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Aims Finerenone reduces the risk of cardiovascular events in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). We investigated the causes of mortality in the FIDELITY population. Methods and results The FIDELITY prespecified pooled data analysis from FIDELIO-DKD and FIGARO-DKD excluded patients with heart failure and reduced ejection fraction. Outcomes included intention-to-treat and prespecified on-treatment analyses of the risk of all-cause and cardiovascular mortality. Of 13 026 patients [mean age, 64.8 years; mean estimated glomerular filtration rate (eGFR), 57.6 mL/min/1.73 m2], 99.8% were on renin–angiotensin system inhibitors. Finerenone reduced the incidence of all-cause and cardiovascular mortality vs. placebo (8.5% vs. 9.4% and 4.9% vs. 5.6%, respectively) and demonstrated significant on-treatment reductions [hazard ratio (HR), 0.82; 95% confidence interval (CI), 0.70–0.96; P = 0.014 and HR, 0.82; 95% CI, 0.67–0.99; P = 0.040, respectively]. Cardiovascular-related mortality was most common, and finerenone lowered the incidence of sudden cardiac death vs. placebo [1.3% (incidence rate 0.44/100 patient-years) vs. 1.8% (0.58/100 patient-years), respectively; HR, 0.75; 95% CI, 0.57–0.996; P = 0.046]. The effects of finerenone on mortality were similar across all Kidney Disease: Improving Global Outcomes risk groups. Event probability with finerenone at 4 years was consistent irrespective of baseline urine albumin-to-creatinine ratio, but seemingly more pronounced in patients with higher baseline eGFR. Conclusion In FIDELITY, finerenone significantly reduced the risk of all-cause and cardiovascular mortality vs. placebo in patients with T2D across a broad spectrum of CKD stages while on treatment, as well as sudden cardiac death in the intention-to-treat population. Clinical trials registration FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG).

Chronic kidney disease (CKD) is projected to become a leading global cause of death by 2040, and its early detection is critical for effective and timely management. The current definition of CKD identifies only advanced stages, when kidney injury has already destroyed >50% of functioning kidney mass as reflected by an estimated glomerular filtration rate six-fold higher than physiological levels (i.e. > 30 mg/g). An elevated urinary albumin-excretion rate is a known early predictor of future cardiovascular events. There is thus a ‘blind spot’ in the detection of CKD, when kidney injury is present but is undetectable by current diagnostic criteria, and no intervention is made before renal and cardiovascular damage occurs. The present review discusses the CKD ‘blind spot’ concept and how it may facilitate a holistic approach to CKD and cardiovascular disease prevention and implement the call for albuminuria screening implicit in current guidelines. Cardiorenal risk associated with albuminuria in the high-normal range, novel genetic and biochemical markers of elevated cardiorenal risk, and the role of heart and kidney protective drugs evaluated in recent clinical trials are also discussed. As albuminuria is a major risk factor for cardiovascular and renal disease, starting from levels not yet considered in the definition of CKD, the implementation of opportunistic or systematic albuminuria screening and therapy, possibly complemented with novel early biomarkers, has the potential to improve cardiorenal outcomes and mitigate the dismal 2040 projections for CKD and related cardiovascular burden.

Even though it has been more than a decade since renal denervation (RDN) was first used to treat hypertension and an intense effort on researching this therapy has been made, it is still not clear how RDN fits into the antihypertensive arsenal. There is no question that RDN lowers blood pressure (BP), it does so to an extent at best corresponding to one antihypertensive drug. The procedure has an excellent safety record. However, it remains clinically impossible to predict whose BP responds to RDN and whose does not. Long-term efficacy data on BP reduction are still unconvincing despite the recent results in the SPYRAL HTN-ON MED trial; experimental studies indicate that reinnervation is occurring after RDN. Although BP is an acceptable surrogate endpoint, there is complete lack of outcome data with RDN. Clear indications for RDN are lacking although patients with resistant hypertension, those with documented increase in activity of the sympathetic system and perhaps those who desire to take fewest medication may be considered. ispartof: JOURNAL OF HYPERTENSION vol:40 issue:10 pages:1859-1875 ispartof: location:Netherlands status: published

Objectives Resting heart rate (HR) taken in the office has been shown to be associated with cardiovascular outcomes in the general population, hypertension and heart failure. It is unknown whether 24-h oscillographic pulse rate measurement as an approximation of HR derived from ambulatory blood pressure monitoring (ABPM) associates with cardiovascular outcomes in hypertensive patients. Methods We evaluated ABPM recordings from 56 901 patients with complete 3373 421 HR measures entering the final analysis from the Spanish Blood Pressure Monitoring Registry for a median follow-up time of 5.1 years. We explored the association of office HR, mean 24-h HR, mean day HR, mean night HR as well as day-night HR differences, morning mean HR, morning HR surge and night peak HR to all-cause death, cardiovascular death and noncardiovascular death. Data were analyzed by Cox regression analysis, analysis of variance and chi-square test. Results The Spanish ABPM Registry recorded data in 223 primary care centers in Spain from 2004 until 31 December 2014 at the end of recruitment. Office HR was 3.5 bpm higher than mean 24-h HR, office mean HR versus mean night was 10.4 bpm higher and mean day versus mean night HR 9.3 bpm higher, while there were no relevant difference between office and mean day HR. Office mean, 24-h day and night HR more than 90 bpm were associated with an increased risk for all-cause and noncardiovascular death, whereas for cardiovascular death only mean night HR was predictive. The strongest association to all-cause death was observed with mean night HR [hazard ratio 3.80 (2.87-5.03)], mean 24-h HR [2.85 (2.30-3.54)] and mean day HR [2.22 (1.83-2.70)]. Day-night dipping of more than 8 bpm was associated with a 20% lesser risk on all-cause, cardiovascular and noncardiovascular death. Results were robust after adjusting for relevant risk indicators. Conclusion HR parameters derived from ABPM provide important information, in particular association with death by mean night HR, mean 24-h HR and reduced day-night HR dipping less than 8 bpm superior to office HR.

