Chronic subclinical myocardial injury, detectable with high-sensitivity assays for cardiac troponin T (hs-cTnT) and I (hs-cTnI), is associated with increased risk for incident heart failure and mortality among asymptomatic individuals without known cardiovascular disease (CVD). Prevention or attenuation of myocardial injury therefore may represent an effective strategy for heart failure prevention. To that end, several preliminary studies have observed favorable effects of higher levels of physical activity on high sensitivity troponin levels,1,2 an observation that may provide mechanistic insight into larger studies demonstrating a dose-dependent reduction in heart failure risk with increased physical activity.3,4 Adults spend significantly more time being sedentary than they do performing moderate to vigorous physical activity (MVPA), and some studies have suggested that exercise does not abrogate the cardiovascular hazards of prolonged sedentary behavior.5 Although increased sedentary time has been associated with an increase in all-cause mortality and heart failure independent of regular exercise,3,5 no data are available describing the effects of sedentary time on chronic myocardial injury. We hypothesized that increased sedentary time would be associated with higher levels of hs-cTnT and hs-cTnI among individuals in the general population who are free from CVD.
To test this hypothesis, we performed a cross-sectional study that included participants completing the Phase 2 visit of the Dallas Heart Study who had at least 4 days of accelerometer wear time as well as measurements of either hs-cTnT or hs-cTnI. Participants with prevalent CVD and those reporting symptoms of chest pain, shortness of breath, or edema were excluded. Sedentary time and MVPA were assessed using an Actical (Phillps Respironics, Bend OR) activity wrist monitor for 7 days. The raw acceleration signal was filtered, digitized and stored in 1 minute epochs as activity counts, which reflect the intensity of activity over the 1 minute time period. Sedentary time was defined as <100 counts/minute, and MVPA as >1500 counts/min. Using thawed frozen plasmas, hs-cTnI was measured with the ARCHITECT STAT High Sensitive Troponin-I assay (Abbott Diagnostics. Abbot Park, IL), and hs-cTnT was measured with the Elecysys-2010 Troponin T hs STAT assay (Roche Diagnostics, Indianapolis, IN). All participants provided written informed consent and the study was approved by the University of Texas Southwestern Medical Center Institutional Review Board.
Crude associations between sedentary time and hs-cTnI and hs-cTnT were assessed using Spearman rank correlation. Linear regression analyses were performed with log-transformed hs-cTnI and hs-cTnT as the dependent variable, adjusting for age, sex, race/ethnicity and time spent in MVPA (Model 1), and then additionally adjusting for chronic kidney disease categories, body mass index, hypertension, and diabetes (Model 2), and finally additionally adjusting for left ventricular mass and end diastolic volume as determined by 3T cardiac magnetic resonance imaging (cMRI, Model 3).
Sedentary activity strongly and inversely correlated with MVPA (Rho=−0.57, p<.0001), and moderately correlated with hs-cTnI (Rho = 0.09, p<0.0001) and hs-cTnT (Rho =0.10, p=0.001). MVPA demonstrated a moderate inverse association with hs-cTnI (Rho= −0.14, p<0.001 and hs-cTnT (Rho = −0.15, p<.0001). In multivariable linear regression analyses, associations between sedentary time and both hs-cTnI and hs-cTnT remained significant after adjusting for demographic variables, cardiovascular risk factors, and measures of left ventricular structure and function (Table). In contrast, no significant association was observed between MVPA and hs-cTnI or hs-cTnT (Table). Findings were insensitive to exclusion of individuals with outlier hs-cTnT or hs-cTnI values (data not shown).
Table.
