Histamine H2 Receptor Antagonists, Left Ventricular Morphology, and Heart Failure Risk: The MESA Study

Abstract

Background: Myocardial H2 receptor activation may promote cardiac fibrosis and apoptosis in pre-clinical models and histamine H2 receptor antagonist (H2RA) use may improve symptoms in participants with heart failure (HF); however, relationships between H2RA use, incident HF, and longitudinal change in left ventricular (LV) morphology are not known.

Objectives: This study sought to determine whether H2RA use is associated with incident HF and change in LV morphology over time.

Methods: We included 6,378 men and women from MESA (Multi-Ethnic Study of Atherosclerosis), a multicenter prospective observational cohort of participants without cardiovascular disease at baseline. Cox proportional hazards were used to estimate the association between H2RA use and incident HF in adjusted models. In participants with cardiac magnetic resonance imaging, associations between H2RA use, baseline LV morphology (n = 4,691), and longitudinal change in the LV (n = 2,806) were estimated using linear regression.

Results: H2RAs were used by 313 participants but not by the other 6,065 individuals. During a median follow-up of 11.2 years, 236 participants developed HF. In adjusted models, baseline H2RA use relative to nonuse was associated with 62% lower risk for incident HF (p = 0.02). H2RA use was associated with preserved stroke volume, LV end-diastolic volume, and mass/volume ratio as measured by cardiac magnetic resonance imaging over approximately 10 years (all p < 0.05). There were no associations between H2RA use and LV mass or ejection fraction.

Conclusions: H2RA use was associated with reduced risk for incident HF. Left heart morphology over time suggests less age-related change in H2RA users. These associations suggest histamine signaling may be important in the pathogenesis of HF. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Keywords: cardiac magnetic resonance imaging; heart failure; prevention.

Figure 1. Study Sample

Flow diagram characterizes MESA participants who contributed to each of the analysis cohorts evaluating the relationships between H₂ receptor antagonists (H2RA) and heart failure (HF), baseline cardiac morphology, and change in cardiac morphology over time. MESA = Multi-Ethnic Study of Atherosclerosis.

Figure 2. Change in Cardiac Morphology over time in H2RA users relative to non-users

Change in left ventricular (LV) (A) mass, (B) end-diastolic volume (EDV), (C) stroke volume (SV), (D) ejection fraction (EF), and (E) mass/volume ratio over approximately 10 years can be seen among users and nonusers of H2RAs. Other abbreviations as in Figure 1.

Central Illustration. H2-receptor antagonists and heart failure: Unadjusted associations between H2 receptor antagonists (H2RA) use and heart failure

(A) unadjusted Kaplan-Meier cumulative event curve for incident heart failure in all participants, (B) locally weighted scatterplot smoothing (LOWESS) comparing incident heart failure occurring at any point during follow-up relative to the baseline predicted risk of heart failure (predicted by the ARIC heart failure score), (C) unadjusted Kaplan-Meier cumulative event curve for incident heart failure in participants at LOW risk for heart failure (predicted by an ARIC heart failure score ≤ 11), (D) and unadjusted Kaplan-Meier cumulative event curve for incident heart failure in participants at HIGH risk for heart failure (predicted by an ARIC heart failure score >11) ARIC = Atherosclerosis Risk in Communities.