Explore the vast range of titles available.

After exposure to dilute diesel exhaust, men with coronary disease had increased exercise-induced myocardial ischemia, along with depressed fibrinolytic function. The data reported suggest possible mechanisms for the detrimental effect of air pollution from traffic in patients with coronary disease. After exposure to dilute diesel exhaust, men with coronary disease had increased exercise-induced myocardial ischemia, along with depressed fibrinolytic function. The World Health Organization (WHO) estimates that air pollution is responsible for 800,000 premature deaths worldwide each year. 1 Short-term exposure to air pollution has been associated with increases in cardiovascular morbidity and mortality, with deaths due to ischemia, arrhythmia, and heart failure. 2 In a large cohort study from the United States, Miller et al. recently reported that long-term exposure to air pollution increases the risk of death from cardiovascular disease by 76%. 3 These associations are strongest for fine particulate air pollutants (particulate matter of less than 2.5 μm in aerodynamic diameter [PM 2.5 ]), of which the combustion-derived nanoparticulate in . . .

Background To summarize the four recent sodium-glucose cotransporter 2 inhibitor (SGLT2i) trials: Dapagliflozin Effect on CardiovascuLAR Events (DECLARE-TIMI 58), CANagliflozin CardioVascular Assessment Study (CANVAS) Program, Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients–Removing Excess Glucose (EMPA–REG OUTCOME), Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE), and explore the potential determinants for their cardiovascular, renal, and safety outcomes. Results The composite renal outcome event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 3.7, 7.0, 47%; 5.5, 9.0, 40%; 6.3, 11.5, 46%; 43.2, 61.2, 30% for DECLARE-TIMI 58, CANVAS, EMPA–REG OUTCOME, and CREDENCE, respectively (event definitions varied across trials). The major adverse cardiovascular (CV) event rates per 1000 patient-years for drug and placebo, as well as the corresponding relative risk reductions, were 22.6, 24.2, 7%; 26.9, 31.5, 14%; 37.4, 43.9, 14%; 38.7, 48.7, 20% for DECLARE-TIMI 58, CANVAS, EMPA–REG OUTCOME, and CREDENCE, respectively. DECLARE-TIMI 58 had the fewest cardiorenal events and CREDENCE the most. These differences were presumably due to varying inclusion criteria resulting in DECLARE-TIMI 58 having the best baseline renal filtration function and CREDENCE the worst (mean estimated glomerular filtration rate 85.2, 76.5, 74, 56.2 mL/min/1.73 m 2 for DECLARE-TIMI 58, CANVAS, EMPA–REG OUTCOME, and CREDENCE, respectively). Additionally, CREDENCE had considerably higher rates of albuminuria (median urinary albumin-creatinine ratios (UACR) were 927, 12.3, and 13.1 mg/g for CREDENCE, CANVAS, and DECLARE-TIMI 58, respectively; EMPA–REG OUTCOME had 59.4% UACR < 30, 28.6% UACR > 30–300, 11.0% UACR > 300 mg/g). Conclusions Dapagliflozin, empagliflozin, and canagliflozin have internally and externally consistent and biologically plausible class effects on cardiorenal outcomes. Baseline renal filtration function and degree of albuminuria are the most significant indicators of risk for both CV and renal events. Thus, these two factors also anticipate the greatest clinical benefit for SGLT2i.

Abstract Context Studies of the possible cardiovascular risk of testosterone treatment are inconclusive. Objective To determine the effect of testosterone treatment on cardiovascular biomarkers in older men with low testosterone. Design Double-blind, placebo-controlled trial. Setting Twelve academic medical centers in the United States. Participants In all, 788 men ≥65 years old with an average of two serum testosterone levels <275 ng/dL who were enrolled in The Testosterone Trials. Intervention Testosterone gel, the dose adjusted to maintain the testosterone level in the normal range for young men, or placebo gel for 12 months. Main Outcome Measures Serum markers of cardiovascular risk, including lipids and markers of glucose metabolism, fibrinolysis, inflammation, and myocardial damage. Results Compared with placebo, testosterone treatment significantly decreased total cholesterol (adjusted mean difference, −6.1 mg/dL; P < 0.001), high-density lipoprotein cholesterol (adjusted mean difference, −2.0 mg/dL; P < 0.001), and low-density lipoprotein cholesterol (adjusted mean difference, −2.3 mg/dL; P = 0.051) from baseline to month 12. Testosterone also slightly but significantly decreased fasting insulin (adjusted mean difference, −1.7 µIU/mL; P = 0.02) and homeostatic model assessment‒insulin resistance (adjusted mean difference, −0.6; P = 0.03). Testosterone did not change triglycerides, d-dimer, C-reactive protein, interleukin 6, troponin, glucose, or hemoglobin A1c levels more than placebo. Conclusions and Relevance Testosterone treatment of 1 year in older men with low testosterone was associated with small reductions in cholesterol and insulin but not with other glucose markers, markers of inflammation or fibrinolysis, or troponin. The clinical importance of these findings is unclear and requires a larger trial of clinical outcomes. Compared with placebo, testosterone treatment of older men with low testosterone was associated with small reductions in total, HDL, and LDL cholesterol and in insulin and HOMA-IR but not glucose.

