Incident Health Outcomes Research Articles

Health outcomes after myocardial infarction: a population study of 56 million people in England

Abstract Background Information about the health outcomes of people with myocardial infarction (MI) is required to determine individual health needs, enable earlier detection and treatment of new onset disease, and inform health service planning. Although estimating 10 year cardiovascular disease risk is an established part of primary prevention, this is not the case for MI where comprehensive evidence for the long term impact of MI on subsequent major health outcomes is lacking. Such information is critical not only for the development of guideline recommendations, but also to underpin shared decision making. Methods This nationwide cohort study includes 34,116,257 adults in England, contributing 145,912,852 hospitalisations between 1st January 2008 and 31st January 2017 (final follow-up 27th March 2017). The absolute risk of 11 non-fatal health outcomes following MI (subsequent MI and new hospitalisations of heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes, dementia, depression, cancer) and all-cause mortality was calculated via standardised cumulative incidence functions (CIFs) over nine years of follow-up. CIFs were estimated from flexible parametric survival models adjusted for age, sex, year, deprivation and competing risk of death. Risk-set matching by age, sex, and year of hospitalisation determined the relative risk of incident health outcomes compared with non-MI cases. Findings: There were 433,361 individuals with MI (mean age 67·4 years (SD 14·4); n=286,728 (65·3%) male). Following MI, all-cause mortality was the most frequent event (CIF 37·8%, 95% CI 37·6─37·9%), followed by heart failure (29·6%; 29·4─29·7%), renal failure (27·2%; 27·0─27·4%), atrial fibrillation (22·3%; 22·2─22·5%), severe bleeding (19·0%; 18·8-19·1%), diabetes (17·0%; 16·9─17·1%), cancer (13·5%; 13·3─13·6%), cerebrovascular disease (12·5%; 12·4─12·7%), depression (8·9%; 8·7─9·0%), dementia (7·8%; 7·7─7·9%), subsequent MI (7·1%; 7·0─7·2%), and peripheral arterial disease (6·5%; 6·4─6·6%). Compared with 2,001,301 matched controls, first hospitalisation of all non-fatal health outcomes were increased after MI, except for dementia (HR 1·01; 0·99─1·02) and cancer (HR 0·56; 0·56─0·57). Interpretation: Up to a third of patients with MI develop heart failure or renal failure, 7% have another MI and four in ten die within ten years. The incidence of heart failure, atrial fibrillation, cerebrovascular disease, peripheral arterial disease, severe bleeding, renal failure, diabetes, and depression, but not dementia or cancer, was higher than expected during the normal life course without MI. Improved post-MI preventative strategies, encompassing enhanced surveillance and detection, are required to tackle the high incidences of heart failure, atrial fibrillation, cerebrovascular disease, and renal failure observed in this population.

Abstract P535: Associations of Genetically Determined Favourable and Unfavourable Adiposity Across the Phenome

Background: The large-scale investigation of the genetic architecture of favourable adiposity (FA) and unfavourable adiposity (UFA) may unravel mechanisms coupling higher adiposity and cardiometabolic comorbidities, and may in turn aid in the prevention, prediction and management of these diseases. Aims and Objectives: We aimed to interrogate FA and UFA in relation to a plethora of clinical outcomes, investigate their causality, and test whether a healthy lifestyle interacts with FA/UFA for the risk of disease. Materials and Methods: We performed a Mendelian randomisation-phenome-wide association study (MR-PheWAS) to identify health outcomes associated with FA and UFA. We first conducted a PheWAS of FA and UFA with 988 phenotypes in 426,295 UK Biobank individuals. Health outcomes passing false-discovery rate (FDR) correction for multiple testing were taken forward to MR analyses. SNP-outcome associations were extracted from external GWAS consortia data. Finally, we examined the association between FA/UFA tertiles of genetic risk and tertiles of lifestyle score and incident health outcomes using proportional hazards models. Results: Our two sample MR results suggest that a 1-SD higher genetically instrumented FA is associated with lower odds of type 2 diabetes (OR: 0.05, 95% CI: 0.02 to 0.11), hypertension (0.30, 0.18 to 0.50) and coronary atherosclerosis (0.25, 0.10 to 0.62), and with higher odds of ventral hernia (18.15, 4.22-77.97). Moreover, 1-SD higher genetically determined UFA was associated with increased odds of type 2 diabetes (5.30, 3.27-8.61), hypertension (2.40, 1.55-3.71), myocardial infarction (1.99, 1.49-2.65), cholelithiasis (2.92, 1.87-4.56), and atrial fibrillation (2.17, 1.28-3.69) at significance passing FDR q<0.05. Sensitivity analyses were consistent with the main results. Our Cox regression model indicated that a favourable lifestyle is associated with a more pronounced risk reduction in cardiometabolic health outcomes and can have a more substantial impact on cardiometabolic and inflammatory conditions for individuals with either a high FA and a low UFA GRS profiles. Conclusions: Our findings offer novel insight into previously unreported effects of favourable and unfavourable adiposity, suggesting that a healthy lifestyle can benefit individuals with both favourable and unfavourable genetic risk scores. This highlights the importance of population-wide lifestyle approaches to address the problem of obesity and risk-stratifying the population according to favourable and unfavourable adiposity.

