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Aging; Arteriosclerosis; Hemodynamics Envelliment; Arteriosclerosi; Hemodinàmica Envejecimiento; Arteriosclerosis; Hemodinámica Arterial pulse waves (PWs) such as blood pressure and photoplethysmogram (PPG) signals contain a wealth of information on the cardiovascular (CV) system that can be exploited to assess vascular age and identify individuals at elevated CV risk. We review the possibilities, limitations, complementarity, and differences of reduced-order, biophysical models of arterial PW propagation, as well as theoretical and empirical methods for analyzing PW signals and extracting clinically relevant information for vascular age assessment. We provide detailed mathematical derivations of these models and theoretical methods, showing how they are related to each other. Finally, we outline directions for future research to realize the potential of modeling and analysis of PW signals for accurate assessment of vascular age in both the clinic and in daily life. This article is based upon work from COST Action “Network for Research in Vascular Ageing” (VascAgeNet, CA18216), supported by COST (European Cooperation in Science and Technology, www.cost.eu). This work was supported by British Heart Foundation Grants PG/15/104/31913 (to J.A. and P.H.C.), FS/20/20/34626 (to P.H.C.), and AA/18/6/34223, PG/17/90/33415, SPG 2822621, and SP/F/21/150020 (to A.D.H.); Kaunas University of Technology Grant INP2022/16 (to B.P.); European Research Executive Agency, Marie-Sklodowska Curie Actions Individual Fellowship Grant 101038096 (to S.P.); Istinye University, BAP Project Grant 2019B1 (to S.P.); “la Caixa” Foundation Grant LCF/BQ/PR22/11920008 (to A.G.); and National Institute for Health and Care Research Grant AI AWARD02499 and EU Horizon 2020 Grant H2020 848109 (to A.D.H.).

Context Data on long-term safety of growth hormone (GH) replacement in adults with GH deficiency (GHD) are needed. Objective We aimed to evaluate the safety of GH in the full KIMS (Pfizer International Metabolic Database) cohort. Methods The worldwide, observational KIMS study included adults and adolescents with confirmed GHD. Patients were treated with GH (Genotropin [somatropin]; Pfizer, NY) and followed through routine clinical practice. Adverse events (AEs) and clinical characteristics (eg, lipid profile, glucose) were collected. Results A cohort of 15 809 GH-treated patients were analyzed (mean follow-up of 5.3 years). AEs were reported in 51.2% of patients (treatment-related in 18.8%). Crude AE rate was higher in patients who were older, had GHD due to pituitary/hypothalamic tumors, or adult-onset GHD. AE rate analysis adjusted for age, gender, etiology, and follow-up time showed no correlation with GH dose. A total of 606 deaths (3.8%) were reported (146 by neoplasms, 71 by cardiac/vascular disorders, 48 by cerebrovascular disorders). Overall, de novo cancer incidence was comparable to that in the general population (standard incidence ratio 0.92; 95% CI, 0.83-1.01). De novo cancer risk was significantly lower in patients with idiopathic/congenital GHD (0.64; 0.43-0.91), but similar in those with pituitary/hypothalamic tumors or other etiologies versus the general population. Neither adult-onset nor childhood-onset GHD was associated with increased de novo cancer risks. Neutral effects were observed in lipids/fasting blood glucose levels. Conclusion These final KIMS cohort data support the safety of long-term GH replacement in adults with GHD as prescribed in routine clinical practice.

The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorti-coids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity-sex hormone-breast cancer pathway. The con-firmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer.

Introduction Hormonal contraception is a well-known risk factor for venous thromboembolism (VTE). APC resistance and impaired functions of protein S and TFPI are thought to play an important role in the pathogenesis of hormone-related VTE. It is unknown, whether women, who develop VTE during hormonal contraception possess a vulnerability in these pathways, making them susceptible to thrombosis. Materials and methods Plasma samples were obtained from 57 premenopausal women in average 15.3 years after hormone-associated VTE and from 31 healthy controls. Thrombin generation at high tissue factor (TF) in the absence and in the presence of activated protein C (APC) and at low TF without and with inhibiting anti-protein S- and anti-TFPI-antibodies was measured via calibrated automated thrombography. Results Women with previous hormone-related thrombosis had higher thrombin generation at low TF, higher APC resistance, protein S- and TFPI ratios, differences: 219.9 nM IIa.min (95%CI:90.4 to 349.3); 1.88 (95%CI:0.71 to 3.05); 0.13 (95%CI:0.01 to 0.26) and 0.19 (95%CI:0.08 to 0.30), respectively. Thrombin generation at high TF without APC did not differ between the groups. Smoking decreased thrombin generation at low TF by −222.6 nM IIa.min (95%CI: −381.1 to −64.1), the APC sensitivity ratio by −2.20 (95%CI: −3.63 to −0.77) and the TFPI ratio by −0.16 (95%CI: −0.29 to −0.03), but did not influence thrombin generation at high TF. Discussion We demonstrated impairment of the protein S/TFPI system and increased APC resistance in women with previous hormone-induced VTE. Smoking decreased thrombin generation at assay conditions, dependent on the function of the TFPI system.

