Zhang Y, Guo S, Ma Y
… +19 more, Chen W, Jiang L, Wang T, Lin Y, Cai X, Wang J, Chen Y, Li S, Zhao N, Hou Z, Zhang X, Huang H, Jiang H, Zhu S, Zhao L, Kristiansen K, Zhang J, Wang Y, Su X
BACKGROUNDS: White matter hyperintensities (WMH), a marker of cerebral small vessel disease, are associated with cardiovascular risk factors and disease. However, the extent to which these associations are driven by shar...BACKGROUNDS: White matter hyperintensities (WMH), a marker of cerebral small vessel disease, are associated with cardiovascular risk factors and disease. However, the extent to which these associations are driven by shared genetic architecture remains unclear. METHODS: Using data from 44 996 UK Biobank participants, we evaluated associations between WMH subtypes (total WMH, deep WMH, and periventricular WMH) and polygenic risk scores (PRSs) for 35 diseases and traits. Associations were tested using χ and multivariable linear regression models. Cox models assessed whether WMH burden modified cardiovascular risk across genetic risk strata. Multiomics data were examined to identify biomarkers jointly associated with WMH and disease-specific PRSs. RESULTS: Higher WMH burden was associated with increased PRSs for cardiovascular disease (CVD), hypertension, ischemic stroke, and blood pressure, with the strongest associations observed for total WMH. WMH burden was prospectively associated with higher CVD incidence among individuals with high CVD PRS (hazard ratio, 2.54 [95% CI, 1.44-4.45]), but not among those with low PRS. For hypertension, WMH burden was associated with increased risk in both PRS strata, with stronger associations in individuals with high hypertension PRS, indicating additive contributions of genetic susceptibility and WMH burden. Lifestyle influences varied by genetic background: longer sleep duration and lower body mass index were protective only with low CVD PRS. Multiomics analyses identified 46 circulating biomarkers jointly associated with WMH and CVD PRSs, predominantly related to lipid metabolism. CONCLUSIONS: The association between WMH burden and cardiovascular-related disease risk is influenced by genetic background, supporting precision risk stratification and prevention in clinical practice.
BACKGROUND: Perivascular inflammation induced by abnormal hemodynamic stress is increasingly recognized as a key driver of secondary microvasculopathy in chronic thromboembolic pulmonary hypertension. Although circulatin...BACKGROUND: Perivascular inflammation induced by abnormal hemodynamic stress is increasingly recognized as a key driver of secondary microvasculopathy in chronic thromboembolic pulmonary hypertension. Although circulating CXCL10 (C-X-C motif chemokine ligand 10) is elevated in chronic thromboembolic pulmonary hypertension and correlates with pulmonary hemodynamics, its mechanistic contribution to vascular remodeling remains unclear. METHODS: Experiments were performed using pulmonary endarterectomy specimens from patients with chronic thromboembolic pulmonary hypertension and a left pulmonary artery ligation rat model. RESULTS: In pulmonary endarterectomy specimens, CXCL10 was predominantly localized to CD68+ mannose receptor C-type 1+ macrophages, whereas CXCR3 (C-X-C motif chemokine receptor 3) was broadly expressed in the vascular wall and enriched in distal nonoccluded pulmonary arteries with increased mannose receptor C-type 1+ macrophage accumulation. In left pulmonary artery ligation rats, pulmonary hypertension and vascular remodeling were accompanied by perivascular accumulation of CXCL10+CXCR3+ mannose receptor C-type 1+ macrophages, increased plasma CXCL10, and upregulation of CXCL10 and CXCR3 in the right lung. CXCR3 expression was also increased in pulmonary arterial smooth muscle cells (PASMCs), and CXCL10 directly promoted proliferation of left pulmonary artery ligation-derived PASMCs in a CXCR3-dependent manner. In parallel, CXCL10 drove macrophages toward a proinflammatory, pro-proliferative secretory phenotype, and conditioned medium from macrophages enhanced PASMC proliferation. Pharmacological CXCR3 inhibition with AMG487 attenuated pulmonary hypertension, vascular remodeling, PASMC proliferation, and perivascular macrophage accumulation in both preventive and therapeutic settings. Similarly, cell type-specific CXCR3 knockdown in smooth muscle cells or macrophages ameliorated left pulmonary artery ligation-induced pulmonary hypertension, vascular remodeling, and associated perivascular inflammation. CONCLUSIONS: The CXCL10/CXCR3 axis links hemodynamic stress to pulmonary vascular remodeling in chronic thromboembolic pulmonary hypertension by coordinating PASMC hyperproliferation and macrophage-driven inflammation, and may represent a therapeutic target.
