Publications by authors named "Michel Azizi"

208 Publications

Feasibility of Imaging-Guided Adrenalectomy in Young Patients With Primary Aldosteronism.

Hypertension 2022 01 17;79(1):187-195. Epub 2021 Nov 17.

3rd Department of Medicine, Charles University Prague, General Hospital, Czech Republic (J.W., Z.K.).

Many of the patients with primary aldosteronism (PA) are denied curative adrenalectomy because of limited availability or failure of adrenal vein sampling. It has been suggested that adrenal vein sampling can be omitted in young patients with a unilateral adrenal nodule, who show a florid biochemical PA phenotype. As this suggestion was based on a very low quality of evidence, we tested the applicability and accuracy of imaging, performed by computed tomography and/or magnetic resonance, for identification of unilateral PA, as determined by biochemical and/or clinical cure after unilateral adrenalectomy. Among 1625 patients with PA submitted to adrenal vein sampling in a multicenter multiethnic international study, 473 were ≤45 years of age; 231 of them had exhaustive imaging and follow-up data. Fifty-three percentage had a unilateral adrenal nodule, 43% had no nodules, and 4% bilateral nodules. Fifty-six percentage (n=131) received adrenalectomy and 128 were unambiguously diagnosed as unilateral PA. A unilateral adrenal nodule on imaging and hypokalemia were the strongest predictors of unilateral PA at regression analysis. Accordingly, imaging allowed correct identification of the responsible adrenal in 95% of the adrenalectomized patients with a unilateral nodule. The rate raised to 100% in the patients with hypokalemia, who comprised 29% of the total, but fell to 88% in those without hypokalemia. Therefore, a unilateral nodule and hypokalemia could be used to identify unilateral PA in patients ≤45 years of age if adrenal vein sampling is not easily available. However, adrenal vein sampling remains indispensable in 71% of the young patients, who showed no nodules/bilateral nodules at imaging and/or no hypokalemia. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01234220.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.18284DOI Listing
January 2022

Blood pressure-lowering medicines implemented in 12 African countries: the cross-sectional multination EIGHT study.

BMJ Open 2021 Dec 2;11(12):e049632. Epub 2021 Dec 2.

Department of Pharmacy, St Antoine Hospital, AP-HP Sorbonne Université, Paris, France.

Objective: In Africa, the number of patients with hypertension is expected to reach 216.8 million by 2030. Large-scale data on antihypertensive medications used in Sub-Saharan Africa (SSA) are scarce.Here, we describe antihypertensive drug strategies and identify treatment factors associated with blood pressure (BP) control in 12 Sub-Saharan countries.

Setting: Outpatient consultations for hypertension in urban tertiary cardiology centres of 29 hospitals from 17 cities across 12 SSA countries between January 2014 and November 2015.

Participants: Patients ≥18 years of age with hypertension were enrolled at any visit during outpatient consultations in the cardiology departments MAIN OUTCOME MEASURE: We collected BP levels, demographic characteristics and antihypertensive treatment use (including traditional medicine) of patients with hypertension attending outpatient visits. BP control was defined as seated office BP <140/90 mm Hg. We used logistic regression with a random effect on countries to assess factors of BP control.

Results: Overall, 2198 hypertensive patients were included and a total of 96.6% (n=2123) were on antihypertensive medications. Among treated patients, 653 (30.8%) patients received a monotherapy by calcium channel blocker (n=324, 49.6%), renin-angiotensin system blocker (RAS) (n=126, 19.3%) or diuretic (n=122, 18.7%). Two-drug strategies were prescribed in 927 (43.6%) patients including mainly diuretics and RAS (n=327, 42% of two-drug strategies). Prescriptions of three-drugs or more were used in 543 (25.6%) patients. Overall, among treated patients, 1630 (76.7%) had uncontrolled BP, of whom 462 (28.3%) had BP levels ≥180/110 mm Hg, mainly in those on monotherapy. After adjustment for sociodemographic factors, the use of traditional medicine was the only factor significantly associated with uncontrolled BP (OR 1.72 (1.19 to 2.49) p<0.01).

Conclusion: Our study provided large-scale data on antihypertensive prescriptions in the African continent. Among patients declared adherent to drugs, poor BP control was significantly associated with the use of traditional medicine.
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http://dx.doi.org/10.1136/bmjopen-2021-049632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8640662PMC
December 2021

Aetiological classification and prognosis in patients with heart failure with preserved ejection fraction.

ESC Heart Fail 2021 Nov 29. Epub 2021 Nov 29.

Université de Paris, INSERM, PARCC, Paris, F-75006, France.

Aims: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with various causes that may influence prognosis.

Methods And Results: We extracted the electronic medical records for 2180 consecutive patients hospitalized between 2016 and 2019 for decompensated heart failure. Using a text mining algorithm looking for a left ventricular ejection fraction ≥50% and plasma brain natriuretic peptide level >100 pg/mL, we identified 928 HFpEF patients. We screened for a prevailing cause of HFpEF according to European guidelines and found that 418 (45.0%) patients had secondary HFpEF due to either myocardial (n = 125, 13.5%) or loading condition abnormalities (n = 293, 31.5%), while the remaining 510 (55.0%) patients had idiopathic HFpEF. We assessed the association between the causes of HFpEF and survival collected up to 31 December 2020 using Cox proportional hazards analysis. Even though patients with idiopathic HFpEF were older, frequently female, and had frequent co-morbidities and a higher crude mortality rate compared with secondary HFpEF patients, their prognosis was similar after adjustment for age and sex. Unsupervised clustering analysis revealed three main phenogroups with different distribution of idiopathic vs. secondary HFpEF. The phenogroup with the highest proportion of idiopathic HFpEF (69%) had (i) an excess rate of non-cardiac co-morbidities including chronic obstructive pulmonary disease (31%) or obesity (41%) and (ii) a better prognosis compared with the two other phenogroups enriched with secondary HFpEF.

Conclusions: Aetiological classification provides clinical and prognostic information and may be useful to better decipher the clinical heterogeneity of HFpEF.
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http://dx.doi.org/10.1002/ehf2.13717DOI Listing
November 2021

Nonadherence in Hypertension: How to Develop and Implement Chemical Adherence Testing.

