Risk results from screening for a high cardiovascular disease risk by means of traditional risk factor measurement or coronary artery calcium scoring in the ROBINSCA trial

Abstract Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease (CHD)-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or Coronary Artery Calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized (1:1:1) into the control arm (n=14,519; usual care); screening arm A (n=14,478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n=14,450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. 12,185 participants (84.2%) in arm A and 12,950 (89.6%) in arm B were screened. 48.7% were women, and median age was 62 (InterQuartile Range 10) years. SCORE screening identified 45.1% at low risk (SCORE<10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE≥20%). According to CAC screening, 76.0% were at low risk (Agatston<100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston≥400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. ROBINSCA flowchart Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Advanced Research Grant

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Screening for cardiovascular disease risk using traditional risk factor assessment or coronary artery calcium scoring: the ROBINSCA trial

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jeaa168 ◽

2020 ◽

Vol 21 (11) ◽

pp. 1216-1224 ◽

Cited By ~ 2

Author(s):

Carlijn M van der Aalst ◽

Sabine J A M Denissen ◽

Marleen Vonder ◽

Jan Willem C Gratama ◽

Henk J Adriaansen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

Risk Score ◽

Coronary Artery Calcium ◽

Preventive Treatment ◽

Low Risk ◽

Relative Reduction ◽

Cvd Risk ◽

Increased Risk

Abstract Aims Screening for a high cardiovascular disease (CVD) risk followed by preventive treatment can potentially reduce coronary heart disease-related morbidity and mortality. ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) is a population-based randomized controlled screening trial that investigates the effectiveness of CVD screening in asymptomatic participants using the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring. This study describes the distributions in risk and treatment in the ROBINSCA trial. Methods and results Individuals at expected elevated CVD risk were randomized into screening arm A (n = 14 478; SCORE, 10-year fatal and non-fatal risk); or screening arm B (n = 14 450; CAC scoring). Preventive treatment was largely advised according to current Dutch guidelines. Risk and treatment differences between the screening arms were analysed. A total of 12 185 participants (84.2%) in arm A and 12 950 (89.6%) in arm B were screened. In total, 48.7% were women, and median age was 62 (interquartile range 10) years. SCORE screening identified 45.1% at low risk (SCORE < 10%), 26.5% at intermediate risk (SCORE 10–20%), and 28.4% at high risk (SCORE ≥ 20%). According to CAC screening, 76.0% were at low risk (Agatston < 100), 15.1% at high risk (Agatston 100–399), and 8.9% at very high risk (Agatston ≥ 400). CAC scoring significantly reduced the number of individuals indicated for preventive treatment compared to SCORE (relative reduction women: 37.2%; men: 28.8%). Conclusion We showed that compared to risk stratification based on SCORE, CAC scoring classified significantly fewer men and women at increased risk, and less preventive treatment was indicated. Trial registration number NTR6471.

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P3397Risk Or Benefit IN Screening for CArdiovascular disease (ROBINSCA): results from screening for a high cardiovascular disease risk by using a risk prediction model or coronary artery calcium scoring

European Heart Journal ◽

10.1093/eurheartj/ehz745.0273 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Denissen ◽

