Cardiovascular disease in Alpha 1 antitrypsin deficiency: an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools.

BACKGROUND: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development. RESULTS: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment. CONCLUSION: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD.

Relationship between addictions and obesity, physical activity and vascular aging in young adults (EVA-Adic study): a research protocol of a cross-sectional study.

Background: Behavioral and substance addictions are prevalent health problems that, alongside obesity, are linked to reduced physical activity and increased sedentary time. Similarly, arterial stiffness and vascular aging are processes that begin gradually at an early age and are closely associated with morbidity and mortality from cardiovascular diseases. The main objective of this study is to analyze how addictions are related to obesity and body fat distribution, physical activity, sedentary time, arterial stiffness and vascular aging, as well as sleep quality, cognitive function and gender differences in young adults aged between 18 and 34 years. Methods: This cross-sectional descriptive observational study will analyze data from 500 subjects (250 men and 250 women) aged 18-34 without cardiovascular disease, selected by simple random sampling with replacement from the urban population of the city center of Salamanca (34,044 people aged 18-34, with 18,450 women and 15,594 men). Behavioral and substance addictions, as well as sleep quality and cognitive impairment will be assessed using questionnaires. The Pittisburg Sleep Quality Index (PSQI) will be used to measure sleep quality and the Ford questionnaire will be used to measure insomnia in response to stress. For obesity, weight, height, waist and hip circumference, body composition will be measured with the Inbody 230® impedance meter. For physical activity and sedentary time, we will use the Actigraph® accelerometer alongside the international physical activity questionnaire (IPAQ) and the Marshall questionnaire. The Sphygmocor System® will be used for pulse wave analysis and carotid-femoral pulse wave velocity (cfPWV), while the Vasera VS-2000® will measure cardio ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV). Vascular aging will be calculated with the 10th and 90th percentiles of cfPWV or baPWV. Demographic, analytical variables will be collected, as will data to assess vascular, cardiac, renal, and brain injury. Discussion: Addictions are on the rise in today's society, affecting the mental health and well-being of those who suffer from them, generating important social problems such as job loss, family dysfunction, debt and social isolation. Together with obesity, they are prevalent health problems in young adults and are associated with lower physical activity and higher sedentary time. Meanwhile, arterial stiffness and vascular aging are processes that begin gradually at an early age and determine morbidity and mortality caused by cardiovascular diseases. The results of this project will allow us to understand the situation regarding behavioral and substance addictions in young adults. Better understanding of these addictions will in turn facilitate the development of more effective prevention strategies and intervention programs, which can then reduce the negative impact at both the individual and societal levels. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT05819840].

Gender-related differences in cardiometabolic risk factors and oxidative stress among prepubertal children with obesity.

OBJECTIVES: Gender-related differences in oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors were examined in a cross-sectional study involving 313 prepubertal children (8-9 years old) from the generation XXI birth-cohort. METHODS: Anthropometric measurements, cardiometabolic variables, and redox markers were assessed, including plasma and urinary isoprostanes (P-Isop, U-Isop), plasma total antioxidant status (P-TAS), serum myeloperoxidase (MPO), plasma and urinary nitrates and nitrites (P-NOX, U-NOX), and urinary hydrogen peroxide (U-H2O2). RESULTS: Girls showed higher levels of total/non-HDL cholesterol, triglycerides, and insulin resistance (HOMA-IR) compared to boys. Notably, U-H2O2 values were lower in girls. When stratifying by body mass index (BMI) and gender, both girls and boys exhibited higher MPO concentration and U-Isop values. Uric acid concentration was higher in overweight and obese girls than in normal weight girls, while no significant differences were observed among boys across BMI categories. Furthermore, U-NOX values differed only in boys, with higher levels observed in overweight and obese individuals compared to those with normal weight. Multivariate analysis, adjusted for age and BMI z-score, demonstrated inverse associations between U-H2O2 and pulse wave velocity values, as well as between U-NOX and total or non-HDL cholesterol, exclusively in boys. In girls, a positive association between U-Isop and HOMA-IR values was observed. CONCLUSIONS: In conclusion, gender differentially impacts oxidative stress, nitric oxide bioavailability, and cardiometabolic risk factors in prepubertal children. Prepubertal girls appear more susceptible to oxidative stress-induced metabolic dysfunction, while in boys, elevated levels of redox and nitric oxide bioavailability markers seem to provide protection against arterial stiffness and lipid homeostasis.

