Publications by authors named "Ana Paula de Faria"

39 Publications

Effects of Anti-TNF alpha Therapy on Blood Pressure in Resistant Hypertensive Subjects: A Randomized, Double-Blind, Placebo-Controlled Pilot Study.

Arq Bras Cardiol 2021 03;116(3):443-451

Universidade Estadual de Campinas, Campinas, SP - Brasil.

Background: The cytokine tumor necrosis factor-alpha (TNF-α) is elevated in resistant hypertension (RH), but the effects of a TNF-α inhibitor in this population is unknown.

Objective: The aim of this trial was to evaluate whether a single dose of infliximab controlled by placebo acutely reduces blood pressure (BP) in RH subjects.

Methods: A double-blind, placebo-controlled, crossover trial was conducted, and randomized RH subjects received either infliximab or placebo. The primary endpoint was the change in mean BP levels relative to the baseline immediately after the infusion obtained by continuously beat-to-beat non-invasive hemodynamic assessment. Secondary endpoints included changes in office, ambulatory and central BP measurements; endothelial function; and inflammatory biomarkers after 7 days. The level of significance accepted was alpha=0.05.

Results: Ten RH subjects were enrolled. The primary endpoint analysis showed an acute decrease in mean BP values (mean of differences ± standard deviation = -6.3 ± 7.2 mmHg, p=0.02) from baseline, after the application of infliximab compared with placebo. Diastolic BP levels (-4.9 ± 5.5 mmHg, p=0.02), but not systolic BP levels (-9.4 ± 19.7 mmHg, p=0.16), lowered after infliximab infusion. No further significant differences were identified in either the other hemodynamic parameters or in secondary endpoints, except for TNF-α levels, which increased continuously after infliximab infusion. No adverse events were reported during the protocol.

Conclusions: A single-dose of infliximab decreased the mean and diastolic BP levels immediately after its infusion, when compared to the placebo in RH. The anti-TNF-α therapy was found to be safe and well-tolerated. The results of this proof-of-concept are hypothesis-generating and need to be further investigated. (Arq Bras Cardiol. 2021; 116(3):443-451).
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http://dx.doi.org/10.36660/abc.202190703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8159563PMC
March 2021

Combined Aerobic and Resistance Exercises Evokes Longer Reductions on Ambulatory Blood Pressure in Resistant Hypertension: A Randomized Crossover Trial.

Cardiovasc Ther 2020 20;2020:8157858. Epub 2020 Jul 20.

Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.

Aim: The present study compared the acute effects of aerobic (AER), resistance (RES), and combined (COM) exercises on blood pressure (BP) levels in people with resistant hypertension (RH) and nonresistant hypertension (NON-RH).

Methods: Twenty patients (10 RH and 10 NON-RH) were recruited and randomly performed three exercise sessions and a control session. Ambulatory BP was monitored over 24 hours after each experimental session.

Results: Significant reductions on ambulatory BP were found in people with RH after AER, RES, and COM sessions. Notably, ambulatory BP was reduced during awake-time and night-time periods after COM. On the other hand, the effects of AER were more prominent during awake periods, while RES caused greater reductions during the night-time period. In NON-RH, only RES acutely reduced systolic BP, while diastolic BP was reduced after all exercise sessions. However, the longest postexercise ambulatory hypotension was observed after AER (~11 h) in comparison to RES (~8 h) and COM (~4 h) exercises.

Conclusion: Findings of the present study indicate that AER, RES, and COM exercises elicit systolic and diastolic postexercise ambulatory hypotension in RH patients. Notably, longer hypotension periods were observed after COM exercise. In addition, NON-RH and RH people showed different changes on BP after exercise sessions, suggesting that postexercise hypotension is influenced by the pathophysiological bases of hypertension.
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http://dx.doi.org/10.1155/2020/8157858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7416229PMC
September 2020

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS.

Can J Cardiol 2020 05 19;36(5):747-755. Epub 2019 Oct 19.

Galway University Hospital, National University of Ireland, Galway, Ireland. Electronic address:

Background: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population.

Methods: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated.

Results: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008).

Conclusions: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.
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http://dx.doi.org/10.1016/j.cjca.2019.10.015DOI Listing
May 2020

Pro-inflammatory Cytokines and Resistant Hypertension: Potential for Novel Treatments?

Curr Hypertens Rep 2019 11 26;21(12):95. Epub 2019 Nov 26.

Department of Pharmacology, FCM 10 Building, School of Medical Sciences - University of Campinas (FCM-UNICAMP), Tessália Vieira de Camargo, 126, Campinas, SP, 13083-970, Brazil.

Purpose Of Review: To gather data from studies evaluating the pro-inflammatory profile of individuals with resistant hypertension (RH), and bring a clinical update of new and potential complementary therapies to treat inflammation in RH.

Recent Findings: Increases in pro-inflammatory cytokines are related to elevated blood pressure and target organ damage in RH patients. Clinical and experimental studies have shown that some biological therapies, especially TNF-α inhibitors, regulated pro- and anti-inflammatory cytokines associated with improvements in clinical outcomes, although they are not yet reported in RH. New emerging therapies to treat inflammation in RH, although promising, are still hypotheses that have not been scientifically confirmed in clinical trials. For this reason, inflammation-target treatments, such as the TNF-α and IL-6 inhibitors, should be encouraged for testing as complementary therapies in RH in order to elucidate their potential benefits.
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http://dx.doi.org/10.1007/s11906-019-1003-2DOI Listing
November 2019

A Proposed Inflammatory Score of Circulating Cytokines/Adipokines Associated with Resistant Hypertension, but Dependent on Obesity Parameters.

