Social isolation, loneliness, and inflammation: A multi-cohort investigation in early and mid-adulthood.

Social isolation and loneliness have been associated with poor health and increased risk for mortality, and inflammation might explain this link. We used data from the Danish TRIAGE Study of acutely admitted medical patients (N = 6,144, mean age 60 years), and from two population-representative birth cohorts: the New Zealand Dunedin Longitudinal Study (N = 881, age 45) and the UK Environmental Risk (E-Risk) Longitudinal Twin Study (N = 1448, age 18), to investigate associations of social isolation with three markers of systemic inflammation: C-reactive protein (CRP), interleukin-6 (IL-6), and a newer inflammation marker, soluble urokinase plasminogen activator receptor (suPAR), which is thought to index systemic chronic inflammation. In the TRIAGE Study, socially isolated patients (those living alone) had significantly higher median levels of suPAR (but not CRP or IL-6) compared with patients not living by themselves. Social isolation prospectively measured in childhood was longitudinally associated with higher CRP, IL-6, and suPAR levels in adulthood (at age 45 in the Dunedin Study and age 18 in the E-Risk Study), but only suPAR remained associated after controlling for covariates. Dunedin Study participants who reported loneliness at age 38 or age 45 had elevated suPAR at age 45. In contrast, E-Risk Study participants reporting loneliness at age 18 did not show any elevated markers of inflammation. In conclusion, social isolation was robustly associated with increased inflammation in adulthood, both in medical patients and in the general population. It was associated in particular with systemic chronic inflammation, evident from the consistently stronger associations with suPAR than other inflammation biomarkers.

Attainment of Target Antibiotic Levels by Oral Treatment of Left-Sided Infective Endocarditis: A POET Substudy.

BACKGROUND: In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of the present study was to perform pharmacokinetic/pharmacodynamic analyses for oral treatments of infective endocarditis to assess the probabilities of target attainment (PTAs). METHODS: Plasma concentrations of oral antibiotics were measured at day 1 and 5. Minimal inhibitory concentrations (MICs) were determined for the bacteria causing infective endocarditis (streptococci, staphylococci, or enterococci). Pharmacokinetic/pharmacodynamic targets were predefined according to literature using time above MIC or the ratio of area under the curve to MIC. Population pharmacokinetic modeling and pharmacokinetic/pharmacodynamic analyses were done for amoxicillin, dicloxacillin, linezolid, moxifloxacin, and rifampicin, and PTAs were calculated. RESULTS: A total of 236 patients participated in this POET substudy. For amoxicillin and linezolid, the PTAs were 88%-100%. For moxifloxacin and rifampicin, the PTAs were 71%-100%. Using a clinical breakpoint for staphylococci, the PTAs for dicloxacillin were 9%-17%.Seventy-four patients at day 1 and 65 patients at day 5 had available pharmacokinetic and MIC data for 2 oral antibiotics. Of those, 13 patients at day 1 and 14 patients at day 5 did only reach the target for 1 antibiotic. One patient did not reach target for any of the 2 antibiotics. CONCLUSIONS: For the individual orally administered antibiotic, the majority reached the target level. Patients with sub-target levels were compensated by the administration of 2 different antibiotics. The findings support the efficacy of oral step-down antibiotic treatment in patients with infective endocarditis.

Graph Machine Learning for Improved Imputation of Missing Tropospheric Ozone Data.

Gaps in the measurement series of atmospheric pollutants can impede the reliable assessment of their impacts and trends. We propose a new method for missing data imputation of the air pollutant tropospheric ozone by using the graph machine learning algorithm "correct and smooth". This algorithm uses auxiliary data that characterize the measurement location and, in addition, ozone observations at neighboring sites to improve the imputations of simple statistical and machine learning models. We apply our method to data from 278 stations of the year 2011 of the German Environment Agency (Umweltbundesamt - UBA) monitoring network. The preliminary version of these data exhibits three gap patterns: shorter gaps in the range of hours, longer gaps of up to several months in length, and gaps occurring at multiple stations at once. For short gaps of up to 5 h, linear interpolation is most accurate. Longer gaps at single stations are most effectively imputed by a random forest in connection with the correct and smooth. For longer gaps at multiple stations, the correct and smooth algorithm improved the random forest despite a lack of data in the neighborhood of the missing values. We therefore suggest a hybrid of linear interpolation and graph machine learning for the imputation of tropospheric ozone time series.

