Introduction
Why estimate CVD risk in individuals with diabetes?
Systematic review of CVD risk assessment tools
Search strategy
Selection criteria
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Fatal or non-fatal CVD
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Fatal or non-fatal CHD
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Fatal or non-fatal cerebrovascular disease or stroke
Data extraction
Name of risk score | Derivation population (setting) | Definition of diabetes | Follow-up time | Main outcome | Risk factors included in score |
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UKPDS risk engine (UKPDS 56) [47] | 4,540 men and women aged 25–65 years with diabetes, without history of MI, angina or heart failure (UK) | Newly physician-diagnosed diabetes and FPG >6 mmol/l on two further occasions | Median F/U 10.3 years | Fatal or non-fatal MI, or sudden death (verified by two independent clinical assessors) | Age at diagnosis of DM, sex, ethnicity, smoking, HbA1c, systolic BP, total-cholesterol:HDL-cholesterol ratio, duration of DM |
Oxford risk engine (UKPDS risk engine version 3) [48] | 3,465 men and women aged 25–65 years with and without diabetes with no known CVD (UK) | Newly physician-diagnosed diabetes and FPG >6 mmol/l on two further occasions | Median F/U 5 years | CVD (first occurrence of fatal or non-fatal MI, sudden cardiac death, other ischaemic heart disease, fatal or non-fatal stroke, or fatal peripheral vascular disease) | Age at diagnosis of DM, sex, ethnicity, smoking, HbA1c, systolic BP, total cholesterol:HDL-cholesterol ratio, duration of DM |
Diabetes Audit and Research in Tayside, Scotland (DARTS) [17] | 4,569 men and women of any age with diabetes without previous cardiovascular events (Scotland) | Those at any age treated with diet or oral hypoglycaemic agents or those aged >35 years with diagnosis of diabetes (Web-based information system) (Sensitivity/specificity of the ascertainment 97%) | Mean (SD) F/U 4.7 (6.1) years | First major CHD event (fatal or non-fatal acute MI or CHD death) | Age at diagnosis of DM, sex, systolic BP, duration of DM, smoking, total cholesterol, HbA1c, treated hypertension, height |
Swedish National Diabetes Register (NDR) [23] | 5,823 men and women aged 18–70 years with diabetes and no previous CVD (Sweden) | Diagnosis of diabetes from the Swedish National Diabetes Register | Mean F/U 5.6 years | Fatal or non-fatal CVD (CHD or stroke, including coronary intervention) retrieved by data linkage | Age at diagnosis of DM, sex, smoking, duration of diabetes, BMI, systolic BP, HbA1c, antihypertensive drugs, lipid-lowering drugs |
Atherosclerosis Risk in Communities (ARIC) [15] | 1,500 men and women aged 45–64 years with diabetes, initially free of CHD (USA) (no validation) | FPG >7.0 mmol/l, non-fasting glucose >11.1 mmol/l, self-reported physician-diagnosed diabetes or pharmacological treatment for diabetes | Median F/U 10.2 years | CHD (validated definite or probable hospitalised MI, definite CHD death, an unrecognised MI defined by ECG readings, or coronary revascularisation) | Age, ethnicity, smoking, systolic BP, use of antihypertensive medication, total cholesterol, HDL; alternative model includes: BMI, WHR, sport activity, Keys score for diet, serum creatinine, serum albumin, WBC, factor VIII, LVH, and IMT |
Hong Kong Diabetes Registry [18] | 3,521 Chinese men and women with median age of 57 years without a history of CHD or heart failure (Hong Kong) | Type 2 diabetes referred from GP and special clinics, and patients discharged from hospitals | Median F/U 5.59 years | Total CHD (MI or IHD) retrieved from discharge diagnosis | Age, sex, smoking, duration of diabetes, systolic BP, GFR, ACR, non-HDL-cholesterol |