Association of Sedentary time and Moderate to Vigorous Physical Activity with High Sensitivity Troponin I and T
| Log Troponin I | Log Troponin T | ||||||
|---|---|---|---|---|---|---|---|
| n | Beta | P value | n | Beta | P value | ||
| Model 1: Adjusted for Age, Sex, Race/Ethnicity | Sedentary time | 1755 | 0.067 (0.012, 0.122) | 0.02 | 1144 | 0.067 (0.001, 0.115) | 0.04 |
| MVPA time | 0.007 (−0.041, 0.052) | 0.79 | 0.014 (−0.053, 0.075) | 0.68 | |||
| Model 2: Adjusted for Model 1 variables plus CKD stage, hypertension, hyperlipidemia, and diabetes mellitus | Sedentary time | 1727 | 0.038 (0.001–0.076) | 0.04 | 1129 | 0.102 (0.044–0.161) | 0.0006 |
| MVPA time | −0.008 (−0.063–0.047) | 0.77 | 0.043 (−0.017–0.102) | 0.16 | |||
| Model 3: Adjusted for Model 2 variables plus left ventricular mass and end diastolic volume | Sedentary time | 1272 | 0.076 (0.005–0.147) | 0.04 | 946 | 0.087 (0.016–0.159) | 0.02 |
| MVPA time | −0.012 (−0.085–0.06) | 0.74 | 0.047 (−0.024–0.119) | 0.2 | |||
Beta coefficients reflect the mean difference in hs-cTnT and hs-cTnI (in SD units) per 1 SD changes in the exposure.
These preliminary findings support an association between increased sedentary time and chronic myocardial injury, and suggest that this relationship may be independent of relevant confounders including MVPA. In contrast to prior reports,1,2 MVPA was not independently associated with hs-cTnI or hs-cTnT in our analyses. However, these prior reports did not account for sedentary time and utilized self-reported measurements of physical activity. Additional studies are necessary to more completely characterize the individual and joint effects of sedentary time and MVPA on cardiac injury, and to determine whether threshold effects for these objectively measured activity parameters exist.
Strengths of the present study include the large sample size, multi-ethnic population-based sample, and the use of accelerometry (with previously validated activity thresholds) rather than self-report to define activity levels. The primary limitation of the study is that it is observational with a cross sectional design, and is therefore at risk for residual confounding and reverse causation. We attempted to address these limitations through extensive multivariable analyses, as well as exclusion of participants with prior CVD and any symptoms suggestive of undiagnosed CVD. Finally, it is possible that sampling bias is present, whereby the wear time of the accelerometer does not reflect the participants’ usual activity patterns.
In conclusion, this study demonstrates that increased sedentary time is associated with chronic, subclinical myocardial injury. Additional study is needed to determine whether reducing sedentary time may prevent or attenuate myocardial injury, and reduce heart failure risk.
Acknowledgments
Funding Sources: The Dallas Heart Study was funded by a grant from the Donald W. Reynolds Foundation. Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award number UL1TR001105 to UT Southwestern Medical Center. Biomarker measurements were supported by investigator-initiated grants to Dr. de Lemos from Abbott Diagnostics and Roche Diagnostics.
Disclosures: Dr. de Lemos has received grant support and consulting income from Roche Diagnostics and Abbott Diagnostics, and consulting income from Abbott Diagnostics, Roche Diagnostics, Siemen’s Health Care Diagnostics Radiometer, Inc, and Ortho Clinical Diagnostics. Dr. Omland has received grant support and consulting income from Abbott Diagnostics, Siemens Healthcare, Roche Diagnostics, Novartis, Thermo-Fisher, and Biomedica. Dr. Seliger has received grant support from Roche Diagnostics. Dr. Ballantyne has received grant support and consulting income from Roche Diagnostics and Abbott Diagnostics, and consulting income from Abbott Diagnostics and Roche Diagnostics and is listed on provisional patent (patent no. 61721475) entitled “Biomarkers to Improve Prediction of Heart Failure Risk” filed by Baylor College of Medicine and Roche. Dr. Barry has received grant support from Abbott Diagnostics. Dr. de Filippi receives grant support from Roche Diagnostics and Abbott Diagnostics and consulting income from Roche Diagnostics, Alere, Ortho Diagnostics, Metanomics, Siemens Healthcare, is on Endpoint committees for Quintiles and Radiometer and has received royalties from UpToDate.
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