Longitudinal Sleep Study in Pregnancy: Cohort Profile and Prevalence and Risk Factors for Sleep Symptoms in the First Trimester.

Sleep disorders could influence pregnancy outcomes but evidence for longitudinal associations is scarce. We established a prospective cohort of women to determine incident sleep issues and their adverse health outcomes during pregnancy and beyond, and present here the baseline cohort profile. Antenatal women in gestational weeks 8-12 were recruited (n = 535) and followed-up in each trimester and at 5-6 weeks postpartum (no attrition). Sleep symptoms and disorders were measured using STOP-Bang and Berlin questionnaires and Pittsburgh Sleep Quality Index. Incident health outcomes were extracted from clinical records. At the time of recruitment, habitual snoring was present in 13.8% of participants; "excessive sleepiness during the day" (EDS) in 42.8%; short (<7 h) sleep duration in 46.4%; "having trouble sleeping" in 15.3%; and "poor subjective sleep quality" in 8.6%. Habitual snoring was strongly associated with irregular menstrual periods for one year preceding pregnancy (p = 0.014) and higher BMI (p < 0.001). Higher age was associated with less "trouble sleeping" (OR 0.9, p = 0.033) and longer sleep duration was associated with better "subjective sleep quality" (OR 0.8, p = 0.005). Sleep issues were highly prevalent at baseline and associated with age, irregular menstruation, and obesity. This cohort will provide a robust platform to investigate incident sleep disorders during pregnancy and their effects on adverse pregnancy outcomes and long-term health of women and their offspring.

Global priorities for large-scale biomarker-based prospective cohorts

The focus of this paper is on strategic approaches for establishing population-based prospective cohorts that collect and store biological samples from very large numbers of participants to help identify the determinants of common health outcomes. In particular, it aims to address key issues related to investigation of genetic, as well as social, environmental, and ancestral, diversity; generation of detailed genetic and other types of assay data; collection of detailed lifestyle and environmental exposure information; follow-up and characterization of incident health outcomes; and overcoming obstacles to data sharing and access (including capacity building). It concludes that there is a need for strategic planning at an international level (rather than the current ad hoc approach) toward the development of a carefully selected set of deeply characterized large-scale prospective cohorts that are readily accessible by researchers around the world.

Validation of the Integrated Care for Older People Screening Tool: Focus on the Chair Rise Test to Assess Locomotion

The Integrated Care for Older People (ICOPE) is a function- and person-centered healthcare pathway developed by the World Health Organization (WHO). ICOPE's first step (Step 1) consists of screening for impairments in the intrinsic capacity (IC) domains (namely sensorial, cognition, nutrition, psychological, and locomotion). For instance, the ICOPE Step1 tool suggests a cut-point of 14 seconds for five-repetition chair rise time as a marker of impaired locomotion. Given the lack of validation of this tool in the literature, we aimed to validate the ICOPE screening tool concerning incident health outcomes, focusing on the locomotion assessment. First, we analyzed the five-domain screening tool's ability to identify older adults (OA) at higher risk of incident outcomes (frailty, disability, dementia) using longitudinal data from the Multidomain Alzheimer Preventive Trial (MAPT). For the locomotion assessment (chair rise test), we derived and cross-validated age-specific cut points from two population-based cohorts using ROC (receiver operating characteristic) analysis. We further verified those cut points among OA real-life users of the health system and clinical trial participants. In conclusion, the ICOPE Step 1 screening tool was able to identify OA at higher risk of incident frailty, disability, and dementia. New chair-rise-time cut points for age groups 70-79 years old and 80 years and older were valid in populations from different settings. The ICOPE Step 1 tool provides a practical and integrative way of screening older adults for impairments in IC and detecting those at higher risk of functional decline.