Aims Finerenone, a selective, non-steroidal mineralocorticoid receptor antagonist, improves cardiovascular (CV) and kidney outcomes in patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). This subgroup analysis of FIDELITY, a pre-specified, pooled, individual patient-data analysis of FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049), compared finerenone vs. placebo in patients with and without baseline history of atherosclerotic CV disease (ASCVD). Methods and results Outcomes included a composite CV outcome [CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure (HHF)]; CV death or HHF; a composite kidney outcome (kidney failure, sustained estimated glomerular filtration rate decrease ≥57%, or kidney-related death); all-cause mortality; and safety by baseline history of ASCVD. Of 13 026 patients, 5935 (45.6%) had a history of ASCVD. The incidence of the composite CV outcome, CV death or HHF, and all-cause mortality was higher in patients with ASCVD vs. those without, with no difference between groups in the composite kidney outcome. Finerenone consistently reduced outcomes vs. placebo in patients with and without ASCVD (P-interaction for the composite CV outcome, CV death or HHF, the composite kidney outcome, and all-cause mortality 0.38, 0.68, 0.33, and 0.38, respectively). Investigator-reported treatment-emergent adverse events were consistent between treatment arms across ASCVD subgroups. Conclusion Finerenone reduced the risk of CV and kidney outcomes consistently across the spectrum of CKD in patients with T2D, irrespective of prevalent ASCVD.

La pandemia producida por el coronavirus SARS-CoV-2 (COVID-19) ha obligado, en muchos casos a sustituir la consulta presencial por la consulta telemática para reducir el riesgo de contagio asociado a la presencia de pacientes en los centros sanitarios. Este cambio puede representar una oportunidad para una comunicación diferente y más eficiente entre profesionales y pacientes, permitiendo mejorar la accesibilidad a la atención médica y un abordaje más sistemático e integral a los pacientes con hipertensión y riesgo cardiovascular. No obstante, se necesitan herramientas organizativas que faciliten la comunicación entre pacientes y profesionales, específicamente con intercambio de datos clínicos que favorezcan la monitorización remota de las variables asociadas a la hipertensión y riesgo cardiovascular (presión arterial, peso, talla, variables analíticas…) y permitan realizar un seguimiento adecuado en aspectos como la adherencia a los tratamientos, estilos de vida y factores de riesgo. Todo ello sería deseable que fuera realizado por equipos multidisciplinares, tanto de atención primaria como hospitalaria y farmacia comunitaria, con una coordinación adecuada del cuidado en este tipo de pacientes. Este documento de la Sociedad Española de Hipertensión-Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA) trata de dar las claves para mejorar la calidad asistencial de las consultas telemáticas de los pacientes con hipertensión y riesgo cardiovascular, proporcionar criterios básicos de atención telemática o presencial y sistematizar el contenido de estas. Así mismo se plantean los criterios de seguimiento por los diferentes profesionales.

Finerenone is a selective nonsteroidal mineralocorticoid receptor antagonist with a short half-life. Its effects on cardiorenal outcomes were thought to be mediated primarily via nonhemodynamic pathways, but office blood pressure (BP) measurements were insufficient to fully assess hemodynamic effects. This analysis assessed the effects of finerenone on 24-h ambulatory BP in patients with chronic kidney disease and type 2 diabetes.ARTS-DN (NCT01874431) was a phase 2b trial that randomized 823 patients with type 2 diabetes and chronic kidney disease, with urine albumin-to-creatinine ratio ≥30 mg/g and estimated glomerular filtration rate of 30-90 ml/min per 1.73 m2 to placebo or finerenone (1.25-20 mg once daily in the morning) administered over 90 days. Ambulatory BP monitoring (ABPM) over 24 h was performed in a subset of 240 patients at screening, Day 60, and Day 90.Placebo-adjusted change in 24-h ABPM systolic BP (SBP) at Day 90 was -8.3 mmHg (95% confidence interval [CI], -16.6 to 0.1) for finerenone 10 mg (n = 27), -11.2 mmHg (95% CI, -18.8 to -3.6) for finerenone 15 mg (n = 34), and -9.9 mmHg (95% CI, -17.7 to -2.0) for finerenone 20 mg (n = 31). Mean daytime and night-time SBP recordings were similarly reduced and finerenone did not increase the incidence of SBP dipping. Finerenone produced a persistent reduction in SBP over the entire 24-h interval.Finerenone reduced 24-h, daytime, and night-time SBP. Despite a short half-life, changes in BP were persistent over 24 h with once-daily dosing in the morning.

Instituto de Salud Carlos III FIS/Fondos FEDER (PI17/01093, PI17/01193, CP15/00129, CPII20/00022, PI18/01366, PI19/00588, PI19/00815, PI20/00763, DTS18/00032) ERA-PerMedJTC2018 (KIDNEY ATTACK AC18/00064 and PERSTIGAN AC18/00071, ISCIII-RETIC REDinREN RD016/0009) Sociedad Española de Nefrología, FRIAT, Comunidad de Madrid en Biomedicina (B2017/BMD-3686 CIFRA2- CM) 35.855 JCR (2021) Q1, 3/143 Cardiac & Cardiovascular Systems 4.118 SJR (2021) Q1, 9/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

