Therapeutic CFTR Correction Normalizes Systemic and Lung-Specific S1P Level Alterations Associated with Heart Failure

Heart failure (HF) is among the main causes of death worldwide. Alterations of sphingosine-1-phosphate (S1P) signaling have been linked to HF as well as to target organ damage that is often associated with HF. S1P’s availability is controlled by the cystic fibrosis transmembrane regulator (CFTR), which acts as a critical bottleneck for intracellular S1P degradation. HF induces CFTR downregulation in cells, tissues and organs, including the lung. Whether CFTR alterations during HF also affect systemic and tissue-specific S1P concentrations has not been investigated. Here, we set out to study the relationship between S1P and CFTR expression in the HF lung. Mice with HF, induced by myocardial infarction, were treated with the CFTR corrector compound C18 starting ten weeks post-myocardial infarction for two consecutive weeks. CFTR expression, S1P concentrations, and immune cell frequencies were determined in vehicle- and C18-treated HF mice and sham controls using Western blotting, flow cytometry, mass spectrometry, and qPCR. HF led to decreased pulmonary CFTR expression, which was accompanied by elevated S1P concentrations and a pro-inflammatory state in the lungs. Systemically, HF associated with higher S1P plasma levels compared to sham-operated controls and presented with higher S1P receptor 1-positive immune cells in the spleen. CFTR correction with C18 attenuated the HF-associated alterations in pulmonary CFTR expression and, hence, led to lower pulmonary S1P levels, which was accompanied by reduced lung inflammation. Collectively, these data suggest an important role for the CFTR-S1P axis in HF-mediated systemic and pulmonary inflammation.

Relationship between serum 25-hydroxyvitamin D and target organ damage in children with essential hypertension

Researchers have shown that 25-hydroxyvitamin D (25[OH] D), a kind of active vitamin D in the human body, plays a role in cardiovascular disease (CVD). Low serum 25(OH) D levels have been found to be associated with elevated blood pressure (BP) in adults. However, measurement of 25(OH) D in hypertensive children has not been documented. The aim of this study was to investigate the relationship between 25(OH) D and target organ damage (TOD) in children with essential hypertension. We recruited a total of 346 children with essential hypertension and analyzed the correlation between serum 25(OH) D and TOD. Serum 25(OH) D concentration was significantly lower in the TOD than in the no-TOD group (t = 2.416, P = 0.016), as well as significantly lower in the two-organ damage than in the single-organ damage group (t = 3.140, P = 0.002). Pearson’s correlation coefficient (PCC) indicated that serum 25(OH) D levels were negatively correlated with left ventricular mass index (LVMI; r = −0.110, P = 0.041) and albuminuria (r = −0.120, P = 0.026). Linear- regression analysis showed that 25(OH) D was a risk factor for left ventricular hypertrophy (LVH; β ± s.e. =−0.074 ± 0.036; 95% confidence interval [CI], − 0.145 to –0.003; P < 0.001) and renal damage (β ± s.e.= −0.018 ± 0.008; 95% CI, − 0.035 to –0.002; P = 0.004). In total, our data revealed that serum 25(OH) D was independently associated with hypertensive cardiac and renal damage, meaning that it was a risk factor for LVH and albuminuria in childhood hypertension.

Clinical profile of patients with hypertensive crisis in a tertiary care hospital in Haryana, India – A retrospective cross-sectional study

Background: A hypertensive crisis may manifest as hypertensive emergency or urgency. Hypertensive emergency is characterized by target organ damage and poses immediate threat to life, a situation not seen in urgency. Aims and Objectives: The aims of the study were as follows: (1) To determine the prevalence of hypertensive crisis classified as emergency, urgency, and pseudocrisis. (2) To assess the various systems (neurological, cardiovascular, and renal) affected in relation to a particular type of hypertensive crisis. Materials and Methods: The retrospective study comprised analysis of medical records of 100 patients of hypertensive crisis admitted to emergency unit of BPS Government Medical College and Hospital for Women, Sonepat, Haryana, India, in the 2 years period from January 2018 to December 2019 and study their prevalence among hospital emergencies and clinical presentation. Results: Total number of clinical emergencies analyzed during this time interval was 6666. The prevalence of hypertensive crisis accounted to 1.5% of all the clinical emergencies received. About 66% presented as hypertensive emergencies, 32% as hypertensive urgency, and 2% presented as hypertensive pseudocrisis. Males of the fifth decade of life while females of the sixth decade of life were most affected by hypertensive crisis. Headache (58%) followed by giddiness (44%) was the most common clinical presentation in the emergency. About 34% of patients had associated neurological deficit. Only 16% of patients had cardiovascular system involvement. Conclusion: Symptoms provided by patients in the emergency department are of paramount importance for the outcome of hypertensive crisis. Severe complication of hypertensive crisis can be prevented if hypertension is timely diagnosed and appropriately managed.

