Objective
To mitigate the burden associated with heart failure (HF), primary prevention is of the utmost importance. To improve early risk stratification, advanced computational methods such as ...machine learning (ML) capturing complex individual patterns in large data might be necessary. Therefore, we compared the predictive performance of incident HF risk models in terms of (a) flexible ML models and linear models and (b) models trained on a single cohort (single-center) and on multiple heterogeneous cohorts (multi-center).
Design and methods
In our analysis, we used the meta-data consisting of 30,354 individuals from 6 cohorts. During a median follow-up of 5.40 years, 1,068 individuals experienced a non-fatal HF event. We evaluated the predictive performance of survival gradient boosting (SGB), CoxNet, the PCP-HF risk score, and a stacking method. Predictions were obtained iteratively, in each iteration one cohort serving as an external test set and either one or all remaining cohorts as a training set (single- or multi-center, respectively).
Results
Overall, multi-center models systematically outperformed single-center models. Further, c-index in the pooled population was higher in SGB (0.735) than in CoxNet (0.694). In the precision-recall (PR) analysis for predicting 10-year HF risk, the stacking method, combining the SGB, CoxNet, Gaussian mixture and PCP-HF models, outperformed other models with PR/AUC 0.804, while PCP-HF achieved only 0.551.
Conclusion
With a greater number and variety of training cohorts, the model learns a wider range of specific individual health characteristics. Flexible ML algorithms can be used to capture these diverse distributions and produce more precise prediction models.
Fractal analysis provides a global assessment of vascular networks (e.g., geometric complexity). We examined the association of diastolic left ventricular (LV) function with the retinal microvascular ...fractal dimension. A lower fractal dimension signifies a sparser retinal microvascular network. In 628 randomly recruited Flemish individuals (51.3% women; mean age, 50.8 years), we measured diastolic LV function by echocardiography and the retinal microvascular fractal dimension by the box-counting method (Singapore I Vessel Assessment software, version 3.6). The left atrial volume index (LAVI), e', E/e' and retinal microvascular fractal dimension averaged (±SD) 24.3 ± 6.2 mL/m
, 10.9 ± 3.6 cm/s, 6.96 ± 2.2, and 1.39 ± 0.05, respectively. The LAVI, E, e' and E/e' were associated (P < 0.001) with the retinal microvascular fractal dimension with association sizes (per 1 SD), amounting to -1.49 mL/m
(95% confidence interval, -1.98 to -1.01), 2.57 cm/s (1.31-3.84), 1.34 cm/s (1.07-1.60), and -0.74 (-0.91 to -0.57), respectively. With adjustments applied for potential covariables, the associations of E peak and E/e' with the retinal microvascular fractal dimension remained significant (P ≤ 0.020). Over a median follow-up of 5.3 years, 18 deaths occurred. The crude and adjusted hazard ratios expressing the risk of all-cause mortality associated with a 1-SD increment in the retinal microvascular fractal dimension were 0.36 (0.23-0.57; P < 0.001) and 0.57 (0.34-0.96; P = 0.035), respectively. In the general population, a lower retinal microvascular fractal dimension was associated with greater E/e', a measure of LV filling pressure. These observations can potentially be translated into new strategies for the prevention of diastolic LV dysfunction.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The formation of natural gas hydrates during processing and transport of natural has historically been one of the motivations for research on hydrates. In recent years, there has been much focus on ...the use of hydrate as a phase for compact transport of natural gas, as well as many other applications such as desalination of seawater and the use of hydrate phase in heat pumps. The huge amounts of energy in the form of hydrates distributed in various ways in sediments is a hot topic many places around the world. Common to all these situations of hydrates in nature or industry is that temperature and pressure are both defined. Mathematically, this does not balance the number of independent variables minus conservation of mass and minus equilibrium conditions. There is a need for thermodynamic models for hydrates that can be used for non-equilibrium systems and hydrate formation from different phase, as well as different routes for hydrate dissociation. In this work we first discuss a residual thermodynamic model scheme with the more commonly used reference method for pressure temperature stability limits. However, the residual thermodynamic method stretches far beyond that to other routes for hydrate formation, such as hydrate formation from dissolved hydrate formers. More important, the residual thermodynamic method can be utilized for many thermodynamic properties involved in real hydrate systems. Consistent free energies and enthalpies are only two of these properties. In non-equilibrium systems, a consistent thermodynamic reference system (ideal gas) makes it easier to evaluate most likely distribution of phases and compositions.