Evaluation of changes in glycemic control and diabetic complications over time and factors associated with the progression of diabetic complications in Japanese patients with juvenile-onset type 1 diabetes mellitus.

BACKGROUND: This study aimed to evaluate the changes in glycemic control and diabetic complications over time in Japanese patients with juvenile-onset type 1 diabetes mellitus and to clarify the factors associated with the progression of diabetic complications. METHODS: We tracked 129 patients with type 1 diabetes mellitus (21.8 ± 4.1 years old [mean ± SD] with a diabetes duration of 12.6 ± 5.7 years) for up to 19 years and analyzed data on glycated hemoglobin (HbA1c) and indicators related to the severity of diabetic complications (estimated glomerular filtration rate [eGFR], urinary albumin excretion rate [UAE], carotid intima-media thickness [CIMT], and brachial-ankle pulse wave velocity [baPWV]) using linear mixed model and decision tree analysis. RESULTS: Although the HbA1c and UAE levels improved over time, the eGFR, CIMT, and baPWV worsened. Decision tree analysis showed that HbA1c and the glycoalbumin/HbA1c ratio for eGFR; HbA1c and systolic blood pressure for UAE; low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio, glycoalbumin/HbA1c ratio, and body mass index (BMI) for CIMT; and HbA1c for baPWV were associated factors. CONCLUSIONS: In this retrospective observational study, glycemic control and albuminuria improved; however, renal function and arteriosclerosis worsened over time. HbA1c levels, glycemic excursion, and blood pressure are associated with nephropathy progression. HbA1c levels, glycemic excursion, lipid levels, and BMI are associated with the progression of atherosclerosis.

Lack of Association between Serum Chitotriosidase Activity and Arterial Stiffness in Type 2 Diabetes without Cardiovascular Complications.

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6-17.9] vs. 11.4 [8.8-15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle-brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD.

Non-albumin proteinuria marks tubular involvement and is associated with arterial stiffness in subjects affected by severe obesity.

INTRODUCTION: Obesity is a well-established risk factor for kidney disease, and tubular damage can play a pivotal role in the development of obesity-related kidney damage. This study aimed to investigate the pathophysiological pathways involved in the development of non-albumin proteinuria (NAP), a marker of tubular involvement, in a cohort of subjects with severe obesity and preserved kidney function. METHODS: A total of 106 subjects with BMI ≥ 35 kg/m2 in waiting list for bariatric surgery underwent blood chemistry analysis including metabolic and lipid profile, vascular tests for cardiovascular risk stratification and a comprehensive assessment of kidney function, including renal resistive index (RRI) and NAP measurement. RESULTS: Nineteen patients with ACR ≥ 30 mg/g regardless of NAP values (ALB+), nineteen with NAP≥ 150 mg/g and albuminuria < 30 mg/g (iNAP) and sixty-eight without proteinuria (No-P) were found. Both ALB+ and iNAP groups exhibited a higher prevalence of hypertension and anti-hypertensive treatment compared to No-P, while the prevalence of diabetes was similar between groups. Concerning lipid profile, no differences in total, HDL and LDL cholesterol were found, while ALB+ patients had higher serum triglyceride levels than the other two groups. RRI and carotid-femoral pulse wave velocity (cf-PWV) was significantly higher in ALB+ and iNAP groups compared to No-P. Remarkably, cf-PWV remained still significant after adjustment for age, sex and MBP (p = 0.0004). In overall population, a multiple regression analysis showed that cf-PWV was an independent determinant of NAP in a model including age, sex, glycated hemoglobin, systolic and mean blood pressure (R2 =0.17, p = 0.031). CONCLUSION: iNAP subjects showed increased arterial stiffness comparable to that observed in ALB+ group, suggesting that they may represent a subgroup at higher cardiovascular risk, often unrecognized in clinical practice.