Study design: Sub-study of a randomized controlled trial. Objectives: To examine if hybrid cycling (cycling with the legs via electrical stimulation combined with voluntary handcycling) compared to handcycling leads to different systemic vascular adaptations in individuals with a long-term spinal cord injury (SCI). Setting: Two rehabilitation centers in the Netherlands. Methods: Ten individuals with a SCI trained on a hybrid bicycle (N = 5) or a handcycle (N = 5) for 16 weeks twice a week. Prior to and following the training the intima media thickness (IMT) of the common coronary artery (CCA) and superficial femoral artery (SFA) were measured and the flow-mediated dilation (FMD) of the brachial artery (BA) was analyzed. Results: Before training, there were no significant differences in any of the outcome measures between the groups. We found no change in CCA IMT (pre: 0.616 mm, post: 0.586 mm), or in SFA (pre: 0.512 mm, post: 0.520 mm) after hybrid cycling. We also found no change in FMD % of BA after hybrid cycling (pre: 9.040%, post: 9.220%). There were no changes in CCA IMT, SFA IMT, and FMD% after handcycling either. Conclusions: It appears that 16 weeks of twice-weekly training of up to 30 min on a hybrid bicycle or handcycle does not lead to systemic vascular adaptations. A larger sample size and training protocol with more frequent and higher intensity training (which might involve a home-based setting and an adapted period prior to the training) might show different results.

Background: Cannabis legalization and use have risen globally. However, the association between cannabis use, eating behaviors and body weight among adolescents is yet unexplored. Objectives: This study examined the association between cannabis use, fast-food consumption, overweight and obesity in 28 countries using data from the 2010–2016 Global School-Based Student Health Survey. Methods: Multivariable logistic regression and meta-analysis were performed among a sample of 83,726 adolescents (48.7% females) aged 12–15 years, mean (SD) age of 13.8 (0.9) years. Results: The overall prevalence of cannabis use (in past 30 days) and fast-food consumption (in past 7 days) were 2.8% and 57.3% respectively. The overall prevalence of overweight and obesity was 14.7% and 4.2%, respectively. Cannabis use was significantly associated with fast-food consumption (OR = 1.33; 95%CI = 1.13–1.57) but not with overweight (OR = 0.95; 95%CI = 0.80–1.14) or obesity (OR = 1.16; 95%CI = 0.85–1.59). For obesity, there was a moderate level of between-country heterogeneity (I 2 = 51.9%) and significant positive associations with cannabis use were observed in Bahamas, Bangladesh, Namibia and Nepal. Conclusion: The results highlight the association between cannabis use and dietary risks, providing evidence for public health interventions on the interrelated nature of cannabis use and fast-food consumption.

This Review provides insight into sexual dimorphism in adipose tissue distribution and substrate metabolism in adipose tissue, skeletal muscle and liver, as well as the underlying mechanisms. The effects of these sex differences on cardiometabolic health are outlined and the potential for developing sex-specific prevention and treatment strategies is discussed.Obesity is associated with many adverse health effects, such as an increased cardiometabolic risk. Despite higher adiposity for a given BMI, premenopausal women are at lower risk of cardiometabolic disease than men of the same age. This cardiometabolic advantage in women seems to disappear after the menopause or when type 2 diabetes mellitus develops. Sexual dimorphism in substrate supply and utilization, deposition of excess lipids and mobilization of stored lipids in various key metabolic organs (such as adipose tissue, skeletal muscle and the liver) are associated with differences in tissue-specific insulin sensitivity and cardiometabolic risk profiles between men and women. Moreover, lifestyle-related factors and epigenetic and genetic mechanisms seem to affect metabolic complications and disease risk in a sex-specific manner. This Review provides insight into sexual dimorphism in adipose tissue distribution, adipose tissue, skeletal muscle and liver substrate metabolism and tissue-specific insulin sensitivity in humans, as well as the underlying mechanisms, and addresses the effect of these sex differences on cardiometabolic health. Additionally, this Review highlights the implications of sexual dimorphism in the pathophysiology of obesity-related cardiometabolic risk for the development of sex-specific prevention and treatment strategies.

Introduction: As the only part of the human vasculature, the retina is available for direct, noninvasive inspection. Retinal vascular fractal dimension (DF) is a method to measure the structure of the retinal vascular tree, with higher noninteger values between 1 and 2 representing a more complex and dense retinal vasculature. Retinal vascular structure has been associated with a variety of systemic diseases, and this study examined the association of DF and macrovascular cardiac disease in a case-control design. Methods: Retinal fundus photos were captured with Topcon TRC-50X in 38 persons that had coronary artery bypass grafting (CABG, cases) and 37 cardiovascular healthy controls. The semiautomatic software VAMPIRE was used to measure retinal DF. Results: Patients with CABG had lower DF of the retinal main venular vessels compared to the control group (1.15 vs. 1.18, p = 0.01). In a multivariable regression model adjusted for gender and age, eyes in the fourth quartile with higher DF were less likely to have CABG compared to patients in the first (OR, 7.20; 95% confidence interval: 1.63–31.86; p = 0.009) and second (OR, 8.25; 95% confidence interval: 1.70–40.01; p = 0.009) quartiles. Conclusions: This study demonstrates that lower complexity of main venular vessels associates with higher risk of having CABG. The research supports the hypothesis that the retinal vascular structure can be used to assess nonocular macrovascular disease.

Peripheral artery disease (PAD) affects 3%-10% of the Western population and if remains untreated can have devastating consequences to patients and their families. This review article analyzes how healthy dietary habits can decrease PAD rates when applied in the general population. The aim is to focus on dietary, nutritional and weight management interventions in patients with established PAD. Most adults with PAD are overweight or obese, while three out of four patients are characterized by deficiencies in vitamins and minerals. Weight loss interventions when needed and specialized dietary plans should be routinely recommended in patients with PAD. Appropriate nutritional support is of paramount importance in patients with advanced stages of PAD (critical limb ischemia).

