Blood pressure (BP) variability (BPV) is an independent predictor of cardiovascular (CV) events. The role of BPV in defining risk of cancer therapy-related cardiovascular toxicity (CTR-CVT) is currently unknown. The aims of this study were: (i) to evaluate BPV in a population of patients with Multiple Myeloma, undergoing proteasome inhibitors therapy; (ii) to assess the predictive value of BPV for CTR-CVT; (iii) to analyze clusters of subjects based on BPV. One hundred twenty-four patients underwent a baseline evaluation, including Ambulatory Blood Pressure Monitoring (ABPM), PWV, and Echocardiography. BPV was assessed through ABPM-based standard deviation (SD), weighted standard deviation (wSD), coefficient of variation (CoV), average real variability (ARV), and variability independent of the mean (VIM). Individuals who developed CTR-CVT had a higher baseline BPV. Furthermore, night-time BPV was associated with CTR-CVT, independently of age, smoking, BP, diabetes, dyslipidemia, and kidney function (night-time systolic CoV: adjusted OR 1.09 [1.01-1.21]; night-time systolic VIM: adjusted OR 1.18 [1.01-1.39]). Cut-offs for these BPV parameters were identified as predictors of CTR-CVT occurrence: 10.5 for night-time systolic CoV; 7.8 and 6.4 for systolic and diastolic night-time VIM. Clustering analysis identified subgroups of subjects characterized by the highest BPV, who had a greater prevalence of events, but no differences in other CV risk determinants. Short-term BPV is an independent predictor of CTR-CVT. BPV may enhance the precision of risk stratification in cancer patients, enabling identification of individuals at higher risk who would not be recognized, if traditional prognostic indicators were the sole applied criteria. On the left panel in the figure, the distribution of blood pressure variability (BPV) in the population according to cancer therapy-related cardiovascular toxicity occurrence; in the central panel, association of blood pressure variability with events and cutoffs values; in the right panel, clustering analysis results based on BPV levels. Histogram and radar plot represent events and BPV indexes distribution in the three clusters, respectively. ARV, average real variability; BPV, Blood Pressure Variability; CTR-CVT, cancer therapy-related cardiovascular toxicity; CoV, coefficient of variation; DBP, Diastolic blood pressure; SBP, Systolic blood pressure; SD, standard deviation; VIM, variability independent of the mean; wSD, weighted standard deviation.

The prevalence of hypertension in Japan remains high, owing to the high salt content of the typical Japanese diet. Dairy-based foods may reduce blood pressure and hypertension risk. However, dairy consumption is low in Japan, and the relationships between dairy intake and blood pressure or the mechanisms by which dairy products affect blood pressure are not fully understood. This cross-sectional study was conducted as part of the Iwaki Health Promotion Project in Aomori, Japan. A total of 1071 participants were included from those who underwent annual medical checkups in June 2015. Adjusted multivariate linear and logistic regression analyses were performed to analyze the relationships between dairy consumption and blood pressure or hypertension risk. Comprehensive blood biomarker measurements were also performed. Whole- and high-fat dairy consumption was found to have significant inverse associations with systolic blood pressure (SBP) for all participants (β = -0.0213, P = 0.044) and with SBP and systolic hypertension risk for non-users of antihypertensive medicines (β = -0.0306, P = 0.011; and OR = 0.9927, P = 0.016; respectively). Three blood biomarkers related to phosphorus metabolism (inorganic phosphorus, intact parathyroid hormone, and interleukin-6) were associated with both dairy consumption and SBP. Dairy consumption had a partial inverse association with SBP and hypertension risk in a Japanese population with high salt and low dairy consumption. Analysis of blood biomarkers suggested that phosphorus metabolism is involved in the associations between dairy consumption and blood pressure.

