Dataset Information

On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin).

ABSTRACT: The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), trigylcerides, or lipid ratios, and how they compare with on-treatment LDL-C.Guidelines focus on LDL-C as the primary target of therapy, yet residual risk for cardiovascular disease (CVD) among statin-treated individuals remains high and not fully explained.Participants in the randomized placebo-controlled JUPITER (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) trial were adults without diabetes or CVD, with baseline LDL-C levels <130 mg/dl, high-sensitivity C-reactive protein levels ?2 mg/l, and triglyceride concentrations <500 mg/dl. Individuals allocated to receive rosuvastatin 20 mg daily with baseline and on-treatment lipids and lipoproteins were examined in relation to the primary endpoint of incident CVD (nonfatal myocardial infarction or stroke, hospitalization for unstable angina, arterial revascularization, or cardiovascular death).Using separate multivariate Cox models, statistically significant associations of a similar magnitude with residual risk of CVD were found for on-treatment LDL-C, non-HDL-C, apolipoprotein B, total cholesterol/HDL-C, LDL-C/HDL-C, and apolipoprotein B/A-I. The respective adjusted standardized hazard ratios (95% confidence intervals) for each of these measures were 1.31 (1.09 to 1.56), 1.25 (1.04 to 1.50), 1.27 (1.06 to 1.53), 1.22 (1.03 to 1.44), 1.29 (1.09 to 1.52), and 1.27 (1.09 to 1.49). The overall residual risk and the risk associated with these measures decreased among participants achieving on-treatment LDL-C ?70 mg/dl, on-treatment non-HDL-C ?100 mg/dl, or on-treatment apolipoprotein B ?80 mg/dl. In contrast, on-treatment triglycerides showed no association with CVD.In this primary prevention trial of nondiabetic individuals with low LDL-C and elevated high-sensitivity C-reactive protein, on-treatment LDL-C was as valuable as non-HDL-C, apolipoprotein B, or ratios in predicting residual risk. (JUPITER-Crestor 20mg Versus Placebo in Prevention of Cardiovascular [CV] Events; NCT00239681).

SUBMITTER: Mora S

PROVIDER: S-EPMC3338194 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin).

Mora Samia S Glynn Robert J RJ Boekholdt S Matthijs SM Nordestgaard Børge G BG Kastelein John J P JJ Ridker Paul M PM

Journal of the American College of Cardiology 20120401 17

<h4>Objectives</h4>The goal of this study was to determine whether residual risk after high-dose statin therapy for primary prevention individuals with reduced levels of low-density lipoprotein cholesterol (LDL-C) is related to on-treatment apolipoprotein B, non-high-density lipoprotein cholesterol (non-HDL-C), trigylcerides, or lipid ratios, and how they compare with on-treatment LDL-C.<h4>Background</h4>Guidelines focus on LDL-C as the primary target of therapy, yet residual risk for cardiovas ...[more]

