Peter Brindle

Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2

Objective To develop and validate version two of the QRISK cardiovascular disease risk algorithm (QRISK2) to provide accurate estimates of cardiovascular risk in patients from different ethnic groups in England and Wales and to compare its performance with the modified version of Framingham score recommended by the National Institute for Health and Clinical Excellence (NICE). Design Prospective open cohort study with routinely collected data from general practice, 1 January 1993 to 31 March 2008. Setting 531 practices in England and Wales contributing to the national QRESEARCH database. Participants 2.3 million patients aged 35-74 (over 16 million person years) with 140 000 cardiovascular events. Overall population (derivation and validation cohorts) comprised 2.22 million people who were white or whose ethnic group was not recorded, 22 013 south Asian, 11 595 black African, 10 402 black Caribbean, and 19 792 from Chinese or other Asian or other ethnic groups. Main outcome measures First (incident) diagnosis of cardiovascular disease (coronary heart disease, stroke, and transient ischaemic attack) recorded in general practice records or linked Office for National Statistics death certificates. Risk factors included self assigned ethnicity, age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative under 60 years, Townsend deprivation score, treated hypertension, type 2 diabetes, renal disease, atrial fibrillation, and rheumatoid arthritis. Results The validation statistics indicated that QRISK2 had improved discrimination and calibration compared with the modified Framingham score. The QRISK2 algorithm explained 43% of the variation in women and 38% in men compared with 39% and 35%, respectively, by the modified Framingham score. Of the 112 156 patients classified as high risk (that is, ≥20% risk over 10 years) by the modified Framingham score, 46 094 (41.1%) would be reclassified at low risk with QRISK2. The 10 year observed risk among these reclassified patients was 16.6% (95% confidence interval 16.1% to 17.0%)—that is, below the 20% treatment threshold. Of the 78 024 patients classified at high risk on QRISK2, 11 962 (15.3%) would be reclassified at low risk by the modified Framingham score. The 10 year observed risk among these patients was 23.3% (22.2% to 24.4%)—that is, above the 20% threshold. In the validation cohort, the annual incidence rate of cardiovascular events among those with a QRISK2 score of ≥20% was 30.6 per 1000 person years (29.8 to 31.5) for women and 32.5 per 1000 person years (31.9 to 33.1) for men. The corresponding figures for the modified Framingham equation were 25.7 per 1000 person years (25.0 to 26.3) for women and 26.4 (26.0 to 26.8) for men). At the 20% threshold, the population identified by QRISK2 was at higher risk of a CV event than the population identified by the Framingham score. Conclusions Incorporating ethnicity, deprivation, and other clinical conditions into the QRISK2 algorithm for risk of cardiovascular disease improves the accuracy of identification of those at high risk in a nationally representative population. At the 20% threshold, QRISK2 is likely to be a more efficient and equitable tool for treatment decisions for the primary prevention of cardiovascular disease. As the validation was performed in a similar population to the population from which the algorithm was derived, it potentially has a “home advantage.” Further validation in other populations is therefore advised.

Derivation and validation of QRISK, a new cardiovascular disease risk score for the United Kingdom: prospective open cohort study

Objective To derive a new cardiovascular disease risk score (QRISK) for the United Kingdom and to validate its performance against the established Framingham cardiovascular disease algorithm and a newly developed Scottish score (ASSIGN). Design Prospective open cohort study using routinely collected data from general practice. Setting UK practices contributing to the QRESEARCH database. Participants The derivation cohort consisted of 1.28 million patients, aged 35-74 years, registered at 318 practices between 1 January 1995 and 1 April 2007 and who were free of diabetes and existing cardiovascular disease. The validation cohort consisted of 0.61 million patients from 160 practices. Main outcome measures First recorded diagnosis of cardiovascular disease (incident diagnosis between 1 January 1995 and 1 April 2007): myocardial infarction, coronary heart disease, stroke, and transient ischaemic attacks. Risk factors were age, sex, smoking status, systolic blood pressure, ratio of total serum cholesterol to high density lipoprotein, body mass index, family history of coronary heart disease in first degree relative aged less than 60, area measure of deprivation, and existing treatment with antihypertensive agent. Results A cardiovascular disease risk algorithm (QRISK) was developed in the derivation cohort. In the validation cohort the observed 10 year risk of a cardiovascular event was 6.60% (95% confidence interval 6.48% to 6.72%) in women and 9.28% (9.14% to 9.43%) in men. Overall the Framingham algorithm over-predicted cardiovascular disease risk at 10 years by 35%, ASSIGN by 36%, and QRISK by 0.4%. Measures of discrimination tended to be higher for QRISK than for the Framingham algorithm and it was better calibrated to the UK population than either the Framingham or ASSIGN models. Using QRISK 8.5% of patients aged 35-74 are at high risk (20% risk or higher over 10 years) compared with 13% when using the Framingham algorithm and 14% when using ASSIGN. Using QRISK 34% of women and 73% of men aged 64-75 would be at high risk compared with 24% and 86% according to the Framingham algorithm. UK estimates for 2005 based on QRISK give 3.2 million patients aged 35-74 at high risk, with the Framingham algorithm predicting 4.7 million and ASSIGN 5.1 million. Overall, 53 668 patients in the validation dataset (9% of the total) would be reclassified from high to low risk or vice versa using QRISK compared with the Framingham algorithm. Conclusion QRISK performed at least as well as the Framingham model for discrimination and was better calibrated to the UK population than either the Framingham model or ASSIGN. QRISK is likely to provide more appropriate risk estimates to help identify high risk patients on the basis of age, sex, and social deprivation. It is therefore likely to be a more equitable tool to inform management decisions and help ensure treatments are directed towards those most likely to benefit. It includes additional variables which improve risk estimates for patients with a positive family history or those on antihypertensive treatment. However, since the validation was performed in a similar population to the population from which the algorithm was derived, it potentially has a “home advantage.” Further validation in other populations is therefore required.

Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC)

Objective: To improve equity in cardiovascular disease prevention by developing a cardiovascular risk score including social deprivation and family history. Design: The ASSIGN score was derived from cardiovascular outcomes in the Scottish Heart Health Extended Cohort (SHHEC). It was tested against the Framingham cardiovascular risk score in the same database. Setting: Random-sample, risk-factor population surveys across Scotland 1984–87 and North Glasgow 1989, 1992 and 1995. Participants: 6540 men and 6757 women aged 30–74, initially free of cardiovascular disease, ranked for social deprivation by residence postcode using the Scottish Index of Multiple Deprivation (SIMD) and followed for cardiovascular mortality and morbidity through 2005. Results: Classic risk factors, including cigarette dosage, plus deprivation and family history but not obesity, were significant factors in constructing ASSIGN scores for each sex. ASSIGN scores, lower on average, correlated closely with Framingham values for 10-year cardiovascular risk. Discrimination of risk in the SHHEC population was significantly, but marginally, improved overall by ASSIGN. However, the social gradient in cardiovascular event rates was inadequately reflected by the Framingham score, leaving a large social disparity in future victims not identified as high risk. ASSIGN classified more people with social deprivation and positive family history as high risk, anticipated more of their events, and abolished this gradient. Conclusion: Conventional cardiovascular scores fail to target social gradients in disease. By including unattributed risk from deprivation, ASSIGN shifts preventive treatment towards the socially deprived. Family history is valuable not least as an approach to ethnic susceptibility. ASSIGN merits further evaluation for clinical use.

Predictive accuracy of the Framingham coronary risk score in British men: prospective cohort study

Abstract Objective To establish the predictive accuracy of the Framingham risk score for coronary heart disease in a representative British population. Design Prospective cohort study. Setting 24 towns in the United Kingdom. Participants 6643 British men aged 40-59 years and free from cardiovascular disease at entry into the British regional heart study. Main outcome measures Comparison of observed 10 year coronary heart disease mortality and event rates with predicted rates for each individual, using the relevant Framingham risk equation. Results Of 6643 men, 2.8% (95% confidence interval 2.4% to 3.2%) died from coronary heart disease compared with 4.1% predicted (relative overestimation 47%, P < 0.0001). A fatal or non-fatal coronary heart disease event occurred in 10.2% (9.5% to 10.9%) of the men compared with 16.0% predicted (relative overestimation 57%, P < 0.0001). These relative degrees of overestimation were similar at all levels of coronary heart disease risk, so that overestimation of absolute risk was greatest for those at highest risk. A simple adjustment provided an improved level of accuracy. In a “high risk score” approach, most cases occur in the low risk group. In this case, 84% of the deaths from coronary heart disease and non-fatal events occurred in the 93% of men classified at low risk (< 30% in 10 years) by the Framingham score. Conclusion Guidelines for the primary prevention of coronary heart disease advocate offering preventive measures to individuals at high risk. Currently recommended risk scoring methods derived from the Framingham study significantly overestimate the absolute coronary risk assigned to individuals in the United Kingdom.

