Abstract
BackgroundImmunomodulatory therapy may help prevent heart failure (HF). Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited.MethodsIn the Multi-Ethnic Study of Atherosclerosis cohort, 869 adults had 19 peripheral immune cell subsets measured and underwent cardiac MRI during the baseline exam, of which 321 had assessment of left ventricular global circumferential strain (LV-GCS). We used linear regression with adjustment for demographics, cardiovascular risk factors, and cytomegalovirus serostatus to evaluate the cross-sectional association of immune cell subsets with left ventricular mass index (LVMI) and LV-GCS.ResultsThe average age of the cohort was 61.6 ± 10.0 years and 53% were women. Higher proportions of γ/δ T cells were associated with lower absolute (worse) LV-GCS (–0.105% [95% CI –0.164%, –0.046%] per 1 SD higher proportion of γ/δ T cells, P = 0.0006). This association remained significant after Bonferroni’s correction. Higher proportions of classical monocytes were associated with worse absolute LV-GCS (–0.04% [95% CI –0.07%, 0.00%] per 1 SD higher proportion of classical monocytes, P = 0.04). This did not meet significance after Bonferroni’s correction. There were no other significant associations with LV-GCS or LVMI.ConclusionPathways associated with γ/δ T cells may be potential targets for immunomodulatory therapy targeted at HF prevention in populations at risk.FundingContracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 and grant R01 HL98077 from the National Heart, Lung, and Blood Institute/NIH and grants KL2TR001424, UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences/NIH.
Highlights
In adults without heart failure (HF), higher levels of circulating proinflammatory cytokines, such as TNF-α, IL-6, and C-reactive protein, have been associated with future HF events [1,2,3]
We leveraged data obtained from a case-cohort substudy of the Multi-Ethnic Study of Atherosclerosis (MESA) evaluating peripheral blood mononuclear cells (PBMCs) and myocardial infarction (MI) to investigate associations of innate and adaptive immune cell subsets with measures of cardiac structure and function on cardiac magnetic resonance imaging (CMR)
In a multicenter cohort of middle-aged adults free of cardiovascular disease (CVD), who had PBMCs collected and CMR performed during the same period, we observed a significant association between higher proportions of γ/δ T cells and worse cardiac function, as measured by absolute left ventricular global circumferential strain (LV-GCS) (Table 2)
Summary
In adults without heart failure (HF), higher levels of circulating proinflammatory cytokines, such as TNF-α, IL-6, and C-reactive protein, have been associated with future HF events [1,2,3]. Targeting these inflammatory cytokines in adults who have developed HF has not been successful in slowing disease progression [4, 5]. Investigating the associations of innate and adaptive immune cells, integral in regulating the inflammatory milieu, with cardiac structure and function in older adults with cardiovascular risk factors but without HF can provide important insights into potential immune targets for HF prevention. Data on immune cells and myocardial remodeling in older adults with cardiovascular risk factors are limited
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