Arq Bras Cardiol 2019 04 28;112(4):383-389. Epub 2019 Feb 28.

Departamento de Medicina Interna da Faculdade de Ciências Médicas da Universidade Estadual de Campinas, Campinas, SP - Brazil.

Background: There is evidence that subclinical systemic inflammation is present in resistant hypertension (RHTN).

Objective: The aim of the study was to develop an integrated measure of circulating cytokines/adipokines involved in the pathophysiology of RHTN.

Methods: RHTN (n = 112) and mild to moderate hypertensive (HTN) subjects (n=112) were studied in a cross-sectional design. Plasma cytokines/adipokines (TNF-alpha, interleukins [IL]-6, -8, -10, leptin and adiponectin) values were divided into tertiles, to which a score ranging from 1 (lowest tertile) to 3 (highest tertile) was assigned. The inflammatory score (IS) of each subject was the sum of each pro-inflammatory cytokine scores from which anti-inflammatory cytokines (adiponectin and IL-10) scores were subtracted. The level of significance accepted was alpha = 0.05.

Results: IS was higher in RHTN subjects compared with HTN subjects [4 (2-6) vs. 3 (2-5); p = 0.02, respectively]. IS positively correlated with body fat parameters, such as body mass index (r = 0.40; p < 0.001), waist circumference (r = 0.30; p < 0.001) and fat mass assessed by bioelectrical impedance analysis (r = 0.31; p < 0.001) in all hypertensive subjects. Logistic regression analyses revealed that IS was an independent predictor of RHTN (OR = 1.20; p = 0.02), independent of age, gender and race, although it did not remain significant after adjustment for body fat parameters.

Conclusion: A state of subclinical inflammation defined by an IS including TNF-alpha, IL-6, IL-8, IL-10, leptin and adiponectin is associated with obese RHTN. In addition, this score correlates with obesity parameters, independently of hypertensive status. The IS may be used for the evaluation of conditions involving low-grade inflammation, such as obesity-related RHTN. Indeed, it also highlights the strong relationship between obesity and inflammatory process.
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http://dx.doi.org/10.5935/abc.20190032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6459424PMC
April 2019

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest.

Ecology 2019 02;100(2):e02541

Centro de Ensino Superior em Juiz de Fora (CESJF), Campus Arnaldo Janssen, Luz Interior, 345, Santa Luzia, Juiz de Fora, Minas Gerais, 36030-776, Brazil.

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events.
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http://dx.doi.org/10.1002/ecy.2541DOI Listing
February 2019

White coat syndrome and its variations: differences and clinical impact.

Integr Blood Press Control 2018 8;11:73-79. Epub 2018 Nov 8.

Department of Pharmacology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil,

Hypertension is closely linked to increased cardiovascular risk and development of target organ damage (TOD). Therefore, proper clinical follow-up and treatment of hypertensive subjects are mandatory. A great number of individuals present a variation on blood pressure (BP) levels when they are assessed either in the office or in the out-of-office settings. This phenomenon is defined as white coat syndrome - a change in BP levels due to the presence of a physician or other health professional. In this context, the term "white coat syndrome" may refer to three important and different clinical conditions: 1) white coat hypertension, 2) white coat effect, and 3) masked hypertension. The development of TOD and the increased cardiovascular risk play different roles in these specific subgroups of white coat syndrome. Correct diagnose and clinical guidance are essential to improve the prognosis of these patients. The aim of this review was to elucidate contemporary aspects of these types of white coat syndrome on general and hypertensive population.
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http://dx.doi.org/10.2147/IBPC.S152761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233698PMC
November 2018

Metabolic Syndrome-Related Features in Controlled and Resistant Hypertensive Subjects.

Arq Bras Cardiol 2018 Jun;110(6):514-521

Faculdade de Ciências Médicas - Universidade Estadual de Campinas (UNICAMP), Campinas, SP - Brazil.

Background: Metabolic syndrome (MetS) is widespread among hypertensive patients. Clinical features and potential biomarkers of MetS in the presence of hypertension and resistant hypertension (RHTN) represent a great area of interest for investigation.

Objective: The purpose of this study was to evaluate the prevalence of MetS and the clinical features associated with it in resistant and mild to moderate hypertensives.

Methods: This cross-sectional study included 236 patients, (i) 129 mild to moderate hypertensive patients and (ii) 107 patients with RHTN. We measured blood pressure (BP) and adipokines levels, and performed bioelectrical impedance analysis. Microalbuminuria (MA), cardiac hypertrophy and arterial stiffness were also assessed. The significance level of alpha = 0.05 was adopted.

Results: We found a MetS prevalence of 73% in resistant and 60% in mild-to-moderate hypertensive patients. In a multiple regression analysis, MA (odds ratio = 8.51; p = 0.01), leptin/adiponectin ratio (LAR) (odds ratio = 4.13; p = 0.01) and RHTN (odds ratio = 3.75; p = 0.03) were independently associated with the presence of MetS apart from potential confounders.

Conclusions: Our findings suggest that both resistant and controlled hypertensive subjects have a high prevalence of MetS. In addition, MetS-related metabolic derangements may cause early renal and hormonal changes. Finally, LAR may be useful as a reliable biomarker for identifying those hypertensive subjects who are at risk for developing MetS.
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http://dx.doi.org/10.5935/abc.20180076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6023630PMC
June 2018

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

J Clin Hypertens (Greenwich) 2018 05 5;20(5):910-917. Epub 2018 May 5.

Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.

This study aimed to evaluate the effects of glycated hemoglobin (HbA ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function.
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http://dx.doi.org/10.1111/jch.13293DOI Listing
May 2018

The rs243866/243865 polymorphisms in MMP-2 gene and the relationship with BP control in obese resistant hypertensive subjects.