Accuracy and impact of risk assessment in the primary prevention of cardiovascular disease: a systematic review

Objective: To determine the accuracy of assessing cardiovascular disease (CVD) risk in the primary prevention of CVD and its impact on clinical outcomes. Design: Systematic review. Data sources: Published studies retrieved from Medline and other databases. Reference lists of identified articles were inspected for further relevant articles. Selection of studies: Any study that compared the predicted risk of coronary heart disease (CHD) or CVD, with observed 10-year risk based on the widely recommended Framingham methods (review A). Randomised controlled trials examining the effect on clinical outcomes of a healthcare professional assigning a cardiovascular risk score to people predominantly without CVD (review B). Review methods: Data were extracted on the ratio of the predicted to the observed 10-year risk of CVD and CHD (review A), and on cardiovascular or coronary fatal or non-fatal events, risk factor levels, absolute cardiovascular or coronary risk, prescription of risk-reducing drugs and changes in health-related behaviour (review B). Results: 27 studies with data from 71 727 participants on predicted and observed risk for either CHD or CVD were identified. For CHD, the predicted to observed ratios ranged from an underprediction of 0.43 (95% CI 0.27 to 0.67) in a high-risk population to an overprediction of 2.87 (95% CI 1.91 to 4.31) in a lower-risk population. In review B, four randomised controlled trials confined to people with hypertension or diabetes found no strong evidence that a cardiovascular risk assessment performed by a clinician improves health outcomes. Conclusion: The performance of the Framingham risk scores varies considerably between populations and evidence supporting the use of cardiovascular risk scores for primary prevention is scarce.

Predicting risk of type 2 diabetes in England and Wales: prospective derivation and validation of QDScore

Objective To develop and validate a new diabetes risk algorithm (the QDScore) for estimating 10 year risk of acquiring diagnosed type 2 diabetes over a 10 year time period in an ethnically and socioeconomically diverse population. Design Prospective open cohort study using routinely collected data from 355 general practices in England and Wales to develop the score and from 176 separate practices to validate the score. Participants 2 540 753 patients aged 25-79 in the derivation cohort, who contributed 16 436 135 person years of observation and of whom 78 081 had an incident diagnosis of type 2 diabetes; 1 232 832 patients (7 643 037 person years) in the validation cohort, with 37 535 incident cases of type 2 diabetes. Outcome measures A Cox proportional hazards model was used to estimate effects of risk factors in the derivation cohort and to derive a risk equation in men and women. The predictive variables examined and included in the final model were self assigned ethnicity, age, sex, body mass index, smoking status, family history of diabetes, Townsend deprivation score, treated hypertension, cardiovascular disease, and current use of corticosteroids; the outcome of interest was incident diabetes recorded in general practice records. Measures of calibration and discrimination were calculated in the validation cohort. Results A fourfold to fivefold variation in risk of type 2 diabetes existed between different ethnic groups. Compared with the white reference group, the adjusted hazard ratio was 4.07 (95% confidence interval 3.24 to 5.11) for Bangladeshi women, 4.53 (3.67 to 5.59) for Bangladeshi men, 2.15 (1.84 to 2.52) for Pakistani women, and 2.54 (2.20 to 2.93) for Pakistani men. Pakistani and Bangladeshi men had significantly higher hazard ratios than Indian men. Black African men and Chinese women had an increased risk compared with the corresponding white reference group. In the validation dataset, the model explained 51.53% (95% confidence interval 50.90 to 52.16) of the variation in women and 48.16% (47.52 to 48.80) of that in men. The risk score showed good discrimination, with a D statistic of 2.11 (95% confidence interval 2.08 to 2.14) in women and 1.97 (1.95 to 2.00) in men. The model was well calibrated. Conclusions The QDScore is the first risk prediction algorithm to estimate the 10 year risk of diabetes on the basis of a prospective cohort study and including both social deprivation and ethnicity. The algorithm does not need laboratory tests and can be used in clinical settings and also by the public through a simple web calculator (www.qdscore.org).

Derivation, validation, and evaluation of a new QRISK model to estimate lifetime risk of cardiovascular disease: cohort study using QResearch database