Fontes MT, Townsend P, Butler L
… +12 more, Parente JM, Araujo FA, Costa TJ, Bomfim GF, Pernomian L, Tan W, VanderVeen BN, Murphy EA, Stark RJ, Butcher JT, McCarthy CG, Wenceslau CF
Hypertension
· 2026 Jul · PMID 42017232
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BACKGROUND: Emerging evidence suggests a critical interplay between skeletal muscle metabolism and vascular function in the context of hypertension. Elevated plasma lactate levels precede the onset of hypertension and ar...BACKGROUND: Emerging evidence suggests a critical interplay between skeletal muscle metabolism and vascular function in the context of hypertension. Elevated plasma lactate levels precede the onset of hypertension and are inversely associated with skeletal muscle mass, highlighting skeletal muscle atrophy and metabolic dysregulation as key contributors to cardiovascular dysfunction. METHODS: Male and female Wistar rats and spontaneously hypertensive rats were studied. Skeletal muscle performance was evaluated using in vivo plantarflexion torque measurements. Femoral arteries with surrounding skeletal muscle were isolated to assess contractility and relaxation. Plasma and muscle lactate levels were quantified using colorimetric assays. Structural remodeling and mitochondrial function were assessed via wheat germ agglutinin staining, succinate dehydrogenase activity, and high-resolution respirometry. Protein lactylation was evaluated by mass spectrometry-based lactylated proteomics. Human translational relevance was examined using publicly available skeletal muscle transcriptomic data. RESULTS: Spontaneously hypertensive rats exhibited skeletal muscle dysfunction marked by increased fatigability, reduced muscle mass, impaired mitochondrial activity, and elevated muscle lactate levels. Despite upregulation of oxidative markers, persistent lactate accumulation suggested a maladaptive metabolic shift. Proteomics revealed differential lactylation of key structural proteins (myosins, nebulin) and metabolic enzymes (Nampt, GAPDH [glyceraldehyde-3-phosphate dehydrogenase]). The anticontractile effect of skeletal muscle on femoral arteries was completely lost in spontaneously hypertensive rats, accompanied by impaired vascular relaxation and increased arterial lactylation. Human transcriptomic data supported parallel metabolic alterations in hypertension. CONCLUSIONS: Hypertension disrupts skeletal muscle metabolic homeostasis and muscle-vascular communication, driven in part by persistent lactate accumulation and altered protein lactylation. Targeting lactate-mediated signaling may offer new therapeutic avenues for hypertensive vascular dysfunction.
