Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima–media thickness: A longitudinal twin study

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time

Prognostic value of early, conventional proton magnetic resonance spectroscopy in cooled asphyxiated infants

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) commonly leads to neurodevelopmental impairment, raising the need for prognostic tools which may guide future therapies in time. Prognostic value of proton MR spectroscopy (H-MRS) between 1 and 46 days of age has been extensively studied; however, the reproducibility and generalizability of these methods are controversial in a general clinical setting. Therefore, we investigated the prognostic performance of conventional H-MRS during first 96 postnatal hours in hypothermia-treated asphyxiated neonates. METHODS: Fifty-one consecutive hypothermia-treated HIE neonates were examined by H-MRS at three echo-times (TE = 35, 144, 288 ms) between 6 and 96 h of age, depending on clinical stability. Patients were divided into favorable (n = 35) and unfavorable (n = 16) outcome groups based on psychomotor and mental developmental index (PDI and MDI, Bayley Scales of Infant Development II) scores (>/= 70 versus < 70 or death, respectively), assessed at 18-26 months of age. Associations between 36 routinely measured metabolite ratios and outcome were studied. Age-dependency of metabolite ratios in whole patient population was assessed. Prognostic performance of metabolite ratios was evaluated by Receiver Operating Characteristics (ROC) analysis. RESULTS: Three metabolite ratios showed significant difference between outcome groups after correction for multiple testing (p < 0.0014): myo-inositol (mIns)/N-acetyl-aspartate (NAA) height, mIns/creatine (Cr) height, both at TE = 35 ms, and NAA/Cr height at TE = 144 ms. Assessment of age-dependency showed that all 3 metabolite ratios (mIns/NAA, NAA/Cr and mIns/Cr) stayed constant during first 96 postnatal hours, rendering them optimal for prediction. ROC analysis revealed that mIns/NAA gives better prediction for outcome than NAA/Cr and mIns/Cr with cut-off values 0.6798 0.6274 and 0.7798, respectively, (AUC 0.9084, 0.8396 and 0.8462, respectively, p < 0.00001); mIns/NAA had the highest specificity (95.24%) and sensitivity (84.62%) for predicting outcome of neonates with HIE any time during the first 96 postnatal hours. CONCLUSIONS: Our findings suggest that during first 96 h of age even conventional H-MRS could be a useful prognostic tool in predicting the outcome of asphyxiated neonates; mIns/NAA was found to be the best and age-independent predictor

Nocturnal Hypoglycaemia in Patients with Diabetes Mellitus: Database Analysis of a Cohort Using Telemedicine Support for Self-Monitoring of Blood Glucose over a 10-Year-Long Period

Background and Objectives: In patients with diabetes mellitus, hypoglycaemic episodes, especially during night hours, carry a significant risk. Data about the occurrence of nocturnal hypoglycaemia in real-world settings are of clinical importance. The aim of our study was to evaluate the occurrence of nocturnal hypoglycaemia among patients with diabetes using self-monitoring of blood glucose (SMBG) with telemedicine support. Materials and Methods: We retrospectively analysed the central database of an internet-based supportive system between 2010 and 2020 when 8190 SMBG users uploaded nearly 10 million capillary blood glucose values. Nocturnal hypoglycaemia was defined as capillary blood glucose Results: The database contained 914,146 nocturnal blood glucose values from 7298 users; 24,623 (2.7%) glucose values were below the hypoglycaemic threshold and 2363 patients (32.4%) had at least one hypoglycaemic glucose value. Nocturnal hypoglycaemia was more often found in patients with type 1 vs. type 2 diabetes (n = 1890 (80.0%) vs. n = 387 (16.4%), respectively). Hypoglycaemic blood glucose values were most frequently observed in the age group of 10.0–19.9 years (n = 481 (20.4%)). Patients with nocturnal hypoglycaemia were mostly on insulin treatment (1854 (78.5%) patients with 20,727 (84.1%) hypoglycaemic glucose values). Only 356 patients (15.1%) with nocturnal hypoglycaemia performed a retest within 120 min. Within a one-day-long (1440 min) timeframe, the elapsed median time until a retest, yielding a safe blood glucose value (>3.9 mml/L), was 273 min (interquartile range: 157–300 min). Conclusions: Nocturnal hypoglycaemia should be considered as a persisting challenge to antihyperglycaemic treatment in patients living with diabetes. Continuous efforts are needed to improve both antihyperglycaemic treatment and patient education for preventing nocturnal hypoglycaemia, and to act adequately if hypoglycaemic values are detected

Evidence for a Strong Genetic Influence on Carotid Plaque Characteristics

Background and Purpose— Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. Methods— One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. Results— Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%–90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%–87%), 69% for plaque size (area in mm 2 in longitudinal plane; 50 percentile; 95% CI, 16%–86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%–90%), 74% for plaque numerosity (95% CI, 26%–86%), 68% (95% CI, 40%–84%), and 66% (95% CI, 32%–90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%–34%). Controlling for relevant covariates did not change the results significantly. Conclusions— The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits