Hypertension
· 2026 Jun · PMID 42233180
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BACKGROUND: Excessive gestational weight gain (GWG) may cause maladaptive sympathetic neural responses and increase pregnancy risk, which may differ by maternal body mass index. We hypothesized that excessive GWG would f...BACKGROUND: Excessive gestational weight gain (GWG) may cause maladaptive sympathetic neural responses and increase pregnancy risk, which may differ by maternal body mass index. We hypothesized that excessive GWG would further increase muscle sympathetic nerve activity across gestation, particularly in women with overweight or obesity. METHODS: Ninety pregnant women were studied longitudinally during early and late gestation and postpartum. Participants were classified by body mass index in early pregnancy and by GWG in late pregnancy based on the 2009 Institute of Medicine guidelines, forming 4 groups: normal-weight women with normal (n=17) or excessive GWG (n=26), and overweight/obese women with normal (n=16) or excessive GWG (n=31). Resting systolic and diastolic blood pressure, heart rate, and muscle sympathetic nerve activity were measured. Pregnancy outcomes were obtained from hospital maternity records, and complications were diagnosed according to established clinical criteria. RESULTS: Muscle sympathetic nerve activity increased across gestation and was greater in overweight/obese groups than in normal-weight groups (=0.017), with no difference between excessive and normal GWG groups (=0.845). Heart rate and systolic blood pressure increased from early to late pregnancy and were higher in overweight/obese groups, irrespective of GWG. Diastolic blood pressure increased most in normal-weight women with excessive GWG (<0.05), reaching levels comparable to those in the overweight/obese groups. Among all groups, women with overweight/obesity and excessive GWG had the numerically highest complication rate. CONCLUSIONS: The changes in muscle sympathetic nerve activity across gestation did not differ by GWG, even among women with overweight/obesity, suggesting that the increased risk from excessive GWG is unlikely to be mediated by sympathetic activity.
Gao X, Hailu EM, Tabb LP
… +2 more, Lewis TT, Mujahid MS
Hypertension
· 2026 Jun · PMID 42227346
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BACKGROUND: Historical redlining may contribute to racial inequities in cardiovascular health. Longitudinal studies are needed to investigate the influence of historical redlining on blood pressure (BP) and its changes o...BACKGROUND: Historical redlining may contribute to racial inequities in cardiovascular health. Longitudinal studies are needed to investigate the influence of historical redlining on blood pressure (BP) and its changes over time, and to understand the role contemporary residential segregation plays in this relationship. METHODS: Using the MESA (Multi-Ethnic Study of Atherosclerosis), this study examined associations between redlining, measured using 1930s Home Owners' Loan Corporation grades, and repeated BP measures. We used race/ethnicity-stratified 3-level mixed-effects models to assess associations between redlining and average BP, as well as changes in BP, across 6 follow-up examinations from 2000 to 2018, accounting for time-varying sociodemographic and health factors. RESULTS: The sample included 4774 adults with a mean baseline age of 61.9 years; the racial/ethnic composition was 26.7% Black, 23.9% Hispanic, 13.3% Chinese, and 36.1% White. Independent of sociodemographic factors, Black participants in redlined neighborhoods graded had 7.26 mm Hg higher average systolic BP (95% CI, 0.99-13.54) and 3.62 mm Hg higher average diastolic BP (95% CI, 0.64-6.60), compared with those in non-redlined tracts graded . Contemporary residential segregation modified this association such that the increase was larger in currently segregated Black neighborhoods. When assessing BP changes, we found that the difference in systolic BP for participants in -graded neighborhoods decreased among Black participants over follow-up. There was no statistically significant association with average BP or BP changes in other racial/ethnic groups. CONCLUSIONS: These findings demonstrated that historical discriminatory policies may have a harmful impact on BP outcomes among Black adults in the United States.
