Combining renal cell arrest and damage biomarkers to predict progressive AKI in patient with sepsis

Background Sepsis is the most common trigger for AKI and up to 40% of mild or moderate septic AKI would progress to more severe AKI, which is associated with significantly increased risk for death and later CKD/ESRD. Early identifying high risk patients for AKI progression is a major challenge in patients with septic AKI. Methods This is a prospective, multicenter cohort study which enrolled adult patients with sepsis and initially developed stage 1 or 2 AKI in the intensive care unit from January 2014 to March 2018. AKI was diagnosed and staged according to 2012 KDIGO-AKI guidelines. Renal cell arrest biomarkers (urinary TIMP2*IGFBP7, u[TIMP-2]*[IGFBP7]) and renal damage biomarkers (urinary KIM-1[uKIM-1] and urinary IL-18 [uIL-18]) were measured at time of AKI clinical diagnosis, and the performance of biomarkers for predicting septic AKI progression alone or in combination were evaluated. The primary outcome was AKI progression defined as worsening of AKI stage. The secondary outcome was AKI progression with subsequent death during hospitalization. Results Among 433 screened patients, 149 patients with sepsis and stage 1 or 2 AKI were included, in which 63 patients developed progressive AKI and 49 patients subsequently died during hospitalization. u[TIMP-2]*[IGFBP7], uKIM-1 and uIL-18 independently predicted the progression of septic AKI in which u[TIMP-2]*[IGFBP7] showed the greatest AUC (0.745; 95%CI, 0.667-0.823) as compared to uKIM-1 (AUC 0.719; 95%CI 0.638-0.800) and uIL-18 (AUC 0.619; 95%CI 0.525-0.731). Combination of u[TIMP-2]*[IGFBP7] with uKIM-1 improved the performance of predicting septic AKI progression with AUC of 0.752. u[TIMP-2]*[IGFBP7], alone or combined with uKIM-1/uIL-18, improved the risk reclassification over the clinical risk factor model alone both for the primary and secondary outcomes, as evidenced by significant category-free net reclassification index. Conclusions Combination of renal cell arrest and damage biomarkers enhanced the prediction of AKI progression in patients with sepsis and improved risk reclassification over the clinical risk factors.

Atrioventricular Longitudinal Mechanics Using Novel Speckle-Tracking Improved Risk Stratification Beyond Baseline Thyroid Hormone in Asymptomatic Subclinical Hypothyroidism

Background: Hypothyroidism is reportedly associated with increased cardiovascular risk and heart failure. We aimed to elucidate the mechanistic influence of atrio-ventricular deformations and their prognostic utilizations in asymptomatic subclinical hypothyroidism (SCH). Methods: We assessed speckle-tracking of deformations among 4173 population-based asymptomatic individuals classified as euthyroid (0.25< thyroid-stimulating hormone [TSH] ≤4.0 μIU/mL, n=3799) or having mild (4< TSH ≤10.0 μIU/mL, n=349) or marked (TSH >10 μIU/mL, n=25) SCH. We further related deformational indices to outcomes of atrial fibrillation and heart failure. Results: Despite borderline differences in indexed left ventricular mass and left atrial volume ( P =0.054 and 0.051), those classified as mild and marked SCH presented with modest but significant reductions of global longitudinal strain, and showed elevated E/tissue Doppler imaging (TDI)-e′, markedly diminished peak atrial longitudinal strain and higher left atrial stiffness (all P <0.05) when compared with euthyroid subjects. A higher TSH level was independently associated with reduced TDI-s′/TDI-e′, worse global atrio-ventricular strains (global longitudinal strain/peak atrial longitudinal strain), elevated E/TDI-e′, and worsened left atrial strain rate components (all P <0.05). Over a median 5.6 years (interquartile range, 4.7–6.5 years) follow-up, myocardial deformations yielded independent risk prediction using Cox regression in models adjusted for baseline covariates, N-terminal pro-brain natriuretic peptide, E/e′, and treatment effect. Incorporation of global atrio-ventricular strain (global longitudinal strain/peak atrial longitudinal strain) and strain rates further showed improved risk reclassification when added to the baseline TSH strata (classified as euthyroid and mild and marked SCH; all P <0.05). Cox regression models remained significant with improved risk reclassification beyond TSH-based strata by using slightly different deformational cutoffs after excluding marked SCH group. Conclusions: Hypothyroidism, even when asymptomatic, may widely influence subclinical atrio-ventricular mechanical functions that may lead to higher heart failure and atrial fibrillation risk. We proposed the potential usefulness and prognostic utilization of myocardial strains in such population.