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Low birth weight and prematurity are risk factors for hypertension in adulthood. Few studies in preterm or full-term born children reported on plasma renin activity (PRA). We tested the hypothesis ...that renin might modulate the incidence of hypertension associated with prematurity. We enrolled 93 prematurely born children with birth weight <1000 g and 87 healthy controls born at term, who were all examined at ≈11 years. Renal length and glomerular filtration rate derived from serum cystatin C were 0.28 cm (95% confidence interval, 0.09–0.47) and 11.5 mL/min per 1.73 m (6.4–16.6) lower in cases, whereas their systolic/diastolic blood pressure (BP) was 7.5 mm Hg (4.8–10.3)/4.0 mm Hg (2.1–5.8) higher (P<0.001 for all). The odds of having systolic prehypertension or systolic hypertension associated with extreme low birth weight were 6.43 (2.52–16.4; P<0.001) and 10.9 (2.46–48.4; P=0.002). Twenty-four hours of urinary sodium excretion was similar in cases and controls (102.1 versus 106.8 mmol; P=0.47). Sodium load per nephron was estimated as sodium excretion divided by kidney length (mmol/cm). PRA was 0.54 ng/mL per hour (0.23–0.85; P=0.001) lower in cases. PRA, systolic BP, and sodium load were available in 43 cases and 56 controls. PRA decreased with systolic BP (slope −0.022 ng/mL per hour/; P=0.048), but was unrelated to sodium load (slope +0.13 mmol/cm; P=0.54). The slope of PRA on systolic BP was similar (P=0.17) in cases and controls. In conclusion, extremely low birth weight predisposes young adolescents to low-renin hypertension, but does not affect the inverse association between PRA and BP.
CLINICAL TRIAL REGISTRATION—URLhttps://www.clinicaltrials.gov. Unique identifierNCT02147457.
Aims
Timely detection of subclinical left ventricular diastolic dysfunction (LVDDF) is of importance for precise risk stratification of asymptomatic subjects. Here, we evaluated the prevalence of ...LVDDF and its prognostic significance in the general population using two grading approaches: the 2016 ASE/EACVI recommendations and population‐derived, age‐specific criteria.
Methods and results
We randomly recruited 1407 community‐dwelling participants (mean age, 51.2 years; 51.1% women; 53.5% with cardiovascular risk factors). We measured left heart dimensions, strain, tricuspid regurgitation, transmitral blood flow, and mitral annular tissue velocities using conventional echocardiography and Doppler imaging. We utilized these measurements to grade of LVDDF according to the 2016 recommendations and population‐derived, age‐specific approach. According to the 2016 recommendations, 26 subjects (1.85%) were classified as having the advanced stage (Grade 2), whereas in 109 participants (7.75%) diastolic function was indeterminate. When applying the population‐derived criteria, the prevalence of advanced LVDDF was 17.9% (n = 252). During the follow‐up period (8.4 years), 100 participants experienced adverse cardiac events. After full adjustment, we did not observe any significant differences in the risk of events between subjects with indeterminate or any grade of LVDDF and subjects with normal diastolic function when classified according to the 2016 recommendation (P ≥ 0.25). In contrast, the adjusted risks of adverse cardiac events (HR = 1.28; P = 0.0045) were significantly elevated in participants with LVDDF when classified according to the population‐derived criteria.
Conclusions
Our study underscored the importance of considering age‐ and population‐derived thresholds in LVDDF grading in subjects at high cardiovascular risk which led to a better risk stratification and outcome prediction.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Because the process of myocardial remodelling starts before the onset of symptoms, recent heart failure (HF) guidelines place special emphasis on the detection of subclinical left ventricular (LV) ...systolic and diastolic dysfunction and the timely identification of risk factors for HF. Our goal was to describe the prevalence and determinants (risk factors) of LV diastolic dysfunction in a general population and to compare the amino terminal probrain natriuretic peptide level across groups with and without diastolic dysfunction.
In a randomly recruited population sample (n=539; 50.5% women; mean age, 52.5 years), we measured early and late diastolic peak velocities of mitral inflow (E and A), pulmonary vein flow by pulsed-wave Doppler, and the mitral annular velocities (Ea and Aa) at 4 sites by tissue Doppler imaging. A healthy subsample of 239 subjects (mean age, 43.7 years) provided age-specific cutoff limits for normal E/A and E/Ea ratios and the differences in duration between the mitral A and the reverse pulmonary vein flows during atrial systole (DeltaAd-ARd). The number of subjects in diastolic dysfunction groups 1 (impaired relaxation), 2 (elevated LV end-diastolic filling pressure), and 3 (elevated E/Ea and abnormally low E/A) were 53 (9.8%), 76 (14.1%), and 18 (3.4%), respectively. We used Delta(Ad<ARd+10) to confirm possible elevation of LV filling pressures in group 2. Compared with subjects with normal diastolic function (n=392, 72.7%), group 1 (209 versus 251 pmol/L; P=0.015) and group 2 (209 versus 275 pmol/L; P=0.0003) but not group 3 (209 versus 224 pmol/L; P=0.65) had a significantly higher adjusted NT-probrain natriuretic peptide. Higher age, body mass index, heart rate, systolic blood pressure, serum insulin, and creatinine were significantly associated with a higher risk of LV diastolic dysfunction.