PMID: 22516441

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Project description:Lipoprotein(a) [Lp(a)] is a low-density lipoprotein-like particle largely independent of known risk factors and predictive of cardiovascular disease. Statins may offset the risk associated with elevated Lp(a), but it is unknown whether Lp(a) is a determinant of residual risk in the setting of low low-density lipoprotein cholesterol after potent statin therapy.Baseline and on-treatment Lp(a) concentrations were assessed in 9612 multiethnic participants in the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin) before and after random allocation to rosuvastatin 20 mg/d or placebo, with outcomes reported for whites (n=7746). Lp(a) concentrations (median [25th-75th percentile], in nmol/L) were highest in blacks (60 [34-100]), then Asians (38 [18-60]), Hispanics (24 [11-46]), and whites (23 [10-50]; P<0.001). Although the median change in Lp(a) with rosuvastatin and placebo was zero, rosuvastatin nonetheless resulted in a small but statistically significant positive shift in the overall Lp(a) distribution (P<0.0001). Baseline Lp(a) concentrations were associated with incident cardiovascular disease (adjusted hazard ratio per 1-SD increment in Ln[Lp(a)], 1.18; 95% confidence interval, 1.03-1.34; P=0.02). Similarly, on-statin Lp(a) concentrations were associated with residual risk of cardiovascular disease (adjusted hazard ratio, 1.27; 95% confidence interval, 1.01-1.59; P=0.04), which was independent of low-density lipoprotein cholesterol and other factors. Rosuvastatin significantly reduced incident cardiovascular disease among participants with baseline Lp(a) greater than or equal to the median (hazard ratio, 0.62; 95% confidence interval, 0.43-0.90) and Lp(a) less than the median (hazard ratio, 0.46; 95% confidence interval, 0.30-0.72), with no evidence of interaction. Similar results were obtained when analyses included nonwhites.Among white JUPITER participants treated with potent statin therapy, Lp(a) was a significant determinant of residual risk. The magnitude of relative risk reduction with rosuvastatin was similar among participants with high or low Lp(a).http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Project description:BackgroundCardiovascular disease (CVD) can occur in individuals with low low-density lipoprotein (LDL) cholesterol (LDL-C). We investigated whether detailed measures of LDL subfractions and other lipoproteins can be used to assess CVD risk in a population with both low LDL-C and high C-reactive protein who were randomized to high-intensity statin or placebo.Methods and resultsIn 11 186 Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) participants, we tested whether lipids, apolipoproteins, and ion mobility-measured particle concentrations at baseline and after random allocation to rosuvastatin 20 mg/d or placebo were associated with first CVD events (n=307) or CVD/all-cause death (n=522). In placebo-allocated participants, baseline LDL-C was not associated with CVD (adjusted hazard ratio [HR] per SD, 1.03; 95% confidence interval [CI], 0.88-1.21). In contrast, associations with CVD events were observed for baseline non-high-density lipoprotein (HDL) cholesterol (HR, 1.18; 95% CI, 1.01-1.38), apolipoprotein B (HR, 1.28; 95% CI, 1.11-1.48), and ion mobility-measured non-HDL particles (HR, 1.19; 95% CI, 1.05-1.35) and LDL particles (HR, 1.21; 95% CI, 1.07-1.37). Association with CVD events was also observed for several LDL and very-low-density lipoprotein subfractions but not for ion mobility-measured HDL subfractions. In statin-allocated participants, CVD events were associated with on-treatment LDL-C, non-HDL cholesterol, and apolipoprotein B; these were also associated with CVD/all-cause death, as were several LDL and very-low-density lipoprotein subfractions, albeit with a pattern of association that differed from the baseline risk.ConclusionsIn JUPITER, baseline LDL-C was not associated with CVD events, in contrast with significant associations for non-HDL cholesterol and atherogenic particles: apolipoprotein B and ion mobility-measured non-HDL particles, LDL particles, and select subfractions of very-low-density lipoprotein particles and LDL particles. During high-intensity statin therapy, on-treatment levels of LDL-C and atherogenic particles were associated with residual risk of CVD/all-cause death.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Project description:BackgroundRecent failures of drugs that raised high-density lipoprotein (HDL) cholesterol levels to reduce cardiovascular events in clinical trials have led to increased interest in alternative indices of HDL quality, such as cholesterol efflux capacity, and HDL quantity, such as HDL particle number. However, no studies have directly compared these metrics in a contemporary population that includes potent statin therapy and low low-density lipoprotein cholesterol.MethodsHDL cholesterol levels, apolipoprotein A-I, cholesterol efflux capacity, and HDL particle number were assessed at baseline and 12 months in a nested case-control study of the JUPITER trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin), a randomized primary prevention trial that compared rosuvastatin treatment to placebo in individuals with normal low-density lipoprotein cholesterol but increased C-reactive protein levels. In total, 314 cases of incident cardiovascular disease (CVD) (myocardial infarction, unstable angina, arterial revascularization, stroke, or cardiovascular death) were compared to age- and gender-matched controls. Conditional logistic regression models adjusting for risk factors evaluated associations between HDL-related biomarkers and incident CVD.ResultsCholesterol efflux capacity was moderately correlated with HDL cholesterol, apolipoprotein A-I, and HDL particle number (Spearman r= 0.39, 0.48, and 0.39 respectively; P<0.001). Baseline HDL particle number was inversely associated with incident CVD (adjusted odds ratio per SD increment [OR/SD], 0.69; 95% confidence interval [CI], 0.56-0.86; P<0.001), whereas no significant association was found for baseline cholesterol efflux capacity (OR/SD, 0.89; 95% CI, 0.72-1.10; P=0.28), HDL cholesterol (OR/SD, 0.82; 95% CI, 0.66-1.02; P=0.08), or apolipoprotein A-I (OR/SD, 0.83; 95% CI, 0.67-1.03; P=0.08). Twelve months of rosuvastatin (20 mg/day) did not change cholesterol efflux capacity (average percentage change -1.5%, 95% CI, -13.3 to +10.2; P=0.80), but increased HDL cholesterol (+7.7%), apolipoprotein A-I (+4.3%), and HDL particle number (+5.2%). On-statin cholesterol efflux capacity was inversely associated with incident CVD (OR/SD, 0.62; 95% CI, 0.42-0.92; P=0.02), although HDL particle number again emerged as the strongest predictor (OR/SD, 0.51; 95% CI, 0.33-0.77; P<0.001).ConclusionsIn JUPITER, cholesterol efflux capacity was associated with incident CVD in individuals on potent statin therapy but not at baseline. For both baseline and on-statin analyses, HDL particle number was the strongest of 4 HDL-related biomarkers as an inverse predictor of incident events and biomarker of residual risk.Clinical trial registrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00239681.