Hypertension
· 2026 Jun · PMID 42227118
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Hypokalemia occurs frequently in elderly hypertensives treated with diuretics, where it enhances cardiovascular, cerebrovascular, and renal risk. Literature Review. We review the evidence that hypertensive patients with...Hypokalemia occurs frequently in elderly hypertensives treated with diuretics, where it enhances cardiovascular, cerebrovascular, and renal risk. Literature Review. We review the evidence that hypertensive patients with diuretic-induced hypokalemia are at special risk from increased penetration of aldosterone into the brain, enhanced mineralocorticosteroid receptor and postreceptor signaling, and enhanced activation of the mineralocorticosteroid receptor by cortisol. This leads to unique considerations for the preferred strategy to prevent or treat hypokalemia in this vulnerable group.
Grobe CC, Hamilton AJ, Treesukosol Y
… +3 more, Grobe JL, Segar JL, Sigmund CD
Hypertension
· 2026 Jun · PMID 42220234
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BACKGROUND: Altered detection and preference for sodium are associated with increased sodium intake, and increased sodium intake is associated with increased risk of hypertension. ATR (angiotensin II type 1 receptor) sec...BACKGROUND: Altered detection and preference for sodium are associated with increased sodium intake, and increased sodium intake is associated with increased risk of hypertension. ATR (angiotensin II type 1 receptor) second-messenger signaling is mediated and modulated by ARRB2 (β-arrestin-2), and both ATR and ARRB2 in the brain influence sodium intake. Here, we examined the hypotheses that ARRB2 influences sodium taste hedonics and that these effects involve ATR. METHODS: Sodium intake behaviors and hedonic reactions of mice carrying a null mutation of the endogenous ARRB2 gene (-KO mice) were evaluated using 2-bottle choice testing, brief-access paradigms, and intraoral taste reactivity assays. RESULTS: -KO mice of both sexes exhibited dose-dependent increases in licking to sodium chloride and sucrose, but not quinine or citric acid, during a brief-access paradigm; rapid recovery of spontaneous isotonic saline intake after acute adulteration by quinine or exposure to hypertonic saline; persistently elevated isotonic saline intake even when dietary sodium content was increased from 0.15% to 1.00%; and reduced aversive reactions to acute intraoral isotonic saline. Finally, the spontaneous increase in isotonic saline intake by -KO mice was abolished by administration of the ATR antagonist losartan. CONCLUSIONS: Together, these findings highlight a major role for ARRB2 in sodium taste processing, which appears to be mediated through an ATR-dependent mechanism.
Si F, Ma X, Li C
… +5 more, Wang Y, Ma J, Feng C, Liu Q, Yu J
Hypertension
· 2026 May · PMID 42186811
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BACKGROUND: Apatinib is a tyrosine kinase inhibitor used for targeted cancer therapy, but its cardiovascular toxicity, particularly hypertension, limits its clinical application. We observed significant mitochondrial fra...BACKGROUND: Apatinib is a tyrosine kinase inhibitor used for targeted cancer therapy, but its cardiovascular toxicity, particularly hypertension, limits its clinical application. We observed significant mitochondrial fragmentation in endothelial cells after apatinib treatment. This study aims to investigate the role of Drp1 (dynamin-related protein 1)-mediated mitochondrial fission in apatinib-induced hypertension in endothelial cells. METHODS: We established an apatinib-targeted gastric cancer-bearing nude mice model. Apatinib was also administered to human umbilical vein endothelial cells in vitro. Mitochondrial morphology changes in endothelial cells were examined. The role of Drp1 in this process was validated using various experimental methods. In addition, we explored the mechanisms by which March5 (membrane-associated RING-CH finger 5) regulates Drp1 ubiquitination and its role in endothelial dysfunction induced by apatinib. RESULTS: In apatinib-treated human umbilical vein endothelial cells, mitochondrial fragmentation was evident, accompanied by a significant upregulation of Drp1 expression, leading to endothelial dysfunction. In tumor-bearing nude mice treated with apatinib, mitochondrial fragmentation in thoracic aortic endothelial cells increased, and Drp1 expression was significantly elevated. Drp1 knockdown or inhibition by Mdivi-1 alleviated endothelial dysfunction and hypertension. Interestingly, Mdivi-1 did not affect the antitumor efficacy of apatinib. Further mechanistic exploration revealed that apatinib partially inhibits the expression of March5, reducing Drp1 ubiquitination and degradation, thus promoting excessive mitochondrial fission. CONCLUSIONS: This study demonstrates that apatinib induces endothelial dysfunction and hypertension by inhibiting March5 expression and reducing Drp1 ubiquitination. Inhibiting Drp1 alleviates excessive mitochondrial fission in endothelial cells, alleviating apatinib-induced endothelial dysfunction and hypertension, without compromising its antitumor effects.
