Anticoagulation control in different ethnic groups receiving vitamin K antagonist therapy for stroke prevention in atrial fibrillation.

BACKGROUND: Efficacy and safety of vitamin K antagonists (VKAs) is optimised in atrial fibrillation (AF) patients when the International Normalised Ratio (INR) is 2.0-3.0. Anticoagulation control comparing different ethnic groups is limited, although epidemiological studies suggest poorer INR control in non-white cohorts. METHODS: VKA control was assessed retrospectively by time-in-the-therapeutic range (TTR) (Rosendaal method) and percentage INR-in-range (PINRR) in 991 White, Afro-Caribbean and South-Asian AF patients [overall mean (SD) age 71.6 (9.4) years; 55% male; mean (SD) CHA2DS2-VASc score 3.4 (1.6)] over a median (IQR) follow-up of 5.2 (3.2-7.0) years. RESULTS: Compared to Whites, mean (SD) TTR and PINRR were significantly lower in South-Asians [TTR 67.9% vs. 60.5%; PINRR 58.8% vs. 51.6%, respectively] and Afro-Caribbeans [TTR 67.9% vs. 61.3%; PINRR 58.8% vs. 53.1%, respectively], despite similar INR monitoring intensity. Logistic regression revealed non-white ethnicity [OR 2.62; 95% Confidence Interval [CI] (1.67-4.10) and OR 3.47 (1.44-8.34)] and anaemia [OR 1.65 (1.00-2.70) and OR 6.27 (1.89-20.94)] as independent predictors of both TTR and PINRR < 70%, respectively. At follow-up, 329 (33.2%) patients experienced ≥1 major adverse clinical event. Cardiovascular hospitalisation was significantly higher among South-Asians (32.3%) compared to the Whites and Afro-Caribbeans (21.3% vs 25.6% respectively). CONCLUSIONS: Ethnic disparities in quality of anticoagulation control are evident, with South-Asians and Afro-Caribbeans having poorer control compared to Whites, despite similar intensity INR monitoring. Non-white ethnicity remained the strongest independent predictor of poor TTR and PINRR. Interventions to improve anticoagulation control need to be implemented, particularly targeting ethnic minority patients.

Is There an Obesity Paradox for Outcomes in Atrial Fibrillation? A Systematic Review and Meta-Analysis of Non-Vitamin K Antagonist Oral Anticoagulant Trials.

BACKGROUND AND PURPOSE: Obesity is a risk factor for all-cause and cardiovascular death but, despite this, an inverse relationship between overweight or obesity and a better cardiovascular prognosis in long-term follow-up studies has been observed; this phenomenon, described as obesity paradox, has also been found evident in atrial fibrillation cohorts. METHODS: We performed a systematic review on the relationship between body mass index and major adverse outcomes in atrial fibrillation patients. Moreover, we provided a meta-analysis of non-vitamin K antagonist oral anticoagulants (NOACs) trials. RESULTS: An obesity paradox was found for cardiovascular death and all-cause death in the subgroup analyses of randomized trial cohorts; however, observational studies fail to show this relationship. From the meta-analysis of NOAC trials, a significant obesity paradox was found, with both overweight and obese patients reporting a lower risk for stroke/systemic embolic event (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.66-0.84 and OR, 0.62; 95% CI, 0.54-0.70, respectively). For major bleeding, only obese patients were at lower risk compared with normal weight patients (OR, 0.84; 95% CI, 0.72-0.98). A significant treatment effect of NOACs was found in normal weight patients, both for stroke/systemic embolic event (OR, 0.66; 95% CI, 0.56-0.78) and for major bleeding (OR, 0.72; 95% CI, 0.54-0.95). Major bleeding risk was lower in overweight patients treated with NOACs (OR, 0.84; 95% CI, 0.71-1.00). CONCLUSIONS: There may be an obesity paradox in atrial fibrillation patients, particularly for all-cause and cardiovascular death outcomes. An obesity paradox was also evident for stroke/systemic embolic event outcome in NOAC trials, with a treatment effect favoring NOACs over warfarin for both efficacy and safety that was significant only for normal weight patients.

Balancing thromboembolic and bleeding risk with non-vitamin K antagonist oral anticoagulants (NOACs): A systematic review and meta-analysis on gender differences.