BACKGROUND: A hallmark of pulmonary hypertension (PH) is the progressive increase in pulmonary arterial resistance caused by impaired pulmonary artery (PA) relaxation and vascular remodeling. Salusin-α, a cardiovascular-...BACKGROUND: A hallmark of pulmonary hypertension (PH) is the progressive increase in pulmonary arterial resistance caused by impaired pulmonary artery (PA) relaxation and vascular remodeling. Salusin-α, a cardiovascular-active peptide, has been implicated in several cardiovascular diseases; however, its role in PH remains undefined. METHODS: PAs were isolated from rats for isometric tension recording to assess relaxation. PA remodeling was quantified using histological morphometric analysis. Right ventricular pressure and hypertrophy were measured to evaluate PH severity. RESULTS: Salusin-α levels were significantly decreased in both plasma and PAs from PH rats compared with controls. Both acute and chronic salusin-α administration improved endothelium-dependent and -independent PA relaxation, increased endothelial nitric oxide synthase activity and nitric oxide levels in PA endothelial cells, enhanced Nrf2 (nuclear factor erythroid 2-related factor 2) and superoxide dismutase expression and activity in PA smooth muscle cells, and decreased NAD(P)H oxidase expression, activity, and reactive oxygen species levels. Salusin-α also inhibited PA smooth muscle cell proliferation and migration, attenuated pulmonary vascular remodeling, and decreased right ventricular pressure, hypertrophy, and mortality in PH rats. Neutralizing endogenous salusin-α exerted opposite effects. Pharmacological inhibition demonstrated that endothelial nitric oxide synthase and superoxide dismutase contributed to the protective actions of salusin-α, whereas NAD(P)H oxidase inhibition or reactive oxygen species scavenging prevented the effects of salusin-α neutralization. CONCLUSIONS: Salusin-α improves endothelium-dependent vasodilation via endothelial nitric oxide synthase mediated nitric oxide release in PA endothelial cells, and promotes endothelium-independent vasodilation while attenuating pulmonary vascular remodeling via inhibition of NAD(P)H oxidase-reactive oxygen species signaling and activation of the Nrf2/superoxide dismutase signaling. Restoring reduced salusin-α may present a novel therapeutic strategy for PH treatment.
Hypertension
· 2026 Jun · PMID 41958375
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Preeclampsia is a pregnancy-specific hypertensive disorder affecting up to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality globally. It is increasingly recognize...Preeclampsia is a pregnancy-specific hypertensive disorder affecting up to 5% of pregnancies worldwide and is one of the leading causes of maternal and fetal morbidity and mortality globally. It is increasingly recognized that preeclampsia, from both clinical and pathophysiological standpoints, is a heterogeneous disease and that several mechanisms may lead to a clinical syndrome of hypertension, systemic disease, and proteinuria. Beyond its acute obstetric consequences, preeclampsia confers a significantly increased risk of future hypertension, cardiovascular disease, chronic kidney disease, and multimorbidity. Distinct underlying pathological mechanisms at the time of pregnancy may not only define clinical presentation and subtype of preeclampsia but may also make varying contributions to future cardiovascular and kidney disease. Emerging evidence implicates cellular senescence, a state of irreversible cell-cycle arrest accompanied by a proinflammatory senescence-associated secretory phenotype, as one of the mechanisms of preeclampsia that may serve as a mechanistic link between preeclampsia, accelerated cardiovascular aging, and future cardiovascular and kidney disease. This review synthesizes current evidence supporting the role of senescence in the pathophysiology of preeclampsia, demonstrated as accelerated epigenetic aging, increased senescence burden, and mesenchymal stem cell dysfunction, and discusses how persistence of senescence and propagation of senescent cells may contribute to vascular dysfunction decades after affected pregnancies. We further explore the translational implications of senolytic and senomorphic therapies as potential disease-modifying strategies in women with a history of preeclampsia.
Long Y, Lai Y, Ren Y
… +10 more, Ma X, Li D, Chen L, Liao X, Xia T, Liu Z, Ling Z, Chen Y, Zhou H, Yin Y
Hypertension
· 2026 Jul · PMID 41954001
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BACKGROUND: The aorticorenal ganglion (ARG), an upstream component of renal sympathetic fibers, may represent a novel target for autonomic modulation in hypertension. This study evaluated the effects of adjunctive ARG ab...BACKGROUND: The aorticorenal ganglion (ARG), an upstream component of renal sympathetic fibers, may represent a novel target for autonomic modulation in hypertension. This study evaluated the effects of adjunctive ARG ablation after renal denervation (RDN) on blood pressure (BP) and its autonomic mechanisms. METHODS: Patients with uncontrolled hypertension scheduled for RDN were enrolled, and additional ablation was performed if an elevation in SBP was observed by high-frequency stimulation at the ARG region (RDN+ARG ablation). This exploratory analysis assessed the change in 24-hour average ambulatory systolic BP from baseline to 3 months. To explore the effects of ARG ablation on BP and sympathetic activity, we compared ARG ablation with RDN in a canine model. RESULTS: A total of 41 patients (n=20 RDN; n=21 RDN+ARG ablation) were enrolled. At 3 months, the reduction in 24-hour average ambulatory systolic BP from baseline was -9.7±10.8 mm Hg in the RDN group and -18.2±10.8 mm Hg in the RDN+ARG ablation group, with a between-group difference of -7.5 mm Hg (95% CI, -13.9 to -1.2 mm Hg; =0.021) after adjusting for baseline ambulatory systolic BP. No major procedure-related complications were observed in both groups. In canines, ARG ablation significantly reduced the renal sympathetic innervation and the systemic sympathetic activity compared with RDN, with enhancing SBP-lowering effect. CONCLUSIONS: These results establish the ARG as a pivotal regulator of systemic sympathetic tone and a promising therapeutic target for hypertension. Additional ARG ablation to RDN may represent a more effective interventional strategy, warranting validation in large-scale clinical trials. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT05590871.