Pivotal trial of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from CMERC-HI.

OBJECTIVE: The potential of using retinal images as a biomarker of cardiovascular disease (CVD) risk has gained significant attention, but regulatory approval of such artificial intelligence (AI) algorithms is lacking. In this regulated pivotal trial, we validated the efficacy of Reti-CVD, an AI-Software as a Medical Device (AI-SaMD), that utilizes retinal images to stratify CVD risk. MATERIALS AND METHODS: In this retrospective study, we used data from the Cardiovascular and Metabolic Diseases Etiology Research Center-High Risk (CMERC-HI) Cohort. Cox proportional hazard model was used to estimate hazard ratio (HR) trend across the 3-tier CVD risk groups (low-, moderate-, and high-risk) according to Reti-CVD in prediction of CVD events. The cardiac computed tomography-measured coronary artery calcium (CAC), carotid intima-media thickness (CIMT), and brachial-ankle pulse wave velocity (baPWV) were compared to Reti-CVD. RESULTS: A total of 1106 participants were included, with 33 (3.0%) participants experiencing CVD events over 5 years; the Reti-CVD-defined risk groups (low, moderate, and high) were significantly associated with increased CVD risk (HR trend, 2.02; 95% CI, 1.26-3.24). When all variables of Reti-CVD, CAC, CIMT, baPWV, and other traditional risk factors were incorporated into one Cox model, the Reti-CVD risk groups were only significantly associated with increased CVD risk (HR = 2.40 [0.82-7.03] in moderate risk and HR = 3.56 [1.34-9.51] in high risk using low-risk as a reference). DISCUSSION: This regulated pivotal study validated an AI-SaMD, retinal image-based, personalized CVD risk scoring system (Reti-CVD). CONCLUSION: These results led the Korean regulatory body to authorize Reti-CVD.

Prevalence of Pediatric Masked Hypertension and Risk of Subclinical Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

Masked hypertension (MH) occurs when office blood pressure is normal, but hypertension is confirmed using out-of-office blood pressure measures. Hypertension is a risk factor for subclinical cardiovascular outcomes, including left ventricular hypertrophy, increased left ventricular mass index, carotid intima media thickness, and pulse wave velocity. However, the risk factors for ambulatory blood pressure monitoring defined MH and its association with subclinical cardiovascular outcomes are unclear. A systematic literature search on 9 databases included English publications from 1974 to 2023. Pediatric MH prevalence was stratified by disease comorbidities and compared with the general pediatric population. We also compared the prevalence of left ventricular hypertrophy, and mean differences in left ventricular mass index, carotid intima media thickness, and pulse wave velocity between MH versus normotensive pediatric patients. Of 2199 screened studies, 136 studies (n=28 612; ages 4-25 years) were included. The prevalence of MH in the general pediatric population was 10.4% (95% CI, 8.00-12.80). Compared with the general pediatric population, the risk ratio (RR) of MH was significantly greater in children with coarctation of the aorta (RR, 1.91), solid-organ or stem-cell transplant (RR, 2.34), chronic kidney disease (RR, 2.44), and sickle cell disease (RR, 1.33). MH patients had increased risk of subclinical cardiovascular outcomes compared with normotensive patients, including higher left ventricular mass index (mean difference, 3.86 g/m2.7 [95% CI, 2.51-5.22]), left ventricular hypertrophy (odds ratio, 2.44 [95% CI, 1.50-3.96]), and higher pulse wave velocity (mean difference, 0.30 m/s [95% CI, 0.14-0.45]). The prevalence of MH is significantly elevated among children with various comorbidities. Children with MH have evidence of subclinical cardiovascular outcomes, which increases their risk of long-term cardiovascular disease.

Hypertension-Mediated Organ Damage In Young Patients With First-Diagnosed And Never Treated Systolic Hypertension.