Gene 2018 Mar 27;646:129-135. Epub 2017 Dec 27.

Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil; Department of Internal Medicine, Faculty of Medical Sciences, University of Campinas, SP, Brazil.

We sought to investigate whether the polymorphisms rs243865 (-1306C>T); rs243866 (-1575G>A) and rs2285053 (-735C>T) in metalloproteinases 2 - MMP-2 gene and rs17576 (Q279R), rs17577 (Q668R) and rs3918242 (-1562C>T) in MMP-9 gene are associated with clinical outcomes in obese resistant hypertensive (RH) subjects. One hundred and twenty RH were enrolled in this cross-sectional study and divided into obese (n=63) and non-obese (n=57) according to body mass index. Genotypes were determined by real-time PCR using TaqMan probes. We determined pulse wave velocity (PWV), microalbuminuria and left ventricular mass index (LVMI) to assess TODs. Obese and non-obese RH had similar allele, genotype and haplotype distributions for all polymorphisms assessed but obese RH subjects carrying the low frequency allele for SNPs in MMP-2 gene had higher ambulatory diastolic blood pressure. Also, PWV and LVMI were higher in subjects carrying the low frequency allele for SNPs in MMP-2 gene. Regarding MMP-9 gene, office diastolic BP levels were higher in the AA genotype individuals compared to the G allele group for rs17576 polymorphism, while the opposite was found regarding the microalbuminuria level. Independent multiple linear regression analyses revealed that both A allele for rs243865 and T allele for rs243866 in MMP-2 gene were associated with ambulatory diastolic levels in obese RH subjects, apart from potential confounders. Our study suggests that rs243866/rs243865 in the MMP-2 gene are related to BP levels in obese RH subjects, although TODs present in this population seem to be dependent of a combination of other factors besides the genetic polymorphisms.
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http://dx.doi.org/10.1016/j.gene.2017.12.023DOI Listing
March 2018

Managing resistant hypertension: focus on mineralocorticoid-receptor antagonists.

Vasc Health Risk Manag 2017 16;13:403-411. Epub 2017 Oct 16.

School of Medical Sciences, University of Campinas (UNICAMP), Campinas, Brazil.

Mineralocorticoid-receptor antagonists (MRAs) have proven to be effective in some types of hypertension, especially in resistant hypertension (RHTN). In this phenotype of hypertension, the renin-angiotensin-aldosterone pathway plays an important role, with MRAs being especially effective in reducing blood pressure. In this review, we show the relevance of aldosterone in RHTN, as well as some clinical characteristics of this condition and the main concepts involving its pathophysiology and cardiovascular damage. We analyzed the mechanisms of action and clinical effects of two current MRAs - spironolactone and eplerenone - both of which are useful in RHTN, with special attention to the former. RHTN represents a significant minority (10%-15%) of hypertension cases. However, primary-care physicians, cardiologists, nephrologists, neurologists, and geriatricians face this health problem on a daily basis. MRAs are likely one of the best pharmacological options in RHTN patients; however, they are still underused.
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http://dx.doi.org/10.2147/VHRM.S138599DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652936PMC
November 2017

Effect of oil palm on the Plecoptera and Trichoptera (Insecta) assemblages in streams of eastern Amazon.

Environ Monit Assess 2017 Aug 13;189(8):393. Epub 2017 Jul 13.

Laboratório de Ecologia e Conservação (LABECO), Universidade Federal do Pará, Instituto de Ciências Biológicas, Rua Augusto Correia 1, Belém, Pará, 66075-110, Brazil.

The production of oil palm is expected to increase in the Amazon region. However, expansion of oil palm plantation leads to significant changes in the physical structure of aquatic ecosystems, mainly through the reduction of riparian vegetation that is essential for aquatic biodiversity. Here, we evaluated the effects of oil palm on the physical habitat structure of Amazonian stream environments and assemblages of Plecoptera and Trichoptera (PT), ​both found in these streams. We compared streams sampled in oil palm plantations (n = 13) with natural forest areas ("reference" streams, n = 8), located in the eastern Amazon, Brazil. Our results showed that oil palm streams were more likely to be in close proximity to roads, had higher pH values, and higher amounts of fine substrate deposited in the channel than reference streams. Further, these environmental changes had important effects on the aquatic invertebrate assemblages, reducing the abundance and richness of PT. Nevertheless, the genera composition of the assemblages did not differ between reference and oil palm (PERMANOVA, pseudo-F  = 1.891; p = 0.111). We conclude that oil palm production has clear negative impacts on aquatic environments and PT assemblages in Amazonian streams. We recommend that oil palm producers invest more in planning of road networks to avoid the construction of roads near to the riparian vegetation. This planning can minimize impacts of oil palm production on aquatic systems in the Amazon.
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http://dx.doi.org/10.1007/s10661-017-6116-yDOI Listing
August 2017

Matrix metalloproteinase-2 -735C/T polymorphism is associated with resistant hypertension in a specialized outpatient clinic in Brazil.

Gene 2017 Jul 5;620:23-29. Epub 2017 Apr 5.

Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, SP, Brazil.

Background: Matrix metalloproteinases (MMPs) are enzymes involved in cardiovascular (CV) remodeling and hypertension-mediated target organ damage (TOD). Genetic polymorphisms in matrix metalloproteinase 2 (MMP-2) gene [-1575G/A (rs243866); -1306C/T (rs243865); and -735C/T (rs2285053)] are associated with several CV conditions, however the relationship between MMP-2 polymorphisms and resistant hypertension (RH) is unknown. We evaluated whether these genetic single nucleotide polymorphisms (SNPs) in MMP-2 gene are associated with 1) MMP-2 and tissue inhibitor of metalloproteinase-2 (TIMP-2) levels in RH and mild to moderate hypertensive (HT) subjects, 2) left ventricular hypertrophy (LVH) and arterial stiffness and 3) the presence of RH.

