Hypertension最新文献

Background: Although the concept of the intrarenal renin-angiotensin system (RAS) in renal disease is well-described in the literature, the precise pathogenic role and mechanism of this local system have not been directly assessed in the absence of confounding influence from the systemic RAS. The present study used novel mouse models of collecting duct (CD)-specific deletion of (pro)renin receptor (PRR) or renin together with pharmacological inhibition of soluble PRR production to unravel the precise contribution of the intrarenal RAS to renal injury induced by unilateral ureteral obstruction.

Methods: We examined the impact of CD-specific deletion of PRR, CD-specific deletion of renin, and S1P (site-1 protease) inhibitor PF429242 treatment on renal fibrosis and inflammation and the indices of the intrarenal RAS in a mouse model of unilateral ureteral obstruction.

Results: After 3 days of unilateral ureteral obstruction, the indices of the intrarenal RAS including the renal medullary renin content, activity and mRNA expression, and Ang (angiotensin) II content in obstructed kidneys of floxed mice were all increased. That effect was reversed with CD-specific deletion of PRR, CD-specific deletion of renin, and PF429242 treatment, accompanied by consistent improvement in renal fibrosis and inflammation. On the other hand, renal cortical renin levels were unaffected by unilateral ureteral obstruction, irrespective of the genotype. Similar results were obtained via pharmacological inhibition of S1P, the key protease for the generation of soluble PRR.

Conclusions: Our results reveal that PRR-dependent/soluble PRR-dependent activation of CD renin represents a key determinant of the intrarenal RAS and, thus, obstruction-induced renal inflammation and fibrosis.

More than 1.5 billion people worldwide have arterial hypertension. Hypertension increases the risks of death and cardiovascular disease, such as atrial fibrillation and heart failure. The autonomic nervous system plays an essential role in hypertension development and disease progression. While lifestyle factors, such as obesity and obstructive sleep apnea, predispose to hypertension by increasing sympathetic activity, hypertension itself maintains the autonomic nervous imbalance, providing the substrate for atrial fibrillation and heart failure. Therefore, autonomic nervous system modulation either by direct targeting or indirect treatment of comorbidities has the potential to treat both hypertension and related atrial and ventricular end-organ damage. We discuss interventions for the modulation of the autonomic nervous system for hypertension and related cardiac end-organ damage, including pharmacological adrenergic beta-receptor blockade, renal denervation, carotid baroreceptor stimulation, low-level vagal stimulation, and ablation of ganglionated plexuses. In summary, the literature suggests that targeting the autonomic nervous system potentially represents a therapeutic approach to prevent atrial and ventricular end-organ damage in patients with hypertension. However, clinical trials specifically designed to test the effect of autonomic modulation on hypertension-mediated cardiac end-organ damage are scarce.

Background: Left ventricular global longitudinal strain (LV GLS) on echocardiography is a sensitive yet clinically significant marker of myocardial dysfunction. Reduced LV GLS is prevalent in adults with chronic kidney disease and hypertension and is associated with adverse cardiovascular outcomes. It may be a biomarker of chronic kidney disease-associated myocardial dysfunction in children, but data are limited. Our objective was to describe LV GLS in the CKiD study (Chronic Kidney Disease in Children) and to examine the association between blood pressure (BP) and reduced LV GLS.

Methods: A single apical 4-chamber view was used to estimate LV GLS. Our main analyses examined the association of clinic BP with the absolute value of LV GLS and LV GLS dichotomized at 16. Sensitivity analyses using 24-hour ambulatory BP monitoring data were also performed. Generalized estimating equations were used to account for within-person correlation and to estimate robust SEs for 95% CIs. Covariates in adjusted models included: age, sex, race, estimated glomerular filtration rate, urine protein, hemoglobin, left ventricular hypertrophy, and the use of renin-angiotensin system inhibitors.

Results: LV GLS was measured in 962 person-visits. A total of 77 assessments had an LV GLS <16. In adjusted models, both clinic systolic BP (odds ratio, 1.02 [95% CI, 1.01-1.03]) and diastolic BP (odds ratio, 1.02 [95% CI, 1.00-1.03]) percentiles were associated with LV GLS <16. Having awake or nighttime diastolic BP hypertension on ambulatory BP monitoring was significantly associated with a lower absolute value of LV GLS.

