scholarly journals Mildly Abnormal Lipid Levels, but Not High Lipid Variability, Are Associated With Increased Risk of Myocardial Infarction and Stroke in “Statin-Naive” Young Population A Nationwide Cohort Study

2020 ◽  
Vol 126 (7) ◽  
pp. 824-835 ◽  
Author(s):  
Jun-Bean Park ◽  
Da Hye Kim ◽  
Heesun Lee ◽  
In-Chang Hwang ◽  
Yeonyee E. Yoon ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiovascular Disease ◽  
Young Adults ◽  
Total Cholesterol ◽  
Density Lipoprotein ◽  
Lipid Profiles ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Young Population ◽  
Lipid Levels

Rationale: In young adults, the role of mildly abnormal lipid levels and lipid variability in the risk of atherosclerotic cardiovascular diseases remains uncertain. Objective: To investigate the association of these abnormalities in lipid profiles with the risk of myocardial infarction (MI) and stroke in young population. Methods and Results: From the Korean National Health Insurance Service, a nationwide population-based cohort of 1 934 324 statin-naive adults aged 20 to 39 years, with ≥3 lipid profile measurements and without a history of MI and stroke, were followed-up until the date of MI or stroke, or December 31, 2017. The primary measure of lipid variability was variability independent of the mean. Higher baseline total cholesterol, LDL-C (low-density lipoprotein-cholesterol), and triglycerides and lower HDL-C (high-density lipoprotein-cholesterol) levels were significantly associated with increased MI risk; respective adjusted hazard ratios and 95% CIs comparing the highest versus lowest quartiles were 1.35 (1.20–1.53) for total cholesterol, 1.41 (1.25–1.60) for LDL-C, 1.28 (1.11–1.47) for triglycerides, and 0.82 (0.72–0.94) for HDL-C. Adjusted analyses for deciles of lipid profiles showed that MI risk was significantly elevated among participants with total cholesterol ≥223.4 mg/dL, LDL-C ≥139.5 mg/dL, HDL-C ≤41.8 mg/dL, and triglycerides ≥200.1 mg/dL. The associations between lipid levels and stroke risk were less prominent. Multivariable-adjusted restricted cubic spline analysis demonstrated that the increase in MI risk was not exclusively driven by extreme values of lipid profiles. Similar results were obtained on sensitivity analyses of baseline lipid levels. However, associations between lipid variability and the risk of MI and stroke varied depending on the measure of lipid variability used. Conclusions: Mildly abnormal baseline lipid levels were associated with an increased future risk of atherosclerotic cardiovascular disease events, particularly MI, whereas measures of lipid variability were not. Therefore, in young adults, achieving optimal lipid levels could be valuable in the prevention of atherosclerotic cardiovascular disease.

Abstract P102: Variability In Lipid Levels And Risk For Cardiovascular Disease: An Electronic Health Record-based Population Cohort Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Sheila M Manemann ◽  
Suzette J Bielinski ◽  
Ethan D Moser ◽  
Jennifer L St. Sauver ◽  
Paul Y Takahashi ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Electronic Health Record ◽  
Total Cholesterol ◽  
Index Date ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Health Record ◽  
Lipid Levels ◽  
Population Cohort ◽  
Increased Risk

Background: Larger within-patient variability of lipid levels has been associated with an increased risk of cardiovascular disease (CVD). However, measures of lipid variability are not currently used clinically. We investigated the feasibility of calculating lipid variability within a large electronic health record (EHR)-based population cohort and assessed associations with incident CVD. Methods: We identified all individuals ≥40 years of age who resided in Olmsted County, MN on 1/1/2006 (index date) without prior CVD. CVD was defined as myocardial infarction, coronary artery bypass graft surgery, percutaneous coronary intervention or stroke. Patients with ≥3 measurements of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and/or triglycerides during the 5 years before the index date were retained in the analyses. Lipid variability was calculated using variability independent of the mean (VIM). Patients were followed through 9/30/2017 for incident CVD (including CVD death). Cox regression was used to investigate the association between quintiles of lipid VIMs and incident CVD. Results: We identified 18,642 individuals (mean age 60; 55% female) who were free of CVD at baseline and VIM calculated for at least one lipid measurement. After adjustment, those in the highest VIM quintiles of total cholesterol had a 25% increased risk of CVD (Q5 vs. Q1 HR: 1.25, 95% CI: 1.08-1.45; Table). We observed similar results for LDL-C (Q5 vs. Q1 HR: 1.20, 95% CI: 1.04-1.39) and HDL-C (Q5 vs. Q1 HR: 1.25, 95% CI: 1.09-1.43). There was no association between triglyceride variability quintiles and CVD risk. Conclusion: In a large EHR-based population cohort, high variability in total cholesterol, HDL-C and LDL-C was associated with an increased risk of CVD, independently of traditional risk factors, suggesting it may be a target for intervention. Lipid variability can be calculated in the EHR environment but more research is needed to determine its clinical utility.

