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.).

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.

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.

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 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.

Electrocardiographic markers for the prediction of ventricular arrhythmias in patients with systemic sclerosis.

SSc is an autoimmune disease characterized by microvascular damage, endothelial dysfunction and fibrosis of the skin and the internal organs. Cardiac manifestation in patients with SSc is one of the major organ involvements. Approximately 20% of SSc patients suffer from primary cardiovascular disease and another 20% may have secondary cardiac involvement. Although cardiac arrhythmias are mostly linked to myocardial fibrosis, atrioventricular conduction abnormalities are secondary to the fibrosis of the pulse conduction system. Despite the severe consequences of ventricular rhythm disturbances in patients with SSc, the exact role of electrocardiographic markers in the prediction of these arrhythmias has not yet been clearly elucidated. Therefore, the question is whether certain ECG parameters reflecting ventricular repolarization may help to recognize scleroderma patients with increased risk for ventricular arrhythmias and sudden cardiac death.

Effect of sevoflurane on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity.

BACKGROUND: Sevoflurane is one of the most frequently used inhaled anesthetics for general anesthesia. Previously it has been reported that at clinically used doses of sevoflurane, cerebral vasoreactivity is maintained. However, there are no data how sevoflurane influences systemic and cerebral circulation in parallel. The aim of our study was to assess systemic and cerebral hemodynamic changes as well as cerebral CO2-reactivity during sevoflurane anesthesia. METHODS: Twenty nine patients undergoing general anesthesia were enrolled. Anesthesia was maintained with 1 MAC sevoflurane in 40% oxygen. Ventilatory settings (respiratory rate and tidal volume) were adjusted to reach and maintain 40, 35 and 30 mmHg EtCO2 for 5 min respectively. At the end of each period, transcranial Doppler and hemodynamic parameters using applanation tonometry were recorded. RESULTS: Systemic mean arterial pressure significantly decreased during anesthetic induction and remained unchanged during the entire study period. Central aortic and peripherial pulse pressure and augmentation index as markers of arterial stiffness significantly increased during the anesthetic induction and remained stable at the time points when target CO2 levels were reached. Both cerebral autoregulation and cerebral CO2-reactivity was maintained at 1 MAC sevoflurane. DISCUSSION: Cerebral autoregulation and CO2-reactivity is preserved at 1 MAC sevoflurane. Cerebrovascular effects of anesthetic compounds have to be assessed together with systemic circulatory effects. TRIAL REGISTRATION: The study was registered at http://www.clinicaltrials.gov , identifier: NCT02054143, retrospectively registered. Date of registration: February 4, 2014.

May Measurement Month 2017: an analysis of blood pressure screening in Hungary-Europe.

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. The cardiovascular mortality rate in Hungary is twice as high as the European Union average. In a recent Hungarian screening programme, among those volunteers who claimed to be healthy, BP was above 140/90 mmHg in 24% and 39% in women and men, while the control rate was 45% and 36% in women and men, respectively. May Measurement Month (MMM) is a global initiative by the International Society of Hypertension aimed at raising awareness of high BP and to act as a temporary solution to the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 was carried out in May 2017. BP measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. In Hungary, 97 sites were set-up in primary and secondary care facilities, in pharmacies and in malls. All regions, both cities and villages were involved. A total of 3967 individuals were screened. After multiple imputation, 2052 subjects (51.8%) had hypertension. 553 (22.4%) of untreated individuals had hypertension, and 666 (44.5%) of treated individuals had uncontrolled BP. More than 50% of the screened cohort had hypertension (treated and controlled, treated and uncontrolled or untreated). By identifying almost one-third of the screened cohort with the possibility of newly diagnosed or uncontrolled hypertension, the Hungarian part of MMM17 suggest that opportunistic screening can identify significant numbers with raised BP.

Effect of ertugliflozin on glucose control, body weight, blood pressure and bone density in type 2 diabetes mellitus inadequately controlled on metformin monotherapy (VERTIS MET).

