Nadeem Qureshi, DM; Sarah Armstrong, PhD; Paula Dhiman, MSc; Paula Saukko, PhD; Joan Middlemass, MPhil; Philip H. Evans, MPhil; Joe Kai, MD; ADDFAM (Added Value of Family History in CVD Risk Assessment) Study Group
Evidence of the value of systematically collecting family history in primary care is limited.
To evaluate the feasibility of systematically collecting family history of coronary heart disease in primary care and the effect of incorporating these data into cardiovascular risk assessment.
Pragmatic, matched-pair, cluster randomized, controlled trial. (International Standardized Randomized Controlled Trial Number Register: ISRCTN 17943542).
24 family practices in the United Kingdom.
748 persons aged 30 to 65 years with no previously diagnosed cardiovascular risk, seen between July 2007 and March 2009.
Participants in control practices had the usual Framingham-based cardiovascular risk assessment with and without use of existing family history information in their medical records. Participants in intervention practices also completed a questionnaire to systematically collect their family history. All participants were informed of their risk status. Participants with high cardiovascular risk were invited for a consultation.
The primary outcome was the proportion of participants with high cardiovascular risk (10-year risk ≥20%). Other measures included questionnaire completion rate and anxiety score.
98% of participants completed the family history questionnaire. The mean increase in proportion of participants classified as having high cardiovascular risk was 4.8 percentage points in the intervention practices, compared with 0.3 percentage point in control practices when family history from patient records was incorporated. The 4.5–percentage point difference between groups (95% CI, 1.7 to 7.2 percentage points) remained significant after adjustment for participant and practice characteristics (P = 0.007). Anxiety scores were similar between groups.
Relatively few participants were from ethnic minority or less-educated groups. The potential to explore behavioral change and clinical outcomes was limited. Many data were missing for anxiety scores.
Systematically collecting family history increases the proportion of persons identified as having high cardiovascular risk for further targeted prevention and seems to have little or no effect on anxiety.
Genetics Health Services Research program of the United Kingdom Department of Health.
Information about a patient's family history can improve risk assessment for cardiovascular disease.
This cluster randomized trial, which involved 748 adult patients with no previously diagnosed cardiovascular risk across 24 family practices, found that collecting family history data with mailed questionnaires identified more high-risk patients who were eligible for targeted prevention than did usual practice procedures (4.8% vs. 0.3%).
Effect on long-term clinical outcomes of patients was not evaluated.
Systematic collection of family history data is a feasible practice-level intervention that could improve cardiovascular risk assessment and help target patients who are most in need of preventive interventions.
Figure. Study flow diagram.
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David C., Goff, Professor and Chair, Department of Epidemiology and Prevention
Wake Forest School of Medicine
February 26, 2012
Easy math is not necessarily correct.
I read with concern the article by Qureshi and colleagues. Whereas the clinical trial methodology is admirable, the scientific questions posed are not helpful to understanding the role of data on family history in improving risk assessment. On a superficial level, the idea that risk can only be upgraded is incorrect. If a positive family history is used to upgrade risk, a negative family history should be used to downgrade risk. Otherwise, the calibration of the underlying model is ignored. On a more substantive level, this study provides no evidence regarding whether data on family history provides value by improving model discrimination or calibration, or whether any reclassification is actually correct. As noted by the authors, this paper also does not address patient behaviors, treatments, or outcomes. These results do not support the incorporation of assessments of family history into routine clinical practice. We need results documenting improved discrimination, calibration, and correct reclassification. Easy math is not necessarily correct.
John, Robson, Senior lecturer, Julia Hippisley-Cox, Peter Brindle
Centre for Health Sciences, Queen Mary's School of Medicine and Dentistry, London E1 2AT
February 28, 2012
Family History already included in QRISK which is used widely in the NHS in the UK
We agree with the authors that a positive family history of ischaemic heart disease under age 60 years in a first degree relative has a marked impact on future risk of major cardiovascular . In in the UK, we developed a new cardiovascular risk prediction algorithm QRISK derived from 10.9 million person years and established that for both men and women, in all major ethnic groups, and at all levels of social deprivation, that a positive family history is associated with an increased risk of cardiovascular disease. On multivariate analysis, the magnitude of this increased risk varies with age from a nearly three-fold increase in patients aged 35-40 to a 30% increase among those aged 70-75 years which is similar to findings reported in other multi-ethnic studies. QRISK (www.qrisk.org) has been externally validated by an independent team and is included in national guidelines and routinely used to assess cardiovascular risk as part of the NHS health Checks programme aiming to assess risk in some 15 million people nationally in England. Of these approximately 10%, 1 million people, will have positive family history. ASSIGN similarly incorporates family history in Scotland www.assign-score.com . Around 1 million people in England will have a 10yr risk of cardiovascular disease of 20% or more, for which positive family history will be a contributing factor. For these people current guidance recommends statins together with lifestyle change and antihypertensives where appropriate
1. Qureshi N, Armstrong S, Dhiman P, Saukko P, Middlemass J, Evans PH, et al. Effect of Adding Systematic Family History Enquiry to Cardiovascular Disease Risk Assessment in Primary Care. Annals of Internal Medicine 2012;156(4):253-62.
2. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ 2008:bmj.39609.449676.25.
3. Nasir K, Budoff MJ, Wong ND, Scheuner M, Herrington D, Arnett DK, et al. Family history of premature coronary heart disease and coronary artery calcification: Multi-Ethnic Study of Atherosclerosis (MESA). Circulation 2007;116(6):619-26.
4. Collins GS, Altman DG. An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study. BMJ 2010;340:c2442-.
5. National Institute for Clinical Excellence. Lipid modification - Cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. In: NICE, editor. London: NICE, 2008.
JR and PB were previously members of the NICE Guideline Development Group for Lipid Modification of which JR was chair. JHC is professor of clinical epidemiology at the University of Nottingham and co-director of QResearch? - a not-for-profit organisation which is a joint partnership between the University of Nottingham and EMIS (leading commercial supplier of IT for 60% of general practices in the UK). JHC is also director of ClinRisk Ltd which produces open and closed source software to ensure the reliable and updatable implementation of clinical risk algorithms. This work and any views expressed within it are solely those of the co-authors and not of any affiliated bodies or organisations. There are no other relationships or activities that could appear to have influenced the submitted work.
Paul N., Durrington, Professor of Medicine
University of Manchester
April 10, 2012
Joint British Societies' Recommendations for Cardiovascular Disease Prevention: clarification
John Robson and colleagues are right to point out that family history has a greater influence on cardiovascular disease (CVD) risk in younger people. Thus, incorporating it into CVD risk assessment by simply multiplying by a single factor, as in the interesting article by Qureshi and colleagues, is not ideal. It is ironic, however, that the QRISK2 algorithm may not lead to intervention which is as effective as the Joint British Societies' (JBS) recommendations . The validation to which John Robson et al refer  was not reassuring. In particular, the intervention group identified by QRISK2 had a mean CVD risk of 25% over the next 10 years whereas people with a 20% risk were targeted by the Framingham-based JBS2 assessment, exactly the level recommended for treatment with statins. The difference between the two approaches is exemplified by a man aged 68 having a serum cholesterol of 200mg/dL, LDL cholesterol 120mg/dL, HDL cholesterol 55 mg/dl, serum triglycerides 125 mg/dL, systolic blood pressure 160mmHg, height 172cm and body weight 90kg, whose 10-year risk is 20% by QRISK2 and 25% by JBS2. Prescribing a statin to achieve an LDL cholesterol target of 80mg/dL, will decrease his 10-year risk by one fifth (one fifth for each 40mg/dL decrease in LDL cholesterol ). A younger man aged 60 living in the same location with a much higher serum cholesterol of 280mg/dL and LDL cholesterol of 200mg/dL, but similar HDL cholesterol, triglycerides, height and weight, will have a 10-year risk of 16% by QRISK2 and 20% by JBS2. He would not receive a statin by QRISK2, but would according to JBS2. However, reducing his LDL cholesterol to 80mg/dL will decrease his cardiovascular risk by three fifths. Because examples such as these are commonplace, JBS2 will have a substantially greater impact in decreasing cardiovascular disease incidence in the general population. From the QRISK2 authors' own report  we know it identifies fewer young people than Framingham, but more elderly ones as at >20% 10-year risk. Whilst the concept of targeting younger people at high lifetime risk rather than waiting for them to cross a single threshold of risk is currently controversial , there is certainly no suggestion that we should adopt higher thresholds of risk for intervention in younger people and it is to be hoped the future iterations of QRISK2 will correct this problem.
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2. Collins GS, Altman DG. An independent and external validation of QRISK2 cardiovascular disease risk score: a prospective open cohort study. BMJ 2010; 340: c2442.