Background Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. Methods Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). Results CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1—48 mg/L and Mdn 1.1 mg/L range 0.1—33 mg/L, respectively, r = .18 p = .02). Among Kitavans, there were small negative associations between lnCRP for CRP values Conclusions Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.

Peripheral artery disease (PAD) affects 3%-10% of the Western population and if remains untreated can have devastating consequences to patients and their families. This review article analyzes how healthy dietary habits can decrease PAD rates when applied in the general population. The aim is to focus on dietary, nutritional and weight management interventions in patients with established PAD. Most adults with PAD are overweight or obese, while three out of four patients are characterized by deficiencies in vitamins and minerals. Weight loss interventions when needed and specialized dietary plans should be routinely recommended in patients with PAD. Appropriate nutritional support is of paramount importance in patients with advanced stages of PAD (critical limb ischemia).

Over the past 50 years, many countries around the world have faced an unchecked pandemic of obesity and type 2 diabetes (T2DM). As best practice treatment of T2DM has done very little to check its growth, the pandemic of diabesity now threatens to make health-care systems economically more difficult for governments and individuals to manage within their budgets. The conventional view has been that T2DM is irreversible and progressive. However, in 2016, the World Health Organization (WHO) global report on diabetes added for the first time a section on diabetes reversal and acknowledged that it could be achieved through a number of therapeutic approaches. Many studies indicate that diabetes reversal, and possibly even long-term remission, is achievable, belying the conventional view. However, T2DM reversal is not yet a standardized area of practice and some questions remain about long-term outcomes. Diabetes reversal through diet is not articulated or discussed as a first-line target (or even goal) of treatment by any internationally recognized guidelines, which are mostly silent on the topic beyond encouraging lifestyle interventions in general. This review paper examines all the sustainable, practical, and scalable approaches to T2DM reversal, highlighting the evidence base, and serves as an interim update for practitioners looking to fill the practical knowledge gap on this topic in conventional diabetes guidelines.

BACKGROUND Vitamin D has been suggested to affect peripheral insulin sensitivity. Evidence regarding the effect of vitamin D supplementation on insulin sensitivity is still conflicting. PURPOSE This meta-analysis aimed to assess the effect of vitamin D supplementation on insulin sensitivity in humans with or at risk for insulin resistance. DATA SOURCES AND STUDY SELECTION PubMed, Web of Science, Embase, CINAHL, and Cochrane Library were systematically searched for randomized controlled trials (RCTs) from 1980 until 31 December 2018 reporting treatment effects of vitamin D supplementation on insulin sensitivity. DATA EXTRACTION The main outcome of interest was the change in insulin sensitivity, derived from the gold standard hyperinsulinemic-euglycemic clamp or the Matsuda index derived from the oral glucose tolerance test and insulin sensitivity index from intravenous glucose tolerance test. We extracted data on the standardized mean difference between the vitamin D treatment and placebo groups in change from baseline insulin sensitivity. DATA SYNTHESIS Eighteen RCTs were included in this meta-analysis comparing vitamin D supplementation (n= 612) with placebo (n= 608). Vitamin D supplementation had no effect on insulin sensitivity (standardized mean difference -0.01, 95% CI -0.12, 0.10;P= 0.87,I-2= 0%). Visual inspection of funnel plot symmetry did not suggest potential publication bias. LIMITATIONS The number of individuals who participated in the included studies was relatively small, possibly due to the invasive character of the measurement (e.g., clamp). CONCLUSIONS This meta-analysis provides no evidence that vitamin D supplementation has a beneficial effect on peripheral insulin sensitivity in people with or at risk for insulin resistance.

Physical activity and exercise training are effective strategies for reducing the risk of cardiovascular events, but multiple studies have reported an increased prevalence of coronary atherosclerosis, usually measured as coronary artery calcification, among athletes who are middle-aged and older. Our review of the medical literature demonstrates that the prevalence of coronary artery calcification and atherosclerotic plaques, which are strong predictors for future cardiovascular morbidity and mortality, was higher in athletes compared with controls, and was higher in the most active athletes compared with less active athletes. However, analysis of plaque morphology revealed fewer mixed plaques and more often only calcified plaques among athletes, suggesting a more benign composition of atherosclerotic plaques. This review describes the effects of physical activity and exercise training on coronary atherosclerosis in athletes who are middle-aged and older and aims to contribute to the understanding of the potential adverse effects of the highest doses of exercise training on the coronary arteries. For this purpose, we will review the association between exercise and coronary atherosclerosis measured using computed tomography, discuss the potential underlying mechanisms for exercise-induced coronary atherosclerosis, determine the clinical relevance of coronary atherosclerosis in middle-aged athletes and describe strategies for the clinical management of athletes with coronary atherosclerosis to guide physicians in clinical decision making and treatment of athletes with elevated coronary artery calcification scores.

