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1.
Hypertens Res ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32398795

RESUMO

Patients with coronary heart disease (CHD) can be particularly susceptible to the adverse effects of excessive blood pressure (BP) lowering by antihypertensive treatment. The identification of hypotension is thus especially important. This study estimated the prevalence of hypotension among CHD-treated hypertensive patients undergoing ambulatory blood pressure monitoring (ABPM) in routine clinical practice. We performed a cross-sectional study with 2892 CHD-treated hypertensive patients from the Spanish ABPM Registry. Based on previous studies, hypotension was defined as systolic/diastolic BP < 120 and/or 70 mmHg according to office measurements, <115 and/or 65 mmHg according to daytime ABPM, <100 and/or 50 mmHg according to nighttime ABPM, and <110 and/or 60 mmHg according to 24 h ABPM. The participants' mean age was 67.1 years (69.8% men). A total of 19.6% of the patients had office hypotension, 26.5% had daytime hypotension, 9.0% had nighttime hypotension, and 16.1% had 24-hr ABPM hypotension. Low diastolic BP values were responsible for most cases of hypotension. Fifty-eight percent of the cases of hypotension detected by daytime ABPM did not correspond to hypotension according to office BP. The variables independently associated with daytime ambulatory systolic/diastolic hypotension and diastolic hypotension (the latter being the most frequent type of ambulatory hypotension) were age, female sex, and the number of antihypertensive medications. In conclusion, in a large ABPM registry, one out of every four CHD-treated hypertensive patients was potentially at risk because of hypotension according to daytime ABPM, and more than half of them were not identified if office BP was relied on alone. We suggest that ABPM should be performed in these patients.

2.
J Hypertens ; 38(6): 1005-1015, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32371788

RESUMO

: The issue of a potential danger of antihypertensive drugs related to cancer susceptibility is currently generating a major debate in the scientific community, concerns in the public and emphasized interest from the media. The present article is a thorough review of what is known on the various classes of antihypertensive drugs concerning the risk of developing different neoplasms and about the suggested pathophysiological mechanisms, whenever available. The main limitations of evidence derived from studies currently available in this setting are also discussed, high-lightening the need for newly developed approaches to generate more accurate recommendations and informed advice for physicians.

3.
J Proteomics ; 222: 103816, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32389841

RESUMO

Several models are available to calculate the risk of developing cardiovascular complications in mid-life. The estimation of lifetime risk in the long-term remains an unmet clinical need. We previously identified new molecular plasma signatures for cardiovascular risk stratification in a young population (30-50-years old). The aim of the present study was to determine if the specific signature found in young population changes with age. Proteomic analysis was performed in plasma samples obtained from different age groups, middle-age (50-70-years old, n = 63) and elderly (>70-years old, n = 61), which, in turn were classified into 3 subgroups according to cardiovascular risk. Our previous results in a young population clearly showed two different proteomic signatures. Building on these findings, targeted-mass spectrometry and turbidimetry analyses were used to test these signatures in middle-age and elderly populations. This strategy identified three common proteomic signatures between young and adult patients related to cardiovascular stratification, organ damage and risk prediction. Furthermore, receiver operating characteristic analysis revealed the potential value of these novel markers for lifetime risk stratification. Our results provide new insight into altered molecular mechanisms in the pathogenesis of cardiovascular disease and, more importantly, identify novel protein panels that can stratify patients throughout life. SIGNIFICANCE: Our results revealed three common proteomic signatures between young and adult patients related to cardiovascular stratification, organ damage and risk prediction. The results obtained provide a deeper insight into the pathogenesis of CV diseases and allow the identification of novel protein panels to stratify patients according to CV risk throughout life. While current estimators calculate the risk of having a CV event considering age as the most important factor to CV disease, our results represent an alternative to traditional CV risk factors, allowing the stratification of CV risk regardless of the age. Using a combination of traditional markers and established algorithms with these findings as a future preventive strategy, could facilitate an adequate assessment of CV risk.

