White-coat effect and masked hypertension in patients with high-normal office blood pressure: results of the Hungarian ABPM Registry.

OBJECTIVE: Blood pressure (BP) lowering therapy in hypertension can markedly reduce the risk of cardiovascular diseases. In case of high-normal office blood pressure (oBP), the initiation of antihypertensive medication is recommended by guidelines in patients with very high cardiovascular risk. The aims of this study were to evaluate the presence of white-coat high-normal BP (WhHNBP) and masked hypertension in high-normal oBP and to explore the prevalence of untreated very high cardiovascular risk patients. METHODS: Data of the Hungarian Ambulatory Blood Pressure Monitoring (ABPM) Registry between September 2020 and November 2023 were used in our analysis. RESULTS: From 38 720 uploaded ABPM curves with clinical data, 4300 individuals were categorized as having high-normal oBP. Among those, 3285 (76.4%) were on antihypertensive treatment. Based on the ABPM recordings, high-normal BP was confirmed in 20.5% ( n  = 881), while WhHNBP was present in 27.6% ( n  = 1188) and masked hypertension in 51.9% ( n  = 2231). Similar results were found in treated and untreated subjects or patients as well. Independent predictors of WhHNBP were age [odds ratio (OR) 1.02 (95% confidence interval, 95% CI: 1.01-1.02), P  < 0.001], female sex [OR: 1.59 (1.32-1.92), P  < 0.001] and snoring [OR: 0.70 (0.57-0.86), P  < 0.001]. Independent predictors of masked hypertension were male sex [OR: 1.31 (1.12-1.54), P  < 0.001] and obesity [OR: 1.71 (1.39-2.09), P  < 0.001]. Five hundred and two individuals had very high cardiovascular risk with high-normal oBP and only 25 of them were untreated. CONCLUSION: In high-normal oBP, WhHNBP or masked hypertension is present in three out of four individuals. Most of the patients with high-normal oBP and very high cardiovascular risk are already treated with antihypertensive drugs.

C-peptide: an essential ally in microvascular complications of type 2 diabetes mellitus and obesity.

BACKGROUND: In order to investigate microvascular complications in metabolic diseases, we aimed to investigate cerebral and peripheral microcirculation in relation to peripheral neuropathy and laboratory biomarkers in type 2 diabetes mellitus (T2DM) and obesity. METHODS: Based on the degree of neuropathy (NP), study participants (40 T2DM and 30 obese individuals) were classified into no-NP, mild-NP and severe-NP subgroups. After the injection of Technetium-99 m hexamethylpropylene amine oxime, both T2DM and obese participants underwent single-photon emission computed tomography/computed tomography ([99mTc]Tc-HMPAO SPECT/CT) and SPECT-only examinations to assess lower limb and brain perfusion; respectively. Peripheral nerve function was evaluated with a neurometer and glycaemic markers were measured from plasma in both groups. RESULTS: Compared to the obese individuals, lower extremity perfusion was significantly reduced in the diabetic subjects (p < 0.005), while it showed a positive correlation with C-peptide levels and negative association with HbA1c values. A U-shape pattern of peripheral microcirculation was observed between the NP groups, indicating a surprisingly better perfusion in the severe-NP group than in the mild one, with the highest levels in obese patients. Since changes in the C-peptide levels exhibited a similar U-shaped trend across the NP subgroups, we suggest a positive correlation between C-peptide levels and the extent of peripheral perfusion. Although, C-peptide values and cerebral microcirculation correlated positively (rho = 0.27), brain perfusion did not show any differences neither between the diabetic and the obese patients, nor between the NP subgroups (at p < 0.05). CONCLUSIONS: Establishing the link between neuropathy and peripheral microcirculation, C-peptide seems to be a promising biomarker for the prediction of microvascular alterations in metabolic diseases. Of note, the dominance of metabolic factors over microvascular damage in the development of obesity-related neuropathy should be emphasized as well.

Progranulin, sICAM-1, and sVCAM-1 May Predict an Increased Risk for Ventricular Arrhythmias in Patients with Systemic Sclerosis.

