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1.  Prediction of Coronary Heart Disease Risk in a General, Pre-Diabetic, and Diabetic Population During 10 Years of Follow-up: Accuracy of the Framingham, SCORE, and UKPDS Risk Functions 
Diabetes Care  2009;32(11):2094-2098.
OBJECTIVE
To test the validity of the Framingham, Systematic Coronary Risk Evaluation (SCORE), and UK Prospective Diabetes Study (UKPDS) risk function in the prediction of risk of coronary heart disease (CHD) in populations with normal glucose tolerance (NGT), intermediate hyperglycemia, and type 2 diabetes.
RESEARCH DESIGN AND METHODS
Calibration and discrimination of the three prediction models were tested using prospective data for 1,482 Caucasian men and women, 50–75 years of age, who participated in the Hoorn Study. All analyses were stratified by glucose status.
RESULTS
During 10 years of follow-up, a total of 197 CHD events, of which 43 were fatal, were observed in this population, with the highest percentage of first CHD events in the diabetic group. The Framingham and UKPDS prediction models overestimated the risk of first CHD event in all glucose tolerance groups. Overall, the prediction models had a low to moderate discriminatory capacity. The SCORE risk function was the best predictor of fatal CHD events in the group with NGT (area under the receiver operating characteristic curve 0.79 [95% CI 0.70–0.87]), whereas the UKPDS performed better in the intermediate hyperglycemia group (0.84 [0.74–0.94]) in the estimation of fatal CHD risk. After exclusion of known diabetic patients, all prediction models had a higher discriminatory ability in the group with diabetes.
CONCLUSIONS
The use of the Framingham function for prediction of the first CHD event is likely to overestimate an individual's absolute CHD risk. In CHD prevention, application of the SCORE and UKPDS functions might be useful in the absence of a more valid tool.
doi:10.2337/dc09-0745
PMCID: PMC2768197  PMID: 19875606
2.  Estimation of 10-Year Risk of Coronary Heart Disease in Nepalese Patients with Type 2 Diabetes: Framingham Versus United Kingdom Prospective Diabetes Study 
Background:
Predicting future coronary heart disease (CHD) risk with the help of a validated risk prediction function helps clinicians identify diabetic patients at high risk and provide them with appropriate preventive medicine.
Aim:
The aim of this study is to estimate and compare 10-year CHD risks of Nepalese diabetic patients using two most common risk prediction functions: The Framingham risk equation and United Kingdom Prospective Diabetes Study (UKPDS) risk engine that are yet to be validated for Nepalese population.
Patients and Methods:
We conducted a hospital-based, cross-sectional study on 524 patients with type 2 diabetes. Baseline and biochemical variables of individual patients were recorded and CHD risks were estimated by the Framingham and UKPDS risk prediction functions. Estimated risks were categorized as low, medium, and high. The estimated CHD risks were compared using kappa statistics, Pearson's bivariate correlation, Bland-Altman plots, and multiple regression analysis.
Results:
The mean 10-year CHD risks estimated by the Framingham and UKPDS risk functions were 17.7 ± 12.1 and 16.8 ± 15 (bias: 0.88, P > 0.05), respectively, and were always higher in males and older age groups (P < 0.001). The two risk functions showed moderate convergent validity in predicting CHD risks, but differed in stratifying them and explaining the patients' risk profile. The Framingham equation predicted higher risk for patients usually below 70 years and showed better association with their current risk profile than the UKPDS risk engine.
Conclusions:
Based on the predicted risk, Nepalese diabetic patients, particularly those associated with increased numbers of risk factors, bear higher risk of future CHDs. Since this study is a cross-sectional one and uses externally validated risk functions, Nepalese clinicians should use them with caution, and preferably in combination with other guidelines, while making important medical decisions in preventive therapy of CHD.
doi:10.4103/1947-2714.163642
PMCID: PMC4561440  PMID: 26417557
Convergent validity; coronary heart disease; framingham risk equation; Nepal; risk prediction; type 2 diabetes; UKPDS risk engine
3.  Comparison of four cardiovascular risk prediction functions among Chinese patients with diabetes mellitus in the primary care setting 
Abstract
Aims/Introduction
To assess the feasibility, convergent validity and sensitivity of four cardiovascular risk prediction functions in Chinese diabetic patients in the primary care setting.
Materials and Methods
A cross‐sectional study of 1,140 diabetic patients was carried out to compare four cardiovascular risk functions, which were respectively developed from the Framingham heart study, the USA–People's Republic of China Collaborative Study of Cardiovascular and Cardiopulmonary Epidemiology cohort (PRC), the United Kingdom Prospective Diabetes Study (UKPDS) and the Joint Asia Diabetes Evaluation program (JADE). Feasibility was assessed by the percentage of patients with complete data for risk prediction. Convergent validity was measured by Spearman's rank correlation, paired Wilcoxon signed‐rank sum test and Bland–Altman plots. Effect size differences between clinical risk groups were used to assess the sensitivity.
Results
Risk prediction was feasible by the Framingham, UKPDS and PRC risk functions in more than 98% patients, whereas just 74% of patients had complete data for the JADE function. The annual total coronary heart disease (CHD) risk predicted by the JADE and the UKPDS functions showed excellent agreement with no significant difference, and a correlation of 0.8048. The Framingham and the PRC functions predicted significantly lower CHD risk than those by the UKPDS and the JADE functions. The UKPDS and the Framingham functions were more sensitive in differentiating clinical risk groups.
Conclusions
The UKPDS risk engine showed good feasibility, convergent validity and sensitivity in predicting CHD risk in Chinese diabetic patients. The JADE function showed excellent agreement with the UKPDS risk engine, but it was less feasible in the primary care setting.
doi:10.1111/jdi.12188
PMCID: PMC4188120  PMID: 25411630
Cardiovascular diseases; Diabetes complications; Risk
4.  Development of a New Diabetes Risk Prediction Tool for Incident Coronary Heart Disease Events: The Multi-Ethnic Study of Atherosclerosis and the Heinz Nixdorf Recall Study 
Atherosclerosis  2014;236(2):411-417.