Renal Tissue miRNA Expression Profiles in ANCA-Associated Vasculitis—A Comparative Analysis

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) comprises autoimmune disease entities that cause target organ damage due to relapsing-remitting small vessel necrotizing vasculitis, and which affects various vascular beds. The pathogenesis of AAV is incompletely understood, which translates to considerable disease- and treatment-related morbidity and mortality. Recent advances have implicated microRNAs (miRNAs) in AAV; however, their accurate characterization in renal tissue is lacking. The goal of this study was to identify the intrarenal miRNA expression profile in AAV relative to healthy, non-inflammatory and inflammatory controls to identify candidate-specific miRNAs. Formalin-fixed, paraffin-embedded renal biopsy tissue samples from 85 patients were obtained. Comprehensive miRNA expression profiles were performed using panels with 752 miRNAs and revealed 17 miRNA that differentiated AAV from both controls. Identified miRNAs were annotated to characterize their involvement in pathways and to define their targets. A considerable subset of differentially expressed miRNAs was related to macrophage and lymphocyte polarization and cytokines previously deemed important in AAV pathogenesis, lending credence to the obtained results. Interestingly, several members of the miR-30 family were detected. However, a validation study of these differentially expressed miRNAs in an independent, larger sample cohort is needed to establish their potential diagnostic utility.

Early Vascular Aging in Children With Type 1 Diabetes and Ambulatory Normotension

Background: Preliminary data suggest that target organ damage (TOD) and early vascular aging (EVA) may occur in children with normal blood pressure (BP).Objectives: To analyze TOD and EVA in normotensive (BP &lt;95th percentile on ambulatory BP monitoring) type 1 diabetes children (T1D) in comparison to healthy controls (C).Subjects: 25 T1D aged 13.9 ± 2.6 years and 22 C aged 14.0 ± 3.4 years.Methods: We analyzed age- and height-related pulse wave velocity (PWV) Z-scores and expected PWV based on age, height, and mean arterial pressure (MAP). Expected vascular age based on measured PWV was calculated from pooled pediatric and adult PWV norms. Left ventricular mass index (LVMI), estimated glomerular filtration rate (eGFR), and urinary albumin/creatinine ratio (ACR) were obtained as markers of TOD.Results: T1D and C groups did not differ in anthropometry, ambulatory, LVMI, and ACR. However, median age- and height-related PWV Z-scores were higher in T1D compared to C (1.08 vs. 0.57, p = 0.006; 0.78 vs. 0.36, p = 0.02, respectively). Mean (±SD) difference between measured and expected PWV was 0.58 ± 0.57 in T1D vs. 0.22 ± 0.59 in C, p = 0.02. The mean (±SD) difference between chronological and expected vascular age was 7.53 ± 7.74 years in T1D vs. 2.78 ± 7.01 years in C, p = 0.04.Conclusion: Increased arterial stiffness and increased intraindividual differences between expected and measured PWV as well as between chronological and expected vascular age indicate that EVA may develop in T1D children even at normal ambulatory BP levels.

Cross-Talk Between Large Artery Stiffness and Retinal Microvasculature in Children: The ExAMIN Youth SA Study

Background: Cross-talk between the macro-and microvasculature is considered an important contributor to target organ damage. Previous findings were predominantly in adult populations and investigation into this mechanism in children may provide insight into the development of early adverse vascular changes. Whether any ethnic differences in cross-talk is evident, also remains to be determined.Objective: To determine whether retinal microvascular diameters are associated with large artery stiffness in young children and whether ethnic differences are evident.Materials and Methods: In this cross-sectional study, 730 black (n = 437) and white (n = 293) school children aged 5-9 years were included. Pulse wave velocity (PWV) was measured and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters were calculated from fundus images. The arterio-venous ratio (AVR) was subsequently calculated.Results: Pulse wave velocity was lower (p ≤ 0.001) in the black group when compared to the white group. The black group had a narrower CRAE, wider CRVE and lower AVR (all p &lt; 0.001). Pulse wave velocity associated negatively with CRAE (r = –0.141, p = 0.003) and AVR (r = –0.185, p ≤ 0.001) in the black group only. A positive association between PWV and CRVE was seen in the black (r = 0.174, p ≤ 0.001) and white (r = 0.119, p = 0.043) group.Conclusion: Large artery stiffness is associated with retinal arterial narrowing and venular widening in children, suggesting cross-talk between the macro-and microvasculature. Ethnic differences in these associations are also evident. Our findings warrant further investigation into environmental and sociocultural risk factors contributing to premature cardiovascular disease development.