3. Cholesterol Treatment Trialists' (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010; 376: 1670-81.
4. Hippisley-Cox J, Coupland C, Vinogradova Y, Robson J, Minhas R, Sheikh A, et al. Predicting cardiovascular risk in England and Wales: prospective derivation and validation of QRISK2. BMJ 2008; 336: 1475-82.
5. Liew SM, Jackson R, Glasziou P. Should identical CVD risks in young and old patients be managed identically? Results from two models. BMJ Open 2012; 2: e000728.doi:10.1136/bmjopen-2011-000728 Accessed 4/10/12
Paul Durrington was a member of the JBS Committee developing recommendations for CVD prevention. His employer, the University of Manchester, holds the copyrights for the JBS2 charts and the JBS2 Cardiovascular Risk Assessor computer program, but does so not for profit, but to prevent their commercial exploitation. They are freely available to health professionals.
Nadeem, Qureshi, Professor, Paula Dhiman and Joe Kai
University of Nottingham
April 24, 2012
We agree with Goff that further study of the discriminatory accuracy of positive and negative family history in cardiovascular disease risk assessment algorithms is needed. The communication from Robson et al and other work (1) provide relevant information here. However, our research (2) had a clinical rather than epidemiological aim and so addressed different questions. We were concerned with clinical utility. We assessed the feasibility and impact of systematically collecting family history in comparison to its usual adhoc collection, and its subsequent use in cardiovascular risk assessment in family practice (3). Our paper offers the highest level of evidence for this sort of clinical intervention by use of a cluster randomised trial.
Robson et al provide helpful contextual information about the QRisk2 tool in the UK. On commencing our trial in 2007, the most widely adopted cardiovascular risk assessment tool in English family practice was the JBS tool as described and used in our study (2). This tool remains in the current British National Formulary, issued for use by all UK physicians in primary or secondary care. As the JBS tool uses the Framingham algorithm, which is employed in other developed countries, we hope our study will have wider international resonance, including in the US where it originated.
As noted in our paper, midway through our study, the potential value of family history became more prominent in the UK and we cite guidelines to which Robson et al also refer (4). In addition to JBS, this guidance, reissued with further information in 2010, alerts clinicians in the UK that they have an increasing choice of other risk assessment tools such as QRisk2, and notes the considerable debate about their relative merits (4). Whatever assessment tool is applied, one major challenge in actual practice remains the same: capturing and using authentic family history data. As Berg suggests in his editorial (5), our trial highlights the promise of a potentially low cost and feasible intervention to realise this in primary care practice.
It is encouraging there continues to be interest in the role of family history in cardiovascular risk assessment, and we look forward to further research in this field.
Nadeem Qureshi, Paula Dhiman and Joe Kai
1. Woodward M, Brindle P, Tunstall-Pedoe H, SIGN group on risk estimation. Adding social deprivation and family history to cardiovascular risk assessment: the ASSIGN score from the Scottish Heart Health Extended Cohort (SHHEC). Heart 2007; 93:172-6
2. Qureshi N, Armstrong S, Dhiman P, Saukko P, Middlemass J, Evans PH, Kai J. Effect of Adding Systematic Family History Enquiry to Cardiovascular Disease Risk Assessment in Primary Care. Ann Intern Med 2012; 156: 253-262.
3.Valdez R, Yoon PW, Qureshi N, Green RF, Khoury MJ. Family History in Public Health Practice: A Genomic Tool for Disease Prevention and Health Promotion. Annu. Rev. Public Health 2010; 31:69-87
4. Cooper A, Nherera L, Calvert N, O'Flynn N, Turnbull N, Robson J, et al. Clinical Guidelines and Evidence Review for Lipid Modification: Cardiovascular Risk Assessment and the Primary and Secondary Prevention of Cardiovascular Disease. London: National Collaborating Centre for Primary Care and Royal College of General Practitioners, 2008 (reissued March 2010).
5. Berg AO. Family History Gets a Boost. Ann Intern Med 2012; 156: 315-316.
Qureshi N, Armstrong S, Dhiman P, Saukko P, Middlemass J, Evans PH, et al. Effect of Adding Systematic Family History Enquiry to Cardiovascular Disease Risk Assessment in Primary Care
A Matched-Pair, Cluster Randomized Trial
. Ann Intern Med. 2012;156:253–262. doi: 10.7326/0003-4819-156-4-201202210-00002
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Published: Ann Intern Med. 2012;156(4):253-262.
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