Comparing a novel equation for calculating low-density lipoprotein cholesterol with the Friedewald equation: A VOYAGER analysis

Treating elevated low-density lipoprotein cholesterol (LDL-C) to risk-stratified target levels is recommended in several guidelines. Thus, accurate estimation of LDL-C is required. LDL-C is typically calculated using the Friedewald equation: (total cholesterol) – (non-high-density lipoprotein cholesterol [non-HDL-C]) – (triglycerides [TGs]/5). As the equation uses a fixed value equal to 5 as a divisor for TGs, it does not account for inter-individual variability, often resulting in underestimation of risk and potentially undertreatment. It is specifically inapplicable in patients with fasting triglycerides ≥400 mg/dL. A novel method of LDL-C calculation was derived and validated by Martin et al.: (non-HDL-C) – (triglycerides/adjustable factor). This equation uses an adjustable factor, the median TG:very-low-density lipoprotein cholesterol ratio in strata defined by levels of TG and non-HDLC, as divisor for TGs, and the adjustable factor ranging from 3 to 12 has been shown to provide more accurate estimates of LDL-C compared with the Friedewald equation using a direct assay as the gold standard.We used 70,209 baseline and on-treatment lipid values from the VOYAGER meta-analysis database to determine the difference in calculated LDL-C values using the Friedewald and novel equations. In patients with TGs <400 mg/dL, LDL-C values calculated using the novel equation were plotted against those calculated using the Friedewald equation. The novel equation generally resulted in LDL-C values greater than the Friedewald calculation, with differences increasing with decreasing LDL-C levels; 23% of individuals who reached a LDL-C target of 70 mg/dL with the Friedewald equation did not achieve this target when the novel equation was used to calculate LDL-C; these figures were 8% and 2% for <100 mg/dL and < 130 mg/dL targets, respectively. In patients with triglycerides ≥400 mg/dL, in whom the Friedewald equation is not valid, lipid values calculated using the novel equation were compared with those obtained by β-quantification. Values calculated with the novel equation did not appear to be closely related with those calculated by β-quantification in these patients. In conclusion, the novel equation provides a higher estimation of exact LDL-C values than the Friedewald equation, particularly in patients with low LDL-C levels, which may result in undertreatment of some patients whose LDL-C was calculated using the Friedewald method. However, neither may be suitable for patients with TG ≥400 mg/dL.     

Serum osteoprotegerin is a predictor for incident cardiovascular disease and mortality in a general population: the Tromsø Study

Summary. Background: Osteoprotegerin (OPG) concentration in serum is associated with the presence and severity of atherosclerosis. Objective: To investigate the association between serum osteoprotegerin and the risk of a future myocardial infarction, ischemic stroke and mortality in a general population. Patients/methods: OPG was measured in serum collected from 6265 subjects recruited from a general population without a prior myocardial infarction and ischemic stroke (the Tromsø Study). Incident myocardial infarction, ischemic stroke and mortality were registered during follow‐up. Cox regression models were used to estimate crude and adjusted hazard ratios and 95% confidence intervals (HR; 95% CI). Results: There were 575 myocardial infarctions, 284 ischemic strokes and 824 deaths (146 deaths as a result of ischemic heart disease, 78 deaths because of stroke and 600 deaths due to other causes) in the cohort during a median of 10.6 years of follow‐up. Serum OPG (per SD [1.13 ng mL^?1] increase in OPG) was associated with an increased risk of a myocardial infarction (1.20; 1.11–1.31), ischemic stroke (1.32; 1.18–1.47), total mortality (1.34; 1.26–1.42), death because of ischemic heart disease, (1.35; 1.18–1.54), stroke (1.44; 1.19–1.75) and non‐vascular causes (1.31; 1.22–1.41) after adjustment for age, gender, current smoking, systolic blood pressure, body mass index, high density lipoprotein cholesterol, total cholesterol, creatinine, high sensitivity C‐reactive protein (CRP) and diabetes mellitus or HbA1c > 6.1%. No association was detected between OPG and incident hemorrhagic stroke (1.02; 0.73–1.43). Conclusions: Serum OPG was associated with future risk of myocardial infarction, ischemic stroke, total mortality, mortality of ischemic heart disease, stroke and of non‐vascular causes independent of traditional cardiovascular risk factors.     

