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Pediatric dyslipidemia is associated with increased urinary ACE activity, blood pressure values, and carotidal-femoral pulse wave velocity

Hypertension Research volume 46, pages 1558–1569 (2023)Cite this article

A Comment to this article was published on 18 April 2023

Abstract

This study aimed to evaluate the enzymatic activity of the angiotensin-converting enzyme (ACE) in children and adolescents to investigate their relationship with dyslipidemia and other cardiometabolic alterations. Anthropometric measurements, blood pressure (BP), and fasting lipid concentrations were taken from 360 subjects. Categorization was done according to the levels of each lipoprotein (total cholesterol, triglycerides (TG), LDL-C, HDL-C, and non-HDL-C) into three groups: normolipidemic (NL), borderline (BL), and dyslipidemic (DL). Enzymatic activity in urine was measured using the substrates Z-FHL-OH and hippuryl-HL-OH (h-HL-OH) and the ACE activity ratio (Z-FHL-OH/h-HL-OH) was calculated. Dyslipidemic levels of HDL-C, TG, and LDL-C were observed in 23%, 9%, and 3% of the participants, respectively, and were more frequent in obese children (Chi-square, p < 0.001). ACE activity ratio was augmented in BL(HDL-C) when compared to NL(HDL-C) (5.06 vs. 2.39, p < 0.01), in DL(LDL-C) in comparison to BL(LDL-C) and NL(LDL-C) (8.7 vs. 1.8 vs. 3.0, p < 0.01), and in DL(non-HDL-C) than in BL(non-HDL-C) and in NL(non-HDL-C) (6.3 vs. 2.1 vs. 2.9, p = 0.02). The groups with impaired HDL-C and TG levels presented an increased diastolic BP percentile, and a higher systolic BP percentile was observed in BL(TG) and DL(TG). The carotidal-femoral pulse wave velocity (cfPWV) was higher in the groups with DL levels of TG and LDL-C than in NL groups. Hypertriglyceridemia was associated with higher cfPWV. No direct impact of the ACE activity on BP values was observed in this cohort, however, there was an association between hyperlipidemia and ACE upregulation which can trigger mechanisms driving to early onset of hypertension and cardiovascular disease.

Graphical abstract exemplifying the cohort, categorization of subjects into the groups NL normolipidemic, BL borderline, DL dyslipidemic, methods, and main findings. Pediatric dyslipidemia was consistent with dyslipidemia secondary to obesity (DSO), associated with higher urinary angiotensin-converting enzyme (ACE) activity ratio, BP blood pressure values, and carotidal-femoral pulse wave velocity (cfPWV).

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Funding

This study was supported by São Paulo Research Foundation (FAPESP, processes 2018/16653-7 and 2017/17027-0). We appreciate the support from “Estação Conhecimento” during recruitment and data collection and we acknowledge “Fundação Vale” and the Foundation for support of research and innovation of Espírito Santo (FAPES, process 65854420/2014) for the financial support of Dr. José Mill research from which data and samples were collected and posteriorly used in the present study.

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Authors and Affiliations

  1. Department of Medicine, Discipline of Nephrology, Federal University of São Paulo, São Paulo, Brazil

    Nayara Azinheira Nobrega Cruz, Lilian Caroline Gonçalves de Oliveira & Dulce Elena Casarini

  2. Center of Biological Sciences and Health, Mackenzie Presbyterian University, São Paulo, Brazil

    Fernanda Barrinha Fernandes

  3. Postgraduate Program in Public Health, Federal University of Espírito Santo, Vitória, Brazil

    Divanei dos Anjos Zaniqueli & Polyana Romano Oliosa

  4. Department of Physiological Sciences, Federal University of Espírito Santo, Vitória, Brazil

    José Geraldo Mill

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  1. Nayara Azinheira Nobrega Cruz
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Correspondence to Dulce Elena Casarini.

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Cruz, N.A.N., de Oliveira, L.C.G., Fernandes, F.B. et al. Pediatric dyslipidemia is associated with increased urinary ACE activity, blood pressure values, and carotidal-femoral pulse wave velocity. Hypertens Res 46, 1558–1569 (2023). https://doi.org/10.1038/s41440-023-01240-y

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