The use of electronic cigarettes has increased exponentially since its introduction onto the global market in 2006. However, short- and long-term health effects remain largely unknown due to the novelty of this product. The present study examines the acute effects of e-cigarette aerosol inhalation, with and without nicotine, on vascular and pulmonary function in healthy volunteers. Seventeen healthy subjects inhaled electronic cigarette aerosol with and without nicotine on two separate occasions in a double-blinded crossover fashion. Blood pressure, heart rate, and arterial stiffness measured by pulse wave velocity and pulse wave analysis were assessed at baseline, and then at 0 h, 2 h, and 4 h following exposure. Dynamic spirometry and impulse oscillometry were measured following vascular assessments at these time points, as well as at 6 h following exposure. e-Cigarette aerosol with nicotine caused a significant increase in heart rate and arterial stiffness. Furthermore, e-cigarette aerosol-containing nicotine caused a sudden increase in flow resistance as measured by impulse oscillometry, indicating obstruction of the conducting airways. Both aerosols caused an increase in blood pressure. The present study indicates that inhaled e-cigarette aerosol with nicotine has an acute impact on vascular and pulmonary function. Thus, chronic usage may lead to long-term adverse health effects. Further investigation is warranted.

Abstract Context Postprandial hyperglycemia increases systemic inflammation and is a risk factor for cardiovascular disease. A ketone monoester (KME) drink containing β-hydroxybutyrate (β-OHB) rapidly lowers plasma glucose, which may be a strategy protecting against postprandial hyperglycemia. Objective We hypothesized that KME would attenuate 2-hour postprandial glucose, lower systemic inflammation, and improve vascular function in adults with obesity. Methods In a randomized crossover design, 14 participants with obesity (age = 56 ± 12 years; body mass index = 32.8 ± 7.7 kg/m2) consumed KME (12 g β-OHB) or placebo 15 minutes prior to each meal for 14 days with all meals provided and matched between conditions. Postprandial glycemia was assessed by continuous glucose monitoring. Vascular function and inflammation were assessed before and after treatment periods. Results Postprandial glucose was 8.0% lower in KME versus placebo (g = 0.735; P = 0.011) and 24-hour average glucose reduced by 7.8% (g = 0.686; P = 0.0001). Brachial artery flow-mediated dilation increased from 6.2  ±  1.5% to 8.9 ± 3.3% in KME (g = 1.05; P = 0.0004) with no changes in placebo (condition × time interaction, P = 0.004). There were no changes in plasma cytokines; however, lipopolysaccharide-stimulated monocyte caspase-1 activation was lower following KME supplementation versus placebo (stimulation × condition × time interaction; P = 0.004). The KME supplement was well tolerated by participants and adherence to the supplementation regimen was very high. Conclusions In adults with obesity, 14 days of premeal KME supplementation improves glucose control, enhances vascular function, and may reduce cellular inflammation. KME supplementation may be a viable, nonpharmacological approach to improving and protecting vascular health in people with heightened cardiometabolic risk.

Dietary sodium restriction has been shown to enhance the short-term response of blood pressure and albuminuria to angiotensin receptor blockers (ARBs). Whether this also enhances the long-term renal and cardiovascular protective effects of ARBs is unknown. Here we conducted a post-hoc analysis of the RENAAL and IDNT trials to test this in patients with type 2 diabetic nephropathy randomized to ARB or non-renin–angiotensin–aldosterone system (non-RAASi)–based antihypertensive therapy. Treatment effects on renal and cardiovascular outcomes were compared in subgroups based on dietary sodium intake during treatment, measured as the 24-h urinary sodium/creatinine ratio of 1177 patients with available 24-h urinary sodium measurements. ARB compared to non-RAASi–based therapy produced the greatest long-term effects on renal and cardiovascular events in the lowest tertile of sodium intake. Compared to non-RAASi, the trend in risk for renal events was significantly reduced by 43%, not changed, or increased by 37% for each tertile of increased sodium intake, respectively. The trend for cardiovascular events was significantly reduced by 37%, increased by 2% and 25%, respectively. Thus, treatment effects of ARB compared with non-RAASi–based therapy on renal and cardiovascular outcomes were greater in patients with type 2 diabetic nephropathy with lower than higher dietary sodium intake. This underscores the avoidance of excessive sodium intake, particularly in type 2 diabetic patients receiving ARB therapy.