In systemic sclerosis (SSc), fibrosis of the myocardium along with ongoing autoimmune inflammation can alter the electric function of the cardiac myocytes, which may increase the risk for ventricular arrhythmias and sudden cardiac death. We analyzed the electrocardiographic (ECG) variables describing ventricular repolarization such as QT interval, QT dispersion (QTd), T wave peak-to-end interval (Tpe), and arrhythmogeneity index (AIX) of 26 patients with SSc and 36 healthy controls. Furthermore, echocardiographic and laboratory parameters were examined, with a focus on inflammatory proteins like C-reactive ptotein (CRP), soluble intracellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), and progranulin (PGRN). The CRP, sICAM-1, and sVCAM-1 levels were positively correlated with the length of the QT interval. Although the serum PGRN levels were not increased in the SSc group compared to the controls, in SSc patients, the PGRN levels were positively correlated with the QT interval and the AIX. According to our results, we conclude that there may be a potential association between autoimmune inflammation and the risk for ventricular arrhythmias in patients with SSc. We emphasize that the measurement of laboratory parameters of inflammatory activity including CRP, PGRN, sVCAM-1, and sICAM-1 could be helpful in the prediction of sudden cardiac death in patients with SSc.

May Measurement Month 2021: an analysis of blood pressure screening results from Hungary.

Elevated blood pressure (BP) is the most important risk factor for cardiovascular diseases (CVDs), which are still the leading cause of mortality in Hungary. Therefore, screening programmes identifying subjects with hypertension have an important role in CVD prevention. In 2017, the International Society of Hypertension initiated May Measurement Month (MMM) aimed at raising awareness of elevated BP. Hungary joined the MMM campaigns in 2017, 2019, and 2021, and a summary of the results from 2021 is presented here. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in September 2021. Measurement of BP, the definition of hypertension, and statistical analysis followed the standard MMM protocol. In Hungary, 30 sites were set up in primary and secondary care facilities, in pharmacies, and in malls. Both cities and villages were involved in all regions. A total of 1414 individuals were screened, and 558 subjects (39.5%) had hypertension. Out of 1065 participants not on antihypertensive medication, 209 (19.6%) had elevated BP. Among treated individuals (n = 349), 206 (59.0%) had controlled BP (<140/90 mmHg). Almost 40% of the participants had hypertension. Among untreated participants, one in five had elevated BP, while among patients on antihypertensive medication, 41% had uncontrolled BP. These results confirm the importance of screening of hypertension in untreated individuals and that efforts are required to adequately control BP in treated hypertensive patients.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

Cardio-ankle vascular index for predicting cardiovascular morbimortality and determinants for its progression in the prospective advanced approach to arterial stiffness (TRIPLE-A-Stiffness) study.

BACKGROUND: The cardio-ankle vascular index (CAVI) measure of arterial stiffness is associated with prevalent cardiovascular risk factors, while its predictive value for cardiovascular events remains to be established. The aim was to determine associations of CAVI with cardiovascular morbimortality (primary outcome) and all-cause mortality (secondary outcome), and to establish the determinants of CAVI progression. METHODS: TRIPLE-A-Stiffness, an international multicentre prospective longitudinal study, enrolled >2000 subjects ≥40 years old at 32 centres from 18 European countries. Of these, 1250 subjects (55% women) were followed for a median of 3.82 (2.81-4.69) years. FINDINGS: Unadjusted cumulative incidence rates of outcomes according to CAVI stratification were higher in highest stratum (CAVI > 9). Cox regression with adjustment for age, sex, and cardiovascular risk factors revealed that CAVI was associated with increased cardiovascular morbimortality (HR 1.25 per 1 increase; 95% confidence interval, CI: 1.03-1.51) and all-cause mortality (HR 1.37 per 1 increase; 95% CI: 1.10-1.70) risk in subjects ≥60 years. In ROC analyses, CAVI optimal threshold was 9.25 (c-index 0.598; 0.542-0.654) and 8.30 (c-index 0.565; 0.512-0.618) in subjects ≥ or <60 years, respectively, to predict increased CV morbimortality. Finally, age, mean arterial blood pressure, anti-diabetic and lipid-lowering treatment were independent predictors of yearly CAVI progression adjusted for baseline CAVI. INTERPRETATION: The present study identified additional value for CAVI to predict outcomes after adjustment for CV risk factors, in particular for subjects ≥60 years. CAVI progression may represent a modifiable risk factor by treatments. FUNDING: International Society of Vascular Health (ISVH) and Fukuda Denshi, Japan.