This study aims to delineate the levels of Cd exposure in maternal blood, placenta, and cord blood, and to explore the association between Cd levels and the risk of preeclampsia (PE), as well as its potential impact on fetal growth among affected individuals. A case-control study was performed at the First Hospital of Shanxi Medical University, involving 373 pregnant women diagnosed with PE and 485 controls. Cd was measured in maternal blood, placenta, and cord blood using ICP-MS. The association between Cd and birth weight z-score was analyzed by multivariate linear regression. Logistic regression analysis was used to investigate the relationships between Cd and the risk of PE, and Cd and the risk of fetal growth. The concentration of Cd in the placenta was higher than that in maternal blood and cord blood. The highest tertile of placental Cd was identified as a risk factor for PE (OR = 2.704, 95% CI: 1.865, 3.921). Among pregnant women with PE, higher levels of Cd exposure in the placenta were negatively associated with birth weight z-scores (per doubling: β = -0.134, 95% CI: -0.264, -0.004), and the highest tertile of placental Cd was associated with an elevated risk of SGA (OR = 2.103, 95% CI: 1.164, 3.801). Furthermore, an interaction between Cd and PE was identified. In conclusion, Cd can accumulate in the placenta of pregnant women, and high placental Cd exposure not only increases the risk of PE but also exacerbates the risk of SGA outcome in PE pregnant women.

Long-term blood pressure (BP) variability (BPV) is associated with adverse prognosis in patients with heart failure. However, the clinical significance of very short-term (beat-to-beat) BPV is unclear. We collected data on nighttime pulse transit time-based continuous beat-to-beat BP measurement in patients with heart failure (n = 366, median age 72.0, male sex 53.3%). Coefficient of variation (CoV) of pulse transit time-based BP was considered as very short-term BPV. The primary outcome was a composite of heart failure hospitalization or cardiac death. Median values (25th and 75th percentiles) of systolic and diastolic BP CoV were 3.6% (2.8%, 4.5%) and 5.1% (3.8%, 6.5%), respectively. During a median follow-up period of 1084 days after BPV evaluation, 71 patients experienced the primary outcome. When the patients were divided into tertiles based on the systolic and diastolic BPV, the primary outcome occurred most frequently in the highest tertile of BPV. Multivariable Cox proportional hazard analysis revealed that systolic and diastolic BPV, as continuous variables, were independently associated with the primary outcome (hazard ratio 1.199 and 1.101, respectively). In conclusion, high nighttime very short-term BPV was associated with adverse prognosis in patients with heart failure.

The optimal blood pressure (BP) in patients with chronic kidney disease (CKD) remains uncertain. Therefore, this cohort study aimed to investigate the prognostic value of ambulatory blood pressure (ABP) in patients with CKD and to determine the optimal range for ABP. In total, 1051 hospitalized patients with CKD were enrolled. The prognosis of patients with CKD was evaluated in terms of all-cause death, cardiovascular death, cardiovascular events, and renal events. Our results showed that systolic blood pressure (SBP) had a higher predictive value than diastolic blood pressure in the multivariate-adjusted models. Additionally, nighttime SBP was found to be the best predictor of prognosis in patients with CKD. Furthermore, when dividing the nighttime SBP into quartiles (quartile 1: <110 mmHg, quartile 2: 110-124 mmHg, quartile 3:124-139 mmHg, and quartile 4: ≥139 mmHg). Nighttime SBP ≥ 124 mmHg had an impact on prognosis in patients with CKD, nighttime SBP 124-139 mmHg: total mortality (hazard ratio [HR], 3.017 [95% confidence interval (CI): 1.367-6.660]), cardiovascular death (HR, 2.570 [95% CI, 1.744-6.151]), all cardiovascular events (HR, 2.401 [95% CI, 1.288-4.475]), and 110-124 mmHg had an impact on the renal prognosis (HR, 1.975 [95% CI, 1.311-2.976]). Therefore, nighttime SBP is an independent risk factor for CKD and a significant predictor of prognosis in patients with CKD. Furthermore, the prognosis of patients with CKD improved when the nighttime SBP was maintained below 124 mmHg; however, maintaining it below 110 mmHg can further lower the incidence of renal disease.

Superselective adrenal artery embolization (SAAE) has increasingly emerged as an alternative treatment for primary aldosteronism (PA) patients who either unwilling or unable to undergo surgical adrenalectomy, and cannot tolerate or refuse to mineralocorticoid receptor antagonists (MRAs). Although SAAE has been applied in PA treatment for over two decades, its safety and efficacy are still uncertain due to absence of multi-center, randomized controlled trials, hindering its widespread clinical adoption. Currently, only a few centers could perform this procedure proficiently, leading to variability in technical protocols and clinical outcomes across different institutions. During SAAE procedure, it is crucial to determine the target adrenal artery, while misidentification of the artery could lead to severe complications. To promote the safe and effective performance of SAAE, we aim to explore the application value of ipsilateral superselective adrenal arteriography and adrenal venography during the SAAE procedure. The application value of ipsilateral superselective adrenal arteriography and adrenal venography in patients with primary aldosteronism undergoing adrenal artery embolization. SAAE superselective adrenal artery embolization, AVS adrenal venous sampling.

