Heterogeneity of outcomes within diabetic patients with atrial fibrillation on edoxaban: a sub-analysis from the ETNA-AF Europe registry.

BACKGROUND: Recent data have suggested that insulin-requiring diabetes mostly contributes to the overall increase of thromboembolic risk in patients with atrial fibrillation (AF) on warfarin. We evaluated the prognostic role of a different diabetes status on clinical outcome in a large cohort of AF patients treated with edoxaban. METHODS: We accessed individual patients' data from the prospective, multicenter, ETNA-AF Europe Registry. We compared the rates of ischemic stroke/transient ischemic attack (TIA)/systemic embolism, myocardial infarction (MI), major bleeding and all-cause death at 2 years according to diabetes status. RESULTS: Out of an overall population of 13,133 patients, 2885 had diabetes (22.0%), 605 of whom (21.0%) were on insulin. The yearly incidence of ischemic stroke/TIA/systemic embolism was 0.86% in patients without diabetes, 0.87% in diabetic patients not receiving insulin (p = 0.92 vs no diabetes) and 1.81% in those on insulin (p = 0.002 vs no diabetes; p = 0.014 vs diabetes not on insulin). The annual rates of MI and major bleeding were 0.40%, 0.43%, 1.04% and 0.90%, 1.10% and 1.71%, respectively. All-cause yearly mortality was 3.36%, 5.02% and 8.91%. At multivariate analysis, diabetes on insulin was associated with a higher rate of ischemic stroke/TIA/systemic embolism [adjusted HR 2.20, 95% CI 1.37-3.54, p = 0.0011 vs no diabetes + diabetes not on insulin] and all-cause death [aHR 2.13 (95% CI 1.68-2.68, p < 0.0001 vs no diabetes]. Diabetic patients not on insulin had a higher mortality [aHR 1.32 (1.11-1.57), p = 0.0015], but similar incidence of stroke/TIA/systemic embolism, MI and major bleeding, vs those without diabetes. CONCLUSIONS: In a real-world cohort of AF patients on edoxaban, diabetes requiring insulin therapy, rather than the presence of diabetes per se, appears to be an independent factor affecting the occurrence of thromboembolic events during follow-up. Regardless of the diabetes type, diabetic patients had a lower survival compared with those without diabetes.

Ventricular-vascular coupling in hypertension: methodological considerations and clinical implications.

The present review is addressed to analyse the complex interplay between left ventricle and arterial tree in hypertension. The different methodological approaches to the analysis of ventricular vascular coupling in the time and frequency domain are discussed. Moreover, the role of hypertension-related changes of arterial structure and function (stiffness and wave reflection) on arterial load and how ventricular-vascular coupling modulates the process of left ventricular adaptation to hypertension are analysed.The different interplay between vascular bed and left ventricle emerges as the pathophysiological basis for the development of the multiple patterns of ventricular structural adaptation in hypertension and provides a pathway for the interpretation of systolic and diastolic functional abnormalities observed in hypertensive patients. Targeting the therapeutic approach to improve ventricular-vascular coupling may have relevant impact on reversing left ventricular hypertrophy and improving systolic and diastolic dysfunction.

Mitral annular calcification and incident ischemic stroke in treated hypertensive patients: the LIFE study.