Methods: One hundred and nineteen RH and 136 HT subjects were included in this cross-sectional study. Genotypes were determined by real-time PCR using TaqMan probes. Haplotypes were estimated using Bayesian method.

Results: The levels of MMP-2 and TIMP-2 were similar among genotypes and haplotypes for the three studied polymorphisms in HT and RH groups. RH showed higher frequency for GCC haplotype and lower frequency of GCT and ATC haplotypes (-1575G/A, -1306C/T and -735C/T, respectively) compared to HT (0.77 vs. 0.64; 0.09 vs. 0.17; 0.13 vs. 0.19, p=0.003 respectively). GCC haplotype was associated to RH apart from potential confounders (odds ratio (OR)=2.09; 95% confidence interval (CI)=1.20-3.64; p=0.01). In addition, CC genotype (OR=2.93; 95% CI=1.22-7.01; p=0.02) and C allele (OR=2.81; 95% CI=1.26-6.31; p=0.01) for -735C/T polymorphism were independently associated with RH. GCT haplotype was associated with reduced probability of having RH (OR=0.35; 95% CI=0.16-0.79; p=0.01). Finally, no relationship was found between studied MMP-2 SNPs and left ventricular hypertrophy and arterial stiffness in both groups.

Conclusion: GCC haplotype carriers showed higher probability to have RH (odds ratio>1), while the GCT haplotype carriers showed lower probability to have RH, suggesting that the GCT haplotype may represent a protective genetic factor for the development of RH. These finds suggest that GCC and GCT haplotypes, and C allele and CC genotype of the -735C/T MMP-2 gene polymorphism may have a role in RH.
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http://dx.doi.org/10.1016/j.gene.2017.04.004DOI Listing
July 2017

Crosstalk between obesity and MMP-9 in cardiac remodelling -a cross-sectional study in apparent treatment-resistant hypertension.

Blood Press 2017 Apr 8;26(2):122-129. Epub 2016 Nov 8.

c Laboratory of Pharmacology Cardiovascular, Faculty of Medical Sciences, Department of Internal Medicine , University of Campinas , SP , Brazil.

The balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) plays a key role in the development of hypertension and obesity. We aimed to evaluate the levels of MMP-2 and 9 and TIMP-2 and -1 in obese and non-obese apparent treatment-resistant hypertensive subjects (aTRH) and its association with cardiac hypertrophy. This cross-sectional study enrolled 122 subjects and divided into obese aTRH (n = 67) and non-obese (n = 55) group. Clinical and biochemical data were compared between both groups, including office BP, ambulatory BP, plasma MMP-2 and 9, TIMP-2 and 1 and left ventricular mass index (LVMI). We found higher MMP-9 levels and MMP-9/TIMP-1 ratio in obese aTRH subjects but no difference in MMP-2 and TIMP-1 levels. Obesity influenced MMP-9 levels [β = 20.8 SE =8.6, p = 0.02) independently of potential confounders. In addition, we found a positive correlation between MMP-9 and anthropomorphic parameters. Finally, obese aTRH subjects with left ventricular hypertrophy (LVH) had greater MMP-9 levels compared with non-obese with LVH. Our study suggests that MMP-9 levels are influenced by obesity and may directly participate in the progressive LV remodelling process, suggesting a possible role for a higher cardiovascular risk in apparent resistant hypertensive subjects.
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http://dx.doi.org/10.1080/08037051.2016.1249336DOI Listing
April 2017

Acute Sildenafil Use Reduces 24-Hour Blood Pressure Levels in Patients With Resistant Hypertension: A Placebo-Controlled, Crossover Trial.

J Clin Hypertens (Greenwich) 2016 11 1;18(11):1168-1172. Epub 2016 Jun 1.

Laboratory of Cardiovascular Pharmacology, School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil.

The authors previously demonstrated that acute administration of sildenafil-a phosphodiesterase 5 (PDE5) inhibitor-improves hemodynamic parameters in patients with resistant hypertensive (RH), but its effect on ambulatory blood pressure monitoring (ABPM) is unknown. This interventional, nonrandomized, single-blinded, placebo-controlled, crossover trial included 26 patients with RH. A dose of sildenafil (187.5mg) was given, and after a washout period of 14 days the patients received a single oral dose of placebo and the protocol was repeated. The patients underwent 24-hour ABPM recordings the day before and immediately after the protocols. The reduction of systolic (-8.8±1.4 vs 1.3±1.2 mm Hg, P=.02), diastolic (-5.3±3.3 vs 1.8±1.1 mm Hg, P=.03), and mean (-7.9±3.6 vs 0.8±0.9 mm Hg, P=.01) 24-hour BP were found after the use of sildenafil compared with placebo. Improvement in daytime BP levels was also observed (systolic -6.0±4.7 vs 4.4±1.5 mm Hg [P=.02] and mean -4.8±3.9 vs 3.5±1.4 mm Hg [P=.02] for sildenafil vs placebo, respectively). Considering its antihypertensive effect, sildenafil may represent a therapeutic option for RH treatment.
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http://dx.doi.org/10.1111/jch.12850DOI Listing
November 2016

Increased Circulating Tissue Inhibitor of Metalloproteinase-2 Is Associated With Resistant Hypertension.