UKPDS for stroke (UKPDS 60) [49] | 4,549 men and women aged 25–65 years with diabetes, no known stroke (UK) | Newly physician-diagnosed diabetes, and FPG >6 mmol/l on two further occasions | Median F/U 10.5 years | Stroke defined as neurological deficit with symptoms or signs lasting 1 month or more | Age at diagnosis of DM, sex, smoking, atrial fibrillation, systolic BP, total:HDL-cholesterol ratio, duration of DM |
Hong Kong Diabetes Registry for stroke [26] | 3,668 diabetic patients without history of stroke, referred to the Prince of Wales Hospital (Hong Kong) | Type 2 diabetes referred from GP and special clinics, and patients discharged from hospitals | Median F/U 5.4 years | Fatal and non-fatal haemorrhagic and ischaemic stroke (data retrieved via the Hong Kong hospital authority central computer system) | Age, HbA1c, ACR, history of CHD |
Name of risk score | Study population (setting) | Definition of diabetes | Follow-up time | Main outcome | Risk factors included in score |
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Framingham 1991 [50] | 5,573 US white men and women aged 30–74 years with no overt CHD (6% DM) | Treatment with insulin or oral hypoglycaemic drugs, blood glucose >8.3 mmol/l at two clinic visits, or fasting blood glucose >7.8 mmol/l at initial examination of the Offspring Study [51] | 12 years | Myocardial infarction, CHD, death from CHD, stroke, CVD, death from CVD | Age, sex, blood pressure, total cholesterol, HDL-cholesterol, smoking, glucose intolerance, left ventricular hypertrophy by echocardiogram |
Framingham 1998 [52] | 5,345 US white men and women aged 30–74 years with no overt CHD (6% DM) | Treatment with insulin or oral hypoglycaemic drugs, blood glucose >8.3 mmol/l at two clinic visits, or fasting blood glucose >7.8 mmol/l at initial examination of the Offspring Study [51] | 12 years | CHD (angina pectoris, recognised and unrecognised MI, coronary insufficiency, CHD death) Hard CHD included total CHD without angina pectoris | Age, sex, diabetes, smoking, blood pressure, total or LDL-cholesterol, HDL-cholesterol |
PROCAM score [53] | 5,389 German white working men aged 35–65 years with no history of MI, stroke, angina pectoris or baseline ECG signs of IHD (Germany) (16.1% DM) | N/A | 10 years | Major coronary event (sudden cardiac death, definite fatal or non-fatal MI on basis of ECG and/or cardiac enzyme changes) | Age, smoking, diabetes, family history of premature MI, systolic blood pressure, HDL-cholesterol, LDL-cholesterol, triacylglycerol |
Joint British Societies Risk Chart (JBSRC) [54] | Computerised CHD risk prediction chart based on Framingham risk equations | Not applicable | Not applicable | Coronary heart disease | Age, sex, systolic and diastolic BP, total and HDL-cholesterol, smoking, diabetes, presence of left ventricular hypertrophy from ECG |
CardioRisk Manager calculator (CRM), computerised version of Framingham equation [55] | Computerised version of full equations of Framingham risk score to test against a placebo arm of West of Scotland Coronary Prevention Study (WOSCOPS) [56] | Not applicable | Not applicable | CHD or stroke | CHD: age, sex, blood pressure, total cholesterol, HDL-cholesterol, smoking, glucose intolerance, left ventricular hypertrophy by echocardiogram; stroke: age, systolic blood pressure, diabetes, smoking, prior CVD, atrial fibrillation, left ventricular hypertrophy by electrocardiogram, use of antihypertensive medication prior to occurrence of stroke |
Myocardial Infarction Population Registry of Girona (REGICOR) [57] | Men and women aged 35–74 in Girona, Spain (data from myocardial infarction population registry of Girona, REGICOR) | N/A | 10 years | Fatal or non-fatal AMI, with or without symptoms, or angina | Age, sex, total cholesterol, HDL-cholesterol, blood pressure, smoking, diabetes |
