Lower Risk of Heart Failure and Death in Patients Initiated on Sodium-Glucose Cotransporter-2 Inhibitors Versus Other Glucose-Lowering DrugsClinical Perspective: The CVD-REAL Study (Comparative Effectiveness of Cardiovascular Outcomes in New Users of Sodium-Glucose Cotransporter-2 Inhibitors)

Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class

Подготовка ИТ-консультантов в российских вузах в разрезе проблематики консалтинга

Differences in clinical effectiveness between angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) in the primary treatment of hypertension are unknown. The aim of this retrospective cohort study was to assess the prevention of type 2 diabetes and cardiovascular disease (CVD) in patients treated with ARBs or ACEis. Patients initiated on enalapril or candesartan treatment in 71 Swedish primary care centers between 1999 and 2007 were included. Medical records data were extracted and linked with nationwide hospital discharge and cause of death registers. The 11 725 patients initiated on enalapril and 4265 on candesartan had similar baseline characteristics. During a mean follow-up of 1.84 years, 36 482 patient-years, the risk of new diabetes onset was lower in the candesartan group (hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.69-0.96, P = 0.01) compared with the enalapril group. No difference between the groups was observed in CVD risk (HR 0.99, 95% CI 0.87-1.13, P = 0.86). More patients discontinued treatment in the enalapril group (38.1%) vs the candesartan group (27.2%). In a clinical setting, patients initiated on candesartan treatment had a lower risk of new-onset type 2 diabetes and lower rates of drug discontinuation compared with patients initiated on enalapril. No differences in CVD risk were observed

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (P<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (P <= 0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension

Object shape differences reflected by somatosensory cortical activation in human

Humans can easily by touch discriminate fine details of the shapes of objects. The computation of representations and the representations of objects differing in shape are, when the differences are not founded in different sensory cues or the objects belong to different categories, assumed to take place in a series of cortical areas, which only show differences at the single-neuron level. How the somatosensory cortex computes shape is unknown, but theoretically it should depend heavily on the curvatures of the object surfaces. We measured regional cerebral blood flow (rCBF) of normal volunteers with positron emission tomography (PET) as an index of neuronal activation. One group discriminated a round set of ellipsoids having a narrow spectrum of curvatures and an oblong set of ellipsoids having a broad spectrum of curvatures. Another group discriminated curvatures. When the rCBF from the conditions round and oblong ellipsoid discrimination was contrasted, part of the cortex lining the postcentral sulcus had significantly higher rCBF when ellipsoids having a broader spectrum of curvatures were discriminated. This cortex was also activated by curvature discrimination. The activation is therefore regarded as crucial for the computation of curvature and in accordance with curvature being a major determinant of object form; this cortex is also crucially active in somatosensory shape perception. A comparison of the activation with cytoarchitectural maps, in the anatomical format of the standard brain for both PET and cytoarchitectural brain images, revealed that this part of the cortex lining the postcentral sulcus is situated caudally from cytoarchitectural area 1 and may involve presumptive area 2 on the posterior bank of the sulcus

Object shape differences reflected by somatosensory cortical activation in human

Humans can easily by touch discriminate fine details of the shapes of objects. The computation of representations and the representations of objects differing in shape are, when the differences are not founded in different sensory cues or the objects belong to different categories, assumed to take place in a series of cortical areas, which only show differences at the single-neuron level. How the somatosensory cortex computes shape is unknown, but theoretically it should depend heavily on the curvatures of the object surfaces. We measured regional cerebral blood flow (rCBF) of normal volunteers with positron emission tomography (PET) as an index of neuronal activation. One group discriminated a round set of ellipsoids having a narrow spectrum of curvatures and an oblong set of ellipsoids having a broad spectrum of curvatures. Another group discriminated curvatures. When the rCBF from the conditions round and oblong ellipsoid discrimination was contrasted, part of the cortex lining the postcentral sulcus had significantly higher rCBF when ellipsoids having a broader spectrum of curvatures were discriminated. This cortex was also activated by curvature discrimination. The activation is therefore regarded as crucial for the computation of curvature and in accordance with curvature being a major determinant of object form; this cortex is also crucially active in somatosensory shape perception. A comparison of the activation with cytoarchitectural maps, in the anatomical format of the standard brain for both PET and cytoarchitectural brain images, revealed that this part of the cortex lining the postcentral sulcus is situated caudally from cytoarchitectural area 1 and may involve presumptive area 2 on the posterior bank of the sulcus

Lower Risk of Heart Failure and Death in Patients Initiated on SGLT-2 Inhibitors Versus Other Glucose-Lowering Drugs: The CVD-REAL Study.