Plozasiran (ARO-APOC3) for Severe Hypertriglyceridemia: The SHASTA-2 Randomized Clinical Trial.

Importance: Severe hypertriglyceridemia (sHTG) confers increased risk of atherosclerotic cardiovascular disease (ASCVD), nonalcoholic steatohepatitis, and acute pancreatitis. Despite available treatments, persistent ASCVD and acute pancreatitis-associated morbidity from sHTG remains. Objective: To determine the tolerability, efficacy, and dose of plozasiran, an APOC3-targeted small interfering-RNA (siRNA) drug, for lowering triglyceride and apolipoprotein C3 (APOC3, regulator of triglyceride metabolism) levels and evaluate its effects on other lipid parameters in patients with sHTG. Design, Setting, and Participants: The Study to Evaluate ARO-APOC3 in Adults With Severe Hypertriglyceridemia (SHASTA-2) was a placebo-controlled, double-blind, dose-ranging, phase 2b randomized clinical trial enrolling adults with sHTG at 74 centers across the US, Europe, New Zealand, Australia, and Canada from May 31, 2021, to August 31, 2023. Eligible patients had fasting triglyceride levels in the range of 500 to 4000 mg/dL (to convert to millimoles per liter, multiply by 0.0113) while receiving stable lipid-lowering treatment. Interventions: Participants received 2 subcutaneous doses of plozasiran (10, 25, or 50 mg) or matched placebo on day 1 and at week 12 and were followed up through week 48. Main Outcomes and Measures: The primary end point evaluated the placebo-subtracted difference in means of percentage triglyceride change at week 24. Mixed-model repeated measures were used for statistical modeling. Results: Of 229 patients, 226 (mean [SD] age, 55 [11] years; 176 male [78%]) were included in the primary analysis. Baseline mean (SD) triglyceride level was 897 (625) mg/dL and plasma APOC3 level was 32 (16) mg/dL. Plozasiran induced significant dose-dependent placebo-adjusted least squares (LS)-mean reductions in triglyceride levels (primary end point) of -57% (95% CI, -71.9% to -42.1%; P < .001), driven by placebo-adjusted reductions in APOC3 of -77% (95% CI, -89.1% to -65.8%; P < .001) at week 24 with the highest dose. Among plozasiran-treated patients, 144 of 159 (90.6%) achieved a triglyceride level of less than 500 mg/dL. Plozasiran was associated with dose-dependent increases in low-density lipoprotein cholesterol (LDL-C) level, which was significant in patients receiving the highest dose (placebo-adjusted LS-mean increase 60% (95% CI, 31%-89%; P < .001). However, apolipoprotein B (ApoB) levels did not increase, and non-high-density lipoprotein cholesterol (HDL-C) levels decreased significantly at all doses, with a placebo-adjusted change of -20% at the highest dose. There were also significant durable reductions in remnant cholesterol and ApoB48 as well as increases in HDL-C level through week 48. Adverse event rates were similar in plozasiran-treated patients vs placebo. Serious adverse events were mild to moderate, not considered treatment related, and none led to discontinuation or death. Conclusions and Relevance: In this randomized clinical trial of patients with sHTG, plozasiran decreased triglyceride levels, which fell below the 500 mg/dL threshold of acute pancreatitis risk in most participants. Other triglyceride-related lipoprotein parameters improved. An increase in LDL-C level was observed but with no change in ApoB level and a decrease in non-HDL-C level. The safety profile was generally favorable at all doses. Additional studies will be required to determine whether plozasiran favorably modulates the risk of sHTG-associated complications. Trial Registration: ClinicalTrials.gov Identifier: NCT04720534.

