Negative predictive value of cardiac troponin for predicting adverse cardiac events following blunt chest trauma.

Cardiac-specific troponins (Tns) are sensitive and specific markers of myocardial injury that have been shown to be predictive of outcomes in many cardiac and noncardiac conditions. We sought to determine whether normal cardiac Tn concentrations obtained during the first 24 hours following blunt chest trauma would predict good cardiac outcomes. A PubMed/MEDLINE search was performed to identify prospective studies in patients with blunt chest trauma in which serial cardiac TnT or TnI values were measured within 24 hours of admission and clinical outcomes assessed. Ten studies qualified for review. Studies that used the lower reference limit of Tn as the cutoff for cardiac injury showed 100% negative predictive value (NPV) for developing cardiac complications, whereas studies using higher Tn cutoffs showed wider variation in NPV (50%-98%). Cardiac Tn measured within 24 hours using the lower reference limit (LRL) as the cutoff appears to have excellent NPV for clinically significant adverse cardiac events. This could allow for early discharge after a 24-hour observation period in otherwise uncomplicated blunt chest trauma patients and avoid the need for more expensive cardiac imaging and additional resource utilization.

Racial Differences in Fatal Out-of-Hospital Coronary Heart Disease and the Role of Income in the Atherosclerosis Risk in Communities Cohort Study (1987 to 2017).

Black patients have higher incident fatal coronary heart disease (CHD) rates than do their White counterparts. Racial differences in out-of-hospital fatal CHD could explain the excess risk in fatal CHD among Black patients. We examined racial disparities in in- and out-of-hospital fatal CHD among participants with no history of CHD, and whether socioeconomic status might play a role in this association. We used data from the ARIC (Atherosclerosis Risk in Communities) study, including 4,095 Black and 10,884 White participants, followed between 1987 and 1989 until 2017. Race was self-reported. We examined racial differences in in- and out-of-hospital fatal CHD with hierarchical proportional hazard models. We then examined the role of income in these associations, using Cox marginal structural models for a mediation analysis. The incidence of out-of-hospital and in-hospital fatal CHD was 1.3 and 2.2 in Black participants, and 1.0 and 1.1 in White participants, respectively, per 1,000 person-years. The gender- and age-adjusted hazard ratios comparing out-of-hospital and in-hospital incident fatal CHD in Black with that in White participants were 1.65 (1.32 to 2.07) and 2.37 (1.96 to 2.86), respectively. The income-controlled direct effects of race in Black versus White participants decreased to 1.33 (1.01 to 1.74) for fatal out-of-hospital and to 2.03 (1.61 to 2.55) for fatal in-hospital CHD in Cox marginal structural models. In conclusion, higher rates of fatal in-hospital CHD in Black participants than in their White counterparts likely drive the overall racial differences in fatal CHD. Income largely explained racial differences in both fatal out-of-hospital CHD and fatal in-hospital CHD.

Physical Activity, Inflammation, Coronary Artery Calcification, and Incident Coronary Heart Disease in African Americans: Insights From the Jackson Heart Study.

OBJECTIVE: To examine associations between physical activity (PA), inflammation, coronary artery calcification (CAC), and incident coronary heart disease (CHD) in African Americans. METHODS: Among Jackson Heart Study participants without prevalent CHD at baseline (n=4295), we examined the relationships between PA and high-sensitivity C-reactive protein, the presence of CAC (Agatston score ≥100), and incident CHD. Based on the American Heart Association's Life's Simple 7 metrics, participants were classified as having poor, intermediate, or ideal PA. RESULTS: After adjustment for possible confounding factors, ideal PA was associated with lower high-sensitivity C-reactive protein levels (ß, -0.15; 95% CI, -0.15 to -0.002) and a lower prevalence of CAC (odds ratio, 0.70; 95% CI, 0.51-0.96) compared with poor PA. During a median of 12.8 years of follow-up, there were 164 incident CHD events (3.3/1000 person-years). Ideal PA was associated with a lower rate of incident CHD compared with poor PA (hazard ratio, 0.55; 95% CI, 0.31-0.98). CONCLUSION: In a large community-based African American cohort, ideal PA was associated with lower inflammation levels, a lower prevalence of CAC, and a lower rate of incident CHD. These findings suggest that promotion of ideal PA may be an important way to reduce the risk of subclinical and future clinical CHD in African Americans.

Remnant-Like Particle Cholesterol, Low-Density Lipoprotein Triglycerides, and Incident Cardiovascular Disease.

