Biomarkers of Chronic Cardiac Injury and Hemodynamic Stress Identify a Malignant Phenotype of Left Ventricular Hypertrophy in the General Population

Study Questions:

Are biomarkers of myocardial injury predictive of adverse outcomes in subjects with left ventricular hypertrophy (LVH)?

Methods:

A total of 2,413 participants in the Dallas Heart Study underwent measurement of LV mass by magnetic resonance imaging, cardiac troponin T (cTnT) by highly sensitive assay, and N-terminal pro–B-type natriuretic peptide (NT-proBNP) analysis. Subjects were stratified according to LVH and by detectable cTnT (≥3 pg/ml) and increased NT-proBNP (>75th age- and sex-specific percentile) levels. For each analysis, participants were categorized into groups based on the presence (+) or absence (–) of LVH and biomarker levels above (+) or below (–) the predefined threshold.

Results:

Of the participants, 9% were LVH+, 25% were cTnT+, and 24% were NT-proBNP+. Those LVH+ and cTnT+ and/or NT-proBNP+ (n = 144) were older and more likely to be male, with a greater risk factor burden and more severe LVH compared with those who were LVH+ biomarker– (p < 0.01 for each). The cumulative incidence of heart failure (HF) or cardiovascular (CV) death over 8 years among LVH+ cTnT+ was 21% versus 1% (LVH– cTnT–), 4% (LVH– cTnT+), and 6% (LVH+ cTnT–) (p < 0.0001). The interactions between LVH and cTnT (Pinteraction = 0.0005) and LVH and NT-proBNP (Pinteraction = 0.014) were highly significant. Individuals who were LVH+ and either cTnT+ or NTproBNP+ remained at >4-fold higher risk for HF or CV death after multivariable adjustment for CV risk factors, renal function, and LV mass compared with those who were LVH– biomarker–.

Conclusions:

The authors concluded that minimal elevations in biomarkers of subclinical cardiac injury and hemodynamic stress modify the association of LVH with adverse outcomes, identifying a malignant subphenotype of LVH with high risk for progression to HF and CV death.

Perspective:

LVH is associated with increased CV morbidity and mortality, although there is marked heterogeneity in the rate of progression from asymptomatic LVH to an adverse cardiac outcome such as CHF- or CV-related death. If LVH subjects could be identified who are at particularly high risk for adverse outcomes, then more intensive control of risk factors might be beneficial—a hypothesis that will need to be tested in future trials. These biomarkers could also be useful surrogates in designing future studies to address biological underpinnings of LVH transition to CHF, and to test experimental therapeutics.

Clinical Topics: Anticoagulation Management, Heart Failure and Cardiomyopathies, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Sleep Apnea

Keywords: Hypertrophy, Left Ventricular, Life Style, Heart Injuries, Troponin T, Sleep, Cost of Illness, Cardiomegaly, Fruit, Biological Markers, Troponin I, Heart Failure, Peptide Fragments, Pregnancy, Natriuretic Peptide, Brain


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