Finding very high lipoprotein(a): the need for routine assessment

Aims To validate the reported increased atherosclerotic cardiovascular disease (ASCVD) risk associated with very high lipoprotein(a) [Lp(a)] and to investigate the impact of routine Lp(a) assessment on risk reclassification. Methods and results We performed a cross-sectional case-control study in the Amsterdam UMC, a tertiary hospital in The Netherlands. All patients in whom a lipid blood test was ordered between October 2018 and October 2019 were included. Individuals with Lp(a) &gt;99th percentile were age and sex matched to individuals with Lp(a) ≤20th percentile. We computed odds ratios (ORs) for myocardial infarction (MI) and ASCVD using multivariable logistic regression adjusted for age, sex, and systolic blood pressure. Furthermore, we assessed the additive value of Lp(a) to established ASCVD risk algorithms. Lipoprotein(a) levels were determined in 12 437 individuals, out of whom 119 cases [Lp(a) &gt;99th percentile; &gt;387.8 nmol/L] and 119 matched controls [Lp(a) ≤20th percentile; ≤7 nmol/L] were included. Mean age was 58 ± 15 years, 56.7% were female, and 30.7% had a history of ASCVD. Individuals with Lp(a) levels &gt;99th percentile had an OR of 2.64 for ASCVD [95% confidence interval (CI) 1.45–4.89] and 3.39 for MI (95% CI 1.56–7.94). Addition of Lp(a) to ASCVD risk algorithms led to 31% and 63% being reclassified into a higher risk category for Systematic Coronary Risk Evaluation (SCORE) and Second Manifestations of ARTerial disease (SMART), respectively. Conclusion The prevalence of ASCVD is nearly three-fold higher in adults with Lp(a) &gt;99th percentile compared with matched subjects with Lp(a) ≤20th percentile. In individuals with very high Lp(a), addition of Lp(a) resulted in one-third of patients being reclassified in primary prevention, and over half being reclassified in secondary prevention.

Translational research in nephrology: prognosis

Translational research aims at reducing the gap between the results of studies focused on diagnosis, prognosis and therapy, and every day clinical practice. Prognosis is an essential component of clinical medicine. It aims at estimating the risk of adverse health outcomes in individuals, conditional to their clinical and non-clinical characteristics. There are three fundamental steps in prognostic research: development studies, in which the researcher identifies predictors, assigns the weights to each predictor, and assesses the model’s accuracy through calibration, discrimination and risk reclassification; validation studies, in which investigators test the model’s accuracy in an independent cohort of individuals; and impact studies, in which researchers evaluate whether the use of a prognostic model by clinicians improves their decision-making and patient outcome. This article aims at clarifying how to reduce the disconnection between the promises of prognostic research and the delivery of better individual health.

Heart-centered positioning and tailored beam-shaping filtration for reduced radiation dose in coronary artery calcium imaging: a MESA study

Purpose: Cardiac CT has a clear clinical role in the evaluation of coronary artery disease and assessment of coronary artery calcium (CAC) but the use of ionizing radiation limits clinical use. Beam shaping 'bow-tie' filters determine the radiation dose and the effective scan field-of-view diameter (SFOV) by delivering higher X-ray fluence to a region centered at the isocenter. A method for positioning the heart near the isocenter could enable reduced SFOV imaging and reduce dose in cardiac scans. However, a predictive approach to center the heart, the extent to which heart centering can reduce the SFOV, and the associated dose reductions have not been assessed. The purpose of this study is to build a heart-centered patient positioning model, to test whether it reduces the SFOV required for accurate CAC scoring, and to quantify the associated reduction in radiation dose. Methods: The location of 38,184 calcium lesions (3,151 studies) in the Multi-Ethnic Study of Atherosclerosis (MESA) were utilized to build a predictive heart-centered positioning model and compare the impact of SFOV on CAC scoring accuracy in heart-centered and conventional body-centered scanning. Then, the positioning model was applied retrospectively to an independent, contemporary cohort of 118 individuals (81 with CAC>0) at our institution to validate the model's ability to maintain CAC accuracy while reducing the SFOV. In these patients, the reduction in dose associated with a reduced SFOV beam-shaping filter was quantified. Results: Heart centering reduced the SFOV diameter 25.7% relative to body centering while maintaining high CAC scoring accuracy (0.82% risk reclassification rate). In our validation cohort, imaging at this reduced SFOV with heart-centered positioning and tailored beam-shaping filtration led to a 26.9% median dose reduction (25-75th percentile: 21.6 to 29.8%) without any calcium risk reclassification. Conclusions: Heart-centered patient positioning enables a significant radiation dose reduction while maintaining CAC accuracy.

