The COVID-19 pandemic spurred publication of a rapid proliferation of studies on potential therapeutic agents. While important for the advancement of clinical care, pressure to collect, analyze, and ...report data in an expedited manner could potentially increase the rate of important errors, some of which would be captured in published errata. We hypothesized that COVID-19 therapeutic studies published in the early years of the pandemic would be associated with a high rate of published errata and that, within these errata, there would be a high prevalence of serious errors.
We performed a review of published errata associated with empirical studies of COVID-19 treatments. Errata were identified via a MEDLINE and Embase search spanning January 2020 through September 2022. Errors located within each published erratum were characterized by location within publication, error type, and error seriousness.
Of 47 studies on COVID-19 treatments with published errata, 18 met inclusion criteria. Median time from publication of the original article to publication of the associated erratum was 76 days (range, 12-511 days). A majority of errata addressed issues with author attribution or conflict of interest disclosures (39.5%) or numerical results (25.6%). Only one erratum contained a serious error: a typographical error which could have misled readers into believing that the treatment in question had serious adverse effects when in fact it did not.
Despite accelerated publication times, we found among studies of COVID-19 treatments the majority of errata (17/18) reported minor errors that did not lead to misinterpretation of the study results. Retractions, an indicator of scientific misdirection even more concerning than errata, were beyond the scope of this review.
Novel urinary biomarkers reflecting kidney tubule health are associated with chronic kidney disease (CKD) risk in persons living with HIV. However, it is unknown whether these biomarkers provide ...mechanistic insight into the associations between clinical risk factors for CKD and subsequent CKD risk.
Among 636 women living with HIV in the Women's Interagency HIV Study with estimated glomerular filtration rate (eGFR) >60 ml/min/1.73 m 2 , we used a counterfactual approach to causal mediation analysis to evaluate the extent to which systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin a1c (Hba1c) and serum albumin associations with incident CKD were mediated by eight urine proteins. These biomarkers reflect proximal tubular reabsorptive dysfunction (α1-microglobulin a1m, β2-microglobulin, trefoil factor 3); tubular injury (interleukin 18 IL-18, kidney injury molecule 1 KIM-1); kidney repair (epidermal growth factor); tubular reserve (uromodulin); and glomerular injury (urinary albumin). Incident CKD was defined as eGFR <60 ml/min/1.73 m 2 measured at two consecutive 6-month visits with an average annual eGFR decline ≥3% per year.
During a median follow-up of 7 years, 11% developed CKD. Urinary albumin and KIM-1 mediated 32% (95% CI: 13.4%, 76.6%) and 23% (6.9%, 60.7%) of the association between SBP and incident CKD, respectively; and 19% (5.1%, 42.3%) and 22% (8.1%, 45.7%) of the association between DBP and incident CKD, respectively. Urinary albumin, α1m, and IL-18 were significant mediators of the association between Hba1c and incident CKD. None of the eight biomarkers mediated the association between serum albumin and incident CKD.
Among women living with HIV, several urinary biomarkers reflecting distinct dimensions of kidney health may partially explain the associations between SBP, DBP, and Hba1c and subsequent CKD risk.
Given the important role of cardiac injury and neurohormonal activation in the pathways leading from hypertension to heart failure and strong associations observed between hypertension and its ...sequelae on hs-cTnT (high-sensitivity cardiac troponin T) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels, we hypothesized that intensive systolic blood pressure (SBP) lowering would decrease levels of hs-cTnT and NT-proBNP.
hs-cTnT and NT-proBNP were measured at baseline and 1 year from stored specimens in SPRINT (Systolic Blood Pressure Intervention Trial). Changes in biomarkers were evaluated continuously on the log scale and according to categories (≥50% increase, ≥50% decrease, or <50% change). The effect of intensive SBP lowering on continuous and categorical changes in biomarker levels were assessed using linear and multinomial logistic regression models, respectively. The association between changes in biomarkers on heart failure and death was assessed using multivariable-adjusted Cox proportional hazards models.
