Troponin I as a Predictor of Coronary Heart Disease and Mortality in 70-Year-Old Men A Community-Based Cohort Study
TL;DR: In this first longitudinal report, cTnI was shown to predict death and first CHD event in men free from CVD at baseline, indicating the importance of silent cardiac damage in the development of CHD and mortality.
Abstract: Background— Cardiac troponin I (cTnI), a standard for detection of myocardial damage, has recently been reported to predict acute myocardial infarction or death in patients with unstable coronary heart disease (CHD). Cardiac TnI concentrations increase with age in subjects free from clinical signs of CHD, suggesting silent myocardial damage. We investigated the association between cTnI and future CHD and mortality in a community-based cohort of men. Methods and Results— A community-based study was conducted from August 1991 to May 1995 among 1203 men in Uppsala, Sweden, aged 70 years at baseline with a follow-up of up to 10.4 years with the use of registry data (National Board of Health and Welfare, Sweden). CHD was defined with the use of data taken from the Cause of Death Registry or from first-time hospitalization for CHD as recorded in the Hospital Discharge Registry. Cardiac TnI concentrations were measured blinded for outcome, in frozen baseline plasma samples, with the use of the AccuTnI from Beckm...
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TL;DR: A Report of the American College of Cardiology Foundation/AmericanHeart Association Task Force on Practice Guidelines, and the AmericanCollege of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for CardiovascularAngiography and Interventions, and Society of ThorACic Surgeons
Abstract: Jeffrey L. Anderson, MD, FACC, FAHA, Chair
Jonathan L. Halperin, MD, FACC, FAHA, Chair-Elect
Alice K. Jacobs, MD, FACC, FAHA, Immediate Past Chair 2009–2011 [§§][1]
Sidney C. Smith, Jr, MD, FACC, FAHA, Past Chair 2006–2008 [§§][1]
Cynthia D. Adams, MSN, APRN-BC, FAHA[§§][1]
Nancy M
2,469 citations
TL;DR: In this population-based cohort, cTnT detected with a highly sensitive assay was associated with structural heart disease and subsequent risk for all-cause mortality.
Abstract: Context Detectable levels of cardiac troponin T (cTnT) are strongly associated with structural heart disease and increased risk of death and adverse cardiovascular events; however, cTnT is rarely detectable in the general population using standard assays. Objectives TodeterminetheprevalenceanddeterminantsofdetectablecTnTinthepopu- lationusinganewhighlysensitiveassayandtoassesswhethercTnTlevelsmeasuredwith the new assay associate with pathological cardiac phenotypes and subsequent mortality. Design, Setting, and Participants Cardiac troponin T levels were measured using both the standard and the highly sensitive assays in 3546 individuals aged 30 to 65 years enrolled between 2000 and 2002 in the Dallas Heart Study, a multiethnic, popu- lation-based cohort study. Mortality follow-up was complete through 2007. Partici- pants were placed into 5 categories based on cTnT levels. Main Outcome Measures Magnetic resonance imaging measurements of car- diac structure and function and mortality through a median of 6.4 (interquartile range, 6.0-6.8) years of follow-up. Results InDallasCounty,theprevalenceofdetectablecTnT(0.003ng/mL)was25.0% (95% confidence interval (CI), 22.7%-27.4%) with the highly sensitive assay vs 0.7% (95% CI, 0.3%-1.1%) with the standard assay. Prevalence was 37.1% (95% CI, 33.3%- 41.0%)inmenvs12.9%(95%CI,10.6%-15.2%)inwomenand14.0%(95%CI,11.2%- 16.9%)inparticipantsyoungerthan40yearsvs57.6%(95%CI,47.0%-68.2%)inthose 60 years and older. Prevalence of left ventricular hypertrophy increased from 7.5% (95% CI,6.4%-8.8%)inthelowestcTnTcategory(0.003ng/mL)to48.1%(95%CI,36.7%- 59.6%) in the highest (0.014 ng/mL) (P.001); prevalence of left ventricular systolic dysfunctionandchronickidneydiseasealsoincreasedacrosscategories(P.001foreach). During a median follow-up of 6.4 years, there were 151 total deaths, including 62 car- diovascular disease deaths. All-cause mortality increased from 1.9% (95% CI, 1.5%- 2.6%) to 28.4% (95% CI, 21.0%-37.8%) across higher cTnT categories (P.001). Af- ter adjustment for traditional risk factors, C-reactive protein level, chronic kidney disease, and N-terminal pro-brain-type natriuretic peptide level, cTnT category remained inde- pendently associated with all-cause mortality (adjusted hazard ratio, 2.8 (95% CI, 1.4- 5.2) in the highest category). Adding cTnT categories to the fully adjusted mortality model modestlyimprovedmodelfit(P=.02)andtheintegrateddiscriminationindex(0.010(95% CI, 0.002-0.018); P=.01). Conclusion In this population-based cohort, cTnT detected with a highly sensitive assay was associated with structural heart disease and subsequent risk for all-cause mortality.