Exploring the direct and indirect effects of cardiovascular disease risk factors on exercise blood pressure.

OBJECTIVE: Exaggerated exercise blood pressure (BP) is independently associated with cardiovascular disease (CVD) outcomes. However, it is unknown how individual CVD risk factors may interact with one another to influence exercise BP. The aim of this study was to quantify direct and indirect associations between CVD risk factors and exercise BP, to determine what CVD risk factor/s most-strongly relate to exercise BP. METHODS: In a cross-sectional design, 660 participants (44 ± 2.6 years, 54% male) from the population-based Childhood Determinants of Adult Health Study had BP measured during low-intensity fixed-workload cycling. CVD risk factors were measured, including body composition, clinic (rest) BP, blood biomarkers, and cardiorespiratory fitness. Associations between CVD risk factors and exercise BP were assessed using linear regression, with direct and indirect pathways of association assessed via structural equation model. RESULTS: Sex, waist-to-hip ratio, fitness, and clinic BP were independently associated with exercise systolic BP (SBP), and along with age, had direct associations with exercise SBP (p < 0.05 all). Most CVD risk factors were indirectly associated with exercise SBP via a relation with clinic BP (p < 0.05 all). Clinic BP, waist-to-hip ratio, and fitness were most-strongly associated (direct and indirect association) with exercise SBP (ß[95% CI]: 9.35 [8.04, 10.67], 4.91 [2.56, 7.26], and -2.88 [-4.25, -1.51] mm Hg/SD, respectively). CONCLUSION: Many CVD risk factors are associated with exercise BP, mostly with indirect effects via clinic BP. Clinic BP, body composition, and fitness were most-strongly associated with exercise BP. These results may elucidate how lifestyle modification could be a primary strategy to decrease exaggerated exercise BP-related CVD risk.

Incidence of Positive Severe Acute Respiratory Syndrome Coronavirus Polymerase Chain Reaction After Coronavirus Disease 2019 Vaccination With up to 8 Months of Follow-up: Real-life Data From the Capital Region of Denmark.

BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccines are implemented worldwide in efforts to curb the pandemic. This study investigates the risk of a positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction (RT-PCR) test following BNT162b2 vaccination in a large real-life population in Denmark. METHODS: Vaccination status and positive SARS-CoV-2 RT-PCR results from adults in the Capital Region of Denmark (n = 1 549 488) were obtained from national registries. PCR testing was free and widely available. The number of positive PCR tests per individual at risk was calculated as weekly rates. Time to positive PCR test was modelled using Kaplan-Meier methods and hazard ratios (HRs) were calculated using Cox regression. RESULTS: A total of 1 119 574 individuals received the first dose of BNT162b2 and 1 088 879 received a second dose of BNT162b2. Individuals were followed up to 8.7 months after first dose (median: 5.5 months; interquartile ratio: 4.1-8.7). Rates of PCR-confirmed SARS-CoV-2 infection 2-4 months after the second dose were 0.21, 0.33, and 0.36 per 1000 individuals per week at risk for July, August, and September, respectively. Four or more months after the second dose, the rates were 0.56, 0.76, and 0.53 per 1000 individuals per week at risk for July, August, and September, respectively. HR of SARS-CoV-2 infection after the second dose was 0.2 (95% confidence interval, .05-.48; P = .001) for individuals with 8 months' follow-up. CONCLUSIONS: Individuals who received 2 doses of the BNT162b2 COVID-19 vaccine had a low risk of breakthrough infection after up to 8 months of follow-up. However, there was a tendency toward higher rates with longer follow-up.

Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis.