Hypertension 2022 01 5;79(1):12-23. Epub 2021 Nov 5.

Renal Unit, Heartlands Hospital, Birmingham and Warwick Medical School, University of Warwick, Coventry, United Kingdom (I.D.).

Nonadherence to antihypertensive medication is common, especially in those with apparent treatment-resistant hypertension (true treatment-resistant hypertension requires exclusion of nonadherence), and its routine detection is supported by clinical guidelines. Chemical adherence testing is a reliable and valid method to detect adherence, yet methods are unstandardized and are not ubiquitous. This article describes the principles of chemical adherence testing for hypertensive patients and provides a set of recommendations for centers wishing to develop the test. We recommend testing should be done in either of two instances: (1) in those who have resistant hypertension or (2) in those on 2 antihypertensives who have a less than 10 mm Hg drop in systolic blood pressure on addition of the second antihypertensive medication. Furthermore, we recommend that verbal consent is secured before undertaking the test, and the results should be discussed with the patient. Based on medications prescribed in United Kingdom, European Union, and United States, we list top 20 to 24 drugs that cover >95% of hypertension prescriptions which may be included in the testing panel. Information required to identify these medications on mass spectrometry platforms is likewise provided. We discuss issues related to ethics, sample collection, transport, stability, urine versus blood samples, qualitative versus quantitative testing, pharmacokinetics, instrumentation, validation, quality assurance, and gaps in knowledge. We consider how to best present, interpret, and discuss chemical adherence test results with the patient. In summary, this guidance should help clinicians and their laboratories in the development of chemical adherence testing of prescribed antihypertensive drugs.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17596DOI Listing
January 2022

Genetic investigation of fibromuscular dysplasia identifies risk loci and shared genetics with common cardiovascular diseases.

Nat Commun 2021 10 15;12(1):6031. Epub 2021 Oct 15.

Department of Biostatistics and Center for Statistical Genetics, University of Michigan School of Public Health, Ann Arbor, MI, USA.

Fibromuscular dysplasia (FMD) is an arteriopathy associated with hypertension, stroke and myocardial infarction, affecting mostly women. We report results from the first genome-wide association meta-analysis of six studies including 1556 FMD cases and 7100 controls. We find an estimate of SNP-based heritability compatible with FMD having a polygenic basis, and report four robustly associated loci (PHACTR1, LRP1, ATP2B1, and LIMA1). Transcriptome-wide association analysis in arteries identifies one additional locus (SLC24A3). We characterize open chromatin in arterial primary cells and find that FMD associated variants are located in arterial-specific regulatory elements. Target genes are broadly involved in mechanisms related to actin cytoskeleton and intracellular calcium homeostasis, central to vascular contraction. We find significant genetic overlap between FMD and more common cardiovascular diseases and traits including blood pressure, migraine, intracranial aneurysm, and coronary artery disease.
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http://dx.doi.org/10.1038/s41467-021-26174-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8521585PMC
October 2021

Cardiometabolic Disorders and the Risk of Critical COVID-19 as Compared to Influenza Pneumonia.

J Clin Med 2021 Oct 8;10(19). Epub 2021 Oct 8.

Université de Paris, F-75006 Paris, France.

We aimed to compare the influence of cardiometabolic disorders on the incidence of severe COVID-19 vs. non-COVID pneumonia. We included all consecutive patients admitted with SARS-CoV-2-positive pneumonia between 12 March 2020 and 1 April 2020 and compared them to patients with influenza pneumonia hospitalized between December 2017 and December 2019 at the same tertiary hospital in Paris. Patients with COVID-19 were significantly younger and more frequently male. In the analysis adjusted for age and sex, patients with COVID-19 were more likely to be obese (adjOR: 2.25; 95% CI 1.24-4.09; = 0.0076) and receive diuretics (adjOR: 2.13; 95% CI 1.12-4.03; = 0.021) but were less likely to be smokers (adjOR: 0.40; 95% CI 0.24-0.64; = 0.0002), have COPD (adjOR: 0.25; 95% CI 0.11-0.56; = 0.0008), or have a previous or active cancer diagnosis (adjOR: 0.54, 95% CI 0.32-0.91; = 0.020). The rate of ICU admission was significantly higher in patients with COVID-19 (32.4% vs. 5.2% < 0.0001). Obesity was significantly associated with the risk of direct ICU admission in patients with COVID-19 but not in patients with influenza pneumonia. Likewise, pre-existing hypertension was significantly associated with mortality in patients with COVID-19 but not in patients with influenza pneumonia. Cardiometabolic disorders differentially influenced the risk of presenting with severe COVID-19 or influenza pneumonia.
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http://dx.doi.org/10.3390/jcm10194618DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8509116PMC
October 2021

Renal artery variations in patients with mild-to-moderate hypertension from the RADIANCE-HTN SOLO trial.

Cardiovasc Revasc Med 2021 Sep 30. Epub 2021 Sep 30.

Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.

Purpose: To assess the variability of renal artery (RA) anatomy and presence of RA-pathology in patients with mild-to-moderate hypertension enrolled in the RADIANCE-HTN SOLO trial.

Background: RADIANCE-HTN SOLO was a multicenter, international, blinded, randomized, sham-controlled trial evaluating ultrasound-based endovascular renal denervation (RDN) in patients with mild-to-moderate hypertension while off antihypertensive medications.

Methods: Eligible subjects had pre-randomization renal CT- or MR- angiography (CTA, MRA) to confirm anatomic suitability and to define RA ablation sites. All images were sent for independent review for evaluation of RA anatomy and other vascular pathology.