Conclusions: Office systolic and diastolic hypertension was associated with diminished LV GLS. Only diastolic hypertension detected on ambulatory BP monitoring was associated with lower LV GLS.

Background: Alcohol consumption is associated with cardiovascular disease, and the sympathetic nervous system is a suspected mediator. The present study investigated sympathetic transduction of muscle sympathetic nerve activity to blood pressure at rest and in response to cold pressor test following evening binge alcohol or fluid control, with the hypothesis that sympathetic transduction would be elevated the morning after binge alcohol consumption.

Methods: Using a randomized, fluid-controlled (FC) crossover design, 26 healthy adults (12 male, 14 female, 25±6 years, 27±4 kg/m²) received an evening binge alcohol dose and a FC. All participants underwent next-morning autonomic-cardiovascular testing consisting of muscle sympathetic nerve activity, beat-to-beat blood pressure, and heart rate during a 10-minute rest period and a 2-minute cold pressor test. Sympathetic transduction was assessed at rest and during the cold pressor test in both experimental conditions.

Results: Evening alcohol increased heart rate (FC: 60±9 versus alcohol: 64±9 bpm; P=0.010) but did not alter resting mean arterial pressure (FC: 80±6 versus alcohol: 80±7 mm Hg; P=0.857) or muscle sympathetic nerve activity (FC: 18±9 versus alcohol: 20±8 bursts/min; P=0.283). Sympathetic transduction to mean arterial pressure (time×condition; P=0.003), diastolic blood pressure (time×condition; P=0.010), and total vascular conductance (time×condition; P=0.004) was augmented after alcohol at rest. Sympathetic transduction during the cold pressor test was also elevated after evening binge alcohol consumption (P=0.002).

Conclusions: These findings suggest that evening binge alcohol consumption leads to augmented morning-after sympathetic transduction of muscle sympathetic nerve activity to blood pressure, highlighting a new mechanism whereby chronic or excessive alcohol consumption contributes to cardiovascular disease progression via altered end-organ responsiveness to sympathetic neural outflow.

Registration: URL: https://clinicaltrials.gov/study/NCT03567434; Unique identifier: NCT03567434.

Low-renin hypertension is common and affects 1 in 4 people with hypertension. Understanding the different causes and management of low-renin hypertension is becoming increasingly relevant as renin measurements are more widely ordered in clinical practice. Importantly, many people with low-renin hypertension do not fit traditional definitions of known causes, and the approach to management of these people is not unclear. This review provides an overview of our evolving understanding of the causes of low-renin hypertension, the expanding spectrums of pathophysiology, key differentiating characteristics, distinct management strategies, and highlights our knowledge gaps. It is important to distinguish the underlying pathophysiology of an individual with low-renin hypertension to individualize treatment.

Background: Hypoperfusion due to blood pressure (BP) reduction is a potential mechanism of cerebral ischemia after intracerebral hemorrhage. However, prior evaluations of the relationship between BP reduction and ischemia have been conflicting. Untreated chronic hypertension is common in intracerebral hemorrhage and alters cerebral autoregulation. We hypothesized that the risk of diffusion-weighted imaging (DWI) hyperintensities from acute BP reduction is modified by premorbid BP control.

Methods: Individuals enrolled in the ERICH study (Ethnic/Racial Variations of Intracerebral Hemorrhage) from 2010 to 2015 were categorized as untreated, treated, or nonhypertensive based on preintracerebral hemorrhage diagnosis and antihypertensive medication use. The percent reduction of systolic BP (SBP) was calculated between presentation and 24 hours from admission. The primary outcome was the presence of DWI lesions. Using logistic regression, we tested the association between chronic hypertension status, SBP reduction, and their interaction with DWI lesion presence.

