Elevated Cardiac Biomarkers in Relatively Healthy U.S. Adults

Background Despite the importance of early cardiovascular disease (CVD) intervention, little data exists for evaluating cardiovascular risk in adults without traditional CVD risk factors (e.g., diabetes, hypertension). Methods We included 4,544 adults from the 1999-2004 National Health and Nutrition Examination Survey without prevalent diabetes, hypertension, chronic kidney disease, or CVD. We used multi-variable adjusted Cox proportional hazards regression modeling to assess the relationship between logarithmically transformed cardiac biomarkers (high sensitivity cardiac troponin T (hs-cTnT), hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP) and CVD mortality among a nationally representative cohort of relatively healthy adults. Results The mean age was 38.2 years (SD 12.8) and 53.9% were women. 8.7% had elevated levels of hs-cTnT or NT-proBNP above previously established thresholds for subclinical CVD. In multivariable adjusted models, each doubling of hs-cTnT was associated with a 49% increased risk of CVD mortality (Hazard Ratio (HR) 1.49, 95%CI 1.02-2.17, p =0.04). Only two of the hs-cTnI assays (Abbott and Ortho) were significantly associated with CVD mortality (Abbott HR 1.48, 95%CI 1.06-2.07, p =0.02; Ortho HR 1.47, 95%CI 1.23-1.77, p =0.0001). Each doubling of NT-proBNP was associated with a 41% increased risk of CVD mortality (HR 1.38, 95%CI 1.09-1.74, p =0.008). Conclusion Younger patients who maintain relatively good health may still carry occult CVD risk. Efforts to reduce population-wide CVD should consider novel methods for risk stratification, as standard CVD risk factors may overlook subpopulations at risk. Clinical Significance Among relatively healthy adults without significant CVD risk factors, elevated cardiac troponins and NT-proBNP are associated with cardiovascular and all-cause mortality. Subclinical cardiovascular disease poses higher cardiovascular risk among relatively healthy adults than previously appreciated. Efforts to reduce population-wide CVD should consider novel methods for risk stratification and early intervention to mitigate preventable CVD.