Results: A total of 324 patients underwent RA imaging (282 CTA and 42 MRA). Of those, 178 had simple anatomy with a single left and single right RA with mean diameters of 5.4 ± 0.9 and 5.1 ± 0.8 mm and mean lengths of 40.0 ± 12.9 and 52.0 ± 13.1 mm, respectively. Twenty-seven patients (8.3%) had unilateral or bilateral dual RAs with mean diameters of 4.0 ± 0.9 mm on the left and 3.9 ± 0.9 mm on the right. Forty percent (129/324) of patients had at least 1 accessory RA, with mean accessory diameters of 2.4 ± 0.8 mm on the left and 2.3 ± 0.8 mm on the right. Twenty-eight patients (8.6%) had at least 1 short (<25 mm) main RA. Incidental findings included: 9 patients (2.8%) with atherosclerotic RA stenosis ≥30%, 9 patients (2.8%) with fibromuscular dysplasia of RA and 2 patients (0.6%) with kidney and adrenal gland tumors.

Conclusions: Pre-procedure CTA or MRA imaging is a valuable aid in assessing RA anatomy prior to RDN because of variable RA anatomy. CTA or MRA may detect RA lesions, and renal or adrenal tumors which may need additional workup prior to consideration of RDN.

Clinical Trial Registration: ClinicalTrials.gov NCT02649426.
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http://dx.doi.org/10.1016/j.carrev.2021.09.008DOI Listing
September 2021

Urine N-acetyl-Ser-Asp-Lys-Pro measurement as a versatile biomarker to assess adherence to angiotensin-converting enzyme inhibitors.

J Hypertens 2022 Feb;40(2):348-355

INSERM UMRS970.

Background: Poor adherence to treatment is a major health issue in hypertension. The large number of drugs to be detected limits the implementation of chemical adherence testing by liquid chromatography/mass spectrometry (LC-MS/MS). AcSDKP, a peptide accumulating in the presence of angiotensin-converting-enzyme inhibitor (ACEI) treatment, has been validated as a proven marker of adherence by enzyme-linked immunosorbent assay. Our aim was to validate urine measurements of AcSDKP compared with active metabolites of various ACEI, measured simultaneously by LC-MS/MS.

Method: We first studied the time-dependent relationships between urinary perindoprilat and AcSDKP in a pharmacokinetic/pharmacodynamic study in healthy volunteers. We then compared the sensitivity and specificity of urinary AcSDKP vs. three ACEI active metabolites (enalaprilat, perindoprilat, ramiprilat) taken as reference to detect nonadherence in spot urine samples from a prospective cohort of hypertensive outpatients.

Results: The urinary excretion profiles of AcSDKP and perindoprilat were similar, exhibited a significant correlation, and showed excellent agreement in healthy volunteers. In patients, we found a similar agreement between AcSDKP and the three ACEI metabolites urinary concentrations. The sensitivity and specificity for adherence assessment of urine AcSDKP was 92.2 and 100%, respectively. We observed a difference in the evaluation of good adherence between ACEI metabolites (85.7%) and AcSDKP (79.0%) because of discrepancies in samples where AcSDKP reached undetectability quicker than ACEI metabolites. This characteristic of AcSDKP is of particular interest and could better reflect the true adherence status of patients.

Conclusion: Overall, spot urine AcSDKP measurement by LC-MS/MS is a reliable marker of the intake of ACEI treatment and could substitute ACEI metabolites detection.
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http://dx.doi.org/10.1097/HJH.0000000000003018DOI Listing
February 2022

Beyond Atherosclerosis and Fibromuscular Dysplasia: Rare Causes of Renovascular Hypertension.

Hypertension 2021 09 30;78(4):898-911. Epub 2021 Aug 30.

Department of Hypertension, National Institute of Cardiology, Warsaw, Poland (A.P., P.D., M.J., A.J.).

Renovascular hypertension is one of the most common forms of secondary hypertension. Over 95% of cases of renovascular hypertension are due either to atherosclerosis of the main renal artery trunks or to fibromuscular dysplasia. These two causes of renal artery stenosis have been extensively discussed in recent reviews and consensus. The aim of the current article is to provide comprehensive and up-to-date information on the remaining causes. While these causes are rare or extremely rare, etiologic and differential diagnosis matters both for prognosis and management. Therefore, the clinician cannot ignore them. For didactic reasons, we have grouped these different entities into stenotic lesions (neurofibromatosis type 1 and other rare syndromes, dissection, arteritis, and segmental arterial mediolysis) often associated with aortic coarctation and other arterial abnormalities, and nonstenotic lesions, where hypertension is secondary to compression of adjacent arteries and changes in arterial pulsatility (aneurysm) or to the formation of a shunt, leading to kidney ischemia (arteriovenous fistula). Finally, thrombotic disorders of the renal artery may also be responsible for renovascular hypertension. Although thrombotic/embolic lesions do not represent primary vessel wall disease, they are characterized by frequent macrovascular involvement. In this review, we illustrate the most characteristic aspects of these different entities responsible for renovascular hypertension and discuss their prevalence, pathophysiology, clinical presentation, management, and prognosis.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415524PMC
September 2021

Plasma renin and aldosterone concentrations related to endovascular ultrasound renal denervation in the RADIANCE-HTN SOLO trial.

J Hypertens 2022 Feb;40(2):221-228

Université de Paris.

Objective: The RADIANCE-HTN SOLO trial demonstrated a greater reduction in daytime ambulatory SBP at 2 months by endovascular ultrasound renal denervation than sham procedure. We hypothesized that plasma renin and aldosterone concentrations would be associated with the SBP response to renal denervation.

Methods: Hypertensive patients were randomized to renal denervation (n = 74) or sham (n = 72) after a 4-week washout of antihypertensive medications. In a 53-patient subset, 2-month and 6-month plasma renin and aldosterone concentration were measured. Dietary sodium was not controlled.

Results: Mean age of the 29 treatment and 24 sham patients was 54 years; 62% were men; 17% black. Daytime ambulatory SBP fell in the denervation but not the sham group at 2 months (-7.8 ± 10.7 vs. -0.1 ± 10.1 mmHg; P = 0.048). Baseline plasma renin and aldosterone concentrations were in the low-normal range, did not change significantly at 2 months in either group and did not predict response to renal denervation. At 6 months, after the addition of antihypertensive medications, there was a significant rise in renin in the sham but not the denervation group.