Objective
We develop a new diabetes CHD risk estimator using traditional risk factors plus coronary artery calcium (CAC), ankle-brachial index (ABI), high sensitivity C-reactive protein, family history of CHD, and carotid intima-media thickness and compared it with United Kingdom Prospective Diabetes study (UKPDS), Framingham risk and the NCEP/ATP III risk scores in type 2 diabetes mellitus (T2DM).
Methods and Results
We combined data from T2DM without clinical CVD in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Heinz Nixdorf Recall Study (N=1343). After a mean follow-up of 8.5 years, 85(6.3%) participants had incident CHD. Among the novel risk markers, CAC best predicted CHD independent of the FRS [hazard ratio: HR (95% CI): log (CAC +25):1.69(1.45 – 1.97), p<0.0001; CAC categories: CAC ≤ 25 as reference, >25 and ≤ 125:2.29(0.87 – 5.95), >125 and ≤ 400: 3.87(1.57– 9.57), >400: 5.97(2.57– 13.84), respectively). The MESA-HNR diabetes CHD risk score has better accuracy for the main outcome versus the FRS or UKPDS [area under curve (AUC) of 0.76 vs. 0.70 and 0.69, respectively; all p<0.05]. The MESA-HNR risk score improved risk classification versus the FRS (net reclassification improvement (NRI) = 0.19 and integrated discrimination improvement (IDI) =0.046, p<0.05) and UKPDS (NRI=0.215 and IDI = 0.046, p<0.05). Compared with the ATP III guidelines, the MESA-HNR score has an NRI of 0.74 for the main outcome.
Conclusions
This new CHD risk estimator has better discriminative ability for incident CHD than the FRS, UKPDS, and the ATP III/NCEP recommendations in a multi-ethnic cohort with T2DM.
doi:10.1016/j.atherosclerosis.2014.07.035
PMCID: PMC4170005  PMID: 25150939
Diabetes mellitus; coronary calcium score; risk assessment; coronary heart disease
5.  An independent external validation and evaluation of QRISK cardiovascular risk prediction: a prospective open cohort study 
Objective To independently evaluate the performance of the QRISK score for predicting 10 year risk of cardiovascular disease in an independent UK cohort of patients from general practice and compare the performance with Framingham equations.
Design Prospective open cohort study.
Setting 274 practices from England and Wales contributing to the THIN database.
Participants 1.07 million patients, registered between 1 January 1995 and 1 April 2006, aged 35-74 years (5.4 million person years) with 43 990 cardiovascular events.
Main outcome measures First diagnosis of cardiovascular disease (myocardial infarction, coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records.
Results This independent validation indicated that QRISK offers an improved performance in predicting the 10 year risk of cardiovascular disease in a large cohort of UK patients over the Anderson Framingham equation. Discrimination and calibration statistics were better with QRISK. QRISK explained 32% of the variation in men and 37% in women, compared with 27% and 31% respectively for Anderson Framingham. QRISK underpredicted risk by 13% for men and 10% for women, whereas Anderson Framingham overpredicted risk by 32% for men and 10% for women. In total, 85 010 (8%) of patients would be reclassified from high risk (≥20%) with Anderson Framingham to low risk with QRISK, with an observed 10 year cardiovascular disease risk of 17.5% (95% confidence interval 16.9% to 18.1%) for men and 16.8% (15.7% to 18.0%) for women. The incidence rate of cardiovascular disease events among men was 30.5 per 1000 person years (95% confidence interval 29.9 to 31.2) in high risk patients identified with QRISK and 23.7 per 1000 person years (23.2 to 24.1) in high risk patients identified with Anderson Framingham. Similarly, the incidence rate of cardiovascular disease events among women was 26.7 per 1000 person years (25.8 to 27.7) in high risk patients identified with QRISK compared with 22.2 per 1000 person years (21.4 to 23.0) in high risk patients identified with Anderson Framingham.
Conclusions The QRISK cardiovascular disease risk equation offers an improvement over the long established Anderson Framingham equation in terms of identifying a high risk population for cardiovascular disease in the United Kingdom. QRISK underestimates 10 year cardiovascular disease risk, but the magnitude of underprediction is smaller than the overprediction with Anderson Framingham.
doi:10.1136/bmj.b2584
PMCID: PMC2714681  PMID: 19584409
6.  An independent external validation and evaluation of QRISK cardiovascular risk prediction: a prospective open cohort study 
The BMJ  2009;339:b2584.
Objective To independently evaluate the performance of the QRISK score for predicting 10 year risk of cardiovascular disease in an independent UK cohort of patients from general practice and compare the performance with Framingham equations.
Design Prospective open cohort study.
Setting 274 practices from England and Wales contributing to the THIN database.
Participants 1.07 million patients, registered between 1 January 1995 and 1 April 2006, aged 35-74 years (5.4 million person years) with 43 990 cardiovascular events.
Main outcome measures First diagnosis of cardiovascular disease (myocardial infarction, coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records.
Results This independent validation indicated that QRISK offers an improved performance in predicting the 10 year risk of cardiovascular disease in a large cohort of UK patients over the Anderson Framingham equation. Discrimination and calibration statistics were better with QRISK. QRISK explained 32% of the variation in men and 37% in women, compared with 27% and 31% respectively for Anderson Framingham. QRISK underpredicted risk by 13% for men and 10% for women, whereas Anderson Framingham overpredicted risk by 32% for men and 10% for women. In total, 85 010 (8%) of patients would be reclassified from high risk (≥20%) with Anderson Framingham to low risk with QRISK, with an observed 10 year cardiovascular disease risk of 17.5% (95% confidence interval 16.9% to 18.1%) for men and 16.8% (15.7% to 18.0%) for women. The incidence rate of cardiovascular disease events among men was 30.5 per 1000 person years (95% confidence interval 29.9 to 31.2) in high risk patients identified with QRISK and 23.7 per 1000 person years (23.2 to 24.1) in high risk patients identified with Anderson Framingham. Similarly, the incidence rate of cardiovascular disease events among women was 26.7 per 1000 person years (25.8 to 27.7) in high risk patients identified with QRISK compared with 22.2 per 1000 person years (21.4 to 23.0) in high risk patients identified with Anderson Framingham.