4.
J Physiother ; 66(2): 89-96, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32291224

RESUMO

QUESTIONS: Does neuromuscular electrical stimulation (NMES) applied during haemodialysis sessions improve functional capacity in people with end-stage renal disease? Does NMES used in this way also improve muscle strength, muscle mass/architecture, psychological outcomes, cardiovascular outcomes and biochemical variables? Does it have any adverse effects? DESIGN: Systematic review of randomised controlled trials with meta-analysis. PubMed, Web of Science, Scopus and SPORTDiscus were searched from inception to 15 October 2019. PARTICIPANTS: Patients receiving haemodialysis for end-stage renal disease. INTERVENTION: NMES administered during haemodialysis sessions versus control. OUTCOMES MEASURES: Functional capacity, muscle strength, muscle mass, psychological outcomes, cardiovascular outcomes, biochemical variables and adverse events. DATA ANALYSIS: Data were meta-analysed where possible and results were expressed as the pooled mean difference between groups with a 95% confidence interval. RESULTS: Eight studies (221 patients) were included in the analysis. Overall, the methodological quality of the studies was fair to good. NMES improved functional capacity as assessed by the 6-minute walk distance test (MD 31 m, 95% CI 13 to 49) and peak workload attained in incremental exercise (MD 12.5 W, 95% CI 3.2 to 21.9). NMES increased knee extensor muscle strength (MD 3.5 kg, 95% CI 2.3 to 4.7) and handgrip strength (MD 2.4 kg, 95% CI 0.4 to 4.4). Muscle mass/architecture was not substantially affected. NMES was estimated to be beneficial for several domains of quality of life in several studies, although most of these estimates were imprecise. No benefits were found for cardiovascular outcomes. The available data did not establish any clear effects on cardiovascular outcomes or biochemical variables (dialysis efficiency, urea and creatinine). No major NMES-related adverse events were observed. CONCLUSIONS: NMES is safe, practical and effective for improving functional capacity and muscle strength in haemodialysis patients. Further research is needed to confirm the clinical relevance of these findings. REGISTRATION: PROSPERO CRD42018107323.

5.
Nefrologia ; 2020 Mar 03.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-32144010

RESUMO

BACKGROUND AND AIM: Albuminuria is an indicator of sub-clinical organ damage and a marker of cardiovascular risk and renal disease. A percentage of hypertensive patients develop albuminuria despite being under chronic suppression of the renin-angiotensin system (RAS). We previously identified urinary metabolites associated with the development of albuminuria. In this study, we searched for metabolic alterations which reflect different levels within the condition of normoalbuminuria. PATIENTS, MATERIALS AND METHODS: Urine from 48 hypertensive patients under chronic RAS suppression was analysed. They were classified according to the albumin/creatinine ratio (ACR) into 3groups: Normoalbuminuria (<10mg/g); high-normal (10-30mg/g in men, or 20-40mg/g in women); and moderately high albuminuria (microalbuminuria, 30-200mg/g or 40-300mg/g, respectively). The metabolome was analysed by mass spectrometry and a correlation analysis was performed between altered metabolite levels and ACR. RESULTS: Oxaloacetate, 3-ureidopropionate, guanidoacetate and malate show significant variation between the normo and micro groups. Additionally, these metabolites are able to differentiate between patients in the normo and high-normal range. A significant correlation between metabolites and ACR was found. Observed variations point to alterations in the energy metabolism already in patients with albuminuria in the high-normal range. CONCLUSIONS: The association between the molecular panel consisting of 3-ureidopropionate, oxaloacetate, malate and guanidoacetate and different levels of albuminuria is confirmed. A metabolic fingerprint was also identified showing variations within the condition of normoalbuminuria allowing an earlier molecular stratification of patients.

6.
Am J Nephrol ; 51(4): 294-303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32088716

RESUMO

BACKGROUND: Development of albuminuria and arterial stiffness in Munich Wistar Frömter (MWF) rats, a model of chronic kidney disease, is related to alterations in extracellular matrix, increased oxidative stress, and endothelial dysfunction. Finerenone (FIN), a novel, nonsteroidal, potent, and selective mineralocorticoid receptor antagonist, improves endothelial dysfunction through enhancing nitric oxide (NO) bioavailability and decreasing superoxide anion levels due to an upregulation in vascular and renal superoxide dismutase activity. We hypothesize that FIN reduces arterial stiffness in this model associated to the reduction in albuminuria and matrix metalloproteinase (MMP)-2/9 activity. METHODS: Twelve-week-old MWF rats with established albuminuria and age-matched normoalbuminuric Wistar (W) rats were treated with FIN (10 mg/kg/day, once-daily oral gavage) or with vehicle (control, C) for 4 weeks. RESULTS: Arterial stiffness was significantly higher in mesenteric arteries (MA) of MWF-C as compared to W-C. FIN treatment significantly lowered ß-index, a measure of intrinsic stiffness independent of geometry, in MWF (ßMWF-FIN = 7.7 ± 0.4 vs. ßMWF-C = 9.2 ± 0.5, p < 0.05) positively correlating with urinary albumin excretion. Elastin fenestrae area in the internal elastic lamina of MA from MWF-FIN was significantly larger (+377%, p < 0.05). FIN increased plasma pro-MMP-2 and decreased plasma MMP-2 and MMP-9 activities, correlating with reductions in ß-index. MA from MWF-FIN exhibited higher NO bioavailability and reduced superoxide anion levels compared to MWF-C. CONCLUSION: FIN treatment reduces intrinsic arterial stiffness in MA from MWF rats associated with changes in elastin organization, normalization of MMP-2 and MMP-9 activities, and reduction of oxidative stress. Moreover, reduction of arterial stiffness correlates with reduction in albuminuria.