BACKGROUND: Patients with infective endocarditis on the left side of the heart are typically treated with intravenous antibiotic agents for up to 6 weeks. Whether a shift from intravenous to oral antibiotics once the patient is in stable condition would result in efficacy and safety similar to those with continued intravenous treatment is unknown. METHODS: In a randomized, noninferiority, multicenter trial, we assigned 400 adults in stable condition who had endocarditis on the left side of the heart caused by streptococcus, Enterococcus faecalis, Staphylococcus aureus, or coagulase-negative staphylococci and who were being treated with intravenous antibiotics to continue intravenous treatment (199 patients) or to switch to oral antibiotic treatment (201 patients). In all patients, antibiotic treatment was administered intravenously for at least 10 days. If feasible, patients in the orally treated group were discharged to outpatient treatment. The primary outcome was a composite of all-cause mortality, unplanned cardiac surgery, embolic events, or relapse of bacteremia with the primary pathogen, from the time of randomization until 6 months after antibiotic treatment was completed. RESULTS: After randomization, antibiotic treatment was completed after a median of 19 days (interquartile range, 14 to 25) in the intravenously treated group and 17 days (interquartile range, 14 to 25) in the orally treated group (P=0.48). The primary composite outcome occurred in 24 patients (12.1%) in the intravenously treated group and in 18 (9.0%) in the orally treated group (between-group difference, 3.1 percentage points; 95% confidence interval, -3.4 to 9.6; P=0.40), which met noninferiority criteria. CONCLUSIONS: In patients with endocarditis on the left side of the heart who were in stable condition, changing to oral antibiotic treatment was noninferior to continued intravenous antibiotic treatment. (Funded by the Danish Heart Foundation and others; POET ClinicalTrials.gov number, NCT01375257 .).

Cardiorespiratory Fitness, Workload, and the Blood Pressure Response to Exercise Testing.

We propose that for correct clinical interpretation of exaggerated exercise blood pressure (EEBP), both cardiorespiratory fitness and exercise workload must be considered. A key recommendation toward achieving the correct clinical interpretation of EEBP is that exercise BP should be measured during submaximal exercise with a fixed external workload.

Self-assessed health status and associated mortality in endocarditis: secondary findings from the POET trial.

PURPOSE: Self-assessed poor health status is associated with increased risk of mortality in several cardiovascular conditions, but has not been investigated in patients with endocarditis. We examined health status and mortality in patients with endocarditis. METHODS: This is a re-specified substudy of the randomized POET endocarditis trial, which included 400 patients. Patients completed the single-question self-assessed health status from the Short-Form 36 questionnaire at time of randomization and were categorized as having poor or non-poor (excellent/very good, good, or fair) health status. Self-assessed health status and all-cause mortality were examined by a Cox regression model. RESULTS: Self-assessed health status was completed by 266 (67%) patients with a mean age of 68.0 years (± 11.8), 54 (20%) were females, and 86 (32%) had one or more major concurrent medical conditions besides endocarditis. The self-assessed health status distribution was poor (n = 21, 8%) and non-poor (n = 245, 92%). The median follow-up was 3.3 years and death occurred in 9 (43%) and 48 (20%) patients reporting poor and non-poor health status, respectively, and mortality rates [mortality/100 person-years, 95% confidence interval (CI)] were 18.1 (95% CI 9.4-34.8) and 5.4 (95% CI 4.1-7.2), i.e., the crude hazard ratio for death was 3.4 (95% CI: 1.7-7.0, p < 0.01). CONCLUSION: Self-assessed poor health status compared with non-poor health status as assessed by a single question was associated with a threefold increased long-term mortality in patients with endocarditis. POET ClinicalTrials.gov number, NCT01375257. TRIAL REGISTRY: POET ClinicalTrials.gov number, NCT01375257.

The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).

BACKGROUND: Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored. METHODS: The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL). RESULTS: Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008). CONCLUSION: Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02748811.

Mapping Yearly Fine Resolution Global Surface Ozone through the Bayesian Maximum Entropy Data Fusion of Observations and Model Output for 1990-2017.