Conclusion: Although renal denervation but not sham resulted in a decrease in daytime ambulatory SBP at 2 months, renin and aldosterone concentrations did neither predict the BP response to renal denervation; nor did they fall after denervation. A rise in renin at 6 months in the sham group likely represents confounding from antihypertensive medications. Whether the BP-lowering effect of renal denervation depends on reducing local intrarenal renin release requires further study.
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http://dx.doi.org/10.1097/HJH.0000000000002994DOI Listing
February 2022

Hypertension healthcare professional beliefs and behaviour regarding patient medication adherence: a survey conducted among European Society of Hypertension Centres of Excellence.

Blood Press 2021 10 14;30(5):282-290. Epub 2021 Aug 14.

Institute of Clinical Pharmacology and Toxicology, Humboldt-Universität zu Berlin, Berlin, Germany.

Purpose: Little is known on the beliefs, perceptions and practices of hypertension specialists in addressing non-adherence to therapy. Therefore, a survey was undertaken amongst healthcare professionals (HCPs) managing hypertension in the European Society of Hypertension (ESH) Centres of Excellence.

Materials And Methods: Cross-sectional data were obtained between December 2020 and April 2021 using an online anonymous structured questionnaire including 26 questions/136 items, that was sent to all ESH Excellence centres.

Results: Overall 67 from 187 centres (37.3%) responded and 200 HCPs from 30 countries answered the questionnaire. Participants (60% men) were mainly physicians (91%) and nurses (8%) from University hospitals (77%). Among physicians, 83% had >10 years professional experience. Average time dedicated to discuss medications was 1-5 min in 48% and 6-10 min in 29% of cases. Interviews with patients about adherence were the most frequently used assessment method. Chemical detection of medications in urine was available in 36% of centres. One third of physicians involved their patients regularly in treatment decisions. The most frequent methods to improve adherence included simplification of medication therapy, more frequent visits, and home blood pressure monitoring.

Conclusions: The level of implementation of tools to detect and improve adherence in hypertension management by HCPs in ESH excellence centres is low. Structured educational activities focussing on adherence management and access to the newest objective measures to detect non-adherence might improve these deficits.
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http://dx.doi.org/10.1080/08037051.2021.1963209DOI Listing
October 2021

Changes in blood pressure after crossover to ultrasound renal denervation in patients initially treated with sham in the RADIANCE-HTN SOLO trial.

EuroIntervention 2021 Dec 17;17(12):e1024-e1032. Epub 2021 Dec 17.

Klinik für Innere Medizin III, Saarland University Hospital, Homburg/Saar, Germany.

Background: The multicentre, randomised, sham-controlled RADIANCE-HTN SOLO trial reported the blood pressure (BP)-lowering efficacy and safety of ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 and 12 months) of antihypertensive medications in patients with mild-to-moderate hypertension.

Aims: The aim of this report was to evaluate patients originally assigned to the sham group who crossed over to RDN.

Methods: After the primary endpoint was met, patients in the sham arm who remained uncontrolled were allowed to cross over to receive RDN. All patients were unblinded and treated with standard of care medications at the time of crossover. Ambulatory BP was evaluated 2 and 6 months after crossover.

Results: Among 72 subjects of the sham arm, 33 underwent ultrasound RDN after an average follow-up of 23±6 months. Prior to crossover, patients had a daytime ambulatory BP of 144.1±10.1/89.9±8.4 mmHg and received 1.2±0.8 antihypertensive medications. Mean change in daytime ambulatory BP from pre-crossover to 2 and 6 months post RDN was -11.2±13.7/-7.1±8.9 mmHg (n=33; p<0.001; p<0.001) and -10.8±17.3/-7.8±11.6 mmHg (n=27; p=0.002; p<0.001). The number of antihypertensive medications did not change from pre-crossover baseline to 2 and 6 months. Eighteen of 33 (54.5%) patients had their daytime ambulatory BP controlled (<135/85 mmHg) at 2 months and 44.4% (12/27) at 6 months post RDN. No major procedure-related adverse events occurred.

Conclusions: During unblinded long-term follow-up of the RADIANCE-HTN SOLO study, patients originally assigned to a sham procedure who remained uncontrolled had significant reductions in BP following crossover treatment with ultrasound RDN.
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http://dx.doi.org/10.4244/EIJ-D-21-00295DOI Listing
December 2021

Identification of Surgically Curable Primary Aldosteronism by Imaging in a Large, Multiethnic International Study.

J Clin Endocrinol Metab 2021 10;106(11):e4340-e4349

3rd Department of Medicine, Charles University, General Faculty Hospital, Prague, Czech Republic.

Context: Adrenal gland imaging is recommended by the current guidelines for the workup of primary aldosteronism (PA). However, its diagnostic performance has not been established in large, multiethnic cohorts of patients who undergo adrenal vein sampling (AVS) and adrenalectomy.

Objective: This work aims to assess the diagnostic accuracy of cross-sectional adrenal imaging.

Methods: This international multicenter study took place in tertiary referral centers. A total of 1625 PA patients seeking surgical cure were enrolled in an international study involving 19 centers in North America, Europe, Asia, and Australia. Of these, 1311 (81%) had imaging data available and 369 (23%), who received a final diagnosis of surgically cured unilateral PA, were examined. Patients underwent AVS and imaging by computed tomography and/or magnetic resonance imaging. The accuracy of detection of unilateral PA at imaging was estimated by the area under the receiver operator characteristics curve using cure (biochemical and/or full clinical success) as the reference at follow-up after unilateral adrenalectomy.

Results: In the cohort of 1311 patients with imaging data available, 34% and 7% of cases showed no detectable or bilateral nodules, respectively. Imaging did not detect the culprit adrenal in 28% of the surgically cured unilateral PA patients. Moreover, the clinical outcome did not differ significantly between the imaging-positive and imaging-negative patients.

Conclusion: Cross-sectional imaging did not identify a lateralized cause of disease in around 40% of PA patients and failed to identify the culprit adrenal in more than one-fourth of patients with unilateral PA.
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http://dx.doi.org/10.1210/clinem/dgab482DOI Listing
October 2021

["Inhibitors of the renin-angiotensin system and cardiovascular protection: the case of atheromatous stenosis of the renal artery and chronic kidney disease"].