Abstract P494: Association of Lipid Components With Mortality,Myocardial Infarction, and Stroke in Statin-Naïve Young Adults: A Nationwide Cohort Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Heesun Lee ◽  
Jun-bean Park ◽  
Hyo Eun Park ◽  
Su-yeon Choi ◽  
Kyungdo Han ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Young Adults ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Study Endpoint ◽  
Lipid Levels ◽  
Lipid Management ◽  
Risk Of Death ◽  
Clinical Events ◽  
Lipid Components

Background: Dyslipidemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We sought to investigate the risk of death and cardiovascular disease in relation to lipid components to establish evidence for primary prevention in young adults. Methods: In a nationwide cohort using the National Health Insurance claims database, we analyzed 5,688,055 statin-naïve subjects, aged 20-39 years, undergoing health check-up between 2009 and 2014. The study endpoint was a composite of clinical events, including death, myocardial infarction (MI), and stroke. We compared the incidence and the risk of clinical events according to lipid variables, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides. Results: During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%); 16,262 deaths (0.29%), 8,578 MIs (0.15%), and 5,967 strokes (0.10%). The risk of clinical events gradually increased with increasing TC and triglycerides, and decreasing HDL-C, with a great contribution by MI. LDL-C had a J-shaped association with the study endpoint, showing the lowest risk in LDL-C of 84-101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted HR 1.20, p <0.001), after adjusting for conventional risk factors. Conclusions: In ‘statin-naïve’ young adults aged 20-39 years, the risk of clinical events was proportional to lipid levels; positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had the strongest and independent association with clinical events. Screening and intervention of abnormal lipid levels, particularly triglycerides, from an early age might be required.

scholarly journals ASSOCIATION OF LIPID PROFILES WITH 10-YEAR ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK: STUDY AMONG SUBJECTS IN SLEMAN DISTRICT OF YOGYAKARTA INDONESIA

2017 ◽  
Vol 10 (12) ◽  
pp. 166
Author(s):  
Rita Suhadi ◽  
Dita Maria Virginia ◽  
Christianus Heru Setiawan
Keyword(s):  
Cardiovascular Disease ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Lipid Profiles ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cross Sectional ◽  
Lipid Ratio ◽  
Ascvd Risk

  Objectives: The subjects in the Sleman District of Yogyakarta had medium Framingham risk score (FRS) in the preceding year study. The 10-year atherosclerotic cardiovascular disease (ASCVD) risk was a newer risk estimator than FRS. This study aimed to associate the lipid profiles with the ASCVD risk.Methods: The study was conducted with a cross-sectional design and the subjects were selected with cluster random sampling. The association of lipid profiles and ASCVD risk was analyzed with Mann–Whitney/Kruskal–Wallis tests and Spearman’s rho correlation, whereas the categorical scores within sub-groups were analyzed Chi-square statistics, respectively.Results: The eligible subjects (n=221) had the age at 51.7±8.1 years, systolic/diastolic blood pressure 136.8±22.4/85.0±12.4 mmHg, total-cholesterol (total-C), high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglyceride at 202.0±34.9 mg/dl, 52.6±12.5 mg/dl, 126.3±30.0 mg/dl, and 135.9±95.4 mg/dl, respectively; with hypertension treatment 16.7%, smoking 52.9%, diabetes 10.4%, and the median ASCVD risk at 4.4 (0.2-41.4). The ASCVD risk has significant association with non-lipid profiles, total-C, lipid ratio of triglyceride/HDL-C, total-C/HDL-C, and LDL-C/HDL-C, to a lesser extent, HDL-C, LDL-C, and triglyceride.Conclusion: The 10-year ASCVD risk of the subjects was categorized as low and had a significant association with total-C and lipid ratio of triglyceride/ HDL-C, total-C/HDL-C, and LDL-C/HDL-C.

