A model of lifetime health outcomes in cardiovascular disease based on clinical trials and large cohorts

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Wu ◽  
C Williams ◽  
I Schlackow ◽  
J Zhou ◽  
J Emberson ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Life Expectancy ◽  
Remaining Life ◽  
Uk Biobank ◽  
Cvd Risk ◽  
Micro Simulation ◽  
History Of ◽  
Remaining Life Expectancy ◽  
The Uk

Abstract Background and purpose Cardiovascular disease (CVD) risk of individuals depends on their socio-demographic characteristics, clinical risk factors, and treatments, and strongly influences their quality of life and survival. Individual-based long-term disease models, which aim to more accurately calculate the lifetime consequences, can help to target treatments, develop disease management programmes, and assess the value of new therapies. We present a new micro-simulation CVD model. Methods This micro-simulation model was developed using individual participant data from the Cholesterol Treatment Trialists' collaboration (CTT: 118,000 participants; 15 trials) and calibrated (with added socioeconomic deprivation, ethnicity, physical activity, mental illness, cancer and incident diabetes) in the UK Biobank cohort (UKB: 502,000 participants). Parametric survival models estimated risks of key endpoints (myocardial infarction (MI), stroke, coronary revascularisation (CRV), diabetes, cancer and vascular (VD) and nonvascular death (NVD) using participants' age, sex, ethnicity, physical activity, socioeconomic deprivation, smoking history, lipids, blood pressure, creatinine, previous cardiovascular diseases, diabetes, mental illness and cancer at entry and non-fatal incidents of the key endpoints during follow-up. The model integrates the risk equations and enables annual projection of endpoints and survival over individuals' lifetimes. The model was used to project remaining life expectancy across UK Biobank participants. Results Nonfatal cardiovascular events and age were the major determinants of CVD risk and, together with incident diabetes and cancer, of individuals' survival. The cumulative incidence of the key endpoints predicted by the CTT-UKB model corresponded well to their observed incidence in the UK Biobank cohort, overall (Figure 1) and in categories of participants by age, sex, prior CVD and CVD risk. Predicted remaining life expectancy across UK Biobank participants without history of CVD ranged between 22 and 43 years in men and between 24 and 46 years in women, depending on their age and CVD risk (Figure 2). Among UK Biobank participants with history of CVD, depending on their age, predicted remaining life expectancy ranged from 20 to 32 years in men and from 26 to 38 years in women. Conclusion This new lifetime CVD model accurately predicts morbidity and mortality in a large UK population cohort. It will be made available to provide individualised projections of expected lifetime health outcomes and benefits of treatments. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): UK National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Programme, UK Medical Research Council (MRC), British Heart Foundation Figure 1. Predicted (in black) versus observed (95% CI; in red) incidence of major clinical outcomes in the UK Biobank. Figure 2. Predicted remaining life expectancy of participants in UK Biobank cohort, by age and CVD risk or previous CVD at entry. QRISK, a 10-year CVD risk scoring algorithm for people without previous CVD, recommended for use in the UK National Health Service.

scholarly journals Associations of discretionary screen time with mortality, cardiovascular disease and cancer are attenuated by strength, fitness and physical activity: findings from the UK Biobank study

BMC Medicine ◽  
2018 ◽  
Vol 16 (1) ◽  
Author(s):  
Carlos A. Celis-Morales ◽  
Donald M. Lyall ◽  
Lewis Steell ◽  
Stuart R. Gray ◽  
Stamatina Iliodromiti ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Screen Time ◽  
Uk Biobank ◽  
The Uk

scholarly journals Changes in exercise frequency and cardiovascular outcomes in older adults

2019 ◽  
Vol 41 (15) ◽  
pp. 1490-1499 ◽  
Author(s):  
Kyuwoong Kim ◽  
Seulggie Choi ◽  
Seo Eun Hwang ◽  
Joung Sik Son ◽  
Jong-Koo Lee ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Older Adults ◽  
Vigorous Physical Activity ◽  
Previous History ◽  
Cvd Risk ◽  
Exercise Frequency ◽  
History Of ◽  
Reduced Risk ◽  
Physically Inactive

