American Journal of Hypertension最新文献

Background: Vascular endothelial growth factor receptor inhibitors (VEGFRis) improve cancer patient survival by inhibiting tumor angiogenesis. However, VEGFRis induce treatment-limiting hypertension which has been associated with impaired vascular endothelial cell (EC) function and kidney damage. The mineralocorticoid receptor (MR) regulates blood pressure (BP) via its effects on the vasculature and the kidney. Thus, we interrogated the role of the MR in EC dysfunction, renal impairment, and hypertension in a mouse model of VEGFRi-induced hypertension using sorafenib.

Methods: EC dysfunction in mesenteric arterioles was assessed by immunoblotting for phosphorylation of endothelial nitric oxide synthase (eNOS) at serine 1177. Renal damage was measured by assessing glomerular endotheliosis histologically. BP was measured using implanted radiotelemetry.

Results: Six days of sorafenib treatment significantly impaired mesenteric resistance vessel EC function, induced renal damage, and increased BP. Pharmacologic MR blockade with spironolactone prevented the sorafenib-induced decline in eNOS phosphorylation and renal glomerular endotheliosis, without affecting systolic BP (SBP) or diastolic BP. Mice with the MR knocked out specifically in ECs (EC-MR-KO) were protected from sorafenib-induced EC dysfunction and glomerular endotheliosis, whereas smooth muscle cell-specific MR (SMC-MR) knockout mice were not. Neither EC-MR nor SMC-MR knockout affected the degree to which sorafenib increased SBP or diastolic BP.

Conclusions: These results reveal that the MR, specifically in EC but not in SMCs, is necessary for VEGFRi-induced renal and vascular injury. While ineffective at lowering SBP, these data suggest potential therapeutic benefits of MR antagonists, like spironolactone, to protect the vasculature and the kidneys from VEGFRi-induced injury.

Background: Prior studies have reported a decrease in the proportion of US adults with hypertension who had controlled blood pressure (BP).

Methods: We analyzed data from the National Health and Nutrition Examination Survey (n = 25,128, ≥18 years of age) to determine changes in BP control from 2013-2014 to 2021-2023. Hypertension was defined as systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or antihypertensive medication use. BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg.

Results: The age-adjusted prevalence of hypertension (95% CI) was 32.8% (31.2%-34.4%) in 2013-2014 and 32.0% (30.1%-33.9%) in 2021-2023. Among US adults with hypertension, the age-adjusted proportion (95% CI) with controlled BP was 54.1% (49.1%-59.2%), 48.6% (44.5%-52.7%), and 48.3% (45.8%-50.8%) in 2013-2014, 2015-2016, and 2017-2020, respectively, (P-trend = 0.058), and 51.1% (47.9%-54.3%) in 2021-2023 (P-value = 0.184 comparing 2021-2023 vs. 2017-2020). The proportion (95% CI) of US adults taking antihypertensive medication with controlled BP was 72.0% (68.5%-75.5%), 66.7% (62.9%-70.5%), and 67.8% (65.3%-70.3%) in 2013-2014, 2015-2016, and 2017-2020, respectively, (P-trend = 0.085), and 68.3% (64.8%-71.9%) in 2021-2023 (P-value = 0.654 comparing 2021-2023 vs. 2017-2020). Among non-Hispanic Black adults, BP control increased from 37.4% (95% CI 33.6%-41.1%) to 49.6% (95% CI 42.3%-56.9%) between 2017-2020 and 2021-2023 for those with hypertension (P-value = 0.005), and from 52.6% (95% CI 47.4%-57.8%) to 62.6% (95% CI 55.6%-69.7%) for those taking antihypertensive medication (P-value = 0.033). There was no difference in BP control across race/ethnicity groups in 2021-2023.

Conclusions: The decline in BP control from 2013-2014 to 2017-2020 did not continue through 2021-2023. An increase in BP control occurred from 2017-2020 and 2021-2023 among non-Hispanic Black adults.

Background: Wide pulse pressure (PP) is associated with cardiovascular events and the progression of chronic kidney disease (CKD) to kidney failure. PP naturally widens with age, but it is unclear whether the risks associated with greater PP are the same across all ages.

Methods: We used Cox proportional hazards models to investigate the association of PP with (i) atherosclerotic cardiovascular disease (ASCVD) events or death and (ii) a 50% reduction in estimated glomerular filtration rate or kidney failure in the chronic renal insufficiency cohort (CRIC). We evaluated the association of time-updated PP with these outcomes, accounting for time-updated confounders using inverse probability weighting.

