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      Heterogeneous associations between smoking and a wide range of initial presentations of cardiovascular disease in 1 937 360 people in England: lifetime risks and implications for risk prediction

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          Abstract

          Background It is not known how smoking affects the initial presentation of a wide range of chronic and acute cardiovascular diseases (CVDs), nor the extent to which associations are heterogeneous. We estimated the lifetime cumulative incidence of 12 CVD presentations, and examined associations with smoking and smoking cessation.

          Methods Cohort study of 1.93 million people aged ≥30years, with no history of CVD, in 1997–2010. Individuals were drawn from linked electronic health records in England, covering primary care, hospitalizations, myocardial infarction (MI) registry and cause-specific mortality (the CALIBER programme).

          Results During 11.6 million person-years of follow-up, 114 859 people had an initial non-fatal or fatal CVD presentation. By age 90 years, current vs never smokers’ lifetime risks varied from 0.4% vs 0.2% for subarachnoid haemorrhage (SAH), to 8.9% vs 2.6% for peripheral arterial disease (PAD). Current smoking showed no association with cardiac arrest or sudden cardiac death [hazard ratio (HR) = 1.04, 95% confidence interval (CI) 0.91–1.19).The strength of association differed markedly according to disease type: stable angina (HR = 1.08, 95% CI 1.01–1.15),transient ischaemic attack (HR = 1.41, 95% CI 1.28-1.55), unstable angina (HR = 1.54, 95% CI 1.38–1.72), intracerebral haemorrhage (HR = 1.61, 95% CI 1.37–1.89), heart failure (HR = 1.62, 95% CI 1.47–1.79), ischaemic stroke (HR = 1.90, 95% CI 1.72–2.10), MI (HR = 2.32, 95% CI 2.20–2.45), SAH (HR = 2.70, 95% CI 2.27–3.21), PAD (HR = 5.16, 95% CI 4.80–5.54) and abdominal aortic aneurysm (AAA) (HR = 5.18, 95% CI 4.61–5.82). Population-attributable fractions were lower for women than men for unheralded coronary death, ischaemic stroke, PAD and AAA. Ten years after quitting smoking, the risks of PAD, AAA (in men) and unheralded coronary death remained increased (HR = 1.36, 1.47 and 2.74, respectively).

          Conclusions The heterogeneous associations of smoking with different CVD presentations suggests different underlying mechanisms and have important implications for research, clinical screening and risk prediction.

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          Most cited references58

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          Multiple imputation of discrete and continuous data by fully conditional specification.

          The goal of multiple imputation is to provide valid inferences for statistical estimates from incomplete data. To achieve that goal, imputed values should preserve the structure in the data, as well as the uncertainty about this structure, and include any knowledge about the process that generated the missing data. Two approaches for imputing multivariate data exist: joint modeling (JM) and fully conditional specification (FCS). JM is based on parametric statistical theory, and leads to imputation procedures whose statistical properties are known. JM is theoretically sound, but the joint model may lack flexibility needed to represent typical data features, potentially leading to bias. FCS is a semi-parametric and flexible alternative that specifies the multivariate model by a series of conditional models, one for each incomplete variable. FCS provides tremendous flexibility and is easy to apply, but its statistical properties are difficult to establish. Simulation work shows that FCS behaves very well in the cases studied. The present paper reviews and compares the approaches. JM and FCS were applied to pubertal development data of 3801 Dutch girls that had missing data on menarche (two categories), breast development (five categories) and pubic hair development (six stages). Imputations for these data were created under two models: a multivariate normal model with rounding and a conditionally specified discrete model. The JM approach introduced biases in the reference curves, whereas FCS did not. The paper concludes that FCS is a useful and easily applied flexible alternative to JM when no convenient and realistic joint distribution can be specified.
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            Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people