C M Van Der Aalst ◽

M Vonder ◽

J W Gratama ◽

H J Adriaansen ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

Risk Score ◽

Preventive Treatment ◽

Population Based ◽

Low Risk ◽

Screening Tools ◽

Cvd Risk ◽

Score Model

Abstract Introduction The ROBINSCA (Risk Or Benefit IN Screening for CArdiovascular disease) trial is a large-scale population-based randomized controlled screening trial with the aim to investigate whether screening for a high risk of cardiovascular disease (CVD) by means of either the Systematic COronary Risk Evaluation (SCORE) model or coronary artery calcium (CAC) scoring followed by preventive treatment is effective in reducing morbidity and mortality from coronary heart disease (CHD). This study shows the results of the CVD risks as assessed by the two screening tools. Methods Based on the Dutch population registry, 394,058 men aged 45–74 years and women aged 55–74 years received an information brochure, an invitation to participate in the trial, a baseline questionnaire with waist circumference tape and an informed consent form. Eligible individuals with an expected high CVD risk were randomized (1:1:1) into a control arm (n=14,519), intervention arm A (n=14,478) or intervention arm B (n=14,450). In the control arm, usual care was continued. In intervention arm A, participants were screened for a high risk of CVD using the SCORE model based on traditional risk factors. In intervention arm B, CAC scoring after computed tomography scanning was used for screening. After screening en risk communication, preventive treatment according to the Dutch guidelines is advised for high risk persons. Results Screening uptake was 84.2% in intervention arm A and 89.6% in intervention arm B. Of the screened participants, 48.7% was female, median age at screening was 62 (Interquartile Range 10), 35.2% was high educated, 19.6% was baseline smoker and 41.4% had a positive family history of myocardial infarction. The assessed CVD risk status according to SCORE screening was stratified into three risk categories; 45.1% was at low risk (SCORE<10%), 26.5% was at intermediate risk (SCORE 10–20%), and 28.4% was at high risk (SCORE ≥20%). According to CAC screening, 76.0% was at low risk (Agatston <100), 15.1% was at high risk (Agatston 100–399), and 8.9% was at very high risk (Agatston ≥400). Associations between baseline variables and increased CVD risk will be analyzed soon and will be available in summer 2019. Conclusions Using different screening tools resulted in reclassification of the CVD risk. CAC screening caused a substantial shift to more low risk individuals. This might, when screening is found to be effective, lead to less overtreatment in prevention of CVD events. Future 5-year follow-up data should provide evidence about whether population-based screening with subsequent preventive treatment is (cost-)effective in reducing CHD-related morbidity and mortality.

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Abstract 17065: Performance of Cardiovascular Disease Risk Scores to Identify Coronary Artery Calcium Burden in Retired National Football League Players

Circulation ◽

10.1161/circ.142.suppl_3.17065 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Genevieve E Smith ◽

Jonathan A Drezner ◽

Camilo Fernandez ◽

Gregory W Stewart

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

Coronary Artery Calcium ◽

National Football League ◽

Elite Athlete ◽

Risk Scores ◽

Cvd Risk ◽

Discriminative Ability ◽

C Statistic ◽

Increased Risk

Introduction: Coronary artery calcium (CAC) is a robust predictor of coronary events in asymptomatic individuals with latent atherosclerotic cardiovascular disease (CVD). While evidence suggests CAC scoring may augment traditional CVD risk scores in clinical decision making, evidence is limited on the compared ability of CVD risk scores to identify the degree of coronary atherosclerosis as quantified by absolute CAC, particularly in former elite athlete populations. We investigated this in a cohort of retired National Football League (NFL) players. Methods: We analyzed data on 752 retired NFL players (aged 55.2 ± 9.0 years, 53.7% African-American] that underwent health screening and CAC scoring with the NFL Player Care Foundation. Three 10-year CVD risk scores were compared: Framingham Coronary Heart Disease (FCHD), Framingham CVD (FCVD), and Atherosclerotic CVD Risk Pooled Cohort Equations (PCE). Receiver operating characteristic curves were fitted in 3 models: FCHD (Model 1), FCVD (Model 2), and PCE (Model 3, used as reference based on 2013 AHA guidelines). Contrast analyses identified the model with highest discriminative ability (c statistic) versus CAC = 0 for each CAC score category: >0 and <100, 100-400, and >400. Results: Compared to PCE , FCVD exhibited the highest discriminative ability for CAC > 0 and < 100 ( c statistic 0.7071 vs 0.6706, p<0.0001), while FCHD had the lowest for both CAC 100-400 ( c statistic 0.7198 vs 0.7664, p=0.0165) and CAC >400 ( c statistic 0.7728 vs 0.8460, p<0.0001). No additional differences were identified (Figure 1). Conclusion: Traditional CVD risk scores differ in performance to predict absolute CAC among retired NFL players, underscoring a need for refinement of coronary event risk prediction models to enhance the ability of such models to identify, specifically, low CAC, as even low CAC burden confers increased risk compared to CAC absence. This may include accounting for elite athlete-specific characteristics.

