Difference between calculated and direct-measured low-density lipoprotein cholesterol in subjects with diabetes mellitus or taking lipid-lowering medications

Objectives: The accurate and precise measurement of low-density lipoprotein-cholesterol (LDL-C) is important in the assessment of atherosclerotic cardiovascular disease risk (ASCVD) in people with diabetes mellitus. This study aimed at comparing directly measured LDL-C with Friedewald formula (FF)-calculated LDL-C (c-LDL-C) in people with type-2 diabetes. Methods: Fasting lipid profiles of 1905 people with type-2 diabetes, whose LDL-C was estimated by direct LDL assay, were chosen for the study. In the same group, LDL-C was calculated with FF. Correlation and agreement between these methods were analyzed at various strata of triglycerides (TGs). The possibility of misclassifying people at various levels of LDL-C targets proposed in literature was calculated. Results: The mean LDL-C levels were lower in the c-LDL-C group across various TG strata. A significant correlation was found between c-LDL-C and direct LDL-C for all the study samples ( r = 0.948, P < .001) and across all TG strata. Analysis of agreement showed a positive bias for direct LDL-C which increased at higher strata of TGs. c-LDL-C underestimated ASCVD by misclassifying people at various LDL-C target levels. Conclusion: There is a difference between direct LDL-C and c-LDL-C values in people with diabetes and this may result in misclassifying ASCVD especially at lower levels of LDL-C and higher levels of TGs.

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Correlation of Serum Low Density Lipoprotein Cholesterol and High Density Lipoprotein Cholesterol with Type 2 Diabetes Mellitus

Journal of Dhaka Medical College ◽

10.3329/jdmc.v26i2.38832 ◽

2018 ◽

Vol 26 (2) ◽

pp. 140-147

Author(s):

Nahid Yeasmin ◽

Qazi Shamima Akhter ◽

Sayeeda Mahmuda ◽

Sultana Yeasmin ◽

Rumana Afroz ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Fasting Serum ◽

Medical College

Background: Diabetes mellitus is one of the most widespread endocrine disorders in female and its complications are increasing all over the world, leading to life threatening medical problems like cardiovascular diseases, stroke and end stage renal diseases. A correlation between hyperlipidemia and type 2 diabetes mellitus has been identified. The study was carried out to observe the correlation of serum low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) level with type 2 diabetes mellitus in adult female subjects.Method: This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, during the period of January 2011 to December 2011. Total sixty female subjects were selected with age ranging from 30 to 50 years. Among them 30 female subjects with diabetes mellitus were included from out-patient department of Endocrinology, Dhaka Medical College Hospital, Dhaka as study group (B) and 30 apparently healthy females were taken as control group (A) for comparison. Estimation of serum fasting serum LDL-C and HDL-C levels was done by enzymatic method in the department of Physiology, Dhaka Medical College Dhaka in both groups. Fasting serum insulin level was measured by ELISA method in the laboratory of National Institute of ENT, Dhaka and fasting blood glucose was estimated by glucose oxidase method in the department of Physiology, Dhaka Medical College in both groups. Data were analyzed by Unpaired Student’s- test and Pearson’s correlation co-efficient (r) test as applicable.Results: The value of fasting serum LDL-C level was significantly higher in study subjects than those of control. Again, fasting serum HDL-C level was significantly lower in study subjects in comparison to controls. In study subjects fasting serum LDL showed positive correlation and fasting serum HDL-C levels showed negative correlation with fasting blood glucose and serum insulin level.Conclusion: Present study reveals that serum insulin and blood glucose level have positive relationship with low density lipoprotein cholesterol (LDL-C) and negative relationship with high density lipoprotein cholesterol (HDL-C) levels.J Dhaka Medical College, Vol. 26, No.2, October, 2017, Page 140-147

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U-Shaped Relationship of Low-Density Lipoprotein Cholesterol With Risk of Severe COVID-19 From a Multicenter Pooled Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.604736 ◽

2021 ◽

Vol 8 ◽

Author(s):

Jiao Gong ◽

Yaqiong Chen ◽

Yusheng Jie ◽

Mingkai Tan ◽

Zhaofang Jiang ◽

...