In patients with type 2 diabetes (T2D), risks of cardiovascular mortality and heart failure (HF) increase with decreasing kidney function (estimated glomerular filtration rate [eGFR]) and increasing albuminuria (urine albumin-to-creatinine ratio [UACR]). Finerenone, a selective, nonsteroidal mineralocorticoid receptor antagonist, improved cardiorenal outcomes in patients with chronic kidney disease (CKD) and T2D in FIDELITY (Finerenone in Chronic Kidney Disease and Type 2 Diabetes: Combined FIDELIO-DKD and FIGARO-DKD Trial Programme Analysis).This study sought to evaluate the effects of finerenone on HF outcomes by eGFR and/or UACR categories.FIDELITY included 13,026 patients with T2D and CKD (UACR 30-5,000 mg/g and eGFR ≥25 mL/min/1.73 mCompared with placebo, finerenone significantly reduced risk of first HHF (HR: 0.78 [95% CI: 0.66-0.92]; P = 0.003), cardiovascular death or first HHF (HR: 0.83 [95% CI: 0.74-0.93]; P = 0.002), recurrent HHF (HR: 0.79 [95% CI: 0.64-0.96]; P = 0.021), and cardiovascular death or recurrent HHF (HR: 0.82 [95% CI: 0.72-0.95]; P = 0.006). The risk of outcomes increased across baseline eGFR and UACR categories; lowest incidences were seen in patients with an eGFR ≥60 mL/min/1.73 mCompared with placebo, finerenone improved HF-related outcomes in patients with CKD and T2D, with consistent benefits across eGFR and/or UACR categories. (Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD], NCT02540993; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and the Clinical Diagnosis of Chronic Kidney Disease [FIGARO-DKD], NCT02545049).

Hypertension affects approximately one third of the world's adult population and is a major cause of premature death despite considerable advances in pharmacological treatments. Growing evidence supports the use of lifestyle interventions for the prevention and adjuvant treatment of hypertension. In this Review, we provide a summary of the epidemiological research supporting the preventive and antihypertensive effects of major lifestyle interventions (regular physical exercise, body weight management and healthy dietary patterns), as well as other less traditional recommendations such as stress management and the promotion of adequate sleep patterns coupled with circadian entrainment. We also discuss the physiological mechanisms underlying the beneficial effects of these lifestyle interventions on hypertension, which include not only the prevention of traditional risk factors (such as obesity and insulin resistance) and improvements in vascular health through an improved redox and inflammatory status, but also reduced sympathetic overactivation and non-traditional mechanisms such as increased secretion of myokines. Sin financiación 32.419 JCR (2020) Q1, 1/142 Cardiac & Cardiovascular Systems 5.495 SJR (2020) Q2, 6/349 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Background and aim Blood pressure variability (BPV) is recognized as a prognostic contributor in hypertension. We aimed to assess differences in short-term BPV in treated hypertensive patients depending on the number, classes, combinations and individual compounds of the antihypertensive treatment. Methods We selected 38 188 treated patients from the Spanish Ambulatory BP Monitoring (ABPM) Registry. SBP and DBP standard deviations (SD) from 24-h, daytime and night-time, weighted SD (WSD), and average real variability (ARV) were calculated through ABPM. They were compared (after adjustment for clinical confounders and BP) depending on the number of antihypertensive drugs, antihypertensive drug classes and compounds (in 13 765 patients on monotherapy), or combinations (in 12 716 patients treated with two drugs and 7888 treated with three drugs). Results Systolic and diastolic BPV significantly increased in patients treated with multiple drugs with respect to monotherapy. Among drug classes, calcium channel blockers, especially amlodipine, and diuretics were associated with lower systolic BPV, including daytime and night-time SD, WSD and ARV, compared with beta blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Likewise, in patients treated with two-drug and three-drug combinations, those which included a calcium channel blocker showed lower BPV in comparison to those without such drug class. Conclusion Treatment with calcium channel blockers, especially amlodipine, and with diuretics is associated with slight, but significant lower values of short-term BPV in comparison to other major drug classes, both in monotherapy and in combination. These results could be helpful when considering BPV reduction as an additional treatment target.

AimsThe aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH).Methods and resultsAmbulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24 h systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24 h PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway.ConclusionWe propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH.

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

Physical exercise reduces blood pressure (BP) in patients with hypertension in general but more evidence is needed specifically for a high-risk phenotype associated with intensive medication, resistant hypertension (RH). In this systematic review and meta-analysis, we aimed to summarize current evidence of the exercise effects on BP in patients with RH. A systematic search was conducted in PubMed, Web of Science and Cochrane Library (from inception to 3rd November, 2021). A random effects meta-analysis was performed when at least two trials assessed the effect of either acute or regular exercise (vs. a control condition) on the same outcome. Ten studies (N = 380 participants; 51% female; mean age 52 to 67 years) were included in the review, of which four (N = 58) and six (N = 322) assessed the effects of acute and regular exercise, respectively. Evidence overall suggests that a single bout of acute exercise results in a short-term (≤ 24 h) reduction of BP, although no meta-analysis could be performed. As for regular exercise, three randomized controlled trials (N = 144, 50% female) could be meta-analyzed, which showed that exercise training intervention (8–12 weeks, 3 sessions/week) significantly reduces 24-h (−9.9 mmHg, 95% confidence interval −15.4−4.4 for systolic BP; and −5 mmHg, −7.0−3.0 for diastolic BP) and daytime ambulatory BP (−11.7 mmHg, −17.8−5.7; and −7.4 mmHg, −11.9−2.9). In summary, physical exercise appears as an effective option to reduce BP in patients with RH, although more research is needed to confirm these findings as well as to determine the most effective exercise characteristics.

Aims: This prespecified analysis of the FIDELIO-DKD trial compared the effects of finerenone, a selective non-steroidal mineralocorticoid receptor antagonist, on cardiorenal outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) by history of heart failure (HF). Methods and results: Patients with T2D and CKD (urine albumin-to-creatinine ratio ≥30–5000 mg/g and estimated glomerular filtration rate [eGFR] ≥25–2), without symptomatic HF with reduced ejection fraction (New York Heart Association II–IV) and treated with optimized renin–angiotensin system blockade were randomized to finerenone or placebo. The composite cardiovascular (CV) outcome (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for HF) and composite kidney outcome (kidney failure, sustained ≥40% decrease in eGFR from baseline, or renal death) were analysed by investigator-reported medical history of HF. Of 5674 patients, 436 (7.7%) had a history of HF. Over a median follow-up of 2.6 years, the effect of finerenone compared with placebo on the composite CV outcome was consistent in patients with and without a history of HF (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50–1.06 and HR 0.90, 95% CI 0.77–1.04, respectively; interaction p = 0.33). The effect of finerenone on the composite kidney outcome did not differ by history of HF (HR 0.79, 95% CI 0.52–1.20 and HR 0.83, 95% CI 0.73–0.94, respectively; interaction p = 0.83). Conclusion: In FIDELIO-DKD, finerenone improved cardiorenal outcome in patients with CKD and T2D irrespective of baseline HF history.

