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NHS Health Check attendance is associated with reduced multiorgan disease risk: a matched cohort study in the UK Biobank.
McCracken, C, Raisi-Estabragh, Z, Szabo, L, Robson, J, Raman, B, Topiwala, A, Roca-Fernández, A, Husain, M, Petersen, SE, Neubauer, S, et al
BMC medicine. 2024;(1):1
Abstract
BACKGROUND The NHS Health Check is a preventive programme in the UK designed to screen for cardiovascular risk and to aid in primary disease prevention. Despite its widespread implementation, the effectiveness of the NHS Health Check for longer-term disease prevention is unclear. In this study, we measured the rate of new diagnoses in UK Biobank participants who underwent the NHS Health Check compared with those who did not. METHODS Within the UK Biobank prospective study, 48,602 NHS Health Check recipients were identified from linked primary care records. These participants were then covariate-matched on an extensive range of socio-demographic, lifestyle, and medical factors with 48,602 participants without record of the check. Follow-up diagnoses were ascertained from health records over an average of 9 years (SD 2 years) including hypertension, diabetes, hypercholesterolaemia, stroke, dementia, myocardial infarction, atrial fibrillation, heart failure, fatty liver disease, alcoholic liver disease, liver cirrhosis, liver failure, acute kidney injury, chronic kidney disease (stage 3 +), cardiovascular mortality, and all-cause mortality. Time-varying survival modelling was used to compare adjusted outcome rates between the groups. RESULTS In the immediate 2 years after the NHS Health Check, higher diagnosis rates were observed for hypertension, high cholesterol, and chronic kidney disease among health check recipients compared to their matched counterparts. However, in the longer term, NHS Health Check recipients had significantly lower risk across all multiorgan disease outcomes and reduced rates of cardiovascular and all-cause mortality. CONCLUSIONS The NHS Health Check is linked to reduced incidence of disease across multiple organ systems, which may be attributed to risk modification through earlier detection and treatment of key risk factors such as hypertension and high cholesterol. This work adds important evidence to the growing body of research supporting the effectiveness of preventative interventions in reducing longer-term multimorbidity.
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Spot-scanning proton therapy for early breast cancer in free breathing versus deep inspiration breath-hold.
Stick, LB, Nielsen, LL, Trinh, CB, Bahij, I, Jensen, MF, Kronborg, CJS, Petersen, SE, Thai, LMH, Martinsen, ML, Precht, H, et al
Acta oncologica (Stockholm, Sweden). 2024;:56-61
Abstract
BACKGROUND AND PURPOSE Proton therapy for breast cancer is usually given in free breathing (FB). With the use of deep inspiration breath-hold (DIBH) technique, the location of the heart is displaced inferiorly, away from the internal mammary nodes and, thus, the dose to the heart can potentially be reduced. The aim of this study was to explore the potential benefit of proton therapy in DIBH compared to FB for highly selected patients to reduce exposure of the heart and other organs at risk. We aimed at creating proton plans with delivery times feasible with treatment in DIBH. MATERIAL AND METHODS Sixteen patients with left-sided breast cancer receiving loco-regional proton therapy were included. The FB and DIBH plans were created for each patient using spot-scanning proton therapy with 2-3 fields, robust and single field optimization. For the DIBH plans, minimum monitor unit per spot and spot spacing were increased to reduce treatment delivery time. RESULTS All plans complied with target coverage constraints. The median mean heart dose was statistically significant reduced from 1.1 to 0.6 Gy relative biological effectiveness (RBE) by applying DIBH. No statistical significant difference was seen for mean dose and V17Gy RBE to the ipsilateral lung. The median treatment delivery time for the DIBH plans was reduced by 27% compared to the FB plans without compromising the plan quality. INTERPRETATION The median absolute reduction in dose to the heart was limited. Proton treatment in DIBH may only be relevant for a subset of these patients with the largest reduction in heart exposure.
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Associations between moderate alcohol consumption, brain iron, and cognition in UK Biobank participants: Observational and mendelian randomization analyses.
Topiwala, A, Wang, C, Ebmeier, KP, Burgess, S, Bell, S, Levey, DF, Zhou, H, McCracken, C, Roca-Fernández, A, Petersen, SE, et al
PLoS medicine. 2022;(7):e1004039
Abstract
BACKGROUND Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits. METHODS AND FINDINGS Observational associations between brain iron markers and alcohol consumption (n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-sample mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippocampi, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 ± 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the "Snap" card game. Mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and never drinkers comprised 2.7% of the sample. Alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p < 0.001), caudate (β = 0.05 [0.04 to 0.07], p < 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p < 0.001) and lower iron in the thalami (β = -0.06 [-0.07 to -0.04], p < 0.001). Quintile-based analyses found these associations in those consuming >7 units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippocampus susceptibility; however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed; however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just >11 units (88 g) alcohol weekly c.f. <7 units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy. CONCLUSIONS To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.
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Multi-organ imaging demonstrates the heart-brain-liver axis in UK Biobank participants.