OBJECTIVE: Early onset of untreated arterial hypertension is associated with an increased risk for cardiovascular (CV) diseases. The evaluation of hypertension-mediated organ damage (HMOD) helps estimating CV risk. We investigated the incidence of HMOD in young first, diagnosed and nevertreated patients with systolic arterial hypertension (SH) to identify high CV-risk patients based on the presence of HMOD. METHODS: CV risk factors [smoking, obesity (body mass index, BMI)], hyperlipidemia and 5 HMODs [arterial stiffness (pulse wave velocity, PWV), left ventricular diastolic dysfunction [(DD (E/Ea)], cardiac hypertrophy (left ventricular mass index, LVMI), coronary artery microcirculation (CFR), and carotid intima-media thickness (cIMT)] were evaluated before treatment initiation in 220 patients, aged ≤50 years [median (interquartile range, IQR) age=43(38-47)], with SH diagnosed by ambulatory blood pressure monitoring (24-h ABPM). RESULTS: Smoking (40%) and obesity [median (IQR) BMI=30(26-32) kg/m2](40%) were found in young hypertensives. HMOD was found in 50% of hypertensives (10% had ≥2 HMOD). The most prevalent HMODs were increased by cIMT (32%) and PWV (19%), LVH (9%), impaired CFR (6%) and DD (1%). Only PWV (beta=0.27, p<0.001) and LVMI (beta=0.41, p<0.001) were associated with systolic BP burden. In a subgroup analysis, patients with ≥2 HMOD were older with increased office BP and 24- h ABPM, impaired lipid profile, and increased LVMI, PWV, CFR, and cIMT compared with the rest of the hypertensives. CONCLUSION: The presence of ≥2 of the studied HMOD (PWV, LVMI, cIMT, E/Ea, CFR) in young hypertensives characterizes a "high-risk population". Arterial stiffness represents the predominant HMOD and in the whole population and "high-risk population".

Effect of bariatric surgery on NAFLD/NASH: a single-centre observational prospective cohort study.

INTRODUCTION: The prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 25% in the general population to 90% in patients with obesity scheduled for bariatric surgery. NAFLD can progress towards non-alcoholic steatohepatitis (NASH) associated with complications such as cirrhosis, hepatocellular carcinoma and cardiovascular disease. To date, losing weight and lifestyle modifications are the best known treatments for NASH. Bariatric surgery significantly improves NAFLD/NASH in the short term. However, the extent of this improvement is not yet clear and long-term data on the natural course of NAFLD/NASH after bariatric surgery are lacking. The factors involved in NAFLD/NASH regression after bariatric surgery have not been elucidated. METHODS AND ANALYSIS: This is an observational prospective cohort study including patients scheduled for bariatric surgery. Extensive metabolic and cardiovascular analyses will be carried out including measurements of carotid intima media thickness and pulse wave velocity. Genomic, proteomic, lipidomic and metabolomic studies will be done. Microbioma analyses before and 1 year after surgery will be done. Transient elastography measurements will be performed before and at 1, 3 and 5 years after surgery. For those with an elevated preoperative transient elastography measurement by Fibroscan, a laparoscopic liver biopsy will be performed during surgery. Primary outcome measures are the change of steatosis and liver fibrosis 5 years after surgery. Secondary outcome measure is the comparison of the transient elastography measurements with the NAFLD Activity Score from the biopsies. ETHICS AND DISSEMINATION: The protocol has been approved by the Medical Research Ethics Committees United, Nieuwegein, on 1 March 2022 (registration code R21.103/NL79423.100.21). The study results will be submitted for publication in peer-reviewed journals and data will be presented at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05499949.

The incidence of subclinical atherosclerosis in subjects with low and moderate cardiovascular risk.