BACKGROUND: Hypertriglyceridemia is associated with increased remnant-like particle cholesterol (RLP-C) and triglycerides in low-density lipoprotein (LDL-TG). Recent studies have focused on atherogenicity of RLP-C, with few data on LDL-TG. OBJECTIVES: The aim of this study was to examine associations of RLP-C and LDL-TG with incident cardiovascular disease (CVD) events and genetic variants in the ARIC (Atherosclerosis Risk In Communities) study. METHODS: Fasting plasma RLP-C and LDL-TG levels were measured in 9,334 men and women without prevalent CVD. Participants were followed for incident CVD events (coronary heart disease and ischemic stroke) for up to 16 years. Associations between LDL-TG and RLP-C levels and genetic variants were assessed by whole-exome sequencing using single-variant analysis for common variants and gene-based burden tests for rare variants; both an unbiased and a candidate gene approach were explored. RESULTS: RLP-C and LDL-TG levels were correlated with triglyceride levels (r = 0.85 and r = 0.64, p < 0.0001). In minimally adjusted analyses, RLP-C and LDL-TG were associated with CVD risk, but in models adjusted for traditional risk factors including lipids, only LDL-TG was associated with incident CHD (hazard ratio: 1.28; 95% confidence interval: 1.10 to 1.50) and stroke (hazard ratio: 1.47; 95% confidence interval: 1.13 to 1.92). A common APOE variant, rs7412, had the strongest association with LDL-TG and RLP-C (p < 5 × 10-8). CONCLUSIONS: RLP-C and LDL-TG levels were predictive of CVD and associated with APOE variants. LDL-TG may represent a marker of dysfunctional remnant lipoprotein metabolism associated with increased CVD risk. Further research is needed to determine whether LDL-TG plays a causal role in CVD and may be a target for therapy.

Medication, reperfusion therapy and survival in a community-based setting of hospitalised myocardial infarction.

OBJECTIVE: To examine the survival benefit of multiple medical therapies in a large, community-based population of validated myocardial infarction (MI) events. DESIGN: Retrospective observational cohort study. SETTING: Population-based sample of 30 986 definite or probable MIs in residents of four US communities aged 35-74 years randomly sampled between 1987 and 2008 as part of the Atherosclerosis Risk in Communities Surveillance Study. INTERVENTIONS: None. MAIN OUTCOME MEASURES: All-cause mortality 30, 90 and 365 days after discharge. RESULTS: We used unadjusted and propensity score (PS) adjusted models to examine the relationship between medical therapy use and mortality. In unadjusted models, each medication and procedure was inversely associated with 30-day mortality. After PS adjustment, the crude survival benefits were attenuated for all therapies except for intravenous tissue plasminogen activator therapy (IV-tPA) and stent use. After inclusion of other therapies received during the event in regression models, risk ratio effect estimates (RR; (95% CI)) were attenuated for aspirin (0.66; (0.58 to 0.76) to 0.91 (0.80 to 1.03)), non-aspirin antiplatelets (0.74; (0.59 to 0.92) to 0.92 (0.72 to 1.18)), IV-tPA (0.50; (0.41 to 0.62) to 0.65 (0.52 to 0.80)) and stents (0.53 (0.40 to 0.69) to 0.68 (0.49 to 0.94)). Effect estimates remained stable for all other therapies and were similar for 90- and 365-day mortality endpoints. CONCLUSIONS: We observed inverse associations between receipt of six medications and procedures for MI and all-cause mortality at 30, 90 and 365 days after adjustment for PS. The mortality benefits observed in this population-based setting are consistent with those reported in clinical trials.

APOE modulates the correlation between triglycerides, cholesterol, and CHD through pleiotropy, and gene-by-gene interactions.

Relationship loci (rQTL) exist when the correlation between multiple traits varies by genotype. rQTL often occur due to gene-by-gene (G × G) or gene-by-environmental interactions, making them a powerful tool for detecting G × G. Here we present an empirical analysis of apolipoprotein E (APOE) with respect to lipid traits and incident CHD leading to the discovery of loci that interact with APOE to affect these traits. We found that the relationship between total cholesterol (TC) and triglycerides (ln TG) varies by APOE isoform genotype in African-American (AA) and European-American (EA) populations. The e2 allele is associated with strong correlation between ln TG and TC while the e4 allele leads to little or no correlation. This led to a priori hypotheses that APOE genotypes affect the relationship of TC and/or ln TG with incident CHD. We found that APOE*TC was significant (P = 0.016) for AA but not EA while APOE*ln TG was significant for EA (P = 0.027) but not AA. In both cases, e2e2 and e2e3 had strong relationships between TC and ln TG with CHD while e2e4 and e4e4 results in little or no relationship between TC and ln TG with CHD. Using ARIC GWAS data, scans for loci that significantly interact with APOE produced four loci for African Americans (one CHD, one TC, and two HDL). These interactions contribute to the rQTL pattern. rQTL are a powerful tool to identify loci that modify the relationship between risk factors and disease and substantially increase statistical power for detecting G × G.