Background Fibro-calcification of the mitral annulus (MAC) has been associated with increased risk of ischemic stroke in general populations. This study was performed to assess whether MAC predicts incidence of ischemic stroke in treated hypertensive patients with left ventricular hypertrophy (LVH). Methods Baseline and follow-up clinical and echocardiographic parameters were assessed in 939 hypertensive patients with electrocardiogram (ECG) LVH participating in the Losartan Intervention for Endpoint reduction in hypertension (LIFE) echocardiography substudy (66±7 years; 42% women; 11% with diabetes) who did not have aortic or mitral valve stenosis or prosthesis. Results MAC was found in 458 patients (49%). Patients with MAC were older (68±7 vs. 65±7 years); were more often women (47% vs. 37%); had higher baseline systolic blood pressure (BP) (175±14 vs. 172±15mm Hg), left atrial diameter (4.0±0.5 vs. 3.8±0.6cm), and left ventricular mass index (58±13 vs. 55±12g/m(2.7)) and included more patients with proteinuria (30% vs. 21%; all P < 0.01). During a mean follow-up of 4.8 years, 58 participants had an ischemic stroke. Risk of incident ischemic stroke was significantly related to presence of MAC (log rank = 9; P < 0.01). In multivariable Cox regression analysis models, MAC was associated with increased risk of ischemic stroke (hazard ratio = 1.78-2.35), independent of age, baseline or time-varying systolic BP, prevalence or incidence of atrial fibrillation, history of previous cerebrovascular disease, and other well-recognized confounders, such as sex, time-varying left ventricular mass, left atrial diameter, and urinary albumin/creatinine ratio (all P < 0.05). Conclusions MAC is common in treated hypertensive patients with ECG LVH and is an independent predictor of incident ischemic stroke.

Arterial stiffness is associated with carotid atherosclerosis in hypertensive patients (the Campania Salute Network).

BACKGROUND: Pulse pressure/stroke volume indexed to height(2.04) (PP/SVi) is a validated measure of arterial stiffness, but its relation to carotid atherosclerosis is unknown. METHODS: Clinical, echocardiographic, and carotid ultrasound data from 6,209 hypertensive patients without prevalent cardiovascular (CV) disease in the Campania Salute Network were analyzed. The population was grouped into tertiles of PP/SVi. From carotid ultrasound, peak and mean intima-media thickness (IMT) and presence of carotid plaques in the common and internal carotid arteries were reported. RESULTS: Increasing PP/SVi tertile was associated with a parallel increase in age, blood pressure, total serum cholesterol and the number of antihypertensive drugs used (all P < 0.01). Higher PP/SVi was also associated with greater peak and mean IMT (all P < 0.01), also when adjusting for age, gender, blood pressure, lipid profile, and diabetes mellitus (all P < 0.01). Similarly, compared to the lower PP/SVi tertile, the multiple adjusted prevalence ratio of carotid plaque was 7 (95% confidence interval (CI) 1-13, P < 0.03) in the middle tertile and 21 (95% CI 15-28, P < 0.0001) in the upper tertile, independently of confounders. CONCLUSION: In treated hypertensive patients participating in the Campania Salute Network, higher PP/SVi is associated with carotid atherosclerosis independent of well-known clinical confounders.

Does information on systolic and diastolic function improve prediction of a cardiovascular event by left ventricular hypertrophy in arterial hypertension?

Left ventricular (LV) mass (LVM) is the most important information requested in hypertensive patients referred for echocardiography. However, LV function also predicts cardiovascular (CV) risk independent of LVM. There is no evidence that addition of LV function significantly improves model prediction of CV risk compared with LVM alone. Thus, composite fatal and nonfatal CV or cerebrovascular events were evaluated in 5380 hypertensive outpatients (2336 women, 298 diabetics, and 1315 obese subjects) without prevalent CV disease (follow-up: 3.5+/-2.8 years). We compared 5 risk models using Cox regression and adjusting for age and sex: (1) LV mass normalized for height in meters(2.7) (LVMi); (2) LVMi, concentric LV geometry, by relative wall thickness (>0.43), ejection fraction, and transmitral diastolic pattern (by thirtiles of mitral deceleration index); (3) LVMi, LV geometry, midwall shortening, and mitral deceleration index thirtiles; (4) as No. 2 with the addition of left atrial dilatation (>23 mm); and (5) as No. 3 with the addition of left atrial dilatation. Individual hazard functions were compared using receiving operating characteristic curves and z statistics. Areas under the curves increased from 0.60 in the model with the sole LVMi to 0.62 in the others (all P values for differences were not significant). The additional information on systolic and diastolic function decreased the contribution (Wald statistics) of LVMi in the Cox model without improving the model ability to predict CV risk. We conclude that risk models with inclusion of information on LV geometry and systolic and diastolic function, in addition to LVMi, do not improve the prediction of CV events but rather redistribute the impact of individual predictors within the risk variance.