BACKGROUND: Time in target range (TTR) reflects the proportion of time that blood pressure (BP) stays within guideline-recommended levels. However, the distribution of home BP TTR and its association with subclinical cer...BACKGROUND: Time in target range (TTR) reflects the proportion of time that blood pressure (BP) stays within guideline-recommended levels. However, the distribution of home BP TTR and its association with subclinical cerebrovascular disease in community-based populations remain unclear. METHODS: We investigated annual and seasonal TTR of Internet of Things-based home BP and its association with brain lesions on magnetic resonance imaging in a community-based cohort. Home BP was measured twice daily (morning and evening). Weekly mean BP was calculated from ≥3 valid daily readings, and TTR was defined in those with ≥2 valid weeks/season as the percentage of weeks meeting guideline-based targets (systolic and diastolic BP <135 and <85 mm Hg, respectively, for participants not receiving antihypertensive medication; <125 and <75 mm Hg, respectively, for those receiving medication). Brain lesions included ≥1 magnetic resonance imaging-detected lacunar infarct, white matter hyperintensities, cerebral microbleeds, or intracranial artery stenosis. RESULTS: Among 306 participants (mean age, 56 years; 57% women), median annual TTR was 100% (interquartile range, 92.6%-100%) in participants not receiving antihypertensive medication and 1.9% (0%-19.2%) in those receiving medication. TTR tended to be lower in winter than in summer. In Poisson regression with robust variance, adjusted for demographic, lifestyle, and clinical factors, higher TTR was associated with a lower prevalence of brain lesions (prevalence ratio per 10% higher, 0.85 [95% CI, 0.79-0.91]). The association was stronger among participants not receiving antihypertensive medication (interaction =0.047), with no heterogeneity across seasons (interaction =0.958). CONCLUSIONS: Home BP TTR may help characterize longitudinal BP control and provide complementary information regarding cerebrovascular health.
Aggarwal M, Joehanes R, Huan T
… +4 more, Courchesne P, Dupuis J, O'Connor G, Levy D
Hypertension
· 2026 Jun · PMID 41953991
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BACKGROUND: Hypertension affects one-third of adults worldwide and is largely idiopathic. Identifying protein biomarkers of hypertension may reveal underlying mechanisms and potential treatments. METHODS: We examined ass...BACKGROUND: Hypertension affects one-third of adults worldwide and is largely idiopathic. Identifying protein biomarkers of hypertension may reveal underlying mechanisms and potential treatments. METHODS: We examined associations between 2922 plasma proteins and blood pressure (BP) traits (systolic BP [SBP] and diastolic BP [DBP], and prevalent hypertension) in 45 991 UK Biobank participants with validation in 5759 FHS (Framingham Heart Study) participants. Analysis of new-onset hypertension was performed in 3995 UK Biobank participants and validated in 3073 FHS participants. Functional enrichment analysis linked proteins to biological functions and diseases. Mendelian randomization assessed causal relations between proteins using -protein quantitative trait loci as exposures and BP traits as outcomes. RESULTS: In the UK Biobank, 342 proteins were associated (false discovery rate knockoff <0.1) with SBP, 276 with DBP, and 200 with prevalent hypertension (N=24 724). In the FHS, 115 proteins were validated (Bonferroni-corrected <0.05) for SBP, 108 for DBP, and 102 for hypertension. New-onset hypertension was associated with 60 (17 validated) proteins. Mendelian randomization analyses revealed significant associations for 206, 210, and 82 proteins with SBP, DBP, and hypertension, respectively. Several of these proteins are involved in blood vessel and cardiac muscle morphogenesis, vasoconstriction, and inflammation. BP-related proteins are enriched for atherosclerotic cardiovascular, liver, and kidney diseases. NHERF2 (Na/H exchange regulatory cofactor 2) demonstrated putatively causal associations with SBP, DBP, and with prevalent and new-onset hypertension. CONCLUSIONS: This large-scale proteomic study revealed protein signatures of BP traits and hypertension risk, highlighting inflammation and cardiac and vascular remodeling processes; NHERF2 and several other proteins emerged as promising therapeutic targets.