Frequency of office blood pressure measurements and the seasonal variability of blood pressure: results of the Hungarian Hypertension Registry.

PURPOSE: Hypertension is a major public health problem, thus, its timely and appropriate diagnosis and management are crucial for reducing cardiovascular morbidity and mortality. The aim of the new Hungarian Hypertension Registry is to evaluate the blood pressure measurement practices of general practitioners (GPs), internists and cardiologists in outpatient clinics, as well as to assess the seasonal variability of blood pressure. MATERIALS AND METHODS: Omron M3 IT devices were used during four-month periods between October 2018 and April 2023 in GP practices and in hypertension clinics. The blood pressure data were then transmitted online from the monitors' cuffs to a central database using the Medistance system of Omron. RESULTS: Family physicians (n = 2491), and internists/cardiologists (n = 477) participated in the study. A total of 4804 821 blood pressure measurements were taken during 10 four-month evaluation periods. In the ten periods, the daily average number of measurements was between 3.0 and 5.6. Following ESH diagnostic criteria, the proportion of subjects in optimal, normal and high-normal blood pressure categories were 14, 13.4 and 16.7%, respectively. Altogether 56% of the measurements belonged to stage 1, stage 2 or stage 3 hypertension categories (31.6, 17.1 and 7.4%, respectively). On average, a difference of 5/2 mmHg was observed between winter and summer data in systolic and diastolic blood pressures, respectively. The average systolic blood pressure values were higher in GP practices with more than 2000 patients than in the ones with less than 1500 patients (141.86 mmHg versus 140.02 mmHg, p < 0.05). CONCLUSION: In conclusion, the low daily average number of blood pressure measurements indicates a limited blood pressure screening awareness/capacity in the case of Hungarian family physicians. In GP practices with more patients, blood pressure is usually less well-controlled. These results suggest that the further promotion of home blood pressure monitoring is necessary.

What is the background?The standard method for the diagnosis of hypertension and for the control of treatment efficacy in hypertensive patients is office blood pressure measurement.Until now we had no real-life data on the blood pressure measurement practices of general practitioners (GPs), internists and cardiologists.Although seasonal differences in blood pressure values are well known, we had no data on the extent of these changes.What is new?In this real-world, nationwide observational study we were able to measure the frequency of blood pressure measurements in the daily practice of GPs, internists and cardiologists in Hungary, which was found to be very low compared to the number of patients they treat. In practices with more patients, blood pressure is generally less well-controlled.We could also detect a significant seasonal variation in systolic and diastolic blood pressure values over the observed time periods.What is the impact?The low daily average number of blood pressure measurements indicates a limited blood pressure screening awareness/capacity in the case of Hungarian family physicians, supporting the further promotion of home blood pressure measurement.The marked seasonal blood pressure changes demonstrated by our study require attention and the individual adjustment of treatment in different seasons.

Assessment of Hypertensive Patients' Complex Metabolic Status Using Data Mining Methods.

Cardiovascular diseases are among the leading causes of mortality worldwide. Hypertension is a preventable risk factor leading to major cardiovascular events. We have not found a comprehensive study investigating Central and Eastern European hypertensive patients' complex metabolic status. Therefore, our goal was to calculate the prevalence of hypertension and associated metabolic abnormalities using data-mining methods in our region. We assessed the data of adults who visited the University of Debrecen Clinical Center's hospital (n = 937,249). The study encompassed data from a period of 20 years (2001-2021). We detected 292,561 hypertensive patients. The calculated prevalence of hypertension was altogether 32.2%. Markedly higher body mass index values were found in hypertensive patients as compared to non-hypertensives. Significantly higher triglyceride and lower HDL-C levels were found in adults from 18 to 80 years old. Furthermore, significantly higher serum glucose and uric acid levels were measured in hypertensive subjects. Our study confirms that the calculated prevalence of hypertension is akin to international findings and highlights the extensive association of metabolic alterations. These findings emphasize the role of early recognition and immediate treatment of cardiometabolic abnormalities to improve the quality of life and life expectancy of hypertensive patients.

Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 2. How to manage high blood pressure in children and adolescents.

