Background We evaluated whether cardiac troponin T (cTnT) measured with a new highly sensitive assay was associated with incident coronary heart disease (CHD), mortality, and hospitalization for heart failure (HF) in a general population of participants in the Atherosclerosis Risk in Communities (ARIC) Study. Methods and Results Associations between increasing cTnT levels and CHD, mortality, and HF hospitalization were evaluated using Cox proportional-hazards models adjusted for traditional CHD risk factors, kidney function, high-sensitivity C-reactive protein (hs-CRP), and N-terminal pro–B-type natriuretic peptide (NT-proBNP) in 9,698 participants aged 54–74 years who at baseline were free from CHD and stroke (and HF in the HF analysis). Measurable cTnT levels (≥0.003 μg/L) were detected in 66.5% of individuals. In fully adjusted models, compared with participants with undetectable levels, those with cTnT levels in the highest category (≥0.014 μg/L, 7.4% of the ARIC population) had significantly increased risk for CHD (hazard ratio [HR] 2.29, 95% confidence interval [CI] 1.81–2.89), fatal CHD (HR 7.59, 95% CI 3.78–15.25), total mortality (HR 3.96, 95% CI 3.21–4.88), and HF (HR 5.95, 95% CI 4.47–7.92). Even minimally elevated cTnT (≥0.003 μg/L) was associated with increased risk for mortality and HF (p<0.05). Adding cTnT to traditional risk factors improved risk prediction parameters; the improvements were similar to those with NT-proBNP and better than that with the addition of hs-CRP. Conclusions cTnT detectable with a highly sensitive assay was associated with incident CHD, mortality, and HF in individuals from a general population without known CHD/stroke.

STRUCTURED ABSTRACT Objectives We evaluated whether carotid intima-media thickness (C-IMT) and the presence or absence of plaque improved coronary heart disease (CHD) risk prediction when added to traditional risk factors (TRF). Background Traditional CHD risk prediction schemes need further improvement as the majority of the CHD events occur in the “low” and “intermediate” risk groups. C-IMT and presence of plaque on an ultrasound are associated with CHD and therefore could potentially help improve CHD risk prediction. Methods Risk prediction models (overall, in men and women) considered included TRF-only, TRF+C-IMT, TRF+plaque, and TRF+C-IMT+ plaque. Model predictivity was determined by calculating the area under the receiver operating characteristic curve (AUC) adjusted for optimism. Cox-proportional hazards models were used to estimate 10-year CHD risk for each model, and the number of individuals reclassified determined. Observed events were compared with expected events; and, the net reclassification index (NRI) was calculated. Results Of 13,145 eligible individuals (5,682 men; 7,463 women), ~23% were reclassified by adding C-IMT+plaque information. Overall, the addition of C-IMT and plaque separately or together to the TRF model improved the AUC which increased from 0.742 to 0.750, 0.751 and 0.755 for the TRF-only, TRF+C-IMT, TRF+plaque and TRF+C-IMT+plaque model respectively. The C-IMT+TRF+plaque model had a NRI of 9.9% when compared to TRF-only in the overall population. However, comparison of TRF+C-IMT+plaque with TRF+C-IMT or TRF+plaque only resulted in non-significant or modestly significant changes of the various statistical tests. Sex-specific analyses are presented in the manuscript. Conclusion Adding plaque and C-IMT to TRF improves CHD risk prediction in the ARIC study.

Background C-reactive protein (CRP) is a heritable marker of chronic inflammation that is strongly associated with cardiovascular disease. We aimed to identify genetic variants that are associated with CRP levels. Methods and Results We performed a genome wide association (GWA) analysis of CRP in 66,185 participants from 15 population-based studies. We sought replication for the genome wide significant and suggestive loci in a replication panel comprising 16,540 individuals from ten independent studies. We found 18 genome-wide significant loci and we provided evidence of replication for eight of them. Our results confirm seven previously known loci and introduce 11 novel loci that are implicated in pathways related to the metabolic syndrome (APOC1, HNF1A, LEPR, GCKR, HNF4A, and PTPN2), immune system (CRP, IL6R, NLRP3, IL1F10, and IRF1), or that reside in regions previously not known to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4, ASCL1, RORA, and BCL7B). We found significant interaction of body mass index (BMI) with LEPR (p<2.9×10−6). A weighted genetic risk score that was developed to summarize the effect of risk alleles was strongly associated with CRP levels and explained approximately 5% of the trait variance; however, there was no evidence for these genetic variants explaining the association of CRP with coronary heart disease. Conclusion We identified 18 loci that were associated with CRP levels. Our study highlights immune response and metabolic regulatory pathways involved in the regulation of chronic inflammation.

A single initial measurement of plasma myeloperoxidase independently predicts the early risk of myocardial infarction, as well as the risk of major adverse cardiac events in the ensuing 30-day and 6-month periods. Myeloperoxidase levels, in contrast to troponin T, creatine kinase MB isoform, and C-reactive protein levels, identified patients at risk for cardiac events in the absence of myocardial necrosis, highlighting its potential usefulness for risk stratification among patients who present with chest pain.