Integrated Central Blood Pressure-aortic Stiffness Risk Categories and Cardiovascular Mortality in End-stage Renal Disease

BACKGROUND: Our aim was to study the predictive power of integrated central blood pressure-aortic stiffness (ICPS) risk categories on cardiovascular (CV) mortality in end-stage renal disease (ESRD) patients. METHODS: This is a secondary analysis of a prospective study of 91 ESRD patients on hemodialysis therapy. At baseline, pulse wave velocity (PWV), central systolic blood pressure (cSBP) and central pulse pressure (cPP) were measured and patients were followed up for CV mortality for a median 29.5 months. Based on the shape of the association of each individual ICPS parameter with the CV outcome, patients were assigned ICPS scores: one point was given, if either the cSBP value was in the 3rd, or if the PWV or cPP was in the 2nd or 3rd tertiles (ICPS range: 0–3). We then evaluated the role of ICPS risk categories (average: 0–1, high: 2, very high: 3 points) in the prediction of CV outcomes using Cox proportional hazard regression analysis and compared its discrimination (Harrell’s C) to that of each of its components. RESULTS: We found a strong dose–response association between ICPS risk categories and CV outcome (high risk HR = 2.62, 95% CI: 0.82–8.43, p for trend = 0.106; very high risk HR = 10.03, 95% CI: 1.67–60.42, p = 0.02) even after adjustment for multiple potential confounders. ICPS risk categories had a modest discrimination (C: 0.622, 95% CI: 0.525–0.719) that was significantly better than that of cSBP (dC: 0.061, 95% CI: 0.006–0.117). CONCLUSIONS: The ICPS risk categories may improve the identification of ESRD patients with high CV mortality risk

Effect of secular trends on age-related trajectories of cardiovascular risk factors: the Whitehall II longitudinal study 1985-2009

Secular trends in cardiovascular risk factors have been described, but few studies have examined simultaneously the effects of both ageing and secular trends within the same cohort

Serum transthyretin and risk of cognitive decline and dementia: 22-year longitudinal study

Serum transthyretin (TTR) may be an early biomarker for Alzheimer's disease and related disorders (ADRD). We investigated associations of TTR measured at baseline with cognitive decline and incident ADRD and whether TTR trajectories differ between ADRD cases and non-cases, over 22 years before diagnosis. A total of 6024 adults aged 45-69 in 1997-1999 were followed up until 2019. TTR was assessed three times, and 297 cases of dementia were recorded. Higher TTR was associated with higher cognitive function at baseline; however, TTR was unrelated to subsequent change in cognitive function. TTR at baseline did not predict ADRD risk (hazard ratio per SD TTR (4.8 mg/dL) = 0.97; 95% confidence interval: 0.94-1.00). Among those later diagnosed with ADRD, there was a marginally steeper downward TTR trajectory than those free of ADRD over follow-up (P=0.050). Our findings suggest TTR is not neuroprotective. The relative decline in TTR level in the preclinical stage of ADRD is likely to be a consequence of disease processes

Age trajectories of glycaemic traits in non-diabetic South Asian and white individuals: the Whitehall II cohort study.

South Asian individuals have an increased prevalence of type 2 diabetes, but little is known about the development of glycaemic traits in this ethnic group. We compared age-related changes in glycaemic traits between non-diabetic South Asian and white participants

Pregnancy outcomes of women with untreated ‘mild’ gestational diabetes (gestational diabetes by the WHO 2013 but not by the WHO-1999 diagnostic criteria) – A population-based cohort study

AIMS: We compared pregnancy outcomes of untreated 'mild' GDM (GDM by WHO 2013 but not by WHO-1999) to normal glucose tolerant women (NGT). METHODS: In a universal screening program 4333 pregnant women had a 3-point 75 g OGTT in Hungary in 2009-2013. By WHO-2013 untreated NGT was diagnosed in n = 3303, 'mild' GDM in n = 336 cases. RESULTS: 'Mild' GDM women were older (mean difference, SE: 1.4, 0.3 yrs), had higher fasting (1.0, 0.02), 60-minute (1.0, 0.09), and 120-minute (0.4, 0.06 mmol/l) blood glucose, and blood pressure (2.6, 0.5/2.0, 0.5 mmHg). Weight gain was similar in both groups (-0.3, 0.3 kg). GDM newborns were heavier (142, 50 g) and were more frequently macrosomic (>4000 g, OR 1.85, 95 %CI 1.35-2.54). Hypertension during pregnancy was more prevalent in the GDM group (OR 1.55, 95 %CI 1.05-2.28), as well as induced (OR 1.38, 95 %CI 1.10-1.74) and instrumental delivery (OR 1.34, 95 %CI 1.07-1.68), and acute caesarean section (OR 1.32, 95 %CI 1.04-1.64). Most of these differences substantially attenuated or became non-significant after adjustment for pre-pregnancy BMI. CONCLUSIONS: Pregnancy outcomes of 'mild' GDM were worse compared to normal glucose tolerant women however these differences were explained by the pre-pregnancy BMI difference between groups