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. Arterial hypertension is not only the most important risk factor for cardiovascular morbidity and mortality, but also the most important modifiable risk factor. Early hypertension-mediated organ damage may already occur in childhood. The duration of existing hypertension plays an important role in risk assessment, and structural and functional organ changes may still be reversible or postponed with timely treatment. Therefore, appropriate therapy should be initiated in children as soon as the diagnosis of arterial hypertension has been confirmed and the risk factors for hypertension-mediated organ damage have been thoroughly evaluated. Lifestyle measures should be recommended in all hypertensive children and adolescents, including a healthy diet, regular exercise, and weight loss, if appropriate. If lifestyle changes in patients with primary hypertension do not result in normalization of blood pressure within six to twelve months or if secondary or symptomatic hypertension or hypertension-mediated organ damage is already present, pharmacologic therapy is required. Regular follow-up to assess blood pressure control and hypertension-mediated organ damage and to evaluate adherence and side effects of pharmacologic treatment is required. Timely multidisciplinary evaluation is recommended after the first suspicion of hypertension. A grading system of the clinical evidence is included.

Joint statement for assessing and managing high blood pressure in children and adolescents: Chapter 1. How to correctly measure blood pressure in children and adolescents.

The joint statement is a synergistic action between HyperChildNET and the European Academy of Pediatrics about the diagnosis and management of hypertension in youth, based on the European Society of Hypertension Guidelines published in 2016 with the aim to improve its implementation. The first and most important requirement for the diagnosis and management of hypertension is an accurate measurement of office blood pressure that is currently recommended for screening, diagnosis, and management of high blood pressure in children and adolescents. Blood pressure levels should be screened in all children starting from the age of 3 years. In those children with risk factors for high blood pressure, it should be measured at each medical visit and may start before the age of 3 years. Twenty-four-hour ambulatory blood pressure monitoring is increasingly recognized as an important source of information as it can detect alterations in circadian and short-term blood pressure variations and identify specific phenotypes such as nocturnal hypertension or non-dipping pattern, morning blood pressure surge, white coat and masked hypertension with prognostic significance. At present, home BP measurements are generally regarded as useful and complementary to office and 24-h ambulatory blood pressure for the evaluation of the effectiveness and safety of antihypertensive treatment and furthermore remains more accessible in primary care than 24-h ambulatory blood pressure. A grading system of the clinical evidence is included.

Narrative update of clinical trials with antihypertensive drugs in children and adolescents.

Introduction: To date, our knowledge on antihypertensive pharmacological treatment in children and adolescents is still limited because there are few randomized clinical trials (CTs), hampering appropriate management. The objective was to perform a narrative review of the most relevant aspects of clinical trials carried out in primary and secondary hypertension. Methods: Studies published in PubMed with the following descriptors: clinical trial, antihypertensive drug, children, adolescents were selected. A previous Cochrane review of 21 randomized CTs pointed out the difficulty that statistical analysis could not assess heterogeneity because there were not enough data. A more recent meta-analysis, that applied more stringent inclusion criteria and selected 13 CTs, also concluded that heterogeneity, small sample size, and short follow-up time, as well as the absence of studies comparing drugs of different classes, limit the utility. Results: In the presented narrative review, including 30 studies, there is a paucity of CTs focusing only on children with primary or secondary, mainly renoparenchymal, hypertension. In trials on angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARBs), calcium channel blockers (CCBs) and diuretics, a significant reduction of both SBP and DBP in mixed cohorts of children with primary and secondary hypertension was achieved. However, few studies assessed the effect of antihypertensive drugs on hypertensive organ damage. Conclusions: Given the increasing prevalence and undertreatment of hypertension in this age group, innovative solutions including new design, such as 'n-of-1', and optimizing the use of digital health technologies could provide more precise and faster information about the efficacy of each antihypertensive drug class and the potential benefits according to patient characteristics.

Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk.

