The Importance of Arterial Stiffness Assessment in Patients with Familial Hypercholesterolemia.

Cardiovascular diseases are still the leading cause of mortality due to increased atherosclerosis worldwide. In the background of accelerated atherosclerosis, the most important risk factors include hypertension, age, male gender, hereditary predisposition, diabetes, obesity, smoking and lipid metabolism disorder. Arterial stiffness is a firmly established, independent predictor of cardiovascular risk. Patients with familial hypercholesterolemia are at very high cardiovascular risk. Non-invasive measurement of arterial stiffness is suitable for screening vascular dysfunction at subclinical stage in this severe inherited disorder. Some former studies found stiffer arteries in patients with familial hypercholesterolemia compared to healthy controls, while statin treatment has a beneficial effect on it. If conventional drug therapy fails in patients with severe familial hypercholesterolemia, PCSK9 inhibitor therapy should be administered; if these agents are not available, performing selective LDL apheresis could be considered. The impact of recent therapeutic approaches on vascular stiffness is not widely studied yet, even though the degree of accelerated athero and arteriosclerosis correlates with cardiovascular risk. The authors provide an overview of the diagnosis of familial hypercholesterolemia and the findings of studies on arterial dysfunction in patients with familial hypercholesterolemia, in addition to presenting the latest therapeutic options and their effects on arterial elasticity parameters.

Determination of Serum Progranulin in Patients with Untreated Familial Hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant trait characterized by elevated LDL-C concentrations and is associated with an increased risk of premature atherosclerosis. Progranulin (PGRN) is a multifunctional protein that is known to have various anti-atherogenic effects. To date, the use of serum PGRN in patients with FH has not been studied. METHODS: In total, 81 untreated patients with heterozygous FH (HeFH) and 32 healthy control subjects were included in this study. Serum PGRN, sICAM-1, sVCAM-1, oxLDL and TNFα concentrations were determined by ELISA. Lipoprotein subfractions were detected by Lipoprint. We diagnosed FH using the Dutch Lipid Clinic Network criteria. RESULTS: We could not find a significant difference between the PGRN concentrations of the HeFH patients and controls (37.66 ± 9.75 vs. 38.43 ± 7.74 ng/mL, ns.). We found significant positive correlations between triglyceride, TNFα, sVCAM-1, the ratio of small HDL subfraction and PGRN, while significant negative correlations were found between the ratio of large HDL subfraction and PGRN both in the whole study population and in FH patients. PGRN was predicted by sVCAM-1, logTNFα and the ratio of small HDL subfraction. CONCLUSIONS: The strong correlations between HDL subfractions, inflammatory markers and PGRN suggest that PGRN may exert its anti-atherogenic effect in HeFH through the alteration of HDL composition and the amelioration of inflammation rather than through decreasing oxidative stress.

Effects of alpha-lipoic acid treatment on serum progranulin levels and inflammatory markers in diabetic neuropathy.

OBJECTIVES: Progranulin (PGRN) is a secreted growth factor that helps to regulate neuronal survival by blocking tumor necrosis factor-alpha (TNFα) receptors. The antioxidant alpha-lipoic acid (ALA) is used in diabetic neuropathy to improve nerve conduction and relieve neuropathic pain, but its effects on PGRN levels have not yet been elucidated. METHODS: In this prospective study, 54 patients with type 2 diabetes and peripheral neuropathy received 600 mg of ALA daily for 6 months. Twenty-four patients with diabetes without neuropathy were also included in the study. Serum PGRN and TNFα levels were determined using enzyme-linked immunosorbent assays. In addition, current perception threshold (CPT) testing was used to assess sensory neuropathy. RESULTS: After ALA treatment, serum PGRN levels were significantly increased and CPT values were significantly improved. Furthermore, there were significant positive correlations among TNFα, ICAM-1, and PGRN levels both before and after ALA treatment. A significant negative correlation was observed between the improvements in CPT and the PGRN levels. Furthermore, ICAM-1 levels were an independent predictor of PGRN levels. CONCLUSIONS: Changes in serum PGRN levels indicate that ALA treatment may have beneficial effects on endothelial function and neuronal inflammation.

[Diagnostic and prognostic roles of serum progranulin, a novel marker of the carbohydrate metabolism and inflammation]. / A szénhidrát-anyagcsere és a gyulladásos folyamatok jellemzésére szolgáló új marker, a szérumprogranulin diagnosztikai és prognosztikai szerepérol.

Progranulin is a recently recognized multifunctional glycopeptide shown to be related to obesity and diabetes mellitus. Progranulin is an endogenous antagonist of tumor necrosis factor-α by competitively binding to its receptor, therefore, it exerts anti-inflammatory activity. Paradoxically, previous studies have shown that serum levels of progranulin were elevated in patients with diabetes and associated to its complications including micro- and macroangiopathies, macroalbuminuria or reduced renal function. Moreover, hyperprogranulinemia may be involved in the pathogenesis of obesity-associated insulin resistance. The review summarizes the currently available data on progranulin as a novel marker of the carbohydrate metabolism and inflammation. Orv Hetil. 2019; 160(25): 973-979.