Evaluation of alternative calculation methods for determining low-density lipoprotein cholesterol in hemodialysis patients

OBJECTIVES: To evaluate alternative equations for the estimation of low-density lipoprotein cholesterol (LDL-C) than the Friedewald equation in hemodialysis patients. DESIGN AND METHODS: The equations LDL-C = 0.41TC - 0.14TG + 0.66ApoB - 10.43 and LDL-C = 0.94TC - 0.94HDL-C - 0.19TG were evaluated in 86 patients and compared with the Friedewald equation and the ultracentrifugation procedure. RESULTS: The alternative equations yield significantly lower bias than the Friedewald equation and are less affected by increased triglycerides (TG) levels. CONCLUSION: The alternative equations for LDL-C yield slightly better results than the Friedewald equation especially in hypertriglyceridemia.     

Associations of prediabetes with all-cause and cardiovascular mortality: A meta-analysis

Abstract

Background. Reports on the association of prediabetes with all-cause mortality and cardiovascular mortality are inconsistent.

Objective. To evaluate the risk of all-cause and cardiovascular mortality in association with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).

Methods. Prospective cohort studies with data on prediabetes and mortality were included. The relative risks (RRs) of all-cause and cardiovascular mortality were calculated and reported with 95% confidence intervals (95% CIs).

Results. Twenty-six studies were included. The risks of all-cause and cardiovascular mortality were increased in participants with prediabetes defined as IFG of 110–125 mg/dL (IFG 110) (RR 1.12, 95% CI 1.05–1.20; and RR 1.19, 95% CI 1.05–1.35, respectively), IGT (RR 1.33, 95% CI 1.24–1.42; RR 1.23, 95% CI 1.11–1.36, respectively), or combined IFG 110 and/or IGT (RR 1.21, 95% CI 1.11–1.32; RR 1.21, 95% CI 1.07–1.36, respectively), but not when IFG was defined as 100–125 mg/dL (RR 1.07, 95% CI 0.92–1.26; and RR 1.16, 95% CI 0.94–1.42, respectively).

Conclusions. Prediabetes, defined as IFG 110, IGT, or combined IFG 110 and/or IGT, was associated with increased all-cause and cardiovascular mortality.     

Factores asociados a mortalidad intrahospitalaria en pacientes adultos mayores con asistencia ventilatoria mecánica invasiva en el servicio de urgencias

AimsTo identify factors associated with in-hospital mortality, to estimate the intubation rate and to describe in-hospital mortality in patients over 65 years old with invasive mechanical ventilation (IMV) in the emergency department (ED).MethodsRetrospective cohort study of patients over 65 years old, who were intubated in an ED of a high complexity hospital between 2016 and 2018. Demographic data, comorbidities, and severity scores on admission were described. Bivariate and multivariate analyses were performed with logistic regression according to mortality and possible confounders.ResultsA total of 285 patients with a mean age of 80 years required IMV in the emergency department, for a median of 3 days, and with a mean APACHE II score of 20 points of severity. The IMV rate was .48% (95% CI .43-.54), and 55.44% (158) died. Mortality-associated factors after age and sex adjustment were stroke (OR 2.13; 95%CI 1.21-3.76), chronic kidney failure, (OR 4.,38; 95%CI 1.91-10.04), Charlson index (OR 1.19; 95%CI 1.02-1.38), APACHE II score (OR 1.07; 95%CI 1.02-1.12), and SOFA score (OR 1.14; 95%CI 1.03-1.27).DiscussionOur IMV rate was lower than that stated by Johnson et al. in the United States in 2018 (.59%). In-hospital mortality in our study exceeded that predicted by the APACHE II score (40%) and SOFA (33%). However it was consistent with that reported by Lieberman et al. in Israel and Esteban et al. in the United States.ConclusionsAlthough the IMV rate was low in the ED, more than half the patients died during hospitalization. Pre-existing cerebrovascular and renal diseases and high results in the comorbidities index and severity scores on admission were independent factors associated with in-hospital mortality.     