Cardiovascular risk factors are usually better tolerated, and can therefore be perceived as less harmful, at a young age. However, over time the effects of these adverse factors may persist or accumulate and lead to excess morbidity and mortality from cardiovascular diseases later in life. Until now, reference values for the basic cardiovascular health characteristics of 4-to-6 year-old children are lacking. Within a follow-up study of the ENVIRONAGE (ENVIRonmental influence ON early AGE) birth cohort we assessed various cardiovascular measurements in 288 children aged 4-5 years. For the macrovasculature, we measured their blood pressure and examined the intima-media thickness of the carotid artery (CIMT), the arterial elasticity (including the pulse-wave velocity (PWV), carotid distensibility (DC) and compliance (CC) coefficients), the carotid beta stiffness index (SI beta) and Young's Elastic Modulus (YEM). Retinal microvascular traits included the Central Retinal Arteriolar Equivalent (CRAE) and Central Retinal Venular Equivalent (CRVE). Age of the study population averaged (+/- SD) 4.2 (+/- 0.4 years. Mean systolic and diastolic blood pressure were 97.9 (+/- 8.1) mmHg and 54.7(+/- 7.6) mmHg, respectively. CIMT for the total population averaged 487.1 (+/- 68.1) mu m. The average stiffness values for DC, CC, SI beta, and PWV were 78.7 (+/- 34.2) 10-(3)/kPa, 1.61 (+/- 0.59) mm(2)/kPa and 4.4 (+/- 2.4), and 3.7 m/s (+/- 0.9) respectively. The mean determined for YEM was 163.2 kPa (+/- 79.9). Concerning the microvasculature, the average CRAE was 180.9 (+/- 14.2) mu m and the corresponding value for CRVE was 251.0 (+/- 19.7) mu m. In contrast to the macrovasculature, a significant gender-related difference existed for the microvasculature: in boys, both the CRAE (178.8 mu m vs 182.6 mu m; p = 0.03) and CRVE (247.9 mu m vs 254.0 mu m; p = 0.01) were narrower than in girls. We have provided reference values for young children to understand changes in the early cardiovascular health trajectory. Establishing these reference values of cardiovascular phenotypes at this young age is necessary to develop targeted health promotion strategies as well as for better understanding of the life course changes of both small and large blood vessels. The authors thank all children and parents for taking part in the study. The ENVIRONAGE birth cohort and follow-up study are supported by grants from the European Research Council (ERC-2012-StG310898) and the Flemish Scientific Fund (FWO, 1516112 N/G.0873.11.N.10). Nawrot, TS (corresponding author), Hasselt Univ, Ctr Environm Sci, Hasselt, Belgium ; Leuven Univ, Dept Publ Hlth & Primary Care, Occupat & Environm Med, Leuven, Belgium. tim.nawrot@uhasselt.be

Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing incidence, leading to a health care problem of epidemic proportions for which no curative treatments exist. Consequently, an urge exists to better understand the pathophysiology of HFpEF. Accumulating evidence suggests a key pathophysiological role for coronary microvascular dysfunction (MVD), with an underlying mechanism of low-grade pro-inflammatory state caused by systemic comorbidities. The systemic entity of comorbidities and inflammation in HFpEF imply that patients develop HFpEF due to systemic mechanisms causing coronary MVD, or systemic MVD. The absence or presence of peripheral MVD in HFpEF would reflect HFpEF being predominantly a cardiac or a systemic disease. Here, we will review the current state of the art of cardiac and systemic microvascular dysfunction in HFpEF (Graphical Abstract), resulting in future perspectives on new diagnostic modalities and therapeutic strategies.

Heart failure with preserved ejection fraction (HFpEF) is a condition with increasing incidence, leading to a health care problem of epidemic proportions for which no curative treatments exist. Consequently, an urge exists to better understand the pathophysiology of HFpEF. Accumulating evidence suggests a key pathophysiological role for coronary microvascular dysfunction (MVD), with an underlying mechanism of low-grade pro-inflammatory state caused by systemic comorbidities. The systemic entity of comorbidities and inflammation in HFpEF imply that patients develop HFpEF due to systemic mechanisms causing coronary MVD, or systemic MVD. The absence or presence of peripheral MVD in HFpEF would reflect HFpEF being predominantly a cardiac or a systemic disease. Here, we will review the current state of the art of cardiac and systemic microvascular dysfunction in HFpEF (Graphical Abstract), resulting in future perspectives on new diagnostic modalities and therapeutic strategies.

Background Migraine has been associated with several diseases. This population-based prospective Finnish postal survey Health and Social Support Study explored whether self-reported migraine predicted incident hypertension independently in a working-age population by utilizing two data sources: the baseline survey from the year 1998 in combination with the follow-up survey data from the years 2003 and 2012 with linkage to the national Social Insurance Institution registry data of the special reimbursement medication for hypertension from 1999 to 2013. The survey follow-up reached until the second follow-up in the year 2012. The register follow-up also included the year 2013. Methods The present population-based prospective cohort study, utilizing two different data sources, included 8593 respondents (22.7% response rate) who participated in 1998, 2003, and 2012 but who did not report hypertension at the baseline in 1998, and whose responses could be linked with the Social Insurance Institution registry data from the beginning of 1999 to the end of 2013. The multivariable logistic regression analysis was based on the combined two data sets. Results A significant association of self-reported migraine and incident hypertension (odds ratio 1.37; 95% confidence interval 1.20–1.57) prevailed in the multiple logistic regression analysis adjusted for central socio-demographic and health behaviour variables. Conclusion Extra attention should be paid to prevention and control of hypertension in working-age migraine patients.

