both low-density lipoprotein and lipoprotein(a) particles. To clarify the consequences of this methodological limitation for clinical care, our study aimed to compare associations of "LDL-C" and corrected LDL-C with risk of cardiovascular disease and to assess the impact of this correction on the classification of patients into guideline-recommended LDL-C categories. Methods and Results Lipoprotein(a) cholesterol content was estimated as 30% of lipoprotein(a) mass and subtracted from "LDL-C" to obtain corrected LDL-C values (LDL-Ccorr30). Hazard ratios for cardiovascular disease (defined as coronary heart disease, stroke, or coronary revascularization) were quantified by individual-patient-data meta-analysis of 5 statin landmark trials from the Lipoprotein(a) Studies Collaboration (18 043 patients; 5390 events; 4.7 years median follow-up). When comparing top versus bottom quartiles, the multivariable-adjusted hazard ratio for cardiovascular disease was significant for "LDL-C" (1.17; 95% CI, 1.05-1.31; P=0.005) but not for LDL-Ccorr30 (1.07; 95% CI, 0.93-1.22; P=0.362). In a routine laboratory database involving 531 144 patients, reclassification of patients across guideline-recommended LDL-C categories when using LDL-Ccorr30 was assessed. In "LDL-C" categories of 70 to <100, 100 to <130, 130 to <190, and ?190 mg/dL, significant proportions (95% CI) of participants were reassigned to lower LDL-C categories when LDL-Ccorr30 was used: 30.2% (30.0%-30.4%), 35.1% (34.9%-35.4%), 32.9% (32.6%-33.1%), and 41.1% (40.0%-42.2%), respectively. Conclusions "LDL-C" was associated with incident cardiovascular disease only when lipoprotein(a) cholesterol content was included in its measurement. Refinement in techniques to accurately measure LDL-C, particularly in patients with elevated lipoprotein(a) levels, is warranted to assign risk to the responsible lipoproteins.
| S-EPMC7763787 | biostudies-literature
Project description:Cardiovascular disease (CVD) is among the leading causes of death and disability worldwide. Since its beginning, the Framingham study has been a leader in identifying CVD risk factors. Clinical trials have demonstrated that when the modifiable risk factors are treated and corrected, the chances of CVD occurring can be reduced. The Framingham study also recognized that CVD risk factors are multifactorial and interact over time to produce CVD. In response, Framingham investigators developed the Framingham Risk Functions (also called Framingham Risk Scores) to evaluate the chance or likelihood of developing CVD in individuals. These functions are multivariate functions (algorithms) that combine the information in CVD risk factors such as sex, age, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, smoking behavior, and diabetes status to produce an estimate (or risk) of developing CVD or a component of CVD (such as coronary heart disease, stroke, peripheral vascular disease, or heart failure) over a fixed time, for example, the next 10 years. These estimates of CVD risk are often major inputs in recommending drug treatments such as cholesterol-lowering drugs.
| S-EPMC3673738 | biostudies-other
Project description:Although patients with diabetes have 2 to 4 times increased risk of cardiovascular morbidity and mortality than individuals without diabetes, recent studies indicate that a significant part of patients are in a lower cardiovascular risk category. Men younger than 35 years, women younger than 45 years, patients with diabetes duration of less than 10 years without other risk factors have a much lower risk than patients who have traditional cardiovascular risk factors, and subclinical or established coronary artery disease (CAD). These patients are not risk equivalent as stated in previous studies. On the contrary, when in the presence of traditional risk factors or evidence of subclinical coronary disease (e.g. high coronary calcium score), the coronary risk is much increased and patients may be classified at a higher-risk category. Recent guidelines do not anymore consider diabetes as a CAD risk equivalent and recommend cardiovascular risk stratification for primary prevention. Stratification of diabetic patients improves accuracy in prediction of subclinical CAD, silent ischemia and future cardiovascular events. Stratification also discriminates higher from lower risk patients who may need intensive statin or aspirin prevention, while avoiding overtreatment in lower risk cases. It may also allow the clinician to decide whether to intensify risk reduction actions through specific newer drugs for glucose control such as SGLT-2 inhibitors or GLP-1 agonists, which recently have shown additional cardiovascular protector effect. This review addresses the assessment of cardiovascular disease risk using traditional and non-traditional cardiovascular risk factors. It also reviews the use of risk calculators and new reclassification tools, focusing on the detection of subclinical atherosclerosis as well as silent ischemia in the asymptomatic patients with diabetes.
| S-EPMC5397821 | biostudies-other