J Clin Hypertens (Greenwich) 2016 10 14;18(10):969-975. Epub 2016 Jul 14.

Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences and Teaching Hospital, University of Campinas (Unicamp), Campinas, Sao Paulo, Brazil.

Resistant hypertension (RH) is associated with organ damage and cardiovascular risk. Evidence suggests the involvement of matrix metalloproteinase 2 (MMP-2) and tissue inhibitor of metalloproteinase 2 (TIMP-2) in hypertension and in cardiovascular remodeling. The aim of this study was to assess the levels of MMP-2 and TIMP-2 in RH and its relation with organ damage, including arterial stiffness and cardiac hypertrophy. MMP-2 and TIMP-2 levels were compared among 19 patients with normotension (NT), 116 with nonresistant hypertension (HTN) and 116 patients with resistant HTN (RH). MMP-2 levels showed no differences among NT, HTN, and RH groups, while TIMP-2 levels were higher in RH compared with HTN and NT groups (90.0 [76.1-107.3] vs 70.1 [57.7-88.3] vs 54.7 [40.9-58.1] ng/mL, P<.01), respectively. MMP-2/TIMP-2 ratio was reduced in the RH group compared with the HTN and NT groups (2.7 [1.9-3.4] vs 3.3 [2.6-4.2] vs 4.9 [4.5-5.3], P<.01), respectively. No associations were found between MMP-2 levels, TIMP-2, and MMP-2/TIMP-2 ratio with cardiac hypertrophy and arterial stiffness in the RH and HTN groups. Finally, in a regression analysis, reduced MMP-2/TIMP-2 ratio and increased TIMP-2 levels were independently associated with RH. The present findings provide evidence that TIMP-2 is associated with RH and might be a possible biomarker for screening RH patients.
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http://dx.doi.org/10.1111/jch.12865DOI Listing
October 2016

Effects of leptin and leptin receptor SNPs on clinical- and metabolic-related traits in apparent treatment-resistant hypertension.

Blood Press 2017 Apr 16;26(2):74-80. Epub 2016 Jun 16.

a Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas , Campinas , SP , Brazil.

Leptin is associated to the lack of blood pressure control as well as target organ damage in resistant hypertensive (RH) subjects. Single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) genes, respectively, are associated with cardiovascular disease and metabolic syndrome. We evaluated the association of these two SNPs with clinical and biochemical features in 109 apparent treatment-RH subjects (aTRH) and 125 controlled hypertensives. Homozygous genotypes GG (n = 43) vs. AA (n = 14) for rs7799039 and AA (n = 34) vs. GG (n = 26) genotypes for rs1137101 were compared in aTRH subjects. There was no difference in leptin levels among both SNPs. On the other hand, LEP SNP (GG vs. AA) associated with the levels of glycated haemoglobin (6.4 ± 1.4 vs. 7.8 ± 2.3%, p = 0.03), insulin (8.6 ± 4.6 vs. 30.6 ± 27.7 uUI/mL, p = 0.01), HDL-cholesterol (51 ± 16 vs. 39 ± 11 mg/dL, p = 0.001) and PWV (9.5 ± 2.1 vs. 11.2 ± 2.8 m/s, p = 0.03). LEPR SNP (AA vs. GG), associated with heart rate (69 ± 12 vs. 67 ± 12 bpm, p = 0.03), fat mass (31 ± 11 vs. 24 ± 8 kg, p = 0.03) and triglycerides levels (175 ± 69 vs. 135 ± 75 mg/dL, p = 0.03). These findings may be clinically useful for identifying a group of aTRH who may have a LEP and/or LEPR gene variants, which may predispose this specific group to worse or better outcomes.
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http://dx.doi.org/10.1080/08037051.2016.1192945DOI Listing
April 2017

A practical approach for measurement of antihypertensive medication adherence in patients with resistant hypertension.

J Am Soc Hypertens 2016 06 5;10(6):510-516.e1. Epub 2016 Apr 5.

Cardiovascular Pharmacology Laboratory, Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil. Electronic address:

Confirmation of medication adherence is a challenge in clinical practice and essential for the accurate diagnosis of resistant hypertension. Although it is well established that drug adherence is critical for controlling blood pressure, there are still difficulties applying a simple, inexpensive, and reliable assessment of adherence in the clinical setting. We aimed to test a simple method to assess adherence in resistant hypertensive (RH) patients. A pilot study with normotensives or mild/moderate hypertensive subjects was performed to provide a fluorescence cutoff point for adherence. After that, 21 patients referred to the Resistant Hypertension Clinic had triamterene prescribed and were monitored for a 30-day period. We conducted two unannounced randomly selected home visits for urine collection to test drug intake that day. Office, home and 24-hour ambulatory blood pressure, biochemical data, and the 8-item Morisky Medication Adherence Scale (MMAS-8) were systematically acquired. According to adherence indicated by urine fluorescence, subjects were divided into adherent and nonadherent groups. We found 57% of nonadherence. No differences were found between groups regarding baseline characteristics or prescribed medications; Kappa's test showed concordance between adherence through MMAS-8 items and fluorescence (kappa = 0.61; 95% confidence interval: 0.28-0.94; P = .005). Nonadherent patients had higher office (81 ± 11 vs. 73 ± 6 mm Hg, P = .03), 24-hour ambulatory blood pressure monitoring (75 ± 9 vs. 66 ± 7 mm Hg, P = .01), and home blood pressure measurement (77 ± 9 vs. 67 ± 8 mm Hg, P = .01) diastolic blood pressure than their counterparts. Nonadherence to antihypertensive therapy is high in patients with RH, even when assessed in clinics specialized in this condition. Fluorometry to detect a drug in the urine of RH patients is safe, easy, and reliable method to assess adherence.
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http://dx.doi.org/10.1016/j.jash.2016.03.194DOI Listing
June 2016

Deregulation of Soluble Adhesion Molecules in Resistant Hypertension and Its Role in Cardiovascular Remodeling.