Objective: The aim of this study is to look at the relationship between hyperthyrotropinemia and anthropometric measurements as well as cardiometabolic risk factors in obese children and adolescents. Materials and Methods: A total of 100 patients with isolated hyperthyrotropinemia and 124 patients with normal thyroid functions, between 10 and 18 years of age, were included in the study. Anthropometric and blood pressure measurements and biochemical parameters were recorded. Non-high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol, and triglyceride/high-density lipoprotein cholesterol ratios were calculated. Results: The subjects' mean age was 12.6 +/- 1.9 years and their mean body mass index was 29.8 +/- 4 kg/m2. The isolated hyperthyrotropinemia group had considerably greater levels of triglyceride, non-high-density lipoprotein cholesterol, and the triglyceride/high-density lipoprotein cholesterol ratio. Higher prevalences of hypertriglyceridemia and increased triglyceride/ high-density lipoprotein cholesterol ratio were found in the group with isolated hyperthyrotropinemia. Thyroid-stimulating hormone had a statistically significant positive relationship with triglyceride, non-high-density lipoprotein cholesterol, total cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride/high-density lipoprotein cholesterol ratio, as well as an inverse relationship with high-density lipoprotein cholesterol. Thyroid-stimulating hormone was positively correlated with triglyceride and triglyceride/high-density lipoprotein cholesterol ratio in both females and males; however, only in females, thyroid-stimulating hormone was positively correlated with non-high-density lipoprotein cholesterol and total cholesterol/highdensity lipoprotein cholesterol ratio. The triglyceride/high-density lipoprotein cholesterol ratio, as well as the rates of hypertriglyceridemia were higher in children with isolated hyperthyrotropinemia in the female subgroup. Male children with isolated hyperthyrotropinemia had significantly higher triglyceride levels in comparison with males with normal thyroid-stimulating hormone. Conclusion: The present study suggested that isolated hyperthyrotropinemia is associated with the deterioration of lipid metabolism, especially in females. Since dyslipidemia is accepted as a cardiovascular disease risk factor, isolated hyperthyrotropinemia might negatively influence cardiovascular functions in obese children and adolescents.

IntroductionPreeclampsia, an endothelial disorder of pregnancy, predisposes to remote cardiovascular diseases (CVD). Whether there is an accelerated effect of aging on endothelial decline in former preeclamptic women is unknown. We investigated if the arterial aging regarding endothelial-dependent and -independent vascular function is more pronounced in women with a history of preeclampsia as compared to women with a history of solely normotensive gestation(s).MethodsData was used from the Queen of Hearts study (ClinicalTrials.gov Identifier NCT02347540); a large cross-sectional study on early detection of cardiovascular disease among young women (≥18 years) with a history of preeclampsia and a control group of low-risk healthy women with a history of uncomplicated pregnancies. Brachial artery flow-mediated dilation (FMD; absolute, relative and allometric) and sublingually administered nitroglycerine-mediated dilation (NGMD; absolute and relative) were measured using ultrasound. Cross-sectional associations of age with FMD and NGMD were investigated by linear regression. Models were adjusted for body mass index, smoking, antihypertensive drug use, mean arterial pressure, fasting glucose, menopausal state, family history of CVD and stress stimulus during measurement. Effect modification by preeclampsia was investigated by including an interaction term between preeclampsia and age in regression models.ResultsOf the 1,217 included women (age range 22–62 years), 66.0% had a history of preeclampsia and 34.0% of normotensive pregnancy. Advancing age was associated with a decrease in relative FMD and NGMD (unadjusted regression coefficient: FMD: −0.48%/10 years (95% CI:−0.65 to −0.30%/10 years), NGMD: −1.13%/10 years (−1.49 to −0.77%/10 years)) and increase in brachial artery diameter [regression coefficient = 0.16 mm/10 years (95% CI 0.13 to 0.19 mm/10 years)]. Similar results were found when evaluating FMD and NGMD as absolute increase or allometrically, and after confounder adjustments. These age-related change were comparable in former preeclamptic women and controls (p-values interaction ≥0.372). Preeclampsia itself was independently associated with consistently smaller brachial artery diameter, but not with FMD and NGMD.ConclusionIn young- to middle-aged women, vascular aging in terms of FMD and NGMD was not accelerated in women after preeclampsia compared to normotensive pregnancies, even though former preeclamptic women consistently have smaller brachial arteries.

The effect of physical activity on breast cancer risk may be partly mediated by sex steroid hormones. This review synthesized and appraised the evidence for an effect of physical activity on sex steroid hormones. Systematic searches were performed using MEDLINE (Ovid), EMBASE (Ovid), and SPORTDiscus to identify experimental studies and prospective cohort studies that examined physical activity and estrogens, progestins, and/or androgens, as well as sex hormone binding globulin (SHBG) and glucocorticoids in pre- and postmenopausal women. Meta-analyses were performed to generate effect estimates. Risk of bias was assessed, and the GRADE system was used to appraise quality of the evidence. Twenty-eight randomized controlled trials (RCT), 81 nonrandomized interventions, and six observational studies were included. Estrogens, progesterone, and androgens mostly decreased, and SHBG increased, in response to physical activity. Effect sizes were small, and evidence quality was graded moderate or high for each outcome. Reductions in select sex steroid hormones following exercise supports the biological plausibility of the first part of the physical activity–sex hormone–breast cancer pathway. The confirmed effect of physical activity on decreasing circulating sex steroid hormones supports its causal role in preventing breast cancer. See related reviews by Lynch et al., p. 11 and Drummond et al., p. 28

Obesity and metabolic syndrome (O&MS) due to the worldwide obesity epidemic affects children at all stages of chronic kidney disease (CKD) including dialysis and after kidney transplantation. The presence of O&MS in the pediatric CKD population may augment the already increased cardiovascular risk and contribute to the loss of kidney function. The Pediatric Renal Nutrition Taskforce (PRNT) is an international team of pediatric renal dietitians and pediatric nephrologists who develop clinical practice recommendations (CPRs) for the nutritional management of children with kidney diseases. We present CPRs for the assessment and management of O&MS in children with CKD stages 2–5, on dialysis and after kidney transplantation. We address the risk factors and diagnostic criteria for O&MS and discuss their management focusing on non-pharmacological treatment management, including diet, physical activity, and behavior modification in the context of age and CKD stage. The statements have been graded using the American Academy of Pediatrics grading matrix. Statements with a low grade or those that are opinion-based must be carefully considered and adapted to individual patient needs based on the clinical judgment of the treating physician and dietitian. Research recommendations are provided. The CPRs will be periodically audited and updated by the PRNT. Supplementary Information The online version contains supplementary material available at 10.1007/s00467-021-05148-y.

