Statin utilisation in a real-world setting: a retrospective analysis in relation to arterial and cardiovascular autonomic function

Randomized trials suggest that statin treatment may lower blood pressure and influence cardiovascular autonomic function (CVAF), but the impact of duration of usage, discontinuation, and adherence to this therapy is unknown. We examined these issues with regard to blood pressure (BP)-related variables in a large, population-based study. Participants were 4942 adults (58% male; aged 50–84 years): 2179 on statin treatment and 2763 untreated. Days of utilization, adherence (proportion of days covered ≥0.8), and discontinuation (non-use for ≥30 days immediately prior to BP measurement) of three statins (atorvastatin, pravastatin, and simvastatin) over a period of up to 2 years was monitored retrospectively from electronic databases. Systolic BP (SBP), diastolic BP (DBP), augmentation index, excess pressure, reservoir pressure, and CVAF (pulse rate and BP variability) parameters were calculated from aortic pressure waveforms derived from suprasystolic brachial measurement. Days of statin treatment had inverse relationships with pulse rate variability parameters in cardiac arrhythmic participants (20–25% lower than in statin non-users) and with most arterial function parameters in everyone. For example, compared to untreated participants, those treated for ≥659 days had 3.0 mmHg lower aortic SBP (P < 0.01). Discontinuation was associated with higher brachial DBP and aortic DBP (for both, β = 2.0 mmHg, P = 0.008). Compared to non-adherent statin users, adherent users had lower levels of brachial SBP, brachial DBP, aortic DBP, aortic SBP, and peak reservoir pressure (β = −1.4 to −2.6 mmHg). In conclusion, in a real-world setting, statin-therapy duration, non-discontinuation and adherence associate inversely with BP variables and, in cardiac arrhythmias, CVAF parameters

Digital Overuse and Addictive Traits and Their Relationship With Mental Well-Being and Socio-Demographic Factors: A National Population Survey for Wales

Introduction: Population health concerns have been raised about negative impacts from overuse of digital technologies. We examine patterns of online activity predictive of Digital Overuse and Addictive Traits (DOAT). We explore associations between DOAT and mental well-being and analyse how both relate to self-reported changes in self-esteem, perceived isolation, and anxiety about health when individuals use the internet for health purposes. Methods: A cross-sectional nationally representative household survey of adults using stratified random sampling (compliance 75.4%, n = 1,252). DOAT was measured using self-reported questions adapted from a social media addiction scale (failure to cut down use, restlessness when not using, and impact on job/studies and home/social life in the last year), combined into a single DOAT score. Higher DOAT score was defined as >1 standard deviation above population mean. The Short Warwick-Edinburgh Mental Well-being Scale was used to measure mental well-being. Analyses were limited to those with internet access (n = 1,003). Results: Negative impacts of digital technology use on work and home/social lives were reported by 7.4% of respondents. 21.2% had tried but failed to cut down use in the past year. Higher DOAT was associated with higher social media and internet use but also independently associated with greater risks of low mental well-being. Higher DOAT was associated with both improvement and worsening of self-esteem, perceived isolation and anxiety about health when using the internet for health reasons, with no change in these outcomes most likely in those with lower DOAT. Lower mental well-being was associated with a similar bi-directional impact on perceived isolation and was also associated with worsening self-esteem. Conclusions: Substantial proportions of individuals report negative impacts on home, social and working lives from digital technology use, with many trying but failing to cut down use. Individuals with higher DOAT may experience improvements or worsening in self-esteem and other measures of mental well-being when using the internet for health purposes. From a public health perspective, a greater understanding of risk factors for digital overuse, its impacts on well-being and how to reasonably limit use of technology are critical for a successful digital revolution

Exploring the health and service utilisation of general practice patients with a history of adverse childhood experiences (ACEs): An observational study using electronic health records

Objectives To examine the relationships between adverse childhood experiences (ACEs), chronic health and health service utilisation among a sample of general practice patients. Design Cross-sectional observational study using anonymised data from electronic health records for 763 patients. Setting Four general practices in northwest England and North Wales. Outcome measures Patient demographic data (age, gender); body mass index; self-reported smoking status; self-reported ACEs; diagnosis of chronic health conditions; current mental health problems; total number of service contacts and repeat medication use in the previous 6 months. Results A history of ACEs (experiencing abuse or neglect as a child, and/or growing up in a household characterised by violence, substance use, mental health problems or criminal behaviour) was strongly independently associated with current mental health problems, smoking and chronic obstructive pulmonary disease, showing a dose-response relationship with level of ACE exposure. Medication use and contact were significantly greater among patients with high ACE exposure (≥4 ACEs), compared with those with no ACEs. However, contrary to findings from population studies, health service utilisation was not significantly different for patients with increased ACE exposure (1-3 ACEs) and their ACE-free counterparts. Conclusions Findings highlight the contribution ACEs make to unequal distributions of risk to health and well-being and patterns of health service use in the UK

