Yana Vinogradova

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.

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.

Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

Objective To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. Design Two nested case-control studies. Setting General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). Participants Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. Main outcome measures Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. Results 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). Conclusions In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral contraceptives were, with the exception of norgestimate, higher for newer drug preparations than for second generation drugs.

Exposure to statins and risk of common cancers: a series of nested case-control studies

1 AbstractBackgroundMany studies and meta-analyses have investigated the effects of statins on cancer incidence but without showing consistent effects.MethodsA series of nested case-control studies was conducted covering 574 UK general practices within the QResearch database. Cases were patients with primary cancers diagnosed between 1998 and 2008. The associations between statin use and risk of ten site-specific cancers were estimated with conditional logistic regression adjusted for co-morbidities, smoking status, socio-economic status, and use of non-steroidal anti-inflammatory drugs, cyclo-oxygenase-2 inhibitors and aspirin.Results88125 cases and 362254 matched controls were analysed. The adjusted odds ratio for any statin use and cancer at any site were 1.01 (95%CI 0.99 to 1.04). For haematological malignancies there was a significant reduced risk associated with any statin use (odds ratio 0.78, 95%CI 0.71 to 0.86). Prolonged (more than 4 years) use of statins was associated with a significantly increased risk of colorectal cancer (odds ratio 1.23, 95%CI 1.10 to 1.38), bladder cancer (odds ratio 1.29, 95%CI 1.08 to 1.54) and lung cancer (odds ratio 1.18, 95%CI 1.05 to 1.34). There were no significant associations with any other cancers.ConclusionIn this large population-based case-control study, prolonged use of statins was not associated with an increased risk of cancer at any of the most common sites except for colorectal cancer, bladder cancer and lung cancer, while there was a reduced risk of haematological malignancies.

Inequalities in the primary care of patients with coronary heart disease and serious mental health problems: a cross-sectional study

Objective: To determine whether UK patients with coronary heart disease (CHD) who also have schizophrenia or bipolar disorder are less likely to receive primary care in accordance with the agreed national standards of the UK than patients without these mental health problems. Design: Cross-sectional study. Setting: 485 UK general practices contributing anonymised medical records of over 3.26 million patients to the QRESEARCH database. Participants: 127 932 patients with CHD of whom 701 had a diagnosis of schizophrenia or bipolar disorder. Main outcome measures: The relative risks of receiving statin medication and each of the CHD care indicators defined in the UK General Medical Services contract, for patients with schizophrenia or bipolar disorder compared with patients with neither condition. The results were adjusted for age, sex, deprivation, diabetes, stroke and smoking status, and allowed for clustering by practice. Results: Patients with schizophrenia were 15% less likely to have a recent prescription for a statin (95% CI 8% to 20%) and 7% less likely to have a recent record of cholesterol level (95% CI 3% to 11%). There were no significant differences in the adjusted analyses between mental health groups on recording smoking status, advising on smoking cessation, recording blood pressure, achieving target blood pressure or cholesterol values, or prescribing aspirin, antiplatelets, anticoagulants or β blockers. Conclusions: Although the majority of CHD care indicators are achieved equally for patients who also have a serious mental health problem, there is a shortfall in identifying and treating raised cholesterol among patients with schizophrenia, despite their higher level of risk factors.

Identification of new risk factors for pneumonia: population-based case-control study

BACKGROUND Certain conditions are established as risk factors for community-acquired pneumonia. There are a number of other conditions that may also be risk factors, but information on these is limited. AIM To determine new independent risk factors for community-acquired pneumonia using a very large primary care database. DESIGN OF STUDY Nested case-control study. SETTING Four hundred and forty-three general practices in the UK contributing to the QRESEARCH database. METHOD A total of 17 172 incident cases of all ages diagnosed with pneumonia between 1996 and 2005 were matched with up to five controls by age, sex, general practice, and calendar year. Associations between pneumonia and each established condition and potential risk factors were determined with odds ratios (ORs), using multiple conditional logistic regression analysis adjusted for smoking, socioeconomic status, and use of influenza and pneumococcal vaccines. RESULTS The analysis confirmed the higher risk of pneumonia among patients with at least one of the established risk factors; the adjusted OR was 2.29 (95% confidence interval [CI]=2.20 to 2.39). In addition, patients with the following conditions had a higher risk of pneumonia despite adjustment for known risk factors and confounders: stroke or transient ischaemic attack, rheumatoid arthritis, Parkinsons disease, cancers, multiple sclerosis, dementia, and osteoporosis. The adjusted OR for pneumonia among patients without an established risk factor but with at least one of the new conditions was 2.44 (95% CI=2.24 to 2.65). CONCLUSION As well as confirming some established risk factors, this study has determined seven new independent risk factors for community-acquired pneumonia.

