Dataset Information

Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

ABSTRACT:

Background

As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate.

Methods

In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines.

Results

Friedewald values were less than ultracentrifugation measurement, with a median difference (25th to 75th percentile) of -2.4 (-7.4 to 0.6) at 50-69 mg/dL, -7.0 (-16.2 to -1.2) at 25-39 mg/dL, and -29.0 (-37.4 to -19.6) at < 15 mg/dL. The respective values by novel estimation were -0.1 (-1.5 to 1.3), -1.1 (-2.5 to 0.3), and -2.7 (-4.9 to 0.0) mg/dL. Among those with Friedewald LDL-C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation.

Conclusions

Estimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method.

SUBMITTER: Quispe R

PROVIDER: S-EPMC5399386 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Publications

Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

Quispe Renato R Hendrani Aditya A Elshazly Mohamed B MB Michos Erin D ED McEvoy John W JW Blaha Michael J MJ Banach Maciej M Kulkarni Krishnaji R KR Toth Peter P PP Coresh Josef J Blumenthal Roger S RS Jones Steven R SR Martin Seth S SS

BMC medicine 20170420 1

<h4>Background</h4>As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate.<h4>Methods</h4>In 191,333 individuals wit ...[more]

PMID: 28427464

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Project description:ImportanceIn the Cholesterol Treatment Trialists Collaboration (CTTC), in patients starting with low-density lipoprotein cholesterol (LDL-C) levels of approximately 3.4 mmol/L (131.5 mg/dL), there was a 22% reduction in major vascular events per 1-mmol/L (38.7-mg/dL) lowering of LDL-C. The magnitude of clinical benefit of further LDL-C lowering in patients already with very low LDL-C levels remains debated.ObjectiveTo evaluate efficacy and safety of further lowering LDL-C levels in patient populations presenting with median LDL-C levels of 1.8 mmol/L (70 mg/dL) or less.Data sources and study selectionThe CTTC was used for statin data. For nonstatin therapy, Medline database was searched (2015-April 2018). Key inclusion criteria were a randomized, double-blind, controlled cardiovascular outcome trial of LDL-C lowering with data in populations starting with LDL-C levels averaging 1.8 mmol/L (70 mg/dL) or less.Data extraction and synthesisTwo authors independently extracted data into standardized data sheets, and data were analyzed using meta-analysis.Main outcomes and measuresThe risk ratio (RR) of major vascular events (a composite of coronary heart death, myocardial infarction, ischemic stroke, or coronary revascularization) per 1-mmol/L (38.7-mg/dL) reduction in LDL-C level.ResultsIn the subgroup of patients from the CTTC meta-analysis of statins with a mean LDL-C in the control arm of 1.7 mmol/L (65.7 mg/dL), 1922 major vascular events occurred and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.78 (95% CI, 0.65-0.94). For 3 trials of nonstatin LDL-C-lowering therapies added to statins, there were 50 627 patients, the median LDL-C in the control arms ranged from 1.6 mmol/L to 1.8 mmol/L (63 mg/dL to 70 mg/dL), and 9570 major vascular events occurred. Nonstatin therapy lowered LDL-C by 0.3 to 1.2 mmol/L (11 mg/dL to 45 mg/dL), and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.79 (95% CI, 0.70-0.88). For statins and nonstatins combined, the RR was 0.79 (95% CI, 0.71-0.87; P < .001). Low-density lipoprotein cholesterol lowering was not associated with an increased risk of serious adverse events, myalgias and/or myositis, elevation in the level of aminotransferases, new-onset diabetes, hemorrhagic stroke, or cancer.Conclusions and relevanceThere is a consistent relative risk reduction in major vascular events per change in LDL-C in patient populations starting as low as a median of 1.6 mmol/L (63 mg/dL) and achieving levels as low as a median of 0.5 mmol/L (21 mg/dL), with no observed offsetting adverse effects. These data suggest further lowering of LDL-C beyond the lowest current targets would further reduce cardiovascular risk.

Project description:ImportanceIn the Improved Reduction of Outcomes: Vytorin Efficacy International Trial, intensive low-density lipoprotein cholesterol (LDL-C)-reducing therapy with ezetimibe/simvastatin compared with simvastatin alone was associated with a significant reduction in cardiovascular events in 18 144 patients after acute coronary syndrome. The safety of very low LDL-C levels over the long-term is unknown.ObjectiveTo assess the safety and clinical efficacy of achieving a very low (<30 mg/dL) level of LDL-C at 1 month using data from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial.Design, setting, and participantsThis prespecified analysis compared outcomes in patients stratified by achieved LDL-C level at 1 month in the Improved Reduction of Outcomes: Vytorin Efficacy International Trial and adjusted for baseline characteristics during 6 years' median follow-up. Patients were enrolled from October 26, 2005, to July 8, 2010, and the data analysis was conducted from December 2014 to February 2017.Main outcomes and measuresSafety end points included adverse events leading to drug discontinuation; adverse muscle, hepatobiliary, and neurocognitive events; and hemorrhagic stroke, heart failure, cancer, and noncardiovascular death. Efficacy events were as specified in the overall trial.ResultsAmong the 15 281 patients included in the study, 11 645 (76.2%) were men and the median age was 63 years (interquartile range, 56.6-70.7 years). In these patients without an event in the first month, the achieved LDL-C values at 1 month were less than 30 mg/dL, 30 to 49 mg/dL, 50 to 69 mg/dL, and 70 mg/dL or greater in 6.4%, 31%, 36%, and 26% of patients, respectively. Patients with LDL-C values less than 30 mg/dL (median, 25 mg/dL; interquartile range, 21-27 mg/dL) at 1 month were more likely randomized to ezetimibe/simvastatin (85%), had lower baseline LDL-C values, and were more likely older, male, nonwhite, diabetic, overweight, statin naive, and presenting with a first myocardial infarction. After multivariate adjustment, there was no significant association between the achieved LDL-C level and any of the 9 prespecified safety events. The adjusted risk of the primary efficacy composite of cardiovascular death, major coronary events, or stroke was significantly lower in patients achieving an LDL-C level less than 30 mg/dL at 1 month (adjusted hazard ratio, 0.79; 95% CI, 0.69-0.91; P = .001) compared with 70 mg/dL or greater.Conclusions and relevancePatients achieving an LDL-C level less than 30 mg/dL at 1 month had a similar safety profile (and numerically the lowest rate of cardiovascular events) over a 6-year period compared with patients achieving higher LDL-C concentrations. These data provide reassurance regarding the longer-term safety and efficacy of the continuation of intensive lipid-lowering therapy in very higher-risk patients resulting in very low LDL-C levels.Trial registrationclinicaltrials.gov Identifier: NCT00202878.

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Dataset Information

Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

Background

Methods

Results

Conclusions

Publications

Accuracy of low-density lipoprotein cholesterol estimation at very low levels.

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