Background and Purpose Increased levels of plasma troponins and natriuretic peptides are associated with increased risk of cardiovascular disease, but only limited information exists on these biomarkers and stroke occurrence. In a prospective epidemiological study, we tested the hypothesis that high-sensitivity troponin T (TnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) are associated positively with incidence of stroke. Methods The Atherosclerosis Risk in Communities (ARIC) Study measured plasma TnT and NT-proBNP in 10,902 men or women initially free of stroke and followed them for a mean of 11.3 years for stroke occurrence (n=507). Results Both biomarkers were associated positively with total stroke, nonlacunar ischemic, and especially, cardioembolic stroke, but not with lacunar or hemorrhagic stroke. For example, after adjustment for prevalent risk factors and cardiac diseases, the hazard ratios (95% confidence intervals) for jointly high values of TnT and NT-proBNP (versus neither biomarker high) were 2.70 (1.92, 3.79) for total stroke and 6.26 (3.40, 11.5) for cardioembolic stroke. Associations with stroke appeared somewhat stronger for NT-proBNP than TnT. Strikingly, approximately 58% of cardioembolic strokes occurred in the highest quintile of pre-stroke NT-proBNP, and 32% of cardioembolic strokes occurred in participants who had both NT-proBNP in the highest quintile and were known by ARIC to have atrial fibrillation sometime before their cardioembolic stroke occurrence. Conclusions In the general population, elevated plasma TnT and NT-proBNP concentrations are associated with increased risk of cardioembolic and other nonlacunar ischemic strokes.

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Noninvasive quantification of myocardial fibrosis in end-stage renal disease is challenging. Gadolinium contrast agents previously used for cardiac magnetic resonance imaging (MRI) are contraindicated because of an association with nephrogenic systemic fibrosis. In other populations, increased myocardial native T1 times on cardiac MRI have been shown to be a surrogate marker of myocardial fibrosis. We applied this method to 33 incident hemodialysis patients and 28 age- and sex-matched healthy volunteers who underwent MRI at 3.0T. Native T1 relaxation times and feature tracking–derived global longitudinal strain as potential markers of fibrosis were compared and associated with cardiac biomarkers. Left ventricular mass indices were higher in the hemodialysis than the control group. Global, Septal and midseptal T1 times were all significantly higher in the hemodialysis group (global T1 hemodialysis 1171 ± 27 ms vs. 1154 ± 32 ms; septal T1 hemodialysis 1184 ± 29 ms vs. 1163 ± 30 ms; and midseptal T1 hemodialysis 1184 ± 34 ms vs. 1161 ± 29 ms). In the hemodialysis group, T1 times correlated with left ventricular mass indices. Septal T1 times correlated with troponin and electrocardiogram-corrected QT interval. The peak global longitudinal strain was significantly reduced in the hemodialysis group (hemodialysis -17.7±5.3% vs. -21.8±6.2%). For hemodialysis patients, the peak global longitudinal strain significantly correlated with left ventricular mass indices (R = 0.426), and a trend was seen for correlation with galectin-3, a biomarker of cardiac fibrosis. Thus, cardiac tissue properties of hemodialysis patients consistent with myocardial fibrosis can be determined noninvasively and associated with multiple structural and functional abnormalities.

Background Greater public awareness of venous thromboembolism may be an important next step for optimizing venous thromboembolism prevention and treatment. “Lifetime risk” is an easily interpretable way of presenting risk information. Therefore, we sought to calculate the lifetime risk of venous thromboembolism (deep vein thrombosis and/or pulmonary embolism) using data from two large, prospective cohort studies: the Cardiovascular Health Study (CHS) and the Atherosclerosis Risk in Communities (ARIC) study. Methods We followed participants aged 45–64 years in ARIC (n=14,185) and ≥65 in CHS (n=5,414) at baseline visits (1987-89 in ARIC, 1989-90 and 1992–93 in CHS) for incident venous thromboembolism (n=728 in ARIC through 2011 and n=172 in CHS through 2001). We estimated lifetime risks and 95% confidence intervals of incident venous thromboembolism using a modified Kaplan-Meier method, accounting for the competing risk of death from other causes. Results At age 45, the remaining lifetime risk of venous thromboembolism in ARIC was 8.1% (95% confidence interval: 7.1-8.7). High-risk groups were African Americans (11.5% lifetime risk), those with obesity (10.9%), heterozygous for the factor V Leiden (17.1%), or with sickle cell trait or disease (18.2%). Lifetime risk estimates differed by cohort; these differences were explained by differences in time period of venous thromboembolism ascertainment. Conclusions At least 1 in 12 middle-aged adults will develop venous thromboembolism in their remaining lifetime. This estimate of lifetime risk may be useful to promote awareness of venous thromboembolism and guide decisions at both clinical and policy levels.