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Coronary Artery Calcium Score for Personalization of Antihypertensive Therapy

Hypertension ◽

10.1161/hypertensionaha.120.16689 ◽

2021 ◽

Vol 77 (4) ◽

pp. 1106-1118

Author(s):

Vibhu Parcha ◽

Gargya Malla ◽

Rajat Kalra ◽

Peng Li ◽

Ambarish Pandey ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

Cardiovascular Event ◽

Coronary Artery Calcium ◽

Cardiovascular Events ◽

Low Risk ◽

Stage I ◽

Number Needed To Treat ◽

Hypertension Therapy

The 2017 American College of Cardiology/American Heart Association high blood pressure (BP) guidelines recommend risk assessment of atherosclerotic cardiovascular disease to inform hypertension treatment in adults with elevated BP or low-risk stage I hypertension. The use of coronary artery calcium (CAC) score to guide hypertension therapy has not been adequately evaluated. Participants free of cardiovascular disease were pooled from Multi-Ethnic Study of Atherosclerosis, Coronary Artery Risk Development in Young Adults, and Jackson Heart Study. The risk for incident cardiovascular events (heart failure, stroke, coronary heart disease), by CAC status (CAC-0 or CAC>0) and BP treatment group was assessed using multivariable-adjusted Cox regression. The 10-year number needed to treat to prevent a single cardiovascular event was also estimated. This study included 6461 participants (median age 53 years; 53.3% women; 32.3% Black participants). Over a median follow-up of 8.5 years, 347 incident cardiovascular events occurred. Compared with those with normal BP, the risk of incident cardiovascular event was higher among those with elevated BP/low-risk stage I hypertension and CAC>0 (hazard ratio, 2.4 [95% CI, 1.7–3.4]) and high-risk stage I/stage II hypertension (BP, 140–160/80–100 mm Hg) with CAC>0 (hazard ratio, 2.9 [95% CI, 2.1–4.0]). A similar pattern was evident across racial subgroups and for individual study outcomes. Among those with CAC-0, the 10-year number needed to treat was 160 for elevated BP/low-risk stage I hypertension and 44 for high-risk stage I or stage II hypertension (BP, 140–160/80–100 mm Hg). Among those with CAC>0, the 10-year number needed to treat was 36 and 22, respectively. Utilization of the CAC score may guide the initiation of hypertension therapy and preventive approaches to personalize cardiovascular risk reduction among individuals where the current guidelines do not recommend treatment.

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Vitamin D and Cardiovascular Disease: An Updated Narrative Review

International Journal of Molecular Sciences ◽

10.3390/ijms22062896 ◽

2021 ◽

Vol 22 (6) ◽

pp. 2896

Author(s):

Armin Zittermann ◽

Christian Trummer ◽

Verena Theiler-Schwetz ◽

Elisabeth Lerchbaum ◽

Winfried März ◽

...

Keyword(s):

