Biomarkers boost short-term CVD risk prediction for older patients
Adding biomarkers to the validated Pooled Cohort Equation (PCE) can improve predictions of cardiovascular events including heart attack, stroke and heart failure among older patients, researchers reported in the Journal of the American College of Cardiology.
Current guidelines recommend clinicians estimate the 10-year atherosclerotic cardiovascular disease (CVD) risk of patients before deciding how to treat their high blood pressure or cholesterol. This may be useful for most patients, but what about those already in their 80s or 90s, for whom a shorter time horizon may be more important?
For now, the guidelines suggest an approach that is more art than science. For individuals older than 75, the American College of Cardiology/American Heart Association recommend clinicians speak with patients and their families to help decide a course of treatment.
“However, it is difficult to discuss potential benefits and risks of therapy without comprehensive risk assessment,” wrote lead author Anum Saeed, MD, with Baylor College of Medicine, and colleagues. Also, heart failure hospitalizations aren’t included in the PCE, and heart failure is particularly relevant to the older population.
Saeed et al. added three biomarkers to the PCE to see whether it would improve predictions for a cohort of 4,760 adults with an average age of 75.4.
Individually, each biomarker improved the model over a median follow-up of about four years. The addition of all three—high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein—led to the greatest improvement, bumping up the C-statistic by 0.103 with a net reclassification improvement of 0.484.
The PCE model had what would be considered “fair” discrimination with a C-statistic of 0.647, while adding the three biomarkers improved the C-statistic to 0.750.
Saeed and colleagues also found a separate lab-based model with the three biomarkers plus age, sex and race performed better than the PCE, with a C-statistic of 0.738.
“We postulate that traditional risk factors work better in younger individuals because subclinical CVD tracks very closely with the presence of clinical risk factors, whereas in older individuals, risk factors such as hypertension are present in the vast majority of the population (70% in this study), and thus markers of subclinical ‘injury’ such as hs-cTnT and NT-proBNP provide greater benefit in predicting short-term risk,” the authors wrote.
The biomarkers better encompass the risk of developing heart failure, which was the most common CVD event during follow-up, Saeed et al. noted. In analyzing the study cohort during an earlier follow-up period—when the average age was 62—the researchers found the PCE was much more accurate. This further demonstrates the PCE is progressively less effective once patients pass a certain age.
However, the authors cautioned their study was observational and requires further confirmation before their updated risk model enters routine practice.
“A prospective trial would be necessary to examine the clinical effectiveness of an approach in which biomarkers were used for risk stratification to determine initiation and intensity of pharmacotherapy along with the cost-effectiveness of such an approach; particularly given the paucity of data in older adults, our results could be used to design clinical trials with more reasonable sample sizes, endpoints, and duration to test preventive strategies in this understudied population,” they wrote.
The authors of a related editorial agreed with the suggestion of further research, but added additional caveats.
“We cannot assume one size fits all for estimating the net benefit from a preventive therapy,” wrote Jennifer G. Robinson, MD, MPH, and Adrian F. Hernandez, MD, MHS. “Biological age, sex, race, ethnicity, socioeconomic status, comorbidities, and frailty are all likely to influence the benefit-risk ratio for any preventive therapy, including statins, antihypertensive, aspirin, other anticoagulant, and diabetes drugs.”
Additional factors such as quality of life and caregiver preferences might also be weighed differently in older versus younger patients, the editorialists said.