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Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality among women. Both US [1] and European [2] prevention guidelines tailor interventions according to the individual risk estimate. The American College of Cardiology (ACC) and American Heart Association (AHA) recommend risk assessment by the Pooled Cohort Equations (PCE), which estimate 10-year risk of ASCVD, with 4 separate equations for African American and white women and men. Some studies have reported substantial risk overestimation by PCE, which may translate in a potential overtreatment of millions of patients with statins and other interventions [3]. More reassuring data come from a recent paper by Mora S. et al. [4], which examined the performance of the PCE in a large and multiethnic cohort of postmenopausal women of the Women’s Health Initiative (WHI). From the whole study cohort, the authors identified 19995 participants with data on the risk equation variables at baseline and who met the guideline inclusion and exclusion criteria. Cardiovascular events were generally self-reported by annual questionnaires and then further reviewed and adjudicated; additional events were also retrieved by linkage with the Centers for Medicare and Medicaid Services (CMS) claims for a group 6071 of women 65 years and older, enrolled in Medicare A or A/B. The average 10-year observed risks in these cohorts were constantly lower than the PCE-predicted risks; adjustment for the time-varying change in statin and aspirin use only resulted in a slight increase in the observed risks. With CMS claims data, 64 new events were recorded for the subgroup of elderly women enrolled in Medicare. After including 85% of these events, predicted risks became closely aligned with observed risks. Comment The main results of this study are that, at least for older (65 years old or more) postmenopausal women, the PCE provides an accurate estimate of cardiovascular risk and that studies which rely only on self-reported events may be biased by substantial underreporting. Nevertheless, the issue seems far from being settled. Yadlowsky S. et al. [3] have recently shown that revising the PCE with more modern cohort data and employing statistical methods that avoid overfitting, they could substantially improve the accuracy of cardiovascular risk estimates. How can we deal with these conflicting results? Clinicians know well that “prediction is very difficult, especially about the future” and are used to face a certain degree of imprecision of their tools. A call to a more pragmatic approach, involving physician “wisdom” and patient-physician relationship also comes from the very recent AHA/ACC cholesterol guidelines, presented in November [5], that also specifically recommend the use of risk assessment tools [6]. These new guidelines still endorse the use of the PCE as a starting point for cardiovascular risk assessment and patient-physician discussion on prevention but do recognise the potential for overestimation but also underestimation in certain situations. For patients with borderline and intermediate risk, risk enhancer factors (not present in PCE) should be considered, including history of premature cardiovascular disease and items particularly relevant for women such as premature menopause and history of preeclampsia. Risk refinement by measurement of coronary artery calcium score is also suggested. In conclusion, the paper by Mora et al. is reassuring with regards to the accuracy of cardiovascular risk prediction by PCE in elderly postmenopausal women of different ethnic groups. However, while the science of cardiovascular risk prediction advances, clinicians will always have to face uncertainties at the individual patient level. Discussion with the patients including risk enhancer factors, as recently proposed by AHA/ACC, may overcome limitations of risk scores and provide a framework for a rational and informed decision on preventive strategies.


  • Stefano Coli
    Division of Cardiology, Parma University Hospital, Parma, Italy


  1. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129 (25) (suppl 2):S49-S73.
  2. Piepoli MF, Hoes AW, Agewall S, et al; 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts) Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J 2016; 37(29):2315-2381.
  3. Yadlowsky S, Hayward RA, Sussman JB, et al. Clinical implications of revised pooled cohort equations for estimating atherosclerotic cardiovascular disease risk. Ann Intern Med 2018; 169(1):20-29.
  4. Mora S, Wenger NK, Cook NR, et al. Evaluation of the pooled cohort risk equations for cardiovascular risk prediction in a multiethnic cohort from the Women’s Health Initiative. JAMA Intern Med 2018; 178(9):1231-1240.
  5. Grundy SM, Stone NJ, Bailey AL, et al; 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol 2018 Nov 3. pii: S0735-1097(18)39033-8.
  6. Lloyd-Jones DM, Braun LT, Ndumele CE, et al. Use of Risk Assessment Tools to Guide Decision-Making in the Primary Prevention of Atherosclerotic Cardiovascular Disease: A Special Report From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2018 Nov 3. pii: S0735-1097(18)39036-3
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