Abstract Aims Little is known about the association of changes in moderate to vigorous physical activity (MVPA) level with cardiovascular disease (CVD), especially in older adults whose ability to engage in frequent MVPA naturally wanes as they age. We aimed to examine the association of changes in MVPA and CVD in older adults. Methods and results In a nationwide cohort study of older adults aged 60 years or older, we identified more than 1.1 million subjects without previous history of CVD at baseline who underwent two consecutive national health screening from 2009 to 2012. We prospectively assessed the risk of CVD occurred between 2013 and 2016 according to changes in frequency of MVPA by initial MVPA status. Compared to those who were continuously physically inactive, those who increased their frequency of MVPA from physically inactive to 1–2 times per week [0.7/1000 person-years (PY) decrease in incidence rate (IR); adjusted hazard ratio (aHR) 0.95; 95% confidence interval (CI) 0.92–0.99], 3–4 times per week (1.5/1000 PY decrease in IR; aHR 0.89; 95% CI 0.84–0.94), ≥5 times per week (0.4/1000 PY decrease in IR; aHR 0.91; 95% CI 0.85–0.97) had a significantly reduced risk for total CVD (P for trend <0.001). Older adults who became physically inactive from engaging in more than 1–2 times of MVPA per week had a higher CVD risk compared to those who maintained their frequency of MVPA. Conclusion Among older adults, engaging in higher frequency of MVPA or maintaining MVPA level was associated with reduced risk of CVD.

scholarly journals Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (1) ◽  
pp. e1003487
Author(s):  
Rema Ramakrishnan ◽  
Aiden Doherty ◽  
Karl Smith-Byrne ◽  
Kazem Rahimi ◽  
Derrick Bennett ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Lower Risk ◽  
Cox Regression ◽  
Moderate Intensity ◽  
Inverse Association ◽  
Uk Biobank ◽  
Reverse Causality ◽  
Vigorous Intensity ◽  
The Uk

Background Higher levels of physical activity (PA) are associated with a lower risk of cardiovascular disease (CVD). However, uncertainty exists on whether the inverse relationship between PA and incidence of CVD is greater at the highest levels of PA. Past studies have mostly relied on self-reported evidence from questionnaire-based PA, which is crude and cannot capture all PA undertaken. We investigated the association between accelerometer-measured moderate, vigorous, and total PA and incident CVD. Methods and findings We obtained accelerometer-measured moderate-intensity and vigorous-intensity physical activities and total volume of PA, over a 7-day period in 2013–2015, for 90,211 participants without prior or concurrent CVD in the UK Biobank cohort. Participants in the lowest category of total PA smoked more, had higher body mass index and C-reactive protein, and were diagnosed with hypertension. PA was associated with 3,617 incident CVD cases during 440,004 person-years of follow-up (median (interquartile range [IQR]): 5.2 (1.2) years) using Cox regression models. We found a linear dose–response relationship for PA, whether measured as moderate-intensity, vigorous-intensity, or as total volume, with risk of incident of CVD. Hazard ratios (HRs) and 95% confidence intervals for increasing quarters of the PA distribution relative to the lowest fourth were for moderate-intensity PA: 0.71 (0.65, 0.77), 0.59 (0.54, 0.65), and 0.46 (0.41, 0.51); for vigorous-intensity PA: 0.70 (0.64, 0.77), 0.54 (0.49,0.59), and 0.41 (0.37,0.46); and for total volume of PA: 0.73 (0.67, 0.79), 0.63 (0.57, 0.69), and 0.47 (0.43, 0.52). We took account of potential confounders but unmeasured confounding remains a possibility, and while removal of early deaths did not affect the estimated HRs, we cannot completely dismiss the likelihood that reverse causality has contributed to the findings. Another possible limitation of this work is the quantification of PA intensity-levels based on methods validated in relatively small studies. Conclusions In this study, we found no evidence of a threshold for the inverse association between objectively measured moderate, vigorous, and total PA with CVD. Our findings suggest that PA is not only associated with lower risk for of CVD, but the greatest benefit is seen for those who are active at the highest level.