Fischer R, Wysocki J, Hassler L
… +1 more, Batlle D
Hypertension
· 2026 May · PMID 42186799
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BACKGROUND: Acute hypertensive crises can induce intravascular hemolysis, but its impact on the renin-angiotensin system remains unclear. METHODS: Acute blood pressure elevations were induced in wild-type and PEP (prolyl...BACKGROUND: Acute hypertensive crises can induce intravascular hemolysis, but its impact on the renin-angiotensin system remains unclear. METHODS: Acute blood pressure elevations were induced in wild-type and PEP (prolyl endopeptidase)-deficient mice via Ang II (angiotensin II) injections. Systolic blood pressure, hemolysis index, and plasma enzymatic activities were evaluated. Native and cryo-hemolyzed plasma samples were incubated ex vivo with Ang II, with or without a PEP inhibitor, and Ang-(1-7; angiotensin-[1-7]) formation was measured over time. Ang II formation from Ang I (angiotensin I) was also assessed ex vivo. Plasma ACE (angiotensin-converting enzyme) protein levels were determined by Western blotting. RESULTS: Ang II-induced blood pressure elevations led to hemolysis and a ≈3.5-fold increase in plasma PEP activity, while the activities of other Ang II-degrading enzymes were unchanged. Pretreatment with recombinant ACE2 before Ang II infusion markedly attenuated both the systolic blood pressure and the hemolysis index. Cryo-hemolyzed plasma from mice and humans showed markedly increased ex vivo Ang-(1-7) formation from Ang II compared with native plasma, which was obliterated by PEP inhibition. In addition, ex vivo Ang II formation from Ang I was markedly decreased in cryo-hemolyzed plasma, and this was associated with reduced ACE activity, while ACE protein levels remained unchanged. CONCLUSIONS: Acute severe hypertension induced by Ang II infusion causes intravascular hemolysis associated with increased plasma PEP activity and decreased plasma ACE activity that, based on ex vivo findings, enhance Ang II degradation to form Ang-(1-7) and reduce Ang II formation from Ang I, respectively. These previously unrecognized effects of hemolysis on renin-angiotensin system enzymes may be involved in mechanisms that influence acute blood pressure responses.
