John Robson

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.

Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease

The National Institute for Health and Clinical Excellence (NICE) guideline, Lipid modification: Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease 1 is a significant advance over earlier more fragmented approaches to cardiovascular risk. The guideline provides strategies for identification of patients at risk, suggests lipid modification in primary and secondary prevention and unifies treatment approaches to coronary heart disease, stroke and peripheral vascular disease. This guideline does not give recommendations for patients with underlying disorders that increase cardiovascular disease risk, but NICE guidance on diabetes, which includes lipid modification, has also just been published2 and NICE guidance on familial hypercholesterolaemia is due shortly. A 20% cardiovascular disease (CVD) 10-year risk threshold for statin treatment was established by the technology appraisal on statins.3 This is considerably lower than the previously recommended National Service Framework threshold, which is equivalent to a 40% CVD risk. The new 20% CVD risk threshold increases the numbers of people targeted for further clinical assessment and possible statin treatment for primary prevention in England and Wales from around one million to over three million.4 The guideline endorses this threshold and sets out a strategy for the identification of people at high CVD risk and clarifies their management and treatment. The guidance recommends a systematic strategy to identify people …

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.

Improving uptake of breast screening in multiethnic populations: a randomised controlled trial using practice reception staff to contact non-attenders

Abstract Objectives: To determine whether a two hour training programme for general practice reception staff could improve uptake in patients who had failed to attend for breast screening, and whether women from different ethnic groups benefited equally. Design: Controlled trial, randomised by general practice. Setting: Inner London borough of Newham. Subjects: 2064 women aged 50–64 years who had failed to attend for breast screening. Women came from 26 of 37 eligible practices. 31% were white, 17% were Indian, 10% Pakistani, 14% black, 6% Bangladeshi, 1% Chinese, 4% were from other ethnic groups, and in 16% the ethnic group was not reported. Main outcome measures: Attendance for breast screening in relation to ethnic group in women who had not taken up their original invitation. Results: Attendance in the intervention group was significantly better than in the control group (9% v 4%). The response was best in Indian women—it was 19% in the intervention group and 5% in the control group. Conclusions: This simple, low cost intervention improved breast screening rates modestly. Improvement was greatest in Indian women—probably because many practice staff shared their cultural and linguistic background. This intervention could be effective as part of a multifaceted strategy to improve uptake in areas with low rates. Key messages The uptake of breast screening is inadequate and inequitable in some deprived areas—often those with large minority ethnic populations Training general practice receptionists to contact women who had not responded to an initial invitation for breast screening made a small but important improvement in attendance Improvement was most pronounced among Indian women—perhaps because most practices employed staff who spoke an Indian language Resources of local general practices could be used as part of multifaceted programmes to increase screening rates in areas of low uptake.

Using nurses for preventive activities with computer assisted follow up: a randomised controlled trial.

OBJECTIVE--To assess whether an organised programme of prevention including the use of a health promotion nurse noticeably improved recording and follow up of cardiovascular risk factors and cervical smears in a general practice that had access to computerised cell and recall. DESIGN--Randomised controlled trial. SETTING--General practice in inner London. PATIENTS--All 3206 men and women aged 30-64 registered with the practice. INTERVENTION--The intervention group had their risk factors ascertained and followed up by the health promotion nurse and the general practitioner, whereas those in the control group were managed by the general practitioner alone. END POINT--Recording and follow up of blood pressure and cervical smears after three years. Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations were also examined. MEASUREMENTS and MAIN RESULTS--When the trial was stopped after two years the measurements of blood pressure in the preceding five years were 93% (1511/1620) v 73% (1160/1586) (95% confidence interval for difference 17.5 to 22.7%) for intervention and control groups respectively. For patients with hypertension the figures were 97% (104/107) v 69% (80/116) (18.2 to 38.2%). For women the proportion who had had a cervical smear in the preceding three years were 76% (606/799) v 49% (392/806) (22.5 to 31.9%). Recording of smoking, family history of ischaemic heart disease, and serum cholesterol concentrations was also higher in the intervention group compared with the control group. CONCLUSION--An organised programme, which includes a nurse with specific responsibility for adult prevention, is likely to make an important contribution to recording of risk factors and follow up of those patients with known risks.

The NHS Health Check in England: an evaluation of the first 4 years.

Objectives To describe implementation of a new national preventive programme to reduce cardiovascular morbidity. Design Observational study over 4 years (April 2009—March 2013). Setting 655 general practices across England from the QResearch database. Participants Eligible adults aged 40–74 years including attendees at a National Health Service (NHS) Health Check. Intervention NHS Health Check: routine structured cardiovascular check with support for behavioural change and in those at highest risk, treatment of risk factors and newly identified comorbidity. Results Of 1.68 million people eligible for an NHS Health Check, 214 295 attended in the period 2009–12. Attendance quadrupled as the programme progressed; 5.8% in 2010 to 30.1% in 2012. Attendance was relatively higher among older people, of whom 19.6% of those eligible at age 60–74 years attended and 9.0% at age 40–59 years. Attendance by population groups at higher cardiovascular disease (CVD) risk, such as the more socially disadvantaged 14.9%, was higher than that of the more affluent 12.3%. Among attendees 7844 new cases of hypertension (38/1000 Checks), 1934 new cases of type 2 diabetes (9/1000 Checks) and 807 new cases of chronic kidney disease (4/1000 Checks) were identified. Of the 27 624 people found to be at high CVD risk (20% or more 10-year risk) when attending an NHS Health Check, 19.3% (5325) were newly prescribed statins and 8.8% (2438) were newly prescribed antihypertensive therapy. Conclusions NHS Health Check coverage was lower than expected but showed year-on-year improvement. Newly identified comorbidities were an important feature of the NHS Health Checks. Statin treatment at national scale for 1 in 5 attendees at highest CVD risk is likely to have contributed to important reductions in their CVD events.

Estimating cardiovascular risk for primary prevention: outstanding questions for primary care

Editorial by Jackson The recent joint British recommendations on the prevention of coronary heart disease, 1 the British Hypertension Society guidelines for the management of hypertension, 2 and comparable recommendations from the United States3 all conclude that the decision to start drug treatment in people at high risk but without cardiovascular disease should be based on their risk of coronary heart disease as estimated by the Framingham risk equations. We review some implications of their use in primary care. #### Summary points Prediction of coronary risk on the basis of multiple risk factors is more accurate than with any single factor alone People with a 30% or greater risk of a coronary heart disease event in 10 years should be considered for treatment with aspirin, antihypertensives, and statins Risk assessment for coronary heart disease should be routinely added to the existing screening programme for smoking and raised blood pressure The measurement of serum lipid concentrations in all adults is not necessary for the identification of people at high risk A national programme is required to support the identification and treatment of the 10% of the population who have coronary risks of 30% or more For 50 years the Framingham heart study has documented blood pressure, smoking, lipid concentrations, and other characteristics of 5300 white men and women, together with their causes of death and disease.4 These data have been used to predict death or major vascular events. It is important to be clear which outcome is being predicted and over what period. Expressed as risks at one, five, or 10 years the predicted outcomes include fatal and non-fatal coronary heart disease, 5 stroke, 6 and total cardiovascular disease including congestive cardiac failure and peripheral vascular disease.7 8 The risk of a coronary heart disease event in 10 years (myocardial infarction …