1,015 citations
TL;DR: The analytical performance of hs-cTnT complies with the ESC-ACCF-AHA-WHF Global Task Force recommendations for use in the diagnosis of MI.
Abstract: Background: We report the development of a novel high-sensitivity cardiac troponin T (hs-cTnT) assay, a modification of the Roche fourth-generation cTnT assay, and validation of the analytical performance of this assay.
Methods: Validation included testing of analytical sensitivity, specificity, interferences, and precision. We established the 99th percentile cutoff from healthy reference populations (n = 616). In addition, we studied differences in time to a positive result when using serial measurements of hs-cTnT vs cTnT in patients with a confirmed diagnosis of non-ST elevation myocardial infarction (non-STEMI).
Results: The hs-cTnT assay had an analytical range from 3 to 10 000 ng/L. At the 99th percentile value of 13.5 ng/L, the CV was 9% using the Elecsys® 2010 analyzer. The assay was specific for cTnT without interferences from human cTnI or cTnC, skeletal muscle TnT, or hemoglobin concentrations up to 1000 mg/L, above which falsely lower values would be expected. When the assay was evaluated clinically, a hs-cTnT higher than the 99th percentile concentration identified a significantly higher number of patients with non-STEMI on presentation (45 vs 20 patients, P = 0.0004) compared with cTnT, and a final diagnosis of non-STEMI was made in 9 additional patients (55 vs 46 patients, P = 0.23) after serial sampling. Time to diagnosis was significantly shorter using hs-cTnT compared with cTnT [mean 71.5 (SD 108.7) min vs 246.9 (82.0) min, respectively; P < 0.01].
Conclusions: The analytical performance of hs-cTnT complies with the ESC-ACCF-AHA-WHF Global Task Force recommendations for use in the diagnosis of MI.
998 citations
TL;DR: It is suggested that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.
Abstract: Background The incremental usefulness of adding multiple biomarkers from different disease pathways for predicting the risk of death from cardiovascular causes has not, to our knowledge, been evaluated among the elderly. Methods We used data from the Uppsala Longitudinal Study of Adult Men (ULSAM), a community-based cohort of elderly men, to investigate whether a combination of biomarkers that reflect myocardial cell damage, left ventricular dysfunction, renal failure, and inflammation (troponin I, N-terminal pro–brain natriuretic peptide, cystatin C, and C-reactive protein, respectively) improved the risk stratification of a person beyond an assessment that was based on the established risk factors for cardiovascular disease (age, systolic blood pressure, use or nonuse of antihypertensive treatment, total cholesterol, high-density lipoprotein cholesterol, use or nonuse of lipid-lowering treatment, presence or absence of diabetes, smoking status, and body-mass index). Results During follow-up (median, 10.0 years), 315 of the 1135 participants in our study (mean age, 71 years at baseline) died; 136 deaths were the result of cardiovascular disease. In Cox proportional-hazards models adjusted for established risk factors, all of the biomarkers significantly predicted the risk of death from cardiovascular causes. The C statistic increased significantly when the four biomarkers were incorporated into a model with established risk factors, both in the whole cohort (C statistic with biomarkers vs. without biomarkers, 0.766 vs. 0.664; P<0.001) and in the group of 661 participants who did not have cardiovascular disease at baseline (0.748 vs. 0.688, P=0.03). The improvement in risk assessment remained strong when it was estimated by other statistical measures of model discrimination, calibration, and global fit. Conclusions Our data suggest that in elderly men with or without prevalent cardiovascular disease, the simultaneous addition of several biomarkers of cardiovascular and renal abnormalities substantially improves the risk stratification for death from cardiovascular causes beyond that of a model that is based only on established risk factors.
885 citations
TL;DR: Cardiac troponin T concentrations as measured with a highly sensitive assay were significantly associated with the incidence of cardiovascular death and heart failure but not with myocardial infarction in patients with stable coronary artery disease.
