Low Levels of Troponin Predict HF, Death in Older Adults

November 26, 2010

November 26, 2010 (Chicago, Illinois) — Low levels of cardiac troponin T--as measured by high-sensitivity assays--are associated with new-onset heart failure and cardiovascular death in older adults, independent of other risk factors, a new study has shown [1].

The findings indicate that high-sensitivity troponin "might be a good prognostic marker," because it is difficult to predict who will develop HF in this population, lead author Dr Christopher R deFilippi (University of Maryland School of Medicine, Baltimore) told heartwire .

Although raised troponin levels are indicative of events in patients with unstable coronary disease, a new analysis from the PEACE trial published last year showed that very low levels, as detected by novel high sensitivity assays, were associated with heart failure and death in a stable CHD population [2]. This new paper, says deFilippi "is the first to show this in a general population without underlying cardiovascular disease."

This is a wake-up call for lifestyle changes in older adults who perhaps are feeling fine but are relatively sedentary.

However, he acknowledges that the clinical importance of monitoring changes in cardiac troponin T for risk of progression to symptomatic HF is yet to be determined. "It will be important to show that this is a wake-up call for lifestyle changes in older adults who perhaps are feeling fine but are relatively sedentary. People respond better to an objective measure. Our hope is that if we tell people-- 'This is a marker of cell death in your heart and if we can keep that flat, your chance of developing heart failure is less'-- then that could be a compelling message".

The study findings featured in two presentations at the American Heart Association (AHA) 2010 Scientific Sessions last week: DeFilippi reported on the heart failure outcomes and senior author Dr Stephen L Seliger (University of Maryland School of Medicine, Baltimore) discussed the results with respect to cardiovascular mortality; the results were also published online in JAMA.

Troponin Found in Two Thirds of Older Adults: "Gradient of Risk"

deFilippi and colleagues explain that elderly individuals comprise the largest subgroup of patients hospitalized for heart failure, but it is difficult to risk-stratify them because traditional prediction models have limited accuracy for this outcome.

He and his colleagues set out to see whether low levels of troponin would be detectable in the majority of community-dwelling older adults and whether serial measures were associated with risks of HF hospitalization and CV death. They examined 4221 participants in a longitudinal, nationwide US cohort study, the Cardiovascular Health Study , who were aged 65 years or older without prior HF and who had cardiac troponin T measured with a highly sensitive assay at baseline (1989-1990) and repeated after two to three years (n=2918).

The primary outcome measures were incident HF and CV mortality, as ascertained through semi-annual study visits and through examination of Medicare claims data. Analyses were adjusted for demographic variables, traditional risk factors, and two other cardiovascular biomarkers, C-reactive protein (CRP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP).

The high-sensitivity troponin assay used in this study (Roche) is widely available in Europe, but not yet in use in the US, deFilippi noted. "It is my understanding that it costs around the same as a regular troponin test, which is $1-$2 ($10-$12 in reimbursement costs)," and that it can be measured on existing machines, he says.

They found that troponin was detectable--at a level of 3.00 pg/mL or greater--in two thirds of all participants (n=2794, 66.2%), and that there was "a gradient of risk," as deFilippi explained.

During a median follow-up of 11.8 years, 1279 participants experienced new-onset HF and there were 1102 cardiovascular deaths, with a greater independent risk of either end point associated with higher troponin concentrations. Those with the highest concentration (>12.94 pg/mL) had an incidence rate of 6.4 per 100 person years for HF, giving an almost 2.5-fold higher risk (adjusted hazard ratio 2.48) and an incidence rate of 4.8 for CV death, to give an almost threefold higher risk (adjusted HR 2.91) compared with participants with undetectable troponin (incidence rate 1.6 and 1.1 for HF and CV death respectively).

The markedly increased range of measurable troponin in our study enables estimation of a gradient of risk across the majority of older individuals.

The associations of troponin with HF were also independent of other biomarkers such as renal function and electrocardiographic evidence of left ventricular hypertrophy, the researchers note.

"Compared with studies that used conventional troponin assays, the markedly increased range of measurable troponin in our study enables estimation of a gradient of risk across the majority of older individuals, including those with an absence of clinical risk factors (other than age)," they add.

"Unique" Finding: Major Changes in Troponin Track Dynamic Risks

The researchers also showed that among those with detectable troponin at baseline, longitudinal changes in troponin concentrations were common and corresponded with a dynamic change in risk over time. A subsequent increase of more than 50%--which occurred in 393 patients (22%)--was associated with a greater risk for HF (adjusted HR 1.61) and CV death (HR 1.65) while a drop of more than 50%--seen in 247 patients (14%)--was associated with a lower risk for HF (HR 0.73) and CV death (HR 0.71) compared with those with 50% or less change.

This is an exclusive finding, says deFilippi; these changes "were really intriguing, we can see the significance of changes taking place over a relatively short period of time, and we need to see if we can change that trajectory," he observes.

We can see the significance of changes taking place over a relatively short period of time, and we need to see if we can change that trajectory.

The measurement of troponin by highly sensitive assays for risk stratification of older individuals has "unique performance characteristics compared with other biomarkers that have been advocated by some for risk stratification in general populations, such as CRP and NT-proBNP," he and his colleagues observe.

And for the prediction of either HF and cardiovascular death, the addition of baseline cardiac troponin T levels to clinical risk factor models significantly improved classification, "albeit modestly," they note.

"Further studies are needed to assess whether monitoring low levels of cardiac troponin T may provide an opportunity to motivate specific changes in lifestyle or prompt medical interventions before progression to symptoms or cardiac structural abnormalities and to track the outcomes associated with these interventions," they conclude.

deFilippi has received honoraria, consulting and grant support from Roche Diagnostics and Siemens Healthcare Diagnostics, and consulting and grant support from Critical Diagnostics and BG Medicine. Conflicts for other authors are listed in the manuscript.

 

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