Cardiovascular Disease ◽

Vitamin D ◽

High Risk ◽

General Population ◽

Vitamin D Deficiency ◽

Specific Gene ◽

Vitamin D Status ◽

Cvd Risk ◽

Severe Vitamin ◽

Increased Risk

During the last two decades, the potential impact of vitamin D on the risk of cardiovascular disease (CVD) has been rigorously studied. Data regarding the effect of vitamin D on CVD risk are puzzling: observational data indicate an inverse nonlinear association between vitamin D status and CVD events, with the highest CVD risk at severe vitamin D deficiency; however, preclinical data and randomized controlled trials (RCTs) show several beneficial effects of vitamin D on the surrogate parameters of vascular and cardiac function. By contrast, Mendelian randomization studies and large RCTs in the general population and in patients with chronic kidney disease, a high-risk group for CVD events, largely report no significant beneficial effect of vitamin D treatment on CVD events. In patients with rickets and osteomalacia, cardiovascular complications are infrequently reported, except for an increased risk of heart failure. In conclusion, there is no strong evidence for beneficial vitamin D effects on CVD risk, either in the general population or in high-risk groups. Whether some subgroups such as individuals with severe vitamin D deficiency or a combination of low vitamin D status with specific gene variants and/or certain nutrition/lifestyle factors would benefit from vitamin D (metabolite) administration, remains to be studied.

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Abstract P159: Coronary Artery Calcium Score Improves the Net Reclassification Index of Prevalent Cardiovascular Disease In African Americans: The Jackson Heart Study

Circulation ◽

10.1161/circ.125.suppl_10.ap159 ◽

2012 ◽

Vol 125 (suppl_10) ◽

Author(s):

Joseph Yeboah ◽

Che L Smith ◽

Mario Sims ◽

Ervin Fox ◽

Yaorong Ge ◽

...

Keyword(s):

Cardiovascular Disease ◽

Coronary Artery ◽

High Risk ◽

African Americans ◽

Diagnostic Accuracy ◽

Coronary Artery Calcium ◽

Smoking Status ◽

Jackson Heart Study ◽

Net Reclassification Improvement ◽

Heart Study

Background: Prior studies suggest that African Americans (AA) have lower prevalence of coronary artery calcium (CAC) compared to whites, yet CAC has similar ability to predict coronary heart disease (CHD) events. The role of CAC as a screening tool for CHD risk in AA is unclear. We compared the diagnostic accuracy for CHD prevalence using the CAC score and the Framingham Risk Score (FRS) in an adult population of AA. Methods: CAC was measured in 2944 participants in the Jackson Heart Study, an NHLBI funded study of AA based in Jackson, MS. Approximately 8% of this cohort had known cardiovascular disease (CVD) defined as prior MI, angina, stroke, PTCA, CABG or PVD. Logistic regression, ROC and net reclassification index (NRI) analysis were used adjusting for age, gender, SBP, total and HDL cholesterol, smoking status, DM and BMI. FRS was calculated and those with DM were classified as high risk. Results: The mean age was 60, 65% were females, 26% had DM, 50% were obese and 30% were current or former smokers. Prevalent CVD was associated with older age, higher SBP, lower HDL and total cholesterol, and higher CAC. CAC was independently associated with prevalent CVD in our multivariable model [OR (95% CI): 1.26 (1.17, 1.35), p< 0.0001]. In ROC analysis, CAC improved the diagnostic accuracy (c statistic) of the FRS from 0.617 to 0.757 (p < 0.0001) for prevalent CVD. The FRS classified 30% of the cohort as high risk, 38.5% as intermediate risk and 31.5% as low risk. FRS classfied 51% of subjects with prevalent CVD as high risk. Addition of CAC to FRS resulted in net reclassification improvement of 4% for subjects with known CVD and 28.5% in those without CVD (see figure). Conclusion: In AA, the CAC is independently associated with prevalent CVD and improves the diagnostic accuracy of FRS for prevalent CVD by 14%. Addition of CAC improves the NRI of those with prevalent CVD by 4% and the NRI of individuals without CVD by 28.5%. Determination of CAC in AA may be useful in identifying individuals at risk of CVD and reclassifying individuals with low and intermediate FRS.

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Associations of recreational and non-recreational physical activity with coronary artery calcium density vs. volume and cardiovascular disease events: the Multi-Ethnic Study of Atherosclerosis

European Heart Journal - Cardiovascular Imaging ◽

10.1093/ehjci/jez271 ◽

2019 ◽

Cited By ~ 1

Author(s):

Isac C Thomas ◽

Michelle L Takemoto ◽

Nketi I Forbang ◽

Britta A Larsen ◽

Erin D Michos ◽

...