Abstract: Background In most patients with stable coronary artery disease, plasma cardiac troponin T levels are below the limit of detection for the conventional assay. The distribution and determinants of very low circulating troponin T levels, as well as their association with cardiovascular events, in such patients are unknown. Methods We used a new, high-sensitivity assay to determine the concentration of cardiac troponin T in plasma samples from 3679 patients with stable coronary artery disease and preserved left ventricular function. Results of the assay were analyzed in relation to the incidence of cardiovascular events during a median follow-up period of 5.2 years. Results With the highly sensitive assay, concentrations of cardiac troponin T were at or above the limit of detection (0.001 μg per liter) in 3593 patients (97.7%) and at or above the 99th percentile for apparently healthy subjects (0.0133 μg per liter) in 407 patients (11.1%). After adjustment for other independent prognostic indicators, there w...
822 citations
References
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TL;DR: An analysis of methods and results of coronary event registration in 1985 through 1987 provides data on the relation between CHD morbidity and mortality, and refute suggestions that high CHD mortality rates are associated with high case-fatality rates or a relative excess of sudden deaths.
Abstract: BACKGROUNDThe WHO MONICA Project is a 10-year study that monitors deaths due to coronary heart disease (CHD), acute myocardial infarction, coronary care, and risk factors in men and women aged 35 to 64 years in defined communities. This analysis of methods and results of coronary event registration in 1985 through 1987 provides data on the relation between CHD morbidity and mortality.METHODS AND RESULTSFatal and nonfatal coronary events were monitored through population-based registers. Hospital cases were found by pursuing admissions ("hot pursuit") or by retrospective analysis of discharges ("cold pursuit"). Availability of diagnostic data on identified nonfatal myocardial infarction was good. Information on fatal events (deaths occurring within 28 days) was limited and constrained in some populations by problems with access to sources such as death certificates. Age-standardized annual event rates for the main diagnostic group in men aged 35 to 64 covered a 12-fold range from 915 per 100,000 for North ...
2,230 citations
TL;DR: Programmed death of myocytes occurs in the decompensated human heart in spite of the enhanced expression of BCL2; this phenomenon may contribute to the progression of cardiac dysfunction.
Abstract: Background Loss of myocytes is an important mechanism in the development of cardiac failure of either ischemic or nonischemic origin. However, whether programmed cell death (apoptosis) is implicated in the terminal stages of heart failure is not known. We therefore studied the magnitude of myocyte apoptosis in patients with intractable congestive heart failure. Methods Myocardial samples were obtained from the hearts of 36 patients who underwent cardiac transplantation and from the hearts of 3 patients who died soon after myocardial infarction. Samples from 11 normal hearts were used as controls. Apoptosis was evaluated histochemically, biochemically, and by a combination of histochemical analysis and confocal microscopy. The expression of two proto-oncogenes that influence apoptosis, BCL2 and BAX, was also determined. Results Heart failure was characterized morphologically by a 232-fold increase in myocyte apoptosis and biochemically by DNA laddering (an indicator of apoptosis). The histochemical demonst...
1,679 citations
TL;DR: Elevated levels of troponin T and C-reactive protein are strongly related to the long-term risk of death from cardiac causes and these markers are independent risk factors, and their effects are additive with respect to each other and other clinical indicators of risk.
Abstract: Background In patients with unstable coronary artery disease, there is a relation between the short-term risk of death and blood levels of troponin T (a marker of myocardial damage) and C-reactive protein and fibrinogen (markers of inflammation). Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial, we evaluated the usefulness of troponin T, C-reactive protein, and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes. Methods Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease. The patients were followed for a mean of 37.0 months (range, 1.6 to 50.6). Results During follow-up, 1.2 percent of the 173 patients with maximal blood troponin T levels of less tha...
1,244 citations
TL;DR: The full text of this document is available on the Website of the European Society of Cardiology: www.escardio.org in the section ‘Scientific Information’, Guidelines.
Abstract: The full text of this document is available on the Website of the European Society of Cardiology: www.escardio.org in the section ‘Scientific Information’, Guidelines. Introduction 1809 Pathophysiology 1810 Plaque rupture and erosion 1810 Inflammation 1812 Thrombosis 1812 Vasoconstriction 1812 Myocardium 1813 Diagnosis 1813 Clinical presentation 1813 Physical examination 1813 Electrocardiogram 1813 Biochemical markers of myocardial damage 1814 Recommendations 1815 Risk assessment 1815 Risk factors 1815 Clinical presentation 1815 Electrocardiogram 1816 Markers of myocardial damage 1816 Markers of inflammatory activity 1816 Markers of thrombosis 1817 Echocardiography 1817 Predischarge stress testing 1817 Coronary angiography 1817 Recommendations for risk stratification 1818 Treatment options 1818 Anti-ischaemic agents 1818 Beta-blockers 1818 Nitrates 1818
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