Sex and gender differences have been reported in atrial fibrillation (AF), especially in relation to differences in thromboembolic and bleeding risks. More recently, pharmacological treatments have changed following the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) progressively replacing vitamin K antagonists (VKAs). The aims of this systematic review are to summarize the available evidence on NOACs and the relationship to major adverse outcomes according to sex. Moreover, we performed a meta-analysis of data from the phase III clinical trials investigating the sex effect on stroke/systemic embolic events (SEE) and major bleeding. Our literature review found small differences in NOACs efficacy and safety between male and female patients, even if so far available literature is limited to post-hoc ancillary analyses from randomized trials and one cohort study. Meta-analysis from NOAC trials found a differential effect of NOACs, with male patients being more protected from stroke/SEE and female patients more protected from major bleeding events. Further data are needed to fully elucidate sex differences in AF patients treated with NOACs.

Tea, flavonoids, and cardiovascular health: endothelial protection.

Several studies have suggested that tea consumption might protect against the development and progression of cardiovascular disease, one of the leading causes of morbidity and mortality worldwide. The endothelium plays a pivotal role in arterial homeostasis. Reduced nitric oxide (NO) bioavailability with endothelial dysfunction is considered the earliest step in the pathogenesis of atherosclerosis. Endothelial dysfunction has been considered an important and independent predictor of future development of cardiovascular risk and events. The association between brachial NO-dependent flow-mediated dilation (FMD) and cardiovascular disease risk has been investigated in several prospective studies, suggesting that FMD is inversely associated with future cardiovascular events. Dietary flavonoids and tea consumption have been described to improve endothelial function and FMD. A proposed mechanism by which dietary flavonoids could affect FMD is that they improve the bioactivity of the endothelium-derived vasodilator NO by enhancing NO synthesis or by decreasing superoxide-mediated NO breakdown. This could be of clinical relevance and may suggest a mechanistic explanation for the reduced risk of cardiovascular events and stroke observed among tea drinkers in the different studies. The purpose of this article is to provide an overview of the relation between tea consumption and cardiovascular disease, with a focus on clinical implications resulting from the beneficial effects of tea consumption on endothelial function.

Chronic hyperuricemia, uric acid deposit and cardiovascular risk.

Hyperuricemia is commonly associated with traditional risk factors such as dysglicemia, dyslipidemia, central obesity and abnormal blood pressure, i.e. the metabolic syndrome. Concordantly, recent studies have revived the controversy over the role of circulating uric acid, hyperuricemia, and gout as an independent prognostic factor for cardiovascular morbidity and mortality. In this regard, different studies also evaluated the possible role of xanthine inhibitors in inducing blood pressure reduction, increment in flow-mediated dilation, and improved cardiovascular prognosis in various patient settings. The vast majority of these studies have been conducted with either allopurinol or its active metabolite oxypurinol, i.e. two purine-like non-selective inhibitors of xanthine oxidase. More recently, the role of uric acid as a risk factor for cardiovascular disease and the possible protective role exerted by reduction of hyperuricemia to normal level have been evaluated by the use of febuxostat, a selective, non purine-like xanthine oxidase inhibitor. In this review, we will report current evidence on hyperuricemia in cardiovascular disease. The value of uric acid as a biomarker and as a potential therapeutic target for tailored old and novel "cardiometabolic" treatments will be also discussed.

Cognitive decline as a consequence of essential hypertension.

Hypertension is a leading cardiovascular risk for cardiovascular morbidity and mortality. Age is the strongest risk factor for dementia and with the increasing life expectancy the number of patients living with dementia worldwide is estimated to progressively rise. A number of studies support an association between hypertension, particularly in midlife, and the development of cognitive disorders and dementia, including Alzheimer's disease. According to this, considering hypertension as a possible modifiable risk factor for the cognitive decline is of great clinical interest. Treatment of hypertension in midlife seems to promote considerable benefits with regard to cardiovascular outcomes. Longitudinal studies examining the possible benefit of anti-hypertensive treatments on cognitive decline have produced promising results. Nevertheless, the results from randomised controlled clinical trials on treatment of hypertension are not conclusive for the effect on cognitive decline and dementia. New randomized controlled trials are needed to definitively clarify clinical advantages and specifically elucidate the relationship between anti-hypertensive treatments and cognitive function or dementia.