Showing papers by "Kimon Stamatelopoulos published in 2020"

Predictors of adverse prognosis in COVID-19: A systematic review and meta-analysis.

Abstract: Background Identification of reliable outcome predictors in coronavirus disease 2019 (COVID-19) is of paramount importance for improving patient's management. Methods A systematic review of literature was conducted until 24 April 2020. From 6843 articles, 49 studies were selected for a pooled assessment; cumulative statistics for age and sex were retrieved in 587 790 and 602 234 cases. Two endpoints were defined: (a) a composite outcome including death, severe presentation, hospitalization in the intensive care unit (ICU) and/or mechanical ventilation; and (b) in-hospital mortality. We extracted numeric data on patients' characteristics and cases with adverse outcomes and employed inverse variance random-effects models to derive pooled estimates. Results We identified 18 and 12 factors associated with the composite endpoint and death, respectively. Among those, a history of CVD (odds ratio (OR) = 3.15, 95% confidence intervals (CIs) 2.26-4.41), acute cardiac (OR = 10.58, 5.00-22.40) or kidney (OR = 5.13, 1.78-14.83) injury, increased procalcitonin (OR = 4.8, 2.034-11.31) or D-dimer (OR = 3.7, 1.74-7.89), and thrombocytopenia (OR = 6.23, 1.031-37.67) conveyed the highest odds for the adverse composite endpoint. Advanced age, male sex, cardiovascular comorbidities, acute cardiac or kidney injury, lymphocytopenia and D-dimer conferred an increased risk of in-hospital death. With respect to the treatment of the acute phase, therapy with steroids was associated with the adverse composite endpoint (OR = 3.61, 95% CI 1.934-6.73), but not with mortality. Conclusions Advanced age, comorbidities, abnormal inflammatory and organ injury circulating biomarkers captured patients with an adverse clinical outcome. Clinical history and laboratory profile may then help identify patients with a higher risk of in-hospital mortality.

Anti-Müllerian Hormone Concentrations Are Inversely Associated With Subclinical Atherosclerosis in Premenopausal Women:

Abstract: Anti-Mullerian hormone (AMH), which is secreted by granulosa cells of late preantral and small antral follicles, is a marker of ovarian reserve. The association of ovarian reserve with subclinical atherosclerosis in women of reproductive age is currently unknown. We primary investigated whether AMH levels are associated with markers of subclinical atherosclerosis in healthy, normally menstruating women. In this cross-sectional study, vascular structure and function were assessed by measurement of carotid and femoral intima-media thickness (IMT), flow-mediated dilation, carotid-femoral pulse wave velocity and augmentation index. Lipid profile and serum AMH concentrations were also measured. Seventy premenopausal women, aged 32.7 ± 6.5 years, were included. Mean AMH levels were lower in smokers than in non-smokers and negatively associated with total cholesterol (TC) levels. An inverse association between mean AMH concentrations and femoral and carotid IMT in all segments was observed. No correlation with other markers of subclinical atherosclerosis or established cardiovascular (CV) risk factors was found. After multivariable adjustment, the association between AMH concentrations and combined carotid IMT or carotid bulb IMT remained significant. In conclusion, in healthy, normally ovulating women, AMH concentrations are negatively associated with subclinical atherosclerosis indices and TC levels, independently of established CV risk factors.

Physical activity is associated with lower arterial stiffness in normal-weight postmenopausal women.

Abstract: The impact of physical exercise, as preventative measure, to control the progression of cardiovascular disease in midlife remains under investigation. We aimed to investigate the effect of different levels of intensity of physical activity on metabolic and vascular profile in healthy postmenopausal women. A total of 625 healthy postmenopausal women (mean age 57.7 ± 7.6 years) were evaluated using the short IPAQ questionnaire for quantification of physical activity. The energy expenditure was estimated in metabolic equivalent of energy (MET) hours per week. Pulse wave velocity (PWV) was measured as an index of arterial stiffness. Intima-media thickness of both right and left common carotid artery, carotid bulb and internal carotid artery, and combined carotid IMT were also assessed by non-invasive and well-validated methods. Mean values of PWV decreased linearly with increasing intensity of physical activity (classes of physical activity: sedentary vs walking vs moderate vs vigorous activity: 9.07 ± 1.22 m/s vs 9.12 ± 1.72 m/s vs 8.47 ± 1.31m/s vs 7.94 ± 0.40 m/s, ANOVA P for linear trend .003). In non-obese postmenopausal women, PWV values associated with: (a) the total number of METs (b-coefficient = -0.261, P = .002) as well as with SBP; (b) or with the number of moderate METs (b-coefficient = -0.192, P = .025) as well as with age and SBP. No significant associations were observed between the intensity of physical exercise and arterial stiffness in the overweight-obese group. Physical activity is negatively associated with arterial stiffness in postmenopausal women with normal weight. This association was not observed in overweight or obese women.