Keyword(s):

Physical Activity ◽

Cardiovascular Disease ◽

Coronary Artery ◽

Standard Deviation ◽

Coronary Artery Calcium ◽

Recreational Physical Activity ◽

Cvd Risk ◽

Ethnic Study ◽

Subclinical Marker

Abstract Aims The benefits of physical activity (PA) on cardiovascular disease (CVD) are well known. However, studies suggest PA is associated with coronary artery calcium (CAC), a subclinical marker of CVD. In this study, we evaluated the associations of self-reported recreational and non-recreational PA with CAC composition and incident CVD events. Prior studies suggest high CAC density may be protective for CVD events. Methods and results We evaluated 3393 participants of the Multi-Ethnic Study of Atherosclerosis with prevalent CAC. After adjusting for demographics, the highest quintile of recreational PA was associated with 0.07 (95% confidence interval 0.01–0.13) units greater CAC density but was not associated with CAC volume. In contrast, the highest quintile of non-recreational PA was associated with 0.08 (0.02–0.14) units lower CAC density and a trend toward 0.13 (−0.01 to 0.27) log-units higher CAC volume. There were 520 CVD events over a 13.7-year median follow-up. Recreational PA was associated with lower CVD risk (hazard ratio 0.88, 0.79–0.98, per standard deviation), with an effect size that was not changed with adjustment for CAC composition or across levels of prevalent CAC. Conclusion Recreational PA may be associated with a higher density but not a higher volume of CAC. Non-recreational PA may be associated with lower CAC density, suggesting these forms of PA may not have equivalent associations with this subclinical marker of CVD. While PA may affect the composition of CAC, the associations of PA with CVD risk appear to be independent of CAC.

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Antidepressant Use and the Risk of Major Adverse Cardiovascular Events in Patients Without Known Cardiovascular Disease: A Retrospective Cohort Study

Frontiers in Pharmacology ◽

10.3389/fphar.2020.594474 ◽

2020 ◽

Vol 11 ◽

Author(s):

Ha Young Jang ◽

Jae Hyun Kim ◽

Yun-Kyoung Song ◽

Ju-Young Shin ◽

Hae-Young Lee ◽

...

Keyword(s):

Cardiovascular Disease ◽

Risk Score ◽

Cardiovascular Events ◽

Major Adverse Cardiovascular Events ◽

Cvd Risk ◽

Hazard Ratios ◽

Increased Risk ◽

History Of ◽

Antidepressant Use ◽

Cox Proportional Hazard Regression

Aims: Conflicting data exist on whether an association exists between antidepressants and the risk of major adverse cardiovascular events (MACEs) in patients with depression. This may be due to the use of various study designs and residual or unmeasured confounding. We aimed to assess the association between antidepressant use and the risk of MACEs while considering various covariates, including severity of depression and the cardiovascular disease (CVD) risk score.Methods: Patients newly diagnosed with depression with no history of ischemic heart disease and stroke were followed-up from 2009 to 2015. We conducted Cox proportional hazard regression analysis to estimate hazard ratios (HRs) for each antidepressant for MACE risk.Result: We followed-up (median, 4.4 years) 31,830 matched patients with depression (15,915 antidepressant users and 15,915 non-users). In most patients (98.7%), low-dose tricyclic antidepressants (TCAs) were related with a significantly increased risk of MACEs [adjusted HR = 1.20, 95% confidence interval (CI) = 1.03–1.40]. Duration response relationship showed a gradually increasing HR from 1.15 (95% CI = 0.98–1.33; <30 days of use) to 1.84 (95% CI = 1.35–2.51; ≥365 days of use) (p for trend <0.01). High Korean atherosclerotic CVD risk score (≥7.5%) or unfavorable lifestyle factors (smoking, alcohol intake, and exercise) were significantly associated with MACEs.Conclusion: Even at low doses, TCA use was associated with MACEs during primary prevention. Longer duration of TCA use correlated with higher HR. Careful monitoring is needed with TCA use in patients with no known CVD history.

