scholarly journals Low‐Density Lipoprotein Cholesterol Corrected for Lipoprotein(a) Cholesterol, Risk Thresholds, and Cardiovascular Events

2020 ◽  
Vol 9 (23) ◽  
Author(s):  
Peter Willeit ◽  
Calvin Yeang ◽  
Patrick M. Moriarty ◽  
Lena Tschiderer ◽  
Stephen A. Varvel ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Care ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Content ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
The Impact

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‐C corr30 ). 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‐C corr30 (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‐C corr30 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‐C corr30 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.

scholarly journals Risks of Incident Cardiovascular Disease Associated With Concomitant Elevations in Lipoprotein(a) and Low‐Density Lipoprotein Cholesterol—The Framingham Heart Study

2020 ◽  
Vol 9 (18) ◽  
Author(s):  
Mehdi Afshar ◽  
Jian Rong ◽  
Yang Zhan ◽  
Hao Yu Chen ◽  
James C. Engert ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Absolute Risk ◽  
Clinical Care ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
Incident Cardiovascular Disease

Background Elevated lipoprotein(a) is a well‐established risk factor for atherosclerotic vascular disease but is not measured in routine clinical care. Screening of high lipoprotein(a) in individuals with moderate elevations of low‐density lipoprotein cholesterol (LDL‐C) may identify individuals at high risk of cardiovascular disease. Methods and Results We examined 2606 Framingham Offspring participants (median age, 54 years; 45% men) prospectively with a median follow‐up of 15 years (n=392 incident cardiovascular events). Individuals with higher (≥100 nmol/L) versus lower lipoprotein(a) were divided into groups based on LDL‐C <135 mg/dL versus ≥135 mg/dL. In Cox models, after adjustment for known risk factors, high lipoprotein(a) (≥100 nmol/L) and LDL‐C ≥135 mg/dL were each significant predictors of cardiovascular disease (LDL‐C ≥135 mg/dL: hazard ratio [HR], 1.34; 95% CI, 1.09–1.64; P =0.006; high lipoprotein (a): HR, 1.31; 95% CI, 1.03–1.66; P =0.026). Across the groups of high/low lipoprotein (a) and LDL‐C ≥135 mg/dL or <135 mg/dL, the absolute cardiovascular disease risks at 15 years were 22.6% (high lipoprotein(a)/LDL‐C ≥135 mg/dL, n=248), 17.3% (low lipoprotein(a)/LDL‐C ≥135 mg/dL, n=758), 12.7% (high lipoprotein(a)/LDL‐C <135 mg/dL, n=275) and 11.5% (low lipoprotein(a)/LDL‐C <135 mg/dL, n=1328, reference group). Among individuals with LDL‐C ≥135 mg/dL, those with high lipoprotein(a) had a 43% higher risk (HR, 1.43; 95% CI, 1.05–1.97; P =0.02). Presence of high lipoprotein(a) with moderate LDL‐C levels (135–159 mg/dL) yielded absolute risks equivalent to those with LDL‐C ≥160 mg/dL (23.5%, 95% CI, 17.4%–31.3%; and 20.7%, 95% CI, 16.8%–25.3%, respectively). Conclusions Concomitant elevation of LDL‐C ≥135 mg/dL and lipoprotein(a) ≥100 nmol/L is associated with a high absolute risk of incident cardiovascular disease. lipoprotein(a) measurement in individuals with moderate elevations in LDL‐C, who do not otherwise meet criteria for statins, may identify individuals at high cardiovascular risk.

Eligibility for PCSK9 inhibitors based on the 2019 ESC/EAS and 2018 ACC/AHA guidelines

2020 ◽  
pp. 204748732094010
Author(s):  
Konstantinos C Koskinas ◽  
Baris Gencer ◽  
David Nanchen ◽  
Mattia Branca ◽  
David Carballo ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
High Risk ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Coronary Syndrome ◽  
Coronary Syndromes