Conclusions The QRISK cardiovascular disease risk equation offers an improvement over the long established Anderson Framingham equation in terms of identifying a high risk population for cardiovascular disease in the United Kingdom. QRISK underestimates 10 year cardiovascular disease risk, but the magnitude of underprediction is smaller than the overprediction with Anderson Framingham.
doi:10.1136/bmj.b2584
PMCID: PMC2714681  PMID: 19584409
7.  Performance of the UK Prospective Diabetes Study Risk Engine and the Framingham Risk Equations in Estimating Cardiovascular Disease in the EPIC- Norfolk Cohort 
Diabetes Care  2008;32(4):708-713.
OBJECTIVE
The purpose of this study was to examine the performance of the UK Prospective Diabetes Study (UKPDS) Risk Engine (version 3) and the Framingham risk equations (2008) in estimating cardiovascular disease (CVD) incidence in three populations: 1) individuals with known diabetes; 2) individuals with nondiabetic hyperglycemia, defined as A1C ≥6.0%; and 3) individuals with normoglycemia defined as A1C <6.0%.
RESEARCH DESIGN AND METHODS
This was a population-based prospective cohort (European Prospective Investigation of Cancer-Norfolk). Participants aged 40–79 years recruited from U.K. general practices attended a health examination (1993–1998) and were followed for CVD events/death until April 2007. CVD risk estimates were calculated for 10,137 individuals.
RESULTS
Over 10.1 years, there were 69 CVD events in the diabetes group (25.4%), 160 in the hyperglycemia group (17.7%), and 732 in the normoglycemia group (8.2%). Estimated CVD 10-year risk in the diabetes group was 33 and 37% using the UKPDS and Framingham equations, respectively. In the hyperglycemia group, estimated CVD risks were 31 and 22%, respectively, and for the normoglycemia group risks were 20 and 14%, respectively. There were no significant differences in the ability of the risk equations to discriminate between individuals at different risk of CVD events in each subgroup; both equations overestimated CVD risk. The Framingham equations performed better in the hyperglycemia and normoglycemia groups as they did not overestimate risk as much as the UKPDS Risk Engine, and they classified more participants correctly.
CONCLUSIONS
Both the UKPDS Risk Engine and Framingham risk equations were moderately effective at ranking individuals and are therefore suitable for resource prioritization. However, both overestimated true risk, which is important when one is using scores to communicate prognostic information to individuals.
doi:10.2337/dc08-1918
PMCID: PMC2660447  PMID: 19114615
8.  Agreement between Framingham Risk Score and United Kingdom Prospective Diabetes Study Risk Engine in Identifying High Coronary Heart Disease Risk in North Indian Population 
Diabetes & Metabolism Journal  2015;39(4):321-327.
Background
The aim of the study is to evaluate the concurrence between Framingham Risk score (FRS) and United Kingdom Prospective Diabetes Study (UKPDS) risk engine in identifying coronary heart disease (CHD) risk in newly detected diabetes mellitus patients and to explore the characteristics associated with the discrepancy between them.
Methods
A cross-sectional study involving 489 subjects newly diagnosed with type 2 diabetes mellitus was conducted. Agreement between FRS and UKPDS in classifying patients as high risk was calculated using kappa statistic. Subjects with discrepant scores between two algorithms were identified and associated variables were determined.
Results
The FRS identified 20.9% subjects (range, 17.5 to 24.7) as high-risk while UKPDS identified 21.75% (range, 18.3 to 25.5) as high-risk. Discrepancy was observed in 17.9% (range, 14.7 to 21.7) subjects. About 9.4% had high risk by UKPDS but not FRS, and 8.6% had high risk by FRS but not UKPDS. The best agreement was observed at high-risk threshold of 20% for both (κ=0.463). Analysis showed that subjects having high risk on FRS but not UKPDS were elderly females having raised systolic and diastolic blood pressure. Patients with high risk on UKPDS but not FRS were males and have high glycosylated hemoglobin.
Conclusion
The FRS and UKPDS (threshold 20%) identified different populations as being at high risk, though the agreement between them was fairly good. The concurrence of a number of factors (e.g., male sex, low high density lipoprotein cholesterol, and smoking) in both algorithms should be regarded as increasing the CHD risk. However, longitudinal follow-up is required to form firm conclusions.
doi:10.4093/dmj.2015.39.4.321
PMCID: PMC4543196  PMID: 26301194
Coronary heart disease; Diabetes mellitus; Predictive value of tests; Risk assessment
9.  Prediction of morbidity and mortality in patients with type 2 diabetes 
PeerJ  2013;1:e87.
Introduction. The objective of this study was to create a tool that accurately predicts the risk of morbidity and mortality in patients with type 2 diabetes according to an oral hypoglycemic agent.
Materials and Methods. The model was based on a cohort of 33,067 patients with type 2 diabetes who were prescribed a single oral hypoglycemic agent at the Cleveland Clinic between 1998 and 2006. Competing risk regression models were created for coronary heart disease (CHD), heart failure, and stroke, while a Cox regression model was created for mortality. Propensity scores were used to account for possible treatment bias. A prediction tool was created and internally validated using tenfold cross-validation. The results were compared to a Framingham model and a model based on the United Kingdom Prospective Diabetes Study (UKPDS) for CHD and stroke, respectively.
Results and Discussion. Median follow-up for the mortality outcome was 769 days. The numbers of patients experiencing events were as follows: CHD (3062), heart failure (1408), stroke (1451), and mortality (3661). The prediction tools demonstrated the following concordance indices (c-statistics) for the specific outcomes: CHD (0.730), heart failure (0.753), stroke (0.688), and mortality (0.719). The prediction tool was superior to the Framingham model at predicting CHD and was at least as accurate as the UKPDS model at predicting stroke.