Bleeding and thrombosis are major clinical problems with high morbidity and mortality. Treatment modalities for these diseases have improved in recent years, but there are many clinical questions remaining and a need to advance diagnosis, management, and therapeutic options. Basic research plays a fundamental role in understanding normal and disease processes, yet this sector has observed a steady decline in funding prospects thereby hindering support for studies of mechanisms of disease and therapeutic development opportunities. With the financial constraints faced by basic scientists, the ISTH organized a basic science task force (BSTF), comprising Scientific and Standardization Committee subcommittee chairs and co-chairs, to identify research opportunities for basic science in hemostasis and thrombosis. The goal of the BSTF was to develop a set of recommended priorities to build support in the thrombosis and hemostasis community and to inform ISTH basic science programs and policy making. The BSTF identified three principal opportunity areas that were of significant overarching relevance: mechanisms causing bleeding, innate immunity and thrombosis, and venous thrombosis. Within these, five fundamental research areas were highlighted: blood rheology, platelet biogenesis, cellular contributions to thrombosis and hemostasis, structure-function protein analyses, and visualization of hemostasis. This position paper discusses the importance and relevance of these opportunities and research areas, and the rationale for their inclusion. These findings have implications for the future of fundamental research in thrombosis and hemostasis to make transformative scientific discoveries and tackle key clinical questions. This will permit better understanding, prevention, diagnosis, and treatment of hemostatic and thrombotic conditions. ispartof: JOURNAL OF THROMBOSIS AND HAEMOSTASIS vol:20 issue:6 pages:1496-1506 ispartof: location:England status: published

The safety considerations of food-based solutions for vitamin D deficiency prevention, such as fortification and supplementation, are critical. On the basis of collective data from 20 randomized controlled trials (RCTs) and 20 national healthy surveys, as well as prospective cohort studies (PCSs) across the ODIN project (“Food-based solutions for optimal vitamin D nutrition and health through the life cycle”, FP7-613977), we analyzed the potential safety issues arising from vitamin D intakes and/or supplementation. These adverse consequences included high serum 25-hydroxyvitamin D (S-25(OH)D) concentrations (>125 nmol/L), high serum calcium concentrations, and vitamin D intakes in excess of the tolerable upper intake levels (ULs). In the RCTs (n = 3353, with vitamin D doses from 5–175 µg/day), there were no reported adverse effects. The prevalence of high S-25(OH)D was 125 nmol/L were rare in the RCTs and PCSs, and no associated adverse effects were observed.

Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardio-metabolic disorders, autoimmune diseases, and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. In this study, we carried out a genome-wide association meta-analysis of BW in 42 212 twin individuals and found a positive correlation of beta values (Pearson's r = 0.66, 95% confidence interval [CI]: 0.47-0.77) with 150 previously reported genome-wide significant variants for singleton BW. We identified strong positive genetic correlations between BW in twins and numerous anthropometric traits, most notably with BW in singletons (genetic correlation [rg] = 0.92, 95% CI: 0.66-1.18). Genetic correlations of BW in twins with a series of health-related traits closely resembled those previously observed for BW in singletons. Polygenic scores constructed from a genome-wide association study on BW in UK Biobank demonstrated strong predictive power in a target sample of Dutch twins and singletons. Together, our results indicate that a similar genetic architecture underlies BW in twins and singletons and that future genome-wide studies might benefit from including data from large twin registers. Birth weight (BW) is an important predictor of newborn survival and health and has associations with many adult health outcomes, including cardiometabolic disorders, autoimmune diseases and mental health. On average, twins have a lower BW than singletons as a result of a different pattern of fetal growth and shorter gestational duration. Therefore, investigations into the genetics of BW often exclude data from twins, leading to a reduction in sample size and remaining ambiguities concerning the genetic contribution to BW in twins. In this study, we carried out a genome-wide association meta-analysis of BW in 42 212 twin individuals and found a positive correlation of beta values (Pearson's r = 0.66, 95% confidence interval [CI]: 0.47-0.77) with 150 previously reported genome-wide significant variants for singleton BW. We identified strong positive genetic correlations between BW in twins and numerous anthropometric traits, most notably with BW in singletons (genetic correlation [rg] = 0.92, 95% CI: 0.66-1.18). Genetic correlations of BW in twins with a series of health-related traits closely resembled those previously observed for BW in singletons. Polygenic scores constructed from a genome-wide association study on BW in the UK Biobank demonstrated strong predictive power in a target sample of Dutch twins and singletons. Together, our results indicate that a similar genetic architecture underlies BW in twins and singletons and that future genome-wide studies might benefit from including data from large twin registers.

