Recommendations for statin management in primary prevention: disparities among international risk scores.

BACKGROUND AND AIMS: Statin recommendations in primary prevention depend upon risk algorithms. Moreover, with intermediate risk, risk enhancers and de-enhancers are advocated to aid decisions. The aim of this study was to compare algorithms used in North America and Europe for the identification of patients warranting statin or consideration of risk enhancers and de-enhancers. METHODS: A simulated population (n = 7680) equal in males and females, with/without smoking, aged 45-70 years, total cholesterol 3.5-7.0 mmol/L, high-density lipoprotein cholesterol 0.6-2.2 mmol/L, and systolic blood pressure 100-170 mmHg, was evaluated. High, intermediate, and low risks were determined using the Framingham Risk Score (FRS), Pooled Cohort Equation (PCE), four versions of Systematic Coronary Risk Evaluation 2 (SCORE2), and Multi-Ethnic Study of Atherosclerosis (MESA) algorithm (0-1000 Agatston Units). RESULTS: Concordance for the three levels of risk varied from 19% to 85%. Both sexes might be considered to have low, intermediate, or high risk depending on the algorithm applied, even with the same burden of risk factors. Only SCORE2 (High Risk and Very High Risk versions) identified equal proportions of males and females with high risk. Excluding MESA, the proportion with moderate risk was 25% (SCORE2, Very High Risk Region), 32% (FRS), 39% (PCE), and 45% (SCORE2, Low Risk Region). CONCLUSION: Risk algorithms differ substantially in their estimation of risk, recommendations for statin treatment, and use of ancillary testing, even in identical patients. These results highlight the limitations of currently used risk-based approaches for addressing lipid-specific risk in primary prevention.

Imputation of Baseline LDL Cholesterol Concentration in Patients with Familial Hypercholesterolemia on Statins or Ezetimibe.

BACKGROUND: Familial hypercholesterolemia (FH) is the most frequent genetic disorder seen clinically and is characterized by increased LDL cholesterol (LDL-C) (>95th percentile), family history of increased LDL-C, premature atherosclerotic cardiovascular disease (ASCVD) in the patient or in first-degree relatives, presence of tendinous xanthomas or premature corneal arcus, or presence of a pathogenic mutation in the LDLR, PCSK9, or APOB genes. A diagnosis of FH has important clinical implications with respect to lifelong risk of ASCVD and requirement for intensive pharmacological therapy. The concentration of baseline LDL-C (untreated) is essential for the diagnosis of FH but is often not available because the individual is already on statin therapy. METHODS: To validate a new algorithm to impute baseline LDL-C, we examined 1297 patients. The baseline LDL-C was compared with the imputed baseline obtained within 18 months of the initiation of therapy. We compared the percent reduction in LDL-C on treatment from baseline with the published percent reductions. RESULTS: After eliminating individuals with missing data, nonstandard doses of statins, or medications other than statins or ezetimibe, we provide data on 951 patients. The mean ± SE baseline LDL-C was 243.0 (2.2) mg/dL [6.28 (0.06) mmol/L], and the mean ± SE imputed baseline LDL-C was 244.2 (2.6) mg/dL [6.31 (0.07) mmol/L] (P = 0.48). There was no difference in response according to the patient's sex or in percent reduction between observed and expected for individual doses or types of statin or ezetimibe. CONCLUSIONS: We provide a validated estimation of baseline LDL-C for patients with FH that may help clinicians in making a diagnosis.

Effects of adaptive or fixed thresholds and different platforms on the assessment of plaque characteristics using coronary computed tomography angiography.