scholarly journals 10-YEAR RISK ESTIMATION OF ATHEROSCLEROTIC CARDIOVASCULAR DISEASE IN HYPERTENSIVE PATIENTS

2021 ◽  
Vol 9 (2) ◽  
pp. 145-150
Author(s):  
Olha M. Chernatska ◽  
Xaba Sibongumusa
Keyword(s):  
Cardiovascular Disease ◽  
Arterial Hypertension ◽  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Hypertensive Patients

Arterial hypertension is one of the most common causes of atherosclerotic cardiovascular disease, which is still the reason of mortality for a lot of persons. Assessment of 10-year risk of atherosclerotic cardiovascular disease in hypertensive patients is very important for further treatment improvement. The aim is the absolute 10-year risk assessment of atherosclerotic cardiovascular disease in hypertensive patients for further correction of treatment. We included 61 patients with stage 1 to 2 arterial hypertension into our study. Most of them are women (70%). The patients were (56.84 ± 8.1) years old. The total cholesterol was (4.32 ± 1.0) mmol/l, high and low density lipoprotein cholesterol – (1.35 ± 0.2) mmol/l and (2.44 ± 0.7) mmol/l, respectively. Online calculator «ASCVD Risk Estimator Plus» was used. It included the assessment of age, sex, race, systolic and diastolic blood pressure, total cholesterol, high and low density lipoprotein cholesterol, presence of diabetes, smoking status, hypertension treatment, consumption of statins or aspirin. The risk was classified as low (< 5%), borderline (5% to < 7.5%), intermediate (≥ 7.5% to < 20%), or high (≥ 20%). The results were analyzed statistically using Microsoft Excel. For five persons it was not possible to calculate this risk using the online calculator because of too low values of total cholesterol and low density lipoprotein cholesterol. Low 10-year risk of atherosclerotic cardiovascular disease was confirmed in 30 (53.6%) people, borderline – in 2 (3.6 %), intermediate – in 11 (19.6%), high – in 13 (23.2%). Low absolute 10-year risk of atherosclerotic cardiovascular disease was determined in more than half (53.6%) of patients, high – in about quarter (23.2%), intermediate – in the fifth part (19.6%) of patients with arterial hypertension. For patients with borderline and intermediate risks, it is reasonable to continue therapy with moderate-intensity statins. For hypertensive patients with high risk, high-intensity statin therapy can be recommended and low-dose aspirin might be considered if bleeding risk is not increased. If the absolute 10-year risk of atherosclerotic cardiovascular disease is low, it is reasonable to assess additionally total cardiovascular risk categories and continue moderate-intensity statin therapy in the case of absence of low-density lipoprotein cholesterol goal levels with the next lipid profile assessment in 8 (± 4) weeks.

scholarly journals Association of four lipid components with mortality, myocardial infarction, and stroke in statin-naïve young adults: A nationwide cohort study

2020 ◽  
Vol 27 (8) ◽  
pp. 870-881 ◽  
Author(s):  
Heesun Lee ◽  
Jun-Bean Park ◽  
In-Chang Hwang ◽  
Yeonyee E Yoon ◽  
Hyo Eun Park ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Young Adults ◽  
Cohort Study ◽  
Density Lipoprotein ◽  
Population Based ◽  
Lipoprotein Cholesterol ◽  
Lipid Levels ◽  
Clinical Value ◽  
Lipid Management ◽  
Clinical Events