Laboratory validation of a low density lipoprotein apolipoprotein-B assay

ObjectivesNumerous publications have shown strong association between CHD risk and either apolipoprotein B (Apo-B) or low density lipoprotein (LDL) particle number (LDL-P). It is however unknown if Apo-B or LDL-P has a stronger predictive ability for future CHD. This uncertainty may be due to the inability of current Apo-B assays to separate the contribution of very low-density lipoprotein particles from the total Apo-B concentration. As such we have performed a laboratory validation of the Maine Standards® LDL Apo-B assay on the Roche Cobas 6000 analyzer.Design and methodsImprecision, linear range, and limit of quantitation studies were performed using quality control materials. Plasma samples collected for lipid profile analysis were analyzed via the LDL Apo-B assay and compared to the LDL cholesterol (LDL-C) concentration determined via direct LDL assay and Friedewald equation.ResultsThe LDL Apo-B within-run imprecision was 2.3% at 62 mg/dL and 2.2% at 109 mg/dL. The within-laboratory imprecision was 9.7% at 57 mg/dl and 6.1% at 104 mg/dL. Linear regression analysis of LDL Apo-B versus calculated and measured LDL-c resulted in equations of LDL Apo-B = 0.620 1 (LDL) + 45.4, R = 0.9063 and LDL-Apo-B = 0.607 1 (LDL) + 38.8, R = 0.9393, respectively. Bias plot analyses revealed that at low LDL-C concentration, there was a tendency for a higher than anticipated LDL Apo-B concentration.ConclusionsThe Maine Standards LDL Apo-B assay is a precise automated assay and comparison of LDL Apo-B to LDL-c concentration demonstrates that low LDL-C concentrations may still carry residual risk of CHD due to increased concentration of small dense LDL particles.     

Cardiovascular disease risk factors in a population‐based sample of Norwegian children and adolescents

Objective. The objective of the study was to describe the distribution of cardiovascular disease (CVD) risk factors, and to evaluate the extent of clustering of CVD risk factors in Norwegian children and adolescents. Material and methods. A randomly selected cohort of 9‐year‐olds and 15‐year‐olds from all regions of the country was sampled. Of 2,818 subjects invited to participate, 2,299 accepted, giving an overall participation rate of 82?%. Results. Mean (SD) values for the main risk factors for 9‐year‐old and 15‐year‐old girls and boys were: total cholesterol (TC) (mmol/L) 4.49 (0.73), 4.37 (0.68), 4.19 (0.76) and 3.80 (0.69), respectively; triglycerides (TG) (mmol/L) 0.72 (0.33), 0.63 (0.32), 0.79 (0.32) and 0.82 (0.47), respectively; high density lipoprotein cholesterol (HDL‐c) (mmol/L) 1.70 (0.35), 1.79 (0.40), 1.61 (0.34) and 1.42 (0.30), respectively; systolic blood pressure (mmHg) 102.6 (7.7), 103.3 (7.7), 109.0 (8.8) and 115.3 (9.0), respectively; and homeostasis model assessment score (HOMA) 1.29 (0.83), 1.19 (0.78), 2.10 (1.37) and 2.14 (1.49), respectively. At least five risk factors were found in 11.1 (95?% confidence interval (CI) 8.76 to 13.44) times as many participants as expected. A significant degree of clustering of CVD risk factors was found in 11.4?% (95?% CI, 9.8 to 13.0) of the study population, and these had mean Z scores of 1.24 (0.06) and 1.04 (0.08) for the 9‐year‐olds and 15‐year‐olds, respectively. Conclusion. This study presents national reference data on selected CVD risk factors in children and adolescents.     

Marked effects of extreme levels of lipoprotein(a) on estimation of low-density lipoprotein cholesterol

Background

Low-density lipoprotein cholesterol (LDL-C) is usually calculated using the Friedewald equation. However, this calculation method does not account for the cholesterol associated with lipoprotein(a) [Lp(a)]. Using the Dahlen equation, Li et al. have shown a strong positive correlation between serum Lp(a) levels and overestimation of LDL-C levels.

Objective

To determine how the extreme levels of Lp(a) influence the LDL-C calculation.

Methods

We performed a retrospective chart review of the lipid profile and Lp(a) of 223 patients (men and women). LDL-C was calculated using the Friedewald equation. Lp(a) concentrations were measured by an ELISA. Other serum lipids were measured enzymatically by standard methodology. Corrected LDL-C was calculated using the Dahlen equation.

Results

We found that this overestimation is very significant in individuals with extreme levels of Lp(a) (mean overestimation of 40% at Lp(a) > 1200 mg/L).

Conclusions

Calculated LDL-C is markedly overestimated in patients with extreme levels of Lp(a).     