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Odds Ratios ◽

Lowering Therapy ◽

Severe Group

Low-density lipoprotein cholesterol (LDL-C) is a well-known risk factor for coronary heart disease but protects against infection and sepsis. We aimed to disclose the exact association between LDL-C and severe 2019 novel coronavirus disease (COVID-19). Baseline data were retrospectively collected for 601 non-severe COVID-19 patients from two centers in Guangzhou and one center in Shenzhen, and patients on admission were medically observed for at least 15 days to determine the final outcome, including the non-severe group (n = 460) and the severe group (severe and critical cases) (n = 141). Among 601 cases, 76 (12.65%) received lipid-lowering therapy; the proportion of patients taking lipid-lowering drugs in the severe group was higher than that in the non-severe group (22.7 vs. 9.6%). We found a U-shaped association between LDL-C level and risk of severe COVID-19 using restricted cubic splines. Using univariate logistic regression analysis, odds ratios for severe COVID-19 for patients with LDL-C ≤1.6 mmol/L (61.9 mg/dL) and above 3.4 mmol/L (131.4 mg/dL) were 2.29 (95% confidence interval 1.12–4.68; p = 0.023) and 2.02 (1.04–3.94; p = 0.039), respectively, compared to those with LDL-C of 2.81–3.40 mmol/L (108.6–131.4 mg/dL); following multifactorial adjustment, odds ratios were 2.61 (1.07–6.37; p = 0.035) and 2.36 (1.09–5.14; p = 0.030). Similar results were yielded using 0.3 and 0.5 mmol/L categories of LDL-C and sensitivity analyses. Both low and high LDL-C levels were significantly associated with higher risk of severe COVID-19. Although our findings do not necessarily imply causality, they suggest that clinicians should pay more attention to lipid-lowering therapy in COVID-19 patients to improve clinical prognosis.

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Abstract P43: Frequency and Predictors of Low-Density Lipoprotein Cholesterol Control and Appropriate Response to Elevated LDL-C Levels in Patients with Cardiovascular Disease

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.4.suppl_2.ap43 ◽

2011 ◽

Vol 4 (suppl_2) ◽

Author(s):

Salim S Virani ◽

Lechauncy D Woodard ◽

Supicha Sookanan ◽

Cassie R Landrum ◽

Tracy H Urech ◽

...

Keyword(s):

Cardiovascular Disease ◽

Low Density Lipoprotein ◽

Medication Possession Ratio ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

To Receive

Background: Although current cholesterol performance measures define good quality as low density lipoprotein cholesterol (LDL-C) levels < 100mg/dl in cardiovascular disease (CVD) patients, they provide a snap shot at one time point and do not inform whether an appropriate action was taken to manage elevated LDL-C levels. We assessed frequency and predictors of this appropriate response (AR). Methods: We used administrative data to assess 22,902 CVD patients receiving care in a Veterans Affairs network of 7 hospitals and affiliated clinics. We determined the proportion of CVD patients at LDL-C goal <100 mg/dl, and the proportion of patients with uncontrolled LDL-C levels (>100 mg/dl) who had an AR [defined as the initiation or dosage increase of a lipid lowering medication (LLM), addition of a new LLM, receipt of maximum dosage or >1 LLM, or LDL-C reading <100 mg/dl] at 45 days follow-up. Logistic regression was performed to evaluate facility, provider and patient characteristics associated with AR. Results: LDL-C levels were at goal in 16,350 (71.4%) patients. An additional 2,110 (9.2%) had an AR at 45 days of follow-up. Controlling for clustering between facilities and patient's illness severity, history of diabetes (OR 1.18, 95% CI 1.03-1.35), hypertension (OR 1.21, 95% CI 1.02-1.44), patients showing good medication adherence (medication possession ratio > 0.8) [OR 2.29, 95% CI 1.99-2.64] were associated with AR. Older CVD patients (age >75 years) were less likely to receive AR (OR 0.60, 95% CI 0.52-0.70). Teaching vs. non-teaching facility (p=0.40), physician vs. non-physician provider (p=0.14), specialist vs. non-specialist primary care provider (p=0.12), and patient's race (p=0.12) were not predictors of AR. Conclusion: Among patients with CVD and LDL-C above guideline recommended levels, only one-third receive AR. Diabetic and hypertensive CVD patients are more likely to receive AR, whereas older Veterans with CVD receive AR less often likely reflecting providers' belief of lack of efficacy from treatment intensification in older CVD patients. Our findings are important for quality improvement and policy making initiatives as they provide more actionable information compared with isolated LDL-C goal attainment as a quality indicator.