Estimates of ground-level ozone concentrations are necessary to determine the human health burden of ozone. To support the Global Burden of Disease Study, we produce yearly fine resolution global surface ozone estimates from 1990 to 2017 through a data fusion of observations and models. As ozone observations are sparse in many populated regions, we use a novel combination of the M3Fusion and Bayesian Maximum Entropy (BME) methods. With M3Fusion, we create a multimodel composite by bias-correcting and weighting nine global atmospheric chemistry models based on their ability to predict observations (8834 sites globally) in each region and year. BME is then used to integrate observations, such that estimates match observations at each monitoring site with the observational influence decreasing smoothly across space and time until the output matches the multimodel composite. After estimating at 0.5° resolution using BME, we add fine spatial detail from an additional model, yielding estimates at 0.1° resolution. Observed ozone is predicted more accurately (R2 = 0.81 at the test point, 0.63 at 0.1°, and 0.62 at 0.5°) than the multimodel mean (R2 = 0.28 at 0.5°). Global ozone exposure is estimated to be increasing, driven by highly populated regions of Asia and Africa, despite decreases in the United States and Russia.

General practitioner perceptions of assessment and reporting of absolute cardiovascular disease risk via pathology services: a qualitative study.

BACKGROUND: Guidelines for cardiovascular disease (CVD) prevention recommend assessment of absolute CVD risk to guide clinical management. Despite this, use among general practitioners (GPs) remains limited. OBJECTIVE: Pathology services may provide an appropriate setting to assess and report absolute CVD risk in patients attending for cholesterol measurement. This study aimed to explore GPs perceptions of such a service. METHODS: A focus group and semi-structured interviews were conducted with GPs (n = 18) in Tasmania, Australia, to identify perceptions of assessment and reporting of absolute CVD risk via pathology services. An example pathology report including absolute CVD risk was provided and discussed. Audio-recordings were transcribed and thematically coded by two researchers. RESULTS: Almost all GPs identified that absolute CVD risk assessed and reported via pathology services could address deficits in practice. First, by reducing the number of appointments required to collect risk factors. Second, by providing a systematic (rather than opportunistic) approach for assessment of absolute CVD risk. Third, by reducing misclassification of patient CVD risk caused by overreliance on clinical intuition. All GPs reported they would order absolute CVD risk when issuing a cholesterol referral if such a service was offered. GPs recommended improving the service by providing information on methods used to measure risk factors on the pathology report. CONCLUSIONS: Absolute CVD risk assessed and reported via pathology services may address challenges of screening CVD risk experienced by GPs in practice and encourage dedicated follow-up care for CVD prevention.

Cardiorespiratory fitness, fatness, and the acute blood pressure response to exercise in adolescence.

OBJECTIVE: Exaggerated exercise blood pressure (BP) is associated with cardiovascular risk factors in adolescence. Cardiorespiratory fitness and adiposity (fatness) are independent contributors to cardiovascular risk, but their interrelated associations with exercise BP are unknown. This study aimed to determine the relationships between fitness, fatness, and the acute BP response to exercise in a large birth cohort of adolescents. METHODS: 2292 adolescents from the Avon Longitudinal Study of Parents and Children (aged 17.8 ± 0.4 years, 38.5% male) completed a sub-maximal exercise step test that allowed fitness (VO2 max ) to be determined from workload and heart rate using a validated equation. Exercise BP was measured immediately on test cessation and fatness calculated as the ratio of total fat mass to total body mass measured by DXA. RESULTS: Post-exercise systolic BP decreased stepwise with tertile of fitness (146 (18); 142 (17); 141 (16) mmHg) but increased with tertile of fatness (138 (15); 142 (16); 149 (18) mmHg). In separate models, fitness and fatness were associated with post-exercise systolic BP adjusted for sex, age, height, smoking, and socioeconomic status (standardized ß: -1.80, 95%CI: -2.64, -0.95 mmHg/SD and 4.31, 95%CI: 3.49, 5.13 mmHg/SD). However, when fitness and fatness were included in the same model, only fatness remained associated with exercise BP (4.65, 95%CI: 3.69, 5.61 mmHg/SD). CONCLUSION: Both fitness and fatness are associated with the acute BP response to exercise in adolescence. The fitness-exercise BP association was not independent of fatness, implying the cardiovascular protective effects of cardiorespiratory fitness may only be realized with more favorable body composition.

Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Previous trials have suggested that vasopressin and methylprednisolone administered during in-hospital cardiac arrest might improve outcomes. Objective: To determine whether the combination of vasopressin and methylprednisolone administered during in-hospital cardiac arrest improves return of spontaneous circulation. Design, Setting, and Participants: Multicenter, randomized, double-blind, placebo-controlled trial conducted at 10 hospitals in Denmark. A total of 512 adult patients with in-hospital cardiac arrest were included between October 15, 2018, and January 21, 2021. The last 90-day follow-up was on April 21, 2021. Intervention: Patients were randomized to receive a combination of vasopressin and methylprednisolone (n = 245) or placebo (n = 267). The first dose of vasopressin (20 IU) and methylprednisolone (40 mg), or corresponding placebo, was administered after the first dose of epinephrine. Additional doses of vasopressin or corresponding placebo were administered after each additional dose of epinephrine for a maximum of 4 doses. Main Outcomes and Measures: The primary outcome was return of spontaneous circulation. Secondary outcomes included survival and favorable neurologic outcome at 30 days (Cerebral Performance Category score of 1 or 2). Results: Among 512 patients who were randomized, 501 met all inclusion and no exclusion criteria and were included in the analysis (mean [SD] age, 71 [13] years; 322 men [64%]). One hundred of 237 patients (42%) in the vasopressin and methylprednisolone group and 86 of 264 patients (33%) in the placebo group achieved return of spontaneous circulation (risk ratio, 1.30 [95% CI, 1.03-1.63]; risk difference, 9.6% [95% CI, 1.1%-18.0%]; P = .03). At 30 days, 23 patients (9.7%) in the intervention group and 31 patients (12%) in the placebo group were alive (risk ratio, 0.83 [95% CI, 0.50-1.37]; risk difference: -2.0% [95% CI, -7.5% to 3.5%]; P = .48). A favorable neurologic outcome was observed in 18 patients (7.6%) in the intervention group and 20 patients (7.6%) in the placebo group at 30 days (risk ratio, 1.00 [95% CI, 0.55-1.83]; risk difference, 0.0% [95% CI, -4.7% to 4.9%]; P > .99). In patients with return of spontaneous circulation, hyperglycemia occurred in 77 (77%) in the intervention group and 63 (73%) in the placebo group. Hypernatremia occurred in 28 (28%) and 27 (31%), in the intervention and placebo groups, respectively. Conclusions and Relevance: Among patients with in-hospital cardiac arrest, administration of vasopressin and methylprednisolone, compared with placebo, significantly increased the likelihood of return of spontaneous circulation. However, there is uncertainty whether this treatment results in benefit or harm for long-term survival. Trial Registration: ClinicalTrials.gov Identifier: NCT03640949.

Cuff Under Pressure for Greater Accuracy.

PURPOSE OF REVIEW: To present the evidence that describes what is being measured by upper-arm cuff blood pressure (BP) and the level of accuracy compared with invasive central aortic and brachial BP. Potential causes of inaccuracy and emerging methods are also discussed. RECENT FINDINGS: On average cuff systolic BP systematically underestimates invasive brachial systolic BP, although in a given individual it may substantially under- or over-estimate central aortic systolic BP. Such errors may affect individual health management outcomes and distort population level data on hypertension prevalence and control. Oscillometric cuff BP is particularly susceptible to inaccuracy in people with high arterial stiffness and with pathophysiological BP waveform shapes. Emerging cuff-less BP methods will be susceptible to inaccuracy if oscillometric cuff BP is used for calibration. The original purpose of cuff BP was to estimate central aortic BP. Recent evidence has shown substantial inaccuracy of oscillometric cuff BP exists for the measurement of invasive central aortic and brachial BP. Thus, development of more accurate BP methods, through better understanding of oscillometric and BP waveform morphology, is needed to improve health outcomes related to high BP.

Impact of U.S. Oil and Natural Gas Emission Increases on Surface Ozone Is Most Pronounced in the Central United States.

