Higher urinary angiotensin converting enzyme activity is observed in brazilian children and adolescents with dyslipidemia

Angiotensin converting enzyme (ACE) is upregulated in patients with hyperlipidemia and atherosclerosis and contributes to oxidation and accumulation of low-density lipoproteins in blood vessels. Blockage of dyslipidemia and ACE have a synergic effect preventing or ameliorating cardiovascular disease. Objective: Investigate whether ACE activity is modulated in childhood dyslipidemia and can be associated with high cardiovascular risk profile. Design and methods: a cross-sectional study with 360 individuals (190 boys and 170 girls) aged from 6 to 19 year (mean 11.6) was performed. Anthropometric measurements, blood pressure assessment and fasting lipid concentrations were evaluated. Participants were divided according to the levels of each lipoprotein (Total cholesterol (TC), triglycerides (TG), LDL-C, HDL-C, and non-HDL) into three groups: normolipidemic, borderline and dyslipidemic. Reference values were according to American Academy of Pediatrics and Brazilian Pediatric Society. ACE activity in urine was measured with the fluorogenic substrates Z-Phe-His-Leu-OH (Z-FHL) and hippuryl-His-Leu-OH (h-HL). ACE activity ratio to infer N-domain activity was calculated (Z-FHL/h-HL). Results: Dyslipidemic levels of HDL-C, TG and LDL-C were observed in 23%, 9% and 3% of the participants, respectively. These clinical alterations were more frequent in obese children (Chi-square, p < 0.001). ACE activity measured with Z-FHL was higher in the groups with borderline and dyslipidemic values of HDL-C than in normolipidemic group (0.077 vs 0.070 vs 0.037 nmol/min/mg of creatinine, p = 0.01). The ratio of ACE activity was augmented in HDL-C borderline group when compared to HDL-C normolipidemic group (5.06 vs 2.39, p < 0.01) and in LDL-C dyslipidemic group than in LDL-C borderline and LDL-C normolipidemic groups (8.66 vs 1.84 vs 2.88, p = 0.02). Additionally, volunteers with normal levels of TG presented lower diastolic blood pressure (DBP) mmHg (p = 0.02), percentile of DBP (p < 0.01), and percentile of systolic blood pressure (SBP) (p < 0.01) than volunteers with borderline and dyslipidemic levels of TG. Also, increased DBP mmHg was observed in borderline and dyslipidemic HDL-C groups when compared to normolipidic HDL-C group. Conclusion: ACE presented a cross-link with dyslipidemia in childhood and adolescence, as hypertriglyceridemia, HDL-C deficiency and high LDL-C were related to higher ACE activity (mainly N-domain able to inactivate angiotensin 1–7, a vasodilator peptide). ACE upregulation, dyslipidemia and obesity are known to activate molecular mechanism contributing to high cardiovascular risk profile, in agreement, impairment in lipoprotein levels was associated with higher blood pressure. This is relevant evidence that ACE modulation can contribute to higher risk of hypertension and other cardiometabolic alterations still in childhood and adolescence.