Validation of a point of care troponin assay in real life emergency department conditions

Objective: To validate the accuracy of a Point of care (POC) troponin device (Abbott i‐Stat) in real life ED conditions. Methods: Design: A three‐way comparison between troponin I results obtained by experienced POC operators, inexperienced ED staff and central laboratory criterion standard. Participants: Convenience sample of 332 patients presenting to the ED with possible coronary syndromes. Results: Spearman correlation coefficient for experienced versus laboratory was 0.83 (95% CI 0.78–0.87), occasional users versus laboratory was 0.76 (95% CI 0.71–0.81), and experienced versus occasional users on POC was 0.82 (95% CI 0.76–0.87). Using local troponin cut‐off of 0.1 ng/mL, kappa coefficient was 0.94 for occasional users versus laboratory, 0.91 for experienced versus laboratory and 0.94 for experienced versus occasional users. Bland–Altman plots showed good agreement across the range of measured values. The sensitivity of i‐Stat (vs laboratory as criterion standard) was 92.2% (95% CI 83.8%–97.0%) with the local cut‐off but only 70.1% (95% CI 60.5%–78.6%) using the lowest cut‐off associated with acceptable reproducibility (10% coefficient of variation). Conclusions: The i‐Stat POC device produces similar results in the hands of experienced and occasional operators in ED. There is good agreement between the POC and laboratory at levels used to diagnose infarction by older, more specific criteria. When compared using new lower cut‐offs, the i‐Stat had poor sensitivity.     

One-year changes in methamphetamine use,dependence and remission in a community-recruited cohort

Aims: Investigate changes to a prospective cohort of methamphetamine users over 12 months, predictors of remission from methamphetamine dependence and past-month abstinence from methamphetamine use.

Method: Structured interviews were administered to 255 regular methamphetamine users at baseline (2010) and 12 months (2011). A multivariate generalised estimating equation (GEE) model identified adjusted associations with past-month abstinence at follow-up. A multivariate logistic regression analysis identified factors independently associated with remission from methamphetamine dependence.

Results: Most (60%) participants were methamphetamine-dependent at baseline. Remission from dependence (n?=?38) was independently associated with age (OR: 0.93; 95% CI: 0.88–1.00), maintaining/gaining employment since baseline (OR: 3.14; 95% CI: 1.21–8.14) and a greater increase in self-perceived social support (OR: 1.08; 95% CI: 1.01–1.16). Past-month abstinence at follow-up was independently associated with being female (OR: 1.94; 95% CI: 1.10–3.44), recent criminal behaviours (OR: 0.46; 95% CI: 0.26–0.82), recent ecstasy (OR: 0.30; 95% CI: 0.12–0.72) and benzodiazepine use (OR: 0.53; 95% CI: 0.29–0.96), and being less methamphetamine-dependent (OR: 0.79; 95% CI: 0.72–0.88). Drug treatment was not independently associated with either outcome at follow-up.

Conclusions: Our findings highlight the potential for natural remission from methamphetamine dependence; however, targeted interventions should be developed for individuals who are likely to maintain dependent/harmful use patterns.     

Evaluation of five methods for determining low-density lipoprotein cholesterol (LDL-C) in hemodialysis patients(1)

Objectives: Current recommendations for the management of dyslipidemia are largely based on the concentration of LDL-C. Most clinical laboratories estimate the concentration of LDL-C by the recommended routine method, the equation of Friedewald, in specimens from fasting subjects and with TG concentrations < 4.52 mmol/L. Because of the limitations of the Friedewald calculation, direct methods for an accurate quantification of LDL-C are needed.

Design and Methods: In the present study we evaluated the accuracy of the following 5 different procedures for LDL-C in 98 patients on hemodialysis: the Friedewald equation, where LDL-C is calculated from HDL-C, measured either by the precipitation procedure with dextran sulfate-Mg²⁺ (Method 1), or by a direct HDL-C assay (Method 2), the Direct LDL™ assay (Method 3), the homogeneous N-geneous™ LDL assay (Method 4) and the calculated LDL-C values deriving from the ApoB based equation: 0.41TC - 0.32TG + 1.70ApoB - 0.27, (Clin Chem 1997;43:808–815) (Method 5).