Observations of volatile organic compounds (VOCs) from a surface sampling network and simulation results from the EMAC (ECHAM5/MESSy for Atmospheric Chemistry) model were analyzed to assess the impact of increased emissions of VOCs and nitrogen oxides from U.S. oil and natural gas (O&NG) sources on air quality. In the first step, the VOC observations were used to optimize the magnitude and distribution of atmospheric ethane and higher-alkane VOC emissions in the model inventory for the base year 2009. Observation-based increases of the emissions of VOCs and NOx stemming from U.S. oil and natural gas (O&NG) sources during 2009-2014 were then added to the model, and a set of sensitivity runs was conducted for assessing the influence of the increased emissions on summer surface ozone levels. For the year 2014, the added O&NG emissions are predicted to affect surface ozone across a large geographical scale in the United States. These emissions are responsible for an increased number of days when the averaged 8-h ozone values exceed 70 ppb, with the highest sensitivity being in the central and midwestern United States, where most of the O&NG growth has occurred. These findings demonstrate that O&NG emissions significantly affect the air quality across most of the United States, can regionally offset reductions of ozone precursor emissions made in other sectors, and can have a determining influence on a region's ability to meet National Ambient Air Quality Standard (NAAQS) obligations for ozone.

Integration of absolute cardiovascular disease risk assessment into routine blood cholesterol testing at pathology services.

BACKGROUND: Absolute cardiovascular disease (CVD) risk assessment is recommended for primary prevention of CVD, yet uptake in general practice is limited. Cholesterol requests at pathology services provide an opportunity to improve uptake by integrating absolute CVD risk assessment with this service. OBJECTIVE: This study aimed to assess the feasibility of such an additional service. METHODS: Two-hundred and ninety-nine patients (45-74 years) referred to pathology services for blood cholesterol had measurement of all variables required to determine absolute CVD risk according to Framingham calculator (blood pressure, age, sex, smoking and diabetes status via self-report). Data were recorded via computer-based application. The absolute risk score was communicated via the report sent to the referring medical practitioner as per usual practice. Evaluation questionnaires were completed immediately post visit and at 1-, 3- and 6-month follow-up via telephone (n = 262). RESULTS: Absolute CVD risk reports were issued for 90% of patients. Most patients (95%) reported that the length of time for the pathology service assessment was acceptable, and 91% that the self-directed computer-based application was easy to use. Seventy-eight per cent reported a preference for pathology services to conduct absolute CVD risk assessment. Only 2% preferred a medical practitioner. Of follow-up patients, 202 (75%) had a consultation with a medical practitioner, during which, aspects of CVD risk prevention were discussed (cholesterol and blood pressure 74% and 69% of the time, respectively). CONCLUSIONS: Measurement of absolute CVD risk in pathology services is feasible, highly acceptable among middle-to-older adults and may increase uptake of guideline-directed care in general practice.

The influence of fitness on exercise blood pressure and its association with cardiac structure in adolescence.

PURPOSE: Exaggerated exercise blood pressure (BP) is associated with altered cardiac structure and increased cardiovascular risk. Fitness modifies these associations, but the effect in healthy adolescents is unknown. We performed an observational study to determine the influence of fitness on post-exercise BP, and on its relationship with cardiac structure in adolescents. METHODS: 4835 adolescents from the Avon Longitudinal Study of Parents and Children, (15.4 (0.3) years, 49% male) completed a submaximal cycle test. Fitness was estimated as physical work capacity 170 adjusted for lean body mass and post-exercise BP measured immediately posttest. Cardiovascular structure and function, including left ventricular (LV) mass (n = 1589), left atrium (LA) size (n = 1466), cardiac output (CO, n = 1610), and total peripheral resistance (TPR, n = 1610) were measured at rest by echocardiography 2.4 (0.4) years later. RESULTS: Post-exercise systolic BP increased stepwise by fitness tertile (131.2 mm Hg [130.4, 132.1]; 137.3 mm Hg [136.5, 138.0]; 142.3 mm Hg [141.5, 143.1]). Each 5 mm Hg of post-exercise systolic BP was associated with 2.46 g [1.91, 3.01] greater LV mass, 0.02 cm [0.02, 0.03] greater LA size, and 0.25 g/m2.7 [0.14, 0.36] greater LV mass index. Adjustment for fitness abolished associations (0.29 g [-0.16, 0.74]; 0.01 cm [-0.001, 0.014] and 0.08 g/m2.7 [-0.001, 0.002]). Similar associations between post-exercise systolic BP and each outcome were found between the lowest and highest fitness thirds. CO increased with fitness third (difference 0.06 L/min [-0.05, 0.17]; 0.23 L/min [0.12, 0.34]) while TPR decreased (difference -0.13 mm Hg·min/L [-0.84,0.59]; -1.08 mm Hg·min/L [-0.1.80, 0.35]). CONCLUSIONS: Post-exercise systolic BP increased with fitness, which modified its association with cardiac structure. Higher CO, but lower TPR suggests a physiologically adapted cardiovascular system with greater fitness, highlighting the importance of fitness in adolescence.