Conclusions. We created an accurate tool for predicting the risk of stroke, coronary heart disease, heart failure, and death in patients with type 2 diabetes. The calculator is available online at http://rcalc.ccf.org under the heading “Type 2 Diabetes” and entitled, “Predicting 5-Year Morbidity and Mortality.” This may be a valuable tool to aid the clinician’s choice of an oral hypoglycemic, to better inform patients, and to motivate dialogue between physician and patient.
doi:10.7717/peerj.87
PMCID: PMC3685323  PMID: 23781409
Type 2 diabetes mellitus; Prediction; Propensity; Coronary heart disease; Heart failure; Stroke; Mortality; Electronic health record; Hypoglycemic agents
10.  External validation of the UK Prospective Diabetes Study (UKPDS) risk engine in patients with type 2 diabetes 
Diabetologia  2010;54(2):264-270.
Aims/hypothesis
Treatment guidelines recommend the UK Prospective Diabetes Study (UKPDS) risk engine for predicting cardiovascular risk in patients with type 2 diabetes, although validation studies showed moderate performance. The methods used in these validation studies were diverse, however, and sometimes insufficient. Hence, we assessed the discrimination and calibration of the UKPDS risk engine to predict 4, 5, 6 and 8 year cardiovascular risk in patients with type 2 diabetes.
Methods
The cohort included 1,622 patients with type 2 diabetes. During a mean follow-up of 8 years, patients were followed for incidence of CHD and cardiovascular disease (CVD). Discrimination and calibration were assessed for 4, 5, 6 and 8 year risk. Discrimination was examined using the c-statistic and calibration by visually inspecting calibration plots and calculating the Hosmer–Lemeshow χ2 statistic.
Results
The UKPDS risk engine showed moderate to poor discrimination for both CHD and CVD (c-statistic of 0.66 for both 5 year CHD and CVD risks), and an overestimation of the risk (224% and 112%). The calibration of the UKPDS risk engine was slightly better for patients with type 2 diabetes who had been diagnosed with diabetes more than 10 years ago compared with patients diagnosed more recently, particularly for 4 and 5 year predicted CVD and CHD risks. Discrimination for these periods was still moderate to poor.
Conclusions/interpretation
We observed that the UKPDS risk engine overestimates CHD and CVD risk. The discriminative ability of this model is moderate, irrespective of various subgroup analyses. To enhance the prediction of CVD in patients with type 2 diabetes, this model should be updated.
Electronic supplementary material
The online version of this article (doi:10.1007/s00125-010-1960-0) contains supplementary material, which is available to authorised users.
doi:10.1007/s00125-010-1960-0
PMCID: PMC3017299  PMID: 21076956
Calibration; Cardiovascular disease; Coronary heart disease; Discrimination; Epidemiology; Multiple imputation; Prediction; Type 2 diabetes mellitus; Validation
11.  Risk Prediction of Coronary Heart Disease based on Retinal Vascular Caliber (From The Atherosclerosis Risk in Communities [ARIC] Study) 
Recent studies show that retinal vascular signs such as quantitative retinal vascular caliber are associated with an increased risk of incident coronary heart disease (CHD), but whether these retinal vascular signs add to the prediction of CHD over and above traditional CHD risk factors has not been addressed. We investigated whether these signs add to the prediction of CHD over and above the Framingham risk score amongst people (n=9,155) without diabetes selected from the Atherosclerosis Risk in Communities (ARIC) study. Incident CHD was ascertained using standardized methods and retinal vascular caliber and other retinal signs were measured from retinal photographs. After a mean of 8.8 years of follow up, there were 700 incident CHD events. Women with wider retinal venular caliber (hazard ratio 1.27 per 1 standard deviation increase [95% confidence interval, 1.08, 1.50]) and narrower retinal arteriolar caliber (1.31 per 1 standard deviation decrease [1.10, 1.56]) had a higher risk of incident CHD after adjusting for the Framingham risk score variables. The area under the receiver operator characteristic curve increased from 0.695 to 0.706 (1.7% increase) with the addition of retinal vascular caliber to the Framingham risk model. The risk prediction models with and without the retinal vascular caliber both fitted the data and were well calibrated for women. In men, retinal vascular caliber was not associated with CHD risk after adjustment. Other retinal vascular signs were not associated with 10-year incident CHD in men or women. In conclusion, although retinal vascular caliber independently predicts CHD risk in women, the incremental predictive ability over that of the Framingham model is modest, and unlikely to translate meaningfully into clinical practice.
doi:10.1016/j.amjcard.2008.02.094
PMCID: PMC2491714  PMID: 18572036
Coronary disease; retinal vascular disease; retinal imaging; risk prediction
12.  Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2 
Objective To evaluate the performance of the QRISK2-2011 score for predicting the 10 year risk of cardiovascular disease in an independent UK cohort of patients from general practice and to compare it with earlier versions of the model and a National Institute for Health and Clinical Excellence version of the Framingham equation.
Design Prospective cohort study to validate a cardiovascular risk score with routinely collected data between June 1994 and June 2008.
Setting 364 practices from the United Kingdom contributing to The Health Improvement Network (THIN) database.
Participants Two million patients aged 30 to 84 years (11.8 million person years) with 93 564 cardiovascular events.
Main outcome measure First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records.
Results Results from this independent and external validation of QRISK2-2011 indicate good performance data when compared with the NICE version of the Framingham equation. QRISK2-2011 had better ability to identify those at high risk of developing cardiovascular disease than did the NICE Framingham equation. QRISK2-2011 is well calibrated, with reasonable agreement between observed and predicted outcomes, whereas the NICE Framingham equation seems to consistently over-predict risk in men by about 5% and shows poor calibration in women.