Results: All five LDL-C methods were found to be in good agreement with ultracentrifugation/dextran sulfate-Mg²⁺ precipitation with the coefficients of correlation of the assays to ranging between 0.93–0.95. However, significant differences in the mean values and biases vs. the reference method were observed. The Friedewald equation and the Direct assay were less affected by high LDL-C levels, and they presented higher sensitivity and higher negative predictive value. The N-geneous assay and the ApoB derived calculation were less affected by high triglyceride levels, and they presented higher specificity and higher positive predictive value. At the diagnostic LDL-C level of 3.37 mmol/L, both Friedewald calculations correctly classified 82/92 patients; Direct assay 86/98; N-geneous assay 88/98; and ApoB derived calculation 88/98. At the diagnostic LDL-C level of 2.98 mmol/L, Friedewald calculations (Method 1 and Method 2) correctly classified 82/92 and 81/92 patients, respectively; Direct assay (LDL-3) 87/98; N-geneous assay (LDL-4) 91/98; and ApoB derived calculation (LDL-5) 91/98.

Conclusions: Among hemodialysis patients, who commonly present “average” LDL-C concentrations and high TG levels, the N-geneous assay and the apoB derived calculation seem to yield more acceptable results for the estimation of LDL-C.     

ABC/2 estimation in intracerebral hemorrhage: A comparison study between emergency radiologists and emergency physicians

ObjectivesWe aimed to define levels of agreement (LOA) between emergency radiologists (RAD) and emergency medicine (EM) physicians for estimating bleed volume in intracranial hemorrhages (ICH) using ABC/2 formula.MethodsA prospective study of a curated sample of head CT's were performed in an emergency department. Raters independently reviewed the scans. Perpendicular maximal dimensions (A and B) were measured on an axial CT image. The ‘C’ dimension was a product of slice thickness and number of slices with visible bleed.ResultsA hundred CT head examinations were included with a median age of 50 years (IQR 43 to 57). The median bleed volume was 11.2 mL (IQR 6.6–18.6) per the index radiologist estimations. The overall mean of differences between the RAD mean and the EM mean estimated bleed volume was 0.3 (95% CI -1.5 to +1.7) in milliliters. The percentage difference between EM and RAD expressed as median was 1.9% (IQR -13.4% to +14.1%). Compared to the index RAD the mean of differences for bleed volume [rater, mean (95% CI) in milliliters] were: second RAD, 1.19 (1.14 to 1.24); EM attending, 1.05 (0.98 to 1.13); senior fellow, 1.05 (1.00 to 1.10); junior fellow, 1.19 (1.06 to 1.33); senior resident, 1.29 (1.19 to 1.39); junior resident, 1.11 (1.03 to 1.20). The difference between EM versus radiologist, junior versus senior EM physician estimation of bleed size was clinically insignificant.ConclusionsExcellent level of agreement was found between emergency physicians and emergency radiologists for estimating ICH bleed volumes using ABC/2 formula.     

Impact of atrial fibrillation on levels of high-sensitivity troponin I in a 75-year-old population

Abstract

Purpose. Atrial fibrillation (AF) has been associated with elevated levels of cardiac troponins; however, it is not clear if this association is independent of underlying cardiovascular disease. The aim of this study was to investigate the impact of AF on cardiac troponin I levels in a 75-year-old cohort from the general population, using a recently introduced, highly sensitive assay. Methods. All 75-year-old citizens in Asker and Baerum counties were invited to participate in a prevalence study of AF. High-sensitive troponin I (hs-TnI) levels were measured (Abbott Diagnostics) in serum samples collected from 62 subjects with AF and a gender-matched control group of 126 subjects in sinus rhythm. Results. Hs-TnI was detectable in all subjects (median 7.3 ng/L [range 3.0–88.7]). Patients with AF had higher levels than subjects in sinus rhythm (8.3 ng/L [3.7–88.7] vs. 6.8 ng/L [3.0–77.5]; p = 0.011). Male gender (p = 0.002), hypertension (p = 0.001), coronary heart disease (p < 0.001), heart failure (p < 0.001), prior stroke or transient ischemic attack (p = 0.013) and serum creatinine (p < 0.001) were all associated with higher levels of hs-TnI in univariate analysis. Heart failure and coronary heart disease remained significantly associated with hs-TnI in multivariate analysis, whereas the relation between AF and hs-TnI was no longer statistically significant. Conclusion. All subjects had detectable levels of hs-TnI. AF patients had higher hs-TnI levels than subjects in sinus rhythm; however, this difference was not statistically significant after adjustment for heart failure and coronary heart disease.     