BACKGROUND: Coronary computed tomography angiography (CCTA) is used to evaluate components of atherosclerosis. Either adaptive or diverse, fixed Hounsfield Units (HU) are used to define components such as low attenuation (LAP), mixed (MP) and calcified plaque (CP). Comparisons of different platforms and different thresholding approaches have not been extensively evaluated. We compare two fixed threshold options to an adaptive threshold option within a specific platform and to fixed threshold options measured with another platform. METHODS: Coronary segments (n â€‹= â€‹24) of good image quality, with well-defined boundaries and representing a broad range of atheroma were analyzed for LAP, MP and CP. Thresholds for LAP vs MP and MP vs CP were either Fixed30/350, Fixed75/350 or based on an automatically determined Adaptive option. Pearson correlation and Bland-Altman analyses were undertaken. RESULTS: Within a single platform, measures were highly correlated irrespective of use of Adaptive or Fixed30/350 and Fixed75/350 thresholds (R â€‹≥ â€‹0.819, p â€‹< â€‹0.000001). The correlation slope for measures of LAP progressively diminished comparing the Adaptive versus Fixed30/350 and the Fixed75/350 versus the Fixed30/350 approaches but bias was small. Between-platform comparisons yielded less optimal results, particularly with respect to measures of LAP and with one platform yielding both very small LAP volumes and very small ranges of volumes. CONCLUSION: Measures of plaque components are highly correlated irrespective of use of Adaptive or Fixed threshold approaches within a given platform. But measures are more affected by the specific proprietary algorithms employed than by specific thresholding options, especially for LAP.

Measurement of Plaque Characteristics Using Coronary Computed Tomography Angiography: Achieving High Interobserver Performance.

BACKGROUND: Coronary computed tomography angiography (CCTA) is used to assess plaque characteristics, remodelling, and progression and regression. Few papers address standard operating procedures that ensure achievement of high interobserver reproducibility. Moreover, assessment of coronary artery bypass grafts has not been reported. METHODS: A training set of images was created of native coronary segments, spanning the full range of atheromatous disease from normal to severe, excluding totally occluded segments, and including segments with or without calcification (n = 24) and completely normal-appearing bypass grafts (n = 16). Three observers used a validated software program during a training phase to establish standard operating procedures and then to achieve high intraobserver performance based on Pearson's correlation coefficient. Subsequently, interobserver variability for the laboratory as a whole was determined with a focus on measures of plaque volume, low- attenuation plaque (LAP), mixed plaque (MP), and calcified plaque (CP). RESULTS: We found no substantive differences in analytical issues between grafts and native vessels and emphasize the aggregated data. The range of mean total plaque percent was approximately 55% of total vessel volume with maximal interobserver mean absolute differences of 2% or less. Percent of LAP, MP, and CP demonstrated interobserver standard errors of 1% to 2% and interobserver mean absolute differences of 0% to 1%. Pearson's correlations were all highly significant and ranged from 0.969 to 0.999. CONCLUSIONS: CCTA provides a rich diversity of measures of atherosclerosis in coronary and bypass segments that are highly reproducible with experience and adherence to standard operating procedures.

INTRODUCTION: L'angiographie cardiaque par tomodensitométrie (TDM) est utilisée pour évaluer les caractéristiques, le remodelage, la progression et la régression de la plaque. Peu d'articles portent sur les procédures opérationnelles normalisées qui permettent d'atteindre une reproductibilité inter-observateurs élevée. De plus, les greffons de pontage aorto-coronarien n'ont pas fait l'objet d'évaluation. MÉTHODOLOGIE: Un ensemble de formation composé d'images de segments d'artères coronaires natives couvrant l'ensemble de la maladie athéromateuse, c'est-à-dire de normale à sérieuse, à l'exclusion des segments totalement obstrués, mais y compris les segments calcifiés ou non (n = 24) et les greffons de pontage qui apparaissent complètement normaux (n = 16) a été créé. Trois observateurs ont utilisé un programme informatique validé durant la phase de formation pour établir des procédures opérationnelles normalisées et ensuite pour atteindre une performance intra-observateurs élevée en fonction du coefficient de corrélation de Pearson. Subséquemment, la variabilité inter-observateurs du laboratoire dans son ensemble a été déterminée plus particulièrement par les mesures du volume de la plaque, la plaque de faible atténuation (PFA), la plaque mixte (PM) et la plaque calcifiée (PC). RÉSULTATS: Nous n'avons constaté aucune différence dans les difficultés analytiques entre les greffons et les vaisseaux natifs et faisons valoir les données regroupées. La fourchette du pourcentage total moyen de la plaque était approximativement de 55 % du volume total du vaisseau avec des différences inter-observateurs absolues moyennes maximales de 2 % ou moins. Le pourcentage de la PFA, de la PM et de la PC a démontré des erreurs types inter-observateurs de 1 % à 2 % et des différences absolues moyennes inter-observateurs de 0 % à 1 %. Les corrélations de Pearson étaient toutes hautement significatives et allaient de 0,969 à 0,999. CONCLUSIONS: La TDM offre une riche diversité de mesures de l'athérosclérose dans les segments d'artères coronaires et de pontage qui, avec l'expérience et le respect des procédures opérationnelles normalisées, sont très reproductibles.