scholarly journals Comparison of accelerometer-derived physical activity levels between individuals with and without cancer: a UK Biobank study

2019 ◽  
Vol 15 (33) ◽  
pp. 3763-3774 ◽  
Author(s):  
Laura McDonald ◽  
Mustafa Oguz ◽  
Robert Carroll ◽  
Pratik Thakkar ◽  
Fei Yang ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cox Regression ◽  
Activity Levels ◽  
Uk Biobank ◽  
Cancer Group ◽  
All Cause Mortality ◽  
History Of ◽  
The Difference ◽  
The Uk ◽  
History Of Cancer

Aim: To identify the difference in physical activity (PA) levels between individuals with and without cancer, and to estimate all-cause mortality associated with this difference. Methods: Current cancer, cancer survivor and cancer-free groups were identified from the UK Biobank. We used multivariate and Cox regression to estimate PA differences and association of PA with all-cause mortality. Results: Compared with the cancer-free individuals, participants in the two cancer groups had fewer minutes in moderate-to-vigorous PA per day in adjusted analyses. The PA difference was associated with higher mortality in the current cancer group. Conclusion: Patients with a history of cancer were less active than those without cancer, and PA is associated with increased mortality. PA improvement strategies in cancer patients must be explored.

Abstract 15887: Clonal Hematopoiesis Links Premature Menopause to Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Michael C Honigberg ◽  
Seyedeh Zekavat ◽  
Abhishek Niroula ◽  
Gabirel K Griffin ◽  
Alexander G Bick ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Strong Association ◽  
Premature Menopause ◽  
Uk Biobank ◽  
Clonal Hematopoiesis ◽  
Age Related ◽  
Cardiovascular Disease In Women ◽  
History Of ◽  
Artery Disease ◽  
The Uk

Introduction: Premature menopause is an independent risk factor for cardiovascular disease in women, but mechanisms underlying this association remain unclear. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related expansion of hematopoietic cells with leukemogenic mutations, is associated with accelerated atherosclerosis. Whether premature menopause is associated with CHIP is unknown. Methods: We included postmenopausal women from the UK Biobank (N=11,509) aged 40-70 years with whole exome sequences and from the Women’s Health Initiative (WHI, N=8,111) aged 50-79 years with whole genome sequences. Premature menopause was defined as natural or surgical menopause occurring before age 40 years. Co-primary outcomes were the presence of (1) any CHIP and (2) CHIP with variant allele fraction (VAF) >0.1. Logistic regression tested the association of premature menopause with CHIP, adjusted for age, race, the first 10 principal components, smoking, diabetes mellitus, and hormone therapy use. Results: Across cohorts, prevalence of CHIP in women with vs. without a history of premature menopause was 8.8% vs. 5.5% (P<0.001), respectively. After multivariable adjustment, premature menopause was independently associated with CHIP, driven by associations with natural premature menopause (OR for all CHIP: 1.73, 95% CI 1.23-2.44; OR for CHIP with VAF >0.1: 1.91, 95% CI 1.30-2.80; Figure ). In gene-specific analyses, DNMT3A CHIP had a strong association with natural premature menopause but no association with surgical premature menopause. Among postmenopausal middle-aged women in the UK Biobank and WHI, CHIP was independently associated with incident coronary artery disease (meta-analyzed HR 1.52, 95% CI 1.17-1.99). Conclusions: Premature menopause, especially natural premature menopause, is independently associated with CHIP. CHIP may contribute to the excess cardiovascular risk associated with premature menopause.

scholarly journals Fitness, Physical Activity, and Cardiovascular Disease: Longitudinal and Genetic Analyses in the UK Biobank Study

