A new study shows that the oft-questioned pooled cohort equation (PCE) accurately assesses the risk of atherosclerotic cardiovascular disease (ASCVD) in a community cohort representing real-world clinical practice. This was true even for subjects whose continuous values were outside the equation’s initial values, including age younger than 40 years or older than 79 years, systolic blood pressure <90 mm or >200 mmHg, or total cholesterol <130 mg/dL or >230 mg/dL. It was also true even with the initiation of statin therapy during follow-up, as this factor did not lead to an overestimation of disease risk. Jose R. Medina-Inojosa, MD, MSc, of the Mayo Clinic, Rochester, Minnesota, and colleagues reported these findings in a manuscript published Monday online and in the Oct. 10 issue of the Journal of the American College of Cardiology. Study setup The PCE included primary data from several large studies during the pre-statin era and was used as part of the 2013 American College of Cardiology/American Heart Association cardiovascular (CV) risk assessment guidelines. The 2018 update recommends that PCE be the first step in assessing CV risk as a way to identify people who could potentially benefit from statin therapy as primary prevention of CV disease. However, the PCE’s validity has been called into question by several publications, and risk has been overestimated when PCE was applied to populations not similar to those in the original studies. Therefore, Medina-Inojosa and colleagues set out to validate the PCE in a contemporary, real-world cohort, evaluate the metric’s performance specifically on subjects who fall outside the range of the original equation, and determine the impact of statin therapy on the PCE’s predictive ability. The authors hypothesized that PCE would accurately predict ASCVD risk, maintain accuracy in individuals whose values do not conform to the original equation, and that statin initiation during follow-up would not result in overestimation of ASCVD risk. The authors validated the PCE in a cohort of consecutive patients who sought primary care in Olmsted County, Minnesota, from 1997 through 2000 and were followed through 2016. The primary outcome was ASCVD, defined as the composite of fatal and nonfatal myocardial infraction and fatal and nonfatal ischemic stroke. Subjects were followed up via review of electronic medical records from the index date of primary care until the occurrence of a first ASCVD or March 1, 2016, follow-up. Results The analysis included 30,042 adults. Their mean age was 48.5 ± 12.2 years, 46% were male, and most were white (94%). Their mean ASCVD risk was 5.6% ± 8.73%. A total of 1,555 ASCVD events (5.2%) were recorded. The PCE revealed good performance in the overall population (c-statistic = 0.78) and in subgroups defined by race and sex. The highest performance was in white female subjects (c-statistic = 0.81), and the lowest was in white male subjects (c-statistic = 0.77). The model’s performance was not affected by out-of-range values or the initiation of statin therapy. The authors listed several limitations to the study, including its observational nature, selection bias (because only individuals seen at primary-care outpatient clinics were included), and the limited racial diversity of Olmstead County. PCE stands ‘tests of time’ In an accompanying editorial, Donald M. Lloyd-Jones, MD, ScM, of the Northwestern University Feinberg School of Medicine, Chicago, generally praised the new analysis of PCE’s performance. He noted that, among other strengths, the study used “a clinical sample rather than population-based cohort data,” which he said gives it “particular relevance to the applicability of the risk assessment tool in clinical practice.” “Taken as a whole, these results should provide clinicians with even greater confidence in the utility of the PCEs for ASCVD risk estimation for middle-aged and older individuals in general practice; the PCEs have stood the tests of time and science, and many valuable insights have been gained,” Lloyd-Jones wrote. He described the PCE as an “initial step” for clinicians to use to evaluate their patients’ risks, after which they can personalize the risk to the individual patient “through consideration of individual risk-enhancing factors and the use of coronary artery calcium testing in selected patients to reclassify risk.” Lloyd-Jones posited that newer risk scores will likely be developed and future guidelines may be more precise. “These advances will be welcome,” he concluded. “In the meantime, we as clinicians would do well to focus on implementing the existing guidelines, given that use of preventive therapies for primary prevention is well below optimal in our patients who face the very real risks of ASCVD events given the increasing burdens of dyslipidemia, hypertension, diabetes, and other comorbidities in the population.” Sources: Medina-Inojosa JR, Somers VK, Garcia M, et al. Performance of the ACC/AHA Pooled Cohort Cardiovascular Risk Equations in Clinical Practice. J Am Coll Cardiol. 2023;82:1499–1508. Lloyd-Jones DM. The Pooled Cohort Equations and the Test of Time. J Am Coll Cardiol. 2023;82:1509–1511. Image Credit: phonlamaiphoto – stock.adobe.com