Background: Chronic kidney disease and type 2 diabetes are independently associated with heart failure (HF), a leading cause of morbidity and mortality. In the FIDELIO-DKD (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) and FIGARO-DKD (Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease) trials, finerenone (a selective, nonsteroidal mineralocorticoid receptor antagonist) improved cardiovascular outcomes in patients with albuminuric chronic kidney disease and type 2 diabetes. These prespecified analyses from FIGARO-DKD assessed the effect of finerenone on clinically important HF outcomes. Methods: Patients with type 2 diabetes and albuminuric chronic kidney disease (urine albumin-to-creatinine ratio ≥30 to 2 , or urine albumin-to-creatinine ratio ≥300 to ≤5000 mg/g and estimated glomerular filtration rate ≥60 mL per min per 1.73 m 2 ), without symptomatic HF with reduced ejection fraction, were randomized to finerenone or placebo. Time-to-first-event outcomes included new-onset HF (first hospitalization for HF [HHF] in patients without a history of HF at baseline); cardiovascular death or first HHF; HF-related death or first HHF; first HHF; cardiovascular death or total (first or recurrent) HHF; HF-related death or total HHF; and total HHF. Outcomes were evaluated in the overall population and in prespecified subgroups categorized by baseline HF history (as reported by the investigators). Results: Overall, 7352 patients were included in these analyses; 571 (7.8%) had a history of HF at baseline. New-onset HF was significantly reduced with finerenone versus placebo (1.9% versus 2.8%; hazard ratio [HR], 0.68 [95% CI, 0.50–0.93]; P =0.0162). In the overall population, the incidences of all HF outcomes analyzed were significantly lower with finerenone than placebo, including an 18% lower risk of cardiovascular death or first HHF (HR, 0.82 [95% CI, 0.70–0.95]; P =0.011), a 29% lower risk of first HHF (HR, 0.71 [95% CI, 0.56–0.90]; P =0.0043) and a 30% lower rate of total HHF (rate ratio, 0.70 [95% CI, 0.52–0.94]). The effects of finerenone on improving HF outcomes were not modified by a history of HF. The incidence of treatment-emergent adverse events was balanced between treatment groups. Conclusions: The results from these FIGARO-DKD analyses demonstrate that finerenone reduces new-onset HF and improves other HF outcomes in patients with chronic kidney disease and type 2 diabetes, irrespective of a history of HF. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02545049.

Introduction: Night BP is the most powerful estimate of cardiovascular prognosis. It has been suggested that bedtime administration of antihypertensive therapy may favour night BP reduction and prognosis. Hypothesis: We aimed to evaluate the mortality risk in treated hypertensives, depending on the schedule of treatment administration (entirely in the morning, entirely at bedtime, or combined morning and evening) at the time ABPM was performed. Methods: Vital status and cardiovascular death were obtained from death certificates in 26751 treated hypertensives (mean age 62, 60% males), enrolled in the Spanish ABPM Registry, and having a valid 24-h ABPM at entry. Cox-models adjusted for clinical confounders and 24-hour systolic BP were used for HR calculation in groups depending on treatment administration. Results: Among the 26751 evaluable patients, most (76.7%) received their medication exclusively in the morning; 13% exclusively in the evening, and 10.3% in a multiple schedule both in the morning and in the evening. Mortality incidence in these 3 groups were 13.7, 17.8 and 21.8 per 1000 patients/year, respectively. Compared to patients receiving their antihypertensive medication entirely in the morning (reference group), those receiving their medication entirely in the evening did not show a significant increase in the HR for total mortality (1.06; 95%CI: 0.93-1.21) or in cardiovascular mortality (1.15; 0.93-1.41) after adjustment for clinical confounders and 24-hour systolic BP. Patients receiving their antihypertensive medication both in the morning and at bedtime had an increased risk for mortality (1.29; 1.14-1.48) and for cardiovascular mortality (1.46; 1.18-1.80). Additional analyses using double-robust propensity score yielded similar results. Conclusions: Morning or bedtime dosing of the antihypertensive medication has no effect on prognosis. We have found that patients receiving their medication in a multiple schedule, including morning and evening dosing have an increased risk of mortality and cardiovascular mortality, even after adjustment for confounders. However, we cannot exclude other aspects, such as a poorer treatment adherence, being the responsible of this worse prognosis.