BACKGROUND: High triglyceride levels are associated with increased cardiovascular risk, but whether reductions in these levels would lower the incidence of cardiovascular events is uncertain. Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels. METHODS: In a multinational, double-blind, randomized, controlled trial, we assigned patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499 mg per deciliter), and high-density lipoprotein (HDL) cholesterol levels of 40 mg per deciliter or lower to receive pemafibrate (0.2-mg tablets twice daily) or matching placebo. Eligible patients were receiving guideline-directed lipid-lowering therapy or could not receive statin therapy without adverse effects and had low-density lipoprotein (LDL) cholesterol levels of 100 mg per deciliter or lower. The primary efficacy end point was a composite of nonfatal myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. RESULTS: Among 10,497 patients (66.9% with previous cardiovascular disease), the median baseline fasting triglyceride level was 271 mg per deciliter, HDL cholesterol level 33 mg per deciliter, and LDL cholesterol level 78 mg per deciliter. The median follow-up was 3.4 years. As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were -26.2% for triglycerides, -25.8% for very-low-density lipoprotein (VLDL) cholesterol, -25.6% for remnant cholesterol (cholesterol transported in triglyceride-rich lipoproteins after lipolysis and lipoprotein remodeling), -27.6% for apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end-point event occurred in 572 patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03; 95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified subgroup. The overall incidence of serious adverse events did not differ significantly between the groups, but pemafibrate was associated with a higher incidence of adverse renal events and venous thromboembolism and a lower incidence of nonalcoholic fatty liver disease. CONCLUSIONS: Among patients with type 2 diabetes, mild-to-moderate hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence of cardiovascular events was not lower among those who received pemafibrate than among those who received placebo, although pemafibrate lowered triglyceride, VLDL cholesterol, remnant cholesterol, and apolipoprotein C-III levels. (Funded by the Kowa Research Institute; PROMINENT ClinicalTrials.gov number, NCT03071692.).

Discriminating Low to High Adherent Type 2 Patients with Diabetes by Glycosylated Hemoglobin A1c, Eating Self-Efficacy and Other Psychosocial Determinants: Difference Between Patient and Physician Adherence Models.

Objective: Develop individual discriminant models using clinical and psychosocial variables for physicians and patients with diabetes based on their perceptions of patient adherence. Methods: This was a cross-sectional research design utilizing a discriminant analysis approach. Type 2 patients on treatment for diabetes for at least 2 years prior to research were selected. Clinical data were obtained from patient records, and psychosocial variables were collected by survey instruments filled out by patients. A final sample of 200 patients was recruited. Results: We found a positive correlation between patient and physician assessment of patient adherence behaviors. Greater adherence efforts were associated with lower HbA1c. Better quality of the patient-physician relationship was linked to better patient adherence. Increased HbA1c, longer therapy duration and higher BMI described low patient adherence for physicians. Lower HbA1c, female gender and fewer difficulties in marital adjustment characterized high adherence for patients. Dietary self-efficacy as well as emotional and social isolation discriminated mid-level adherers in both models. Conclusion: This research confirmed that patients and physicians perceived and judged patients' adherence behaviors differently. Physicians and patients associated different clinical and psychological factors with low and high adherence. Further research is recommended to clarify how the quality of the physician-patient as well as the patient-spouse relationship affect dietary efficacy and patient adherence. A randomized, controlled clinical trial approach is recommended to establish the effectiveness of interventions aiming to improve dietary self-efficacy on adherence outcomes.

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.

Evaluation of the Safety, Tolerability and Immunogenicity of ShigETEC, an Oral Live Attenuated Shigella-ETEC Vaccine in Placebo-Controlled Randomized Phase 1 Trial.