Randomization to intensive SBP lowering (versus standard SBP management) resulted in a 3% increase in hs-cTnT levels over 1-year follow-up (geometric mean ratio, 1.03 95% CI, 1.01-1.04) and a higher proportion of participants with ≥50% increase (odds ratio, 1.47 95% CI, 1.13, 1.90). In contrast, randomization to intensive SBP lowering led to a 10% decrease in NT-proBNP (geometric mean ratio, 0.90 95% CI, 0.87-0.93) and a lower probability of ≥50% increase in NT-proBNP (odds ratio, 0.57 95% CI, 0.46-0.72). The association of randomized treatment assignment on change in hs-cTnT was completely attenuated after accounting for changes in estimated glomerular filtration rate over follow-up, whereas the association of treatment with NT-proBNP was completely attenuated after adjusting for change in SBP. Increases in hs-cTnT and NT-proBNP from baseline to 1 year were associated with higher risk for heart failure and death, with no significant interactions by treatment assignment.
Intensive SBP lowering increased hs-cTnT, mediated by the effect of SBP lowering on reduced kidney filtration. In contrast, intensive SBP lowering decreased NT-proBNP, a finding that was explained by the decrease in SBP. These findings highlight the importance of noncardiac factors influencing variation in cardiac biomarkers and raise questions about the potential role of hs-cTnT as a surrogate marker for heart failure or death in SBP-lowering studies.
Novel approaches to the assessment of kidney disease risk during hypertension treatment are needed because of the uncertainty of how intensive blood pressure (BP) lowering impacts kidney outcomes. We ...determined whether longitudinal N-terminal pro–B-type natriuretic peptide (NT–proBNP) measurements during hypertension treatment are associated with kidney function decline.
Prospective observational study.
8,005 SPRINT (Systolic Blood Pressure Intervention Trial) participants with NT–proBNP measurements at baseline and 1 year.
1-year change in NT–proBNP categorized as a ≥25% decrease, ≥25% increase, or <25% change (stable).
Annualized change in estimated glomerular filtration rate (eGFR) and ≥30% decrease in eGFR.
Linear mixed-effect and logistic regression models were used to evaluate the association of changes in NT–proBNP with subsequent annualized change in eGFR and ≥30% decrease in eGFR, respectively. Analyses were stratified by baseline chronic kidney disease (CKD) status.
Compared with stable 1-year NT–proBNP levels, a ≥25% decrease in NT–proBNP was associated with a slower decrease in eGFR in participants with CKD (adjusted difference, 1.09%/y; 95% CI, 0.35-1.83) and without CKD (adjusted difference, 0.51%/y; 95% CI, 0.21-0.81; P = 0.4 for interaction). Meanwhile, a ≥25% increase in NT–proBNP in participants with CKD was associated with a faster decrease in eGFR (adjusted difference, −1.04%/y; 95% CI, −1.72 to −0.36) and risk of a ≥30% decrease in eGFR (adjusted odds ratio, 1.44; 95% CI, 1.06-1.96); associations were stronger in participants with CKD than in participants without CKD (P = 0.01 and P < 0.001 for interaction, respectively). Relationships were similar irrespective of the randomized BP arm in SPRINT (P > 0.2 for interactions).
Persons with diabetes and proteinuria >1 g/d were excluded.
Changes in NT–proBNP during BP treatment are independently associated with subsequent kidney function decline, particularly in people with CKD. Future studies should assess whether routine NT–proBNP measurements may be useful in monitoring kidney risk during hypertension treatment.
N-terminal pro–B-type natriuretic peptide (NT–proBNP) is a biomarker in the blood that reflects mechanical stress on the heart. Measuring NT–proBNP may be helpful in assessing the risk of long-term losses of kidney function. In this study, we investigated the association of changes in NT–proBNP with subsequent kidney function among individuals with and without chronic kidney disease. We found that increases in NT–proBNP are associated with a faster rate of decline of kidney function, independent of baseline kidney measures. The associations were more pronounced in individuals with chronic kidney disease. Our results advance the notion of considering NT–proBNP as a dynamic tool for assessing kidney disease risk.
