Evidence for the influence of ambulatory blood pressure on prognosis derives mainly from population-based studies and a few relatively small clinical investigations. This study examined the associations of blood pressure measured in the clinic (clinic blood pressure) and 24-hour ambulatory blood pressure with all-cause and cardiovascular mortality in a large cohort of patients in primary care.

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 <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 ( P <0.05). Conclusions: Aerobic exercise is an effective coadjuvant treatment for reducing ABP in medicated patients with hypertension.

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.

Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. Prolongation of the action potential duration and downregulation of several K⁺currents might participate in the genesis of arrhythmias associated with chronic heart failure. Little information is available related to the mechanism by which TNF-α modulates cardiac K⁺channels. The present study analyzes the effect of TNF-α on the transient outward K⁺current ( I_to) in rat ventricular myocytes, using the whole cell patch-clamp technique. We found that TNF-α is able to induce a significant reduction of I_todensity, modifies its inactivation, and downregulates the Kv4.2 protein expression, while calcium current density is not affected. We have also demonstrated that the reduction of I_todensity induced by TNF-α was prevented by the selective inducible nitric oxide synthase (iNOS) inhibitor 1400-W, the protein synthesis inhibitor cycloheximide, the antioxidant tocopherol, and the superoxide dismutase mimetic manganese(III) tetrakis (4-benzoic acid) porphyrin. In addition, a reduced I_todensity was recorded in ventricular myocytes exposed to peroxynitrite, supporting a possible participation of this oxidant in the effects of TNF-α on I_to. We conclude that TNF-α exposure, through iNOS induction and generation of oxidant species, promotes electrophysiological changes (decreased I_toand action potential duration prolongation) in rat ventricular myocytes, providing new insights into how cytokines modulate K⁺channels in the heart.