Aims The complementary studies FIDELIO-DKD and FIGARO-DKD in patients with type 2 diabetes and chronic kidney disease (CKD) examined cardiovascular and kidney outcomes in different, overlapping stages of CKD. The purpose of the FIDELITY analysis was to perform an individual patient-level prespecified pooled efficacy and safety analysis across a broad spectrum of CKD to provide more robust estimates of safety and efficacy of finerenone compared with placebo. Methods and results For this prespecified analysis, two phase III, multicentre, double-blind trials involving patients with CKD and type 2 diabetes, randomized 1:1 to finerenone or placebo, were combined. Main time-to-event efficacy outcomes were a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure, and a composite of kidney failure, a sustained ≥57% decrease in estimated glomerular filtration rate from baseline over ≥4 weeks, or renal death. Among 13 026 patients with a median follow-up of 3.0 years (interquartile range 2.3–3.8 years), the composite cardiovascular outcome occurred in 825 (12.7%) patients receiving finerenone and 939 (14.4%) receiving placebo [hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.78–0.95; P = 0.0018]. The composite kidney outcome occurred in 360 (5.5%) patients receiving finerenone and 465 (7.1%) receiving placebo (HR, 0.77; 95% CI, 0.67–0.88; P = 0.0002). Overall safety outcomes were generally similar between treatment arms. Hyperkalaemia leading to permanent treatment discontinuation occurred more frequently in patients receiving finerenone (1.7%) than placebo (0.6%). Conclusion Finerenone reduced the risk of clinically important cardiovascular and kidney outcomes vs. placebo across the spectrum of CKD in patients with type 2 diabetes. Key Question Does finerenone, a novel selective, nonsteroidal mineralocorticoid receptor antagonist, added to maximum tolerated renin–angiotensin system inhibition reduce cardiovascular disease and kidney disease progression over a broad range of chronic kidney disease in patients with type 2 diabetes? Key Finding In a prespecified, pooled individual-level analysis from two randomized trials, we found reductions both in cardiovascular events and kidney failure outcomes with finerenone. Because 40% of the patients had an estimated glomerular filtration rate of >60 mL/min/1.73m2 they were identified solely on the basis of albuminuria. Take Home Message Finerenone reduces the risk of clinical cardiovascular outcomes and kidney disease progression in a broad range of patients with chronic kidney disease and type 2 diabetes. Screening for albuminuria to identify at-risk patients among patients with type 2 diabetes facilitates reduction of both cardiovascular and kidney disease burden.

OBJECTIVE A continuous association between albuminuria and cardiorenal risk exists further below moderately increased albuminuria ranges. If only based in albumin to creatinine ratio (ACR) higher than 30 mg/g, a significant percentage of individuals may be out of the scope for therapeutic management. Despite epidemiological outcomes, the identification of biochemical changes linked to early albuminuria is underexplored, and normoalbuminuric individuals are usually considered at no risk in clinical practice. Here, we aimed to identify early molecular alterations behind albuminuria development. METHODS Hypertensive patients under renin-angiotensin system (RAS) suppression were classified as control, (ACR

Sin financiación 29.690 JCR (2020) Q1, 3/142 Cardiac & Cardiovascular Systems 7.795 SJR (2020) Q1, 2/349 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

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.

Background: Reductions in albuminuria of more than 30% are considered a strong marker of delay of chronic kidney disease (CKD) progression. Single renin–angiotensin system (RAS) blockade represents the cornerstone of CKD treatment. However, as CKD progression still occurs, other nephroprotective options were explored; mineralocorticoid receptor antagonists (MRA) were tested with generally positive results. Methods: We conducted a systematic review and meta-analysis on the effects of MRAs on albuminuria/proteinuria, and adverse events, such as change in renal function and hyperkalemia incidence. A detailed search in electronic databases, clinical trial registries and grey literature was performed to retrieve randomized controlled trials (RCTs) in which administration of an MRA alone or on-top of ACEi/ARB was compared with placebo or active treatment. Results: Of the 45 initially identified reports, 31, with 2767 participants, were included in analysis of the primary outcome. The use of MRAs (alone or on top of RAS blockade) compared with placebo decreased urine albumin-to-creatinine ratio (UACR) by −24.55% (95% CI −29.57 to −19.53%), urine protein-to-creatinine ratio (UPCR) by −53.93% (95% CI −79% to −28.86%) and 24 h albumin excretion by −32.47% (95% CI −41.1 to −23.85%). MRAs also reduced UACR by −22.48% (95% CI −24.51 to −20.44%) compared with calcium-channel-blockers (CCBs), whereas no differences were found compared with a second ACEi/ARB or nonpotassium-sparing diuretics. Addition of an MRA was associated with change in estimated glomerular filtration rate (eGFR) of −2.38 ml/min per 1.73 m2 (95% CI −3.51 to −1.25), rise in potassium by 0.22 mEq/l (95% CI 0.16–0.28 mEq/l) and a 2.6-fold increase in hyperkalemia risk (RR 2.63, 95% CI 1.69–4.08) compared with placebo/active control. Conclusion: Use of MRAs alone or on top of RAS blockade confers important antiproteinuric effects in patients with CKD, with a slight increase in mean potassium levels. Sin financiación 4.171 JCR (2019) Q1, 13/65 Peripheral Vascular Disease 1.365 SJR (2019) Q1, 42/186 Physiology, 65/362 Cardiology and Cardiovascular Medicine, 21/139 Internal Medicine No data IDR 2019 UEM

Resistant hypertension (RH) is a concept that currently goes beyond the classical definition of blood pressure ≥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. Sin financiación 6.617 JCR (2020) Q1, 22/142 Cardiac & Cardiovascular Systems 1.895 SJR (2020) Q1, 39/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

Objective: Angiotensin receptor blockers (ARB) are among the recommended first-line treatment options in patients with hypertension and chronic kidney disease (CKD). This meta-analysis evaluated the effect of ARB on blood pressure (BP) and renal function in patients with concomitant hypertension and CKD with or without diabetes. Methods: Literature search was performed in PubMed/MEDLINE, EMBASE and BIOSIS to identify parallel-group, randomized controlled trials (≥8 weeks) reporting the effects of ARB on office systolic/diastolic BP (SBP/DBP), estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria in adults with hypertension and CKD. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to report an outcome. Results: Among the 24 studies identified, 19 evaluated ARB as monotherapy, 4 evaluated ARB as combination therapy and one evaluated ARB both as monotherapy and combination therapy. Median (range) duration of the studies was 12 (1.84–54.0) months. ARB monotherapy significantly (p Conclusion: ARB had a favorable impact on BP and renal parameters such as proteinuria with monotherapy as well as with combination therapy, highlighting their potential benefits in patients with hypertension and CKD. During the short follow-up of these studies, no significant change in eGFR was observed.