Project description:BackgroundEven when low-density lipoprotein-cholesterol (LDL-C) levels are lower than guideline thresholds, a residual risk of atherosclerosis remains. It is unknown whether triglyceride (TG) levels are associated with subclinical atherosclerosis and vascular inflammation regardless of LDL-C.ObjectivesThis study sought to assess the association between serum TG levels and early atherosclerosis and vascular inflammation in apparently healthy individuals.MethodsAn observational, longitudinal, and prospective cohort study, including 3,754 middle-aged individuals with low to moderate cardiovascular risk from the PESA (Progression of Early Subclinical Atherosclerosis) study who were consecutively recruited between June 2010 and February 2014, was conducted. Peripheral atherosclerotic plaques were assessed by 2-dimensional vascular ultrasound, and coronary artery calcification (CAC) was assessed by noncontrast computed tomography, whereas vascular inflammation was assessed by fluorine-18 fluorodeoxyglucose uptake on positron emission tomography.ResultsAtherosclerotic plaques and CAC were observed in 58.0% and 16.8% of participants, respectively, whereas vascular inflammation was evident in 46.7% of evaluated participants. After multivariate adjustment, TG levels ≥150 mg/dl showed an association with subclinical noncoronary atherosclerosis (odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08 to 1.68; p = 0.008). This association was significant for groups with high LDL-C (OR: 1.42; 95% CI: 1.11 to 1.80; p = 0.005) and normal LDL-C (OR: 1.85; 95% CI: 1.08 to 3.18; p = 0.008). No association was found between TG level and CAC score. TG levels ≥150 mg/dl were significantly associated with the presence of arterial inflammation (OR: 2.09; 95% CI: 1.29 to 3.40; p = 0.003).ConclusionsIn individuals with low to moderate cardiovascular risk, hypertriglyceridemia was associated with subclinical atherosclerosis and vascular inflammation, even in participants with normal LDL-C levels. (Progression of Early Subclinical Atherosclerosis [PESA]; NCT01410318).