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Comparison of LDL-C calculation by friedewald and martin/hopkins methods in 12,243 adults from the United States of America

European Heart Journal ◽

10.1093/ehjci/ehaa946.2932 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

P Penson ◽

S.S Martin ◽

N.C Henney ◽

M Banach

Keyword(s):

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Threshold Value ◽

The United States ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Lipid Lowering Therapy ◽

Low Density ◽

Strongly Correlated ◽

Low Density Lipoprotein Cholesterol

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is an established risk factor for cardiovascular disease (CVD), and a target for lipid-lowering therapy. LDL-C is typically not measured directly but is estimated using the Friedewald formula, which assumes a fixed factor for the ratio of triglycerides (TG) to very low-density lipoprotein cholesterol (VLDL-C). However this assumption is sometimes not valid. The Martin/Hopkins (M/H) formula estimates LDL-C using an adjustable factor for the TG:VLDL-C ratio and is expected to improve upon Friedewald when predicting measured LDL-C, and apolipoprotein B (ApoB), one molecule of which is associated with each LDL particle. Purpose We compared values of LDL-C calculated by the Friedewald and M/H methods with respect to their correlation with non-high density lipoprotein cholesterol (non-HDL-C) and ApoB, and their classification of individuals based upon attainment of the threshold value of 70 mg/dl (1.8 mmol/l) of LDL-C. This cut-point is a treatment target for individuals at high risk of CVD in the 2019 ESC guidelines for lipid modification, and a threshold for initiating statin therapy in the 2019 ACC/AHA guidelines. Methods In this analysis we included participants in the National Health and Nutrition Examination Survey (NHANES) from 2005–2016, age ≥18, <80 years who had measurements for total cholesterol (TC), TG and HDL-C. LDL-C was calculated using Friedewald and M/H. We correlated LDL-C (calculated using the two methods) with non-HDL-C and ApoB. We identified individuals with LDL-C <70 mg/dl using both methods. When LDL-C (Friedewald) was <70, but LDL-C (M/H) was >70, we classified these participants as discordant. Statistical analyses were performed in IBM SPSS for Windows v26. Results 12,243 individuals were included. 51.8% were female, mean (±SD) age was 45.5±17.4, 15.3% were treated with statins, ApoB was available for 2179 participants. Mean lipid concentrations (mg/dl) were: TC: 191.5±41.0, TG: 120.0±67.0, HDL-C: 54.1±15.7, LDL-C (Friedewald): 113.3±35.4; LDL-C (M/H): 114.9±35.2. In the whole population, LDL-C (M/H) was more strongly correlated than LDL-C (Friedewald) with ApoB (r=0.935 v 0.894) and non-HDL-C (r=0.981 v 0.944). In statin-treated participants, LDL-C (M/H) was also more strongly correlated with ApoB (r=0.951 v 0.914) and non-HDL-C (r=0.979 v 0.928). 1139 participants had LDL-C (Friedewald) <70 mg/dl. Of these, 206 individuals (18.1%) were discordant, having LDL-C (M/H) >70 mg/dl. Amongst statin-treated patients, 22.9% were discordant. Only 5.5% of individuals with LDL-C (M/H) <70 mg/dl showed reverse discordance (LDL-C (Friedewald) >70 mg/dl). Conclusions The M/H method of calculating LDL-C correlates more strongly with non-HDL-C and ApoB than Friedewald. Importantly the discordant results confirm previous observations that Friedewald underestimates LDL-C at low concentrations. This may result in under-use of lipid-lowering therapies. Funding Acknowledgement Type of funding source: None

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Clinical Significance of Electronegative Low-Density Lipoprotein Cholesterol in Atherothrombosis

Biomedicines ◽

10.3390/biomedicines8080254 ◽

2020 ◽

Vol 8 (8) ◽

pp. 254 ◽

Cited By ~ 1

Author(s):

Chih-Sheng Chu ◽

Shi Hui Law ◽

David Lenzen ◽

Yong-Hong Tan ◽

Shih-Feng Weng ◽

...

Keyword(s):

Cardiovascular Diseases ◽

Clinical Significance ◽

Ldl Cholesterol ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Exercise Stress ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Low Density ◽

Low Density Lipoprotein Cholesterol

Despite the numerous risk factors for atherosclerotic cardiovascular diseases (ASCVD), cumulative evidence shows that electronegative low-density lipoprotein (L5 LDL) cholesterol is a promising biomarker. Its toxicity may contribute to atherothrombotic events. Notably, plasma L5 LDL levels positively correlate with the increasing severity of cardiovascular diseases. In contrast, traditional markers such as LDL-cholesterol and triglyceride are the therapeutic goals in secondary prevention for ASCVD, but that is controversial in primary prevention for patients with low risk. In this review, we point out the clinical significance and pathophysiological mechanisms of L5 LDL, and the clinical applications of L5 LDL levels in ASCVD can be confidently addressed. Based on the previously defined cut-off value by receiver operating characteristic curve, the acceptable physiological range of L5 concentration is proposed to be below 1.7 mg/dL. When L5 LDL level surpass this threshold, clinically relevant ASCVD might be present, and further exams such as carotid intima-media thickness, pulse wave velocity, exercise stress test, or multidetector computed tomography are required. Notably, the ultimate goal of L5 LDL concentration is lower than 1.7 mg/dL. Instead, with L5 LDL greater than 1.7 mg/dL, lipid-lowering treatment may be required, including statin, ezetimibe or PCSK9 inhibitor, regardless of the low-density lipoprotein cholesterol (LDL-C) level. Since L5 LDL could be a promising biomarker, we propose that a high throughput, clinically feasible methodology is urgently required not only for conducting a prospective, large population study but for developing therapeutics strategies to decrease L5 LDL in the blood.