β-Amyloid and mitochondrial-derived peptide-c are additive predictors of adverse outcome to high-on-treatment platelet reactivity in type 2 diabetics with revascularized coronary artery disease

Abstract: Increased β-amyloid and decreased mitochondrial-derived peptide (MOTS-c), are reported in diabetes. We investigated their additive value to high on-clopidogrel platelet reactivity (HPR) for adverse outcome in type 2 diabetics after recent revascularization. In 121 type II diabetics, treated with clopidogrel and aspirin, (93 males, mean age 67.2 years) we measured: (a) maximum platelet aggregation to adenosine diphosphate (ADP) by light transmission aggregometry (LTAmax), (b) malondialdehyde (MDA), as oxidative stress marker, (c) MOTS-c, (d) β-amyloid blood levels. Cardiac death and acute coronary syndromes (MACE) were recorded during 2 years of follow-up. Out of 121 patients, 32 showed HPR (LTAmax > 48%,). At baseline, HPR was associated with β-amyloid > 51 pg/ml (p = 0.006) after adjusting clinical variables, HbA1c, MOTS-c, MDA and medication. During follow-up, 22 patients suffered a MACE. HPR, β-amyloid > 51 pg/ml and MOTS-c 51 mg/dl or HPR and MOTS-c concentration < 167 ng/ml had a fourfold higher risk for MACE than patients without these predictors (relative risk 4.694 and 4.447 respectively p < 0.01). The above results were confirmed in an external validation cohort of 90 patients with diabetes and CAD. Increased β-amyloid or low MOTS-c are additive predictors to high on-clopidogrel platelet reactivity for adverse outcome in diabetics with CAD during 2-years follow-up. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT04027712.

Association between anthropometric characteristics and bladder cancer risk: a systematic review and meta-analysis of longitudinal cohort studies

Abstract: Background/ Aims Anthropometric characteristics, namely overweight/obesity, height and waist circumference have been associated with various cancer types. The aim of this systematic review and meta-analysis is to evaluate the potential associations between anthropometric characteristics and bladder cancer risk, synthesizing longitudinal cohort studies. Methods Literature search across MEDLINE, EMBASE, Scopus, Google Scholar and Cochrane Central was performed up to December 31, 2019 and data abstraction was performed independently by two authors. Random-effects (DerSimonian-Laird) models were used to estimate pooled relative risks (RR) and 95% confidence intervals (95%CI); subgroup analyses were performed geographical region, mean age, publication year, length of follow-up, sample size, method of BMI estimation and adjustment for smoking. Results A total of 27 studies were included (88,593 bladder cancer cases in a total cohort of 49,647,098 subjects). Increased bladder cancer risk was noted in overweight men (pooled RR=1.12, 95%CI: 1.04-1.21) but not in overweight women. Both obese men (pooled RR=1.14, 95%CI: 1.06-1.22) and women (pooled RR=1.19, 95%CI: 1.02-1.38) showed increased risk. Interestingly, height increase per 5 cm did not seem to affect risk of bladder cancer in men (pooled RR=1.03, 95%CI: 0.99- 1.06) and women (pooled RR=1.02, 95%CI: 0.97-1.06). Larger waist circumference was associated with bladder cancer risk in men (pooled RR=1.18, 95%CI: 1.09-1.26) but not women. Conclusion In conclusion, bladder cancer risk seems to be related with obesity overall and central obesity in men. In contrast to other cancer types, height does not seem to affect risk, but more studies are needed to extract safe conclusions.

Cathepsin B expression is associated with arterial stiffening and atherosclerotic vascular disease.