Masked hypertension and submaximal exercise blood pressure among adolescents from the Avon Longitudinal Study of Parents and Children (ALSPAC).

PURPOSE: Masked hypertension is associated with increased cardiovascular risk but is undetectable by clinic blood pressure (BP). Elevated systolic BP responses to submaximal exercise reveal the presence of masked hypertension in adults, but it is unknown whether this is the case during adolescence. We aimed to determine if exercise BP was raised in adolescents with masked hypertension, and its association with cardiovascular risk markers. METHODS: A total of 657 adolescents (aged 17.7 ± 0.3 years; 41.9% male) from the Avon longitudinal study of parents and children (ALSPAC) completed a step-exercise test with pre-, post-, and recovery-exercise BP, clinic BP and 24-hour ambulatory BP. Masked hypertension was defined as clinic BP <140/90 mm Hg and 24-hour ambulatory BP ≥130/80 mm Hg. Assessment of left-ventricular (LV) mass index and carotid-femoral pulse wave velocity (aortic PWV) was also undertaken. Thresholds of clinic, pre-, post-, and recovery-exercise systolic BP were explored from ROC analysis to identify masked hypertension. RESULTS: Fifty participants (7.8%) were classified with masked hypertension. Clinic, pre-, post-, and recovery-exercise systolic BP were associated with masked hypertension (AUC ≥ 0.69 for all, respectively), with the clinic systolic BP threshold of 115 mm Hg having high sensitivity and specificity and exercise BP thresholds of 126, 150, and 130 mm Hg, respectively, having high specificity and negative predictive value (individually or when combined) for ruling out the presence of masked hypertension. Additionally, this exercise systolic BP above the thresholds was associated with greater left-ventricular mass index and aortic PWV. CONCLUSIONS: Submaximal exercise systolic BP is associated with masked hypertension and adverse cardiovascular structure in adolescents. Exercise BP may be useful in addition to clinic BP for screening of high BP and cardiovascular risk in adolescents.

Soluble Urokinase Plasminogen Activator Receptor (suPAR) as an Added Predictor to Existing Preoperative Risk Assessments.

BACKGROUND: Risk assessment strategies, such as using the American Society of Anesthesiologists (ASA) physical status classification, attempt to identify surgical high-risk patients. Soluble urokinase plasminogen activator receptor (suPAR) is a biomarker reflecting overall systemic inflammation and immune activation, and it could potentially improve the identification of high-risk surgical patients. METHODS: We included patients acutely admitted to the emergency department who subsequently underwent surgery within 90 days of admission. Patients were stratified into low-risk or high-risk groups, according to ASA classification (ASAlow: ASA I-II; ASAhigh: ASA III-VI) and suPAR level, measured at admission (suPARhigh above and suPARlow below 5.5 ng/ml), respectively. Pre-specified complications were identified in national registries and electronic medical records. The association between ASA classification, suPAR level, CRP and the rate of postoperative complications was analyzed with logistic regression and Cox regression analyses, estimating odds ratios and hazard ratios (HRs). RESULTS: During 90-day follow-up from surgery, 31 (7.0%) patients died and 158 (35.6%) patients had postoperative complications. After adjusting for age, sex, and ASA classification, the HR for 90-day postoperative mortality was 2.5 (95% CI 1.6-4.0) for every doubling of suPAR level. suPAR was significantly better than CRP at predicting mortality and all complications (P = 0.0036 and P = 0.0041, respectively). Combining ASA classification and suPAR level significantly improved prediction of mortality and the occurrence of a postoperative complication within 90 days after surgery (P < 0.0001). CONCLUSION: Measuring suPAR levels in acutely admitted patients may aid in identifying high-risk patients and improve prediction of postoperative complications.