Circ J 2016 Apr 13;80(5):1196-201. Epub 2016 Apr 13.

Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas.

Background: Resistant hypertension (RHTN) and target organ damage are linked to increased inflammatory biomarkers, which may regulate adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1); and the platelet (P-selectin) and endothelial (E-selectin) selectins. We investigated a previously unknown relationship between soluble P-selectin (sP-selectin), E-selectin (sE-selectin), ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) with RHTN and target organ damage.

Methods and results: We included 110 subjects diagnosed for true RHTN and 112 mild-moderate hypertensive (HTN) patients. Blood pressure parameters, pulse wave velocity and left ventricular mass index (LVMI) were measured. Adhesion molecules were measured on ELISA. Both sP-selectin and sE-selectin were increased; in contrast, sICAM-1 was reduced in RHTN compared with HTN patients, while similar sVCAM-1 was noted in the groups. sP-selectin and sVCAM-1 were elevated in the presence of arterial stiffness (sP-selectin: 104±47 vs. 89±45 ng/ml, P<0.05; sVCAM-1: 1,189±411 vs. 1,060±412 ng/ml, P<0.05) and cardiac hypertrophy (sP-selectin: 105±51 vs. 88±43 ng/ml, P<0.05; sVCAM-1: 1,170±433 vs. 1,040±383 ng/ml, P<0.05) in all HTN patients. sP-selectin was associated with target organ damage after adjustment for age and BP. Apart from potential confounders, sE-selectin was a significant indicator of RHTN.

Conclusions: The adhesion molecule sP-selectin plays a role in cardiovascular damage, and sE-selectin in resistance to antihypertensive therapy. (Circ J 2016; 80: 1196-1201).
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http://dx.doi.org/10.1253/circj.CJ-16-0058DOI Listing
April 2016

Defined daily dose (DDD) and its potential use in clinical trials of resistant hypertension.

Int J Cardiol 2016 Jan 28;202:515-6. Epub 2015 Sep 28.

Department of Pharmacology, Faculty of Medical Sciences University of Campinas - UNICAMP, Campinas, SP, Brazil.

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http://dx.doi.org/10.1016/j.ijcard.2015.09.096DOI Listing
January 2016

Does Renal Denervation Fit All Resistant Hypertension? The Role of Genetics.

J Clin Hypertens (Greenwich) 2016 Feb 3;18(2):161-2. Epub 2015 Aug 3.

Department of Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.

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http://dx.doi.org/10.1111/jch.12642DOI Listing
February 2016

Role of MMP-2 and MMP-9 in resistance to drug therapy in patients with resistant hypertension.

Arq Bras Cardiol 2015 Aug 2;105(2):168-75. Epub 2015 Jun 2.

Núcleo de Pós-Graduação e Pesquisa, Santa Casa de Belo Horizonte, Belo Horizonte, MG, BR.

Background: Despite the increased evidence of the important role of matrix metalloproteinases (MMP-9 and MMP‑2) in the pathophysiology of hypertension, the profile of these molecules in resistant hypertension (RHTN) remains unknown.

Objectives: To compare the plasma levels of MMP-9 and MMP-2 and of their tissue inhibitors (TIMP-1 and TIMP-2, respectively), as well as their MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios, between patients with controlled RHTN (CRHTN, n=41) and uncontrolled RHTN (UCRHTN, n=35). In addition, the association of those parameters with clinical characteristics, office blood pressure (BP) and arterial stiffness (determined by pulse wave velocity) was evaluate in those subgroups.

Methods: This study included 76 individuals diagnosed with RHTN and submitted to physical examination, electrocardiogram, and laboratory tests to assess biochemical parameters.

Results: Similar values of MMP-9, MMP-2, TIMP-1, TIMP-2, and MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios were found in the UCRHTN and CRHTN subgroups (P>0.05). A significant correlation was found between diastolic BP (DBP) and MMP-9/TIMP-1 ratio (r=0.37; P=0.02) and DPB and MMP-2 (r=-0.40; P=0.02) in the UCRHTN subgroup. On the other hand, no correlation was observed in the CRHTN subgroup. Logistic regression models demonstrated that MMP-9, MMP-2, TIMP-1, TIMP-2 and their ratios were not associated with the lack of BP control.

Conclusion: These findings suggest that neither MMP-2 nor MMP-9 affect BP control in RHTN subjects.
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http://dx.doi.org/10.5935/abc.20150060DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4559126PMC
August 2015

Refractory and resistant hypertension: characteristics and differences observed in a specialized clinic.

J Am Soc Hypertens 2015 May 19;9(5):397-402. Epub 2015 Mar 19.

Faculty of Medical Sciences, Department of Pharmacology, Laboratory of Cardiovascular Pharmacology, University of Campinas, Campinas, SP, Brazil.