BACKGROUND: Shigella spp. and enterotoxigenic Escherichia coli (ETEC) cause high morbidity and mortality worldwide, yet no licensed vaccines are available to prevent corresponding infections. A live attenuated non-invasive Shigella vaccine strain lacking LPS O-antigen and expressing the ETEC toxoids, named ShigETEC was characterized previously in non-clinical studies. METHODS: ShigETEC was evaluated in a two-staged, randomized, double-blind and placebo-controlled Phase I clinical trial. A single dose of increasing amounts of the vaccine was given to determine the maximum tolerated dose and increasing number of immunizations were administered with an interval based on the duration of shedding observed. RESULTS: Oral immunization with ShigETEC was well tolerated and safe up to 4-time dosing with 5 × 1010 colony forming units. ShigETEC induced robust systemic immune responses against the Shigella vaccine strain, with IgA serum antibody dominance, as well as mucosal antibody responses evidenced by specific IgA in stool samples and in ALS (Antibodies in Lymphocyte Supernatant). Anti- ETEC toxin responses were detected primarily in the 4-times immunized cohort and for the heat-labile toxin correlated with neutralizing capacity. CONCLUSION: ShigETEC is a promising vaccine candidate that is scheduled for further testing in controlled human challenge studies for efficacy as well as in children in endemic setting for safety and immunogenicity.

Determining the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods in the Northeastern region of Hungary.

Objective: Identifying hypertension in children and providing treatment for it have a marked impact on the patients' long-term cardiovascular outcomes. The global prevalence of childhood hypertension is increasing, yet its investigation has been rather sporadic in Eastern Europe. Therefore, our goal was to determine the prevalence of childhood hypertension and its concomitant metabolic abnormalities using data mining methods. Methods: We evaluated data from 3 to 18-year-old children who visited the University of Debrecen Clinical Center's hospital throughout a 15-year study period (n = 92,198; boys/girls: 48/52%). Results: We identified a total of 3,687 children with hypertension (2,107 boys and 1,580 girls), with a 4% calculated prevalence of hypertension in the whole study population and a higher prevalence in boys (4.7%) as compared to girls (3.2%). Among boys we found an increasing prevalence in consecutive age groups in the study population, but among girls the highest prevalences are identified in the 12-15-year age group. Markedly higher BMI values were found in hypertensive children as compared to non-hypertensives in all age groups. Moreover, significantly higher total cholesterol (4.27 ± 0.95 vs. 4.17 ± 0.88 mmol/L), LDL-C (2.62 ± 0.79 vs. 2.44 ± 0.74 mmol/L) and triglyceride (1.2 (0.85-1.69) vs. 0.94 (0.7-1.33) mmol/L), and lower HDL-C (1.2 ± 0.3 vs. 1.42 ± 0.39 mmol/L) levels were found in hypertensive children. Furthermore, significantly higher serum uric acid levels were found in children with hypertension (299.2 ± 86.1 vs. 259.9 ± 73.3 µmol/L), while glucose levels did not differ significantly. Conclusion: Our data suggest that the calculated prevalence of childhood hypertension in our region is comparable to data from other European countries and is associated with early metabolic disturbances. Data mining is an effective method for identifying childhood hypertension and its metabolic consequences.

May Measurement Month 2019: an analysis of blood pressure screening results from Hungary.

Cardiovascular diseases are not only the leading causes of mortality in Hungary but also the mortality rate is twice as high as the European Union average, so screening programmes identifying subjects with elevated blood pressure (BP) are of utmost importance. May Measurement Month (MMM) is an annual global initiative that began in 2017 aimed at raising awareness of high BP. Hungary joined the 3rd campaign of MMM in 2019 and an overview of the results are presented in this paper. An opportunistic cross-sectional survey of participants aged ≥18 years was carried out in May 2019. Hypertension was defined as systolic BP ≥140 mmHg and diastolic BP ≥90 mmHg or treatment for hypertension, statistical analysis followed the standard MMM protocol. In Hungary, 55 sites were set up in primary and secondary care facilities, in pharmacies, and in malls across all regions, in both cities and villages. Out of 2766 individuals screened, 1286 participants (46.5%) had hypertension. Out of 1869 participants not on antihypertensive medication, 389 (20.8%) had elevated BP. In the case of treated individuals (n = 897), 420 (46.8%) had uncontrolled hypertension. Almost every 2nd subject of the screened cohort had hypertension (treated and controlled, treated and uncontrolled, or untreated). In the untreated cohort, every 5th subject had elevated BP, whilst among patients on antihypertensive medication, every second had uncontrolled BP. By identifying almost one-third of the whole screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, our results confirm the importance of BP screening campaigns.

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.