Characterisation of an inflammation-related epigenetic score and its association with cognitive ability

BackgroundChronic systemic inflammation has been associated with incident dementia, but its association with age-related cognitive decline is less clear. The acute responses of many inflammatory biomarkers mean they may provide an unreliable picture of the chronicity of inflammation. Recently, a large-scale epigenome-wide association study identified DNA methylation correlates of C-reactive protein (CRP)—a widely used acute-phase inflammatory biomarker. DNA methylation is thought to be relatively stable in the short term, marking it as a potentially useful signature of exposure.MethodsWe utilise a DNA methylation-based score for CRP and investigate its trajectories with age, and associations with cognitive ability in comparison with serum CRP and a genetic CRP score in a longitudinal study of older adults (n = 889) and a large, cross-sectional cohort (n = 7028).ResultsWe identified no homogeneous trajectories of serum CRP with age across the cohorts, whereas the epigenetic CRP score was consistently found to increase with age (standardised β = 0.07 and 0.01) and to do so more rapidly in males compared to females. Additionally, the epigenetic CRP score had higher test-retest reliability compared to serum CRP, indicating its enhanced temporal stability. Higher serum CRP was not found to be associated with poorer cognitive ability (standardised β = − 0.08 and − 0.05); however, a consistent negative association was identified between cognitive ability and the epigenetic CRP score in both cohorts (standardised β = − 0.15 and − 0.08).ConclusionsAn epigenetic proxy of CRP may provide a more reliable signature of chronic inflammation, allowing for more accurate stratification of individuals, and thus clearer inference of associations with incident health outcomes.

Functional Near-Infrared Spectroscopy to Study Cerebral Hemodynamics in Older Adults During Cognitive and Motor Tasks: A Review.

The integrity of the frontal areas of the brain, specifically the prefrontal cortex, are critical to preserve cognition and mobility in late life. Prefrontal cortex regions are involved in executive functions and gait control and have been related to the performance of dual-tasks. Dual-task performance assessment may help identify older adults at risk of negative health outcomes. As an alternative to neuroimaging techniques that do not allow assessment during actual motion, functional Near-Infrared Spectroscopy (fNIRS) is a non-invasive technique that can assess neural activation through the measurement of cortical oxygenated and deoxygenated hemoglobin levels, while the person is performing a motor task in a natural environment as well as during cognitive tasks. The aim of this review was to describe the use of fNIRS to study frontal lobe hemodynamics during cognitive, motor and dual-tasks in older adults. From the 46 included publications, 20 studies used only cognitive tasks, three studies used motor tasks and 23 used dual-tasks. Our findings suggest that fNIRS detects changes in frontal activation in older adults (cognitively healthy and mild cognitive impairment), especially while performing cognitive and dual-tasks. In both the comparison between older and younger adults, and in people with different neurological conditions, compared to healthier controls, the prefrontal cortex seems to experience a higher activation, which could be interpreted in the context of proposed neural inefficiency and limited capacity models. Further research is needed to establish standardized fNIRS protocols, study the cerebral hemodynamic in different neurological and systemic conditions that might influence cortical activation and explore its role in predicting incident health outcomes such as dementia.

Vaginal estrogen use and chronic disease risk in the Nurses' Health Study.

To examine the associations between vaginal estrogen use and multiple health outcomes including cardiovascular disease (total myocardial infarction, stroke, and pulmonary embolism/deep vein thrombosis), cancer (total invasive, breast, endometrial, ovarian, and colorectal cancer), and hip fracture. We included postmenopausal women from the Nurses' Health Study (1982-2012) who were not current users of systemic hormone therapy at the start of the study or during follow-up. Vaginal estrogen use was self-reported on the biennial questionnaires. Information on incident health outcomes were self-reported and confirmed by medical records. We used Cox proportional hazards regression to model the multivariable adjusted hazard ratios and the 95% confidence intervals for vaginal estrogen use and multiple health outcomes. Over 18 years of follow-up, after adjusting for covariates, risks for cardiovascular disease, cancer, and hip fracture were not different between users and nonusers of vaginal estrogen. No statistically significant increase in risk of any health outcome was observed with vaginal estrogen use. In sensitivity analyses, when we examined associations by hysterectomy status, the stratified results were generally similar to those for the total cohort. Vaginal estrogen use was not associated with a higher risk of cardiovascular disease or cancer. Our findings lend support to the safety of vaginal estrogen use, a highly effective treatment for genitourinary syndrome of menopause.