Relations of Demographic and Clinical Factors With Cardiovascular Autonomic Function in a Population-Based Study: An Assessment By Quantile Regression

BACKGROUND: The relationships of many factors with cardiovascular autonomic function (CVAF) outcome parameters may not be uniform across the entire distribution of the outcome. We examined how demographic and clinical factors varied with different subgroups of CVAF parameters. METHODS: Quantile regression was applied to a cross-sectional analysis of 4,167 adults (56% male; age range, 50–84 years) from 4 ethnic groups (3,419 New Zealand European, 303 Pacific, 227 Maori, and 218 South Asian) and without diagnosed cardiac arrhythmia. Pulse rate variability (root mean square of successive differences (RMSSD) and SD of pulse intervals) and baroreflex sensitivity were response variables. Independent variables were age, sex, ethnicity, brachial and aortic blood pressure (BP) variables, body mass index (BMI), and diabetes. RESULTS: Ordinary linear regression showed that age, sex, Pacific and Maori ethnicity, BP variables, BMI, and diabetes were associated with CVAF parameters. But quantile regression revealed that, across CVAF percentiles, the slopes for these relationships: (i) varied by more than 10-fold in several cases and sometimes changed direction and (ii) noticeably differed in magnitude often (by >3–fold in several cases) compared to ordinary linear regression coefficients. For instance, age was inversely associated with RMSSD at the 10th percentile of this parameter (β = −0.12 ms/year, 95% confidence interval = −0.18 to −0.09 ms/year) but had a positive relationship at the 90th percentile (β = 3.17 ms/year, 95% confidence interval = 2.50 to 4.04 ms/year). CONCLUSIONS: The relationships of demographic and clinical factors with CVAF parameters are, in many cases, not uniform. Quantile regression provides an improved assessment of these associations

Relations of Demographic and Clinical Factors With Cardiovascular Autonomic Function in a Population-Based Study: An Assessment By Quantile Regression

BACKGROUND: The relationships of many factors with cardiovascular autonomic function (CVAF) outcome parameters may not be uniform across the entire distribution of the outcome. We examined how demographic and clinical factors varied with different subgroups of CVAF parameters. METHODS: Quantile regression was applied to a cross-sectional analysis of 4,167 adults (56% male; age range, 50–84 years) from 4 ethnic groups (3,419 New Zealand European, 303 Pacific, 227 Maori, and 218 South Asian) and without diagnosed cardiac arrhythmia. Pulse rate variability (root mean square of successive differences (RMSSD) and SD of pulse intervals) and baroreflex sensitivity were response variables. Independent variables were age, sex, ethnicity, brachial and aortic blood pressure (BP) variables, body mass index (BMI), and diabetes. RESULTS: Ordinary linear regression showed that age, sex, Pacific and Maori ethnicity, BP variables, BMI, and diabetes were associated with CVAF parameters. But quantile regression revealed that, across CVAF percentiles, the slopes for these relationships: (i) varied by more than 10-fold in several cases and sometimes changed direction and (ii) noticeably differed in magnitude often (by >3–fold in several cases) compared to ordinary linear regression coefficients. For instance, age was inversely associated with RMSSD at the 10th percentile of this parameter (β = −0.12 ms/year, 95% confidence interval = −0.18 to −0.09 ms/year) but had a positive relationship at the 90th percentile (β = 3.17 ms/year, 95% confidence interval = 2.50 to 4.04 ms/year). CONCLUSIONS: The relationships of demographic and clinical factors with CVAF parameters are, in many cases, not uniform. Quantile regression provides an improved assessment of these associations

Sex steroids do not affect shigatoxin cytotoxicity on human renal tubular or glomerular cells

BACKGROUND: The greater susceptibility of children to renal injury in post-diarrheal hemolytic-uremic syndrome (HUS) may be related, at least in part, to heightened renal cell sensitivity to the cytotoxic effect of Shiga toxin (Stx), the putative mediator of kidney damage in HUS. We hypothesized that sexual maturation, which coincides with a falling incidence of HUS, may induce a relatively Stx-resistant state in the renal cells. METHODS: Cultured human glomerular endothelial (HGEN), human glomerular visceral epithelial (HGEC) and human proximal tubule (HPT) cells were exposed to Stx-1 after pre-incubation with progesterone, β-estradiol or testosterone followed by determination of cytotoxicity. RESULTS: Under basal conditions, Stx-1 potently and dose-dependently killed HPT and HGEC, but had relatively little effect on HGEN. Pre-incubation for 1, 2 or 7 days with physiologic or pharmacologic concentrations of progesterone, β-estradiol or testosterone had no effect on Stx-1 cytotoxicity dose-response on any cell type. In addition, no steroid altered Gb3 expression (Stx receptor) by any cell type at any time point. CONCLUSION: These data do not support the notion that hormonal changes associated with puberty induce an Stx-resistant state within kidney cells

Prevalence of CADASIL and Fabry Disease in a Cohort of MRI Defined Younger Onset Lacunar Stroke.

BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by mutations in the NOTCH3 gene, is the most common monogenic disorder causing lacunar stroke and cerebral small vessel disease (SVD). Fabry disease (FD) due to mutations in the GLA gene has been suggested as an underdiagnosed cause of stroke, and one feature is SVD. Previous studies reported varying prevalence of CADASIL and FD in stroke, likely due to varying subtypes studied; no studies have looked at a large cohort of younger onset SVD. We determined the prevalence in a well-defined, MRI-verified cohort of apparently sporadic patients with lacunar infarct. METHODS: Caucasian patients with lacunar infarction, aged ≤70 years (mean age 56.7 (SD8.6)), were recruited from 72 specialist stroke centres throughout the UK as part of the Young Lacunar Stroke DNA Resource. Patients with a previously confirmed monogenic cause of stroke were excluded. All MRI's and clinical histories were reviewed centrally. Screening was performed for NOTCH3 and GLA mutations. RESULTS: Of 994 subjects five had pathogenic NOTCH3 mutations (R169C, R207C, R587C, C1222G and C323S) all resulting in loss or gain of a cysteine in the NOTCH3 protein. All five patients had confluent leukoaraiosis (Fazekas grade ≥2). CADASIL prevalence overall was 0.5% (95% CI 0.2%-1.1%) and among cases with confluent leukoaraiosis 1.5% (95% CI 0.6%-3.3%). No classic pathogenic FD mutations were found; one patient had a missense mutation (R118C), associated with late-onset FD. CONCLUSION: CADASIL cases are rare and only detected in SVD patients with confluent leukoaraiosis. No definite FD cases were detected.The UK Young Lacunar Stroke DNA Study was funded by a grants from the Wellcome Trust (WT072952, www.wellcome.ac.uk) and the Stroke Association (TSA 2010/01& TSA 2013/02, www.stroke.org.uk). Fabry disease screening was supported by an unrestricted scientific grant from Shire Human Genetic Therapies (www.shire.com). The sponsors of the study had no role in the study design, data collection, data analysis, interpretation, writing of the manuscript, or the decision to submit the manuscript for publication. L R-J’s salary is funded by a Stroke Association/ British Heart Foundation grant. (TSA/BHF 2010/01). HM is supported by an National Institute for Health Research Senior Investigator award (www.nihr.ac.uk). HM and SB are supported by the Cambridge University Trust National Institute for Health Research Comprehensive Research Centre (www.cambridge-brc.org.uk).This is the final version of the article. It first appeared from PLoS via http://dx.doi.org/10.1371/journal.pone.013635

Health and financial burden of adverse childhood experiences in England and Wales: a combined primary data study of five surveys

Objective To estimate the health and financial burden of adverse childhood experiences (ACEs) in England and Wales. Design The study combined data from five randomly stratified cross-sectional ACE studies. Population attributable fractions (PAFs) were calculated for major health risks and causes of ill health and applied to disability adjusted life years (DALYs), with financial costs estimated using a modified human capital method. Setting Households in England and Wales. Participants 15 285 residents aged 18-69. Outcome measures The outcome measures were PAFs for single (1 ACE) and multiple (2-3 and ≥4 ACEs) ACE exposure categories for four health risks (smoking, alcohol use, drug use, high body mass index) and nine causes of ill health (cancer, type 2 diabetes, heart disease, respiratory disease, stroke, violence, anxiety, depression, other mental illness); and annual estimated DALYs and financial costs attributable to ACEs. Results Cumulative relationships were found between ACEs and risks of all outcomes. For health risks, PAFs for ACEs were highest for drug use (Wales 58.8%, England 52.6%), although ACE-attributable smoking had the highest estimated costs (England and Wales, £7.8 billion). For causes of ill health, PAFs for ACEs were highest for violence (Wales 48.9%, England 43.4%) and mental illness (ranging from 29.1% for anxiety in England to 49.7% for other mental illness in Wales). The greatest ACE-attributable costs were for mental illness (anxiety, depression and other mental illness; England and Wales, £11.2 billion) and cancer (£7.9 billion). Across all outcomes, the total annual ACE-attributable cost was estimated at £42.8 billion. The majority of costs related to exposures to multiple rather than a single ACE (ranging from 71.9% for high body mass index to 98.3% for cancer). Conclusions ACEs impose a substantial societal burden in England and Wales. Policies and practices that prevent ACEs, build resilience and develop trauma-informed services are needed to reduce burden of disease and avoidable service use and financial costs across health and other sectors