Abstract Context Control of multiple cardiovascular (CV) risk factors reduces CV events in individuals with type 2 diabetes. Objective To investigate this association in a contemporary clinical trial population, including how CV risk factor control affects the CV benefits of empagliflozin, a sodium-glucose cotransporter-2 inhibitor. Design Post hoc analysis. Setting Randomized CV outcome trial (EMPA-REG OUTCOME). Participants Type 2 diabetes patients with established CV disease. Intervention Empagliflozin or placebo. Main Outcome Measures Risk of CV outcomes—including the treatment effect of empagliflozin—by achieving 7 goals for CV risk factor control at baseline: (1) glycated hemoglobin <7.5%, (2) low-density lipoprotein cholesterol <100 mg/dL or statin use, (3) systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg, (4) pharmacological renin-angiotensin-aldosterone system blockade, (5) normoalbuminuria, (6) aspirin use, (7) nonsmoking. Results In the placebo group, the hazard ratio (HR) for CV death was 4.00 (95% CI, 2.26–7.11) and 2.48 (95% CI, 1.52–4.06) for patients achieving only 0–3 or 4–5 risk factor goals at baseline, respectively, compared with those achieving 6–7 goals. Participants achieving 0–3 or 4–5 goals also had increased risk for the composite outcome of hospitalization for heart failure or CV death (excluding fatal stroke) (HR 2.89 [1.82–4.57] and 1.90 [1.31–2.78], respectively) and 3-point major adverse CV events (HR 2.21 [1.53–3.19] and 1.42 [1.06–1.89]). Empagliflozin significantly reduced these outcomes across all risk factor control categories (P > 0.05 for treatment-by-subgroup interactions). Conclusions Cardiovascular risk in EMPA-REG OUTCOME was inversely associated with baseline CV risk factor control. Empagliflozin’s cardioprotective effect was consistent regardless of multiple baseline risk factor control.

About one third of patients prescribed blood pressure or lipid-lowering drugs for the prevention of coronary heart disease and stroke do not take their medication as prescribed. We conducted a randomized trial to evaluate text messaging as a means of improving adherence to cardiovascular disease preventive treatment. 303 patients taking blood pressure and/or lipid-lowering medications were randomly assigned to being sent text messages (Text group, 151) or not being sent them (No text group, 152). Texts were sent daily for 2 weeks, alternate days for 2 weeks and weekly thereafter for 22 weeks (6 months overall), using an automated computer programme. Patients were asked to respond on whether they had taken their medication, whether the text reminded them to do so if they had forgotten, and if they had not taken their medication to determine if there was a reason for not doing so. At 6 months, use of medication was assessed. Two patients were lost to follow-up, providing data on 301 for analysis. In the No text group 38/151 (25%) took less than 80% of the prescribed regimen (ie. stopped medication completely or took it on fewer than 22 of the last 28 days of follow-up) compared to 14/150 patients (9%) in the Text group - an improvement in adherence affecting 16 per 100 patients (95% CI 7 to 24), p<0.001. The texts reminded 98/151 patients (65%) to take medication on at least one occasion and lead to 20/151 (13%) who stopped taking medication because of concern over efficacy or side-effects, resuming treatment. In patients taking blood pressure or lipid-lowering treatment for the prevention of cardiovascular disease, text messaging improved medication adherence compared with no text messaging. Controlled-Trials.com ISRCTN74757601.

OBJECTIVE:--Hyperglycemia and Its Effect After Acute Myocardial Infarction on Cardiovascular Outcomes in Patients With Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS--Patients (type 2 diabetes, aged 30-75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose <7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose <6.7 mmol/l). RESULTS:--A total of 1,115 patients were randomly assigned (PRANDIAL n = 557; BASAL n = 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n = 174, 31.2%) and BASAL (n = 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8-1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 ± 0.1 vs. 7.8 ± 0.1%; P = 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P < 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P < 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P < 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P = 0.233) versus the PRANDIAL group. CONCLUSIONS:--Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.

Objective The inflammatory cytokine, tumour necrosis factor α (TNF-α), exerts deleterious cardiovascular effects. We wished to determine the effects of TNF-α antagonism on endothelial function and platelet activation in patients with acute myocardial infarction. Design and setting and patients A double-blind, parallel group, randomised controlled trial performed in a tertiary referral cardiac centre. 26 patients presenting with acute myocardial infarction randomised to receive an intravenous infusion of etanercept (10 mg) or saline placebo. Main outcome measures Leucocyte count, plasma cytokine concentrations, flow cytometric measures of platelet activation and peripheral vasomotor and fibrinolytic function were determined before and 24 h after study intervention. Results Consistent with effective conjugation of circulating TNF-α, plasma TNF-α concentrations increased in all patients following etanercept (254±15 vs 0.12±0.02 pg/ml; p<0.0001), but not saline infusion. Etanercept treatment reduced neutrophil (7.4±0.6 vs 8.8±0.6×109 cells/l; p=0.03) and plasma interleukin-6 concentrations (5.8±2.0 vs 10.6±4.0 pg/ml; p=0.012) at 24 h but increased platelet–monocyte aggregation (30±5 vs 20±3%; p=0.02). Vasodilatation in response to substance P, acetylcholine and sodium nitroprusside, and acute tissue plasminogen activator release were unaffected by either treatment (p>0.1 for all). Conclusions Following acute myocardial infarction, etanercept reduces systemic inflammation but increases platelet activation without affecting peripheral vasomotor or fibrinolytic function. We conclude that TNF-α antagonism is unlikely to be a beneficial therapeutic strategy in patients with acute myocardial infarction.