2017 ◽  
Author(s):  
Emmi Tikkanen ◽  
Stefan Gustafsson ◽  
Erik Ingelsson
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Grip Strength ◽  
Cardiorespiratory Fitness ◽  
Genetic Risk ◽  
Cardiovascular Events ◽  
Large Scale ◽  
Mendelian Randomization ◽  
Uk Biobank ◽  
The Uk

AbstractBackgroundExercise is inversely related with cardiovascular disease (CVD), but large-scale studies of incident CVD events are lacking. Moreover, little is known about genetic determinants of fitness and physical activity, and modifiable effects of exercise in individuals with elevated genetic risk of CVD. Finally, causal analyses of exercise traits are limited.MethodsWe estimated associations of grip strength, physical activity, and cardiorespiratory fitness with CVD and all-cause death in up to 502,635 individuals from the UK Biobank. We also examined these associations in individuals with different genetic burden on coronary heart disease (CHD) and atrial fibrillation (AF). Finally, we performed genome-wide association study (GWAS) of grip strength and physical activity, as well as Mendelian randomization analysis to assess the causal role of grip strength in CHD.FindingsGrip strength, physical activity, and cardiorespiratory fitness showed strong inverse associations with incident cardiovascular events and all-cause death (for composite CVD; HR, 0.78, 95% CI, 0.77-0.80; HR, 0.94, 95% CI, 0.93-0.95, and HR, 0.67, 95% CI, 0.63-0.71, per SD change, respectively). We observed stronger associations of grip strength with CHD and AF for individuals in the lowest tertile of genetic risk (Pinteraction = 0.006, Pinteraction = 0.03, respectively), but the inverse associations were present in each category of genetic risk. We report 27 novel genetic loci associated with grip strength and 2 loci with physical activity, with the strongest associations in FTO (rs56094641, P=3.8×10-24) and SMIM2 (rs9316077, P=1.4×10-8), respectively. By use of Mendelian randomization, we provide evidence that grip strength is causally related to CHD.InterpretationMaintaining physical strength is likely to prevent future cardiovascular events, also in individuals with elevated genetic risk for CVD.FundingNational Institutes of Health (1 R01 HL135313-01), Knut and Alice Wallenberg Foundation (2013.0126), and the Finnish Cultural Foundation.

scholarly journals Women’s reproductive factors and incident cardiovascular disease in the UK Biobank

Heart ◽  
2018 ◽  
Vol 104 (13) ◽  
pp. 1069-1075 ◽  
Author(s):  
Sanne AE Peters ◽  
Mark Woodward
Keyword(s):  
Cardiovascular Disease ◽  
Reproductive Factors ◽  
Age At First Birth ◽  
Uk Biobank ◽  
First Birth ◽  
Early Menopause ◽  
Early Menarche ◽  
History Of ◽  
The Uk ◽  
The Relationship

BackgroundStudies have suggested that women’s reproductive factors are associated with the risk of cardiovascular disease (CVD); however, findings are mixed. We assessed the relationship between reproductive factors and incident CVD in the UK Biobank.MethodsBetween 2006 and 2010, the UK Biobank recruited over 500 000 participants aged 40–69 years across the UK. During 7 years of follow-up, 9054 incident cases of CVD (34% women), 5782 cases of coronary heart disease (CHD) (28% women), and 3489 cases of stroke (43% women) were recorded among 267 440 women and 215 088 men without a history of CVD at baseline. Cox regression models yielded adjusted hazard ratios (HRs) for CVD, CHD and stroke associated with reproductive factors.ResultsAdjusted HRs (95% CI) for CVD were 1.10 (1.01 to 1.30) for early menarche (<12 years), 0.97 (0.96 to 0.98) for each year increase in age at first birth, 1.04 (1.00 to 1.09) for each miscarriage, 1.14 (1.02 to 1.28) for each stillbirth, and 1.33 (1.19 to 1.49) for early menopause (<47 years). Hysterectomy without oophorectomy or with previous oophorectomy had adjusted HRs of 1.16 (1.06 to 1.28) and 2.30 (1.20 to 4.43) for CVD. Each additional child was associated with a HR for CVD of 1.03 (1.00 to 1.06) in women and 1.03 (1.02 to 1.05) in men.ConclusionsEarly menarche, early menopause, earlier age at first birth, and a history of miscarriage, stillbirth or hysterectomy were each independently associated with a higher risk of CVD in later life. The relationship between the number of children and incident CVD was similar for men and women.

