Author + information
- Rajarshi Banerjee, BMBCh, DPhil,
- Belen Rial, DPhil,
- Cameron J. Holloway, DPhil,
- Adam J. Lewandowski, BSc (Hons), DPhil,
- Matthew D. Robson, PhD,
- Chinwe Osuchukwu, MBBS,
- Jurgen E. Schneider, DPhil,
- Paul Leeson, PhD,
- Oliver J. Rider, BMBCh, DPhil∗ ( and )
- Stefan Neubauer, MD, FMedSci
- ↵∗Division of Cardiovascular Medicine, Radcliffe Department of Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom
Previous studies have shown that myocardial steatosis occurs with age, diabetes, and the metabolic syndrome and that myocardial triglyceride content (MTGC) is related to concentric left ventricular hypertrophy (LVH) (1) and diastolic dysfunction (2), suggesting a direct negative effect on the heart. Despite this, whether a relationship between MTGC, concentric LVH, and diastolic function exists in obesity per se is unclear and in childhood obesity remains unknown.
1H-magnetic resonance spectroscopy (1H-MRS) is a technique that can measure MTGC noninvasively (3). We used 1H-MRS and cardiovascular magnetic resonance imaging to explore the relationship between increasing body fat and MTGC; the relationship between MTGC, LVH, and diastolic dysfunction; and whether any changes were present in an adolescent population.
A total of 128 adult subjects (71 female; body mass index [BMI], 18.5 to 53.0 kg/m2) and 22 male adolescents (10 to 15 years of age, BMI percentile 8 to 100) underwent 1H-MRS and left ventricular (LV) studies, as previously described (4,5). Total body fat content (DXA, GE Lunar system, GE Healthcare, New York, New York) and abdominal visceral fat mass (fourth/fifth lumbar water-suppressed turbo spin echo) were also assessed. Age, BMI, systolic blood pressure (SBP), and diastolic blood pressure were similar in men and women. All subjects were normotensive (adults, 121 ± 11/74 ± 8 mm Hg; children, 113 ± 13/67 ± 10 mm Hg), normoglycemic (adults, 5.0 ± 0.5 mmol/l; children, 4.8 ± 0.6 mmol/l), and normocholesterolemic (adults, 5.1 ± 0.8 mmol/l; children, 3.9 ± 0.5 mmol/l). The mean homeostatic model assessment of insulin resistance (HOMA-IR) was 2.7 ± 1.3 (adult population). All subjects had normal LV ejection fraction (>58%).
In adults, although MTGC was positively correlated with all measures of obesity (BMI, r = 0.59; visceral fat, r = 0.46; total fat, r = 0.60; females; BMI, r = 0.53) (Figure 1), only total fat mass (+0.013%/kg fat, p < 0.001) was an independent predictor of MTGC. No sex difference in the regression coefficient for the associations of obesity with MTGC was seen. In adolescents, MTGC was also positively correlated with BMI percentile (r = 0.45, p = 0.035).
Increasing BMI was associated with LV cavity dilation in both males (r = 0.32, p = 0.014) and females (LV end-diastolic volume, r = 0.39, p < 0.001). In contrast, with increasing BMI, concentric LV remodeling was only seen in males (LV mass, volume ratio; r = 0.44, p = 0.01) and was positively correlated with MTGC (r = 0.39, p = 0.003), a relationship that remained after adjustment for SBP and HOMA-IR (r = 0.40, p < 0.005). In adolescent male subjects, increasing BMI percentile was not related to cavity dilation (r = 0.32, p = 0.14), but again was positively correlated with indexed LV mass (g/m2.7, r = 0.54, p = 0.01), again suggesting concentric remodeling. Importantly, in the adolescent group, LV mass index was also positively correlated with MTGC (r = 0.45, p = 0.037), again remaining significant after controlling for SBP (r = 0.45, p = 0.04). Overall, these findings suggest a role for cardiac steatosis, independent of the effects of blood pressure, in the development of concentric LV remodeling in male obesity.
There was no correlation between MTGC and global systolic function in the form of LV ejection fraction in either adults (male, r = −0.15; female, r = 0.12, both p > 0.29) or adolescent males (r = −0.2, p = 0.36). In contrast, even after controlling for LV mass, SBP, and HOMA-IR, increasing MTGC remained correlated with impaired diastolic filling rate (r = −0.34, p < 0.01). This would suggest that the accumulation of myocardial triglyceride per se is related to diastolic dysfunction in obesity. As obstructive sleep apnea was only excluded on an interview basis, it is possible that undiagnosed obstructive sleep apnea is related to some of the diastolic dysfunction in this study.
This study shows that, even in the absence of comorbidities, both adult and childhood obesity is related to cardiac steatosis and that increased MTGC is related to diastolic dysfunction. In addition, we show that significant sex differences exist in the effects of MTGC, with increased levels correlating with concentric LVH in adult men and adolescent males, but not females (adults, sex BMI interaction, p = 0.039). Overall, this suggests not only that myocardial steatosis is related to LV structural and functional changes that occur in obesity, but also that cardiac steatosis occurs early in obesity and has significant effects in childhood.
Please note: The study was supported by a grant from the British Heart Foundation. Dr. Rider and Prof. Neubauer have received support from the Oxford BHF Centre of Research Excellence. Prof. Neubauer has received support from the Oxford NIHR Biomedical Research Centre. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Drs. Rider and Neubauer are joint senior authors.
- American College of Cardiology Foundation