Rev Prat 2021 03;71(3):e82

Centre de soins, de recherche et enseignement en hypertension artérielle, Hôpital européen Georges-Pompidou, 75015, Paris, France - Université de Paris, 75006, Paris, France.

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March 2021

Differential association between inflammatory cytokines and multiorgan dysfunction in COVID-19 patients with obesity.

PLoS One 2021 26;16(5):e0252026. Epub 2021 May 26.

INSERM UMRS 1138, Cordeliers Research Center, Team Inflammation, Complement, and Cancer, Paris, France.

To investigate the mechanisms underlying the SARS-CoV-2 infection severity observed in patients with obesity, we performed a prospective study of 51 patients evaluating the impact of multiple immune parameters during 2 weeks after admission, on vital organs' functions according to body mass index (BMI) categories. High-dimensional flow cytometric characterization of immune cell subsets was performed at admission, 30 systemic cytokines/chemokines levels were sequentially measured, thirteen endothelial markers were determined at admission and at the zenith of the cytokines. Computed tomography scans on admission were quantified for lung damage and hepatic steatosis (n = 23). Abnormal BMI (> 25) observed in 72.6% of patients, was associated with a higher rate of intensive care unit hospitalization (p = 0.044). SARS-CoV-2 RNAaemia, peripheral immune cell subsets and cytokines/chemokines were similar among BMI groups. A significant association between inflammatory cytokines and liver, renal, and endothelial dysfunctions was observed only in patients with obesity (BMI > 30). In contrast, early signs of lung damage (ground-glass opacity) correlated with Th1/M1/inflammatory cytokines only in normal weight patients. Later lesions of pulmonary consolidation correlated with BMI but were independent of cytokine levels. Our study reveals distinct physiopathological mechanisms associated with SARS-CoV-2 infection in patients with obesity that may have important clinical implications.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252026PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153504PMC
June 2021

Predictors of blood pressure response to ultrasound renal denervation in the RADIANCE-HTN SOLO study.

J Hum Hypertens 2021 May 24. Epub 2021 May 24.

Barts NIHR Biomedical Research Centre, William Harvey Research Institute, Queen Mary University of London, London, UK.

The blood pressure (BP) lowering response to renal denervation (RDN) remains variable with about one-third of patients not responding to ultrasound or radiofrequency RDN. Identification of predictors of the BP response to RDN is needed to optimize patient selection for this therapy. This is a post-hoc analysis of the RADIANCE-HTN SOLO study. BP response to RDN was measured by the change in daytime ambulatory systolic blood pressure (dASBP) at 2 months post procedure. Univariate regression was used initially to assess potential predictors of outcome followed by multivariate regression analysis. In the univariate analysis, predictors of response to RDN were higher baseline daytime ambulatory diastolic blood pressure (dADBP), the use of antihypertensive medications at screening, and presence of orthostatic hypertension (OHTN) whilst the presence of untreated accessory arteries was a negative predictor of response. Multivariate analysis determined that dADBP and use of antihypertensive medications were predictors of response to RDN with a trend for OHTN to predict response. Obese females also appeared to be better responders to RDN in an interaction model. RDN is more effective in patients with elevated baseline dADBP and those with OHTN, suggesting increased peripheral vascular resistance secondary to heightened sympathetic tone. These assessments are easy to perform in clinical setting and may help in phenotyping patients who will respond better to RDN.
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http://dx.doi.org/10.1038/s41371-021-00547-yDOI Listing
May 2021

Ultrasound renal denervation for hypertension resistant to a triple medication pill (RADIANCE-HTN TRIO): a randomised, multicentre, single-blind, sham-controlled trial.

Lancet 2021 06 16;397(10293):2476-2486. Epub 2021 May 16.

Columbia University Medical Center/New York-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, NY, USA.

Background: Endovascular renal denervation reduces blood pressure in patients with mild-to-moderate hypertension, but its efficacy in patients with true resistant hypertension has not been shown. We aimed to assess the efficacy and safety of endovascular ultrasound renal denervation in patients with hypertension resistant to three or more antihypertensive medications.

Methods: In a randomised, international, multicentre, single-blind, sham-controlled trial done at 28 tertiary centres in the USA and 25 in Europe, we included patients aged 18-75 years with office blood pressure of at least 140/90 mm Hg despite three or more antihypertensive medications including a diuretic. Eligible patients were switched to a once daily, fixed-dose, single-pill combination of a calcium channel blocker, an angiotensin receptor blocker, and a thiazide diuretic. After 4 weeks of standardised therapy, patients with daytime ambulatory blood pressure of at least 135/85 mm Hg were randomly assigned (1:1) by computer (stratified by centres) to ultrasound renal denervation or a sham procedure. Patients and outcome assessors were masked to randomisation. Addition of antihypertensive medications was allowed if specified blood pressure thresholds were exceeded. The primary endpoint was the change in daytime ambulatory systolic blood pressure at 2 months in the intention-to-treat population. Safety was also assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02649426.

Findings: Between March 11, 2016, and March 13, 2020, 989 participants were enrolled and 136 were randomly assigned to renal denervation (n=69) or a sham procedure (n=67). Full adherence to the combination medications at 2 months among patients with urine samples was similar in both groups (42 [82%] of 51 in the renal denervation group vs 47 [82%] of 57 in the sham procedure group; p=0·99). Renal denervation reduced daytime ambulatory systolic blood pressure more than the sham procedure (-8·0 mm Hg [IQR -16·4 to 0·0] vs -3·0 mm Hg [-10·3 to 1·8]; median between-group difference -4·5 mm Hg [95% CI -8·5 to -0·3]; adjusted p=0·022); the median between-group difference was -5·8 mm Hg (95% CI -9·7 to -1·6; adjusted p=0·0051) among patients with complete ambulatory blood pressure data. There were no differences in safety outcomes between the two groups.