Abstract: Accumulating evidence supports the interaction among vascular aging, inflammation and atherosclerosis. Therefore, exploring underlying pathophysiology may highlight key linking pathways that could be targeted for intervention. Cathepsin B (CTSB), a proteolytic enzyme mainly located in lysosomes and endosomes, can be activated and released by ageing-associated cell acidification. CTSB may also be involved in arterial degeneration, calcification and arterial stiffening by augmenting inflammatory load and by degradation of the elastin-containing arterial extracellular matrix. CTSB is also highly expressed in human carotid plaques and correlates with plaque severity and symptomatic events. Thus, experimental evidence supports a central role of CTSB in ageing processes, atherogenesis and its consequences. However, its clinical role in atherosclerotic cardiovascular disease (ASCVD) has not been sufficiently explored, while its association with vascular aging is unknown. CTSB expression in peripheral blood mononuclear cells (PBMCs) was measured in 224 consecutive subjects (148 without clinically overt coronary artery disease (CAD) (control group), 46 with stable CAD and 30 with acute myocardial infarction (AMI)) using quantitative SYBR Green real-time polymerase chain reaction. Participants underwent peripheral vascular assessment by measurement of aortic stiffness using pulse wave velocity (PWV) (Complior, Artech Medical Saint Quentin Fallavier, France) and by documentation of carotid and femoral atherosclerotic plaques using high-resolution B-mode ultrasound imaging (14.0-MHz multifrequency linear-array probe, Vivid 7 Pro, General Electric Boston, United States). All subjects provided written consent for participation in the study. CTSB in the highest tertile was associated with older age, higher prevalence of arterial hypertension, hyperlipidaemia and with lower estimated glomerular filtration rate (p< 0.05 for all). Overall, CAD patients presented higher CTSB expression than controls (p1⁄4 0.006) (Figure 1). Comparisons by subgroups of CAD showed that AMI patients had increased CTSB expression compared to control subjects (p1⁄4 0.007), while stable CAD and AMI patients did not differ (p1⁄4 0.154). In addition, in control subjects but not in CAD patients, CTSB in the highest tertile presented fourfold increased odds for higher PWV after adjustment for traditional CAD risk factors (TRFs) and renal function (Table 1, Figure 1). CTSB levels were also independently associated with the number of CAD arteries after adjustment for TRFs and renal

A novel optical biosensor for the early diagnosis of sepsis and severe Covid-19: the PROUD study.

Abstract: The accuracy of a new optical biosensor (OB) point-of-care device for the detection of severe infections is studied. The OB emits different wavelengths and outputs information associated with heart rate, pulse oximetry, levels of nitric oxide and kidney function. At the first phase, recordings were done every two hours for three consecutive days after hospital admission in 142 patients at high-risk for sepsis by placing the OB on the forefinger. At the second phase, single recordings were done in 54 patients with symptoms of viral infection; 38 were diagnosed with COVID-19. At the first phase, the cutoff value of positive likelihood of 18 provided 100% specificity and 100% positive predictive value for the diagnosis of sepsis. These were 87.5 and 91.7% respectively at the second phase. OB diagnosed severe COVID-19 with 83.3% sensitivity and 87.5% negative predictive value. The studied OB seems valuable for the discrimination of infection severity.

A cohort-based comprehensive characterization of different patterns of very short-term, within-visit, blood pressure variability.

Abstract: Aim To characterize different patterns of variability of three repeated within-visit blood pressure (BP) readings and to determine the prevalence of specific variation trends in systolic (SBP), diastolic (DBP) blood pressure and pulse pressure (PP). Methods Data from 53 737 subjects from the National Health and Nutrition Examination Survey were analyzed. In each subject, three consecutive BP measurements were performed with a minimum time-interval of at least 30 s. We propose three patterns of within-visit BP variability (separately for SBP, DBP and PP): (1) increasing trend (BP3 > BP2 > BP1); (2) decreasing trend (BP1 > BP2 > BP3) and (3) no trend (BP3 ≈ BP2 ≈ BP1). A threshold of minimum change (ΔP > 3 mmHg) between BP1-BP2 and BP2-BP3 was also applied as a prerequisite for the definition of these trends. Results An increasing trend was observed among three consecutive measurements of SBP, DBP and PP in 7.4, 10.4 and 10.2%, respectively. When a minimum threshold of 3 mmHg was set the respective increasing trends were observed in 1.8, 2.9 and 4.4%, respectively. There was a higher prevalence of decreasing trend within three consecutive SBP, DBP and PP readings: 17, 13.1 and 16.2%, respectively, whereas using a threshold of ΔP >3 mmHg the respective prevalence was 6.3, 4.1 and 7.7%. A maximum absolute difference >10 mmHg within triplicate of SBP/DBP/PP readings was observed in 12.9, 13 and 29.4%, respectively. In the era of personalized medicine, these patterns are well worth further investigation concerning their pathophysiologic and clinical relevance.