Resistant hypertension (RH) is defined as uncontrolled blood pressure (BP) despite the use of ≥3 anti-hypertensive drugs, or controlled requiring use of ≥4 drugs. Recently, a new definition for an extreme phenotype of RH (uncontrolled BP using at least five drugs) has emerged-the refractory hypertension (RfH). Although characteristics of RH are well established, little is known about this newly described subgroup. For this work, 116 subjects with RH were enrolled from a specialized clinic and divided into RH (n = 80) and RfH (n = 36). Subjects were submitted to echocardiography, 24-hour ambulatory BP measurement and biochemical analyses. Logistic regression analysis demonstrated that: (1) white-coat effect (odds ratio [OR], 3.23; 95% confidence interval [CI], 1.12-9.27; P = .03), (2) black race (OR, 6.67; 95% CI, 1.99-16.16; P < .001), and (3) left ventricular mass index (OR, 1.02; 95% CI, 1.01-1.03; P = .04) were independent predictors of refractoriness. In conclusion, RfH and RH present different patient characteristics, and these phenotypic aspects can be useful for better understanding this harder-to-treat subgroup.
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http://dx.doi.org/10.1016/j.jash.2015.03.005DOI Listing
May 2015

Resistant hypertension: a volemic or nervous matter?

J Am Soc Hypertens 2015 May 9;9(5):408-9. Epub 2015 Feb 9.

Faculty of Medical Sciences, Laboratory of Cardiovascular Pharmacology, University of Campinas, Campinas, SP, Brazil.

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http://dx.doi.org/10.1016/j.jash.2015.01.014DOI Listing
May 2015

Adiponectin -11377C/G and +276G/T polymorphisms affect adiponectin levels but do not modify responsiveness to therapy in resistant hypertension.

Basic Clin Pharmacol Toxicol 2015 Jul 14;117(1):65-72. Epub 2015 Jan 14.

Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, Campinas, SP, Brazil.

Resistant hypertension (RHTN) is a multifactorial and polygenic disease, frequently associated with obesity. Low plasma adiponectin levels, a hormone produced by the adipose tissue, were associated with RHTN. Single nucleotide polymorphisms (SNPs) -11377C/G (rs266729) and +276G/T (rs1501299) in ADIPOQ (adiponectin gene) were associated with hypertension. This study evaluated the association between two SNPs (-11377C/G and +276G/T) and adiponectin levels in RHTN. This study comprised 109 patients with RHTN genotyped for both polymorphisms. A cross-sectional study was designed to compare features of CC homozygous versus G allele carriers for -11377C/G and GG homozygous versus T allele carriers for +276G/T. Office and ambulatory BP measurements were similar among genotypes subgroups in both SNPs as well as the markers of target organ damage (arterial stiffness, left ventricular mass index and microalbuminuria). Adiponectin concentrations were significantly higher in CC compared to G carrier for -11377C/G (CC:7.0 (4.0-10.2) versus G allele:5.5 (2.5-7.9), p = 0.04) and lower in GG compared to T carrier for +276G/T (GG:5.3 (2.3-7.7) versus T allele:7.1 (3.6-10.5), p = 0.04). Adjusting for systolic ambulatory BP, body mass index, age, gender, race and presence of type 2 diabetes, multiple linear regression analyses revealed that the minor alleles G (β-coefficient= -0.14, SE=0.07, p = 0.03) and T (β-coefficient=0.12, SE=0.06, p = 0.04) were independent predictors of adiponectin. The -11377C/G and +276G/T SNPs in ADIPOQ were associated with adiponectin levels in RHTN individuals.
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http://dx.doi.org/10.1111/bcpt.12368DOI Listing
July 2015

Adipokines: novel players in resistant hypertension.

J Clin Hypertens (Greenwich) 2014 Oct 4;16(10):754-9. Epub 2014 Sep 4.

Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP, Brazil.

Resistant hypertension (RH) is a multifactorial disease, frequently associated with obesity and characterized by blood pressure above goal (140/90 mm Hg) despite the concurrent use of ≥3 antihypertensive drugs of different classes. The mechanisms of obesity-related hypertension include, among others, aldosterone excess and inflammatory adipokines, which have demonstrated a significant role in the pathogenesis of metabolic syndrome and RH. This review aims to summarize recent studies on the role of the adipokines leptin, resistin, and adiponectin in the pathophysiology of RH and target-organ damage associated with this condition. The deregulation of adipokine levels has been associated with clinical characteristics frequently recognized in RH such as diabetes, hyperactivity of sympathetic and renin-angiotensin-aldosterone systems, and vascular and renal damage. Strategies to regulate adipokines may be promising for the management of RH and some clinical implications must be considered when managing controlled and uncontrolled patients with RH.
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http://dx.doi.org/10.1111/jch.12399DOI Listing
October 2014

Resistant or refractory hypertension: are they different?

Curr Hypertens Rep 2014 Oct;16(10):485

Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas, FCM 10 Building, 1st Floor, Campinas, SP, Brazil, 13083-970.

Resistant hypertension (RHTN) consists in a condition where blood pressure (BP) levels remain uncontrolled despite the use of at least three drugs or if the control happens with four or more drugs. Throughout the last 50 years, it has been increasingly studied, and its phenotypes have been identified. The term refractory hypertension has been used concurrently with RHTN all those years, but in the last decade, it has been applied to the most afflicted part of RHTN--defined as the uncontrolled RHTN or as the uncontrolled RHTN who needs five or more drugs. Differences between those two phenotypes are being recently identified, especially classifying refractory subjects as having more: (1) cardiovascular risk, (2) target organ damage, (3) African-descending race, (4) coronary heart disease and myocardial ischemia, (5) aldosterone excess, (6) deregulation of adipokines, and (7) possible sympathetic hyperactivation. We review the most important studies in both resistant and refractory hypertension to gather the up-to-date data regarding the characteristics of these two high-risk groups of patients.
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http://dx.doi.org/10.1007/s11906-014-0485-1DOI Listing
October 2014

Predictors of silent myocardial ischemia in resistant hypertensive patients.

Am J Hypertens 2015 Feb 25;28(2):200-7. Epub 2014 Jul 25.