Association of raltegravir use with long-term health outcomes in HIV-infected patients: an observational post-licensure safety study in a large integrated healthcare system

Background: Raltegravir became the first integrase inhibitor to gain FDA approval; but with limited evidence documenting long-term risks in real world care, especially for major health outcomes of interest.Objective: Assess raltegravir safety in clinical practice within an integrated health system.Methods: We conducted a cohort study of HIV-infected adults within Kaiser Permanente California from 2005 to 2013. We compared patients initiating raltegravir during the study period with two groups; a historical cohort (started new antiretroviral regimen [ART] 2005–2007) and a concurrent cohort that did not initiate raltegravir (2007–2013). We used multivariate Cox proportional hazard regression to obtain hazard ratios (HR) for pre-specified incident health outcomes, employing propensity scores to adjust for potential confounding.Results: The population included 8,219 HIV-infected adults (raltegravir cohort N = 1,757; 4,798 patient-years), with greater years known HIV-infected among raltegravir patients. The raltegravir cohort had increased HR for AIDS-defining (HR 2.69 [1.53–4.71]; HR 1.85 [1.21–2.82]) and non-AIDS-defining malignancies (HR 2.26 [1.29–3.94]; HR 1.88 [1.26–2.78]) relative to both comparison cohorts. Compared to the historical cohort we found no significant difference in all-cause mortality; the raltegravir cohort experienced increased HR for all-cause mortality compared to concurrent (HR 1.53 [1.02–2.31]). Raltegravir appeared protective of lipodystrophy when compared to the historical cohort but associated with increased incidence compared to concurrent. There were no significant differences in the incidence of hepatic, skin, or cardiovascular events.Conclusions: The potentially elevated risk for malignancy and mortality with raltegravir and residual confounding merits further investigation. We demonstrate the value of observational cohorts for monitoring post-licensure medication safety.

Kidney disease in moderate-to-severe psoriasis: a critical appraisal.

Using a population-based cohort, Wan etal. examined the risk of moderate-to-advanced (stage 3-5) chronic kidney disease (CKD) in patients with psoriasis. A population-based cohort was constructed using The Health Improvement Network (THIN) database. THIN is an electronic primary healthcare records database containing routinely collected medical diagnosis and drug prescribing data on >9million patients in the U.K. Data were collected prospectively on 143883 adults (aged 18-90years) with psoriasis. Of these, 7354 had severe psoriasis, as defined by prescription codes for systemic medication or treatment codes for phototherapy. Patients with psoriasis were matched with up to five nonpsoriasis age- and practice-matched controls. Patients with a diagnosis of CKD before study entry were excluded. In addition, baseline data from the Incident Health Outcomes and Psoriasis Events (iHOPE) study, a cohort of 8731 primary care patients aged 25-64years with psoriasis, was included. Psoriasis severity was categorized according to body surface area (BSA) involvement as estimated by general practitioners. A similar method using a patient-reported BSA assessment tool was previously validated by the same group. Patients were matched by age and practice with 10 nonpsoriasis controls. Psoriasis, identified on the basis of a recorded diagnostic code for psoriasis. Incident CKD was defined as the presence of a recorded diagnostic code consistent with moderate-to-advanced (stage 3-5) CKD or laboratory parameters consistent with the diagnosis (estimated glomerular filtration rate <60mLmin(-1) 1·73m(-2) ) during follow-up. Prevalent CKD (as defined above) in the cross-sectional data from the iHOPE study. The adjusted hazard ratios for incident CKD were 1·05 [95% confidence interval (CI) 1·02-1·07], 0·99 (95% CI 0·97-1·02) and 1·93 (95% CI 1·79-2·08) in the overall, mild and severe psoriasis groups, respectively. In the nested cross-sectional study (iHOPE) the adjusted prevalence odds ratios for CKD were 0·89 (95% CI 0·72-1·10), 1·36 (95% CI 1·06-1·74) and 1·58 (95% CI 1·07-2·34) in the mild, moderate and severe psoriasis groups, respectively. Moderate-to-severe psoriasis is associated with an increased risk of moderate-to-advanced CKD, independently of traditional risk factors.

Effect of psoriasis severity on hypertension control: a population-based study in the United Kingdom.

Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown. To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension. Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age- and practice-matched controls without psoriasis (n = 11,977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners. Uncontrolled hypertension was defined as a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity. There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P = .01 for trend). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, although not statistically significantly so (aOR, 1.10; 95% CI, 0.98-1.24). Among patients with hypertension, psoriasis was associated with a greater likelihood of uncontrolled hypertension in a dose-dependent manner, with the greatest likelihood observed among those with moderate to severe psoriasis defined by 3% or more of the body surface area affected. Our data suggest a need for more effective blood pressure management, particularly among patients with more severe psoriasis.