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Abstract
Background
Cardiac troponins are associated with adverse cardiovascular disease (CVD) outcomes. The value of high-sensitivity cardiac troponin I (hs-cTnI) independently and in concert with ...troponin T (hs-cTnT) in the management of hypertension has not been well studied.
Methods
We assessed the utility of hs-cTnI independently and with hs-cTnT in identifying the highest risk individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). Among 8796 eligible SPRINT participants, hs-cTnI was measured at baseline and 1 year. The association of baseline level and 1-year change in hs-cTnI with CVD events and all-cause death was evaluated using adjusted Cox regression models. We further assessed the complementary value of hs-cTnI and hs-cTnT by identifying concordant and discordant categories and assessing their association with outcomes.
Results
hs-cTnI was positively associated with composite CVD risk myocardial infarction, other acute coronary syndrome, stroke, or cardiovascular death: hazard ratio 1.23, 95% confidence interval 1.08–1.39 per 1-unit increase in log(troponin I) independent of traditional risk factors, N-terminal pro-B-type natriuretic peptide, and hs-cTnT. Intensive blood pressure lowering was associated with greater absolute risk reduction (4.5% vs 1.7%) and lower number needed to treat (23 vs 59) for CVD events among those with higher baseline hs-cTnI (≥6 ng/L in men, ≥4 ng/L in women). hs-cTnI increase at 1 year was also associated with increased CVD risk. hs-cTnI and hs-cTnT were complementary, and elevations in both identified individuals with the highest risk for CVD and death.
Conclusions
Baseline levels and change in hs-cTnI over 1 year identified higher-risk individuals who may derive greater cardiovascular benefit with intensive blood pressure treatment. hs-TnI and hs-TnT have complementary value in CVD risk assessment.
ClinicalTrials.gov Registration Number: NCT01206062.
Left ventricular hypertrophy (LVH) combined with elevations in cardiac biomarkers reflecting myocardial injury and neurohormonal stress (malignant LVH) is associated with a high risk for heart ...failure and death.
The aim of this study was to determine the impact of intensive systolic blood pressure (SBP) control on the prevention of malignant LVH and its consequences.
A total of 8,820 participants in SPRINT (Systolic Blood Pressure Intervention Trial) were classified into groups based on the presence or absence of LVH assessed by 12-lead ECG, and elevations in biomarker levels (high-sensitivity cardiac troponin T ≥14 ng/L or N-terminal pro-B-type natriuretic peptide ≥125 pg/mL) at baseline. The effects of intensive vs standard SBP lowering on rates of acute decompensated heart failure (ADHF) events and death and on the incidence and regression of malignant LVH were determined.
Randomization to intensive SBP lowering led to similar relative reductions in ADHF events and death across the combined LVH/biomarker groups (P for interaction = 0.68). The absolute risk reduction over 4 years in ADHF events and death was 4.4% (95% CI: -5.2% to 13.9%) among participants with baseline malignant LVH (n = 449) and 1.2% (95% CI: 0.0%-2.5%) for those without LVH and nonelevated biomarkers (n = 4,361). Intensive SBP lowering also reduced the incidence of malignant LVH over 2 years (2.5% vs 1.1%; OR: 0.44; 95% CI: 0.30-0.63).
Intensive SBP lowering prevented malignant LVH and may provide substantial absolute risk reduction in the composite of ADHF events and death among SPRINT participants with baseline malignant LVH.
BACKGROUND: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater ...cognitive benefits from lower systolic blood pressure targets. METHODS: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories. RESULTS: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 95% CI, 1.00–1.56). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 95% CI, 0.50–0.81) than those in the intermediate (hazard ratio, 1.01 95% CI, 0.80–1.28) or highest categories (hazard ratio, 0.90 95% CI, 0.72–1.13; P interaction =0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were −2.9% (−4.4%, −1.3%), −0.2% (−3.0%, 2.6%), and −1.9% (−6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively. CONCLUSIONS: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.
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