Type 2 diabetes and incidence of cardiovascular diseases: a cohort study in 1·9 million people

Summary Background The contemporary associations of type 2 diabetes with a wide range of incident cardiovascular diseases have not been compared. We aimed to study associations between type 2 diabetes and 12 initial manifestations of cardiovascular disease. Methods We used linked primary care, hospital admission, disease registry, and death certificate records from the CALIBER programme, which links data for people in England recorded in four electronic health data sources. We included people who were (or turned) 30 years or older between Jan 1, 1998, to March 25, 2010, who were free from cardiovascular disease at baseline. The primary endpoint was the first record of one of 12 cardiovascular presentations in any of the data sources. We compared cumulative incidence curves for the initial presentation of cardiovascular disease and used Cox models to estimate cause-specific hazard ratios (HRs). This study is registered at ClinicalTrials.gov (NCT01804439). Findings Our cohort consisted of 1 921 260 individuals, of whom 1 887 062 (98·2%) did not have diabetes and 34 198 (1·8%) had type 2 diabetes. We observed 113 638 first presentations of cardiovascular disease during a median follow-up of 5·5 years (IQR 2·1–10·1). Of people with type 2 diabetes, 6137 (17·9%) had a first cardiovascular presentation, the most common of which were peripheral arterial disease (reported in 992 [16·2%] of 6137 patients) and heart failure (866 [14·1%] of 6137 patients). Type 2 diabetes was positively associated with peripheral arterial disease (adjusted HR 2·98 [95% CI 2·76–3·22]), ischaemic stroke (1·72 [1·52–1·95]), stable angina (1·62 [1·49–1·77]), heart failure (1·56 [1·45–1·69]), and non-fatal myocardial infarction (1·54 [1·42–1·67]), but was inversely associated with abdominal aortic aneurysm (0·46 [0·35–0·59]) and subarachnoid haemorrhage (0·48 [0·26–0.89]), and not associated with arrhythmia or sudden cardiac death (0·95 [0·76–1·19]). Interpretation Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. The differences between relative risks of different cardiovascular diseases in patients with type 2 diabetes have implications for clinical risk assessment and trial design. Funding Wellcome Trust, National Institute for Health Research, and Medical Research Council.

[1]  Robert J. Hinchliffe,et al.  Pathophysiology and epidemiology of abdominal aortic aneurysms , 2011, Nature Reviews Cardiology.

[2]  Deepak L. Bhatt,et al.  Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. , 2013, The New England journal of medicine.

[3]  E. Barrett-Connor,et al.  Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis. , 2002, Archives of internal medicine.

[4]  Thomas S Riles,et al.  Analysis of risk factors for abdominal aortic aneurysm in a cohort of more than 3 million individuals. , 2010, Journal of vascular surgery.

[5]  B. Zinman,et al.  Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies. , 2000, Diabetes care.

[6]  M. Ashworth,et al.  Quality and Outcomes Framework: smoke and mirrors? , 2010, Quality in primary care.

[7]  J. Danesh,et al.  Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. , 2010, Lancet.

[8]  G. Riccardi,et al.  Cardiovascular risk in women with diabetes. , 2010, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[9]  L. Smeeth,et al.  The Myocardial Ischaemia National Audit Project (MINAP) , 2010, Heart.

[10]  M. Hanefeld,et al.  Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis. , 2007, The New England journal of medicine.

[11]  Craig S. Anderson,et al.  Risk Factors for Subarachnoid Hemorrhage: An Updated Systematic Review of Epidemiological Studies , 2005, Stroke.

[12]  S. Soedamah-Muthu,et al.  Risk of stroke in people with type 2 diabetes in the UK: a study using the General Practice Research Database , 2006, Diabetologia.

[13]  Harry Hemingway,et al.  Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people , 2014, The Lancet.

[14]  M. Woodward,et al.  Diabetes as risk factor for incident coronary heart disease in women compared with men: a systematic review and meta-analysis of 64 cohorts including 858,507 individuals and 28,203 coronary events , 2014, Diabetologia.

[15]  S. Schinner,et al.  Effects of Intensive Glucose Lowering in Type 2 Diabetes , 2009 .

[16]  S. de Lusignan,et al.  Miscoding, misclassification and misdiagnosis of diabetes in primary care , 2012, Diabetic medicine : a journal of the British Diabetic Association.

[17]  S. van Buuren Multiple imputation of discrete and continuous data by fully conditional specification , 2007, Statistical methods in medical research.

[18]  W. Kannel,et al.  Diabetes and cardiovascular disease. The Framingham study. , 1979, JAMA.

[19]  The Emerging Risk Factors Collaboration Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies , 2010, The Lancet.

[20]  E. Barrett,et al.  Cardiac outcomes after screening for asymptomatic coronary artery disease in patients with type 2 diabetes: the DIAD study: a randomized controlled trial. , 2009, JAMA.

[21]  Igor Rudan,et al.  Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis , 2013, The Lancet.

[22]  Michael E. Miller,et al.  ACTION TO CONTROL CARDIOVASCULAR RISK IN DIABETES STUDY GROUP. EFFECTS OF INTENSIVE GLUCOSE LOWERING IN TYPE 2 DIABETES , 2010 .

[23]  A. Go,et al.  Traditional and novel risk factors for clinically diagnosed abdominal aortic aneurysm: the Kaiser multiphasic health checkup cohort study. , 2007, Annals of epidemiology.

[24]  M. Woodward,et al.  Diabetes as a risk factor for stroke in women compared with men: a systematic review and meta-analysis of 64 cohorts, including 775 385 individuals and 12 539 strokes , 2014, The Lancet.

[25]  P. de Rango,et al.  Diabetes and abdominal aortic aneurysms. , 2014, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[26]  Dipak Kalra,et al.  Data Resource Profile: Cardiovascular disease research using linked bespoke studies and electronic health records (CALIBER) , 2012, International journal of epidemiology.

[27]  Diederick E. Grobbee,et al.  The global burden of diabetes and its complications: an emerging pandemic , 2010, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.

[28]  K E Porter,et al.  Diabetes and the abdominal aortic aneurysm. , 2010, European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery.

[29]  B. Sonesson,et al.  Socioeconomic position, comorbidity, and mortality in aortic aneurysms: a 13-year prospective cohort study. , 2012, Annals of vascular surgery.

[30]  Nish Chaturvedi,et al.  Cardiorenal end points in a trial of aliskiren for type 2 diabetes. , 2012, The New England journal of medicine.

[31]  T. Rea,et al.  Type 2 diabetes mellitus and the risk of sudden cardiac arrest in the community , 2010, Reviews in Endocrine and Metabolic Disorders.

[32]  Lord Bourne,et al.  Department for Communities and Local Government: Troubled families programme: transforming the lives of thousands of families , 2016 .

[33]  R. Califf,et al.  Rationale, design, and organization of a randomized, controlled Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) in patients with type 2 diabetes and established cardiovascular disease. , 2013, American heart journal.

[34]  L. Smeeth,et al.  Validation and validity of diagnoses in the General Practice Research Database: a systematic review , 2010, British journal of clinical pharmacology.

[35]  Spiros C. Denaxas,et al.  Completeness and diagnostic validity of recording acute myocardial infarction events in primary care, hospital care, disease registry, and national mortality records: cohort study , 2013, BMJ.

[36]  J. Pankow,et al.  Diabetes and the risk of sudden cardiac death, the Atherosclerosis Risk in Communities study , 2010, Acta Diabetologica.