Results: Among 5,621 participants with CKD, every 10-mmHg greater PP was associated with a 6% higher risk of an ASCVD event or death (hazard ratio [HR] = 1.06, 95% CI 1.04, 1.08) and 17% higher risk of the composite kidney outcome (HR = 1.17, 95% CI 1.16, 1.18). Greater PP was associated with a higher risk of ASCVD events or death among participants in the lowest age tertile (21-61 years), but a higher risk of the composite kidney outcome in the oldest age tertile (71-79 years). While wide PP in participants that experienced the primary outcomes was predominantly driven by elevated SBP, PP remained significantly associated with the composite kidney outcome across all ages and with ASCVD events or death in the first age tertile when SBP was added to the Cox regression model.

Conclusions: Our findings suggest that the mechanism by which PP is associated with adverse outcomes may differ by age.

Background: Lercanidipine, a newer-generation calcium channel blocker, is recognized for its effective antihypertensive properties and reduced side effects. This study aims to compare the effectiveness of lercanidipine and amlodipine in preventing major adverse cardiovascular events (MACE) in hypertensive patients.

Methods: A multicenter, retrospective observational study was conducted using the electronic medical records database from 3 tertiary hospitals in South Korea between 2017 and 2021. Hypertensive patients treated with either amlodipine or lercanidipine were analyzed. Propensity score matching (PSM) was utilized to minimize confounders, matching patients in a 3:1 ratio. The primary endpoint was the incidence of MACE, a composite of cardiovascular death, myocardial infarction, stroke, heart failure hospitalizations, and coronary revascularization over a 3-year follow-up period.

Results: A total of 47,640 patients were evaluated, and 6,029 patients were matched. Before PSM, the lercanidipine group had a higher cardiovascular risk (SCORE-2/SCORE-2OP value: 11.6% ± 9.2 vs. 10.9% ± 8.8, P < 0.01) and a higher incidence of MACE compared to the amlodipine group (4.1% vs. 3.4%, P < 0.01). After PSM, the incidence of MACE was numerically lower in the lercanidipine group compared to the amlodipine group (2.8% vs. 4.1%, P = 0.11), though this difference was not statistically significant. Blood pressure control remained comparable between the 2 groups over the 3-year follow-up period.

Conclusions: Lercanidipine demonstrated comparable effectiveness to amlodipine in preventing MACE among hypertensive patients. Given its comparable antihypertensive efficacy and potential for fewer side effects based on prior studies, lercanidipine may be considered a preferable option for hypertension management.

Background: Bladder dysfunction entails overactive bladder (OAB) defined as symptoms of urinary urgency, frequency, and/or nocturia with or without incontinence if there is no obvious pathology or infection or lower urinary tract symptoms that includes recognized causes of bladder dysfunction.

Methods: Literature search.

Results: Symptoms of OAB are reported in about 15% of the adult US population. This is increased 2- to 3-fold in patients with congestive heart failure (CHF), hypertension, cardiovascular disease (CVD), chronic kidney disease (CKD), or the elderly where it often accompanies prescription for short, rapid-acting loop diuretics. However, less than 2% of patients seeking care for OAB receive treatment. The fear of urinary incontinence from short, rapid-acting loop diuretics may contribute to medication nonadherence and less well-controlled, apparently resistant hypertension. The bladder contracts to rapid stretch. Thus, less rapid-acting diuretics such as thiazides or extended-release formulations of loop diuretics may be preferable for those with bladder dysfunction. Alternatively, the use of a mineralocorticosteroid receptor antagonist, angiotensin receptor antagonist/neprilysin inhibitor, or sodium glucose-linked transport type 2 inhibitor may allow a reduction in the dose of a short, rapid-acting loop diuretic for those with bladder dysfunction.

Conclusions: A worsening of symptoms from bladder dysfunction by short, rapid-acting loop diuretics occurs frequently in patients with CVD, CHF, hypertension, and CKD where it can contribute to impaired quality of life and poor adherence and thereby to worsening outcomes.