SCORE [16] | 205,178 European men and women aged 19–80 years with no history of MI (12 European countries) | Not applicable | Varies among cohorts, up to 25 years | CVD mortality (ICD-9 codes 401–414 and 426–443, with the exception of non-atherosclerotic causes of death: 426.7, 429.0, 430.0, 432.1, 437.3, 437.4 and 437.5; ICD-9 codes 798.1 and 798.2 were also classified as CVD deaths) | Age, sex, systolic blood pressure, smoking, total cholesterol or total cholesterol:HDL-cholesterol ratio |
DECODE score [58] | 25,413 European men and women aged 30–74 years (14 European studies) (4% known DM, 5% screen-detected DM ) | Known diabetes and screen-detected diabetes using OGTT | 4.8 to more than 10 years | CVD mortality (CVD codes 401–448 of the 8th and 9th ICD revisions, code I10–I79 of the 10th revision) | Age, sex, FPG and 2-h plasma glucose, diabetes, smoking, systolic blood pressure, total cholesterol |
Framingham Stroke [59] | 5,734 men and women aged 55–84 years with no history of stroke (USA) | Treatment with insulin or oral hypoglycaemic drugs, and fasting blood glucose | 10 years | Brain infarction and transient ischaemic attack, cerebral embolus, intracranial haemorrhage | Age, systolic blood pressure, diabetes, smoking, prior CVD, atrial fibrillation, left ventricular hypertrophy by electrocardiogram, use of antihypertensive medication prior to occurrence of stroke |
Results
Name of risk score | Validation population | Definition of diabetes | Outcome (n events) | Discrimination | Calibration | Sensitivity and specificity (%) | PPV/NPV (%) |
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UKPDS risk engine [47] | 428 men and women aged 30–74 years with newly diagnosed diabetes without pre-existing CVD, mean F/U 4.2 (0.6) years (GP recruitment in Poole, UK) [21] | Surveillance programme to identify diabetes cases; methods of diagnosis, N/A | CHD determined via hospital and GP notes, death certificates and post-mortem examination record (98) | CHD: aROC 0.670 (0.598–0.742) | Poor calibration for CHD: HL χ
2 17.1 (p = 0.029) | 10 year CHD risk >15%: Sen 89.8 (95% CI 82.0–95.0) Spc 30.3 (95% CI 25.4–35.6) | N/A |
339 diabetic patients with 10 years of follow-up (Greece) [25] | N/A | CHD determined by coronary angiography (108) | aROC 0.61 | N/A | Sen 56; Spc 56 (no data on which risk threshold was used) | PPV 37; NPV 73 (no data on which risk threshold was used) | |
112 patients with type 2 diabetes with 10 years of follow-up (Spain) [22] | 1985 WHO criteria (FPG >7.7 mmol/l or, 2 h OGTT >11.0 mmol/l) | CHD event (19) | N/A | Men: overestimation by 108.8%; women: overestimation by 51.3% | 10 year CHD risk >20%: men: Sen 67; Spc 7; women: Sen 71; Spc 59 | 10 year CHD risk >20%: men: PPV 14; NPV 50; women: PPV 24; NPV 92 | |
798 diabetic patients identified via a computerised clinic database, follow-up 10 years [19] | N/A | CHD and CVD determined through computerised clinical records (358 CVD, including 269 CHD events) | CVD: c = 0.74; CHD: c = 0.65 | Poor calibration (p < 0.001); observed:predicted events ratio 1.20 and 1.60 for CVD and CHD (r = 0.89 and 0.86 respectively) | N/A | N/A | |
3,546 Chinese men and women with median age of 56 years without a history of CHD or HF, median F/U of 5.59 years (Hong Kong) [18] | Type 2 diabetes referred from GP and special clinics, and those discharged from hospitals | Hard CHD: myocardial infarction and CHD death (170) | Overall c statistic 0.610 (95% CI 0.581–0.639) | Poor calibration: HL χ
2 = 230.1; p < 0.0001 | N/A | N/A | |
Oxford risk engine (UKPDS risk engine version 3) [48] | 1,410 men and women aged 40–75 years on the placebo arm of the Collaborative Atorvastatin Diabetes Study (CARDS) (median F/U 3.9 years) [48] | 1985 WHO criteria (computerised registers of patients and by opportunistic assessment of individuals attending diabetes clinics) | CVD event (189) | N/A | Underestimation by 10.6%; 189 observed events vs 169 predicted events over 3.9 years | N/A | N/A |
