Based on the obtained results we showed that in obese children TG/HDL ratio was postively associated with eccentric left ventricular hypertrophy, and BMI and insulin levels are postively associated with concentric left ventricle hypertrophy.
To data only a few studies have been published focusing on the relationship between serum lipid and lipoprotein levels and left ventricular mass and geometry both in children and adults.
Sundstrom et al. showed that dyslipidaemia and unfavorable fatty acid profile at age 50 predicted the prevalence of LVH at age 70, to a similar degree as hypertension and obesity6. One autoptic study of human hearts indicated that the fat deposition in the left ventricle constitutes a direct risk of cardiac hypertrophy22. In addition, by using proton magnetic resonance spectroscopy Kankaanpää et al. demonstrated accumulation of TG in myocardium of moderately obese subjects. They reported that free fatty acid levels were a significant predictor of LV mass, whereas myocardial and epicardial fat were more strongly related to LV work and mechanical load23. Likewise, Kaminaga and others concluded that hypertrophic cardiomyopathy may be associated with the presence of myocardial fat in the LV with a thickened wall.24 One preclinical study has recently shown that increased level of glycosphingolipids, may be an independent factor contributing to cardiac hypertrophy8.
As for children, Dabas et al. reported no correlation between lipids and LV parameters in adolescents with type 1 diabetes25. On the other hand Di Bonito at al. identified a positive association between TG/HDL ratio and left ventricular mass and RWT independently of other cardiovascular (CV) risk factors in obese children which is partly in line with our results 26.
In this respect, our findings are also in agreement with those reported by Al-Daydamony and El-Tahlawi et al, who found a significant positive correlation between LVMI and TG levels in patients with metabolic syndrome without hypertension27.
The disappearance of any relationship between TG/HDL ratio with RWT in multivariable regression equation correlation, indicate that BMI and 24h-average SBP rather than insulin resistance (of which TG/HDL ratio is a surrogate marker) are associated with concentric left ventricular hypertrophy28–31.
Although the pathophysiological explanation of these results is not straightforward, and we didn’t measure aldosterone as well as VLDL levels in our patients, we can’t exclude the effects of potential signaling pathways activated by the VLDL which resulted in aldosterone overproduction and development of left ventricular hypertrophy. It is now appreciated that left ventricular hypertrophy (LVH) in hypertensive obese patients is not only mediated via clear-cut increase in blood pressure but also by various neuro-hormonal and metabolic factors that independently exert trophic effects on myocytes and non-myocytes in the heart.32,46. Experimental and clinical evidence clearly indicates that protracted exposure to inappropriately elevated aldosterone levels induces cardiac inflammation and interstitial fibrosis leading to a maladaptive remodeling in the heart and changes in left ventricular structure and function, regardless of the level of blood pressure. In particular, recent studies reported a possible involvement of aldosterone as a trigger of the activation of p38 mitogen-activated protein kinase (MAPK) and nicotinamide riboside kinase (nRK1/2) which have been involved in signal transduction pathways associated with cardiac hypertrophy33,34
Recently it was shown that adipose tissue, via secretion of factors such as leptin, stimulates adrenal aldosterone secretion as well as that VLDL might induce aldosterone overproduction via induction of steroidogenic acute regulatory (StAR) protein and aldosterone synthase (CYP11B2) expression3536. Given the fact that VLDLs are major transporters of TG accounting for approximately 85% of their weight, as well as the strong positive correlation between TG levels and TG/HDL ratio (r=0,885) in our study, we can’t exclude the possible link between atherogenic dyslipidemia (high TG/HDL ratio), TG, aldosterone and LVH or TG -VLDL - aldosterone - LVH continuity in obese children.
Furthermore, Goodfriend et al. described a negative association between aldosterone concentration and HDL-C and a positive correlation between aldosterone and triglycerides in a group of 30 volunteers. Inverse association between aldosterone levels with HDL-C in the general population was also confirme by Hannich et al19,37. They speculated that HDL-C may inhibit adrenal aldosterone secretion by modulating the sensitivity of the adrenal zona glomerulosa37.These results may possibly explain our finding that only TG/HDL ratio but not only TG levels were associated with eccentric LVH.
We would also like to point out the findings of Brady et al. who recently reported for the first time that serum aldosterone activity was higher in obese children with LVH when compared to those without LVH. Likewise, Somloova et al. found in patients with primary aldosteronism that HDL-C was markedly lower and BMI and TG were significantly higher in those having idiopathic hyperaldosteronism (IHA) than in patients with aldosterone-producing adenoma (APA). In addition, the metabolic syndrome was more prevalent in IHA than in APA.38
In our opinion high TG/HDL ratio (indirectly high VLDL levels and low HLD levels) which has been shown to be associated with increased aldosterone concentration may be one possible explanation of these results. Since the magnitude of aldosterone elevation in obese children has not been object of our scientific research, we guess that further research, including direct measurement of serum aldosteron, VLDL levels and HDL-C levels may identify new subset of at risk obese patients for LVH, as well as novel targets for the treatment of obese children with LVH but without hypertension.
An alternative explanation of our results might be explained by facts that high TG levels (indirectly high VLDL levels) may affect the synthesis of pro-inflammatory cytokines TNF-α further promoting adverse cardiac remodeling, characterised by increased total are metalloproteases (MMP) activity and increased fibrosis39. The functional crosstalk between angiotensin II (Ang II) and tumor necrosis factor (TNF)-α has also been shown to cause adverse left ventricular remodeling and hypertrophy in hypertension28.
Our second finding that BMI and insulin levels are associated with developing concentric left ventricle geometry pattern in obese children was recently confirmed using magnetic resonance imaging in the multi-ethnic study of atherosclerosis and is accordance with results of Gubbio study in adults and results of Urbina et al. study in children41.