Background -Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose co-transporter-2 inhibitor (SGLT-2i) empagliflozin in type 2 diabetes patients with atherosclerotic cardiovascular disease. We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose lowering drugs (oGLDs) in six countries to determine if these benefits are seen in real-world practice, and across SGLT-2i class. Methods -Data were collected via medical claims, primary care/hospital records and national registries from the US, Norway, Denmark, Sweden, Germany and the UK. Propensity score for SGLT-2i initiation was used to match treatment groups. Hazard ratios (HRs) for HHF, death and their combination were estimated by country and pooled to determine weighted effect size. Death data were not available for Germany. Results -After propensity matching, there were 309,056 patients newly initiated on either SGLT-2i or oGLD (154,528 patients in each treatment group). Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42% and 5% of the total exposure time in the SGLT-2i class, respectively. Baseline characteristics were balanced between the two groups. There were 961 HHF cases during 190,164 person-years follow up (incidence rate [IR] 0.51/100 person-years). Of 215,622 patients in the US, Norway, Denmark, Sweden, and UK, death occurred in 1334 (IR 0.87/100 person-years), and HHF or death in 1983 (IR 1.38/100 person-years). Use of SGLT-2i, versus oGLDs, was associated with lower rates of HHF (HR 0.61; 95% CI 0.51-0.73; p<0.001); death (HR 0.49; 95% CI 0.41-0.57; p<0.001); and HHF or death (HR 0.54; 95% CI 0.48-0.60, p<0.001) with no significant heterogeneity by country. Conclusions -In this large multinational study, treatment with SGLT-2i versus oGLDs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of T2D patients in real-world practice (NCT02993614). Clinical Trial Registration -URL: ClinicalTrials.gov; Unique Identifier: NCT02993614

Diagnostic thresholds for ambulatory blood pressure monitoring based on 10-year cardiovascular risk

Current diagnostic thresholds for ambulatory blood pressure (ABP) mainly rely on statistical parameters derived from reference populations. We determined an outcome-driven reference frame for ABP measurement. We performed 24-h ABP monitoring in 5682 participants (mean age 59.0 years; 43.3% women) enrolled in prospective population studies in Copenhagen, Denmark; Noorderkempen, Belgium; Ohasama, Japan; and Uppsala, Sweden. In multivariate analyses, we determined ABP thresholds, which yielded 10-year cardiovascular risks similar to those associated with optimal (120/80 mmHg), normal (130/85 mmHg), and high (140/90 mmHg) blood pressure on office measurement. Over 9.7 years (median), 814 cardiovascular end points occurred, including 377 strokes and 435 cardiac events. Systolic/diastolic thresholds for optimal ABP were 118.3/74.2 mmHg for 24 h, 121.6/78.9 mmHg for daytime, and 104.7/65.3 mmHg for nighttime. Corresponding thresholds for normal ABP were 124.3/76.8,129.9/82.6, and 111.6/68.1 mmHg, respectively, and those for ambulatory hypertension were 130.3/79.4, 138.2/86.4, and 118.5/70.8 mmHg. After rounding, approximate thresholds for optimal ABP amounted to 115/75 mmHg for 24 h, 120/80 mmHg for daytime, and 105/65 mmHg for nighttime. Rounded thresholds for normal ABP were 125/75,130/85, and 110/70 mmHg, respectively, and those for ambulatory hypertension were 130/80, 140/85, and 120/70 mmHg. In conclusion, population-based outcome-driven thresholds for optimal and normal ABP are lower than those currently proposed by hypertension guidelines.status: publishe

Prognostic superiority of daytime ambulatory over conventional blood pressure in four populations: a meta-analysis of 7,030 individuals

OBJECTIVE: To investigate the multivariate-adjusted predictive value of systolic and diastolic blood pressures on conventional (CBP) and daytime (10-20 h) ambulatory (ABP) measurement. METHODS: We randomly recruited 7,030 subjects (mean age 56.2 years; 44.8% women) from populations in Belgium, Denmark, Japan and Sweden. We constructed the International Database on Ambulatory blood pressure and Cardiovascular Outcomes. RESULTS: During follow-up (median = 9.5 years), 932 subjects died. Neither CBP nor ABP predicted total mortality, of which 60.9% was due to noncardiovascular causes. The incidence of fatal combined with nonfatal cardiovascular events amounted to 863 (228 deaths, 326 strokes and 309 cardiac events). In multivariate-adjusted continuous analyses, both CBP and ABP predicted cardiovascular, cerebrovascular, cardiac and coronary events. However, in fully-adjusted models, including both CBP and ABP, CBP lost its predictive value (P >or= 0.052), whereas systolic and diastolic ABP retained their prognostic significance (P or= 0.21). In adjusted categorical analyses, normotension was the referent group (CBP or= 140/90 and or= 135/85 mmHg); and 1.80 (95% CI = 1.59-2.03; P or= 140/90 and >or= 135/85 mmHg). CONCLUSIONS: ABP is superior to CBP in predicting cardiovascular events, but not total and noncardiovascular mortality. Cardiovascular risk gradually increases from normotension over white-coat and masked hypertension to sustained hypertension.status: publishe