7.
Circulation ; 141(4): 240-242, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31986090
10.
Hypertension ; : HYPERTENSIONAHA11914508, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-31983311

RESUMO

The prognostic relevance of short-term blood pressure (BP) variability in hypertension is not clearly established. We aimed to evaluate the association of short-term BP variability, assessed through ambulatory BP monitoring, with total and cardiovascular mortality in a large cohort of patients with hypertension. We selected 63 910 subjects from the Spanish ABPM Registry from 2004 to 2014, with a median follow-up of 4.7 years. Systolic and diastolic BP SD from 24 hours, daytime, and nighttime, weighted SD (mean of daytime and nighttime SD weighted for period duration), average real variability (mean of differences between consecutive readings), variation independent of the mean, and BP variability ratio (ratio between systolic and diastolic 24-hour SD) were calculated through 24-hour ambulatory BP monitoring performed at baseline. Association with total and cardiovascular mortality (obtained through death certificates) were assessed by Cox regression models adjusted for clinical confounders and BP. Patients who died during follow-up had higher values of BP variability compared with those remaining alive. In fully adjusted models, daytime, nighttime, and weighted SD, systolic and diastolic, as well as diastolic average real variability, were all significantly associated with total and cardiovascular mortality. Hazard ratios for 1 SD increase ranged from 1.05 to 1.09 for total mortality and from 1.07 to 1.12 for cardiovascular mortality. A nighttime systolic SD ≥12 mm Hg was independently associated with total (hazard ratio: 1.13 [95% CI, 1.06-1.21]) and cardiovascular mortality (hazard ratio: 1.21 [95% CI, 1.09-1.36]). We conclude that short-term BP variability is independently associated with total and cardiovascular mortality in patients with hypertension.

11.
J Hypertens ; 38(5): 845-849, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31977571

RESUMO

INTRODUCTION: Air in urban areas is usually contaminated with particle matter. High concentrations lead to a rise in the risk of cardiovascular and respiratory diseases. Some studies have reported that ultrafine particles (UFP) play a greater role in cardiovascular diseases than other particle matter, particularly regarding hypertensive crises and DBP, although in the latter such effects were described concerning clinical blood pressure (BP). In this study, we evaluate the relationship between 24-h ambulatory BP monitoring (ABPM) and atmospheric UFP concentrations in Barcelona. METHODS: An observational study of individual patients' temporal and geographical characteristics attended in Primary Care Centres and Hypertensive Units during 2009-2014 was performed. RESULTS: The participants were 521 hypertensive patients, mean age 56.8 years (SD 14.5), 52.4% were women. Mean BMI was 28.0 kg/m and the most prominent cardiovascular risk factors were diabetes (N = 66, 12.7%) and smoking (N = 79, 15.2%). We describe UFP effects at short-term and up to 1 week (from lag 0 to 7). For every 10 000 particle/cm UFP increase measured at an urban background site, a corresponding statistically significant increase of 2.7 mmHg [95% confidence interval = (0.5-4.8)] in 24-h DBP with ABPM for the following day was observed (lag 1). CONCLUSION: We have observed that a rise in UFP concentrations during the day prior to ABPM is significantly associated with an increase in 24 h and diurnal DBP. It has been increasingly demonstrated that UFP play a key role in cardiovascular risk factors and, as we have demonstrated, in good BP control.

