In a registry study of 63,910 adults, 24-hour ambulatory BP was a stronger predictor of mortality than BP measured in the clinic. Masked hypertension (normal BP in the clinic but elevated ambulatory ...BP) was associated with a greater risk of death than sustained hypertension.
Ambulatory blood pressure provides a more comprehensive assessment than clinic blood pressure, and has been reported to better predict health outcomes than clinic or home pressure. We aimed to ...examine associations of clinic and 24-h ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of primary care patients referred for assessment of hypertension.
We did an observational cohort study using clinic and ambulatory blood pressure data obtained from March 1, 2004, to Dec 31, 2014, from the Spanish Ambulatory Blood Pressure Registry. This registry included patients from 223 primary care centres from the Spanish National Health System in all 17 regions of Spain. Mortality data (date and cause) were ascertained by a computerised search of the vital registry of the Spanish National Institute of Statistics. Complete data were available for age, sex, all blood pressure measures, and BMI. For each study participant, follow-up was from the date of their recruitment to the date of death or Dec 31, 2019, whichever occurred first. Cox models were used to estimate associations between usual clinic or ambulatory blood pressure and mortality, adjusted for confounders and additionally for alternative measures of blood pressure. For each measure of blood pressure, we created five groups (ie, fifths) defined by quintiles of that measure among those who subsequently died.
During a median follow-up of 9·7 years, 7174 (12·1%) of 59 124 patients died, including 2361 (4·0%) from cardiovascular causes. J-shaped associations were observed for several blood pressure measures. Among the top four baseline-defined fifths, 24-h systolic blood pressure was more strongly associated with all-cause death (hazard ratio HR 1·41 per 1 – SD increment 95% CI 1·36–1·47) than clinic systolic blood pressure (1·18 1·13–1·23). After adjustment for clinic blood pressure, 24-h blood pressure remained strongly associated with all-cause deaths (HR 1·43 95% CI 1·37–1·49), but the association between clinic blood pressure and all-cause death was attenuated when adjusted for 24-h blood pressure (1·04 1·00–1·09). Compared with the informativeness of clinic systolic blood pressure (100%), night-time systolic blood pressure was most informative about risk of all-cause death (591%) and cardiovascular death (604%). Relative to blood pressure within the normal range, elevated all-cause mortality risks were observed for masked hypertension (HR 1·24 95% CI 1·12–1·37) and sustained hypertension (1·24 1·15–1·32), but not white-coat hypertension, and elevated cardiovascular mortality risks were observed for masked hypertension (1·37 1·15–1·63) and sustained hypertension (1·38 1·22–1·55), but not white-coat hypertension.
Ambulatory blood pressure, particularly night-time blood pressure, was more informative about the risk of all-cause death and cardiovascular death than clinic blood pressure.
Spanish Society of Hypertension, Lacer Laboratories, UK Medical Research Council, Health Data Research UK, National Institute for Health and Care Research Biomedical Research Centres (Oxford and University College London Hospitals), and British Heart Foundation Centre for Research Excellence.
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
<0.05) but not for untreated patients (although differences between medicated and non-medicated patients were not significant), and only aerobic exercise provided significant benefits (
<0.05). Conclusions Aerobic exercise is an effective coadjuvant treatment for reducing ABP in medicated patients with hypertension.
Background
Profound disturbances in mineral metabolism are closely linked to the progression of chronic kidney disease. However, increasing clinical and experimental evidence indicates that ...alterations in phosphate homoeostasis could have an even stronger impact on the heart.
Aim
The aim of this review is to provide the reader with an update of how alterations in mineral metabolism are related to direct and indirect cardiotoxic effects beyond the nephrology setting.
Results
Evidence exists that alterations in mineral metabolism that are related to changes in parathyroid hormone (PTH), vitamin D, and the FGF‐23–klotho axis have direct pathological consequences for the heart. Alterations in plasma PTH levels are associated with cardiac dysfunction and detrimental cardiac remodelling. Several clinical studies have associated vitamin D deficiency with the prevalence of cardiovascular disease (CV) and its risk factors. Recent evidences support deleterious direct and nonphosphaturic effects of FGF‐23 on the heart as hypertrophy development. In contrast, reduced systemic klotho levels are related to CV damage, at least when advanced age is present. In addition, we discuss how these mineral metabolism molecules can counteract each other in some situations, in the context of failed clinical trials on cardiac protection as is the case of vitamin D supplementation.
Conclusions
Among all mineral components, an increase in systemic FGF‐23 levels is considered to have the greatest CV impact and risk. However, it is quite possible that many intracellular mechanisms mediated by FGF‐23, especially those related to cardiomyocyte function, remain to be discovered.
Background and Purpose
The synthetic vitamin D3 analogue paricalcitol acts as a selective activator of the vitamin D receptor (VDR). While there is evidence for cardioprotective effects of ...paricalcitol associated with the VDR pathway, less information is available about the structural and functional cardiac effects of paricalcitol on established heart failure (HF) and particularly its effects on associated electrophysiological or Ca2+ handling remodelling.
