Associations between commute mode and cardiovascular disease, cancer, and all-cause mortality, and cancer incidence, using linked Census data over 25 years in England and Wales: a cohort study

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 >400,000 participants were used as training set and >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 >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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Joint association of modifiable lifestyle and metabolic health status with incidence of cardiovascular disease and all-cause mortality: a prospective cohort study

Endocrine ◽

10.1007/s12020-021-02832-9 ◽

2021 ◽

Author(s):

Yingting Zuo ◽

Haibin Li ◽

Shuohua Chen ◽

Xue Tian ◽

Dapeng Mo ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Health Status ◽

Prospective Cohort Study ◽

Prospective Cohort ◽

Metabolic Health ◽

All Cause Mortality

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Mannose-binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

10.2337/figshare.12240836 ◽

2020 ◽

Author(s):

Anne Gedebjerg ◽

Mette Bjerre ◽

Alisa Devedzic Kjaergaard ◽

Rudi Steffensen ◽

Jens Steen Nielsen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cohort Study ◽

Cardiovascular Events ◽

Cox Regression ◽

Mannose Binding Lectin ◽

Mannose Binding ◽

All Cause Mortality ◽

Binding Lectin

Objective: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease in diabetes, but the nature of the association is unclear. We investigated the association between MBL and risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. Research Design and Methods: In a cohort study of 7588 patients with type 2 diabetes, we measured serum MBL in 7305 and performed MBL expression genotyping in 3043. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, and cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. Results: Serum MBL and CVE showed a U-shaped association. Compared to the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI, 1.34 to 2.46) for the low-MBL category and 1.48 (95% CI, 1.14 to 1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared to the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI, 0.87 to 2.25) for the low-expression genotype and 1.44 (95% CI, 1.01 to 2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. Conclusions: Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for cardiovascular disease in this population.

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Mannose-binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

10.2337/figshare.12240836.v1 ◽

2020 ◽

Author(s):

Anne Gedebjerg ◽

Mette Bjerre ◽

Alisa Devedzic Kjaergaard ◽

Rudi Steffensen ◽

Jens Steen Nielsen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cohort Study ◽

Cardiovascular Events ◽

Cox Regression ◽

Mannose Binding Lectin ◽

Mannose Binding ◽

All Cause Mortality ◽

Binding Lectin

Objective: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease in diabetes, but the nature of the association is unclear. We investigated the association between MBL and risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. Research Design and Methods: In a cohort study of 7588 patients with type 2 diabetes, we measured serum MBL in 7305 and performed MBL expression genotyping in 3043. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, and cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. Results: Serum MBL and CVE showed a U-shaped association. Compared to the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI, 1.34 to 2.46) for the low-MBL category and 1.48 (95% CI, 1.14 to 1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared to the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI, 0.87 to 2.25) for the low-expression genotype and 1.44 (95% CI, 1.01 to 2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. Conclusions: Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for cardiovascular disease in this population.

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Cardiothoracic Ratio and All-Cause Mortality and Cardiovascular Disease Events in Hemodialysis Patients: The Q-Cohort Study

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2016.11.026 ◽

2017 ◽

Vol 70 (1) ◽

pp. 84-92 ◽

Cited By ~ 15

Author(s):

Ryusuke Yotsueda ◽

Masatomo Taniguchi ◽

Shigeru Tanaka ◽

Masahiro Eriguchi ◽

Kiichiro Fujisaki ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Hemodialysis Patients ◽

Cardiothoracic Ratio ◽

All Cause Mortality

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408Albuminuria as a predictor of incident ischemic stroke and myocardial infarction in patients with type 2 diabetes but without cardiovascular disease: A Danish cohort study

European Heart Journal ◽

10.1093/eurheartj/ehz747.0103 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

M V Fangel ◽

P B Nielsen ◽

J K Kristensen ◽

T B Larsen ◽

T F Overvad ◽

...

Keyword(s):

Risk Factors ◽

Myocardial Infarction ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Cohort Study ◽

Ischemic Stroke ◽

Cardiovascular Risk ◽

All Cause Mortality ◽

Patients With Diabetes

Abstract Background Risk stratification in patients with type 2 diabetes continues to be an important priority in the management of diabetes-related morbidity and mortality. International guidelines generally recognize patients with diabetes and cardiovascular disease as high-risk patients. Risk stratification is, however, more uncertain in diabetes patients without cardiovascular disease. Micro- and macroalbuminuria have previously been identified as predictors of cardiovascular events and mortality in general cohorts of diabetes patients. However, less is known about the predictive value of albuminuria in patients with diabetes but without established cardiovascular disease. Purpose We aimed to examine the association between albuminuria level and the risk of ischemic stroke, myocardial infarction, and all-cause mortality in patients with type 2 diabetes and without a diagnosis of cardiovascular disease. Methods We linked Danish nationwide registries to identify patients with type 2 diabetes and without cardiovascular disease from May 2005 through June 2015. Based on two consecutive measurements of the urinary albumin excretion rate or albumin-to-creatinine ratio patients were stratified in categories of normoalbuminuria, microalbuminuria, and macroalbuminuria. Patients were followed for the outcomes ischemic stroke, myocardial infarction, and all-cause mortality until December 31, 2015. Five-year risk of outcomes were presented as cumulative incidence functions (with death as a competing event). Associations between albuminuria level and incidence of ischemic stroke, myocardial infarction, and all-cause mortality were evaluated with Cox proportional hazard regression adjusted for cardiovascular risk factors. Results The study population included 78,841 patients with type 2 diabetes (44.7% females, mean age 63.2). When comparing patients with microalbuminuria to patients with normoalbuminuria in an age- and sex-adjusted analysis, we found hazard ratios (HRs) of 1.45 (95% CI: 1.24–1.69), 1.45 (95% CI: 1.24–1.70), and 1.50 (95% CI: 1.39–1.61) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. Furthermore, macroalbuminuria was associated with HRs of 2.05 (95% CI: 1.70–2.48), 2.25 (95% CI: 1.86–2.71), and 2.03 (95% CI: 1.85–2.23) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. Similar results were found after adjusting for cardiovascular risk factors. Conclusions In this nationwide cohort study of patients with type 2 diabetes but without cardiovascular disease, patients with micro- and macroalbuminuria had a higher risk of incident ischemic stroke, myocardial infarction, and all-cause mortality. This finding supports that patients with micro- or macroalbuminuria should be screened regularly and followed closely in clinical practice. Moreover, these findings suggest that patients with type 2 diabetes and micro- or macroalbuminuria may benefit from intensive vascular risk reduction.