Interpretation: Compared with a sham procedure, ultrasound renal denervation reduced blood pressure at 2 months in patients with hypertension resistant to a standardised triple combination pill. If the blood pressure lowering effect and safety of renal denervation are maintained in the long term, renal denervation might be an alternative to the addition of further antihypertensive medications in patients with resistant hypertension.

Funding: ReCor Medical.
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http://dx.doi.org/10.1016/S0140-6736(21)00788-1DOI Listing
June 2021

Male Sex Is Associated With Cervical Artery Dissection in Patients With Fibromuscular Dysplasia.

J Am Heart Assoc 2021 06 17;10(11):e018311. Epub 2021 May 17.

Department of Neurology Inserm U1237 Normandie UniversitéUniversité Caen NormandieCHU Caen Normandie Caen France.

Background Cervical artery dissection (CeAD) is a frequent manifestation of fibromuscular dysplasia (FMD). However, risk factors for CeAD are unknown. We investigated factors associated with CeAD in the ARCADIA (Assessment of Renal and Cervical Artery Dysplasia) registry. Methods and Results The ARCADIA registry includes women or men aged ≥18 years, with a diagnosis of renal, cervical, or intracranial artery FMD, who were prospectively recruited at 16 university hospitals in France and Belgium. Diagnosis of acute or past CeAD at inclusion was established on imaging according to standard diagnostic criteria. Associations between potential determinants and CeAD were assessed by logistic regression analyses. Among 469 patients (75 men) with FMD, 65 (13.9%) had CeAD. Patients with CeAD were younger, more likely to be men, have a history of migraine, and less likely to have a history of hypertension than patients without CeAD. In the multivariable analysis, male sex (odds ratio [OR], 2.66; 95% CI, 1.34-5.25), history of migraine (OR, 1.90; 95% CI, 1.06-3.39), age ≥50 years (OR, 0.41; 95% CI, 0.23-0.73), history of hypertension (OR, 0.35; 95% CI, 0.20-0.64), and involvement of ≥3 vascular beds (OR, 2.49; 95% CI, 1.15-5.40) were significantly associated with CeAD. To validate the association between CeAD and sex, we performed a systematic review. We collected additional data on sex from 2 published studies and unpublished data from the US Registry for Fibromuscular Dysplasia and the European/International FMD Registry. In the pooled analysis (289 CeAD, 1933 patients), male sex was significantly associated with CeAD (OR, 2.04; 95% CI, 1.41-2.95; =0%). Conclusions In patients with FMD, male sex and multisite involvement are associated with CeAD, in addition to other previously known risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02884141.
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http://dx.doi.org/10.1161/JAHA.120.018311DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8483547PMC
June 2021

Renal Outcome and New-Onset Renal and Extrarenal Dissections in Patients With Nontrauma Renal Artery Dissection Associated With Renal Infarction.

Hypertension 2021 07 10;78(1):51-61. Epub 2021 May 10.

Hypertension Unit (A.-L.F., G.B., A.L., M.A., L.A.), AP-HP, Hôpital Européen Georges Pompidou, Paris, France.

[Figure: see text].
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16540DOI Listing
July 2021

Acute decrease of urine calcium by amiloride in healthy volunteers under high sodium diet.

Nephrol Dial Transplant 2021 Apr 29. Epub 2021 Apr 29.

Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland and Service of Nephrology, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.

Background: Amiloride is a competitive blocker of the epithelial sodium channel (ENaC) in the renal collecting duct. It is a less potent diuretic than thiazides or loop diuretics, but is often used in association for its potassium-sparing profile. Whether amiloride has hypocalciuric effect similar to thiazides remains unclear. Animal studies and experiments on cell lines suggested that amiloride increases calcium reabsorption in the distal nephron, but human studies are scarce.

Methods: We performed a post hoc analysis of a study with 48 healthy males (age, 23.2 ± 3.9 years) who were assigned to a high sodium (Na)/low potassium (K) diet for 7 days before receiving 20 mg of amiloride p.o. Urinary excretions of electrolytes were measured at 3 and 6 hours afterward; we calculated the relative changes in urinary excretion rates after amiloride administration.

Results: The high Na/low K diet led to an expected suppression of plasma renin and aldosterone. Amiloride showed a mild natriuretic effect associated with a decreased kaliuresis. Urinary calcium excretion dropped substantially (by 80%) 3 hours after amiloride administration and remained low at the 6th hour. At the same time, fractional excretion of lithium decreased by a third, reflecting an increased proximal tubular reabsorption.

Conclusion: During a high Na/low K diet, amiloride had a strong acute hypocalciuric effect, most probably mediated by increased proximal calcium reabsorption, even though distal effect cannot be excluded. Further studies should establish if chronic amiloride or combined amiloride/thiazide treatment may decrease calciuria more efficiently and be useful in preventing kidney stones.
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http://dx.doi.org/10.1093/ndt/gfab159DOI Listing
April 2021

Drug-resistant hypertension in primary aldosteronism patients undergoing adrenal vein sampling: the AVIS-2-RH study.

Eur J Prev Cardiol 2021 Mar 20. Epub 2021 Mar 20.

3rd Department of Medicine, Charles University Prague, General Hospital, Prague, Czech Republic.

Aims: We aimed at determining the rate of drug-resistant arterial hypertension in patients with an unambiguous diagnosis of primary aldosteronism (PA). Moreover, we sought for investigating the diagnostic performance of adrenal vein sampling (AVS), and the effect of adrenalectomy on blood pressure (BP) and prior treatment resistance in PA patients subtyped by AVS in major referral centres.

Methods And Results: The Adrenal Vein Sampling International Study-2 (AVIS-2) was a multicentre international study that recruited consecutive PA patients submitted to AVS, according to current guidelines, during 15 years. The patients were over 18 years old with arterial hypertension and had an unambiguous diagnosis of PA. The rate of resistant hypertension was assessed at baseline and after adrenalectomy using the American Heart Association (AHA) 2018 definition. Information on presence or absence of resistant hypertension was available in 89% of the 1625 enrolled PA patients. Based on the AHA 2018 criteria, resistant hypertension was found in 20% of patients, of which about two-thirds (14%) were men and one-third (6%) women (χ2 = 17.1, P < 1*10-4) with a higher rate of RH in men than in women (23% vs. 15% P < 1*10-4). Of the 292 patients with resistant hypertension, 98 (34%) underwent unilateral AVS-guided adrenalectomy, which resolved BP resistance to antihypertensive treatment in all.