Experimental Approach
We used a murine model of transverse aortic constriction (TAC) to study the effect of paricalcitol on established HF. Treatment was initiated 4 weeks after surgery over five consecutive weeks, and mice were sacrificed 9 weeks after surgery. Cardiac MRI (CMRI) was performed 4 and 9 weeks after surgery. Hearts were used for biochemical and histological studies and to isolate ventricular myocytes for electrophysiological and calcium imaging studies.
Key Results
CMRI analysis revealed that, compared with vehicle, paricalcitol treatment prevented the progression of ventricular dilation and hypertrophy after TAC and halted the corresponding decline in ejection fraction. These beneficial effects were related to the attenuation of intracellular Ca2+ mishandling remodelling, antifibrotic and antihypertrophic effects and potentially antiarrhythmic effects by preventing the reduction of K+ current density and the long QT, JT and TpTe intervals observed in HF animals.
Conclusion and Implications
The results suggest that paricalcitol treatment in established HF hampers disease progression and improves adverse electrophysiological and Ca2+ handling remodelling, attenuating the vulnerability to HF‐associated ventricular arrhythmias. Paricalcitol may emerge as a potential therapeutic option in the treatment of HF.
SCOPE: Activation of endothelial adenosine monophosphate‐activated protein kinase (AMPK) contributes to increase nitric oxide (NO) availability. The aim of this study was to assess if high‐fat diet ...(HFD)‐induced endothelial dysfunction is linked to AMPK deregulation. METHODS AND RESULTS: Twelve‐week‐old Sprague Dawley male rats were assigned either to control (10 kcal % from fat) or to HFD (45 kcal % from fat) for 8 wk. HFD rats segregated in obesity‐prone (OP) or obesity‐resistant (OR) rats according to body weight. HFD triggered an impaired glucose management together with impaired endothelium‐dependent relaxation, reduced endothelial AMPK activity and lower NO availability in aortic rings of OP and OR cohorts. Relaxation evoked by AMPK activator, 5‐aminoimidazole‐4‐carboxamide‐1‐β‐d‐ribofuranoside (AICAR) was reduced in both OP and OR rings, which exhibited lower p‐AMPKα‐Thr¹⁷²/AMPKα ratios that negatively correlated with plasma non‐esterified fatty acids (NEFA) and triglycerides (TG). Inhibition of PI3K (wortmannin, 10⁻⁷M) or Akt (triciribine, 10⁻⁵M) reduced relaxation to AICAR only in the control group (p < 0.001). Akt (p‐Akt‐Ser⁴⁷³) and eNOS phosphorylation (p‐eNOS‐Ser¹¹⁷⁷) were significantly reduced in OP and OR (p < 0.01). CONCLUSION: Endothelial dysfunction caused by HFD is related to a dysfunctional endothelial AMPK–PI3K–Akt–eNOS pathway correlating with the increase of plasma NEFA, TG, and an impaired glucose management.
Background and Purpose
Klotho is a membrane‐bound or soluble protein, originally identified as an age‐suppressing factor and regulator of mineral metabolism. Klotho deficiency is associated with the ...development of renal disease, but its role in cardiac function in the context of uraemic cardiomyopathy is unknown.
Experimental Approach
We explored the effects of Klotho on cardiac Ca2+ cycling. We analysed Ca2+ handling in adult cardiomyocytes from Klotho‐deficient (kl/kl) mice and from a murine model of 5/6 nephrectomy (Nfx). We also studied the effect of exogenous Klotho supplementation, by chronic recombinant Klotho treatment, or endogenous Klotho overexpression, using transgenic mice overexpressing Klotho (Tg‐Kl), on uraemic cardiomyopathy. Hearts from Nfx mice were used to study Ca2+ sensitivity of ryanodine receptors and their phosphorylation state.
Key Results
Cardiomyocytes from kl/kl mice showed decreased amplitude of intracellular Ca2+ transients and cellular shortening together with an increase in pro‐arrhythmic Ca2+ events compared with cells from wild‐type mice. Cardiomyocytes from Nfx mice exhibited the same impairment in Ca2+ cycling as kl/kl mice. Changes in Nfx cardiomyocytes were explained by higher sensitivity of ryanodine receptors to Ca2+ and their increased phosphorylation at the calmodulin kinase type II and protein kinase A sites. Ca2+ mishandling in Nfx‐treated mice was fully prevented by chronic recombinant Klotho administration or transgenic Klotho overexpression.
Conclusions and Implications
Klotho emerges as an attractive therapeutic tool to improve cardiac Ca2+ mishandling observed in uraemic cardiomyopathy. Strategies that improve Klotho availability are good candidates to protect the heart from functional cardiac alterations in renal disease.
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