Hypertension is a growing concern worldwide, with increasing prevalence rates in both children and adults. Most cases of hypertension are multifactorial, with various genetic, environmental, socioeconomic, and lifestyle influences. However, monogenic hypertension, a blanket term for a group of rare of hypertensive disorders, is caused by single-gene mutations that are typically inherited in an autosomal dominant fashion, and ultimately disrupt normal blood pressure regulation in the kidney or adrenal gland. Being able to recognize and understand the pathophysiology of these rare disorders is critical for properly diagnosing hypertension, particularly in children and young adults, as treating each form of monogenic hypertension requires specific and targeted treatment approaches. A scoping literature review was conducted on the available knowledge regarding each of the disorders currently categorized as forms of monogenic hypertension. This narrative review serves to highlight the epidemiology, pathophysiology, clinical presentation, recent case reports, and most current methods of evaluation and treatment for familial hyperaldosteronism types I-IV, Gordon Syndrome. Liddle Syndrome, syndrome of apparent mineralocorticoid excess, congenital adrenal hyperplasia, Geller syndrome, and brachydactyly type E. Recent and future advances in genetic analysis techniques will further enhance the diagnosis and early management of these disorders, preventing the consequences of uncontrolled hypertension.

Background: To evaluate the impact of daytime, nighttime and nocturnal blood pressure (BP) fall on heart failure (HF).

Methods: We analyzed data of five cohorts including 15,526 treated hypertensive patients, experiencing 625 HF events, by study-level meta-analysis. The pooled hazard ratios (HR) and 95% confidence intervals (CI) for 1-SD increase in BP parameters or per group were calculated.

Results: When individually analyzed after adjustment for covariates, clinic systolic BP (SBP) (HR 1.20, 95% CI 1.01-1.43), daytime SBP (HR 1.34, 95% CI 1.06-1.70), nighttime SBP (HR 1.43, 95% CI 1.20-1.71), nighttime diastolic BP (DBP) (HR 1.26, 95% CI 1.05-1.52), % of nocturnal SBP fall (HR 0.81, 95% CI 0.75-0.88) and nondipping (HR 1.64, 95% CI 1.54-1.98) were associated with HF. If daytime or nighttime BPs were further adjusted for clinic BP results remained similar. When clinic, daytime and nighttime BPs were mutually adjusted, nighttime SBP (HR 1.43, 95% CI 1.27-1.61) and nighttime DBP (HR 1.37, 95% CI 1.14-1.64) remained associated with outcome. Heterogeneity across cohorts was explained by BP, sex and follow-up duration. In sensitivity analyses, for daytime and nighttime BP, no study had relevant influential effect on overall estimates. Looking for publication bias and adjusting for missing studies by Duval and Tweedie's method, clinic SBP lost significance but daytime SBP, and nighttime SBP and DBP remained significantly associated with HF.

Conclusions: daytime and nighttime BPs are stronger than clinic BP in predicting HF, nighttime BP is stronger than daytime BP and a reduced nocturnal BP fall is associated with outcome.

Background: Polo-like kinase 2 (PLK2) is associated with cardiac fibrosis in patients with atrial fibrillation. However, the role of PLK2 in sepsis-induced cardiac injury has not been fully elucidated. We hypothesize that PLK2 may participate in the progression of sepsis-induced cardiac injury.

Methods: We established a cardiac injury model in C57BL6 mice by injecting lipopolysaccharide (LPS). PLK2 was overexpressed in mice using an adeno-associated virus 9 vector. Cardiac function was evaluated using echocardiography 12 hours after the LPS injection. H9c2 cells were transfected with a PLK2 small interfering RNA. PLK2 was downregulated in the hearts of LPS-treated mice and LPS-stimulated H9c2 cardiomyocytes.

Results: Mice in the LPS group presented aggravated cardiac injury and a reduced survival rate with increased cardiac inflammatory responses and oxidative stress. Moreover, PLK2 relieved LPS-induced cardiac injury and increased the survival rate of the mice by weakening the inflammatory response and decreasing oxidative stress. Moreover, the LPS-induced increase in ferroptosis was inhibited by PLK2 overexpression.LPS caused an increase in inflammation and cell injury in H9c2 cardiomyocytes, and PLK2 silencing aggravated LPS-induced cell injury, inflammation, and oxidative stress. Furthermore, PLK2 overexpression increased the expression levels of the antiferroptotic proteins solute carrier family 7 member 11, glutathione peroxidase 4, and ferritin in heart tissue. PLK2 increased the nuclear NRF2 expression level. Moreover, the overexpression of PLK2 increased the phosphorylation of glycogen synthase kinase 3β and promoted the nuclear translocation of NRF2. NRF2 overexpression relieved cardiac injury in mice induced with LPS. However, NRF2 mitigated the deteriorating effects of PLK2 knockdown in the mouse heart.

Conclusion: PLK2 ameliorated LPS-induced cardiac injury by blocking cardiomyocyte ferroptosis through NRF2 regulation.