High-Sensitivity Cardiac Troponin Concentration and CVD Risk

Study Questions:

Is there an association between high-sensitivity cardiac troponin (hs-cTnI and hs-cTnT) concentration and cardiovascular disease (CVD) outcomes in primary prevention studies?

Methods:

Prospective studies were included if published up to September 2016, and reported on associations of hs-cTn concentration with first-ever CVD outcomes (i.e., coronary heart disease [CHD], stroke, or the combination of both). Study-specific estimates, adjusted for conventional risk factors, were supplemented with de novo data from PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease Study), then pooled by using random-effects meta-analysis.

Results:

Twenty-eight relevant studies were identified involving 154,052 participants. The mean follow-up was 11.9 years, mean age was 56 years, 53% were male, and 88% were white. Hs-cTn was detectable in 80.0% (hs-cTnI in 82.6%; hs-cTnT in 69.7%). The median value in the lowest quartile of detectable hs-cTnT was 4 ng/L and in the highest 16 ng/L. In the PROSPER study, positive associations of log-linear shape were observed between hs-cTnT and CVD outcomes. In the meta-analysis, the relative risks comparing the top versus the bottom troponin third were 43% for CVD (~12,000 events), 67% for fatal CVD (~8,000 events), 59% for CHD (~7,000 events), and 35% for stroke (~2,500 events). For fatal CVD, associations were stronger in North American studies (p = 0.010) and those measuring hs-cTnT rather than hs-cTnI (p = 0.027).

Conclusions:

In the general population, hs-cTn concentrations within the normal range are associated with increased CVD risk. This association is independent of conventional risk factors, strongest for fatal CVD, and applies to both CHD and stroke.

Perspective:

The results are interesting, but should not trigger use of the hs-cTnT or TnI as an important prognostic tool. The ability of hs-cTnT to discriminate risk would be very low, considering the normal hs-cTnT level is <14 ng/L. None of the proposed biological mechanisms readily explains the findings.

Keywords: Biomarkers, Cardiovascular Diseases, Coronary Artery Disease, Pravastatin, Primary Prevention, Risk Factors, Stroke, Troponin I, Troponin T, Vascular Diseases


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