Aims Dyslipidaemia is a modifiable cardiovascular risk factor with prognostic implications. Current strategies for lipid management in young adults are largely based on expert recommendations. We investigated the risks of death and cardiovascular disease in relation to each lipid component to establish evidence for primary prevention in young adults. Methods In this nationwide population-based cohort study, we analysed 5,688,055 statin-naïve subjects, aged 20–39 years, undergoing general health check-ups between 2009 and 2014. The endpoint was a composite of clinical events including death, myocardial infarction (MI), and stroke. We compared the incidence and risk of clinical events according to each lipid variable. Results During follow-up (median 7.1 years), clinical events occurred in 30,330 subjects (0.53%): 16,262 deaths (0.29%), 8578 MIs (0.15%), and 5967 strokes (0.10%). The risk of clinical events gradually increased with increasing total cholesterol (TC) and triglycerides and decreasing high-density lipoprotein cholesterol (HDL-C), largely driven by MI. Low-density lipoprotein cholesterol (LDL-C) had a J-shaped association with clinical events, showing the lowest risk for LDL-C of 84–101 mg/dL. Among lipid variables, triglycerides remained the sole independent predictor (adjusted hazard ratio, 1.20; p < 0.001) after adjusting for conventional risk factors. Conclusions For statin-naïve young adults, the risk of clinical events was proportional to lipid levels, positively with TC and triglycerides, negatively with HDL-C, and J-shaped with LDL-C. Triglycerides had an independent and the strongest association with the clinical events. Screening and intervention for abnormal lipid levels, particularly triglycerides, from an early age might be of clinical value.

Targeting the Cholesterol Paradigm in the Risk Reduction for Atherosclerotic Cardiovascular Disease: Does the Mechanism of Action of Pharmacotherapy Matter for Clinical Outcomes?

2021 ◽  
pp. 107424842110236
Author(s):  
Ruihai Zhou ◽  
George A. Stouffer ◽  
Sidney C. Smith
Keyword(s):  
Cardiovascular Disease ◽  
Clinical Outcomes ◽  
Mechanism Of Action ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Blood Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Lowering ◽  
Cholesterol Levels

Hypercholesterolemia is a well-established risk factor for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) has been labeled as “bad” cholesterol and high-density lipoprotein cholesterol (HDL-C) as “good” cholesterol. The prevailing hypothesis is that lowering blood cholesterol levels, especially LDL-C, reduces vascular deposition and retention of cholesterol or apolipoprotein B (apoB)-containing lipoproteins which are atherogenic. We review herein the clinical trial data on different pharmacological approaches to lowering blood cholesterol and propose that the mechanism of action of cholesterol lowering, as well as the amplitude of cholesterol reduction, are critically important in leading to improved clinical outcomes in ASCVD. The effects of bile acid sequestrants, fibrates, niacin, cholesteryl ester transfer protein (CETP) inhibitors, apolipoprotein A-I and HDL mimetics, apoB regulators, acyl coenzyme A: cholesterol acyltransferase (ACAT) inhibitors, cholesterol absorption inhibitors, statins, and proprotein convertase subtilisin kexin 9 (PCSK9) inhibitors, among other strategies are reviewed. Clinical evidence supports that different classes of cholesterol lowering or lipoprotein regulating approaches yielded variable effects on ASCVD outcomes, especially in cardiovascular and all-cause mortality. Statins are the most widely used cholesterol lowering agents and have the best proven cardiovascular event and survival benefits. Manipulating cholesterol levels by specific targeting of apoproteins or lipoproteins has not yielded clinical benefit. Understanding why lowering LDL-C by different approaches varies in clinical outcomes of ASCVD, especially in survival benefit, may shed further light on our evolving understanding of how cholesterol and its carrier lipoproteins are involved in ASCVD and aid in developing effective pharmacological strategies to improve the clinical outcomes of ASCVD.