低密度脂蛋白胆固醇保护性试剂匀相测定法的临床评价

目的 对低密度脂蛋白胆固醇(LDT-C)保护性试剂匀相测定法进行临床评价。 方法 分析了保护性试剂匀相测定法的精密度、准确性、特异性和干扰因素.并随机选取了219份病人血清标本,比较分析用保护性试剂匀相测定法直接测定与Friedewald公式和Planella公式计算的LDL—C结果。 结果 保护性试剂匀相测定法具有较好的精密度(批内、批间CV和总CV均小于3％)。线性范围至10.4mmol/L,最低检测浓度为0.08mmol/L,平均同收率为101.2％:基本不受极低密度脂蛋白(VLDL)、高密度脂蛋白(HDL)和血红蛋白的影响。在TG<4.52mmol/L时,用匀相测定法与Friedewald公式和Planella公式的计算法结果之间相关性良好,两种公式计算法结果之间的也有较好相关性;而在TG>4.52mmoL/L时,匀相测定法与两种计算法之间的相关性差。结论 保护性试剂匀相测定法简便、快速、结果准确,易于自动分析,适合在临床实验室常规检测应用。     

Impact of the Martin/Hopkins modified equation for estimating LDL-C on lipid target attainment in a high risk patient population

ObjectiveTo evaluate the Martin/Hopkins equation for estimating LDL-C as target in a population composed of high cardiac risk patients.MethodsLipid profile data from patients with TG ≤ 4.52 mmol/L (<400 mg/dl) were used. The high cardiac risk group (N 4150) consisted of patients over 40 years of age that had an A1C level of 6.5% or above and patients with a history of atherosclerotic cardiovascular disease (ASCVD). Comparisons were made between the Martin/Hopkins formula (MH-LDL-C), the Friedewald formula (F-LDL-C), Non-HDL-C and ApoB.ResultsHigher LDL-C values (0.15 mmol/L or 7.3%) were obtained using MH-LDL-C compared to the F-LDL-C. The % within target (%WT) values for F-LDL-C, MH-LDL-C, Non-HDL-C and ApoB were similar when TG levels were ≤ 1.5 mmol/L with a high degree of concordance as measured by the kappa statistic. When compared to F-LDL-C, Non-HDL-C and ApoB showed a profound decrease in the WT value as TG levels increased from normal (67.7%) to intermediate (39.1%) and high levels (20.8%). MH-LDL-C showed an attenuated decrease in the WT value as TG increased from normal (61.4%) intermediate (43.4%) and high levels (32.7%). Concordance with the alternate target parameters was higher for MH-LDL-C than for F-LDL-C when triglycerides levels were increased.ConclusionThe Martin/Hopkins modified equation for estimating LDL-C is a significant improvement on the decade’s old Friedewald formula; however it remains an imperfect tool to estimate the atherogenic load in patients with high TG levels.     

Real-world data of the use and experience of caplacizumab for the treatment of acquired thrombotic thrombocytopenic purpura: Case series

PurposeCaplacizumab was licensed for acquired thrombotic thrombocytopenic purpura (aTTP) based on prospective controlled trials. Real-world evidence is crucial in rare diseases. We aim to describe a patient population with aTTP, receiving caplacizumab in a real-world setting, reporting their outcomes, including safety and tolerability, and contrasting them with a historical cohort from our center.MethodsWe describe data collected retrospectively from 2012 to 2022 for 16 patients with aTTP (8 received caplacizumab and 8 the historical standard-of-care). Patients' characteristics and outcomes were compared between groups.ResultsPatients’ demographic and baseline characteristics were similar in both groups. Caplacizumab led to a rapid normalization of the platelet count of 3.5 (IQR, 2–6) versus 16 (IQR, 9.5–23.5) days in the historical cohort: (p = .002). The median number of plasma exchanges and the length of days requiring them, between the caplacizumab group versus the historical cohort, was 6 (IQR, 6–10) versus 19.5 (IQR, 12.5–29.5) plasma exchanges (p = .006); and 9 (IQR, 8.5–13.5) versus 22 (15–31) days (p = .049), respectively. There were no refractory cases in the caplacizumab group in comparison with 37.5 % in the historical cohort. None of patients treated with caplacizumab experienced a recurrence after 1081 (IQR, 511–3125) days of follow-up. Safety was in line with data reported in clinical trials, with mild adverse events (mostly grade≤2).ConclusionWe provided real-world evidence in the treatment of aTTP, confirming the results obtained in clinical trials. Caplacizumab reduced the time to platelet count recovery and the number and length of plasma exchanges.     