Aims The 2018 American College of Cardiology (ACC)/American Heart Association (AHA) and 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) lipid guidelines recently updated their recommendations regarding proprotein convertase subtilisin/kexin-9 inhibitors (PCSK9i). We assessed the potential eligibility for PCSK9i according to the new guidelines in patients with acute coronary syndromes. Methods and results We analysed a contemporary, prospective Swiss cohort of patients hospitalised for acute coronary syndromes. We modelled a statin intensification effect and an incremental ezetimibe effect on low-density lipoprotein-cholesterol levels among patients who were not on high-intensity statins or ezetimibe. One year after the index acute coronary syndrome event, treatment eligibility for PCSK9i was defined as low-density lipoprotein-cholesterol of 1.4 mmol/l or greater according to ESC/EAS guidelines. For ACC/AHA guidelines, treatment eligibility was defined as low-density lipoprotein-cholesterol of 1.8 mmol/l or greater in the presence of very high-risk atherosclerotic cardiovascular disease, defined by multiple major atherosclerotic cardiovascular disease events and/or high-risk conditions. Of 2521 patients, 93.2% were treated with statins (53% high-intensity statins) and 7.3% with ezetimibe at 1 year, and 54.9% had very high-risk atherosclerotic cardiovascular disease. Low-density lipoprotein-cholesterol levels less than 1.8 mmol/l and less than 1.4 mmol/l at 1 year were observed in 37.5% and 15.7% of patients, respectively. After modelling the statin intensification and ezetimibe effects, these numbers increased to 76.1% and 49%, respectively. The proportion of patients eligible for PCSK9i was 51% according to ESC/EAS criteria versus 14% according to ACC/AHA criteria. Conclusions In this analysis, the 2019 ESC/EAS guidelines rendered half of all post-acute coronary syndrome patients potentially eligible for PCSK9i treatment, as compared to a three-fold lower eligibility rate based on the 2018 ACC/AHA guidelines.

scholarly journals Assessing the Accuracy of Estimated Lipoprotein(a) Cholesterol and Lipoprotein(a)‐Free Low‐Density Lipoprotein Cholesterol

2022 ◽  
Author(s):  
Weili Zheng ◽  
Michael Chilazi ◽  
Jihwan Park ◽  
Vasanth Sathiyakumar ◽  
Leslie J. Donato ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Particle Number ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Interquartile Range ◽  
Lipoprotein Cholesterol ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Lipoprotein A ◽  
C 50

Background Accurate measurement of the cholesterol within lipoprotein(a) (Lp[a]‐C) and its contribution to low‐density lipoprotein cholesterol (LDL‐C) has important implications for risk assessment, diagnosis, and treatment of atherosclerotic cardiovascular disease, as well as in familial hypercholesterolemia. A method for estimating Lp(a)‐C from particle number using fixed conversion factors has been proposed (Lp[a]‐C from particle number divided by 2.4 for Lp(a) mass, multiplied by 30% for Lp[a]‐C). The accuracy of this method, which theoretically can isolate “Lp(a)‐free LDL‐C,” has not been validated. Methods and Results In 177 875 patients from the VLDbL (Very Large Database of Lipids), we compared estimated Lp(a)‐C and Lp(a)‐free LDL‐C with measured values and quantified absolute and percent error. We compared findings with an analogous data set from the Mayo Clinic Laboratory. Error in estimated Lp(a)‐C and Lp(a)‐free LDL‐C increased with higher Lp(a)‐C values. Median error for estimated Lp(a)‐C <10 mg/dL was −1.9 mg/dL (interquartile range, −4.0 to 0.2); this error increased linearly, overestimating by +30.8 mg/dL (interquartile range, 26.1–36.5) for estimated Lp(a)‐C ≥50 mg/dL. This error relationship persisted after stratification by overall high‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol subtypes. Similar findings were observed in the Mayo cohort. Absolute error for Lp(a)‐free LDL‐C was +2.4 (interquartile range, −0.6 to 5.3) for Lp(a)‐C<10 mg/dL and −31.8 (interquartile range, −37.8 to −26.5) mg/dL for Lp(a)‐C≥50 mg/dL. Conclusions Lp(a)‐C estimations using fixed conversion factors overestimated Lp(a)‐C and subsequently underestimated Lp(a)‐free LDL‐C, especially at clinically relevant Lp(a) values. Application of inaccurate Lp(a)‐C estimations to correct LDL‐C may lead to undertreatment of high‐risk patients.

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