Department of Pharmacology, Faculty of Medical Sciences University of Campinas-UNICAMP, Campinas, SP, Brazil;

Background: Hypertension is the most prevalent and significant modifiable risk factor for coronary heart disease. A portion of patients with uncontrolled hypertension are considered to have resistant hypertension (RHTN). Myocardial ischemia incidence increases along with blood pressure (BP) levels. However, the prevalence of myocardial ischemia in patients with RHTN, as well as the factors associated with it, is unknown.

Methods: We enrolled 129 patients with true RHTN regularly followed in our specialty hypertension clinic and evaluated then by resting and dipyridamole pharmacological stress myocardial perfusion scintigraphy. Patients were then divided into 2 groups: those with (I-RHTN; n = 36) and those without (NI-RHTN; n = 93) myocardial ischemia. Echocardiography, 24-hour ambulatory BP monitoring (ABPM), and flow mediated dilation (FMD) were also evaluated.

Results: Thirty six (28%) patients had myocardial ischemia. There was no difference between groups regarding age, sex, biochemical parameters, office, and 24-hour ABPM levels. Patients in the I-RHTN group were more likely diabetic (31% vs. 11%; P < 0.05) and obese (75% vs. 40%; P < 0.001). Adjusting for age and body mass index, multiple logistic regression showed that diabetes (odds ratio (OR) = 6.5; 95% confidence interval (CI) = 1.06-40.14; P = 0.04), FMD (OR = 0.18; 95% CI = 0.07-0.41; P < 0.001), heart rate (OR = 1.23; 95% CI = 1.11-1.36; P < 0.001), left ventricular mass index (OR = 1.02; 95% CI = 1.01-1.04; P = 0.04), and microalbuminuria (OR = 1.02; 95% CI = 1.01-1.04; P = 0.002) were independent predictors of ischemia.

Conclusions: In conclusion, there is a high prevalence of myocardial ischemia in patients with RHTN. Increased microalbuminuria, heart rate, endothelial dysfunction, and left ventricular mass can be useful to guide the investigation for myocardial ischemia in these high risk patients.
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http://dx.doi.org/10.1093/ajh/hpu140DOI Listing
February 2015

Increased arterial stiffness in resistant hypertension is associated with inflammatory biomarkers.

Blood Press 2015 Feb 25;24(1):7-13. Epub 2014 Jul 25.

Laboratory of Cardiovascular Pharmacology, Faculty of Medical Sciences, University of Campinas (Unicamp) , Campinas , Brazil.

Background: Increased levels of inflammatory biomarkers such as interleukin-6 (IL-6), 10 (IL-10), 1β (IL-1β), tumor necrosis factor-α (TNF-α) high-sensitivity C-reactive protein (hs-CRP) are associated with arterial stiffness in hypertension. Indeed, resistant hypertension (RHTN) leads to unfavorable prognosis attributed to poor blood pressure (BP) control and target organ damage. This study evaluated the potential impact of inflammatory biomarkers on arterial stiffness in RHTN.

Methods: In this cross-sectional study, 32 RHTN, 20 mild hypertensive (HTN) and 20 normotensive (NT) patients were subjected to office BP and arterial stiffness measurements assessed by pulse wave velocity (PWV). Inflammatory biomarkers were measured in plasma samples.

Results: PWV was increased in RHTN compared with HTN and NT (p < 0.05). TNF-α levels were significantly higher in RHTN and HTN than NT patients. No differences in IL-6 levels were observed. RHTN patients had a higher frequency of subjects with increased levels of IL-10 and IL-1β compared with HTN and NT patients. Finally, IL-1β was independently associated with PWV (p < 0.001; R(2) = 0.5; β = 0.077).

Conclusion: RHTN subjects have higher levels of inflammatory cytokines (TNF-α, IL-1β and IL-10) as well as increased arterial stiffness, and detectable IL-1β levels are associated arterial stiffness. These findings suggest that inflammation plays a possible role in the pathophysiology of RHTN.
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http://dx.doi.org/10.3109/08037051.2014.940710DOI Listing
February 2015

Seeds' physicochemical traits and mucilage protection against aluminum effect during germination and root elongation as important factors in a biofuel seed crop (Ricinus communis).

Environ Sci Pollut Res Int 2014 Oct 11;21(19):11572-9. Epub 2014 Jun 11.

Plant Physiology Laboratory, Biological Science Institute, Federal University of Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG, 31.270-901, Brazil.

We determined the length, volume, dry biomass, and density in seeds of five castor bean cultivars and verified notable physicochemical trait differences. Seeds were then subjected to different toxic aluminum (Al) concentrations to evaluate germination, relative root elongation, and the role of root apices' rhizosphere mucilage layer. Seeds' physicochemical traits were associated with Al toxicity responses, and the absence of Al in cotyledons near to the embryo was revealed by Al-hematoxylin staining, indicating that Al did not induce significant germination reduction rates between cultivars. However, in the more sensitive cultivar, Al was found around the embryo, contributing to subsequent growth inhibition. After this, to investigate the role of mucilage in Al tolerance, an assay was conducted using NH4Cl to remove root mucilage before or after exposure to different Al concentrations. Sequentially, the roots were stained with hematoxylin and a quantitative analysis of staining intensity was obtained. These results revealed the significant contribution of the mucilage layer to Al toxicity responses in castor bean seedlings. Root growth elongation under Al toxicity confirmed the role of the mucilage layer, which jointly indicated the differential Al tolerance between cultivars and an efficient Al-exclusion mechanism in the tolerant cultivar.
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http://dx.doi.org/10.1007/s11356-014-3147-6DOI Listing
October 2014
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