Biomarkers May Indicate Malignant LV Hypertrophy Phenotype

Familiar biomarkers of cardiac injury may identify a previously unrecognized cohort of patients with left ventricular hypertrophy (LVH) as being at substantially elevated risk for progression to heart failure (HF) or cardiovascular death, according to a study published on Dec. 5 in the Journal of the American College of Cardiology.

An eight-year follow-up of 2,413 individuals in the Dallas Heart Study who did not have clinical HF, impaired LV ejection fraction or renal insufficiency, found that individuals with low levels of cardiac troponin T (cTnT) and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) and LVH are at a fourfold greater risk of HF or cardiovascular death compared to those who were biomarker- and LVH-negative.

Specifically, results showed the cumulative incidence of HF or cardiovascular death in the LVH+ cTnT+ group was 20.6 percent vs. 1.1 percent for those who were LVH-cTnT-, 3.9 percent for LVH-cTnT+ and 5.8 percent for LVH+cTnT- (p<0.0001). For those who were LVH+NT-proBNP+, the cumulative incidence of HF or cardiovascular death was 20.2 percent vs. 1.5 percent for LVH- NT-proBNP-, 2.5 percent for LVH- NT-proBNP+ and 6.5 percent for LVH+ NT-proBNP-. While just 6 percent of the study population was LVH+ with cTnT+ and/or NT-proBNP+, this subgroup accounted for about 40 percent of all HF and cardiovascular deaths.

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Among individuals with LVH, any detectible level of cTnT was associated more than a fourfold increase in the risk of HF or cardiovascular death compared to individuals who were LVH+cTnT-. LVH and elevated NT-proBNP carried a similar elevated risk of HF or cardiovascular death. After multivariate analysis adjusting for age, gender, African-American race, diabetes, hypertension, cardiovascular disease, smoking, body mass index and other factors, LVH plus detectable cTnT or elevated NT-proBNP increased the risk of HF or cardiovascular death by 4.3 (p=0. 0005) and 4.5 (p=0.014) respectively.

"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 cardiovascular death,” said lead author Ian Neeland, MD, University of Texas Southwestern Medical Center, Dallas. "These findings suggest that circulating cTnT and NT-proBNP may identify a subpopulation of those with LVH in need of aggressive prevention and treatment to improve cardiovascular outcomes."

"Preliminary observations suggest that levels of both cTnT and NT-proBNP, as well as the subsequent risk for death and HF associated with elevations in these biomarkers may be modifiable," Dr. Neeland concluded. "Early identification and targeted treatments to modify this malignant phenotype represent an important clinical and research priority, with particular implications for African-American individuals."

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