Conclusions QRISK2-2011 seems to be a useful model, with good discriminative and calibration properties when compared with the NICE version of the Framingham equation. Furthermore, based on current high risk thresholds, concerns exist on the clinical usefulness of the NICE version of the Framingham equation for identifying women at high risk of developing cardiovascular disease. At current thresholds the NICE version of the Framingham equation has no clinical benefit in either men or women.
doi:10.1136/bmj.e4181
PMCID: PMC3380799  PMID: 22723603
13.  Predicting the 10 year risk of cardiovascular disease in the United Kingdom: independent and external validation of an updated version of QRISK2 
The BMJ  2012;344:e4181.
Objective To evaluate the performance of the QRISK2-2011 score for predicting the 10 year risk of cardiovascular disease in an independent UK cohort of patients from general practice and to compare it with earlier versions of the model and a National Institute for Health and Clinical Excellence version of the Framingham equation.
Design Prospective cohort study to validate a cardiovascular risk score with routinely collected data between June 1994 and June 2008.
Setting 364 practices from the United Kingdom contributing to The Health Improvement Network (THIN) database.
Participants Two million patients aged 30 to 84 years (11.8 million person years) with 93 564 cardiovascular events.
Main outcome measure First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records.
Results Results from this independent and external validation of QRISK2-2011 indicate good performance data when compared with the NICE version of the Framingham equation. QRISK2-2011 had better ability to identify those at high risk of developing cardiovascular disease than did the NICE Framingham equation. QRISK2-2011 is well calibrated, with reasonable agreement between observed and predicted outcomes, whereas the NICE Framingham equation seems to consistently over-predict risk in men by about 5% and shows poor calibration in women.
Conclusions QRISK2-2011 seems to be a useful model, with good discriminative and calibration properties when compared with the NICE version of the Framingham equation. Furthermore, based on current high risk thresholds, concerns exist on the clinical usefulness of the NICE version of the Framingham equation for identifying women at high risk of developing cardiovascular disease. At current thresholds the NICE version of the Framingham equation has no clinical benefit in either men or women.
doi:10.1136/bmj.e4181
PMCID: PMC3380799  PMID: 22723603
14.  A coronary heart disease prediction model: the Korean Heart Study 
BMJ Open  2014;4(5):e005025.
Objective
The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score.
Design
A prospective cohort study within a national insurance system.
Setting
18 health promotion centres nationwide between 1996 and 2001 in Korea.
Participants
268 315 Koreans between the ages of 30 and 74 years without CHD at baseline.
Outcome measure
Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI).
Results
The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort.
Conclusions
The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.
doi:10.1136/bmjopen-2014-005025
PMCID: PMC4039825  PMID: 24848088
Epidemiology
15.  Comparison of the Framingham Risk Score, UKPDS Risk Engine, and SCORE for Predicting Carotid Atherosclerosis and Peripheral Arterial Disease in Korean Type 2 Diabetic Patients 
Korean Journal of Family Medicine  2011;32(3):189-196.
Background
To compare the predictability of the Framingham Risk Score (FRS), United Kingdom Prospective Diabetes Study (UKPDS) risk engine, and the Systematic Coronary Risk Evaluation (SCORE) for carotid atherosclerosis and peripheral arterial disease in Korean type 2 diabetic patients.
Methods
Among 1,275 registered type 2 diabetes patients in the health center, 621 subjects with type 2 diabetes participated in the study. Well-trained examiners measured the carotid intima-media thickness (IMT), carotid plaque, and ankle brachial index (ABI). The subject's 10-year risk of coronary heart disease was calculated according to the FRS, UKPDS, and SCORE risk scores. These three risk scores were compared to the areas under the curve (AUC).
Results
The odds ratios (ORs) of all risk scores increased as the quartiles increased for plaque, IMT, and ABI. For plaque and IMT, the UKPDS risk score provided the highest OR (95% confidence interval) at 3.82 (2.36, 6.17) and at 6.21 (3.37, 11.45). For ABI, the SCORE risk estimation provided the highest OR at 7.41 (3.20, 17.18). However, no significant difference was detected for plaque, IMT, or ABI (P = 0.839, 0.313, and 0.113, respectively) when the AUCs of the three risk scores were compared. When we graphed the Kernel density distribution of these three risk scores, UKPDS had a higher distribution than FRS and SCORE.
Conclusion
No significant difference was observed when comparing the predictability of the FRS, UKPDS risk engine, and SCORE risk estimation for carotid atherosclerosis and peripheral arterial disease in Korean type 2 diabetic patients.
doi:10.4082/kjfm.2011.32.3.189
PMCID: PMC3383126  PMID: 22745854
Risk Assessment; Peripheral Arterial Disease; Carotid Artery Thrombosis; Diabetes Mellitus, Type 2
16.  Performance of the Framingham and SCORE cardiovascular risk prediction functions in a non-diabetic population of a Spanish health care centre: a validation study 
Objective
To analyse the 10-year performance of the original Framingham coronary risk function and of the SCORE cardiovascular death risk function in a non-diabetic population of 40–65 years of age served by a Spanish healthcare centre. Also, to estimate the percentage of patients who are candidates for antihypertensive and lipid-lowering therapy.
Design
Longitudinal, observational study of a retrospective cohort followed up for 10 years.
Setting
Primary care health centre.
Patients
A total of 608 non-diabetic patients of 40–65 years of age (mean 52.8 years, 56.7% women), without evidence of cardiovascular disease were studied.
Main outcome measures
Coronary risk at 10 years from the time of their recruitment, using the tables based on the original Framingham function, and of their 10-year risk of fatal cardiovascular disease using the SCORE tables.
Results
The actual incidence rates of coronary and fatal cardiovascular events were 7.9% and 1.5%, respectively. The original Framingham equation over-predicted risk by 64%, while SCORE function over-predicted risk by 40%, but the SCORE model performed better than the Framingham one for discrimination and calibration statistics. The original Framingham function classified 18.3% of the population as high risk and SCORE 9.2%. The proportions of patients who would be candidates for lipid-lowering therapy were 31.0% and 23.8% according to the original Framingham and SCORE functions, respectively, and 36.8% and 31.2% for antihypertensive therapy.