Conclusions: (i) Resistant hypertension is a common presentation in patients seeking surgical cure of PA; (ii) AVS is key for the optimal management of patients with PA due to resistant hypertension; and (iii) AVS-guided adrenalectomy allowed resolution of treatment-resistant hypertension.
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http://dx.doi.org/10.1093/eurjpc/zwaa108DOI Listing
March 2021

Current progress in clinical, molecular, and genetic aspects of adult fibromuscular dysplasia.

Cardiovasc Res 2022 Jan;118(1):65-83

Pole of Cardiovascular Research, Institut de Recherche Expérimentale et Clinique and Division of Cardiology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium.

Fibromuscular dysplasia (FMD) is a non-atherosclerotic vascular disease that may involve medium-sized muscular arteries throughout the body. The majority of FMD patients are women. Although a variety of genetic, mechanical, and hormonal factors play a role in the pathogenesis of FMD, overall, its cause remains poorly understood. It is probable that the pathogenesis of FMD is linked to a combination of genetic and environmental factors. Extensive studies have correlated the arterial lesions of FMD to histopathological findings of arterial fibrosis, cellular hyperplasia, and distortion of the abnormal architecture of the arterial wall. More recently, the vascular phenotype of lesions associated with FMD has been expanded to include arterial aneurysms, dissections, and tortuosity. However, in the absence of a string-of-beads or focal stenosis, these lesions do not suffice to establish the diagnosis. While FMD most commonly involves renal and cerebrovascular arteries, involvement of most arteries throughout the body has been reported. Increasing evidence highlights that FMD is a systemic arterial disease and that subclinical alterations can be found in non-affected arterial segments. Recent significant progress in FMD-related research has led to improve our understanding of the disease's clinical manifestations, natural history, epidemiology, and genetics. Ongoing work continues to focus on FMD genetics and proteomics, physiological effects of FMD on cardiovascular structure and function, and novel imaging modalities and blood-based biomarkers that can be used to identify subclinical FMD. It is also hoped that the next decade will bring the development of multi-centred and potentially international clinical trials to provide comparative effectiveness data to inform the optimal management of patients with FMD.
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http://dx.doi.org/10.1093/cvr/cvab086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8752362PMC
January 2022

12-Month Results From the Unblinded Phase of the RADIANCE-HTN SOLO Trial of Ultrasound Renal Denervation.

JACC Cardiovasc Interv 2020 12;13(24):2922-2933

Columbia University Medical Center/NewYork-Presbyterian Hospital and the Cardiovascular Research Foundation, New York, New York, USA.

Objectives: This study reports the 12-month results of the RADIANCE-HTN (A Study of the ReCor Medical Paradise System in Clinical Hypertension) SOLO trial following unblinding of patients at 6 months.

Background: The blood pressure (BP)-lowering efficacy and safety of endovascular ultrasound renal denervation (RDN) in the absence (2 months) and presence (6 months) of antihypertensive medications were previously reported.

Methods: Patients with daytime ambulatory BP ≥135/85 mm Hg after 4 weeks off medication were randomized to RDN (n = 74) or sham (n = 72) and maintained off medication for 2 months. A standardized medication escalation protocol was instituted between 2 and 5 months (blinded phase). Between 6 and 12 months (unblinded phase), patients received antihypertensive medications at physicians' discretion. Outcomes at 12 months included medication burden, change in daytime ambulatory systolic BP (dASBP) and office or home systolic BP (SBP), visit-to-visit variability in SBP, and safety.

Results: Sixty-five of 74 RDN patients and 67 of 72 sham patients had 12-month dASBP measurements. The proportion of patients on ≥2 medications (27.7% vs. 44.8%; p = 0.041), the number of medications (0 vs. 1.4; p = 0.015), and defined daily dose (1.4 vs. 2.2; p = 0.007) were less with RDN versus sham. The decrease in dASBP from baseline in the RDN group (-16.5 ± 12.9 mm Hg) remained stable at 12 months. The RDN versus sham adjusted difference at 12 months was -2.3 mm Hg (95% confidence interval [CI]: -5.9 to 1.3 mm Hg; p = 0.201) for dASBP, -6.3 mm Hg (95% CI: -11.1 to -1.5 mm Hg; p = 0.010) for office SBP, and -3.4 mm Hg (95% CI: -6.9 to 0.1 mm Hg; p = 0.062) for home SBP. Visit-to-visit variability in SBP was smaller in the RDN group. No renal artery injury was detected on computed tomographic or magnetic resonance angiography.

Conclusions: Despite unblinding, the BP-lowering effect of RDN was maintained at 12 months with fewer prescribed medications compared with sham.
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http://dx.doi.org/10.1016/j.jcin.2020.09.054DOI Listing
December 2020

Ambulatory Blood Pressure Monitoring to Predict Response to Renal Denervation: A Post Hoc Analysis of the RADIANCE-HTN SOLO Study.

Hypertension 2021 02 28;77(2):529-536. Epub 2020 Dec 28.

Université de Paris, F-75006 Paris, France (M.A.).