Huang T, Peng J, Li C
… +14 more, Ren Y, Kuang Y, Zhang W, Yao Y, Wang Y, Du Z, He X, Peng Z, Li H, Zhang Y, Han J, Yu H, Liu L, Yang X
Hypertension
· 2026 Jul · PMID 41948823
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BACKGROUND: Target organ damage is crucial for hypertension risk stratification. However, the lack of sensitive assessment tools for early target organ damage in the presence of elevated blood pressure limits timely inte...BACKGROUND: Target organ damage is crucial for hypertension risk stratification. However, the lack of sensitive assessment tools for early target organ damage in the presence of elevated blood pressure limits timely intervention. This study used the retina to investigate subclinical neurovascular damage and identify early imaging biomarkers. METHODS: We monitored male spontaneously hypertensive rats and Wistar-Kyoto controls weekly from 4 to 9 weeks of age. Weekly assessments included noninvasive blood pressure and multimodal fundus imaging, including optical coherence tomography, optical coherence tomography angiography and electroretinography. Histological analyses and fluorescein fundus angiography validated structural microvascular changes and blood-retinal barrier integrity. RESULTS: The blood pressure of spontaneously hypertensive rats increased significantly from 5 weeks of age (<0.05). At the prehypertensive stage (6 weeks), spontaneously hypertensive rats exhibited decreased superficial vascular plexus density and reduced scotopic electroretinography b-wave amplitude. Fluorescein fundus angiography demonstrated that the blood-retinal barrier remained functionally intact without leakage at this stage. These microvascular and functional deficits preceded structural changes on optical coherence tomography. Subsequently, vascular damage progressed to deeper plexuses, accompanied by inner retinal thinning, apoptosis, and continued functional decline. Linear mixed-effects modeling confirmed a negative correlation between the prehypertensive stage and decreased superficial vascular density (<0.001). CONCLUSIONS: In spontaneously hypertensive rats, superficial microvascular rarefaction and inner retinal dysfunction represent the initiating pathological events, preceding blood-retinal barrier breakdown and macrovascular remodeling. Optical coherence tomography angiography-quantified superficial vascular plexus density is a sensitive and objective imaging biomarker for assessing retinal damage during the prehypertensive stage, which significantly precedes macrovascular signs.
