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Aim: We aimed to determine the macrovascular and microvascular outcomes of intensive versus standard glucose‐lowering strategies in type 2 diabetes (T2D) and investigate the relationships between these outcomes and trial arm glycated haemoglobin (HbA1c) reduction. Materials and Methods: In this systematic review and meta‐analysis, we identified relevant trials from MEDLINE, Embase, the Cochrane Library, and bibliographies up to August 2023. Macrovascular and microvascular outcomes, along with safety outcomes, were evaluated. Pooled study‐specific hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated, and meta‐regression was employed to analyse the relationships between outcomes and HbA1c reduction. Results: We included 11 unique RCTs involving 51 469 patients with T2D (intensive therapy, N = 26 691; standard therapy, N = 24 778). Intensive versus standard therapy reduced the risk of non‐fatal myocardial infarction (MI) (HR 0.84; 95% CI 0.75‐0.94) with no difference in the risk of major adverse cardiovascular events (HR 0.97; 95% CI 0.92‐1.03) and other adverse cardiovascular outcomes. Intensive versus standard therapy reduced the risk of retinopathy (HR 0.85; 0.78‐0.93), nephropathy (HR 0.71; 0.58‐0.87) and composite microvascular outcomes (HR 0.88; 0.77‐1.00). Meta‐regression analyses showed modest evidence of inverse linear relationships between HbA1c reduction and the outcomes of major adverse cardiovascular events, non‐fatal MI, stroke and retinopathy, but these were not statistically significant. Conclusions: In people with T2D, intensive glucose control was associated with a reduced risk of non‐fatal MI and several microvascular outcomes, particularly retinopathy and nephropathy. The lack of an effect of intensive glucose‐lowering on most macrovascular outcomes calls for a more comprehensive approach to managing cardiovascular risk factors alongside glycaemic control. [ABSTRACT FROM AUTHOR]

Objective: A previous study suggests an association between poor medication adherence and excess mortality in chronic disease. The purpose of this study was to assess the association between medication adherence and risk of cardiovascular disease (CVD), all-cause mortality, and hospitalization in type 2 diabetes.Research Design and Methods: We conducted an electronic search on many electronic databases from inception to 27 April 2016. We selected randomized controlled trials and case-control and cohort studies reporting on CVD, all-cause mortality, or hospitalization outcomes by adherence in adults with type 2 diabetes. Two reviewers independently screened for eligible studies and extracted outcome data. Pooled relative risks (RRs) were calculated using a random-effects meta-analysis; risk of bias in each of the included studies was assessed using the GRADE approach.Results: Eight observational studies were included (n = 318,125). The mean rate of poor adherence was 37.8% (95% CI 37.6-38.0). Adjusted estimates were provided by five studies only. The RRs of good (≥80%) versus poor adherence to medication were 0.72 (95% CI 0.62-0.82, I2 = 0%, three studies) for all-cause mortality and 0.90 (0.87-0.94, I2 = 63%, seven studies) for hospitalization. No evidence of small study bias was observed. Only one study reported CVD outcomes by adherence.Conclusions: We identified no trials reporting on outcomes by adherence, suggesting a systematic failure to include this information. Pooled estimates from available observational studies suggest that good medication adherence is associated with reduced risk of all-cause mortality and hospitalization in people with type 2 diabetes, although bias cannot be excluded as an explanation for these findings. [ABSTRACT FROM AUTHOR]

Abstract Background Neutrophil gelatinase-associated lipocalin (NGAL), a novel biomarker of acute kidney injury, might play a role in the development of atherosclerotic cardiovascular disease (CVD). We aimed to assess the association of circulating NGAL with CVD risk. Materials and methods Plasma NGAL concentrations were measured at baseline in 5275 participants in the PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD were estimated. Results After a median follow-up of 8.3 years, 338 participants developed first CVD events. Plasma NGAL was weakly to moderately correlated with several CVD risk markers. There was a non-linear relationship between NGAL and CVD risk. In analyses adjusted for established risk factors, the hazard ratio (95% CI) for CVD in a comparison of the top quartile versus bottom quartiles 1–2 of NGAL values was 1.35 (1.05–1.75; P = 0.022), which was abrogated after additional adjustment for other potential confounders (mainly attributed to high sensitivity C-reactive protein) 1.20 (0.92–1.57; P = 0.176). The association was considerably attenuated following further adjustment for renal function 1.05 (0.79–1.40; P = 0.745). The association between NGAL and CVD risk did not vary importantly in relevant clinical subgroups. Conclusion Evidence suggests a non-linear association between NGAL and CVD risk, which is dependent on inflammation and renal function. Highlights • Increased NGAL is associated with an increased CVD risk in Caucasians. • The association is non-linear and is independent of cardiovascular risk factors. • The association is partly dependent on inflammation and renal function. [ABSTRACT FROM AUTHOR]

Background and aims We aimed to assess the association of circulating calprotectin, an inflammation-associated protein, with cardiovascular disease (CVD) risk and determine whether it improves risk prediction. Methods Plasma calprotectin measurements were made at baseline in 5290 participants in the PREVEND prospective study. Hazard ratios (95% confidence intervals [CI]) for CVD were calculated. Results After a median follow-up of 8.3 years, 339 first CVD events were recorded. Calprotectin concentration was correlated with several conventional risk factors as well as with high-sensitivity C-reactive protein (hsCRP) (r = 0.42). Calprotectin was log-linearly associated with CVD risk. The risk for CVD adjusted for conventional cardiovascular risk factors was 1.26 (95% CI, 1.13–1.41) per 1 standard deviation higher baseline log e calprotectin, and was 1.24 (95% CI, 1.11–1.39) following further adjustment for triglycerides, body mass index, and other potential confounders. The association remained present after further adjustment for hsCRP 1.15 (95% CI, 1.02–1.30). Comparing extreme quartiles of plasma calprotectin levels, the corresponding adjusted HRs for CVD were 1.96 (1.37–2.82), 1.89 (1.31–2.72), and 1.56 (1.07–2.29). The association of calprotectin with CVD risk did not vary importantly in several relevant clinical subgroups. Adding calprotectin to the Framingham CVD Risk Score was associated with a C-index change (0.0016; p =0.42) difference in −2 log likelihood ( p =0.038), IDI (0.0080; p  < 0.001), and NRI (4.03%; p =0.024). Conclusions There is a log-linear association of calprotectin concentration with risk of CVD, which may be partly dependent on hsCRP. Adding calprotectin to conventional risk factors improves CVD risk assessment using measures of reclassification and −2 log likelihood. [ABSTRACT FROM AUTHOR]