Efficacy and Safety of iGlarLixi, Fixed-Ratio Combination of Insulin Glargine and Lixisenatide, Compared with Basal-Bolus Regimen in Patients with Type 2 Diabetes: Propensity Score Matched Analysis

INTRODUCTION: Basal-bolus (BB) regimens are generally used to intensify basal insulin therapy in patients with type 2 diabetes (T2D) not meeting glycemic targets. However, drawbacks include multiple injection burden and risk of weight gain and hypoglycemia. A once-daily titratable fixed-ratio combination of insulin glargine 100 U/mL and lixisenatide (iGlarLixi) may provide a simple, well-tolerated, and efficacious alternative. We compared these treatments in a post hoc propensity score matched analysis using randomized trial data. METHODS: From the LixiLan-L study, 195 patients who had been randomized to iGlarLixi were matched for age, sex, race, T2D duration, baseline body mass index, glycated hemoglobin (HbA1c), fasting plasma glucose, insulin dose, and metformin use to 195 patients who had been randomized to a BB regimen in the GetGoal Duo-2 trial. RESULTS: At study end, estimated treatment differences for reduction in HbA1c and weight change, and ratio of hypoglycemia events per patient-year (BB vs iGlarLixi) were − 0.28% (standard error 0.08, P = 0.0002), − 1.32 kg (standard error 0.30, P < 0.0001), and 2.85 (P < 0.0001), respectively, all favoring iGlarLixi over BB. Also, proportions of patients reaching individual and composite goals (HbA1c < 7% [< 53 mmol/mol], no weight gain, and no hypoglycemia) were higher in the iGlarLixi compared with the BB treatment group. Gastrointestinal side effects were more common with iGlarLixi. CONCLUSIONS: In patients with T2D inadequately controlled on basal insulin, iGlarLixi offers an effective alternative to BB regimen for reducing HbA1c, without increased risk of hypoglycemia and weight gain. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02058160 (LixiLan-L trial); NCT01768559 (GetGoal Duo-2 trial)

Physical Activity, Sedentary Behavior, and Long-Term Changes in Aortic Stiffness: The Whitehall II Study

BACKGROUND: Physical activity is associated with reduced cardiovascular disease risk, mainly through effects on atherosclerosis. Aortic stiffness may be an alternative mechanism. We examined whether patterns of physical activity and sedentary behavior are associated with rate of aortic stiffening. METHODS AND RESULTS: Carotid-femoral pulse wave velocity (PWV) was measured twice using applanation tonometry at mean ages 65 (in 2008/2009) and 70 (in 2012/2013) years in the Whitehall-II study (N=5196). Physical activity was self-reported at PWV baseline (2008/2009) and twice before (in 1997/1999 and 2002/2003). Sedentary time was defined as sitting time watching television or at work/commute. Linear mixed models adjusted for metabolic and lifestyle risk factors were used to analyze PWV change. Mean (SD) PWV (m/s) was 8.4 (2.4) at baseline and 9.2 (2.7) at follow-up, representing a 5-year increase of 0.76 m/s (95% CI 0.69, 0.83). A smaller 5-year increase in PWV was observed for each additional hour/week spent in sports activity (-0.02 m/s [95% CI -0.03, -0.001]) or cycling (-0.02 m/s [-0.03, -0.008]). Walking, housework, gardening, or do-it-yourself activities were not significantly associated with aortic stiffening. Each additional hour/week spent sitting was associated with faster PWV progression in models adjusted for physical activity (0.007 m/s [95% CI 0.001, 0.013]). Increasing physical activity over time was associated with a smaller subsequent increase in PWV (-0.16 m/s [-0.32, -0.002]) compared with not changing activity levels. CONCLUSIONS: Higher levels of moderate-to-vigorous physical activity and avoidance of sedentary behavior were each associated with a slower age-related progression of aortic stiffness independent of conventional vascular risk factors

Trend of pregnancy outcomes in type 1 diabetes compared to control women: a register-based analysis in 1996-2018