Comparison of cardiovascular risk assessment algorithms to determine eligibility for statin therapy: implications for practice in Canada.

BACKGROUND: New lipid management guidelines in the United States have created controversy regarding risk assessment using the new Pooled Cohort Equations (PCE) which might overestimate cardiovascular risk and identify an excessive number of patients as new candidates for statin therapy. METHODS: We compared the Framingham Risk Score (FRS) used in Canada with PCE, the FRS version used in Adult Treatment Panel III (ATP III), Reynolds Risk Score (RRS), and Systematic Coronary Risk Evaluation (SCORE) using patient profile simulation of 10 cohorts of 100,000 each (total n = 1,000,000 for each comparison). Patients with diabetes, established cardiovascular disease, or family history of premature cardiovascular disease were not considered, mimicking uncomplicated primary prevention. Analyses were performed separately for men and women and for black individuals when feasible. RESULTS: SCORE (high-risk version) was most concordant with FRS in men, whereas PCE was most concordant in black women. Compared with FRS, all other algorithms except SCORE (high-risk version) identified more simulations as low risk. Reclassification from low FRS to a higher risk was not seen using RRS or ATP III and seen in < 5% of simulations using PCE, affecting predominantly black subject simulations. CONCLUSIONS: Choice of risk calculator leads to systematic differences in risk categorization that can influence eligibility for lipid-lowering therapy. Compared with FRS, an isolated switch to PCE, RRS, or ATP III is unlikely to lead to substantial reclassification from low to higher risk categories in Canada.

Redefining the normal angiogram using population-derived ranges for coronary size and shape: validation using intravascular ultrasound and applications in diverse patient cohorts.

OBJECTIVES: To develop a method for quantitating coronary angiographic abnormalities of segmental size and shape (tapering) in comparison to gender- and segment-specific, population derived, normal values. BACKGROUND: In the absence of obvious focal stenoses, remodeling renders the angiogram insensitive to the presence of atherosclerosis and invalidates use of a "normal reference segment" for calculation of percent diameter stenosis. METHODS: Equations were created for detection of size/shape abnormalities of coronary angiographic segments. After validation using intravascular ultrasound (IVUS), the equations were applied to a cohort of segments judged to be completely normal by a panel of highly experienced, core laboratory technicians; and a cohort of patients judged by an experienced interventionalist to have completely normal coronaries. RESULTS: In patients assessed by core technicians, 53% (162/303) of males, 39% (209/538) of normal segments in males, 60% (56/94) of females, and 40% (81/205) of normal segments in females had quantifiable abnormalities. In patients with normal coronaries as judged by an experienced interventionalist, 100% of males (n = 14) and females (n = 19), 37% (67/182) of segments in males and 43% (105/247) of segments in females had abnormalities. The left main segment was most commonly abnormal. CONCLUSIONS: We propose a set of equations validated using IVUS and based on gender- and segment-specific normal values for coronary angiographic size and shape that markedly improves the sensitivity of the coronary angiogram for detection of abnormalities. The method should replace the unfounded practice of labeling coronary angiograms as "normal" based solely on the failure to detect focal stenoses.