BACKGROUND: The cardiovascular risk models and subclinical atherosclerotic indicators are both recommended for cardiovascular risk stratification. The accordance between the incidence of subclinical atherosclerosis and subjects with low and moderate cardiovascular risk is unclear. HYPOTHESIS: Subjects with low and moderate cardiovascular risk have a lower incidence of subclinical atherosclerosis compared with subjects with high risk. METHODS: Brachial-ankle pulse wave velocity (BaPWV) and brachial flow-mediated dilation (BFMD) were measured in 421 subjects without a history of atherosclerotic cardiovascular disease (ASCVD) from October 2016 to January 2020. All subjects were classified into low, moderate, and high risk based on Framingham and China-par risk models respectively. RESULTS: Mean age was 57.05 ± 9.35 years and 248 (58.9%) were male. In subjects with low, moderate, and high risk assessed by Framingham and China-par risk models, the percentage of abnormal BaPWV ( > 1400 cm/s) was 42.9%, 70.1%, 85.7%, and 40.4%, 71.4%, 89.7%, respectively. Meanwhile, the percentage of abnormal BFMD ( ≤ 7%) was 43.8%, 68.5%, 77.3%, and 44.9%,72.1%, and 76.6%. According to Framingham-based high-risk categories, positive predictive value (PPV), negative predictive value (NPV), sensitivity and specificity for BaPWV abnormality were 85.7%, 39.4%, 36.1%, and 87.5%, respectively. For BFMD abnormality, the values were 77.3%, 40.1%, 34.1%, and 81.8%, respectively. According to China-par high-risk categories, the values for BaPWV abnormality were 89.7%, 43.8%, 45.6%, and 89.0%, respectively. For BFMD abnormality, the values were 76.6%, 41.3%, 40.7%, and 77%, respectively. In multivariate analysis, age and blood pressure were the independent predictors for subclinical atherosclerosis in subjects with low-moderate risk. CONCLUSIONS: More than one-half of subjects with low and moderate risk already have detectable subclinical atherosclerosis, indicating higher cardiovascular risk beyond the traditional stratification.

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

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

Pulse Wave Analysis in Obese Children with and without Metabolic Syndrome

Objective: To compare pulse wave analysis (PWA) of obese children with and without metabolic syndrome (MS) with healthy, non-obese children and to evaluate the association between PWA findings and additional risk factors present in children with MS and obesity. Methods: From the obese patients examined between June 2019 and June 2021, 41 patients with MS, 36 obese patients without MS, and 34 healthy non-obese children of similar age and gender were evaluated retrospectively. Anthropometric measurements, biochemical evaluation, 24-hour ambulatory blood pressure (BP) measurement (ABPM), left ventricular mass index (LVMI) and PWA measurements were compared. Results: When the three groups were compared, weight standard deviation score (SDS), height SDS and body mass index SDS were all significantly higher in the MS group (p<0.05). The following measurements were significantly higher in both MS and non-MS obese patients compared to the control group: from ABPM measures, the systolic and mean arterial pressure BP SDSs load; from PWA, the night central systolic BP, 24-hour, day and night pulse pressure values and 24-hour, day and night pulse wave velocity (PWV) rates; and from cardiac evaluations, the LVMI and relative wall thickness measurements (all p<0.05). Furthermore, the 24-hour and daytime central systolic (cSBP) and diastolic BP (cDBP) values were significantly different between the three groups, being the highest in the MS group (p<0.05). Conclusion: Obesity causes higher office, ambulatory and central BP, PWV and LVMI. However our results suggest that additional risk factors associated with MS do not contribute to these parameters, except for 24-hour and daytime cSBP and cDBP values.

A Comparative Study on the Presence and Reversibility of Subclinical Arterial Damage in HCV-Infected Individuals and Matched Controls.