Blood pressure variability within a single visit and all-cause mortality.

Abstract: Background Within-visit variability of repeated sequential readings of blood pressure (BP) is an important phenomenon that may affect precision of BP measurement and thus decision making concerning BP-related risk and hypertension management. However, limited data exist concerning predictive ability of within-visit BP variability for clinical outcomes. Therefore, we aimed to investigate the association between the variability of three repeated office BP measurements and the risk of all-cause mortality, independent of BP levels. Methods Data collected through the National Health and Nutrition Examination Survey (NHANES) were analysed. NHANES is a program of studies designed to assess health and nutritional status of adults and children in the United States. A complete set of three sequential BP measurements, together with survival status, were available for 24969 individuals (age 46.8±;19.3 years, 49% males). Multivariable logistic regression models were used to determine the prognostic ability of the examined demographic, clinical, and haemodynamic indices. Results Among various examined indices of variability of systolic (SBP) and diastolic (DBP) blood pressure measurements, the standard deviation of DBP (DBPSD) was the stronger independent predictor of mortality (odds ratio 1.064, 95% Confidence Interval: 1.011-1.12) after adjustment for age, sex, body mass index, smoking, SBP, heart rate, history of hypertension, diabetes mellitus, hypercholesterolaemia, and cardiovascular events. Conclusion Within-visit variability of three sequential office DBP readings may allow for the identification of high-risk patients better than mean SBP and DBP levels. The predictive value of within-visit BP variability and methods to improve its clinical application are worthy of further research.

Breastfeeding is associated with lower subclinical atherosclerosis in postmenopausal women

Abstract: Objective: To evaluate the association between a personal history of lactation and indices of subclinical atherosclerosis in postmenopausal women.Methods: We evaluated the association between a his...

Very-short-term blood pressure variability: complexities and challenges.

Abstract: Theodore G. Papaioannou, Athanase D. Protogerou, Kimon S. Stamatelopoulos, Krystallenia I. Alexandraki, Dimitrios Vrachatis, Antonios Argyris, Vasilios Papaioannou, Manolis Vavuranakis, Christodoulos Stefanadis and Dimitrios Tousoulis, First Department of Cardiology, Biomedical Engineering Unit, Hippokration Hospital, Department of Pathophysiology, Cardiovascular Prevention and Research Unit, Department of Clinical Therapeutics, Vascular Laboratory, Alexandra Hospital, First Department of Propaedeutic and Internal Medicine, Laikon Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Intensive Care Unit, Alexandroupolis General Hospital, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, Third Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Athens, Greece and Cardiovascular Medicine Section, School of Medicine, Yale University, New Haven, USA

Retinol-binding protein 4 is associated with arterial stiffness in early postmenopausal women.

Abstract: Objective Recent evidence in postmenopausal women suggested lack of association between serum levels of retinol-binding protein 4 (RBP4) and subclinical atherosclerosis; however, associations with arterial stiffness in this population remain unexplored. We evaluated the association among RBP4 and cardiovascular risk factors, including homocysteine, a marker involved in retinoic acid synthesis, and indices of arterial stiffness, in a sample of apparently healthy postmenopausal women. Methods This cross-sectional study included 123 healthy postmenopausal women, not on hormone therapy, antihypertensive, or hypolipidemic treatment and with a menopausal age 10 years or less. We performed biochemical/hormonal assessment and sonographic evaluation, including carotid-femoral pulse wave velocity (PWV) and carotid artery stiffness index (SI). Results Univariate analysis showed that RBP4 values correlated with age, low-density lipoprotein-cholesterol and estradiol levels. There was a trend of association of SI and PWV with homocysteine and triglycerides. RBP4 differed according to PWV, using the median PWV value as cut-off (RBP4, PWV ≤8.1 vs >8.1 m/s: 10.09 ± 2.05 vs 10.85 ± 1.91 ng/mL, analysis of covariance P value 0.014 adjusted for age, menopausal age, estradiol, pulse pressure). Linear regression analysis showed that PWV was independently associated with RBP4, age, and pulse pressure, whereas SI was independently associated with RBP4. An increase of one standard deviation in RBP4 levels (2.54 ng/mL) was associated with an increase of 0.577 m/s in PWV. Conclusions RBP4 serum levels are associated with arterial stiffness, in a sample of healthy postmenopausal women. If this association is causative, serum RBP4 levels could serve as a marker of arterial stiffness. Prospective studies are required to investigate the significance of our findings. : Video Summary:http://links.lww.com/MENO/A621.