title: Older Adults, "Malignant" Left Ventricular Hypertrophy, and Associated Cardiac-Specific Biomarker Phenotypes to Identify the Differential Risk of New-Onset Reduced Versus Preserved Ejection Fraction Heart Failure: CHS (Cardiovascular Health Study).
abstract: OBJECTIVE
  This study hypothesized that biomarkers of subclinical myocardial injury (high-sensitivity cardiac troponin T [hs-cTnT]) and hemodynamic stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP]) would differentiate heart failure (HF) risk among older adults with left ventricular hypertrophy (LVH).
  
  
  BACKGROUND
  The natural history of LVH, an important risk factor for HF, is heterogeneous.
  
  
  METHODS
  NT-proBNP and hs-cTnT were measured at baseline and after 2 to 3 years in older adults without prior HF or myocardial infarction in the CHS (Cardiovascular Health Study). LVH and left ventricular ejection fraction were determined by echocardiography. HF events were adjudicated over a median of 13.1 years and classified as preserved or reduced left ventricular ejection fraction (heart failure with preserved ejection fraction or heart failure with reduced ejection fraction [HFrEF]). Adjusted risk of HF by LVH and biomarker tertiles, and by LVH and longitudinal increase in each biomarker was estimated using Cox regression.
  
  
  RESULTS
  Prevalence of LVH was 12.5% among 2,347 participants with complete measures. Adjusted risk of HF (N = 643 events) was approximately 3.8-fold higher among participants with LVH and in the highest biomarker tertile, compared with those with low biomarker levels without LVH (NT-proBNP, hazard ratio [HR]: 3.78; 95% confidence interval [CI]: 2.78 to 5.15 and hs-cTnT, HR: 3.86; 95% CI: 2.84 to 5.26). The adjusted risk of HFrEF was 7.8 times higher among those with the highest tertile of hs-cTnT and LVH (HR: 7.83; 95% CI: 4.43 to 13.83). Those with LVH and longitudinal increases in hs-cTnT or NT-proBNP were approximately 3-fold more likely to develop HF, primarily HFrEF, compared with those without LVH and with stable biomarkers.
  
  
  CONCLUSIONS
  The combination of LVH with greater hs-cTnT or NT-proBNP levels, and their longitudinal increase, identifies older adults at highest risk for symptomatic HF, especially HFrEF. These biomarkers may characterize sub-phenotypes in the transition from LVH to HF and suggest modifiable targets for prevention.
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland. Electronic address: sseliger@medicine.umaryland.edu.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Seliger
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: James
authors.initials: J
authors.lastname: de Lemos
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Neeland
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Robert
authors.initials: R
authors.lastname: Christenson
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: John
authors.initials: J
authors.lastname: Gottdiener
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Drazner
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Jarett
authors.initials: J
authors.lastname: Berry
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: John
authors.initials: J
authors.lastname: Sorkin
authors.affiliation: University of Maryland School of Medicine, Baltimore, Maryland.
authors.forename: Christopher
authors.initials: C
authors.lastname: deFilippi
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D004452:Echocardiography; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010641:Phenotype; D011446:Prospective Studies; D012307:Risk Factors; D020107:Troponin T / Q000097:blood
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D020107:Troponin T; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain
keywords: epidemiology; heart failure; left ventricular hypertrophy; natriuretic peptides; troponin T