Renal denervation (RDN) is effective in lowering blood pressure (BP) in patients with hypertension. The issue remains how to best identify potential responders. Ambulatory BP monitoring may be useful. Baseline nighttime systolic BP (SBP) ≥136 mm Hg and its variability (SD) ≥12 mm Hg in DENER-HTN trial or 24-hour heart rate ≥73.5 bpm in SPYRAL HTN-OFF MED Trial were shown to predict the BP response to RDN. We applied these criteria to the patients with hypertension in the sham-controlled RADIANCE-HTN SOLO trial to predict the BP response to ultrasound RDN at 2 months while patients were maintained off medications. BP responders were defined as: clinical with 24-hour SBP <130 mm Hg (RDN: 22/64 versus sham: 7/58); meaningful with 24-hour SBP reduction ≥10 mm Hg (RDN: 24/64, sham: 7/58); and extreme with 24-hour SBP reduction above mean+2 SD of the SBP decrease in the sham group, that is, ≥16.5 mm Hg (RDN: 10/64 versus sham: 2/58). The predictive criteria reported above were tested for sensitivity, specificity, and positive and negative predictive values. The predictive value varied according to the definition of response, with the clinical definition being strongly influenced by regression to the mean. Baseline nighttime SBP and its variability, especially when combined, offered good specificity (>90% irrespective of definition) but low sensitivity (from 9.1% to 30% depending on the definition) to predict responders; the heart rate criterion had insufficient predictive value. This analysis suggests the potential role of nighttime SBP and its variability to predict BP response to RDN in patients with hypertension. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02649426.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16292DOI Listing
February 2021

Travelling in time and space in the heart of Paris.

Ann Endocrinol (Paris) 2021 Jun 13;82(3-4):131. Epub 2020 Dec 13.

Service d'endocrinologie et des maladies de la reproduction, hôpital Bicêtre, 78, rue du Général-Leclerc, 94275 Le Kremlin-Bicêtre, France.

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http://dx.doi.org/10.1016/j.ando.2020.12.006DOI Listing
June 2021

Is there any Hope for Monitoring Adherence in an Efficient and Feasible Way for Resistant Hypertension Diagnosis and Follow-Up?

Curr Hypertens Rep 2020 10 14;22(11):96. Epub 2020 Oct 14.

Université de Paris, F-75006, Paris, France.

Purpose Of Review: Non-adherence to antihypertensive treatment is highly prevalent and represents a major factor affecting their effectiveness in hypertensive patients, thus contributing to apparent treatment resistance. It is however often overlooked because the methods to assess non-adherence are mainly subjective, limiting their usefulness in clinical practice. Non-adherence to treatment affects daily patient management, resulting in inappropriate, costly, and potentially harmful treatments and loss of the expected benefits from antihypertensive drugs.

Recent Findings: Specialized centers now use a combination of objective screening tools. Firstly, snapshots of adherence levels can be provided by analytical drug detection in various biological matrixes using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and secondly electronic monitoring systems of drug delivery which provide longitudinal data on adherence. Routine utilization of those tools allows the detection of non-adherence in patients with resistant hypertension, thus enabling implementation of appropriate interventions to improve drug adherence and avoid unnecessary treatment intensification. Other complementary techniques, such as digital health feedback system with ingestible sensors, are currently evaluated. In the context of an increasing burden of uncontrolled and apparent treatment-resistant hypertension, detecting non-adherence to antihypertensive therapy is, as acknowledged by the latest guidelines, a top priority to implement in clinical practice but still faces medical conservatism and disbelief.
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http://dx.doi.org/10.1007/s11906-020-01105-6DOI Listing
October 2020

Aldosterone-Related Myocardial Extracellular Matrix Expansion in Hypertension in Humans: A Proof-of-Concept Study by Cardiac Magnetic Resonance.

JACC Cardiovasc Imaging 2020 10 16;13(10):2149-2159. Epub 2020 Sep 16.

Department of Radiology, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Hypertension, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Department of Biological & Statistic, Hôpital Européen Georges-Pompidou, Assistance Publique-Hôpitaux de Paris, Paris, France; Université de Paris, Paris, France; Paris Cardiovascular Research Center, French Institute of Health and Medical Research, Paris, France. Electronic address:

Objectives: This study sought to assess the respective effects of aldosterone and blood pressure (BP) levels on myocardial fibrosis in humans.

Background: Experimentally, aldosterone promotes left ventricular (LV) hypertrophy, and interstitial myocardial fibrosis in the presence of high salt intake.

Methods: The study included 20 patients with primary aldosteronism (PA) (high aldosterone and high BP), 20 patients with essential hypertension (HTN) (average aldosterone and high BP), 20 patients with secondary aldosteronism due to Bartter/Gitelman (BG) syndrome (high aldosterone and normal BP), and 20 healthy subjects (HS) (normal aldosterone and normal BP). Participants in each group were of similar age and sex distributions, and asymptomatic. Cardiac magnetic resonance including cine and T1 mapping was performed blind to the study group to quantify global LV mass index, as well as intracellular mass index and extracellular mass index considered as a measure of myocardial fibrosis in vivo.

Results: Median plasma aldosterone concentration was as follows: PA = 709 pmol/l (interquartile range [IQR]: 430 to 918 pmol/l); HTN = 197 pmol/l (IQR: 121 to 345 pmol/l); BG = 297 pmol/l (IQR: 180 to 428 pmol/l); and HS = 105 pmol/l (IQR: 85 to 227 pmol/l). Systolic BP was as follows: PA = 147 ± 15 mm Hg; HTN = 133 ± 19 mm Hg; BG = 116 ± 9 mm Hg; and HS = 117 ± 12 mm Hg. LV end-diastolic volume showed underloading in BG and overloading in patients with PA (63 ± 13 ml/m vs. 82 ± 15 ml/m; p < 0.0001). Intracellular mass index increased with BP across groups (BG: 36 [IQR: 29 to 41]; HS: 40 [IQR: 36 to 46]; HTN: 51 [IQR: 42 to 54]; PA: 50 [IQR: 46 to 67]; p < 0.0001). Extracellular mass index was similar in BG, HS, and HTN (16 [IQR: 12 to 20]; 15 [IQR: 11 to 18]; and 14 [IQR: 12 to 17], respectively) but 30% higher in PA (21 [IQR: 18 to 29]; p < 0.0001) remaining significant after adjustment for mean BP.

Conclusions: Only primary pathological aldosterone excess combined with high BP increased both extracellular myocardial matrix and intracellular mass. Secondary aldosterone excess with normal BP did not affect extracellular myocardial matrix. (Study of Myocardial Interstitial Fibrosis in Hyperaldosteronism; NCT02938910).
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http://dx.doi.org/10.1016/j.jcmg.2020.06.026DOI Listing
October 2020
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