Introduction The selective, nonsteroidal mineralocorticoid receptor antagonist finerenone was investigated in FIDELIO-DKD in patients with CKD and T2D (NCT02540993). Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are recommended for CKD in T2D to reduce risk of CKD progression. We report a predefined exploratory analysis of patients by SGLT-2i use. Methods Patients (N=5674) with T2D, urine albumin-to-creatinine ratio (UACR) 30–5000 mg/g and estimated glomerular filtration rate (eGFR) 25– Results Of 5674 patients, 259 (4.6%) received SGLT-2i at baseline. Overall, finerenone significantly reduced the primary (time to kidney failure, sustained decrease in eGFR ≥40% from baseline, or renal death) and key secondary CV outcomes (time to CV death, nonfatal MI, nonfatal stroke, or hospitalization for heart failure) vs placebo (p=0.001 and p=0.03, respectively) with no effect on A1C. Results were consistent irrespective of SGLT-2i use at baseline for the primary and key secondary CV outcomes (interaction p-value 0.21 and 0.46, respectively). Reduction in UACR with finerenone was seen without SGLT-2i use (ratio of LS-means 0.68, 0.65–0.71; p Conclusion The benefits of finerenone on kidney and CV outcomes in patients with CKD and T2D appear consistent in the absence or presence of SGLT2i, with UACR improvement observed in patients already receiving SGLT-2i at baseline.

Este artículo se encuentra disponible en la siguiente URL: https://academic.oup.com/eurheartjsupp/article/23/Supplement_B/B138/6279165 En este artículo también participan: Inés Mera-Gallego, Salvador Tous, Nicanor F. de Andrés, Teresa Gijón, David Pérez-Manchon, Neil R. Poulter, Gema Ruiz-Hurtado y Luis Miguel Ruilope. The aim of the May Measurement Month (MMM) is devoted to better understanding the awareness, treatment, and control rates of hypertension in Spain. Presented here are the data corresponding to 2019 campaign. In 2019, a total of 4433 patients (61.5% males) with a mean age of 54.8 years were included. Of all, 96.0% were Caucasian, and 3294 were recruited in pharmacies. The mean values of systolic blood pressure (BP) were 125.6 and of diastolic 76.7mmHg in the whole population. The most recent previous BP measurement took place more than 1 year before in 27.6% of participants. A total of 1883 were hypertensive (systolic BP 140 mmHg or diastolic BP 90mmHg or taking antihypertensive medication), of whom 77.2%/were aware and 71.1% were onmedication. Of all, 64.9% of those on medication and 46.1% of all hypertensive participants had a BP controlled to

Background: Patients with chronic kidney disease (CKD) and type 2 diabetes (T2D) are at risk of atrial fibrillation or flutter (AFF) due to cardiac remodeling and kidney complications. Finerenone, a novel, selective, nonsteroidal mineralocorticoid receptor antagonist, inhibited cardiac remodeling in preclinical models. Objectives: This work aims to examine the effect of finerenone on new-onset AFF and cardiorenal effects by history of AFF in the Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease (FIDELIO-DKD) study. Methods: Patients with CKD and T2D were randomized (1:1) to finerenone or placebo. Eligible patients had a urine albumin-to-creatinine ratio ≥30 to ≤5,000 mg/g, an estimated glomerular filtration rate (eGFR) ≥25 to 2 and received optimized doses of renin–angiotensin system blockade. Effect on new-onset AFF was evaluated as a pre-specified outcome adjudicated by an independent cardiologist committee. The primary composite outcome (time to first onset of kidney failure, a sustained decrease of ≥40% in eGFR from baseline, or death from renal causes) and key secondary outcome (time to first onset of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure) were analyzed by history of AFF. Results: Of 5,674 patients, 461 (8.1%) had a history of AFF. New-onset AFF occurred in 82 (3.2%) patients on finerenone and 117 (4.5%) patients on placebo (hazard ratio: 0.71; 95% confidence interval: 0.53–0.94; p = 0.016). The effect of finerenone on primary and key secondary kidney and cardiovascular outcomes was not significantly impacted by baseline AFF (interaction p value: 0.16 and 0.85, respectively). Conclusions: In patients with CKD and T2D, finerenone reduced the risk of new-onset AFF. The risk of kidney or cardiovascular events was reduced irrespective of history of AFF at baseline. (EudraCT 2015-000990-11 [A randomized, double-blind, placebo-controlled, parallel-group, multicenter, event-driven Phase III study to investigate the efficacy and safety of finerenone, in addition to standard of care, on the progression of kidney disease in subjects with type 2 diabetes mellitus and the clinical diagnosis of diabetic kidney disease]; Efficacy and Safety of Finerenone in Subjects With Type 2 Diabetes Mellitus and Diabetic Kidney Disease [FIDELIO-DKD]; NCT02540993)

Supplemental Digital Content is available in the text., Background: The FIDELIO-DKD trial (Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease) evaluated the effect of the nonsteroidal, selective mineralocorticoid receptor antagonist finerenone on kidney and cardiovascular outcomes in patients with chronic kidney disease and type 2 diabetes with optimized renin–angiotensin system blockade. Compared with placebo, finerenone reduced the composite kidney and cardiovascular outcomes. We report the effect of finerenone on individual cardiovascular outcomes and in patients with and without history of atherosclerotic cardiovascular disease (CVD). Methods: This randomized, double-blind, placebo-controlled trial included patients with type 2 diabetes and urine albumin-to-creatinine ratio 30 to 5000 mg/g and an estimated glomerular filtration rate ≥25 to

Sin financiación 5.525 JCR (2021) Q2, 18/67 Peripheral Vascular Disease 1.119 SJR (2021) Q1, 70/356 Cardiology and Cardiovascular Medicine No data IDR 2021 UEM