Tsur AM, Talmy T, Hershenson R
… +17 more, Fishman B, Derazne E, Tzur D, Pinhas-Hamiel O, Vivante A, Grossman E, Furer A, Rotem RS, Shlomai G, Maor E, Danesh J, Wood AM, Di Angelantonio E, Coresh J, Afek A, Chodick G, Twig G
BACKGROUND: Adolescent blood pressure guidelines rely on expert consensus because evidence on cardiovascular outcomes is limited. This study aimed to examine the link between adolescent blood pressure indices and early c...BACKGROUND: Adolescent blood pressure guidelines rely on expert consensus because evidence on cardiovascular outcomes is limited. This study aimed to examine the link between adolescent blood pressure indices and early cardiovascular events. METHODS: We conducted a cohort study among 902 741 adolescents aged 16 to 19 years who were evaluated for mandatory service from 1979 to 2019, excluding those with preexisting cardiometabolic conditions. Individuals were followed until 50 or death or insurance loss or December 31, 2021, whichever occurred first. Exposures included baseline blood pressure and American Academy of Pediatrics categories: normal (<120/<80 mm Hg), elevated (120/<80-129/<80 mm Hg), stage 1 (130/80-139/89 mm Hg), stage 2 (≥140/90 mm Hg), and hypertension (clinical diagnosis). The primary outcome was incident cardiovascular events (ischemic heart disease or cerebrovascular disease). Hazard ratios were estimated using Cox models adjusted for demographic, socioeconomic, and clinical confounders. RESULTS: During over 18 million person-years of follow-up, 6305 cardiovascular disease events were recorded, yielding an incidence rate of 0.35 per 1000 person-years. Increased diastolic, systolic, and mean arterial blood pressure were significantly associated with increased risk. Compared with the Normal group, adjusted hazard ratios for cardiovascular disease were 1.14 (95% CI, 1.08-1.22) for stage 1, 1.31 (1.20-1.44) for stage 2, and 2.42 (1.87-3.12) for hypertension. Risk in the stage 1 category was particularly sensitive to diastolic blood pressure. CONCLUSIONS: Higher blood pressure indices during adolescence were strongly associated with an elevated risk of early cardiovascular disease, highlighting the potential need to refine current guidelines to better reflect cardiovascular risk.
Jozefczuk E, Szczepaniak P, Mikolajczyk TP
… +9 more, Nosalski R, Dziedzic M, Urbanski K, Wojciechowska E, Filip G, Stefanska M, Blyszczuk P, Guzik TJ, Siedlinski M
Hypertension
· 2026 Jul · PMID 41944022
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BACKGROUND: S1P (sphingosine-1-phosphate) signaling plays a key role in regulating the cardiovascular system. In experimental essential hypertension (HTN), expression of Sphk1 (sphingosine kinase 1), a key S1P-producing...BACKGROUND: S1P (sphingosine-1-phosphate) signaling plays a key role in regulating the cardiovascular system. In experimental essential hypertension (HTN), expression of Sphk1 (sphingosine kinase 1), a key S1P-producing enzyme, is upregulated in the vasculature. Mice with global deletion exhibit alleviated AngII (angiotensin II)-induced HTN. However, cellular mechanisms underlying this protective effect remain unclear due to pleiotropic S1P actions. METHODS: Mice with targeted deletion of in smooth muscle cells (SMCs) or endothelial cells were generated using the Cre-loxP system. To induce HTN, mice were infused with AngII (490 ng/min per kilogram for 14 days), using osmotic minipumps. Blood pressure was monitored, and vascular structure and function were assessed ex vivo using wire/pressure myography and histological analysis. To identify mechanistic pathways, RNA sequencing was performed on mouse aortas and mesenteric arteries, followed by Gene Set Enrichment Analysis and validation by RT-qPCR/Western blotting. RESULTS: SMC-specific deletion of conferred significant protection against HTN (mean systolic blood pressure±SD, 131.5±14.6 versus 168.3±14.3 mm Hg in WT control, <0.05). Endothelial cell-specific knockout developed HTN comparable to WT. Reduced systolic blood pressure in AngII-infused SMC knockout- was linked to reduced myogenic tone and decreased expression of Rock1/2 (Rho-associated protein kinase 1 and 2) in mesenteric arteries. Despite protection from HTN, mesenteric arteries of AngII-infused SMC knockout- mice were stiffer and exhibited impaired vasorelaxation, associated with excessive Fn1 (fibronectin 1) deposition. An inverse correlation between FN1 and SPHK1 protein expression was also observed in human arteries. Notably, these arterial alterations were absent in normotensive SMC knockout- mice. CONCLUSIONS: SMC-derived plays a predominant role in AngII-induced HTN by modulating myogenic tone.