Diabetes Audit and Research in Tayside, Scotland (DARTS) [17] | Salford Diabetes Information System, F/U 5 years [17] | Treatment with diet or oral hypoglycaemic agents/age >35 years | CHD determined via hospital episode statistics (N/A) |
c statistic = 0.69 (95% CI 0.58–0.78) | Included a graph but no statistical test | N/A | N/A |
Swedish National Diabetes Register (NDR) [23] | 5,823 men and women aged 18–70 years with diabetes, no previous CVD, F/U 5.6 years (Swedish) [23] | Diagnosis of diabetes from the Swedish National Diabetes Register | Fatal and non-fatal CVD (N/A) |
c statistic = 0.69 | Good calibration; observed:predicted CVD rate ratio 0.998 | N/A | N/A |
3,068 men and women aged 18–70 years with diabetes, no previous CVD, F/U 4 years (Swedish) [23] | Diagnosis of diabetes from the Swedish National Diabetes Register | Fatal and non-fatal CVD (261) |
c statistic = 0.69 | Good calibration; observed:predicted CVD rate ratio 0.96 | N/A | N/A | |
Hong Kong Diabetes Registry for CHD [18] | 3,546 Chinese men and women with median age of 56 years without CHD or HF, median follow-up of 5.59 years (Hong Kong) [18] | Type 2 diabetes referred from GP and special clinics, and those discharged from hospitals | CHD: myocardial infarction or ischaemic heart disease (170) | Overall aROC 0.704 (95% CI 0.675–0.733) Adjusted aROC 0.737 | Good calibration: HL χ
2 = 14.05; p > 0.05 | 5 year CHD risk >5.2%: Sen 67.6; Spc 68.5 | 5 year CHD risk >5.2%: PPV 8.6; NPV 98.0 |
Framingham 1991 [50] | 3,898 men and women aged 25–65 years with diabetes without history of MI, angina or stroke (UKPDS) [24] | Newly physician-diagnosed diabetes, and FPG >6 mmol/l on two further occasions | Fatal CVD and fatal CHD (CVD: 7.4%, CHD: 6.3%) | aROC 0.76 | 32% underestimation | N/A | N/A |
112 patients with type 2 diabetes with 10 years of follow-up (Spain) [22] | 1985 WHO criteria (FPG >7.7 mmol/l or 2 h OGTT >11.0 mmol/l) | CHD event (19) | N/A | Men: overestimation by 64.8%; women: overestimation by 31.6% | 10 year CHD risk >20%: men: Sen 75; Spc 17; women: Sen 71; Spc 67 | 10 year CHD risk >20%: men: PPV 17; NPV 75; women: PPV 28; NPV 93 | |
428 men and women aged 30–74 years with newly diagnosed diabetes without pre-existing CVD, mean F/U of 4.2 (0.6) years (GP recruitment in Poole, UK) [21] | Surveillance programme to identify diabetes cases, methods of diagnosis, N/A | CVD and CHD determined via hospital and GP notes, death certificates and post-mortem examination record (98) | CVD: aROC 0.673 (0.612–0.734); CHD: aROC 0.657 (0.581–0.732) | Poor calibration for CVD and CHD CVD HL χ
2 = 32.8 (p < 0.001); CHD HL χ
2 = 19.8 (p = 0.011) | 10 year CHD risk >15%: Sen 85.7 (95% CI 77.8–99.5); Spc 33.0 (95% CI 30.7–34.7) | N/A | |
938 men and women with type 1 and type 2 diabetes, F/U 4 years (Cardiff, UK) [20] | Type 1 and type 2 diabetes identified through the Cardiff Diabetes Database; methods of diagnosis, N/A | CHD via primary or subsidiary diagnosis in hospital record linkage (172) | Men: aROC 0.64; women: aROC 0.66 | N/A | 10 year CHD risk >30%: men: Sen 34%, women: Sen25%; 10 year CHD risk >20%: men: Sen 75%; women: Sen 58% | 10 year CHD risk >30%: men: PPV 26%, NPV 83%; women: PPV 33%, NPV 86%; 10 year CHD risk >20%: men: PPV 24%, NPV 88%; women: PPV 24%, NPV 88% | |
Framingham 1998 [52] | 112 patients with type 2 diabetes with 10 years of follow-up (Spain) [22] | 1985 WHO criteria (FPG >7.7 mmol/l or 2 h OGTT >11.0 mmol/l) | CHD event (19) | N/A | Men: overestimation by 97.8%; women: overestimation by 38.2% | 10 year CHD risk >20%: men: Sen 75; Spc 11; women: Sen 71; Spc 69 | 10 year CHD risk >20%: men: PPV 16; NPV 67; women: PPV 29; NPV 93 |