The Role of Indoleamine-2,3-Dioxygenase in Cancer Development, Diagnostics, and Therapy.

Tumors are composed of abnormally transformed cell types and tissues that differ from normal tissues in their genetic and epigenetic makeup, metabolism, and immunology. Molecular compounds that modulate the immune response against neoplasms offer promising new strategies to combat cancer. Inhibitors targeting the indoleamine-2,3-dioxygenase 1 enzyme (IDO1) represent one of the most potent therapeutic opportunities to inhibit tumor growth. Herein, we assess the biochemical role of IDO1 in tumor metabolism and immune surveillance, and review current diagnostic and therapeutic approaches that are intended to increase the effectiveness of immunotherapies against highly aggressive and difficult-to-treat IDO-expressing cancers.

New developments in the pathogenesis of obesity-induced hypertension.

Obesity is a disorder that develops from the interaction between genotype and environment involving social, behavioral, cultural, and physiological factors. Obesity increases the risk for type 2 diabetes mellitus, hypertension, cardiovascular disease, cancer, musculoskeletal disorders, chronic kidney and pulmonary disease. Although obesity is clearly associated with an increased prevalence of hypertension, many obese individuals may not develop hypertension. Protecting factors may exist and it is important to understand why obesity is not always related to hypertension. The aim of this review is to highlight the knowledge gap for the association between obesity, hypertension, and potential genetic and racial differences or environmental factors that may protect obese patients against the development of hypertension and other co-morbidities. Specific mutations in the leptin and the melaninocortin receptor genes in animal models of obesity without hypertension, the actions of α-melanocyte stimulating hormone, and SNS activity in obesity-related hypertension may promote recognition of protective and promoting factors for hypertension in obesity. Furthermore, gene-environment interactions may have the potential to modify gene expression and epigenetic mechanisms could also contribute to the heritability of obesity-induced hypertension. Finally, differences in nutrition, gut microbiota, exposure to sun light and exercise may play an important role in the presence or absence of hypertension in obesity.

Pseudopheochromocytoma induced by anxiolytic withdrawal.

BACKGROUND: Symptomatic paroxysmal hypertension without significantly elevated catecholamine concentrations and with no evidence of an underlying adrenal tumor is known as pseudopheochromocytoma. METHODS: We describe the case of a female patient with paroxysmal hypertensive crises accompanied by headache, vertigo, tachycardia, nausea and altered mental status. Previously, she was treated for a longer period with alprazolam due to panic disorder. Causes of secondary hypertension were excluded. Neurological triggers (intracranial tumor, cerebral vascular lesions, hemorrhage, and epilepsy) could not be detected. RESULTS: Setting of the diagnosis of pseudopheochromocytoma treatment was initiated with alpha- and beta-blockers resulting in reduced frequency of symptoms. Alprazolam was restarted at a daily dose of 1 mg. The patient's clinical condition improved rapidly and the dosage of alpha- and beta-blockers could be decreased. CONCLUSIONS: We conclude that the withdrawal of an anxiolytic therapeutic regimen may generate sympathetic overdrive resulting in life-threatening paroxysmal malignant hypertension and secondary encephalopathy. We emphasize that pseudopheochromocytoma can be diagnosed only after exclusion of the secondary causes of hypertension. We highlight the importance of a psychopharmacological approach to this clinical entity.

[Advances in the prevention, diagnosis and therapy of vascular diseases]. / Újabb ismeretek a különbözo vascularis kórképek megelozésében, diagnosztikájában és terápiájában.

Atherosclerosis is a systemic disease affecting the coronary, carotid, intracerebral, renal and peripherial arteries. The early morphological and functional impairments could be detected in the second or third decades of life and their progression depend on the number and severity of risk factors and individual susceptility. Although the vascular risk factors (smoking, overweight, age, unhealthy diet, lack of physical exercise, hypertension, diabetes mellitus, chronic kidney disease and dyslipidemia) are the same and common in the different vascular diseases, the present clinical routine artificially classifies the diagnosis and therapy of different vascular diseases into different subfields of medicine with the negative impact of possible polypragmasia. Recently, worldwide health surveys (e.g. REACH registry) have proven the usefulness of a holistic approach in the diagnosis and therapy of multiorgan-affected vascular patients. This review summarizes the multidisciplinary advances and future perspective of vascular diseases.

Favorable effect of short-term lifestyle intervention on human paraoxonase-1 activity and adipokine levels in childhood obesity.

