**7. Selected novel cardio-vascular risk factors**

Diagnostic work-up should also include other cardiovascular risk factors that do not belong to the traditional ones that were described above. For example, urate is believed to be an independent indicator of arterial hypertension in children associated also with renal dysfunction [36]. Lipoprotein (a) is not associated with obesity, such as other lipoproteins, but is regarded as an independent cardiovascular risk factor and was found to be high in children with a family history of premature cardiovascular events [37]. Elevated levels of homocysteine were found in children with abdominal obesity [38], however a genetic hyperhomocysteinemia with mutations in methylenetetrahydrofolate reductase (MTHFR gene) was associated with stroke in children and in affected children with hyperhomocysteinemia and recurrent risk of stroke might be prevented with folate supplementation [39]. Vitamin D is frequently deficient in obese potentially leading to osteomalacia, and was additionally associated with insulin resistance and elevated blood pressure [40, 41]. Some studies even showed a higher risk of CVD and mortality when vitamin D was deficient, emphasizing the need for its supplementation [42].

To assess end-organ damage, kidney function, heart anatomy, and ocular background examination are commonly implemented, however, blood vessels, directly damaged by atherosclerosis, can be evaluated with intima media thickness and vessel elasticity evaluation. Intima media thickness is regarded as a subclinical indicator of atherosclerosis but has a lesser predictive value in children than in adults. There were several studies indicating an association between intima media thickness and obesity, familial hypercholesterolemia and hypertension in children, but sometimes associations were not clear cut and intra- and interoperable comparability raised doubts in the method [43]. Arterial stiffness can be commonly assessed with pulse wave velocity measurement that can be performed by several different methods, such as applanation tonometry. The higher the velocity of the pulse wave, the less compliant artery is expected, suggesting subclinical atherosclerosis. In children, several cardiovascular risk factors were associated with higher pulse wave velocity, however, the method is not in routine use [44].