Conclusion
The SCORE function showed better values than the original Framingham function for each of the discrimination and calibration statistics. The original Framingham function selected a greater percentage of candidates for antihypertensive and lipid-lowering therapy.
doi:10.3109/02813432.2010.518407
PMCID: PMC3444797  PMID: 20873973
Antihypertensive treatment; cardiovascular risk functions; coronary risk; hypolipidemic treatment; SCORE risk chart
17.  Validation of the pooled cohort risk score in an Asian population – a retrospective cohort study 
Background
The Pooled Cohort Risk Equation was introduced by the American College of Cardiology (ACC) and American Heart Association (AHA) 2013 in their Blood Cholesterol Guideline to estimate the 10-year atherosclerotic cardiovascular disease (ASCVD) risk. However, absence of Asian ethnicity in the contemporary cohorts and limited studies to examine the use of the risk score limit the applicability of the equation in an Asian population. This study examines the validity of the pooled cohort risk score in a primary care setting and compares the cardiovascular risk using both the pooled cohort risk score and the Framingham General Cardiovascular Disease (CVD) risk score.
Methods
This is a 10-year retrospective cohort study of randomly selected patients aged 40–79 years. Baseline demographic data, co-morbidities and cardiovascular (CV) risk parameters were captured from patient records in 1998. Pooled cohort risk score and Framingham General CVD risk score for each patient were computed. All ASCVD events (nonfatal myocardial infarction, coronary heart disease (CHD) death, fatal and nonfatal stroke) occurring from 1998–2007 were recorded.
Results
A total of 922 patients were studied. In 1998, mean age was 57.5 ± 8.8 years with 66.7% female. There were 47% diabetic patients and 59.9% patients receiving anti-hypertensive treatment. More than 98% of patients with pooled cohort risk score ≥7.5% had FRS >10%. A total of 45 CVD events occurred, 22 (7.2%) in males and 23 (3.7%) in females. The median pooled cohort risk score for the population was 10.1 (IQR 4.7-20.6) while the actual ASCVD events that occurred was 4.9% (45/922). Our study showed moderate discrimination with AUC of 0.63. There was good calibration with Hosmer-Lemeshow test χ2 = 12.6, P = 0.12.
Conclusions
The pooled cohort risk score appears to overestimate CV risk but this apparent over-prediction could be a result of treatment. In the absence of a validated score in an untreated population, the pooled cohort risk score appears to be appropriate for use in a primary care setting.
doi:10.1186/1471-2261-14-163
PMCID: PMC4246627  PMID: 25410585
Pooled cohort risk score; Atherosclerotic cardiovascular disease; Validation; Asian population; Framingham risk score; Cardiovascular events; Primary care; Retrospective cohort; Malaysia
18.  Adding multiple risk factors improves Framingham coronary heart disease risk scores 
Purpose
Since the introduction of the Framingham Risk Score (FRS), numerous versions of coronary heart disease (CHD) prediction models have claimed improvement over the FRS. Tzoulaki et al challenged the validity of these claims by illustrating methodology deficiencies among the studies. However, the question remains: Is it possible to create a new CHD model that is better than FRS while overcoming the noted deficiencies? To address this, a new CHD prediction model was developed by integrating additional risk factors, using a novel modeling process.
Methods
Using the National Health Nutritional Examination Survey III data set with CHD-specific mortality outcomes and the Atherosclerosis Risk in Communities data set with CHD incidence outcomes, two FRSs (FRSv1 from 1998 and FRSv2 from National Cholesterol Education Program Adult Treatment Panel III), along with an additional risk score in which the high density lipoprotein (HDL) component of FRSv1 was ignored (FRSHDL), were compared with a new CHD model (NEW-CHD). This new model contains seven elements: the original Framingham equation, FRSv1, and six additional risk factors. Discrimination, calibration, and reclassification improvements all were assessed among models.
Results
Discrimination was improved for NEW-CHD in both cohorts when compared with FRSv1 and FRSv2 (P<0.05) and was similar in magnitude to the improvement of FRSv1 over FRSHDL. NEW-CHD had a similar calibration to FRSv2 and was improved over FRSv1. Net reclassification for NEW-CHD was substantially improved over both FRSv1 and FRSv2, for both cohorts, and was similar in magnitude to the improvement of FRSv1 over FRSHDL.
Conclusion
While overcoming several methodology deficiencies reported by earlier authors, the NEW-CHD model improved CHD risk assessment when compared with the FRSs, comparable to the improvement of adding HDL to the FRS.
doi:10.2147/VHRM.S69672
PMCID: PMC4162681  PMID: 25228812
risk assessment; atherosclerotic risk in communities; NHANES; epidemiology
19.  Trends in the Risk for Coronary Heart Disease Among Adults With Diagnosed Diabetes in the U.S. 
Diabetes Care  2011;34(6):1337-1343.
OBJECTIVE
Coronary heart disease (CHD) is a major cause of mortality among people with diabetes. The objective of this study was to examine the trend in an estimated 10-year risk for developing CHD among adults with diagnosed diabetes in the U.S.
RESEARCH DESIGN AND METHODS
Data from 1,977 adults, aged 30–79 years, with diagnosed diabetes who participated in the National Health and Nutrition Examination Survey from 1999–2000 to 2007–2008 were used. Estimated risk was calculated using risk prediction algorithms from the UK Prospective Diabetes Study (UKPDS), the Atherosclerosis Risk in Communities study, and the Framingham Heart Study.
RESULTS
Significant improvements in mean HbA1c concentrations, systolic blood pressure, and the ratio of total cholesterol to HDL cholesterol occurred. No significant linear trend for current smoking status was observed. The estimated UKPDS 10-year risk for CHD was 21.1% in 1999–2000 and 16.4% in 2007–2008 (Plinear trend < 0.001). The risk decreased significantly among men, women, whites, African Americans, and Mexican Americans.