Background Although exercise training reduces office blood pressure (BP), scarcer evidence is available on whether these benefits also apply to ambulatory blood pressure (ABP), which is a stronger predictor of cardiovascular disease and mortality. The present study aims to assess the effects of exercise training on ABP in patients with hypertension based on evidence from randomized controlled trials. Methods and Results A systematic search of randomized controlled trials on the aforementioned topic was conducted in PubMed and Scopus (since inception to April 1, 2020). The mean difference between interventions (along with 95% CI) for systolic BP and diastolic BP was assessed using a random‐effects model. Sub‐analyses were performed attending to (1) whether participants were taking antihypertensive drugs and (2) exercise modalities. Fifteen studies (including 910 participants with hypertension) met the inclusion criteria. Interventions lasted 8 to 24 weeks (3–5 sessions/week). Exercise significantly reduced 24‐hour (systolic BP, −5.4 mm Hg; [95% CI, −9.2 to −1.6]; diastolic BP, −3.0 mm Hg [−5.4 to −0.6]), daytime (systolic BP, −4.5 mm Hg [−6.6 to −2.3]; diastolic BP, −3.2 mm Hg [−4.8 to −1.5]), and nighttime ABP (systolic BP, −4.7 mm Hg [−8.4 to −1.0]; diastolic BP, −3.1 mm Hg [−5.3 to −0.9]). In separate analyses, exercise benefits on all ABP measures were significant for patients taking medication (all P P Conclusions Aerobic exercise is an effective coadjuvant treatment for reducing ABP in medicated patients with hypertension.

Sin financiación No data JCR 2020 0.194 SJR (2020) Q4, 266/349 Cardiology and Cardiovascular Medicine No data IDR 2019 UEM

Cardiovascular disease and cancer continue to be the major causes of death worldwide and the two conditions have more in common than previously acknowledged. In fact, both diseases share many predisposing factors and mechanisms, with a common background of low-grade inflammation. Thus, both cardiologists and oncologists should score both cardiovascular and cancer risk factors and develop risk reduction strategies for their patients. Sin financiación 29.983 JCR (2020) Q1, 2/142 Cardiac & Cardiovascular Systems 4.336 SJR (2020) Q1, 9/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

University of Alcalá (FPI2016) Spanish Ministry of Science and Innovation and Fondos FEDER (PI18/00139) 7.804 JCR (2020) Q1, 18/142 Cardiac & Cardiovascular Systems 1.669 SJR (2020) Q1, 48/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

The three more important sequalae of sustained hypertension in the heart, include heart failure (HF), conduction to arrhythmia particularly atrial fibrillation (AF) and coronary artery disease (CAD). In this issue of the journal Sava et al. [1] describe analyzing the data from the INternational VErapamil SR-Trandolapril (INVEST) study [2] the optimal systolic blood pressure (BP) to reduce mortality in women with previous coronary events. In a very recent review by Mehilli and Presbitero [3] the characteristics of women with CAD and acute coronary syndrome (ACS) are amply described. Women with CAD differ from men by several aspects as the clinical presentation, the accompanying comorbidities and risk factors, as well as, by the delivery of medical care. Moreover, women use to be older and present frequent and pronounced frailty. They present more frequently ACS without obstructive coronary arteries which makes it difficult the diagnosis and treatment of ACS. Importantly, in young women compared to men early death is more frequent in women, as well as, in older women during the first year after an ACS. The two main Guidelines for the management of arterial hypertension that of European Society of Cardiology (ESC)/European Society of Hypertension (ESH) [4] and that of the American College of Cardiology (ACC)/American Heart Association (AHA) [5] differ in the recommended BP goal for patients with chronic CAD depending on their age. The European Guideline defines the systolic goal BP in patients with CAD as inferior to 130/80 mmHg when the age of the patient is

Background Renal denervation (RDN) is under investigation for treatment of uncontrolled hypertension and might represent an attractive treatment for patients with high cardiovascular (CV) risk. It is important to determine whether baseline CV risk affects the efficacy of RDN. Objectives The purpose of this study was to assess blood pressure (BP) reduction and event rates after RDN in patients with various comorbidities, testing the hypothesis that RDN is effective and durable in these high-risk populations. Methods BP reduction and adverse events over 3 years were evaluated for several high-risk subgroups in the GSR (Global proSpective registrY for syMPathetic renaL denervatIon in seleCted IndicatIons Through 3 Years Registry), an international registry of RDN in patients with uncontrolled hypertension (n = 2,652). Comparisons were made for patients age ≥65 years versus age

SIN FINANCIACIÓN No data JCR 2020 0.194 SJR (2020) Q4, 266/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

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.