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Cardiovascular event rates increase after each recurrence and associate with poor statin adherence

European Journal of Preventive Cardiology ◽

10.1177/2047487320904334 ◽

2020 ◽

pp. 204748732090433 ◽

Cited By ~ 2

Author(s):

Mariann I Lassenius ◽

Iiro Toppila ◽

Susanne Bergius ◽

Julia Perttilä ◽

KE Juhani Airaksinen ◽

...

Keyword(s):

Cardiovascular Event ◽

Cardiovascular Events ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Increased Risk ◽

Event Rates

Aims The study evaluated the quality of cardiovascular prevention in real-world clinical practice. The recurrence of up to five cardiovascular events was assessed, as data on recurrence beyond the first event and interindividual variations in event rates past the second event have been sparse. Low-density lipoprotein cholesterol concentrations and lipid-lowering therapy use were investigated. Methods This retrospective register-based study included adult patients with an incident cardiovascular event between 2004 and 2016 treated in the hospital district of southwest Finland. Patients were followed for consecutive cardiovascular events or cardiovascular death, low-density lipoprotein cholesterol and statin purchases. The timing of event recurrence was evaluated, and predictive factors were assessed. Results A wide interindividual variation in cardiovascular event recurrence was observed, each additional event caused an increased risk, the median time of recurrence decreased from 7 to one year for the second and fifth event. Event rates increased correspondingly from 12 to 43/100 patient-years and were most pronounced in the first years following the previous event. The low-density lipoprotein cholesterol goal (<1.8 mmol/l) was reached by 18% in the year after the event and statin underuse was associated with an increased risk of recurrence. Six months after the index event high intensity statins were used by only 22% of the cohort. Conclusion The study provides new perspectives on individual risk assessment showing that event rates are not stable for all patients but increase 1.2–1.9-fold per consecutive event. The underuse of statins and poor adherence support the identification of these patients for intensified multifactorial preventive measures.

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Statin-based therapy for primary and secondary prevention of ischemic stroke: A meta-analysis and critical overview

International Journal of Stroke ◽

10.1177/1747493019873594 ◽

2019 ◽

Vol 15 (4) ◽

pp. 377-384 ◽

Cited By ~ 1

Author(s):

Haralampos Milionis ◽

George Ntaios ◽

Eleni Korompoki ◽

Konstantinos Vemmos ◽

Patrik Michel

Keyword(s):

Ischemic Stroke ◽

Secondary Prevention ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Low Density ◽

Low Density Lipoprotein Cholesterol ◽

Primary And Secondary Prevention ◽

Prevention Trials

Background and aims To reassess the effect of statin-based lipid-lowering therapy on ischemic stroke in primary and secondary prevention trials with regard to achieved levels of low-density lipoprotein-cholesterol in view of the availability of novel potent hypolipidemic agents. Methods English literature was searched (up to November 2018) for publications restricted to trials with a minimum enrolment of 1000 and 500 subjects for primary and secondary prevention, respectively, meeting the following criteria: adult population, randomized controlled design, and recorded outcome data on ischemic stroke events. Data were meta-analyzed and curve-estimation procedure was applied to estimate regression statistics and produce related plots. Results Four primary prevention trials and four secondary prevention trials fulfilled the eligibility criteria. Lipid-lowering therapy was associated with a lower risk of ischemic stroke in primary (risk ratio, RR 0.70, 95% confidence interval, CI, 0.60–0.82; p < 0.001) and in the secondary prevention setting (RR 0.80, 95% CI 0.70–0.90; p < 0.001). Curve-estimation procedure revealed a linear relationship between the absolute risk reduction of ischemic stroke and active treatment-achieved low-density lipoprotein-cholesterol levels in secondary prevention (adjusted R-square 0.90) in support of “the lower the better” hypothesis for stroke survivors. On the other hand, the cubic model followed the observed data well in primary prevention (adjusted R-square 0.98), indicating greater absolute risk reduction in high-risk cardiovascular disease-free individuals. Conclusions Statin-based lipid-lowering is effective both for primary and secondary prevention of ischemic stroke. Most benefit derives from targeting disease-free individuals at high cardiovascular risk, and by achieving low treatment targets for low-density lipoprotein-cholesterol in stroke survivors.

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