Derivation of an Outcome-Driven Threshold for Aortic Pulse Wave Velocity: An Individual-Participant Meta-Analysis.

BACKGROUND: Aortic pulse wave velocity (PWV) predicts cardiovascular events (CVEs) and total mortality (TM), but previous studies proposing actionable PWV thresholds have limited generalizability. This individual-participant meta-analysis is aimed at defining, testing calibration, and validating an outcome-driven threshold for PWV, using 2 populations studies, respectively, for derivation IDCARS (International Database of Central Arterial Properties for Risk Stratification) and replication MONICA (Monitoring of Trends and Determinants in Cardiovascular Disease Health Survey - Copenhagen). METHODS: A risk-carrying PWV threshold for CVE and TM was defined by multivariable Cox regression, using stepwise increasing PWV thresholds and by determining the threshold yielding a 5-year risk equivalent with systolic blood pressure of 140 mm Hg. The predictive performance of the PWV threshold was assessed by computing the integrated discrimination improvement and the net reclassification improvement. RESULTS: In well-calibrated models in IDCARS, the risk-carrying PWV thresholds converged at 9 m/s (10 m/s considering the anatomic pulse wave travel distance). With full adjustments applied, the threshold predicted CVE (hazard ratio [CI]: 1.68 [1.15-2.45]) and TM (1.61 [1.01-2.55]) in IDCARS and in MONICA (1.40 [1.09-1.79] and 1.55 [1.23-1.95]). In IDCARS and MONICA, the predictive accuracy of the threshold for both end points was ≈0.75. Integrated discrimination improvement was significant for TM in IDCARS and for both TM and CVE in MONICA, whereas net reclassification improvement was not for any outcome. CONCLUSIONS: PWV integrates multiple risk factors into a single variable and might replace a large panel of traditional risk factors. Exceeding the outcome-driven PWV threshold should motivate clinicians to stringent management of risk factors, in particular hypertension, which over a person's lifetime causes stiffening of the elastic arteries as waypoint to CVE and death.

Predictive performance and clinical application of COV50, a urinary proteomic biomarker in early COVID-19 infection: a prospective multicentre cohort study.

BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p<0·0001 for all). The predictive accuracy of the optimised COV50 thresholds was 74·4% (71·6-77·1%) for mortality (threshold 0·47) and 67·4% (64·4-70·3%) for disease progression (threshold 0·04). When adjusted for covariables and the baseline WHO score, these thresholds improved AUCs from 0·835 to 0·853 (p=0·033) for death and from 0·697 to 0·730 (p=0·0008) for progression. Of 196 participants who received ambulatory care, 194 (99%) did not reach the 0·04 threshold. The cost reductions associated with 1 day less hospitalisation per 1000 participants were million Euro (M€) 0·887 (5-95% percentile interval 0·730-1·039) in participants at a low risk (COV50 <0·04) and M€2·098 (1·839-2·365) in participants at a high risk (COV50 ≥0·04). INTERPRETATION: The urinary proteomic COV50 marker might be predictive of adverse COVID-19 outcomes. Even in people with mild-to-moderate PCR-confirmed infections (WHO scores 1-4), the 0·04 COV50 threshold justifies earlier drug treatment, thereby potentially reducing the number of days in hospital and associated costs. FUNDING: German Federal Ministry of Health.

Relationship among long-term aircraft noise exposure, blood pressure profile, and arterial stiffness.

OBJECTIVE: To assess the impact of long-term exposure to aircraft noise on blood pressure (BP), prevalence of arterial hypertension, and indices of asymptomatic organ damage. METHODS: Using acoustic maps, we selected and further compared people living (average 35 years) in areas exposed to high, more than 60 dB (n = 101), and low aircraft noise, less than 55 dB (n = 100). Medical history taking, office BP measurement, ambulatory BP monitoring, and echocardiographic and arterial stiffness measurements were performed. RESULTS: Exposure to aircraft noise did not increase the prevalence of arterial hypertension (50%, both groups) but was associated with higher office (88.3 ±â€Š11.4 vs. 79.8 ±â€Š8.6 mmHg, P < 0.001) and night-time DBP (66.6 ±â€Š9.5 vs. 63.6 ±â€Š7.3 mmHg, P < 0.01). Participants exposed to a high aircraft noise level had a higher carotid-femoral pulse wave velocity (PWV) (10.3 ±â€Š1.8 vs. 9.4 ±â€Š1.4 m/s, P < 0.01) and lower early mitral annulus velocity (e') (8.4 ±â€Š2.9 vs. 9.2 ±â€Š3.4 cm/s, P = 0.047). These differences were independent of age, sex, BMI, education, time spent at home, smoking status, alcohol consumption, and antihypertensive treatment. Higher office and night-time DBP, PWV, and e' values were explicitly observed in exposed normotensive participants. PWV in aircraft noise-exposed normotensive participants was equal to that of two decades older unexposed normotensive participants and was significantly associated with noise annoyance. CONCLUSION: Long-term aircraft noise exposure is related to higher office and night-time DBP, more advanced arterial stiffness, and unfavourable left ventricle diastolic function changes. Accelerated arterial stiffening was observed in those exposed to aircraft noise, even normotensive participants, to a degree depending on noise annoyance.

Comparison of aortic pulse wave velocity measured by three techniques: Complior, SphygmoCor and Arteriograph.

BACKGROUND: New 2007 European Society of Hypertension guidelines recommend measuring arterial stiffness in patients with arterial hypertension, suggesting a carotid-femoral pulse wave velocity over 12 m/s as an estimate of subclinical organ damage. Considering this cutoff point, it is worth exploring whether or not there are significant differences in results obtained using various techniques for measuring aortic pulse wave velocity. The aim of the study was to compare aortic pulse wave velocity measurements using Complior, SphygmoCor, and Arteriograph devices, and to assess the effect of pulse wave transit time and traveled distance on pulse wave velocity values. METHODS: Aortic pulse wave velocity was measured on a single visit, using these devices, in randomized order, in a group of 64 patients with grade 1 or 2 arterial hypertension. RESULTS: Aortic pulse wave velocity measured using Complior (10.1 +/- 1.7 m/s) was significantly higher than that obtained using SphygmoCor (8.1 +/- 1.1 m/s) or Arteriograph (8.6 +/- 1.3 m/s). No differences were noted between pulse wave velocity measurements using SphygmoCor and Arteriograph. Between-method comparison revealed that differences in traveled distance were significant: Complior versus Arteriograph [0.09 m, Confidence interval (CI): 0.08-0.12 m, P < 0.05], Complior versus SphygmoCor (0.15 m, CI: 0.13-0.16 m, P < 0.05), Arteriograph versus SphygmoCor (0.05 m, CI: 0.03-0.07 m, P < 0.05). No between-method differences were found for transit times. CONCLUSION: Differences in pulse wave velocity obtained by compared devices resulted primarily from using various methods for measuring traveled distance. It appears reasonable to establish uniform principles for the measurement of traveled distance. Because a large number of prognosis/survival studies used direct distance between carotid and femoral sites of pulse wave recording, this distance should be mostly recommended.