Background Chronic kidney disease (CKD) is a multifaceted disease that contributes to cardiac dysfunction. However, the mechanisms underlying the complex relationship between CKD and cardiac impairment remains almost completely unknown. Inflammation is a major player in both CKD and cardiovascular disease (CVD) and, in this context, nucleotide-binding oligomerization domain-containing protein 1 (NOD1) is a newly recognized innate immune receptor involved in both CKD and CVD independently. NOD1 activation is due to the recruitment of the receptor-interacting-serine/threonine-protein kinase 2 (RIP2), which induce NOD1 oligomerization and promotes the inflammatory response, being RIP2 a key partner in the NOD1 activation. Unpublished data from our group has demonstrated that genetic deletion of NOD1 prevents Ca2+ mishandling associated to CKD, next step will be to determine whether the absence of its specific adaptor; RIP2 can also mediate these effects. Purpose The main aim of this study was to determine whether NOD1-RIP2 axis impairs cardiac dysfunction and Ca2+ mishandling prompted by CKD induced by 5/6 nephrectomy (5/6Nx) in a mice model. Methods and results We have analysed intracellular Ca2+ handling in cardiomyocytes obtained from Wild type (Wt), Nod1−/− and Rip2−/− sham operated or nephrectomised mice. Compared with Wt-5/6Nx, cardiomyocytes obtained from Nod1−/−5/6Nx and Rip2−/−5/6Nx mice showed a significant improvement of Ca2+ mishandling, mainly by preventing: i) the reduction in [Ca2+]i transients amplitude; ii) the rise in their decay time; and iii) the lower cell contraction. The lack of NOD1 and RIP2 also prevents the reduced sarcoplasmic reticulum (SR) Ca2+ load and the augmented diastolic Ca2+ leak induced by 5/6Nx. Furthermore, the increased diastolic Ca2+ leak (Ca2+ sparks, spontaneous [Ca2+]i transients and waves) induced by 5/6Nx were also significantly prevented in absence of NOD1 and RIP2. Genetic deletion of NOD1 or RIP2 did not induces any improvement of several markers associated with renal dysfunction (urea, phosphate or fibroblast growth factor-23). Conclusions Our results confirmed that the absence of both NOD1 and RIP2 prevents the intracellular cardiac Ca2+ mishandling in experimental CKD. NOD1 and RIP2 emerge as novel targets for the development of innovative therapeutic strategies for the cardiac remodelling in CKD subjects. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): This work was supported by Spanish ISCIII (PI17/01093 and PI17/01344), Fondo Europeo de Desarrollo Regional (FEDER), FSE, and CIBER-CV, a network funded by ISCIII. MF-V is Miguel Servet II researcher of ISCIII (MSII16/00047 Carlos III Health Institute). GR-H is Miguel Servet I researcher of ISCIII (CP15/00129 Carlos III Health Institute). MT is a PhD student funded by the FPU program of the Spanish Ministry of Science, Innovation and Universities (FPU17/06135).

Este artículo se encuentra disponible en la siguiente URL: https://academic.oup.com/eurheartjsupp/article/22/Supplement_H/H119/5898732 En este artículo también participan: Fernando Martínez, Blanca Carreras, Bettina de Berardinis, Thomas Beaney, Anca Chis Ster, Neil R. Poulter, Xin Xia y Luis M. Ruilope. Elevated blood pressure (BP) is the single most important contributing risk factor to the global disease burden, leading to over 10 million deaths each year. In Spain, hypertension (HTN) affects around 20% of the adult population and remains the greatest attributable cause of cardiovascular mortality. May Measurement Month (MMM) is a worldwide initiative aimed at increasing awareness of HTN and to improve the lack of screening programmes worldwide. An opportunistic cross-sectional survey of volunteers aged 18 and over was carried out in May 2018. Blood pressure measurement, the definition of HTN and statistical analysis followed the standard MMM protocol. Anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were obtained as additional information. Screening sites mainly in community pharmacies, universities, primary care centres, HTN units, and cardiovascular departments in hospitals were set up across Spain as part of this initiative. In total, 7646 individuals (63.5% female) were screened during MMM18. After multiple imputation, 40.0% had HTN, of whom 74.4% were aware of their diagnosis and 69.6% were taking antihypertensive medication. Of individuals not receiving antihypertensive medication, 16.9% were hypertensive. Of individuals receiving antihypertensive medication, 36.4% had uncontrolled BP. MMM18 almost doubled the number of participants of MMM17 and was the largest BP screening campaign ever undertaken in Spain, showing that in the absence of systematic screening programmes for HTN, MMM can identify a great number of individuals at risk, increasing their awareness and attracting the interest of the healthcare system in Spain.

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/m2 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/cm3 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. Sin financiación 4.844 JCR (2020) Q2, 17/65 Peripheral Vascular Disease 1.249 SJR (2020) Q1, 70/349 Cardiology and Cardiovascular Medicine UEM

Sin financiación 3.738 JCR (2020) Q2, 24/65 Peripheral Vascular Disease 0.909 SJR (2020) Q2, 97/349 Cardiology and Cardiovascular Medicine No data IDR 2020 UEM

Aims It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). Methods and results This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17–3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03–4.57, P = 0.041). The mortality rates were similar between the renin–angiotensin–aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28–2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45–0.94, P = 0.20). Conclusion While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.

Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia–reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health. Sin financiación 17.420 JCR (2018) Q1, 4/136 Cardiac & Cardiovascular Systems 4.882 SJR (2018) Q1, 8/365 Cardiology and Cardiovascular Medicine No data IDR 2018 UEM

Background and aim Treatment-resistant hypertension (TRH) is associated with particular clinical features, nonadherence, and suboptimal treatment. We assessed possible associations of antihypertensive drug classes, specific agents inside each class, and types of combinations, with the presence of non-TRH vs. TRH, and with controlled vs. uncontrolled TRH. Methods Comparisons were done in 14 264 patients treated with three drugs (non-TRH: 2988; TRH: 11 276) and in 6974 treated with at least four drugs (controlled TRH: 1383; uncontrolled TRH: 5591). Associations were adjusted for age, sex, and previous cardiovascular event. Results In both groups of patients treated with three or with at least four drugs, aldosterone antagonists among drug classes [adjusted odds ratio (OR): 1.82 and 1.41, respectively], and ramipril (OR: 1.28 and 1.30), olmesartan (OR: 1.31 and 1.37), and amlodipine (OR: 1.11 and 1.41) inside each class were significantly associated with blood pressure control (non-TRH or controlled TRH). In patients treated with three drugs, non-TRH was also associated with the use of chlorthalidone (OR: 1.50) and bisoprolol (OR: 1.19), whereas in patients treated with at least four drugs, controlled TRH was significantly associated with the triple combination of a renin-angiotensin system blocker, a calcium channel blocker, and a diuretic (OR: 1.17). Conclusion The use of aldosterone antagonists is associated with blood pressure control in patients treated with three or more drugs. Similar results are observed with specific agents inside each class, being ramipril, olmesartan, chlorthalidone, amlodipine, and bisoprolol those exhibiting significant results. An increased use of these drugs might probably reduce the burden of TRH.

Sin financiación No data JCR 2018 0.129 SJR (2018) Q4, 297/365 Cardiology and Cardiovascular Medicine, 113/141 Internal Medicine No data IDR 2018 UEM