This systematic review examined the impact of exercise intervention programs on selected cardiometabolic health indicators in adults with overweight or obesity. Three electronic databases were explored for randomized controlled trials (RCTs) that included adults with overweight or obesity and provided exercise-training interventions. Effects on blood pressure, insulin resistance (homeostasis model of insulin resistance, HOMA-IR), and magnetic resonance measures of intrahepatic fat in exercise versus control groups were analyzed using random effects meta-analyses. Fifty-four articles matched inclusion criteria. Exercise training reduced systolic and diastolic blood pressure (mean difference, MD = -2.95 mmHg [95% CI -4.22, -1.68], p < 0.00001, I-2 = 63% and MD = -1.93 mmHg [95% CI -2.73, -1.13], p < 0.00001, I-2 = 54%, 60 and 58 study arms, respectively). Systolic and diastolic blood pressure decreased also when considering only subjects with hypertension. Exercise training significantly decreased HOMA-IR (standardized mean difference, SMD = -0.34 [-0.49, -0.18], p < 0.0001, I-2 = 48%, 37 study arms), with higher effect size in subgroup of patients with type 2 diabetes (SMD = -0.50 [95% CI: -0.83, -0.17], p = 0.003, I-2 = 39%). Intrahepatic fat decreased significantly after exercise interventions (SMD = -0.59 [95% CI: -0.78, -0.41], p < 0.00001, I-2 = 0%), with a larger effect size after high-intensity interval training. In conclusion, exercise training is effective in improving cardiometabolic health in adults with overweight or obesity also when living with comorbitidies.

Structural and functional dysfunction in both the macro- and microvasculature are a feature of essential hypertension. In a healthy cardiovascular system, the elastic properties of the large arteries ensure that pulsations in pressure and flow generated by cyclic left ventricular contraction are dampened, so that less pulsatile pressure and flow are delivered at the microvascular level. However, in response to aging, hypertension, and other disease states, arterial stiffening limits the buffering capacity of the elastic arteries, thus exposing the microvasculature to increased pulsatile stress. This is thought to be particularly pertinent to high flow/low resistance organs such as the brain and kidney, which may be sensitive to excess pressure and flow pulsatility, damaging capillary networks, and resulting in target organ damage. In this review, we describe the clinical relevance of the pulsatile interaction between the macro- and microvasculature and summarize current methods for measuring the transmission of pulsatility between the two sites.

Background Promoting ideal cardiovascular health behaviors is an objective of the American Heart Association 2020 goals. We hypothesized that ideal health behaviors of parents are associated with health behaviors of their adult offspring, and that higher socioeconomic position in either generation enhances intergenerational associations of ideal health behaviors. Design Prospective cohort study. Methods We included 1856 Young Finns Study participants who had repeated measurements of socioeconomic position (education, income, occupation), smoking status, body mass index, physical activity and diet from 2001, 2007 and 2011, and data on parental socioeconomic position and health behaviors from 1980. We calculated the total number of ideal behaviors in both generations using American Heart Association definitions. Intergenerational associations were examined using ordinal and linear multilevel regression with random intercepts, in which each participant contributed one, two or three measurements of adult health behaviors (2001, 2007, 2011). All analyses were adjusted for offspring sex, birth year, age, parental education and single parenthood. Results Overall, parental ideal health behaviors were associated with ideal behaviors among offspring (odds ratio (OR) 1.28, 95% confidence interval 1.17, 1.39). Furthermore, ORs for these intergenerational associations were greater among offspring whose parents or who themselves had higher educational attainment (OR 1.56 for high vs. OR 1.19 for low parental education; P = 0.01 for interaction, OR 1.32 for high vs. OR 1.04 for low offspring education; P = 0.02 for interaction). Similar trends were seen with parental income and offspring occupation. Results from linear regression analyses were similar. Conclusions These prospective data suggest higher socioeconomic position in parents or in their adult offspring strengthens the intergenerational continuum of ideal cardiovascular health behaviors.

Chronic obstructive pulmonary disease (COPD) is characterized by airflow obstruction and often co-exists with cardiovascular disease (CVD), hypertension and diabetes. This international study assessed the association between airflow obstruction and these comorbidities. 23,623 participants (47.5% males, 19.0% current smokers, age: 55.1 +/- 10.8 years) in 33 centers in the Burden of Obstructive Lung Disease (BOLD) initiative were included. 10.4% of subjects had airflow obstruction. Self-reports of physician-diagnosed CVD (heart disease or stroke), hypertension and diabetes were regressed against airflow obstruction (post-bronchodilator FEV1/FVC

Objective: Increased arterial stiffness measured by pulse wave velocity (PWV) has been shown to be an important parameter of cardiovascular risk. Longitudinal development of PWV from youth to early adulthood and its possible sociodemographic, anthropometric, hemodynamic and behavioral moderators will be illustrated.Methods: Individual growth curves of carotid-distal PWV across age were created for 559 African American and European American men and women with a maximum of five assessments over an average of 7-year follow-up (mean age at participants' first assessment, 22.3 +/- 3.4).Results: African Americans and men had significantly higher PWV than did European Americans and women (PsConclusion: We observed significant ethnic and sex differences in longitudinal trajectories of PWV in youth and young adults. In addition, individual differences in PWV growth can largely be explained by mean arterial pressure, waist, marital status of parents and marijuana use.

Background\ud Rural-to-urban migration is associated with increased obesity, yet it remains unknown whether this association exist, and to what extent, with other types of internal migration.\ud \ud Methods\ud We conducted a secondary analysis of the Peruvian Demographic and Health Surveys (2005 to 2012) on data collected from women aged 15–49 years. Participants were classified as rural stayers, urban stayers, rural-to-urban migrants, intra-rural migrants, intra-urban migrants, and urban-to-rural migrants. Marginal effects from a logit regression model were used to assess the probabilities of being and becoming obese given both the length of time in current place of residence and women’s migration status.\ud \ud Results\ud Analysis of cross-sectional survey data generated between 2005 and 2012. Data from 94,783 participants was analyzed. Intra-urban migrants and rural-to-urban migrants had the highest rates of obesity (21% in 2012). A steady increase in obesity is observed across all migration statuses. Relative to rural non-migrants, participants exposed to urban environments had greater odds, two- to three-fold higher, of obesity. The intra-rural migrant group also shows higher odds relative to rural stayers (42% higher obesity odds). The length of exposure to urban settings shows a steady effect over time.\ud \ud Conclusion\ud Both exposure to urban environments and migration are associated with higher odds of obesity. Expanding the characterization of within-country migration dynamics provides a better insight into the relationship between duration of exposure to urban settings and obesity.