            Summary Background The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease. Methods We used linked electronic health records from 1997 to 2010 in the CALIBER (CArdiovascular research using LInked Bespoke studies and Electronic health Records) programme to assemble a cohort of 1·25 million patients, 30 years of age or older and initially free from cardiovascular disease, a fifth of whom received blood pressure-lowering treatments. We studied the heterogeneity in the age-specific associations of clinically measured blood pressure with 12 acute and chronic cardiovascular diseases, and estimated the lifetime risks (up to 95 years of age) and cardiovascular disease-free life-years lost adjusted for other risk factors at index ages 30, 60, and 80 years. This study is registered at ClinicalTrials.gov, number NCT01164371. Findings During 5·2 years median follow-up, we recorded 83 098 initial cardiovascular disease presentations. In each age group, the lowest risk for cardiovascular disease was in people with systolic blood pressure of 90–114 mm Hg and diastolic blood pressure of 60–74 mm Hg, with no evidence of a J-shaped increased risk at lower blood pressures. The effect of high blood pressure varied by cardiovascular disease endpoint, from strongly positive to no effect. Associations with high systolic blood pressure were strongest for intracerebral haemorrhage (hazard ratio 1·44 [95% CI 1·32–1·58]), subarachnoid haemorrhage (1·43 [1·25–1·63]), and stable angina (1·41 [1·36–1·46]), and weakest for abdominal aortic aneurysm (1·08 [1·00–1·17]). Compared with diastolic blood pressure, raised systolic blood pressure had a greater effect on angina, myocardial infarction, and peripheral arterial disease, whereas raised diastolic blood pressure had a greater effect on abdominal aortic aneurysm than did raised systolic pressure. Pulse pressure associations were inverse for abdominal aortic aneurysm (HR per 10 mm Hg 0·91 [95% CI 0·86–0·98]) and strongest for peripheral arterial disease (1·23 [1·20–1·27]). People with hypertension (blood pressure ≥140/90 mm Hg or those receiving blood pressure-lowering drugs) had a lifetime risk of overall cardiovascular disease at 30 years of age of 63·3% (95% CI 62·9–63·8) compared with 46·1% (45·5–46·8) for those with normal blood pressure, and developed cardiovascular disease 5·0 years earlier (95% CI 4·8–5·2). Stable and unstable angina accounted for most (43%) of the cardiovascular disease-free years of life lost associated with hypertension from index age 30 years, whereas heart failure and stable angina accounted for the largest proportion (19% each) of years of life lost from index age 80 years. Interpretation The widely held assumptions that blood pressure has strong associations with the occurrence of all cardiovascular diseases across a wide age range, and that diastolic and systolic associations are concordant, are not supported by the findings of this high-resolution study. Despite modern treatments, the lifetime burden of hypertension is substantial. These findings emphasise the need for new blood pressure-lowering strategies, and will help to inform the design of randomised trials to assess them. Funding Medical Research Council, National Institute for Health Research, and Wellcome Trust.
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              Worldwide stroke incidence and early case fatality reported in 56 population-based studies: a systematic review.

              This systematic review of population-based studies of the incidence and early (21 days to 1 month) case fatality of stroke is based on studies published from 1970 to 2008. Stroke incidence (incident strokes only) and case fatality from 21 days to 1 month post-stroke were analysed by four decades of study, two country income groups (high-income countries and low to middle income countries, in accordance with the World Bank's country classification) and, when possible, by stroke pathological type: ischaemic stroke, primary intracerebral haemorrhage, and subarachnoid haemorrhage. This Review shows a divergent, statistically significant trend in stroke incidence rates over the past four decades, with a 42% decrease in stroke incidence in high-income countries and a greater than 100% increase in stroke incidence in low to middle income countries. In 2000-08, the overall stroke incidence rates in low to middle income countries have, for the first time, exceeded the level of stroke incidence seen in high-income countries, by 20%. The time to decide whether or not stroke is an issue that should be on the governmental agenda in low to middle income countries has now passed. Now is the time for action.
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                Author and article information

                Journal
                Int J Epidemiol
                Int J Epidemiol
                ije
                intjepid
                International Journal of Epidemiology
                Oxford University Press
                0300-5771
                1464-3685
                February 2015
                20 November 2014
                20 November 2014
                : 44
                : 1
                : 129-141
                Affiliations
                1Farr Institute of Health Informatics Research, University College London, London, UK, 2Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, UK and 3National Institute for Health Research, Biomedical Research Unit, Barts Health NHS Trust, London, UK
                Author notes
                *Corresponding author. Farr Institute of Health Informatics Research, University College London, 222 Euston Road, London NW1 2DA, UK. E-mail: mar.pujades@ 123456ucl.ac.uk

                These authors are joint first authors.

                Article
                dyu218
                10.1093/ije/dyu218
                4339760
                25416721
                d155dda6-5f44-4b6c-a4c7-5ca635092daf
                © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 October 2014
                Page count
                Pages: 13
                Categories
                Cardiovascular Disease and Cardiovascular Risk Factors

                Public health
                association study,cardiovascular outcomes,epidemiology,initial presentation,lifetime risks,primary prevention,smoking,risk prediction,risk stratification

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