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 Time-of-day and Meal Size Effects on Clinical Lipid Markers

2020 ◽  
Author(s):  
Leilah K Grant ◽  
Charles A Czeisler ◽  
Steven W Lockley ◽  
Shadab A Rahman
Keyword(s):  
Cardiovascular Disease ◽  
Total Cholesterol ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Density Lipoprotein ◽  
Time Of Day ◽  
Lipoprotein Cholesterol ◽  
Shift Workers ◽  
Postprandial Lipid Metabolism ◽  
Lipid Panel

Abstract Context Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology. Objective To examine the effects of eating at different times of day on lipid profiles. Design Two 24-hour baseline days with 8 hours of sleep, 3 meals (breakfast, lunch, dinner) and a snack, followed by a 40-hour constant routine (CR) with hourly isocaloric meals. Setting Intensive Physiological Monitoring Unit, Brigham and Women’s Hospital. Participants Twenty-one healthy adults [23.4 ± 2.7 years, 5F] Intervention Forty-hour CR. Main Outcome Measures A standard clinical lipid panel, consisting of total cholesterol, triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), was assayed in blood samples collected 4-hourly across ~4 days. Results When participants ate at night, levels of TG were similar to eating during the day, however, these levels at night were reached with consuming approximately half the calories. Additionally, 24-hour levels of TG were 10% higher when meals were consumed hourly across 24 hours compared to consuming a typical 3-meal schedule while awake during the day and sleeping at night. The endogenous circadian rhythms of TG, which peaked at night, were shifted earlier by ~10 hours under baseline conditions, whereas the rhythms in total cholesterol, HDL-C, and LDL-C remained unchanged and peaked in the afternoon. Conclusions The time-of-day dependency on postprandial lipid metabolism, which leads to hypersensitivity in TG responses when eating at night, may underlie the dyslipidemia and elevated cardiovascular disease risk observed in shift workers.

Abstract P181: Atherogenic Lipoproteins and Incident Atherosclerotic Cardiovascular Disease in the Framingham Offspring Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hiroaki Ikezaki ◽  
Elise Lim ◽  
Ching-Ti Liu ◽  
L Adrienne Cupples ◽  
Bela F Asztalos ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Significant Information ◽  
Ascvd Risk

Introduction: Elevated plasma low-density lipoprotein cholesterol (LDL-C), small-dense LDL-C (sdLDL-C), LDL-triglyceride (LDL-TG), triglycerides (TG), remnant-lipoprotein cholesterol (RLP-C), triglyceride-rich lipoprotein-C (TRL-C), very low-density lipoprotein cholesterol (VLDL-C), and lipoprotein(a) [Lp(a)] levels have been associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. However, these parameters have not been included in risk factors for ASCVD in the pooled cohort equation (PCE). Hypothesis: We assessed the hypothesis that these atherogenic lipoprotein parameters add significant information for ASCVD risk prediction in the Framingham Offspring Study. Methods: We evaluated 3,147 subjects without ASCVD at baseline (mean age 58 years) from participants of Framingham Offspring Study cycle 6, 677 (21.5%) of whom developed inclusive ASCVD over 16 years. Biomarkers of risk were assessed in frozen plasma samples. Total cholesterol, TG, HDL-C, direct LDL-C, sdLDL-C, LDL-TG, Lp(a), RLP-C, and TRL-C were measured by standardized automated analysis. Calculated LDL-C, large buoyant low-density lipoprotein cholesterol (lbLDL-C), VLDL-C, and non-HDL-C values were calculated. Data were analyzed using Cox proportional regression analysis and net reclassification improvement (NRI) analysis to identify parameters significantly associated with the incidence of ASCVD after controlling for standard ASCVD risk factor and applying the PCE model. Results: All specialized lipoprotein parameters were significant ASCVD risk factors on univariate analysis, but only direct LDL-C, sdLDL-C, and Lp(a) were significant on multivariate analysis with standard risk factors in the model. Together these parameters significantly improved the model c statistic (0.716 vs 0.732, P < 0.05) and net risk reclassification (mean NRI 0.104, P < 0.01) for ASCVD risk. Using the ASCVD risk pooled cohort equation, sdLDL-C, TG, LDL-TG, LDL-C, RLP-C, and TRL-C individually added significant information, but no other parameter added significant information with sdLDL-C (hazard ratio 1.30 for 75th vs 25th percentile, P < 0.0001) in the model. Conclusions: In multivariate analysis, sdLDL-C, direct LDL-C, and Lp(a) contributed significantly to ASCVD risk, but only sdLDL-C added significant risk information to the PCE model, indicating that sdLDL-C may be the most atherogenic lipoprotein particle.

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