The brainstem plays a vital role in regulating blood pressure, and disruptions to its neural pathways have been linked to hypertension. However, it remains unclear whether subtle microstructural changes in the brainstem are associated with an individual's blood pressure status. This exploratory, cross-sectional study investigated the relationship between brainstem microstructure, myelination, and hypertensive status in 116 cognitively unimpaired adults (aged 22-94 years). Advanced MRI techniques, including relaxometry (R1, R2) and myelin water fraction (MWF) analysis, were employed to assess microstructural integrity and myelin content in ten brainstem subregions. Our results revealed significant associations between higher microstructural damage or lower myelin content (indicated by lower R1, R2, or MWF values) and hypertensive status, particularly in the midbrain tegmentum. Notably, combining these MRI metrics yielded high classification accuracy (AUC > 0.85). Our findings suggest a potential link between disrupted brainstem tissue integrity, myelin content, and elevated blood pressure, warranting further longitudinal investigations to explore this relationship.

To explore the effects of obstructive sleep apnea (OSA) on nocturnal changes in blood pressure (BP), we enrolled 2037 participants who underwent polysomnography (PSG) between 2019 and 2020 and examined BP changes before and after sleep. BP was measured in the evening and the following morning using an electronic wrist sphygmomanometer in the supine position. The severity of OSA was determined by PSG and graded based on the apnea/hypopnea index (AHI). Participants with OSA (AHI ≥ 5 events/h) had significantly higher morning systolic BP (SBP) and diastolic BP (DBP) compared to their evening measurements. BP values, whether measured in the evening or the morning, as well as the nocturnal changes (differences between morning and evening values), showed significant correlations with the AHI for both SBP and DBP, even after adjusting for confounders such as age, sex, body mass index, and the presence of comorbidities, including hypertension, heart failure, coronary artery disease, diabetes, renal disorder, and cerebrovascular attack. After standardization, the extent of nocturnal changes in DBP was greater than SBP, especially among participants with severe OSA. In a logistic regression model with serial multivariate adjustments, OSA was found to be independently associated with morning hypertension, particularly in individuals with moderate to severe OSA.

Hypertension is a major global health issue that contributes significantly to cardiovascular morbidity and mortality. The management and prevention of hypertension often involve nutritional and dietary modifications, which are considered effective non-pharmacological strategies. In 2023, the Hypertension Research published several papers highlighting nutrition and hypertension. In addition, multiple studies published in leading journals explored the relationship between salt intake and blood pressure (BP) in 2023. In this mini-review, we summarize the key findings of nutritional studies published in the Hypertension Research in 2023. This mini-review also highlights significant findings from the latest research on salt intake and its impact on BP. The new findings from nutritional studies will provide deeper insights on planning dietary strategies for the management of hypertension.

The hypertension patient population has doubled since 1990, affecting 1.3 billion globally and >75% live in low-and middle-income countries. Angiotensin Converting Enzyme Inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) are the most prescribed drugs (>160 million times in the US), but mortality increased >30% since 1990s globally. Clinical relevance of Myxomatous Mitral Valve Disease (MMVD) is directly linked to WHO group 2 pulmonary hypertension, with no disease specific therapies. Therefore, MMVD pet dogs with elevated systolic blood pressure treated with ACEI/ARB, were supplemented with oral ACE2 enzyme and Angiotensin1-7 (Ang1-7) bioencapsulated in plant cells. The oral ACE2/Ang1-7 was well tolerated by healthy and MMVD dogs with no adverse events and increased sACE2 activity by 670-755% with ARB (Telmisartan) than with ACEI (Enalapril) background therapy. In vitro rhACE2 activity was inhibited >90% by ACEIs enalapril/benazeprilat at higher doses but lisinopril inhibited at much lower doses. Membrane ACE2 activity evaluated in exosomes was 43-fold higher than the sACE2 and this was also inhibited 211% by ACEI, when compared to ARB. Background ACEI treatment reduced the Ang-II pool by 11-20-fold and proportionately decreased the abundance of Ang1-7 + Ang1-5 peptides. In contrast, ARB treatment increased Ang-II pool 11-20-fold and Ang1-7 + Ang1-5 by 160-260%. Systolic blood pressure was regulated by ARB better than ACEI, despite very high Ang-II levels. This first report on evaluation of metabolic pools in the RAS pathway identifies surprising interactions between ACEI/ARB/ACE2 and significant changes in key molecular dynamics. Affordable biologics developed in plant cells may offer potential new treatment options for hypertension.