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Low-Density Lipoprotein Subfractionation: What Is the Role of the Lab When Reporting Discrepant Results?

American Journal of Clinical Pathology ◽

10.1093/ajcp/aqaa137.015 ◽

2020 ◽

Vol 154 (Supplement_1) ◽

pp. S8-S9

Author(s):

Nicholas E Larkey ◽

Leslie J Donato ◽

Allan S Jaffe ◽

Jeffrey W Meeusen

Keyword(s):

Coronary Artery ◽

High Risk ◽

Clinical Decision Making ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Low Risk ◽

Lipid Lowering ◽

Low Density ◽

Small Dense Ldl ◽

Increased Risk

Abstract Plasma concentrations of low-density-lipoprotein cholesterol (LDL-C) are directly associated with risk for coronary artery disease (CAD). Multisociety guidelines define LDL-C>160mg/dL as a risk factor for CAD and LDL-C>190mg/dL as an indication for lipid lowering medication, regardless of other clinical factors. Subfractionation of LDL according to size (LDL-s) enables differentiation between two LDL phenotypes: large-buoyant LDL and small-dense LDL. The small-dense LDL phenotype reportedly conveys increased risk for CAD. Major societies do not recommend LDL subfractions be used for clinical decision making and most payers do not cover LDL subfraction testing. Despite these restrictions, LDL subfraction is routinely requested by clinicians. Nuclear magnetic resonance (NMR) spectroscopy measures LDL-C and LDL-s. Following inquiries regarding interpretation of conflicting LDL-C and LDL-s results, we investigated associations between LDL-C and LDL-s measured by NMR in order to determine how often they provide contradicting or additive information. Verification of NMR LDL-C accuracy was confirmed by ÃŸ-quantification in a subset of patient samples (n=250). The average bias was -4.5mg/dL and the correlation coefficient was 0.92. High-risk was defined as LDL-C>160mg/dL or LDL-s<20.5 nm (small-dense LDL); and low-risk was defined as LDL-C<70mg/dL or LDL-s>20.5nm (large-buoyant LDL). In 26,710 clinical NMR analyses, the median LDL-C was 94.0mg/dL (range:5-436mg/dL) with median LDL-s of 20.8 nm (range:19.4–23.0nm). LDL-s moderately correlated with LDL-C (Ï#129;=0.51;p<0.01). Small-dense-LDL was identified in only 18% (407/2,191) of patients with elevated LDL-C (>160mg/dL) and was more common (73.2% of 6,093) in patients with low LDL-C (<70mg/dL;p<0.001). Associations with CAD were investigated among patients without cholesterol-lowering medication treatment referred for angiography (n=356). CAD (defined as stenosis >50% in one or more coronary artery) was diagnosed in 14% (1/7) of subjects with low LDL-C (<70mg/dL) compared to 59% (47/80) of subjects with elevated LDL-C (p=0.01). When stratifying by LDL-s, CAD was diagnosed in 50% (57/115) of subjects with small-dense LDL compared to 43% (104/241) of subjects with large-buoyant LDL (p=0.2). Small-dense LDL was identified in only 33% (26/80) of cases with elevated LDL-C. Limiting to subjects with elevated LDL-C, CAD was diagnosed in 50% (13/26) of subjects with concordant (high-risk) small-dense LDL compared to 61% (33/54) of subjects with discordant (low-risk) large-buoyant LDL (LDL-s>20.5nm) (p=0.3). Our data confirm that LDL-s subfraction measured by NMR is reported discordantly in most cases when LDL-C is unequivocally high or low. Furthermore, CAD diagnosis was significantly associated with LDL-C, but not with LDL-s. Our data also show that in discrepant samples, elevated LDL-C correlates better with disease state compared to LDL-s. Therefore, LDL-s should not be used to justify treatment decisions in patients with elevated LDL-C. Laboratories should consider carefully whether or not to report LDL-s when it is known that misleading and discordant values will be reported in a majority of cases.

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