BACKGROUND It is unknown whether warfarin or aspirin therapy is superior for patients with heart failure who are in sinus rhythm. METHODS We designed this trial to determine whether warfarin (with a target international normalized ratio of 2.0 to 3.5) or aspirin (at a dose of 325 mg per day) is a better treatment for patients in sinus rhythm who have a reduced left ventricular ejection fraction (LVEF). We followed 2305 patients for up to 6 years (mean [±SD], 3.5±1.8). The primary outcome was the time to the first event in a composite end point of ischemic stroke, intracerebral hemorrhage, or death from any cause. RESULTS The rates of the primary outcome were 7.47 events per 100 patient-years in the warfarin group and 7.93 in the aspirin group (hazard ratio with warfarin, 0.93; 95% confidence interval [CI], 0.79 to 1.10; P = 0.40). Thus, there was no significant overall difference between the two treatments. In a time-varying analysis, the hazard ratio changed over time, slightly favoring warfarin over aspirin by the fourth year of follow-up, but this finding was only marginally significant (P = 0.046). Warfarin, as compared with aspirin, was associated with a significant reduction in the rate of ischemic stroke throughout the follow-up period (0.72 events per 100 patient-years vs. 1.36 per 100 patient-years; hazard ratio, 0.52; 95% CI, 0.33 to 0.82; P = 0.005). The rate of major hemorrhage was 1.78 events per 100 patient-years in the warfarin group as compared with 0.87 in the aspirin group (P<0.001). The rates of intracerebral and intracranial hemorrhage did not differ significantly between the two treatment groups (0.27 events per 100 patient-years with warfarin and 0.22 with aspirin, P = 0.82). CONCLUSIONS Among patients with reduced LVEF who were in sinus rhythm, there was no significant overall difference in the primary outcome between treatment with warfarin and treatment with aspirin. A reduced risk of ischemic stroke with warfarin was offset by an increased risk of major hemorrhage. The choice between warfarin and aspirin should be individualized.

Recent findings suggest that COVID-19 causes vascular dysfunction during the acute phase of the illness in otherwise healthy young adults. To date, no studies have investigated the longer-term effects of COVID-19 on vascular function. Herein, we hypothesized that young, otherwise healthy adults who are past the acute phase of COVID-19 would exhibit blunted peripheral (brachial artery flow-mediated dilation (FMD) and reactive hyperemia) and cerebral vasodilator function (cerebral vasomotor reactivity to hypercapnia; CVMR) and increased central arterial stiffness. Sixteen young adults who were at least 4 weeks past a COVID-19 diagnosis and 12 controls who never had COVID-19 were studied. Eight COVID subjects were symptomatic (SYM) and 8 were asymptomatic (ASYM) at the time of testing. FMD and reactive hyperemia were not different between COVID and Control groups. However, FMD was lower in SYM (3.8 ± 0.6%) compared to ASYM (6.8 ± 0.9%; P = 0.007) and Control (6.8 ± 0.6%; P = 0.003) with no difference between ASYM and Control. Similarly, peak blood velocity following cuff release was lower in SYM (47 ± 8 cm/s) compared to ASYM (64 ± 19 cm/s; P = 0.025) and Control (61 ± 14 cm/s; P = 0.036). CVMR and arterial stiffness were not different between any groups. In summary, peripheral macro- and microvascular function, but not cerebral vascular function or central arterial stiffness were blunted in young adults symptomatic beyond the acute phase of COVID-19. In contrast, those who were asymptomatic had similar vascular function compared to controls who never had COVID.

We show for the first time that breakthrough cases of COVID-19 during the Omicron wave does not impact vascular health and cardiac autonomic function in young adults. These are promising results considering earlier research showing impaired vascular and autonomic function following previous variants of COVID-19. Collectively, these data demonstrate that the recent Omicron variant is not detrimental to cardiovascular health in young, otherwise healthy, vaccinated adults.

Prolonged sitting for 1-6 h has been shown to impair leg macrovascular [i.e. reduced flow-mediated dilatation (FMD)] and microvascular (i.e. reduced reactive hyperaemia) function. These impairments appear to be mediated through reductions in shear stress. Interestingly, a reduction in shear rate has been observed as early as 10 min into sitting. However, it is unknown whether this acute reduction in shear stress is sufficient to affect vascular function. Accordingly, we studied 18 young men and assessed popliteal artery FMD and reactive hyperaemia before (Baseline) and after (PostSit) a 10 min sitting period. Popliteal artery shear rate was significantly reduced during sitting (Baseline, 62 ± 35 s ; 10 min sitting, 27 ± 13 s ; P < 0.001). Macrovascular function was unaffected by 10 min of sitting (Baseline, 4.4 ± 2.1%; PostSit, 4.3 ± 2.3%; P = 0.97), but microvascular function was reduced (Baseline, 4852 ± 2261 a.u.; PostSit, 3522 ± 1872 a.u.; P = 0.02). In a subset of individuals, we extended the recovery period after sitting and demonstrated that resting shear rate and reactive hyperaemia responses remained low up to 1 h post-sitting (P < 0.001), whereas FMD was unchanged throughout (P = 0.99). Additionally, time control experiments were performed with participants in an immobile supine position, which demonstrated no change in macrovascular function (P = 0.94) but, unexpectedly, a reduction in microvascular function (P = 0.008). Importantly, when calf muscle contractions were performed during supine rest, reactive hyperaemia responses were maintained (P = 0.76), along with FMD (P = 0.88). These findings suggest that the leg microcirculation might be more vulnerable to short periods of inactivity, whereas conduit artery vasodilatation appears well maintained. Moreover, intermittent skeletal muscle contractions are beneficial for microvascular function.

Previous studies have demonstrated that African-American (AA) individuals have heightened vasoconstrictor and reduced vasodilator responses under resting conditions, as compared to Caucasian-American (CA) individuals. However, potential differences in vascular responses to exercise remain unclear. Therefore, we tested the hypothesis that, compared to CA, AA would present an attenuated increase in forearm vascular conductance (FVC) during rhythmic handgrip exercise. Forearm blood flow (FBF; duplex Doppler ultrasound), and mean arterial pressure (MAP; finger photoplethysmography) were measured in healthy young CA (N = 10) and AA (N = 10) men during six trials of rhythmic handgrip performed at workloads of 4, 8, 12, 16, 20, and 24 kg. FVC (calculated as FBF/MAP), FBF, and MAP were similar between groups at rest (FVC: CA: 63 ± 7 vs. AA: 62 ± 7 mL min 100 mmHg; P = 0.862). There was an intensity-dependent increase in FVC during exercise in both groups; however, AA presented lower FVC (interaction P < 0.001) at 8, 12, 16, 20, and 24 kg workloads ( e.g., 24 kg: CA: 324 ± 20 vs. AA: 241 ± 21 mL min 100 mmHg; P < 0.001). FBF responses to exercise were also lower in AA (interaction P < 0.001), whereas MAP responses did not differ between groups ( e.g., ∆MAP at 24 kg: CA: +19 ± 2 vs. AA: +19 ± 2 mmHg; interaction P = 0.950). These findings indicate lower hyperemic responses to rhythmic handgrip exercise in AA men, compared to CA men.