Mechanical forces such as glomerular hyperfiltration are crucial in the pathogenesis and progression of diabetic kidney disease. Piezo2 is a mechanosensitive cation channel and plays a major role in various biological and pathophysiological phenomena. We previously reported Piezo2 expression in mouse and rat kidneys and its alteration by dehydration and hypertension. To elucidate the alteration of Piezo2 expression and its consequences in a mouse model of diabetic kidney disease, we used high salt-fed male KK-A mice, an accelerated genetic model of diabetic kidney disease. KK-A mice exhibited marked obesity, hyperglycemia, elevated blood pressure, higher creatinine clearance, and overt albuminuria. Histopathological analysis revealed glomerular hypertrophy, mesangial expansion, macrophage infiltration, tubular vacuolization, and interstitial fibrosis. The mRNA and protein expression analyses revealed (1) increased fibronectin protein expression in the glomerular areas, (2) upregulated Piezo2 expression in the glomerular mesangial cells and interstitial region, (3) increased Piezo2 and the fibronectin-coding gene Fn1 mRNA, and (4) a strong correlation of Piezo2 expression with that of Fn1 in the kidneys of diabetic kidney disease mice. Piezo2 upregulation and fibronectin accumulation were alleviated by an angiotensin II receptor blocker. In accordance with these in vivo results, in vitro study demonstrated that Piezo2 overexpression increased fibronectin production in HEK293T cells. In conclusion, we demonstrated that Piezo2 expression was upregulated in glomerular mesangial cells in a mouse model of diabetic kidney disease. Our results suggest that Piezo2 contributes to the progression of diabetic kidney disease by mediating glomerular fibronectin production, leading to glomerulosclerosis. Hyperfiltration is crucial in the pathogenesis of diabetic kidney disease. We showed that Piezo2 expression is upregulated in mesangial cells of diabetic kidney disease mice with glomerular fibronectin accumulation. Piezo2 overexpression increased fibronectin production in HEK293T cells. Piezo2 may contribute to diabetic kidney disease progression by mediating glomerular fibronectin production.

Poor blood pressure control in treated patients with hypertension is an important topic in the field of hypertension, and an unmet need for new therapeutic drugs remains. Soluble guanylate cyclase (sGC), a key signal transduction enzyme responsible for vasodilation, has attracted increasing interest as a therapeutic target in various cardiovascular diseases. Two different sGC agonists, sGC stimulators and activators, can increase its enzymatic activity in reduced and oxidized/apo forms, respectively. With some sGC agonists being already in clinical use, drugs in this category are expected to become new therapeutic agents for various conditions, including hypertension. In this review, we summarize the current knowledge on the antihypertensive effects of sGC agonists in various preclinical studies involving animal models of spontaneous hypertension, salt-sensitive hypertension, nitric oxide-deficient hypertension, renin-angiotensin-aldosterone system-dependent hypertension, malignant hypertension, metabolic syndrome, renoprival hypertension, renovascular hypertension, drug-induced hypertension, pregnancy hypertension, and treatment-resistant hypertension. Our compilation provides a comprehensive rationale for advancing the clinical development of sGC agonists for the treatment of hypertension.

Balance between Protective vs. Exacerbating Effects of ACEIs and ARBs in Omicron Variant Infections. The spike protein on the surface of the Omicron variant has a high affinity for ACE2, making it more prone to enter cells and induce ACE2 downregulation. Therefore, the effects of ACEIs and ARBs on Omicron variant infections may differ from those of the previous variants. The current study demonstrates that ACEIs and ARBs do not aggravate or prolong COVID-19 due to Omicron variant infections.