The overall prevalence of LV diastolic dysfunction in a random sample of a general population, as estimated from echocardiographic measurements, was as high as 27.3%.
We studied the epidemiology of drug-resistant tuberculosis (TB) in Vladimir Region, Russia, in 2012. Most cases of multidrug-resistant TB (MDR TB) were caused by transmission of drug-resistant ...strains, and >33% were in patients referred for testing after mass radiographic screening. Early diagnosis of drug resistance is essential for preventing transmission of MDR TB.
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DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
BACKGROUND—Data on risk associated with 24-hour ambulatory diastolic (DBP24) versus systolic (SBP24) blood pressure are scarce.
METHODS AND RESULTS—We recorded 24-hour blood pressure and health ...outcomes in 8341 untreated people (mean age, 50.8 years; 46.6% women) randomly recruited from 12 populations. We computed hazard ratios (HRs) using multivariable-adjusted Cox regression. Over 11.2 years (median), 927 (11.1%) participants died, 356 (4.3%) from cardiovascular causes, and 744 (8.9%) experienced a fatal or nonfatal cardiovascular event. Isolated diastolic hypertension (DBP24≥80 mm Hg) did not increase the risk of total mortality, cardiovascular mortality, or stroke (HRs≤1.54; P≥0.18), but was associated with a higher risk of fatal combined with nonfatal cardiovascular, cardiac, or coronary events (HRs≥1.75; P≤0.0054). Isolated systolic hypertension (SBP24≥130 mm Hg) and mixed diastolic plus systolic hypertension were associated with increased risks of all aforementioned end points (P≤0.0012). Below age 50, DBP24 was the main driver of risk, reaching significance for total (HR for 1-SD increase, 2.05; P=0.0039) and cardiovascular mortality (HR, 4.07; P=0.0032) and for all cardiovascular end points combined (HR, 1.74; P=0.039) with a nonsignificant contribution of SBP24 (HR≤0.92; P≥0.068); above age 50, SBP24 predicted all end points (HR≥1.19; P≤0.0002) with a nonsignificant contribution of DBP24 (0.96≤HR≤1.14; P≥0.10). The interactions of age with SBP24 and DBP24 were significant for all cardiovascular and coronary events (P≤0.043).
CONCLUSIONS—The risks conferred by DBP24 and SBP24 are age dependent. DBP24 and isolated diastolic hypertension drive coronary complications below age 50, whereas above age 50 SBP24 and isolated systolic and mixed hypertension are the predominant risk factors.
Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could ...lead to improved diagnosis, risk stratification and management of HFrEF.
Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS) to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12.6%) in individuals with diastolic left ventricular dysfunction (N = 176). The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin.
CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mean daytime ambulatory blood pressure (BP) values are considered to be lower than conventional BP values, but data on this relation among younger individuals <50 years are scarce. Conventional and ...24-hour ambulatory BP were measured in 9550 individuals not taking antihypertensive treatment from 13 population-based cohorts. We compared individual differences between daytime ambulatory and conventional BP according to 10-year age categories. Age-specific prevalences of white coat and masked hypertension were calculated. Among individuals aged 18 to 30, 30 to 40, and 40 to 50 years, mean daytime BP was significantly higher than the corresponding conventional BP (6.0, 5.2, and 4.7 mm Hg for systolic; 2.5, 2.7, and 1.7 mm Hg for diastolic BP; all P<0.0001). In individuals aged 60 to 70 and ≥70 years, conventional BP was significantly higher than daytime ambulatory BP (5.0 and 13.0 mm Hg for systolic; 2.0 and 4.2 mm Hg for diastolic BP; all P<0.0001).The prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18 to 30 years to those aged ≥70 years, with little variation between men and women (8.0% versus 6.1%; P=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%; P<0.0001). The age-specific prevalences of masked hypertension were 18.2%, 27.3%, 27.8%, 20.1%, 13.6%, and 10.2% among men and 9.0%, 9.9%, 12.2%, 11.9%, 14.7%, and 12.1% among women. In conclusion, this large collaborative analysis showed that the relation between daytime ambulatory and conventional BP strongly varies by age. These findings may have implications for diagnosing hypertension and its subtypes in clinical practice.
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