Childhood blood pressure (BP) levels predict adult subclinical atherosclerosis. However, the best childhood BP component for prediction has not been determined. This study comprised 5925 participants aged 3 to 18 years from 6 cohorts who were followed into adulthood (mean follow-up 25.8±6.2 years). Childhood BP was measured by using a standard mercury sphygmomanometer in all cohorts. Study-specific carotid intima-media thickness ≥90th percentile was used to define subclinical atherosclerosis. Per SD change in the predictor, childhood systolic BP (SBP; age- and sex-adjusted odds ratio [95% CI], 1.24 [1.13–1.37]), mean arterial pressure (1.10 [1.07–1.13]), and pulse pressure (1.15 [1.05–1.27]) were associated with increased adulthood intima-media thickness. In age- and sex-adjusted analyses, area under the receiver operating characteristic curves for SBP ( C value [95% CI], 0.677 [0.657–0.704]) showed significantly improved prediction compared with diastolic BP (0.669 [0.646–0.693], P =0.006) or mean arterial pressure (0.674 [0.653–0.699], P =0.01). Pulse pressure provided a C value that was not different from SBP (0.676 [0.653–0.699], P =0.16). Combining different BP components did not improve prediction over SBP measurement alone. Based on the associations with adult carotid intima-media thickness, cut points for elevated SBP were 105 mm Hg for 3- to 6-year-old boys, 108 mm Hg for 3- to 6-year-old girls, 108 mm Hg for 7- to 12-year-old boys, 106 mm Hg for 7- to 12-year-old girls, 123 mm Hg for 13- to 18-year-old boys, and 115 mm Hg for 13- to 18-year-old girls. Our analyses suggest that several childhood BP measurement components are related to adulthood carotid intima-media thickness. Of these, SBP provided the best predictive ability.

Results of intervention studies on the effects ofα-linolenic acid (ALA; C18 : 3n-3) on blood pressure (BP) are conflicting. Discrepancies between studies may be due to differences in study population, as subjects with increased baseline BP levels may be more responsive. Therefore, we examined specifically the effects of ALA on 24-h ambulatory blood pressure (ABP) in (pre-)hypertensive subjects. In a double-blind, randomised, placebo-controlled parallel study, fifty-nine overweight and obese adults (forty males and nineteen females) with (pre-)hypertension (mean age of 60 (sd8) years) received daily 10 g refined cold-pressed flaxseed oil, providing 4·7 g (approximately 2 % of energy) ALA (n29) or 10 g of high-oleic sunflower oil as control (n30) for 12 weeks. Compliance was excellent as indicated by vial count and plasma phospholipid fatty-acid composition. Compared with control, the changes of –1·4 mmHg in mean arterial pressure (MAP; 24 h ABP) after flaxseed oil intake (95 % CI –4·8, 2·0 mmHg,P=0·40) of –1·5 mmHg in systolic BP (95 % CI –6·0, 3·0 mmHg,P=0·51) and of –1·4 mmHg in diastolic BP (95 % CI –4·2, 1·4 mmHg,P=0·31) were not statistically significant. Also, no effects were found for office BP and for MAP, systolic BP, and diastolic BP when daytime and night-time BP were analysed separately and for night-time dipping. In conclusion, high intake of ALA, about 3–5 times recommended daily intakes, for 12 weeks does not significantly affect BP in subjects with (pre-)hypertension.

Background: Weight gain and obesity can increase liver transplant (LTx) recipients' disease burden. We aimed to summarize and synthesize the evidence on pre- and post-transplant factors related to post-LTx BMI, weight gain, and obesity. Methods: For this systematic review and meta-analysis we searched Medline (PubMed), Cochrane library, CINAHL, PsycINFO, and EMBASE for quantitative studies on 6 classes of factors (i.e., genetic, sociodemographic, behavioral, biomedical, psychological, and environmental) linked to body weight parameters in adult first-time LTx patients. A 19-item instrument was used for quality assessment. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for relationships investigated in >= 5 studies. Factors investigated in Results: Of 16,495 articles retrieved, 43 assessed factors in LTx. These examined 82 mainly biomedical and sociodemographic factors. However, variation between definitions allowed inclusion of only 2 factors (i.e., tacrolimus, cyclosporine) in our meta-analyses of 6 studies examining a shared parameter for body weight (median patient sample: 171 (range: 63-455); Europe n = 3; United States n = 3; publication years: 1997-2015). Neither tacrolimus (OR, 0.75; 95% CI, 0.47-1.21; p = 0.24) nor cyclosporine (OR, 1.40; 95% CI, 0.89-2.18; p = 0.14) were related significantly with post-LTx obesity. Conclusions: Evidence on modifiable factors related to post-LTx body weight parameters is still scarce, as definition variability limits data extraction and pooling for meta-analyses. To facilitate future research, studies should apply theoretical frameworks to guide their study design, select variables of interest and systematically examine interrelationships among selected factors. (C) 2018 Published by Elsevier Inc.