Purpose Although there is substantial evidence that physical activity reduces a person's risk of cardiovascular disease (CVD), few of these studies have included African Americans. The studies that have included African Americans offer inconclusive evidence on the association and none studied heart failure separately. We used data from the Atherosclerosis Risk in Communities study cohort to examine, in African Americans, the association of physical activity with the incidence of CVD and its major components – stroke, heart failure, and coronary heart disease. Methods Participants aged 45 to 64 years (3,707 African Americans and, for comparison, 10,018 Caucasians) had physical activity assessed via questionnaire in 1987 and were followed for incident CVD (n=1,039) through 2008. Results After adjustment for potential confounders, physical activity was inversely related to CVD, heart failure, and coronary heart disease incidence in both races (p-values for trend <.0001), and with stroke in African Americans. Hazard ratios (95% confidence intervals) for CVD for each higher physical activity category were similar by race: 1.0, 0.65 (0.56, 0.75), and 0.59 (0.49, 0.71) for African Americans and 1.0, 0.74 (0.66, 0.83), and 0.67 (0.59, 0.75) for Caucasians (p-value for interaction = 0.38). Conclusions Our findings reinforce recommendations that regular physical activity is important for CVD risk reduction in African Americans as well as Caucasians and support the idea that some physical activity is better than none.

PurposeTo examine predictors of understanding preemptive CYP2D6 pharmacogenomic test results and to identify key features required to improve future educational efforts of preemptive pharmacogenomic testing.Methods1010 participants were surveyed after receiving preemptive CYP2D6 pharmacogenomic test results.ResultsEighty-six percent (n=869) of patients responded. Responders were 98% white, 55% female, 57% had four or more years of post-secondary education, and aged 58.9±5.5 years on average. Among responders, 26% reported they only somewhat understood their results and 7% reported they did not understand them at all. Only education predicted understanding. The most common suggestion for improvement was the use of layperson's terms when reporting results. In addition, responders suggested results should be personalized by referring to medications that they were currently taking. Of those reporting imperfect drug adherence in the past, most (91%) reported they would be more likely to take medication as prescribed if pharmacogenomic information was used to help select the drug or dose.ConclusionDespite great efforts to simplify pharmacogenomic results (or because of them), about one-third of responders did not understand their results. Future efforts need to provide more examples and tailor results to the individual. Incorporation of pharmacogenomics is likely to improve medication adherence.

Diabetes mellitus (DM) may be a risk factor for venous thromboembolism (VTE) but results are inconsistent. Aim We conducted a systematic review and meta-analysis of epidemiologic studies to quantify the association between DM and VTE. Methods and results We included studies identified in PubMed, Web of Science, and CINAHL through 07/31/2014. We identified 19 studies that met our selection criteria. We pooled RRs using a random-effects model: the pooled RR for the association of DM with VTE was 1.10 (95% CI: 0.94–1.29). Between-study heterogeneity was explored with a forest plot, funnel plot, meta-regression, and a stratified analysis. Between-study heterogeneity was observed and not explained by study design, method of DM assessment, or degree of adjustment for confounding. Sensitivity analyses omitted one study at a time to assess the influence of any single study on the pooled estimate. These analyses indicated that one large study was highly influential; when this study was excluded, the pooled estimate increased and just reached statistical significance: 1.16 (95% CI: 1.01–1.34)]. Conclusions This meta-analysis suggests either no association or a modest positive one between DM and VTE in the general population. DM is unlikely to play a major role in VTE development.

BACKGROUND Limited information is available regarding primary care clinicians’ response to pharmacogenomic Clinical Decision Support (PGx-CDS) alerts integrated in the electronic health record. METHODS In February 2015, 159 clinicians in the Mayo Clinic primary care practice were sent e-mail surveys to understand their perspectives on the implementation and use of pharmacogenomic testing in their clinical practice. Surveys assessed how the clinicians felt about pharmacogenomics and whether they thought electronic PGx-CDS alerts were useful. Information was abstracted on the number of CDS alerts the clinicians received between October, 2013 and the date their survey was returned. CDS alerts were grouped into two categories: alert recommended caution using the prescription or the alert recommended an alternate prescription. Finally, data were abstracted regarding whether the clinician changed their prescription in response to the alert recommendation. RESULTS The survey response rate was 57% (n=90). Overall, 52% of the clinicians did not expect to use or did not know whether they would use pharmacogenomic information in their future prescribing practices. Additionally, 53% of the clinicians felt that the alerts were confusing, irritating, frustrating, or that it was difficult to find additional information. Finally, only 30% of the clinicians that received a CDS alert changed their prescription to an alternative medication. CONCLUSIONS Our results suggest a lack of clinician comfort with integration of pharmacogenomic data into primary care. Further efforts to refine PGx-CDS alerts to make them as useful and user-friendly as possible are needed to improve clinician satisfaction with these new tools.