339 diabetic patients, follow-up of 10 years (Greece) [25] | N/A | CHD determined using coronary angiography (108) | aROC 0.65 | N/A | Sen 55; Spc 65 (no data on which risk threshold was used) | PPV 43; NPV 75 (no data on which risk threshold was used) | |
PROCAM score [53] | 798 diabetic patients identified via computerised clinic database with 10 years of follow-up (UK) [19] | N/A | CHD and CVD determined through computerised clinical records (358 CVD, including 269 CHD events) | CVD: c = 0.67; CHD: c = 0.76 | Poor calibration (p < 0.001); observed:predicted events ratio 2.79 and 2.05 for CVD and CHD (r = 0.79 and 0.81 respectively) | N/A | N/A |
Joint British Societies Risk Chart (JBSRC) [54] | 798 diabetic patients identified via computerised clinic database with 10 years of follow-up (UK) [19] | N/A | CHD and CVD determined through computerised clinical records (358 CVD, including 269 CHD events) | CVD: c = 0.80; CHD: c = 0.77 | Poor calibration (p < 0.001) | N/A | At CVD risk >30%: PPV 85%; at CHD risk >30%: PPV 66% |
CardioRisk Manager calculator (CRM) [55] | 798 diabetic patients identified via a computerised clinic database with 10 years of follow-up (UK) [19] | N/A | CHD and CVD determined through computerised clinical records (358 CVD, including 269 CHD events) | CVD: c = 0.76; CHD: c = 0.73 | Poor calibration (p < 0.001) observed:predicted events ratio 2.30 and 1.74 for CVD and CHD (r = 0.98 and 0.97 respectively) | N/A | N/A |
Myocardial Infarction Population Registry of Girona (REGICOR) [57] | 112 patients with type 2 diabetes with 10 years of follow-up (Spain) [22] | 1985 WHO criteria (FPG >7.7 mmol/l or 2 h OGTT >11.0 mmol/l) | CHD event (19) | N/A | Men: underestimation by 17.6%; women: underestimation by 34.2% | 10 year CHD risk >20%: men: Sen 25; Spc 67; women: Sen 0; Spc 100 | 10 year CHD risk >20%: men: PPV 14; NPV 80; women: PPV –; NPV 85 |
SCORE [16] | 3,898 men and women aged 25–65 years with diabetes, without history of MI, angina or stroke within 1 year (UKPDS) [24] | Newly physician-diagnosed diabetes and FPG >6 mmol/l on two further occasions | Fatal CVD and fatal CHD (CVD: 7.4%, CHD: 6.3%) | aROC 0.77 | 18% overestimation | N/A | N/A |
DECODE score [58] | 3,898 men and women aged 25–65 years with diabetes, without history of MI, angina or stroke within 1 year (UKPDS) [24] | Newly physician-diagnosed diabetes and FPG >6 mmol/l on two further occasions | Fatal CVD (CVD: 7.4%, CHD: 6.3%) | aROC 0.67 | 11% underestimation | N/A | N/A |
UKPDS for stroke [49] | 1,370 patients aged >30 years of the Wisconsin Epidemiologic Study of Diabetic Retinopathy cohort, follow-up 8.3 years (USA) [49] | N/A | Fatal stroke (197) | N/A | Underestimation of fatal stroke by 12.5% | N/A | N/A |
3,541 Chinese diabetic patients without history of stroke (Hong Kong) [26] | Physician-diagnosed diabetes (GP and special clinics, and those discharged from hospital) | Stroke: hospital discharge diagnosis confirmed by physicians (182) | Unadjusted aROC 0.588 (95% CI 0.549–0.626) | N/A | N/A | N/A | |
Hong Kong Diabetes Registry for stroke [26] | 3,541 Chinese diabetic patients without history of stroke, median follow-up of 5.37 years (Hong Kong) [26] | Physician-diagnosed diabetes referred from GP and special clinics, and those discharged from hospital | Stroke: hospital discharge diagnosis confirmed by physicians (182) | Adjusted aROC 0.770 for haemorrhagic stroke; 0.785 for ischaemic stroke | N/A | 5 year stroke risk >6.1%: Sen 65.7; Spc 74.9 | 5 year stroke risk >6.1%: PPV 11.6 |
Framingham stroke risk [59] | 178 men and women with diabetes, with or without metabolic syndrome (Spain) [60] | FPG and OGTT based on WHO criteria | Stroke (9) | N/A | Predicted 10 year risk varied from 17.3 to 19.1%; observed 5 year cumulative incidence varied from 3.5 to 5.8 | N/A | N/A |