Anwer TZ, Cantonwine DE, Seely EW
… +2 more, Gray KJ, McElrath TF
Hypertension
· 2026 Jul · PMID 41944012
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BACKGROUND: sFlt-1 (serum soluble fms-like tyrosine kinase-1) to PlGF (placental growth factor) can be used to predict the development of severe preeclampsia. The association between sFlt-1/PlGF during pregnancy and long...BACKGROUND: sFlt-1 (serum soluble fms-like tyrosine kinase-1) to PlGF (placental growth factor) can be used to predict the development of severe preeclampsia. The association between sFlt-1/PlGF during pregnancy and long-term risk of hypertension is unclear. METHODS: This is a retrospective cohort study of patients enrolled from 2006 to 2008 in the ongoing LIFECODES biobank. Mean sFlt-1 and PlGF levels were collected in the second half of pregnancy. Electronic medical record review identified those who developed hypertension over 15 year follow-up. Adjusted Cox proportional hazard models were used to estimate hazard ratios and 95% CI for the time to diagnosis of hypertension. RESULTS: Of the n=993 participants, n=260 (29.18%) were diagnosed with stage 1 and n=169 (17.0%) were diagnosed with stage 2 hypertension. One hundred thirteen of the participants in the database had a diagnosis of gestational hypertension or preeclampsia. A history of preeclampsia or a history of gestational hypertension was both significantly associated with developing hypertension later in life, with adjusted hazard ratios of 2.17 (95% CI, 1.44-3.28) and 3.50 (95% CI, 2.21-5.54), respectively. We observed no significant association between the hazard of developing hypertension and sFlt-1/PlGF. However, mean PlGF levels in those who remained normotensive in the follow-up were significantly higher, 546.7 pg/mL (SD=369.5), compared with those who developed hypertension, 513.7 pg/mL (SD=389.9; =0.008). CONCLUSIONS: A history of hypertensive disease of pregnancy was significantly associated with the hazard of developing HTN later in life, while elevated sFlt-1/PlGF levels were not. PlGF levels alone were significantly lower in those who developed hypertension later.
Yamada M, Griffin BR, Shi Q
… +10 more, Sambharia M, Swee ML, Good MK, Kennelty K, Faro E, Reisinger HS, Girotra S, Lund BC, Vaughan Sarrazin MS, Jalal DI
Hypertension
· 2026 Jun · PMID 41944008
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BACKGROUND: Intensive blood pressure (BP) control reduces mortality and cardiovascular disease in clinical trials. However, real-world BP measurements often differ from standardized protocols. We evaluated the impact of...BACKGROUND: Intensive blood pressure (BP) control reduces mortality and cardiovascular disease in clinical trials. However, real-world BP measurements often differ from standardized protocols. We evaluated the impact of real-world systolic BP on mortality among US Veterans. METHODS: We conducted a retrospective cohort study of Veterans with hypertension, defined by diagnostic codes, antihypertensive prescriptions, or ≥2 office BP readings ≥130/90 mm Hg in 2016 to 2017, with follow-up through March 2021. Systolic BP was treated as a time-dependent covariate and categorized into 7 groups: <110, 110-119, 120-129, 130-139, 140-149, 150-159, and ≥160 mm Hg. Discrete-time survival models assessed associations with all-cause mortality, adjusting for demographics, body mass index, and comorbidities. Stratified analyses were conducted based on cardiovascular disease and chronic kidney disease status. RESULTS: Among >2.3 million Veterans (mean age, 66 years; 36% with diabetes; 22% with cardiovascular disease; and 19% with chronic kidney disease), the lowest mortality risk was observed in those with systolic BP of 130 to 139 mm Hg. In this cohort, adjusted hazard ratios for all-cause mortality per year in each systolic BP category were 1.29 for BP <110; 1.03 for BP 110 to 119; 0.88 for BP 120 to 129; 0.83 for BP 130 to 139; 0.86 for BP 140 to 149; and 0.89 for BP 150 to 159 mm Hg, compared with a year with BP ≥160 mm Hg. These associations remained consistent across cardiovascular disease and chronic kidney disease subgroups. CONCLUSIONS: Veterans with routine systolic BP of 130 to 139 mm Hg had the lowest mortality. These findings suggest that a higher BP target may be appropriate in clinical practice, especially for older adults with comorbidities.