Background: The arterial pathology and mechanisms of increased cardiovascular disease (CVD) risk in HCV-infected individuals are not yet clear. The aim of this study was to identify types of arterial pathology in treatment-naive chronic HCV patients and to test their reversibility after successful treatment. Methods: Consecutive, never-treated, HCV-infected patients were compared with age and CVD-related risk factors, matched controls, healthy individuals (HI), patients with rheumatoid arthritis (RA) and people living with HIV (PLWH), in terms of arterial stiffening by pulse wave velocity, arterial atheromatosis/hypertrophy by carotid plaques/intima-media thickness and impaired pressure wave reflections by augmentation index. After three months of sustained virological response (SVR) administered using direct-acting antivirals, vascular examination was repeated in HCV-infected patients to test drug and viral-elimination effect in subclinical CVD. Results: Thirty HCV patients were examined at baseline; fourteen of them were re-examined post-SVR. Compared with HI, HCV patients had significantly more plaques, which is similar to that of RA patients and the PLWH group. No other differences were found in all other vascular biomarkers, and regression among HCV patients also revealed no differences 3 months post-SVR. Conclusions: Accelerated atheromatosis, rather than arterial stiffening, arterial remodeling and peripheral impaired hemodynamics is the underlying pathology leading to increased CVD risk in HCV patients.

Birth conditions nutritional status in childhood associated with cardiometabolic risk factors at 30 years of age: a cohort study.

This study aimed to assess the association of birth conditions, nutritional status, and childhood growth with cardiometabolic risk factors at 30 years of age. We also evaluated whether body mass index (BMI) at 30 years mediated the association of weight gain in childhood with cardiometabolic risk factors. This is a prospective cohort study that included all live births in 1982 in hospitals in the city of Pelotas, Rio Grande do Sul State, Brazil, whose families lived in the urban area. Mothers were interviewed at birth, and participants were followed at different ages. For our analyses, we used data on weight and height collected at birth, 2 and 4 years and cardiovascular risk factors at 30 years. Multiple linear regressions were performed to obtain adjusted coefficients and G-formula for mediation analysis. Relative weight gain in childhood, despite the age, was positively related to mean arterial pressure, whereas relative weight gain in late childhood was positively associated with carotid intima-media thickness, pulse wave velocity, triglycerides, non-HDL cholesterol, plasma glucose, and C-reactive protein. BMI in adulthood captured the total effect of relative weight gain in the period between 2 and 4 years on carotid intima-media thickness, triglycerides, non-HDL cholesterol, and C-reactive protein. Our findings reinforce the evidence that rapid relative weight gain after 2 years of age may have long-term consequences on the risk of metabolic and cardiovascular disorders.

Reduction of arterial stiffness in depressive individuals responding to multimodal treatment.

BACKGROUND: Depressive individuals are at higher risk for cardiovascular diseases (CVD). Thus, cardiovascular parameters such as arterial stiffness, often measured by pulse wave velocity (PWV), should be monitored. Recent research indicated that depressive individuals exhibit higher PWV, but there is little data on the changeability of PWV through multimodal treatment. This study investigated PWV in moderately to severe depressive individuals before and after undergoing treatment in dependence on responding or not responding to treatment. METHODS: 47 participants (31 females, 16 males) underwent a PWV measurement and filled out a questionnaire surveying depressive symptom severity before and after a six-week psychiatric rehabilitation treatment including multimodal interventions. Subjects were divided in responders and non-responders, depending on their treatment success. RESULTS: A mixed ANCOVA analysis indicated no significant main effect of responder status, but a significant main effect of measurement time and a significant interaction between responder status and measurement time. Responders exhibited a significant decrease in PWV across time, while no significant change in PWV across time was found for non-responders. LIMITATIONS: Results are limited by the lack of a control group. The influence of medication duration or medication type was not considered in the analyses. Causality of the relationship between PWV and depression cannot be determined. CONCLUSION: These findings show that PWV can be positively modified in depressive individuals responding to treatment. This effect cannot solely be attributed to pharmacological interventions but rather the combination of multimodal interventions, thus highlighting the clinical relevance of multimodal treatment in depression and comorbid disorders.

Arterial stiffness and subclinical atherosclerosis in the coronary arteries at different stages of dysglycaemia.