AIM: We evaluated the efficacy and safety of ertugliflozin, an SGLT2 inhibitor, in type 2 diabetes mellitus (T2DM) inadequately controlled (HbA1c, 7.0%-10.5%) with metformin monotherapy (≥1500 mg/d for ≥8 weeks). METHODS: This was a double-blind, 26-week, multicentre study with ongoing 78-week extension (ClinicalTrials.gov identifier: NCT02033889). A total of 621 participants were randomized 1:1:1 to placebo, or ertugliflozin 5 or 15 mg/d. The primary endpoint was change from baseline at week 26 in HbA1c. Secondary efficacy endpoints were change from baseline at week 26 in fasting plasma glucose (FPG), body weight, systolic/diastolic blood pressure (SBP/DBP) and number of participants with HbA1c <7.0% (53 mmol/mol). Pre-specified adverse events (AEs) of special interest and percent change from baseline in bone mineral density (BMD) were also assessed at week 26. RESULTS: At week 26, the placebo-adjusted least-squares mean change from baseline HbA1c (8.1%) was -0.7% and -0.9% for ertugliflozin 5 and 15 mg, respectively (both P < .001), to final means of 7.3% and 7.2%, respectively. The odds of HbA1c <7.0% were significantly greater in both ertugliflozin groups vs placebo. Ertugliflozin significantly reduced FPG, body weight, SBP and DBP vs placebo. The incidence of genital mycotic infections was higher in the ertugliflozin groups (female subjects: placebo, 0.9%; ertugliflozin 5 mg, 5.5%; ertugliflozin 15 mg, 6.3% [P = .032]; male subjects: 0%; 3.1%; 3.2%, respectively), as was the incidence of urinary tract infections and symptomatic hypoglycaemia. The incidence of hypovolaemia AEs was similar across groups. Ertugliflozin had no adverse impact on BMD at week 26. CONCLUSIONS: Ertugliflozin added to metformin in patients with inadequately controlled T2DM improved glycaemic control, reduced body weight and BP, but increased the incidence of genital mycotic infections.

[The role of apolipoprotein M and sphingosine 1-phosphate axis in the prevention of atherosclerosis]. / Az apolipoprotein M és a szfingozin-1-foszfát tengely jelentosége az érelmeszesedés kialakulásának gátlásában.

Previous studies showed that plasma levels of high-density lipoprotein (HDL) cholesterol are inversely related to risk of cardiovascular diseases. However, in the last few decades it became obvious that beyond its plasma level, HDL structure and function have a critical role in its anti-atherogenic efficacy. Apolipoprotein M (ApoM) is an HDL-associated plasma protein affecting HDL metabolism and exhibits various anti-atherosclerotic functions, such as protection against oxidation and regulation of cholesterol efflux. Sphingosine 1-phosphate (S1P) is a potent sphingolipid mediator that regulates numerous cellular responses including cell differentiation and migration, apoptosis and vascular inflammation. The majority of S1P is associated to ApoM containing HDL particles. Therefore, ApoM and S1P content of HDL have an impact on the atherosclerotic process. Moreover, HDL-ApoM and S1P content can be altered in several pathologic conditions such as coronary artery disease. This review covers the currently available data on the contribution of ApoM and S1P to HDL function in health and cardiovascular diseases. Orv Hetil. 2018; 159(5): 168-175.

Non-invasive pulse wave analysis for monitoring the cardiovascular effects of CO2 pneumoperitoneum during laparoscopic cholecystectomy--a prospective case-series study.

BACKGROUND: Peritoneal insufflation results in hemodynamic changes during laparoscopic cholecystectomy. The aim of the present work is to test whether non-invasive applanation tonometry is suitable for reflecting these hemodynamic alterations. METHODS: 41 patients undergoing laparoscopic cholecystectomies were monitored using the SphygmoCor pulse wave analysing system. Peripheral blood pressures (PBP), central aortic blood pressures (CBP), augmentation index (ALX@HR75) and subendocardial viability ratio (SVR) were measured at rest (Phase 1), after anesthetic induction (Phase 2), after peritoneal inflation (Phase 3) and after peritoneal deflation (Phase 4). RESULTS: Induction of anesthesia resulted in a statistically significant reduction in both the peripheral blood pressure and central aortic pressures, accompanied by a decrease in augmentation pressure and augmentation index. Peripheral blood pressures did not change along with the peritoneal cavity insufflation, except for a moderate increase in systolic blood pressure. In contrast to this, an increase could be observed in central aortic pressure (106.77 ± 18.78 vs. 118.05 ± 19.85 mmHg, P < 0.01) which was accompanied by increased augementation pressure (18.97 ± 10.80 vs. 31.55 ± 12.01; P < 0.001) and augmentation index (7.31 ± 5.59 vs. 12.61 ± 7.56, P < 0.001), indicating a rise in peripheral arterial stiffness. CONCLUSIONS: The Sphigmocor pulse wave analysis system can be reliably used for detecting and monitoring cardiovascular changes occurring during laparoscopic cholecystectomy.

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.

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.

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.

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.

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 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.

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.

Importance of ambulatory blood pressure monitoring in adolescent hypertension.

There has been a steady increase in the prevalence of adolescent hypertension in recent years. In order to prevent target organ damages, it is important to determine the group of hypertensive adolescents. If repeatedly elevated blood pressure values are observed, with special emphasis on white coat hypertension, which is particularly frequent at this age, ambulatory blood pressure monitoring is highly recommended before pharmacological treatment is started. In addition, performing ambulatory blood pressure monitoring is recommended with target organ damage, resistance to therapy, and suspicion of secondary hypertension. The results of the widely available, simple-to-use device are easy to reproduce.