OBJECTIVE: The prevalence of obesity is increasing in adult and child populations throughout the world. Childhood obesity has a great impact on adult cardiovascular morbidity and mortality; treatment of this pathological state is important given the significant health consequences. We investigated the effect of short-term lifestyle changes on the alteration of human serum paraoxonase-1 (PON1) activities, leptin, adiponectin, E-selectin, and asymmetric dimethylarginine (ADMA) as atherogenic and antiatherogenic factors in obese children. PON1 protects lipoproteins against oxidation by hydrolyzing lipid peroxides in oxidized low density lipoprotein (LDL) and therefore may protect against atherosclerosis. METHODS: A total of 23 white obese and overweight children (age, 11.43 ± 1.78 years; 8 girls, 15 boys) participated in a 2-week-long lifestyle camp based on a diet and exercise program. Overweight and obesity were defined according to the national body mass index (BMI) reference tables for age and sex. RESULTS: After a 2-week-long supervised diet and aerobic exercise program, obese children had significantly lower leptin (55.02 ± 33.42 ng/ml vs 25.37 ± 19.07 ng/ml; p < 0.0001), ADMA (0.68 ± 0.15 µmol/l vs 0.55 ± 0.16 µmol/l; p < 0.01), and E-selectin levels (67.19 ± 30.35 ng/ml vs 46.51 ± 18.40 ng/ml; p < 0.0001), whereas they had significantly higher PON1 paraoxonase activity (110.48 ± 72.92 U/l vs 121.75 ± 93.48 U/l; p < 0.05) besides the antiatherogenic alteration of the lipid profile and significant weight change (70.32 ± 19.51 kg vs 67.01 ± 18.75 kg, p < 0.0001; BMI, 28.95 ± 5.05 kg/m(2) vs 27.43 ± 4.82 kg/m(2), p < 0.0001). Adiponectin and PON1 arylesterase activity did not change significantly. CONCLUSIONS: Our investigation suggests that modifications in dietary habits and physical activity induce antiatherogenic changes in childhood obesity. These findings emphasize the major role of primary prevention and nonpharmaceutical treatment of childhood obesity through lifestyle changes based on diet and increased physical activity.

Factors influencing adolescent blood pressure: the Debrecen Hypertension Study.

AIM: To obtain epidemiological data on the blood pressure (BP) status of high school students and factors influencing BP. METHODS: Subjects filled out a questionnaire and three repeated BP measurements were taken. All high school attending students in Debrecen (final sample n = 10,194, mean age 16.6 ± 1.0 years) participated in the study. RESULTS: Boys had significantly higher systolic BP (+11.3 mm Hg) and diastolic BP (+2.2 mm Hg) than girls (p < 0.001). There was a positive correlation between weight and BP (r(syst) = 0.42, r(diast) = 0.29), height and BP (r(syst) = 0.33, r(diast) = 0.15), body mass index (BMI) and BP (r(syst) = 0.31, r(diast) = 0.27). Multiple regression was used for statistical analysis. Gender (ß = 0.36), BMI (ß = 0.25), hypertension of parents (father ß = 0.04 and mother ß = 0.02), smoking, alcohol consumption and age determined systolic outcomes in descending order. For the diastolic model, BMI remained a strong determining factor (ß = 0.25) and gender was also significant (ß = -0.09). Entering independents together accounted for 28.2% of the total variance in systolic and for 18.1% in diastolic BP. CONCLUSION: Body weight is central to determining BP. Because that is an alterable cardiovascular risk factor, we presume that lifestyle modification will not only result in reduced weight, but also in decreased BP.

[Epidemiological data of 15-18 year adolescents and the prevalence of hypertension in Debrecen. The Debrecen Hypertension Study]. / A 15-18 éves fiatalok epidemiológiai jellemzoi, és a serdülokori hypertonia elofordulási gyakorisága.

AIM: To perform a blood pressure screening program in Debrecen secondary school students according to international guidelines. To obtain epidemiological data about factors influencing adolescent blood pressure using a questionnaire. To repeat the blood pressure measurements in case of elevated systolic and/or diastolic readings, and to determinate the prevalence of adolescent hypertension in Debrecen. PATIENTS AND METHODS: All high school attending students in Debrecen (n = 10359) participated in the study. Measurements were obtained by a validated, automated, digital OMRON M4 device. RESULTS: Gender distribution was nearly equal in our sample: 50.64% male, 49.36% female. The mean age was 16.55 +/- 0.99 years. Boys were 10 cm taller and 10 kg heavier on average than girls. Hypertension in family history was prevalent in 10.8% of mothers and in 11.7% of fathers. Every fifth adolescent (19.7%) was a regularly smoker, while 12.2% of the studied population drank alcohol in a weekly basis. Leisure time sporting activity was characteristic only for 31.9%, while 11.2% of the young people usually felt stress and 15.1% regularly salted their food. Low birth weight (< 2500 gram) was recorded in 6.7% of the adolescents. Systolic and/or diastolic blood pressure exceeded the 90th percentile for the age, gender and height specific subgroups in 1614 cases. Repeated measurements were performed in 1461 cases on two different occasions. Averaging the 3 x 3 measurements, hypertension was confirmed in 216 cases. The prevalence of the disease in this population was 2.53%. CONCLUSION: The recognition, treatment and follow-up of hypertension among adolescent population, is of immense importance.