AIM: Our aim was to investigate in a large population-based cohort study whether increased arterial stiffness and subclinical atherosclerosis in the coronary arteries differ at different stages of dysglycaemia. METHODS: Data were obtained from SCAPIS, a population-based cohort of participants 50-64 years. The study population of 9379 participants was categorised according to glycaemic status: normoglycaemic, pre-diabetes (fasting glucose: 6.1-6.9 mmol/L and/or HbA1c 6%-6.4%) and diabetes. Pulse wave velocity (PWV) was measured by the SphygmoCor XCEL system and arterial stiffness was defined by PWV ≥10 m/s. Coronary artery calcium score (CACS) was assessed by coronary computed tomography and coronary artery calcification was defined by CACS ≥100. RESULTS: We identified 1964 (21%) participants with dysglycaemia, out of which 742 (7.9%) had diabetes mellitus. PWV ≥10 m/s was present in 808 (11%), 191 (16%), 200 (27%) and CACS ≥100 in 801 (11%), 190 (16%), 191 (28%) participants with normoglycaemia, pre-diabetes and diabetes, respectively, all, p < 0.001. The overlap between PWV ≥10 m/s and CACS ≥100 within each glycaemic category was 188 (2.5%), 44 (3.6%) and 77 (10) respectively. There was an association between glycaemic status and increased PWV in the fully adjusted models, but not for glycaemic status and CACS ≥100, where there was no difference for pre-diabetes compared to normoglycaemia, OR 1.2 (95% CI 0.98-1.4). In the total study population, there was an association between HbA1c and PWV after adjustment, p < 0.001. CONCLUSIONS: Our results show that increased arterial stiffness and subclinical coronary artery atherosclerosis are present in the early stages of dysglycaemia, but the overlap between markers of major subclinical vascular damage was small in all glycaemic categories. This could be explained by different pathways in the pathogenesis of arterial stiffness or atherosclerosis in the coronary arteries.

Markers of arterial stiffness and urinary metabolomics in young adults with early cardiovascular risk: the African-PREDICT study.

INTRODUCTION: Increased exposure to risk factors in the young and healthy contributes to arterial changes, which may be accompanied by an altered metabolism. OBJECTIVES: To increase our understanding of early metabolic alterations and how they associate with markers of arterial stiffness, we profiled urinary metabolites in young adults with cardiovascular disease (CVD) risk factor(s) and in a control group without CVD risk factors. METHODS: We included healthy black and white women and men (N = 1202), aged 20-30 years with a detailed CVD risk factor profile, reflecting obesity, physical inactivity, smoking, excessive alcohol intake, masked hypertension, hyperglycemia, dyslipidemia and low socio-economic status, forming the CVD risk group (N = 1036) and the control group (N = 166). Markers of arterial stiffness, central systolic blood pressure (BP) and pulse wave velocity were measured. A targeted metabolomics approach was followed by measuring amino acids and acylcarnitines using a liquid chromatography-tandem mass spectrometry method. RESULTS: In the CVD risk group, central systolic BP (adjusted for age, sex, ethnicity) was negatively associated with histidine, arginine, asparagine, serine, glutamine, dimethylglycine, threonine, GABA, proline, methionine, pyroglutamic acid, aspartic acid, glutamic acid, branched chain amino acids (BCAAs) and butyrylcarnitine (all P ≤ 0.048). In the same group, pulse wave velocity (adjusted for age, sex, ethnicity, mean arterial pressure) was negatively associated with histidine, lysine, threonine, 2-aminoadipic acid, BCAAs and aromatic amino acids (AAAs) (all P ≤ 0.044). In the control group, central systolic BP was negatively associated with pyroglutamic acid, glutamic acid and dodecanoylcarnitine (all P ≤ 0.033). CONCLUSION: In a group with increased CVD risk, markers of arterial stiffness were negatively associated with metabolites related to AAA and BCAA as well as energy metabolism and oxidative stress. Our findings may suggest that metabolic adaptations may be at play in response to increased CVD risk to maintain cardiovascular integrity.