McCracken, C, Raisi-Estabragh, Z, Veldsman, M, Raman, B, Dennis, A, Husain, M, Nichols, TE, Petersen, SE, Neubauer, S
Nature communications. 2022;(1):7839
Abstract
Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small sample sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.
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Proton therapy for early breast cancer patients in the DBCG proton trial: planning, adaptation, and clinical experience from the first 43 patients.
Fuglsang Jensen, M, Stick, LB, Høyer, M, Kronborg, CJS, Lorenzen, EL, Mortensen, HR, Nyström, PW, Petersen, SE, Randers, P, Thai, LMH, et al
Acta oncologica (Stockholm, Sweden). 2022;(2):223-230
Abstract
BACKGROUND The Danish Breast Cancer Group (DBCG) Proton Trial randomizes breast cancer patients selected on high mean heart dose (MHD) or high lung dose (V20Gy/V17Gy) in the photon plan between photon and proton therapy. This study presents the proton plans and adaptation strategy for the first 43 breast cancer patients treated with protons in Denmark. MATERIAL AND METHODS Forty-four proton plans (one patient with bilateral cancer) were included; 2 local and 42 loco-regional including internal mammary nodes (IMN). Nineteen patients had a mastectomy and 25 a lumpectomy. The prescribed dose was either 50 Gy in 25 fractions (n = 30) or 40 Gy in 15 fractions (n = 14) wherefrom five received simultaneous integrated boost to the tumor bed. Using 2-3 en face proton fields, single-field optimization, robust optimization and a 5 cm range shifter ensured robustness towards breathing motion, setup- and range uncertainties. An anatomical evaluation was performed by evaluating the dose after adding/removing 3 mm and 5 mm tissue to/from the body-outline and used to define treatment tolerances for anatomical changes. RESULTS The nominal and robust criteria were met for all patients except two. The median MHD was 1.5 Gy (0.5-3.4 Gy, 50 Gy) and 1.1 Gy (0.0-1.5 Gy, 40 Gy). The anatomical evaluations showed how 5 mm shrinkage approximately doubled the MHD while 5 mm swelling reduced target coverage of the IMN below constraints. Ensuring 3-5 mm robustness toward swelling was prioritized but not always achieved by robust optimization alone emphasizing the need for a distal margin. Twenty-eight patients received plan adaptation, eight patients received two, and one received five. CONCLUSION This proton planning strategy ensured robust treatment plans within a pre-defined level of acceptable anatomical changes that fulfilled the planning criteria for most of the patients and ensured low MHD.
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Vitamin D and coronavirus disease 2019 (COVID-19): rapid evidence review.
Raisi-Estabragh, Z, Martineau, AR, Curtis, EM, Moon, RJ, Darling, A, Lanham-New, S, Ward, KA, Cooper, C, Munroe, PB, Petersen, SE, et al
Aging clinical and experimental research. 2021;(7):2031-2041
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Abstract
BACKGROUND The rapid global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), has re-ignited interest in the possible role of vitamin D in modulation of host responses to respiratory pathogens. Indeed, vitamin D supplementation has been proposed as a potential preventative or therapeutic strategy. Recommendations for any intervention, particularly in the context of a potentially fatal pandemic infection, should be strictly based on clinically informed appraisal of the evidence base. In this narrative review, we examine current evidence relating to vitamin D and COVID-19 and consider the most appropriate practical recommendations. OBSERVATIONS Although there are a growing number of studies investigating the links between vitamin D and COVID-19, they are mostly small and observational with high risk of bias, residual confounding, and reverse causality. Extrapolation of molecular actions of 1,25(OH)2-vitamin D to an effect of increased 25(OH)-vitamin D as a result of vitamin D supplementation is generally unfounded, as is the automatic conclusion of causal mechanisms from observational studies linking low 25(OH)-vitamin D to incident disease. Efficacy is ideally demonstrated in the context of adequately powered randomised intervention studies, although such approaches may not always be feasible. CONCLUSIONS At present, evidence to support vitamin D supplementation for the prevention or treatment of COVID-19 is inconclusive. In the absence of any further compelling data, adherence to existing national guidance on vitamin D supplementation to prevent vitamin D deficiency, predicated principally on maintaining musculoskeletal health, appears appropriate.
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Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank.
Raisi-Estabragh, Z, McCracken, C, Bethell, MS, Cooper, J, Cooper, C, Caulfield, MJ, Munroe, PB, Harvey, NC, Petersen, SE
Journal of public health (Oxford, England). 2020;42(3):451-460
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The coronavirus disease 2019 (COVID-19) pandemic has to date resulted in over 6 million cases. Growing reports highlight men and Black, Asian and Minority Ethnic (BAME) cohorts as at higher risk of adverse COVID-19 outcomes. The aim of this study was to investigate whether differential patterns of COVID-19 incidence and severity, by sex and ethnicity, might be explained by cardiometabolic, socio-economic, lifestyle and behavioural exposures. This study is a prospective cohort study of over half a million men and women from across the UK. Results showed that male sex, BAME ethnicity, higher body mass index and greater household size were associated with significantly greater odds of a positive result. However, the sex and ethnicity differential pattern of COVID-19 is not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels, socio-economic or behavioural factors. Authors conclude that investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised.