Is There Research to Support a Specific Diet for Psoriasis?

Is There Research to Support a Specific Diet for Psoriasis?

Seizure-Related Injuries, Drowning and Vehicular Crashes – A Critical Review of the Literature

Injury is common in patients with epilepsy, can have serious consequences (fractures, burns), and can sometimes even be fatal (drowning, vehicular crashes). Seizure-related injuries, drowning, and vehicular crashes have been investigated across differing populations using various methodologies hindering consistent estimates with respect to its frequency, magnitude, and potential risk factors. Knowledge is further complicated by the low incidence of injury outcomes, the not insignificant background frequency of injury in the general population, and the emphasis on seizure-related explanatory mechanisms. Although not without its own complexity, privacy preserving data linkage is an emerging powerful technique that is being increasingly used in epilepsy and other chronic conditions to answer important questions, especially when measuring low incidence health outcomes prospectively, such as injury. This review examines the frequency of overall and specific seizure-related injures, describes the known risk factors and finally suggests future directions for research that may improve our understanding in the area.

Childhood Trauma and Health Outcomes in HIV-Infected Patients

Traumatic life histories are highly prevalent in people living with HIV/AIDS and predict sexual risk behaviors, medication adherence, and all-cause mortality. Yet the causal pathways explaining these relationships remain poorly understood. We sought to quantify the association of trauma with negative behavioral and health outcomes and to assess whether those associations were explained by mediation through psychosocial characteristics. In 611 outpatient people living with HIV/AIDS, we tested whether trauma's influence on later health and behaviors was mediated by coping styles, self-efficacy, social support, trust in the medical system, recent stressful life events, mental health, and substance abuse. In models adjusting only for sociodemographic and transmission category confounders (estimating total effects), pasttrauma exposure was associated with 7 behavioral and health outcomes including increased odds or hazard of recent unprotected sex [odds ratio (OR) = 1.17 per each additional type of trauma, 95% confidence interval = 1.07 to 1.29], medication nonadherence (OR = 1.13, 1.02 to 1.25), hospitalizations (hazard ratio = 1.12, 1.04 to 1.22), and HIV disease progression (hazard ratio = 1.10, 0.98 to 1.23). When all hypothesized mediators were included, the associations of trauma with health care utilization outcomes were reduced by about 50%, suggesting partial mediation (eg, OR for hospitalization changed from 1.12 to 1.07), whereas point estimates for behavioral and incident health outcomes remained largely unchanged, suggesting no mediation (eg, OR for unprotected sex changed from 1.17 to 1.18). Trauma remained associated with most outcomes even after adjusting for all hypothesized psychosocial mediators. These data suggest that past trauma influences adult health and behaviors through pathways other than the psychosocial mediators considered in this model.

Health and mortality consequences of abdominal obesity: evidence from the AusDiab study

To provide an estimate of the morbidity and mortality resulting from abdominal overweight and obesity in the Australian population. Prospective, national, population-based study (the Australian Diabetes, Obesity and Lifestyle [AusDiab] study). 6072 men and women aged>or=25 years at study entry between May 1999 and December 2000, and aged<or=75 years, not pregnant and for whom there were waist circumference data at the follow-up survey between June 2004 and December 2005. Incident health outcomes (type 2 diabetes, hypertension, dyslipidaemia, the metabolic syndrome and cardiovascular diseases) at 5 years and mortality at 8 years. Comparison of outcome measures between those classified as abdominally overweight or obese and those with a normal waist circumference at baseline, and across quintiles of waist circumference, and (for mortality only) waist-to-hip ratio. Abdominal obesity was associated with odds ratios of between 2 and 5 for incident type 2 diabetes, dyslipidaemia, hypertension and the metabolic syndrome. The risk of myocardial infarction among obese participants was similarly increased in men (hazard ratio [HR], 2.75; 95% CI, 1.08-7.03), but not women (HR, 1.43; 95% CI, 0.37-5.50). Abdominal obesity-related population attributable fractions for these outcomes ranged from 13% to 47%, and were highest for type 2 diabetes. No significant associations were observed between all-cause mortality and increasing quintiles of abdominal obesity. Our findings confirm that abdominal obesity confers a considerably heightened risk for type 2 diabetes, the metabolic syndrome (as well as its components) and cardiovascular disease, and they provide important information that enables a more precise estimate of the burden of disease attributable to obesity in Australia.