Long-term cardiovascular consequences of adolescent anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is associated with maladaptive cardiovascular changes. This study investigated whether individuals who recovered from AN during adolescence experience long-term cardiovascular risk in early adulthood. METHODS: Former AN patients discharged from the Royal Children's and Monash Children's Hospital Eating Disorder Services in Melbourne, Australia underwent cardiovascular testing. Measurements were performed using an oscillometric device for blood pressure and pulse wave velocity, ultrasound for carotid wall structure/function, resting electrocardiogram for heart-rate variability, and the EndoPat 2000 (Itamar) system for endothelial function. Patient measures were compared to healthy controls and/or normal thresholds. RESULTS: Ninety-one percent of the former AN patients (N = 22) and controls (N = 66) were female, aged approximately 25 years, with a healthy body mass index. The mean time interval from AN recovery to participation was 7.4 years. Pulse wave velocity was lower in the former AN patients than controls. Carotid intima-media thickness was not different; however, carotid distensibility and compliance were lower, and the elastic modulus higher in the former AN patients. Greater vagal tone was observed and endothelial dysfunction was evident in 46% of the former patients. CONCLUSIONS: Young adults who recovered from adolescent AN exhibit persistent cardiovascular adaptations. Routine cardiovascular monitoring could manage potential disease risk. IMPACT: Cardiovascular complications are common in patients with anorexia nervosa (AN) and population studies have revealed that developmental adaptations in response to undernutrition have long-term consequences for cardiovascular health. In this study of young adults treated for AN during adolescence, there was evidence of increased carotid artery stiffness, reduced aortic stiffness, vagal hyperactivity, and endothelial dysfunction in early adulthood when compared to healthy controls. It is important to consider the cardiovascular health of patients with AN beyond achieving medical stability. Interventions that monitor cardiovascular health could minimise the burden of future cardiovascular disease.

Arterial Stiffness as a Predictor of the Index of Atherosclerotic Cardiovascular Disease in Hypertensive Patients.

OBJECTIVE: The aim of this study was to evaluate the predictive value of carotid-femoral pulse wave velocity (cfPWV) and cardiovascular disease in the hypertensive population in China and to determine the specific cfPWV cut-off value for assessing future cardiovascular disease (CVD) risk. METHODS: This cross-sectional study included 630 hospital patients with primary hypertension and multiple cardiovascular risk factors or complications involving damage to clinical target organs. The study was conducted between July 2007 and October 2008. Atherosclerotic cardiovascular disease (ASCVD) risk calculations were computed according to criteria presented by the American College of Cardiology and the American Heart Association. Patients were stratified by a predefined risk threshold of 10% and divided into two groups: ASCVD ≥ 10% or ASCVD < 10%. cfPWV was used as a marker of arterial stiffness. A receiver operating characteristics (ROC) curve was applied to establish the optimal cfPWV cut-off point to differentiate between participants with and without ASCVD risk. RESULTS: In the study cohort of 630 patients (age 63.55.2 ± 8.6 years, 61.7% male) with primary hypertension, the pressure indices (augmented pressure, augmentation index [AIx], aortic pulse pressure, aortic systolic pressure [SBP]) and Framingham Risk Scores (FRS) were greater in females than in males (p < 0.001); ASCVD risk scores and peripheral diastolic pressure (DBP) were higher in males (p < 0.05). All hemodynamic indices showed a significant positive correlation with ASCVD risk scores and FRS; AIx was not correlated with ASCVD risk scores. In multivariate logistic analysis, cfPWV was significantly associated with ASCVD risk (OR: 1.324, 95% confidence interval: 1.119-1.565, p < 0.001) after adjusting for age, gender, smoking, body mass index, total cholesterol, fasting blood glucose, antihypertensive treatment, statin treatment, and DBP. In the ROC analysis, the area under the curve was 0.758 and 0.672 for cfPWV and aortic SBP (p < 0.001 and p < 0.001, respectively); the optimal critical value of cfPWV and aortic SBP was 12.45 m/s (sensitivity 63.2%, specificity 77.8%) and 124.5 mmHg (sensitivity 63.9%, specificity 65.3%). CONCLUSIONS: cfPWV is significantly correlated with the risk of ASCVD. The best cut-off value of cfPWV for assessing future CVD risk in the hypertensive population in China is 12.45 m/s.