Project description:BackgroundThe combination of statin therapy and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibition markedly lowers low-density lipoprotein cholesterol (LDL-C) and reduces cardiovascular event rates. Whether residual inflammatory risk as measured by on-treatment high sensitivity C-reactive protein (hsCRP) remains an important clinical issue in such patients is uncertain.MethodsWe evaluated residual inflammatory risk among 9738 patients participating in the SPIRE-1 and SPIRE-2 cardiovascular outcomes trials (Studies of PCSK9 Inhibition and the Reduction in Vascular Events), who were receiving both statin therapy and bococizumab, according to on-treatment levels of hsCRP (hsCRPOT) and LDL-COT measured 14 weeks after drug initiation. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death.ResultsAt 14 weeks, the mean percentage change in LDL-C among statin-treated patients who additionally received bococizumab was -60.5% (95% confidence interval [CI], -61.2 to -59.8; P<0.001; median change, -65.4%) as compared to 6.6% (95% CI, -1.0 to 14.1; P=0.09; median change, 0.0%) for hsCRP. Incidence rates for future cardiovascular events for patients treated with both statin therapy and bococizumab according to hsCRPOT <1, 1 to 3, and >3 mg/L were 1.96, 2.50, and 3.59 events per 100 person-years, respectively, corresponding to multivariable adjusted hazard ratios of 1.0, 1.16 (95% CI, 0.81-1.66), and 1.62 (95% CI, 1.14-2.30) (P-trend=0.001) after adjustment for traditional cardiovascular risk factors and LDL-COT. Comparable adjusted hazard ratios for LDL-COT (<30, 30-50, >50 mg/dL) were 1.0, 0.87, and 1.21, respectively (P-trend=0.16). Relative risk reductions with bococizumab were similar across hsCRPOT groups (P-interaction=0.87).ConclusionsIn this post hoc analysis of the SPIRE trials of bococizumab in a stable outpatient population, evidence of residual inflammatory risk persisted among patients treated with both statin therapy and proprotein convertase subtilisin-kexin type 9 inhibition.Clinical trial registrationURL: https://www.clinicaltrials.gov. Unique identifiers: NCT01975376, NCT01975389.

Project description:ImportanceOsteoporosis and cardiovascular disease may share common biological pathways, with inflammation playing a role in the development of both. Although observational studies have suggested that statin use is associated with a lower risk of fractures, randomized trial data addressing this issue are scant.ObjectiveTo determine whether statin therapy reduces the risk of fracture and, in a secondary analysis, whether baseline levels of the inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) are associated with the risk of fracture.Design, setting, and participantsThe JUPITER (Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin) trial was an international, randomized, double-blind, placebo-controlled study enrolling 17,802 men older than 50 years and women older than 60 years with hs-CRP level of at least 2 mg/L. Participants were screened from 2003 to 2006 and observed prospectively for up to 5 years (median follow-up, 1.9 years).InterventionRosuvastatin calcium, 20 mg daily, or placebo.Main outcomes and measuresIncident fracture was a prespecified secondary end point of JUPITER. Fractures were confirmed by radiographs, computed tomography, bone scan, or other methods. Cox proportional hazards models were used to calculate hazard ratios (HRs) and associated 95% confidence intervals for the risk of fracture according to randomized treatment assignment, as well as increasing tertiles of hs-CRP, controlling for potential confounders.ResultsDuring the study, 431 incident fractures were reported and confirmed. Among participants allocated to rosuvastatin, 221 fractures were confirmed, compared with 210 among those allocated to placebo, such that the incidence of fracture in the rosuvastatin and placebo groups was 1.20 and 1.14 per 100 person-years, respectively (adjusted HR, 1.06 [95% CI, 0.88-1.28]; P = .53). Overall, increasing baseline hs-CRP level was not associated with an increased risk of fractures (adjusted HR for each unit increase in hs-CRP tertile, 1.06 [95% CI, 0.94-1.20]; P for trend, .34).Conclusions and relevanceAmong men and women with elevated hs-CRP level enrolled in a large trial of rosuvastatin therapy for cardiovascular disease, statin therapy did not reduce the risk of fracture. Higher baseline hs-CRP level was not associated with an increased risk of incident fracture.Trial registrationclinicaltrials.gov Identifier: NCT00239681.

Dataset Information

On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin).

Publications

On-treatment non-high-density lipoprotein cholesterol, apolipoprotein B, triglycerides, and lipid ratios in relation to residual vascular risk after treatment with potent statin therapy: JUPITER (justification for the use of statins in prevention: an intervention trial evaluating rosuvastatin).

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