Results: From 3000 participants, 877 with available magnetic resonance imaging met inclusion (mean age, 60.5±13.3 years; 42.5% women). DWI lesions were detected in 25.9%. Untreated, treated, and no hypertension accounted for 32.6%, 47.9%, and 19.5% of cases, respectively. SBP reduction was not directly associated with DWI lesions; however, an interaction effect was observed between SBP reduction and chronic hypertension status (P=0.036). Nonhypertensive subjects demonstrated a linear risk of DWI lesion presence with greater SBP reduction, whereas untreated hypertension demonstrated a stable risk across a wide range of SBP reduction (P=0.023).

Conclusions: Premorbid BP control, especially untreated hypertension, may influence the relationship between DWI lesions and acute BP reduction after intracerebral hemorrhage.

Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01202864.

Background: Diagnosis of primary aldosteronism (PA) is complicated by the need to withdraw antihypertensive medications that interfere with test results, particularly renin. This study examined whether machine learning-based steroid-probability scores offer a renin measurement-independent approach for testing less prone to interference than the aldosterone-to-renin ratio (ARR).

Methods: This prospective multicenter cohort study involved the use of plasma steroidomics and the ARR in 839 patients tested for PA, including 190 with and 578 without PA (71 indeterminate). Receiver operating characteristic curves for steroid-probability scores and the ARR were examined with and without interfering medications. Impacts of individual medications on plasma aldosterone, 18-oxocortisol, 18-hydroxycortisol, steroid-probability scores, renin, and ARRs were examined by multivariable and paired analyses in patients with and without PA.

Results: Receiver operating characteristic curves indicated a significant impact of interfering antihypertensive medications on the diagnostic performance of the ARR and minimal impact on steroid-probability scores. Mineralocorticoid receptor antagonists increased plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol in patients without PA and resulted in false-positive test results for steroid-probability scores and false-negative results for the ARR. Diuretics increased aldosterone, 18-oxocortisol, and steroid-probability scores in patients without PA, whereas angiotensin-converting enzyme inhibitors decreased aldosterone, steroid-probability scores, and ARRs. Beta-adrenoceptor blockers, dihydropyridine calcium channel blockers, and angiotensin receptor blockers had negligible impact on mineralocorticoids and steroid-probability scores.

Conclusions: Among antihypertensive drugs that impact plasma aldosterone, 18-oxocortisol, and 18-hydroxycortisol, mineralocorticoid receptor antagonists stood out as a cause of false-positive results for derived steroid-probability scores. Other antihypertensives have minimal or no impact, an advantage for use of steroid-probability scores over the ARR when those medications cannot be withdrawn.

Registration: URL: https://drks.de/search/en/trial/DRKS00017084; Unique identifier: DRKS00017084.

Background: Home blood pressure (BP) is more closely associated with cardiovascular event risk than office BP, but cardiovascular risk prediction based on home BP variability is lacking. This study developed a simple cardiovascular event prediction score, including home BP variability data, from the J-HOP study (Japan Morning Surge-Home Blood Pressure).

Methods: The J-HOP study extended follow-up from December 2017 to May 2018 generated the study data set (4231 patients). Cardiovascular events included fatal/nonfatal stroke (n=94), coronary heart disease (n=124), heart failure (n=42), and aortic dissection (n=8). Cox proportional hazards models were used to predict overall cardiovascular risk. Potential covariates included age, sex, body mass index, smoking, history of diabetes, statin use, history of cardiovascular disease, total cholesterol:high-density lipoprotein cholesterol ratio, office systolic BP (SBP), mean of morning-evening average (MEave), home SBP, and average real variability of MEave home SBP. A risk score and models were constructed, and model performance was assessed.

Results: Model performance was best when average real variability of MEave SBP was included (C statistic, 0.760). The risk score assigns points for age (5-year bands), sex, cardiovascular disease history, high-density lipoprotein cholesterol, mean MEave home SBP, and average real variability of MEave home SBP. Estimated 10-year cardiovascular risk ranged from ≤0.6% (score ≤0) to >32% (score ≥26). Calibration 2 statistics values for the model (2.66) and risk score (5.29) indicated excellent goodness of fit.

Conclusions: This simple cardiovascular disease prediction algorithm, including day-by-day home BP variability, could be used as part of a home BP-centered approach to hypertension management in clinical practice.