13.
Eur J Prev Cardiol ; : 2047487319894880, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31850796

RESUMO

AIMS: Our primary objective was to improve risk assessment for fatal and non-fatal cardiovascular events in a working population, mostly young and healthy. METHODS: We conducted a prospective cohort study to derive a survival model to predict fatal and non-fatal 10-year cardiovascular risk. We recruited 992,523 workers, free of diagnosed cardiovascular disease at entry, over six years, from 2004-2009. We divided the sample into two independent cohorts: a derivation one (626,515 workers; from 2004-2006) and a temporal validation one (366,008 workers; over 2007-2009). Then, we followed both cohorts over 10 years and registered all fatal and non-fatal cardiovascular events. We built a new risk calculator using an estimation of cardiovascular biological age as a predictor and named it IberScore. There were remarkable differences between this new model and Systematic Coronary Risk Evaluation (SCORE) (in both the specification and the equation). RESULTS: Over the 10-year follow-up, we found 3762 first cardiovascular events (6‰) in the derivation cohort. Most of them (80.3%) were non-fatal ischaemic events. If we had been able to use our model at the beginning of the study, we had classified in the 'high-risk' or 'very high-risk' groups 82% of those who suffered a cardiovascular event during the follow-up. All the post-estimation tests showed superior performance (true positive rate: 81.8% vs 11.8%), higher discrimination power and better clinical utility (standardised net benefit: 58% vs 13%) for IberScore when compared to SCORE. CONCLUSION: Risk assessment of fatal and non-fatal cardiovascular events in young and healthy workers was improved when compared to the previously used model (SCORE). The latter was not reliable to predict cardiovascular risk in our sample. The new model showed superior clinical utility and provided four useful measures for risk assessment. We gained valuable insight into cardiovascular ageing and its predictors.

14.
Am J Nephrol ; 50(5): 333-344, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31655812

RESUMO

BACKGROUND: Among diabetics, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality, and progression of their underlying disease. Finerenone is a novel, non-steroidal, selective mineralocorticoid-receptor antagonist which has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD), while revealing only a low risk of hyperkalemia. However, the effect of finerenone on renal and CV outcomes has not been investigated in long-term trials yet. METHODS: The Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease -(FIDELIO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important renal and CV outcomes in T2D patients with CKD. FIDELIO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 5.5 years. FIDELIO-DKD randomized 5,734 patients with an estimated glomerular filtration rate (eGFR) ≥25-<75 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30-≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of kidney failure, a sustained decrease of eGFR ≥40% from baseline over at least 4 weeks, or renal death. CONCLUSION: FIDELIO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of renal and CV events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen.

15.
Am J Nephrol ; 50(5): 345-356, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31665733

RESUMO

BACKGROUND: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. PATIENTS AND METHODS: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate ≥25 mL/min/1.73 m2 and albuminuria (urinary albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level α = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. CONCLUSIONS: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. TRIAL REGISTRATION: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049.

16.
Artigo em Inglês | MEDLINE | ID: mdl-31598644

RESUMO

Resistant hypertension (RH) is a concept that currently goes beyond the classical definition of blood pressure (BP) ≥140/90 mmHg in subjects receiving three or more drugs of different classes at maximally tolerated doses. Here we review the clinical relevance of RH and the different types of RH-associated phenotypes, namely refractory hypertension, controlled resistant hypertension, and masked uncontrolled hypertension. We also discuss current drug strategies and future treatments for these high-risk phenotypes.

19.
Eur Heart J ; 40(21): 1660-1661, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31152547
20.
Hypertension ; 74(1): 130-136, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31132953

RESUMO

United States and European guidelines have recommended new treatment goals for office blood pressure (BP). We examined 9784 hypertensives of the Spanish Ambulatory BP Monitoring (ABPM) registry with office BP treated to the prior goal (<140/90 mm Hg); and evaluated the frequency and all-cause mortality of 4 BP strata depending on whether or not they attained more conservative or new office BP goal (130-139/80-89 and <130/80 mm Hg, respectively) and whether or not BP was controlled according to ABPM criteria in the European and US guidelines (24-hour ambulatory BP <130/80 and <125/75 mm Hg, respectively). Whether achieving or not the new office BP goal, the total-mortality risk during a 5-year follow-up was only significantly higher than the reference (normal office BP and ABPM) when 24-hour ambulatory BP was above goal (hazard ratio from multivariable Cox models was in the range of 2.4-2.9; P<0.001). The frequency of patients achieving the new office BP goal was 34.4%, and the frequencies of those not achieving the ABPM goal were 31.6% and 53.7% using the 130/80 or the 125/75 ABPM goal, respectively. Mean office systolic BP was 129 mm Hg for patients not achieving the ABPM goal. In hypertensive patients controlled under prior office BP goal, the frequency of those achieving new office BP goal <130/80 was high, suggesting this goal can be attained. In addition, patients had a higher mortality risk only when ABPM was above goal despite having mean office systolic BP under control, a condition that was also common.


Assuntos
Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial/normas , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Guias de Prática Clínica como Assunto/normas , Sistema de Registros , Idoso , Determinação da Pressão Arterial/normas , Estudos de Coortes , Feminino , Objetivos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Valores de Referência , Espanha , Resultado do Tratamento
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