INTRODUCTION: In 1989, the St Vincent declaration aimed to approximate pregnancy outcomes of diabetes to that of healthy pregnancies. We aimed to compare frequency and trends of outcomes of pregnancies affected by type 1 diabetes and controls in 1996-2018. METHODS: We used anonymized records of a mandatory nation-wide registry of all deliveries between gestational weeks 24 and 42 in Hungary. We included all singleton births (4,091 type 1 diabetes, 1,879,183 controls) between 1996 and 2018. We compared frequency and trends of pregnancy outcomes between type 1 diabetes and control pregnancies using hierarchical Poisson regression. RESULTS: The frequency of stillbirth, perinatal mortality, large for gestational age, caesarean section, admission to neonatal intensive care unit (NICU), and low Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score was 2-4 times higher in type 1 diabetes compared to controls, while the risk of congenital malformations was increased by 51% and SGA was decreased by 42% (all p<0.05). These observations remained significant after adjustment for confounders except for low APGAR scores. We found decreasing rate ratios comparing cases and controls over time for caesarean sections, low APGAR scores (p<0.05), and for NICU admissions (p=0.052) in adjusted models. The difference between cases and controls became non-significant after 2009. No linear trends were observed for the other outcomes. CONCLUSIONS: Although we found that the rates of SGA, NICU care, and low APGAR score improved in pregnancies complicated by type 1 diabetes, the target of the St Vincent Declaration was only achieved for the occurrence of low APGAR scores

Comparison of the efficacy and safety of commercially available fixed ratio combinations of insulin degludec/liraglutide (IDegLira) and insulin glargine/lixisenatide (iGlarLixi) - a network meta-analysis

AIMS: To compare the efficacy and safety of commercially available fixed ratio combinations (FRC) of glucagon-like peptide 1 receptor agonists (GLP-1RA) and basal insulins by a network meta-analysis (NMA) of randomised controlled trials (RCT) of type 2 diabetes patients. METHODS: We report a systematic review and network meta-analyses of RCTs of type 2 diabetes patients randomized to FRCs or to their components for ≥24-weeks reported in PubMed or ClinicalTrials.gov until 28/FEB/2022. Primary outcome was attained HbA1c. Secondary outcomes included fasting plasma glucose, change in body weight, and incident hypoglycaemia. Treatment effects were estimated as mean differences and standard errors (MD; [SE]) or odds ratios (OR) with 95% confidence intervals (95%CI) using iGlarLixi as reference. RESULTS: We included 29 RCTs of the 1404 papers identified. No direct comparison between FRCs were found. After excluding some insulin capped trials to reach model consistency, both FRCs were more efficacious regarding HbA1c than their components, however no difference between FRCs were found (MD: -0.10 [SE: 0.10]%). The effect of IDegLira (-0.47 [0.24] mmol/l) and basal insulins was similar to that of iGlarLixi (ref.) on fasting glucose, while GLP-1RA had lower efficacy than iGlarLixi. Weight gain was lower with GLP-1RAs and IDegLira (-0.72 [0.32] kg) than iGlarLixi (ref.) and higher with basal insulins. Incident hypoglycemia (based on different definitions) was least frequent with GLP-1RAs followed by IDegLira (OR 0.78 95%CI 0.39-1.57), iGlarLixi (ref.) and basal insulins. CONCLUSIONS: Regarding HbA1c, both FRCs were more efficacious over their individual components with similar efficacies of the two FRCs

The impact of currently recommended antihypertensive therapy on depression and other psychometric parameters: preliminary communication.

AIMS: Current evidence on the psychological effects of antihypertensive medications is controversial. The aim of this study was to evaluate the effect of current antihypertensive medication on different psychometric parameters and on serum brain-derived neurotrophic factor (BDNF) level. METHODS: Psychometric, haemodynamic, arterial stiffness and laboratory parameters were evaluated before and 3 months after the initiation of antihypertensive medication in untreated hypertensive patients (HT, n=31), and once in healthy controls (CONT, n=22). Subjects completed the following psychometric tests: Beck Depression Inventory (BDI), Hamilton Anxiety Scale (HAM-A), Symptom Checklist 90 Revised (SCL-90), Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire, Big Five Inventory, Pain Vigilance and Awareness Questionnaire and Berkeley Expressivity Questionnaire. Amlodipine and/or perindopril compounds were preferred medications. Serum BDNF was measured with ELISA. RESULTS: Brachial systolic blood pressure, as well as pulse wave velocity were significantly improved in the HT group over the 3-month follow-up (153.3+/-15.9 mmHg vs. 129.5+/-10.0 mmHg and 8.2+/-1.4 m/s vs 7.5+/-1.6 m/s, respectively). Similarly, we found improvements in BDI (0.73 points) and in several Scl-90 subscales. Serum BDNF was not different between CONT and HT and did not change for therapy. CONCLUSIONS: Our results indicate that initiation of currently recommended antihypertensive medications in newly diagnosed patients may have a significant impact on psychological well-being of patients and could influence quality of life as well