BACKGROUND: The long-term health impacts of dietary nitrate may depend on its food source, since coingested components differ between plant-based (eg, polyphenols) and animal-based (eg, heme iron) foods, likely directing...BACKGROUND: The long-term health impacts of dietary nitrate may depend on its food source, since coingested components differ between plant-based (eg, polyphenols) and animal-based (eg, heme iron) foods, likely directing nitrate toward distinct metabolic pathways and divergent vascular effects. We investigated whether plant- and animal-sourced nitrate intake showed different associations with 5-year blood pressure (BP) changes and whether these associations were modified by key coingested nutrients. METHODS: In a cohort of 2942 Chinese adults, dietary intake was assessed using a validated food frequency questionnaire. Systolic BP and diastolic BP were measured at baseline and after 5 years. Brachial-ankle pulse wave velocity was assessed at follow-up to define arterial stiffness. Linear and logistic regression models were used to estimate β-coefficients and odds ratios, respectively. RESULTS: Higher plant-sourced nitrate was associated with a greater 5-year SBP decline (β, -3.51 [95% CI, -5.89 to -1.13]) and lower arterial stiffness (odds ratio, 0.59 [95% CI, 0.35-0.98]). Conversely, higher animal-sourced nitrate was associated with diastolic BP increase (β, 1.95 [95% CI, 0.54-3.37]). In joint analyses using a 2×2 approach based on median intakes of each component, high intakes of both plant-sourced nitrate and polyphenols or vitamin C showed the strongest inverse associations with systolic BP change, whereas high intakes of both animal-sourced nitrate and heme iron showed the strongest positive associations with DBP change. CONCLUSIONS: The association between dietary nitrate and BP is determined by its food source and might be affected by accompanying nutrients, highlighting the importance of considering the complete dietary context in nutritional epidemiology.
Ky B, Liu T, Margulies KB
… +20 more, Mitchell JD, Haas NB, Gareen IF, Thangarajah M, Sicks JD, Domenico C, Narayan VK, Smith AM, Wilcox NS, Mittal K, Rhee JW, Armenian SH, Saphner T, Paul AK, Gartrell BA, Zaha VG, Anari F, Wong RL, Townsend RR, Wagner LI
Hypertension
· 2026 Jul · PMID 42158981
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BACKGROUND: The objective of this cluster randomized controlled trial was to determine the feasibility and safety of an intensive (systolic blood pressure [SBP] <120 mm Hg) versus usual care (SBP <140 mm Hg) approach to...BACKGROUND: The objective of this cluster randomized controlled trial was to determine the feasibility and safety of an intensive (systolic blood pressure [SBP] <120 mm Hg) versus usual care (SBP <140 mm Hg) approach to SBP control in patients with renal cell or thyroid cancer initiating VEGFR (vascular endothelial growth factor)-tyrosine kinase inhibitors. METHODS: A phase II site-based cluster randomized controlled trial compared intensive SBP control to usual care, incorporating a centralized BP advisory core to guide BP management. Patients underwent home BP monitoring and study visits at baseline, 1, 2, 3, and 6 months. SBP was compared between the 2 study arms using bootstrapped CIs. Common Terminology Criteria for Adverse Events and patient-reported outcomes were summarized. RESULTS: Overall, 61 patients with renal cell (n=58) or thyroid cancer (n=3) from 10 sites were enrolled; 30 at 5 sites were randomized to intensive SBP control and 31 at 5 sites to usual care. A lower SBP was observed in the intensive SBP control arm compared with usual care, with mean differences of -12.2 (95% CI, -18.1 to -7.0) mm Hg at 1 month, -7.6 (95% CI, -15.3 to -0.4) mm Hg at 3 months, and -6.9 (95% CI, -19.3 to 6.0) mm Hg at 6 months. In the usual care arm, Grade 3 Common Terminology Criteria for Adverse Events for kidney injury (n=4), hypotension (n=3), and dyspnea (n=2) were numerically greater compared with the intensive SBP control (n=1, 2, and 0, respectively). Patient-reported outcomes were largely similar between the 2 groups. CONCLUSIONS: This first-ever randomized controlled trial of SBP control in an active cancer population demonstrates the feasibility, safety, and tolerability of intensive SBP control with VEGFR tyrosine kinase inhibitors. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04467021.