CONCLUSIONS
The estimated 10-year risk for CHD among adults with diabetes has improved significantly from 1999–2000 to 2007–2008. Sustained efforts in improving risk factors should further benefit the cardiovascular health of people with diabetes.
doi:10.2337/dc10-2251
PMCID: PMC3114334  PMID: 21505207
20.  Left Ventricular Hypertrophy and Cardiovascular Disease Risk Prediction and Reclassification in Blacks and Whites: The ARIC Study 
American heart journal  2014;169(1):155-161.e5.
Left Ventricular Hypertrophy (LVH) is a major independent predictor of cardiovascular disease (CVD) survival, and is more prevalent in blacks than whites. In a large biracial population, we evaluated the ability of ECG-determined LVH (ECG-LVH) to reclassify CVD/coronary heart disease (CHD) events beyond traditional risk factors in blacks and whites. The analysis included 14,489 participants (mean age 54+/−5.7 years, 43.5% men, 26% black) from the Atherosclerosis Risk in Communities (ARIC) cohort, with baseline (1987–989) ECG, followed for 10 years. Predicted risk for incident CVD and CHD were estimated using the 10-year Pooled Cohort and Framingham risk equations (base models 1a/1b), respectively. Models 2a and 2b included respective base model plus LVH by any of 10 traditional ECG-LVH criteria. Net reclassification improvement (NRI) was calculated, and the distribution of risk was compared using models 2a and 2b vs. models 1a and 1b, respectively. There were 792 (5.5%) 10-year Pooled Cohort CVD events, and 690 (4.8%) 10-year Framingham CHD events. LVH defined by any criteria was associated with CVD and CHD events [HR (95% CI): 1.62 (1.38–1.90) and 1.56 (1.32–1.86), respectively]. LVH did not significantly reclassify or improve C-statistic in models 2a/b [C-statistics: 0.767/0.719; NRI=0.001 (p=NS)], compared with the base models 1a/b (C-statistics: 0.770/0.718), respectively. No racial interactions were observed. In this large cohort of black and white participants, ECG-LVH was associated with CVD/CHD risk, but did not significantly improve CVD and CHD events risk prediction beyond the new Pooled Cohort and most utilized Framingham risk equations in blacks or whites.
doi:10.1016/j.ahj.2014.09.013
PMCID: PMC4269255  PMID: 25497261
left ventricular hypertrophy; race; electrocardiography; risk prediction; coronary heart disease; cardiovascular disease; Pooled Cohort risk equation; Framingham risk equation
21.  Cardiovascular disease risk assessment in older women: can we improve on Framingham? British Women's Heart and Health prospective cohort study 
Heart  2006;92(10):1396-1401.
Objectives
To develop a cardiovascular risk assessment tool that is feasible and easy to use in primary care (general practice (GP) model).
Design
Prospective cohort study.
Setting
23 towns in the United Kingdom.
Participants
3582 women aged 60 to 79 years who were free of coronary heart disease (CHD) at entry into the British Women's Heart and Health Study.
Main outcome measures
Predictive performance of a GP model compared with the standard Framingham model for both CHD and cardiovascular disease (CVD).
Results
The Framingham tool predicted CHD events over 5 years accurately (predicted 5.7%, observed 5.5%) but overpredicted CVD events (predicted 10.5%, observed 6.8%). In higher‐risk groups, Framingham overpredicted both CHD and CVD events and was poorly calibrated for this cohort. Including C‐reactive protein and fibrinogen with standard Framingham risk factors did not improve discrimination of the model. The GP model, which used age, systolic blood pressure, smoking habit and self‐rated health (all of which can be easily obtained in one surgery visit) performed as well as the Framingham risk tool: area under the receiver operating curve discrimination statistic was 0.66 (95% confidence interval (CI) 0.62 to 0.70) for CHD and 0.67 (95% CI 0.64 to 0.71) for CVD compared with 0.65 (95% CI 0.61 to 0.68) and 0.66 (95% CI 0.62 to 0.69) for the corresponding Framingham models.
Conclusions
An alternative risk assessment based on only a simple routine examination and a small number of pertinent questions may be more useful in the primary care setting. This model appears to perform well but needs to be tested in different populations.
doi:10.1136/hrt.2005.085381
PMCID: PMC1861043  PMID: 16547204
22.  Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study: baseline characteristics and short-term effects of fenofibrate [ISRCTN64783481] 
Objective
The Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study is examining the effects of long-term fibrate therapy on coronary heart disease (CHD) event rates in patients with diabetes mellitus. This article describes the trial's run-in phase and patients' baseline characteristics.
Research design and methods
FIELD is a double-blind, placebo-controlled trial in 63 centres in 3 countries evaluating the effects of fenofibrate versus placebo on CHD morbidity and mortality in 9795 patients with type 2 diabetes mellitus. Patients were to have no indication for lipid-lowering therapy on randomization, but could start these or other drugs at any time after randomization. Follow-up in the study was to be for a median duration of not less than 5 years and until 500 major coronary events (fatal coronary heart disease plus nonfatal myocardial infarction) had occurred.
Results
About 2100 patients (22%) had some manifestation of cardiovascular disease (CVD) at baseline and thus high risk status. Less than 25% of patients without CVD had a (UKPDS determined) calculated 5-year CHD risk of <5%, but nearly all had a 5-year stroke risk of <10%. Despite this, half of the cohort were obese (BMI > 30), most were men, two-thirds were aged over 60 years, and substantial proportions had NCEP ATP III features of the metabolic syndrome independent of their diabetes, including low HDL (60%), high blood pressure measurement or treatment for hypertension (84%), high waist measurement (68%), and raised triglycerides (52%).
After a 6-week run-in period before randomisation with all participants receiving 200 mg comicronized fenofibrate, there were declines in total and LDL cholesterol (10%) and triglycerides (26%) and an increase in HDL cholesterol (6.5%).
Conclusion
The study will show the effect of PPAR-alpha agonist action on CHD and other vascular outcomes in patients with type 2 diabetes including substantial numbers with low to moderate CVD risk but with the various components of the metabolic syndrome. The main results of the study will be reported in late 2005.
doi:10.1186/1475-2840-4-13
PMCID: PMC1266033  PMID: 16111499
23.  Clinical implications of carotid artery intima media thickness assessment on cardiovascular risk stratification in hyperlipidemic Korean adults with diabetes: the ALTO study 
Background
The primary objective was to investigate prevalence of subclinical atherosclerosis in Korean individuals with diabetes and hyperlipidemia. Association of subclinical atherosclerosis with cardiovascular risk was assessed.
