*2.2. Diet as a Risk Factor for Obesity and Cardiovascular Complications*

There is no doubt that a high intake of *sugar* causes weight gain, and therefore is associated with the development of obesity, insulin resistance, and dyslipidemia. All of them are the most important risk factors for the development of HTN and CV disorders. The analysis of the data from the National Health and Nutrition Examination Surveys (NHANES) 1988–1994, 1999–2004, and 2005–2010 (*n* = 31,147) revealed a significant direct relationship between added sugar consumption and increased risk for CV morbidity and mortality in adults [17]. Most of the added sugar are glucose, fructose, and sucrose (in the intestine sucrose is broken down into glucose and fructose, which are absorbed as such). Glucose excess is directly associated with hyperinsulinemia, while fructose excess increases uric acid levels and very-low-density lipoprotein (VLDL) levels leading to hyperuricemia and liver steatosis [18]. Moreover, it has been shown, that simultaneous consumption of sugar and salt by obese patients is a greater risk factor for developing high blood pressure than consuming each of them separately [19].

'Salt', properly sodium chloride (NaCl) is the main form of sodium intake. It is added to most of the processed food. Additionally, the source of sodium may be different food additives, such as sodium bicarbonate or sodium nitrate added to bread and meat products respectively [20]. The relationship between salt consumption and arterial HTN has been known since the beginning of the 20th century [21]. According to the traditional model, the relationship between sodium excess and the development of HTN in obese individuals is based on the increase of extracellular fluid volume and higher blood flow in the kidney [22]. High glomerular filtration rate and renal blood flow increase renal sodium reabsorption. Glomerular hyperfiltration and neurohumoral activation, within activation of the sympathetic nervous system, lead to the development of severe HTN, subsequent glomerular injury, and impaired renal sodium excretion capacity, resulting in the gradual loss of nephron function [22]. According to that classical theory of 'salt sensitive' arterial HTN development, massive salt restriction should be of universal benefit. On this basis, recommendations were made for general salt reduction [23]. More recent studies, however, show that dietary salt restriction only has a beneficial effect in certain groups, including patients with obesity and/or with HTN [24,25]. Moreover, not only sodium dose, but its ratio to potassium intake might be important. High Na+/K+ ratio intake is considered to be a stronger risk factor of HTN and cardiovascular disease than each of these nutrients alone [26]. Contrary, the Na+/K+ ratio positively affects the physiological rise of BP in childhood, resulting in smaller BP slopes [26]. Potassium increases urinary sodium excretion which diminishes total sodium content. In addition, potassium is thought to induce vascular smooth muscle relaxation and thus decrease peripheral resistance [27]. Therefore, the so-called DASH (Dietary Approaches to Stop Hypertension) diet, rich in fruits and vegetables, low-fat dairy products, and low saturated and total fat, is an effective tool in the treatment of HTN. It helps not only to reduce sodium load, but also to increase potassium intake.

Uric acid is the final product of purine metabolism in humans, and its production is largely dependent on the activity of xanthine-oxidoreductase (XOR) that is responsible for the final steps of the conversion of xantine to uric acid [28]. The serum levels of uric

acid are also influenced by the renal excretion rate of urate that is controlled by renal tubular transport systems (mainly URAT-1 and GLUT-9) that are more directly involved in the global handling of uric acid metabolism [29]. The activation of XOR is leading to an increase in the production of pro-oxidative compounds that have been reported to be involved in the development of HTN, insulin resistance, MetS, diabetes as well as CV and renal disease [30,31]. In children, the increase in serum urate levels has been proven to be responsible for a significant increase in body weight and BP values that can contribute to cardiometabolic abnormalities early in life [32]. In particular, a close correlation has been reported between the fructose intake (a well-known precursor of uric acid) and the increase in body mass index (BMI) in US children and adolescents with a negative impact on the natural history of HTN and MetS [33]. According to the evidence provided by the Bogalusa Heart study [34] the increase in uric acid can antedate and predict the increase in body weight and BP values in childhood suggesting a primary pathogenetic role for elevated uric acid and/or for the mechanisms involved in its production (e.g., XOR activity). This has been recently confirmed by some interesting studies based on the analysis of temporal trajectories of serum urate and showing and increase in cardiac and metabolic disorders in those subjects bearing serum urate levels persistently elevated or progressively increase while the opposite was observed in subjects with serum urate levels persistently normal or undergoing a progressive reduction [35]. Thus, an increase in serum urate levels in children and adolescents may contribute to promote overweight and CV risk factors with a negative prognostic implication on the risk of cardiometabolic disease later in life.