Abstract
BACKGROUND We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors. METHODS We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. RESULTS There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. CONCLUSIONS In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised.
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Personalized E-Coaching in Cardiovascular Risk Reduction: A Randomized Controlled Trial.
Khanji, MY, Balawon, A, Boubertakh, R, Hofstra, L, Narula, J, Hunink, M, Pugliese, F, Petersen, SE
Annals of global health. 2019;(1)
Abstract
OBJECTIVES To assess whether electronic (e-) coaching, using personalized web-based lifestyle and risk factor counselling with additional email prompts, provides additional risk reduction when added to standard of care (SOC) in individuals at increased risk. METHODS Between June 2013 and May 2015, 402 participants were allocated 1:1 to e-coaching and SOC versus SOC. Participants free of manifest cardiovascular disease, with internet access, and a 10-year QRISK2 cardiovascular risk of ≥10% were enrolled. Change in oscillometric carotid-femoral pulse wave velocity (PWV) from baseline to six months was the primary endpoint. Secondary outcomes included change in blood pressure (BP), weight, and risk scores. Analysis was by intention to treat. RESULTS Mean (±SD) age was 65.5 (5.6) years with 37% females. Primary outcome data were available for 94%. There was no difference in PWV reductions between e-coaching and standard of care groups (-0.16 m/s vs. -0.25 m/s, 95% confidence interval -0.39 to 0.22, p = 0.56). There were no differences in the improvement between groups for BP, weight, Framingham, or QRISK2 scores. Pulse wave velocity change was more favorable in those with a higher level of education (p = 0.04), but was not associated with age, gender, presence of diabetes, baseline QRISK2 score, or logins to the website. CONCLUSIONS In individuals at increased cardiovascular risk, a comprehensive 'health check' program modestly reduced future risk. Personalized e-coaching did not provide added risk reduction. Currently there is no evidence to routinely recommend e-coaching in cardiovascular health check programs. TRIAL REGISTRATION HAPPY London ClinicalTrials.gov: NCT01911910.
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Calcium and Vitamin D Supplementation Are Not Associated With Risk of Incident Ischemic Cardiac Events or Death: Findings From the UK Biobank Cohort.
Harvey, NC, D'Angelo, S, Paccou, J, Curtis, EM, Edwards, M, Raisi-Estabragh, Z, Walker-Bone, K, Petersen, SE, Cooper, C
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2018;(5):803-811
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We investigated associations between calcium/vitamin D supplementation and incident cardiovascular events/deaths in a UK population-based cohort. UK Biobank is a large prospective cohort comprising 502,637 men and women aged 40 to 69 years at recruitment. Supplementation with calcium/vitamin D was self-reported, and information on incident hospital admission (ICD-10) for ischemic heart disease (IHD), myocardial infarction (MI), and subsequent death was obtained from linkage to national registers. Cox proportional hazards models were used to investigate longitudinal relationships between calcium/vitamin D supplementation and hospital admission for men/women, controlling for covariates. A total of 475,255 participants (median age 58 years, 55.8% women) had complete data on calcium/vitamin D supplementation. Of that number, 33,437 participants reported taking calcium supplements; 19,089 vitamin D; and 10,007 both. In crude and adjusted analyses, there were no associations between use of calcium supplements and risk of incident hospital admission with either IHD, or subsequent death. Thus, for example, in unadjusted models, the hazard ratio (HR) for admission with myocardial infarction was 0.97 (95% confidence interval [CI] 0.79-1.20, p = 0.79) among women taking calcium supplementation. Corresponding HR for men is 1.16 (95% CI 0.92-1.46, p = 0.22). After full adjustment, HR (95% CI) were 0.82 (0.62-1.07), p = 0.14 among women and 1.12 (0.85-1.48), p = 0.41 among men. Adjusted HR (95% CI) for admission with IHD were 1.05 (0.92-1.19), p = 0.50 among women and 0.97 (0.82-1.15), p = 0.77 among men. Results were similar for vitamin D and combination supplementation. There were no associations with death, and in women, further adjustment for hormone-replacement therapy use did not alter the associations. In this very large prospective cohort, there was no evidence that use of calcium/vitamin D supplementation was associated with increased risk of hospital admission or death after ischemic cardiovascular events. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
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Prediction model to estimate presence of coronary artery disease: retrospective pooled analysis of existing cohorts.
Genders, TS, Steyerberg, EW, Hunink, MG, Nieman, K, Galema, TW, Mollet, NR, de Feyter, PJ, Krestin, GP, Alkadhi, H, Leschka, S, et al
BMJ (Clinical research ed.). 2012;:e3485
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Abstract
OBJECTIVES To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations. DESIGN Retrospective pooled analysis of individual patient data. SETTING 18 hospitals in Europe and the United States. PARTICIPANTS Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively). MAIN OUTCOME MEASURES Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined. RESULTS We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory. CONCLUSIONS Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.