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Background: Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.Objectives: This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.Methods: This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).Results: Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).Conclusion: In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294). [ABSTRACT FROM AUTHOR]

Abstract Aims With increasing age, physical inactivity and sedentary behaviour levels increase, as does cardiovascular disease (CVD) incidence. We investigate how device-measured sedentary behaviour and physical activity (PA) are related to CVD onset in men aged 70+; whether the total volume of activity is more important than pattern. Methods and results Prospective population-based cohort study of men recruited from 24 UK General Practices in 1978–80. In 2010–12, 3137 survivors were invited to complete questionnaires and wear an Actigraph GT3x accelerometer for 7 days. PA intensity was categorised as sedentary, light and moderate to vigorous (MVPA). Men were followed up for Myocardial Infarction, stroke and heart failure (ICD9 410–414, 430–438 and 428) morbidity and mortality from 2010 to 12 to June 2016. Hazard Ratios (HRs) for incident Cardiovascular Disease (CVD) were estimated. 1528/3137 (49%) men had sufficient accelerometer data. 254 men with pre-existing CVD were excluded. Participants' mean age was 78.4 (range 71–92) years. After median 4.9 years follow-up, 122 first CVD events occurred in 1181 men (22.7/1000 person-years) with complete data. For each additional 30 min in sedentary behaviour, light PA,10 min in MVPA, or 1000 steps/day, HRs for CVD were 1.09(95%CI 1.00, 1.19), 0.94(0.85, 1.04), 0.88(0.81, 0.96) and 0.86(0.78 to 0.95) respectively, adjusted for measurement-related factors, socio-demographics, health behaviours and disability. HRs for accumulating 150 min/week MVPA in bouts ≥1 min and bouts ≥10 min were 0.47(0.32 to 0.69), and 0.49(0.25, 0.98). Conclusions In older men, high volume of steps or MVPA rather than MVPA bouts was associated with reduced CVD risk. Highlights • Prospective studies report that self-reported physical activity protects against cardiovascular disease (CVD). • Yet, self-reported behaviours cannot easily be used to assess the value of the 10 min activity bouts specified in guidelines. • This is the first study of risk of fatal and non-fatal CVD based on device measured physical activity and sedentary behaviour. • Among 1181 men aged over 70 years, more time in moderate to vigorous physical activity and more steps reduced 5-year CVD risk. • The pattern of accumulating moderate to vigorous physical activity in 10 min bouts was not important for CVD risk. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the individual and combined associations of depression and low socioeconomic status (SES) with risk of major cardiovascular events (MCVE), defined as first-ever fatal or non-fatal stroke or myocardial infarction, in a large prospective cohort study.Methods: We used data from 466,238 UK Biobank participants, aged 40-69 years without cardiovascular disease, bipolar disorder or schizophrenia at baseline. We performed Cox proportional hazard models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the individual and combined associations of depression and each of educational attainment, area-based deprivation and income with risk of MCVE. We assessed effect modification and explored interaction on the additive and multiplicative scale.Results: Depression, low education, high area-based deprivation and low income were individually associated with increased risks of MCVE (adjusted HR, 95% CI: 1.28, 1.19-1.38; 1.20, 1.14-1.27; 1.17, 1.11-1.23; and 1.22, 1.16-1.29, respectively). Depression was associated with increased risks of MCVE among individuals with high and low SES. Individuals with depression and each of low education, high area-based deprivation and low income were at particularly high risk of MCVE (HR, 95% CI: 1.50, 1.38-1.63; 1.63, 1.46-1.82; 1.31, 1.23-1.40, respectively). There was interaction between depression and area-based deprivation on multiplicative and additive scales but no interaction with education or income.Conclusion: Depression was associated with increased risks of MCVE among individuals with high and low SES, with particularly high risks among those living in areas of high deprivation. [ABSTRACT FROM AUTHOR]

Background: There are conflicting data regarding the benefits of omega-3 (n-3) fatty acids, most recently in patients with type 2 diabetes. Objective: Our goal was to evaluate the impact of licensed, highly purified n-3 fatty acids on all-cause mortality after myocardial infarction (MI). Methods: This was a retrospective, matched-cohort study using data from the General Practice Research Database. Patients initiating treatment with 1 g of n-3 fatty acids in the 90 days after first MI were identified and each matched to 4 nonexposed patients. Progression to death was compared using time-dependent Cox models to account for potential differences in exposure to other cardiovascular risk-modifying treatments. Results: A total of 2466 eligible subjects exposed to n-3 fatty acids were matched. The majority of patients had concurrent treatment with lipid-lowering therapies, antihypertensives, and antiplatelets after first MI, with subjects exposed to n-3 fatty acids having a greater likelihood of concurrent exposure. For those initiating n-3 fatty acids within 90 days of first MI, the adjusted hazard ratio (aHR) was 0.782 (95% CI, 0.641-0.995; P = 0.0159); for those initiating treatment within 14 days, the aHR was 0.680 (95% CI, 0.481-0.961; P = 0.0288). In patients with type 2 diabetes at baseline, the aHRs were 0.714 (95% CI, 0.454-1.124) and 0.597 (95% CI, 0.295-1.211) when initiation was within 90 and 14 days, respectively. Use of n-3 fatty acids resulted in a consistent survival benefit under a range of scenarios quantitatively consistent with the overall effect. Conclusion: After MI, early treatment with licensed n-3 fatty acids was associated with improvement in all-cause mortality in patients with and without type 2 diabetes, against a background of contemporary cardiovascular risk-modifying treatments. [ABSTRACT FROM AUTHOR]