Objective To develop, validate, and evaluate a new QRISK model to estimate lifetime risk of cardiovascular disease. Design Prospective cohort study with routinely collected data from general practice. Cox proportional hazards models in the derivation cohort to derive risk equations accounting for competing risks. Measures of calibration and discrimination in the validation cohort. Setting 563 general practices in England and Wales contributing to the QResearch database. Subjects Patients aged 30–84 years who were free of cardiovascular disease and not taking statins between 1 January 1994 and 30 April 2010: 2 343 759 in the derivation dataset, and 1 267 159 in the validation dataset. Main outcomes measures Individualised estimate of lifetime risk of cardiovascular disease accounting for smoking status, ethnic group, systolic blood pressure, ratio of total cholesterol:high density lipoprotein cholesterol, body mass index, family history of coronary heart disease in first degree relative aged <60 years, Townsend deprivation score, treated hypertension, rheumatoid arthritis, chronic renal disease, type 2 diabetes, and atrial fibrillation. Age-sex centile values for lifetime cardiovascular risk compared with 10 year risk estimated using QRISK2 (2010). Results Across all the 1 267 159 patients in the validation dataset, the 50th, 75th, 90th, and 95th centile values for lifetime risk were 31%, 39%, 50%, and 57% respectively. Of the 10% of patients in the validation cohort classified at highest risk with either the lifetime risk model or the 10 year risk model, only 18 385(14.5%) were at high risk on both measures. Patients identified as high risk with the lifetime risk approach were more likely to be younger, male, from ethnic minority groups, and have a positive family history of premature coronary heart disease than those identified with the 10 year QRISK2 score. The lifetime risk calculator is available at www.qrisk.org/lifetime/. Conclusions Compared with using a 10 year QRISK2 score, a lifetime risk score will tend to identify patients for intervention at a younger age. Although lifestyle interventions at an earlier age could be advantageous, there would be small gains under the age of 65, and medical interventions carry risks as soon as they are initiated. Research is needed to examine closely the cost effectiveness and acceptability of such an approach.

Performance of the QRISK cardiovascular risk prediction algorithm in an independent UK sample of patients from general practice: a validation study

Aim: To assess the performance of the QRISK score for predicting cardiovascular disease (CVD) in an independent UK sample from general practice and compare with the Framingham score. Design: Prospective open cohort study Setting: UK general practices contributing to the THIN and QRESEARCH databases. Cohort: The THIN validation cohort consisted of 1.07 million patients, aged 35–74 years registered at 288 THIN practices between 1 January 1995 and 1 April 2006. The QRESEARCH validation cohort consisted of 0.61 million patients from 160 practices (one-third of the full database) with data until 1 January 2007. Patients receiving statins, those with diabetes or CVD at baseline were excluded. End point: First diagnosis of CVD (myocardial infarction, coronary heart disease (CHD), stroke and transient ischaemic attack) recorded on the clinical computer system during the study period. Exposures: Age, sex, smoking status, systolic blood pressure, total/high-density lipoprotein cholesterol ratio, body mass index, family history of premature CHD, deprivation and antihypertensive medication. Results: Characteristics of both cohorts were similar, except that THIN patients were from slightly more affluent areas and had lower recording of family history of CHD. QRISK performed better than Framingham for every discrimination and calibration statistic in both cohorts. Framingham overpredicted risk by 23% in the THIN cohort, while QRISK underpredicted risk by 12%. Conclusion: This analysis demonstrated that QRISK is better calibrated to the UK population than Framingham and has better discrimination. The results suggest that QRISK is likely to provide more appropriate risk estimates than Framingham to help identify patients at high risk of CVD in the UK.

Primary prevention of cardiovascular disease: a web-based risk score for seven British black and minority ethnic groups

Objective: To recalibrate an existing Framingham risk score to produce a web-based tool for estimating the 10-year risk of coronary heart disease (CHD) and cardiovascular disease (CVD) in seven British black and minority ethnic groups. Design: Risk prediction models were recalibrated against survey data on ethnic group risk factors and disease prevalence compared with the general population. Ethnic- and sex-specific 10-year risks of CHD and CVD, at the means of the risk factors for each ethnic group, were calculated from the product of the incidence rate in the general population and the prevalence ratios for each ethnic group. Setting: Two community-based surveys. Participants: 3778 men and 4544 women, aged 35–54, from the Health Surveys for England 1998 and 1999 and the Wandsworth Heart and Stroke Study. Main outcome measures: 10-year risk of CHD and CVD. Results: 10-year risk of CHD and CVD for non-smoking people aged 50 years with a systolic blood pressure of 130 mm Hg and a total cholesterol to high density lipoprotein cholesterol ratio of 4.2 was highest in men for those of Pakistani and Bangladeshi origin (CVD risk 12.6% and 12.8%, respectively). CHD risk in men with the same risk factor values was lowest in Caribbeans (2.8%) and CVD risk was lowest in Chinese (5.4%). Women of Pakistani origin were at highest risk and Chinese women at lowest risk for both outcomes with CVD risks of 6.6% and 1.2%, respectively. A web-based risk calculator (ETHRISK) allows 10-year risks to be estimated in routine primary care settings for relevant risk factor and ethnic group combinations. Conclusions: In the absence of cohort studies in the UK that include significant numbers of black and minority ethnic groups, this risk score provides a pragmatic solution to including people from diverse ethnic backgrounds in the primary prevention of CVD.

Memory loss during pregnancy

Objective To investigate possible impairment of memory during pregnancy.