Area Deprivation Index and Cardiac Readmissions: Evaluating Risk‐Prediction in an Electronic Health Record

Background Assessment of the social determinants of post‐hospital cardiac care is needed. We examined the association and predictive ability of neighborhood‐level determinants (area deprivation index, ADI), readmission risk, and mortality for heart failure, myocardial ischemia, and atrial fibrillation. Methods and Results Using a retrospective (January 1, 2011–December 31, 2018) analysis of a large healthcare system, we assess the predictive ability of ADI on 30‐day and 1‐year readmission and mortality following hospitalization. Cox proportional hazards models analyzed time‐to‐event. Log rank analyses determined survival. C‐statistic and net reclassification index determined the model’s discriminative power. Covariates included age, sex, race, comorbidity, number of medications, length of stay, and insurance. The cohort (n=27 694) had a median follow‐up of 46.5 months. There were 14 469 (52.2%) men and 25 219 White (91.1%) patients. Patients in the highest ADI quintile (versus lowest) were more likely to be admitted within 1 year of index heart failure admission (hazard ratio [HR], 1.25; 95% CI, 1.03‒1.51). Patients with myocardial ischemia in the highest ADI quintile were twice as likely to be readmitted at 1 year (HR, 2.04; 95% CI, 1.44‒2.91]). Patients with atrial fibrillation living in areas with highest ADI were less likely to be admitted within 1 year (HR, 0.79; 95% CI, 0.65‒0.95). As ADI increased, risk of readmission increased, and risk reclassification was improved with ADI in the models. Patients in the highest ADI quintile were 25% more likely to die within a year (HR, 1.25 1.08‒1.44). Conclusions Residence in socioeconomically disadvantaged communities predicts rehospitalization and mortality. Measuring neighborhood deprivation can identify individuals at risk following cardiac hospitalization.

Disease activity influences the reclassification of rheumatoid arthritis into very high cardiovascular risk

Background Previous studies have shown that risk chart algorithms, such as the Systematic Coronary Risk Assessment (SCORE), often underestimate the actual cardiovascular (CV) risk of patients with rheumatoid arthritis (RA). In contrast, carotid ultrasound was found to be useful to identify RA patients at high CV. In the present study, we aimed to determine if specific disease features influence the CV risk reclassification of RA patients assessed by SCORE risk charts and carotid ultrasound. Methods 1279 RA patients without previous CV events, diabetes, or chronic kidney disease were studied. Disease characteristics including disease activity scores, CV comorbidity, SCORE calculation, and the presence of carotid plaque by carotid ultrasound were assessed. A multivariable regression analysis was performed to evaluate if the reclassification into very high CV risk category was independently associated with specific features of the disease including disease activity. Additionally, a prediction model for reclassification was constructed in RA patients. Results After carotid ultrasound assessments, 54% of the patients had carotid plaque and consequently fulfilled definition for very high CV risk. Disease activity was statistically significantly associated with reclassification after fully multivariable analysis. A predictive model containing the presence of dyslipidemia and hypertension, an age exceeding 54 years, and a DAS28-ESR score equal or higher than 2.6 yielded the highest discrimination for reclassification. Conclusion Reclassification into very high CV risk after carotid ultrasound assessment occurs in more than the half of patients with RA. This reclassification can be independently explained by the activity of the disease.