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Haemoglobin concentration and survival of haemodialysis patients before and after experiencing cardiovascular disease: a cohort study from Japanese dialysis outcomes and practice pattern study (J-DOPPS)

BMJ Open ◽

10.1136/bmjopen-2019-031476 ◽

2019 ◽

Vol 9 (9) ◽

pp. e031476

Author(s):

Ryo Kido ◽

Tadao Akizawa ◽

Shunichi Fukuhara

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Cardiovascular Events ◽

Haemoglobin Concentration ◽

Time Dependent ◽

Comorbid Condition ◽

Cardiovascular Comorbidity ◽

All Cause Mortality ◽

Before And After ◽

Dialysis Outcomes

ObjectivesDifferences in the association of haemoglobin concentration with mortality or adverse cardiovascular events in haemodialysis patients before and after experiencing cardiovascular disease are unclear. We aimed to assess the influence of cardiovascular-comorbid condition on the association between haemoglobin concentration and mortality.DesignA prospective cohort study.SettingThe Dialysis Outcomes and Practice Patterns Study Dialysis in phases 2 to 4 (2002 to 2011), including 80 randomly selected dialysis facilities in Japan (J-DOPPS).Participants5515 adult haemodialysis patients.Primary and secondary outcome measuresPrimary outcome was all-cause mortality. Cardiovascular mortality and adverse cardiovascular events were also evaluated. The association of these outcomes with haemoglobin concentration, categorised into six classes by 1.0 g/dL units, and cardiovascular-comorbid condition, treated as a time-dependent variable updated every 4 months, was evaluated. Adjusted hazard ratios (aHRs) were computed using a time-dependent Cox model with interaction test for cardiovascular comorbidity.ResultsOver a median 2.0 years, 847 all-cause and 326 cardiovascular deaths, and 1000 adverse cardiovascular events occurred. Compared with haemoglobin 11.0 to 11.9 g/dL, the aHRs of mortality at the lowest range (<9.0 g/dL) were 1.29 (95% CI 0.95 to 1.76) and 2.11 (95% CI 1.47 to 3.06) in cardiovascular-comorbid and non-cardiovascular-comorbid patients, respectively (p=0.04 for cardiovascular-comorbid interaction), with increased cardiovascular mortality in both groups. At the second-lowest range (9.0 to 9.9 g/dL), mortality was increased only in non-cardiovascular-comorbid patients. Respective risks for mortality and adverse cardiovascular events at the second-highest range (12.0 to 12.9 g/dL) were non-significant but increased in both groups, while adverse cardiovascular events were increased at the highest range (≥13.0 g/dL) in non-cardiovascular-comorbid patients.ConclusionsThe association of low haemoglobin concentration with all-cause mortality differed between haemodialysis patients with and without cardiovascular comorbidity. Cardiovascular-comorbid condition should be considered when the association of haemoglobin concentration with mortality is addressed.

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Cardiovascular Disease and All-Cause Mortality in Male Twins With Discordant Cardiorespiratory Fitness: A Nationwide Cohort Study

American Journal of Epidemiology ◽

10.1093/aje/kwaa060 ◽

2020 ◽

Vol 189 (10) ◽

pp. 1114-1123

Author(s):

Marcel Ballin ◽

Anna Nordström ◽

Peter Nordström

Keyword(s):

Cardiovascular Disease ◽

Cohort Study ◽

Confidence Interval ◽

Cardiorespiratory Fitness ◽

Military Service ◽

Lower Risk ◽

Hazard Ratio ◽

Familial Factors ◽

All Cause Mortality

Abstract Whether genetic and familial factors influence the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is unknown. Two cohorts were formed based on data from 1,212,295 men aged 18 years who were conscripted for military service in Sweden during 1972–1996. The first comprised 4,260 twin pairs in which the twins in each pair had different CRF (≥1 watt). The second comprised 90,331 nonsibling pairs with different CRF and matched on birth year and year of conscription. Incident CVD and all-cause mortality were identified using national registers. During follow-up (median 32 years), there was no difference in CVD and mortality between fitter twins and less fit twins (246 vs. 251 events; hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.83, 1.20). The risks were similar in twin pairs with ≥60-watt difference in CRF (HR = 0.96, 95% CI: 0.57, 1.64). In contrast, in the nonsibling cohort, fitter men had a lower risk of the outcomes than less fit men (4,444 vs. 5,298 events; HR = 0.83, 95% CI: 0.79, 0.86). The association was stronger in pairs with ≥60-watt difference in CRF (HR = 0.65, 95% CI: 0.59, 0.71). These findings indicate that genetic and familial factors influence the association of CRF with CVD and mortality.

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