Methods
Assessments of carotid artery intima media thickness (cIMT) and atheromatous plaque were done using B-mode ultrasonography. Subclinical atherosclerosis was diagnosed based on presence of plaque, and/or increased cIMT versus mean cIMT reference values for Korean healthy controls. Atherosclerosis risk factors were analyzed using United Kingdom Prospective Diabetes Study (UKPDS) risk engine and Framingham Risk Score.
Results
In total, 355 patients were included; increased mean cIMT was observed in 15.3 % of patients, 69 % had >1 carotid artery plaque, and 72.7 % were diagnosed with subclinical atherosclerosis. In total, 60 % of subjects were taking statins, with low-density lipoprotein cholesterol level maintained ~80 mg/dL at enrollment. Carotid artery measures were well correlated with UKPDS and Framingham risk scores. Prevalence of subclinical atherosclerosis in the low risk group (<15 % 10-year UKPDS-predicted coronary heart disease risk) was 64.7 %; higher than predicted in previous studies. In multivariate analysis, advanced age was a significant risk factor for subclinical atherosclerosis in men and women, while increased waist circumference and longer diabetes duration were independent predictors only in women.
Conclusion
Subclinical atherosclerosis is more prevalent among individuals with both diabetes and hyperlipidemia than in diabetic patients without additional cardiovascular risk factors. As conventional risk engines, based on modifiable risk factors may underestimate cardiovascular risk, early non-invasive carotid artery imaging screening may be warranted for patients with diabetes and hyperlipidemia, especially if they are elderly, have central obesity or have long duration of diabetes.
Trial registration
www.clinicaltrials.gov NCT01264263
Electronic supplementary material
The online version of this article (doi:10.1186/s12872-015-0109-y) contains supplementary material, which is available to authorized users.
doi:10.1186/s12872-015-0109-y
PMCID: PMC4595332  PMID: 26438201
Subclinical atherosclerosis; Diabetes; Hyperlipidemia; Carotid artery ultrasonography
24.  An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study 
Objective To evaluate the performance of the QRISK2 score for predicting 10-year cardiovascular disease in an independent UK cohort of patients from general practice records and to compare it with the NICE version of the Framingham equation and QRISK1.
Design Prospective cohort study to validate a cardiovascular risk score.
Setting 365 practices from United Kingdom contributing to The Health Improvement Network (THIN) database.
Participants 1.58 million patients registered with a general practice between 1 January 1993 and 20 June 2008, aged 35-74 years (9.4 million person years) with 71 465 cardiovascular events.
Main outcome measures First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic stroke) recorded in general practice records.
Results QRISK2 offered improved prediction of a patient’s 10-year risk of cardiovascular disease over the NICE version of the Framingham equation. Discrimination and calibration statistics were better with QRISK2. QRISK2 explained 33% of the variation in men and 40% for women, compared with 29% and 34% respectively for the NICE Framingham and 32% and 38% respectively for QRISK1. The incidence rate of cardiovascular events (per 1000 person years) among men in the high risk group was 27.8 (95% CI 27.4 to 28.2) with QRISK2, 21.9 (21.6 to 22.2) with NICE Framingham, and 24.8 (22.8 to 26.9) with QRISK1. Similarly, the incidence rate of cardiovascular events (per 1000 person years) among women in the high risk group was 24.3 (23.8 to 24.9) with QRISK2, 20.6 (20.1 to 21.0) with NICE Framingham, and 21.8 (18.9 to 24.6) with QRISK1.
Conclusions QRISK2 is more accurate in identifying a high risk population for cardiovascular disease in the United Kingdom than the NICE version of the Framingham equation. Differences in performance between QRISK2 and QRISK1 were marginal.
doi:10.1136/bmj.c2442
PMCID: PMC2869403  PMID: 20466793
25.  An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study 
The BMJ  2010;340:c2442.
Objective To evaluate the performance of the QRISK2 score for predicting 10-year cardiovascular disease in an independent UK cohort of patients from general practice records and to compare it with the NICE version of the Framingham equation and QRISK1.
Design Prospective cohort study to validate a cardiovascular risk score.
Setting 365 practices from United Kingdom contributing to The Health Improvement Network (THIN) database.
Participants 1.58 million patients registered with a general practice between 1 January 1993 and 20 June 2008, aged 35-74 years (9.4 million person years) with 71 465 cardiovascular events.
Main outcome measures First diagnosis of cardiovascular disease (myocardial infarction, angina, coronary heart disease, stroke, and transient ischaemic stroke) recorded in general practice records.
Results QRISK2 offered improved prediction of a patient’s 10-year risk of cardiovascular disease over the NICE version of the Framingham equation. Discrimination and calibration statistics were better with QRISK2. QRISK2 explained 33% of the variation in men and 40% for women, compared with 29% and 34% respectively for the NICE Framingham and 32% and 38% respectively for QRISK1. The incidence rate of cardiovascular events (per 1000 person years) among men in the high risk group was 27.8 (95% CI 27.4 to 28.2) with QRISK2, 21.9 (21.6 to 22.2) with NICE Framingham, and 24.8 (22.8 to 26.9) with QRISK1. Similarly, the incidence rate of cardiovascular events (per 1000 person years) among women in the high risk group was 24.3 (23.8 to 24.9) with QRISK2, 20.6 (20.1 to 21.0) with NICE Framingham, and 21.8 (18.9 to 24.6) with QRISK1.
Conclusions QRISK2 is more accurate in identifying a high risk population for cardiovascular disease in the United Kingdom than the NICE version of the Framingham equation. Differences in performance between QRISK2 and QRISK1 were marginal.
doi:10.1136/bmj.c2442
PMCID: PMC2869403  PMID: 20466793

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