BACKGROUND: Orthostatic hypotension is thought to be associated with coronary heart disease, falls, and syncope due to low blood pressure (BP) upon standing. METHODS: The ARIC (Atherosclerosis Risk in Communities) study...BACKGROUND: Orthostatic hypotension is thought to be associated with coronary heart disease, falls, and syncope due to low blood pressure (BP) upon standing. METHODS: The ARIC (Atherosclerosis Risk in Communities) study measured supine and standing BP among adult participants aged 45 to 64 years once at baseline and followed them for over 35 years. We evaluated higher and lower supine and standing systolic BP, diastolic BP, mean arterial pressure, pulse pressure, absolute and relative orthostatic changes in BP after standing, and mean BP across positions. Associations with adjudicated coronary heart disease and mortality events, as well as hospitalizations and medical claims-based falls and syncope, were assessed via adjusted Cox models in strata of antihypertensive treatment. RESULTS: Among 11 386 participants (mean age, 54 years [SD, 5.7 years]; 56% female; 25% Black adults), drops in systolic BP upon standing (absolute or relative) were associated with coronary heart disease, syncope, and mortality. Higher supine systolic BP and mean arterial pressure were associated with syncope among untreated participants. Increases in systolic BP ≥20 mm Hg upon standing were associated with falls (hazard ratio, 1.52 [95% CI, 1.14-2.02]) and syncope (hazard ratio, 1.40 [95% CI, 1.03-1.92]), particularly among untreated participants. Lower standing systolic BP was associated with a higher risk of syncope among treated participants (hazard ratio, 1.55 [95% CI, 1.14-2.12]). Regardless of treatment status, a higher pulse pressure was associated with coronary heart disease and mortality, but this was not observed for falls or syncope. CONCLUSIONS: Higher BP, rather than lower standing BP alone, may be an important risk factor for both cardiovascular and hypotension-related events, especially among untreated adults.
Cohen JB, Hossain A, Chittams J
… +10 more, Zhao M, Afable J, Greenip A, Maynard H, Pourmussa B, Prenner SB, Selvaraj S, Townsend RR, Zamani P, Chirinos JA
Hypertension
· 2026 Jul · PMID 42137945
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BACKGROUND: Hypertension is present in 90% of individuals with heart failure with preserved ejection fraction (HFpEF) and is a major modifiable risk factor for the development of HFpEF. However, randomized controlled tri...BACKGROUND: Hypertension is present in 90% of individuals with heart failure with preserved ejection fraction (HFpEF) and is a major modifiable risk factor for the development of HFpEF. However, randomized controlled trial evidence for hypertension management in HFpEF is limited. METHODS: In a double-blind, randomized, crossover trial, we studied the effect of amlodipine 5 to 10 mg versus metoprolol succinate 100 to 200 mg (doses previously demonstrated to have comparable antihypertensive efficacy) for 4 weeks among adults with HFpEF and hypertension, without contraindications to initiating or withholding either drug. The primary outcome was the difference in mean home systolic blood pressure (BP) during the final week of each treatment. RESULTS: The mean age of the 50 enrolled participants was 72±9 years, 34 (68%) were female, 33 (66%) were of Black race, mean blood pressure was 144±15/78±9 mm Hg, and 23 (46%) were receiving β-blockers before enrollment. Compared with metoprolol, systolic BP was 4 (95% CI, -7 to -1; =0.017) mm Hg lower with amlodipine. In addition, peak oxygen uptake during exercise was 1.2 (95% CI, 0.3-2.0; =0.008) mL/min per kg higher, physical activity was 0.1 (95% CI, 0.01-0.1; =0.019) metabolic equivalents of task/d higher, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) was 200 (95% CI, -291 to -109; <0.0001) pg/mL lower with amlodipine versus metoprolol. There was no significant difference in septal E/e', myocardial strain, or systemic vasodilatory reserve. The frequency and severity of adverse events were similar across treatments. CONCLUSIONS: Our findings support the use of dihydropyridine calcium channel blockers as a preferred alternative to β-blockers for the management of hypertension in HFpEF. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT04434664.