Accuracy diagrams: a novel way to illustrate uncertainty of estimated GFR

Most studies that validate GFR equations present accuracy results stratified by measured GFR (mGFR; diagnostic correctness) or by estimated GFR (eGFR; diagnostic predictiveness) only, without a clear distinction in interpretation. The accuracy of a GFR equation is normally reported in percent (e.g. P₃₀), but is often misinterpreted when stratified by eGFR. The aim of the study was to develop new accuracy measures and diagrams that allow straightforward interpretations and illustrations of the uncertainty in eGFR in clinical practice. We applied quantile regression to the distribution of estimation errors for two creatinine-based GFR equations, LM-REV and CKD-EPI, in a clinical cohort (n?=?3495) referred for GFR measurement (plasma clearance of iohexol). Measures of bias and precision and accuracy intervals (AIs) were expressed in mL/min/1.73?m². Diagrams with AIs were chosen as a novel way to present the error margin in eGFR at a pre-specified certainty level. It was shown that creatinine-based equations are still quite inaccurate in that large estimation errors could not be ruled out with satisfactory certainty. As an example, the 75% AI for the most accurate equation, LM-REV, was approximately?±10?mL/min/1.73?m² at eGFR?=?45?mL/min/1.73?m², whereas it ranged between ?13 and +20?mL/min/1.73?m² at eGFR?=?90?mL/min/1.73?m². Accuracy intervals presented in diagrams can be used to illustrate the uncertainty of eGFR. Future validation studies should assess the variability in the predictiveness of eGFR across populations and clinical settings using tools and performance measures that are easy to interpret.     

Atopic dermatitis and risk of ischemic stroke: A nationwide population-based study

Abstract

Background. Epidemiological studies have shown a strong association between systemic inflammatory diseases, particularly allergic diseases, and cardiovascular diseases. However, the relationship between atopic dermatitis (AD) and ischemic stroke remains unclear.

Method. The study identified 20,323 AD patients and 20,323 comorbidity-matched subjects between 2005 and 2008. The two cohorts were followed until 31 December 2009. Ischemic stroke and other cardiovascular events were determined.

Results. During the follow-up period, 301 (1.48%) patients in the AD cohort and 228 (1.12%) matched subjects experienced ischemic stroke. After multivariate adjustment, patients with AD had a 1.33-fold (95% confidence interval (CI), 1.12–1.59; P = 0.001) increased incidence of ischemic stroke. Adjusted hazard ratios for the risk of ischemic stroke in patients with mild, moderate, and severe AD were 1.20 (95% CI, 1.00–1.45; P = 0.052), 1.64 (95% CI, 1.23–2.19; P = 0.001), and 1.71 (95% CI, 1.15–2.56; P = 0.008), respectively. The log-rank test showed a higher cumulative incidence of ischemic stroke in the severe AD group than in the moderate and mild AD groups during the follow-up period (P < 0.001).

Conclusions. AD may be an independent risk factor for ischemic stroke, and risk of ischemic stroke increases with AD severity.     

Estimating glomerular filtration rate in hypertensive subjects: Comparison of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) Study equations

Abstract

Background.The Modification of Diet in Renal Disease (MDRD) Study equation is the most commonly used formula for estimation of glomerular filtration rate (eGFR). Recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) developed a new equation to provide a more accurate estimate of GFR among individuals with normal or mildly reduced renal function.

Aim. To compare the MDRD and CKD-EPI equations in hypertensive population treated in general practice.

Methods. The MDRD and CKD-EPI equations were applied to a cohort of 994 hypertensive subjects aged 45–70 years without cardiovascular or renal disease or previously known diabetes.

Results. The prevalence of CKD stage 3 (eGFR 30–59 mL/min per 1.73 m²) was 6.7% (95% CI 5.3–8.5) (67/994) according to the MDRD formula and 3.7% (95% CI 2.6–5.1) (37/994) according to the CKD-EPI formula. Of the 67 subjects classified as having CKD stage 3 according to the MDRD equation, 30 (44.8%) were reclassified as ‘no-CKD’ by the CKD-EPI equation. These subjects were mostly women 26/30 (87.7%).

Conclusion. Using the CKD-EPI equation leads to lower prevalence estimates for CKD than the MDRD equation in a hypertensive population treated in general practice.