Morning hypertension for stroke and cardiovascular: clinical pearls for primary care

Hypertension is the world’s leading cause of mortality and morbidity. One of the phenomena that commonly occur in hypertensive as well as normotensive patients, is morning hypertension. Blood pressure (BP) follows a diurnal rhythm, reaching its highest level during the morning hours and dropping to the lowest level at midnight. Transient increases in BP in morning hypertension plus persistent stressors within 24 hours are thought to increase target organ damage and trigger cardiovascular events. Therefore, ambulatory BP monitoring or morning home BP monitoring is recommended as a strong predictor of cardiovascular events. There are two types of morning hypertension according to its underlying mechanisms; the first one is called nocturnal hypertensive morning hypertension, and the other one is morning-surge hypertension. Numerous studies have proved that this phenomenon often leads to several acute cardiovascular events, such as stroke, coronary artery disease, and peripheral artery disease. To prevent these complications, cost-effective management is needed, especially for identifying accurate diagnostic tools, as well as creating specific regimens. Therefore, to achieve appropriate management of hypertension, including morning hypertension, long-acting antihypertensive drugs should be used, at full doses and in the form of combination therapy. The clinical usefulness of antihypertensive drugs with specific mechanisms for morning BP or split or timed dosing of long-acting drugs in controlling morning BP remains under investigation. More studies are needed, especially looking for other clinical evidence of the benefits of lowering BP in the morning. Home BP monitoring is recommended as a good choice for BP measurements, especially in the primary care setting.

Feline blood pressure measurement: when is it needed?

Systemic hypertension is a common disorder, primarily affecting older cats. Most cases are secondary to underlying medical conditions, such as chronic kidney disease. If left untreated, systemic hypertension has the potential to cause serious damage to certain target organs and can be fatal. Target organs include the nervous system, cardiovascular system, eyes and kidneys. Target organ damage to the eyes is often pathognomonic and is detected on ophthalmological examination in up to 80% of cats with systemic hypertension. Blood pressure measurement is essential in confirming a diagnosis and should be prioritised in cats showing evidence of target organ damage. Blood pressure screening of apparently healthy older cats is justified, since the risk of hypertension increases with age. Systemic hypertension is diagnosed in cats with persistent elevation in their systolic blood pressure of 160 mmHg or higher. Stress and anxiety can cause a transient increase in systolic blood pressure so measurements should be collected in a manner that is as calm and ‘cat friendly’ as possible. In the presence of confirmed target organ damage, a single high systolic blood pressure reading confirms systemic hypertension. Where no target organ damage is detectable, evidence of elevated systolic blood pressure on two or more occasions is needed to confirm the diagnosis.

Relationship between circulating serum omentin-1 levels and nascent metabolic syndrome in patients with hypertension

The prevalence of metabolic syndrome (MetS) is more common in patients with hypertension and is associated with an increased risk of target organ damage and/or cardiovascular disease (CVD). Omentin-1 is a beneficial adipokine considered to play a role in MetS and MetS-related states such as obesity, diabetes, and coronary artery disease. The aim of this study was to determine the relationship between circulating omentin-1 levels and MetS uncomplicated by diabetes or CVD (nascent MetS) in patients with hypertension. In this study, 110 patients (54 men, 49%; average age: 49.72±11.32 years) treated for hypertension but without overt diabetes and/or CVD were enrolled. 66 patients were stratified into MetS (+) (group 1) and 44 patients into MetS (−) (group 2) according to the American Heart Association/National Heart, Lung, and Blood Institute criteria. The triglyceride glucose (TyG) index was used to assess insulin resistance. Circulating omentin-1 levels in venous blood samples were measured by an ELISA kit. Circulating omentin-1 levels in patients with MetS were significantly lower than in patients without MetS (46.35 ng/mL (42.70–57.70 ng/mL) vs 130.95 ng/mL (62.83–236.48 ng/mL), p<0.001). Omentin-1 was inversely correlated with TyG index (r=−0.204, p=0.033). In a multivariate logistic regression analysis, omentin-1, TyG index, and body mass index were independent predictors of MetS. A receiver operating characteristic curve analysis determined that the best cut-off value for omentin-1 in predicting MetS was 62.20 ng/mL and the area under the curve was 0.880 (95% CI 0.817 to 0.942, p<0.001). The findings of this study suggest that circulating omentin-1 levels are inversely related to the presence of MetS and may be a reliable marker to predict the development of MetS in patients with hypertension.