Kario K, Harada K, Ishiyama Y
… +7 more, Fujiwara T, Narita K, Suzuki Y, Mizuno H, Komi R, Tomitani N, Hoshide S
Hypertension
· 2026 Jul · PMID 42109124
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BACKGROUND: Nighttime blood pressure (BP) assessed by ambulatory BP monitoring is linked to left ventricular hypertrophy and its sequelae, including heart failure. However, the association between nighttime BP measured b...BACKGROUND: Nighttime blood pressure (BP) assessed by ambulatory BP monitoring is linked to left ventricular hypertrophy and its sequelae, including heart failure. However, the association between nighttime BP measured by a wrist-type oscillometric home BP monitor-designed to be less intrusive than brachial devices-and left ventricular hypertrophy remains unclear. METHODS: The WISDOM-HMOD study (Wrist ICT-based Sleep and Circadian Blood Pressure Monitoring Program-Hypertension-Mediated Organ Damage), a substudy of the WISDOM-Night study, included 1218 patients with hypertension or heart failure (mean age, 67.2±12.0 years; 53.9% men) who were recruited between 2021 and 2024. Nighttime BPs (2:00, 3:00, and 4:00 am and 4 hours after bedtime) and morning/evening BPs over 7 days were measured using a wrist-type home BP monitor (HEM9601T; Omron). RESULTS: The average nighttime systolic/diastolic BP was 110.5±13.0/63.5±8.8 mm Hg, and 70.4% of patients had well-controlled nighttime BP (<120/70 mm Hg). The average left ventricular mass index assessed by echocardiography was 90.1±23.6 g/m in men and 80.3±19.3 g/m in women. An increase in nighttime systolic BP was significantly associated with a higher left ventricular mass index, independent of office BP, morning home BP, and evening home BP. Furthermore, elevated nighttime systolic BP was a risk factor for left ventricular hypertrophy in both sexes (odds ratio per 10-mm Hg increase, 1.36 [95% CI, 1.15-1.60] overall; 1.54 [95% CI, 1.19-2.00] in men; and 1.27 [95% CI, 1.01-1.58] in women), independently of covariates including office and morning home BP. CONCLUSIONS: This study shows that nighttime home BP measured using a less sleep-disturbing wrist-type device is an independent risk factor for left ventricular hypertrophy and its potential sequelae, including new-onset or recurrent heart failure, with high-risk nighttime BP thresholds differing by sex.
BACKGROUND: Hypertensive disorders of pregnancy represent a major cause of maternal and fetal morbidity and mortality. Despite primary aldosteronism (PA) being the most common cause of secondary hypertension, there is li...BACKGROUND: Hypertensive disorders of pregnancy represent a major cause of maternal and fetal morbidity and mortality. Despite primary aldosteronism (PA) being the most common cause of secondary hypertension, there is limited data on pregnancy complications in patients with PA. METHODS: We conducted an international survey across 5 Hypertension Centers in Europe to gather data on maternal and neonatal complications in women diagnosed with PA from 2000 to 2022. We included 102 women aged 18 to 45 years at PA diagnosis who were pregnant either after or <1-year before the diagnosis of PA. The first eligible pregnancy for each patient was included. RESULTS: Overall, 56% of pregnancies were complicated, with the most frequent complications being maternal preeclampsia (36%), preterm birth (30%), low birth weight (30%), and neonatal intensive care admission (22%). Hypokalemia occurred in 31% of pregnancies. Pregnancies occurring before PA diagnosis presented a poorer blood pressure control and were associated with higher rates of overall, maternal, and fetal/neonatal complications compared with pregnancies in patients with an established PA diagnosis. Independent predictors of complications included uncontrolled blood pressure values during pregnancy (odds ratio [OR], 7.05), undiagnosed PA (OR, 4.37), North/Black African ethnicity (OR, 3.69), a higher body mass index (OR, 1.09), and treatment with a higher number of antihypertensive drugs at PA diagnosis (OR, 2.18). CONCLUSIONS: PA is associated with a high rate of pregnancy-related complications, predominantly preeclampsia. Undiagnosed PA during gestation significantly increases the risk of adverse outcomes. Early identification and optimized hypertension control in women with PA are critical to improve maternal and fetal outcomes.