scholarly journals Correction: Accelerometer measured physical activity and the incidence of cardiovascular disease: Evidence from the UK Biobank cohort study

PLoS Medicine ◽  
2021 ◽  
Vol 18 (9) ◽  
pp. e1003809
Author(s):  
Rema Ramakrishnan ◽  
Aiden Doherty ◽  
Karl Smith-Byrne ◽  
Kazem Rahimi ◽  
Derrick Bennett ◽  
...  
Keyword(s):  
Physical Activity ◽  
Cardiovascular Disease ◽  
Cohort Study ◽  
Uk Biobank ◽  
The Uk

Advanced cardiometabolic & inflammatory markers for prediction of cardiovascular disease and cancer

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
D Radenkovic ◽  
S.C Chawla ◽  
G Botta ◽  
A Boli ◽  
M.B Banach ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Risk Score ◽  
Cancer Incidence ◽  
Risk Function ◽  
Patient Characteristics ◽  
Risk Scores ◽  
Uk Biobank ◽  
Training Set ◽  
All Cause Mortality ◽  
The Uk

Abstract   The two leading causes of mortality worldwide are cardiovascular disease (CVD) and cancer. The annual total cost of CVD and cancer is an estimated $844.4 billion in the US and is projected to double by 2030. Thus, there has been an increased shift to preventive medicine to improve health outcomes and development of risk scores, which allow early identification of individuals at risk to target personalised interventions and prevent disease. Our aim was to define a Risk Score R(x) which, given the baseline characteristics of a given individual, outputs the relative risk for composite CVD, cancer incidence and all-cause mortality. A non-linear model was used to calculate risk scores based on the participants of the UK Biobank (= 502548). The model used parameters including patient characteristics (age, sex, ethnicity), baseline conditions, lifestyle factors of diet and physical activity, blood pressure, metabolic markers and advanced lipid variables, including ApoA and ApoB and lipoprotein(a), as input. The risk score was defined by normalising the risk function by a fixed value, the average risk of the training set. To fit the non-linear model &gt;400,000 participants were used as training set and &gt;45,000 participants were used as test set for validation. The exponent of risk function was represented as a multilayer neural network. This allowed capturing interdependent behaviour of covariates, training a single model for all outcomes, and preserving heterogeneity of the groups, which is in contrast to CoxPH models which are traditionally used in risk scores and require homogeneous groups. The model was trained over 60 epochs and predictive performance was determined by the C-index with standard errors and confidence intervals estimated with bootstrap sampling. By inputing the variables described, one can obtain personalised hazard ratios for 3 major outcomes of CVD, cancer and all-cause mortality. Therefore, an individual with a risk Score of e.g. 1.5, at any time he/she has 50% more chances than average of experiencing the corresponding event. The proposed model showed the following discrimination, for risk of CVD (C-index = 0.8006), cancer incidence (C-index = 0.6907), and all-cause mortality (C-index = 0.7770) on the validation set. The CVD model is particularly strong (C-index &gt;0.8) and is an improvement on a previous CVD risk prediction model also based on classical risk factors with total cholesterol and HDL-c on the UK Biobank data (C-index = 0.7444) published last year (Welsh et al. 2019). Unlike classically-used CoxPH models, our model considers correlation of variables as shown by the table of the values of correlation in Figure 1. This is an accurate model that is based on the most comprehensive set of patient characteristics and biomarkers, allowing clinicians to identify multiple targets for improvement and practice active preventive cardiology in the era of precision medicine. Figure 1. Correlation of variables in the R(x) Funding Acknowledgement Type of funding source: None

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