Effects of severe mental illness on survival of people with diabetes

BACKGROUND People with mental health problems are more likely to die prematurely than the general population but no study has examined this in individuals with diabetes. AIMS To compare survival rates in people with diabetes with and without schizophrenia or bipolar disorder. METHOD A total of 43,992 people with diabetes were drawn from the QRESEARCH database population of over 9 million patients. Survival rates during the study period, between 1 April 2000 and 1 April 2005, and hazard ratios for deaths associated with schizophrenia and bipolar disorder were adjusted by age and gender and additionally for socioeconomic status, obesity, smoking and use of statins. RESULTS Among the participants, we identified 257 people diagnosed with schizophrenia, 159 with bipolar disorder and 14 with both conditions. Although crude survival rates did not show significant differences between the groups during the study period, people with schizophrenia or bipolar disorder and diabetes, compared with those with diabetes alone, had a significantly increased risk of death after adjusting for age and gender, with hazard ratios for schizophrenia of 1.84 (95% CI 1.42-2.40) and for bipolar disorder of 1.51 (95% CI 1.10-2.07). After adjusting for the other factors, hazard ratios were 1.52 (95 CI 1.17-1.97) for schizophrenia and 1.47 (95% CI 1.07-2.02) for bipolar disorder. CONCLUSIONS People with schizophrenia or bipolar disorder in addition to diabetes have a relatively higher mortality rate. This suggests that diabetes either progresses more rapidly or is more poorly controlled in these individuals, or that they have higher levels of comorbidity and so are more likely to die of other causes.

Exposure to bisphosphonates and risk of gastrointestinal cancers: series of nested case-control studies with QResearch and CPRD data

Objective To investigate the association between use of bisphosphonates estimated from prescription information and risk of gastrointestinal cancers. Design Series of nested case-control studies. Setting General practices in the United Kingdom contributing to the QResearch primary care database (660) and the Clinical Practice Research Datalink (CPRD) (643). Participants Patients aged ≥50 with a diagnosis of a primary gastrointestinal cancer in 1997-2011, each matched with up to five controls by age, sex, practice, and calendar year. Main outcome measures Odds ratios for incident gastrointestinal cancers (colorectal, oesophageal, gastric) and use of bisphosphonates, adjusted for smoking status, ethnicity, comorbidities, and use of other drugs. Results 20 106 and 19 035 cases of colorectal cancer cases, 5364 and 5135 cases of oesophageal cancer cases, and 3155 and 3157 cases of gastric cancer were identified from QResearch and CPRD, respectively. Overall bisphosphonate use (at least one prescription) was not associated with risk of colorectal, oesophageal, or gastric cancers in either database. Adjusted odds ratios (95% confidence interval) for QResearch and CPRD were 0.97 (0.79 to 1.18) and 1.18 (0.97 to 1.43) for oesophageal cancer; 1.12 (0.87 to 1.44) and 0.79 (0.62 to 1.01) for gastric cancer; and 1.03 (0.94 to 1.14) and 1.10 (1.00 to 1.22) for colorectal cancer. Additional analyses showed no difference between types of bisphosphonate for risk of oesophageal and colorectal cancers. For gastric cancer, alendronate use was associated with an increased risk (1.47, 1.11 to 1.95; P=0.008), but only in data from the QResearch database and without any association with duration and with no definitive confirmation from sensitivity analysis. Conclusions In this series of population based case-control studies in two large primary care databases, exposure to bisphosphonates was not associated with an increased risk of common gastrointestinal cancers.

Influenza vaccination for immunocompromised patients: systematic review and meta-analysis from a public health policy perspective.

Background Immunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events. Methodology/Principal Findings Electronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I2 and publication bias was assessed using Beggs funnel plot and Eggers regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR] = 0.23; 95% confidence interval [CI] = 0.16–0.34; p<0.001) and laboratory confirmed influenza infection (OR = 0.15; 95% CI = 0.03–0.63; p = 0.01) through vaccinating immunocompromised patie nts compared to placebo or unvaccinated controls. We found no difference in the odds of influenza-like illness compared to vaccinated immunocompetent controls. The pooled odds of seroconversion were lower in vaccinated patients compared to immunocompetent controls for seasonal influenza A(H1N1), A(H3N2) and B. A similar trend was identified for seroprotection. Meta-analyses of seroconversion showed higher odds in vaccinated patients compared to placebo or unvaccinated controls, although this reached significance for influenza B only. Publication bias was not detected and narrative synthesis supported our findings. No consistent evidence of safety concerns was identified. Conclusions/Significance Infection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.