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Although guidelines recommend strict blood pressure (BP) control in patients with type 2 diabetes mellitus (T2DM) and elevated cardiovascular risk, the long-term effects of this approach are unknown. We investigated the effect of intensive BP control on clinical outcomes in patients with T2DM over 9 years of follow-up. We included Action to Control Cardiovascular Risk in Diabetes - Blood Pressure participants in the standard glucose control arm who had established cardiovascular disease, chronic kidney disease, were ≥75 years of age or who had a 10-year coronary heart risk ≥15%. Participants were randomized to either intensive (systolic BP < 120 mm Hg) or standard (systolic BP < 140 mm Hg) BP control for an average of 5 years. Observational follow-up occurred for an average of 4 years thereafter. After an average total follow-up of 9 years, intensive BP control reduced the composite of cardiovascular death, nonfatal myocardial infarction and nonfatal stroke by 25% (hazard ratio, 0.75; 95% confidence interval, 0.60-0.95; P = .02). The overall benefit was driven by a reduction in nonfatal myocardial infarction (P = .01). In this post-hoc analysis, the benefits of a fixed-duration intensive BP control intervention in patients with T2DM persisted throughout 9 years of follow-up., (© 2018 John Wiley & Sons Ltd.)

Objective: We sought to determine the effect of intensive blood pressure (BP) control on cardiovascular outcomes in participants with type 2 diabetes mellitus (T2DM) and additional risk factors for cardiovascular disease (CVD)., Research Design and Methods: This study was a post hoc, multivariate, subgroup analysis of ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) participants. Participants were eligible for the analysis if they were in the standard glucose control arm of ACCORD-BP and also had the additional CVD risk factors required for SPRINT (Systolic Blood Pressure Intervention Trial) eligibility. We used a Cox proportional hazards regression model to compare the effect of intensive versus standard BP control on CVD outcomes. The "SPRINT-eligible" ACCORD-BP participants were pooled with SPRINT participants to determine whether the effects of intensive BP control interacted with T2DM., Results: The mean baseline Framingham 10-year CVD risk scores were 14.5% and 14.8%, respectively, in the intensive and standard BP control groups. The mean achieved systolic BP values were 120 and 134 mmHg in the intensive and standard BP control groups ( P < 0.001). Intensive BP control reduced the composite of CVD death, nonfatal myocardial infarction (MI), nonfatal stroke, any revascularization, and heart failure (hazard ratio 0.79; 95% CI 0.65-0.96; P = 0.02). Intensive BP control also reduced CVD death, nonfatal MI, and nonfatal stroke (hazard ratio 0.69; 95% CI 0.51-0.93; P = 0.01). Treatment-related adverse events occurred more frequently in participants receiving intensive BP control (4.1% vs. 2.1%; P = 0.003). The effect of intensive BP control on CVD outcomes did not differ between patients with and without T2DM ( P > 0.62)., Conclusions: Intensive BP control reduced CVD outcomes in a cohort of participants with T2DM and additional CVD risk factors., (© 2017 by the American Diabetes Association.)

Background: Hypertension is, amongst others, characterized by endothelial dysfunction and vascular remodeling. As sphingolipids have been implicated in both the regulation of vascular contractility and growth, we investigated whether sphingolipid biology is altered in hypertension and whether this is reflected in altered vascular function., Methods and Findings: In isolated carotid arteries from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto (WKY) rats, shifting the ceramide/S1P ratio towards ceramide dominance by administration of a sphingosine kinase inhibitor (dimethylsphingosine) or exogenous application of sphingomyelinase, induced marked endothelium-dependent contractions in SHR vessels (DMS: 1.4±0.4 and SMase: 2.1±0.1 mN/mm; n = 10), that were virtually absent in WKY vessels (DMS: 0.0±0.0 and SMase: 0.6±0.1 mN/mm; n = 9, p<0.05). Imaging mass spectrometry and immunohistochemistry indicated that these contractions were most likely mediated by ceramide and dependent on iPLA(2), cyclooxygenase-1 and thromboxane synthase. Expression levels of these enzymes were higher in SHR vessels. In concurrence, infusion of dimethylsphingosine caused a marked rise in blood pressure in anesthetized SHR (42±4%; n = 7), but not in WKY (-12±10%; n = 6). Lipidomics analysis by mass spectrometry, revealed elevated levels of ceramide in arterial tissue of SHR compared to WKY (691±42 vs. 419±27 pmol, n = 3-5 respectively, p<0.05). These pronounced alterations in SHR sphingolipid biology are also reflected in increased plasma ceramide levels (513±19 pmol WKY vs. 645±25 pmol SHR, n = 6-12, p<0.05). Interestingly, we observed similar increases in ceramide levels (correlating with hypertension grade) in plasma from humans with essential hypertension (185±8 pmol vs. 252±23 pmol; n = 18 normotensive vs. n = 19 hypertensive patients, p<0.05)., Conclusions: Hypertension is associated with marked alterations in vascular sphingolipid biology such as elevated ceramide levels and signaling, that contribute to increased vascular tone.